GPS Data and Machine Learning Tools, a Practical and Cost-Effective Combination for Estimating Light Vehicle Emissions.

This paper focuses on the emissions of the three most sold categories of light vehicles: sedans, SUVs, and pickups. The research is carried out through an innovative methodology based on GPS and machine learning in real driving conditions. For this purpose, driving data from the three best-selling vehicles in Ecuador are acquired using a data logger with GPS included, and emissions are measured using a PEMS in six RDE tests with two standardized routes for each vehicle. The data obtained on Route 1 are used to estimate the gears used during driving using the K-means algorithm and classification trees. Then, the relative importance of driving variables is estimated using random forest techniques, followed by the training of ANNs to estimate CO2, CO, NOX, and HC. The data generated on Route 2 are used to validate the obtained ANNs. These models are fed with a dataset generated from 324, 300, and 316 km of random driving for each type of vehicle. The results of the model were compared with the IVE model and an OBD-based model, showing similar results without the need to mount the PEMS on the vehicles for long test drives. The generated model is robust to different traffic conditions as a result of its training and validation using a large amount of data obtained under completely random driving conditions.

Non-fitness status of peripheral NK cells defined by decreased NKp30 and perforin, and increased soluble B7H6, in cervical cancer patients.

The NKp30 receptor is one of the three natural cytotoxic receptors reported in NK cells. This receptor is codified by the NCR3 gene, which encodes three isoforms, a consequence of the alternative splicing of exon 4. A greater expression of the three isoforms (A, B, and C), along with low levels of the NKp30 ligand B7H6, has been reported as a positive prognostic factor in different cancer types. Here, in patients with cervical cancer and precursor lesions, we report an altered immune-phenotype, characterized by non-fitness markers, that correlated with increased disease stage, from CIN 1 to FIGO IV. While overall NK cell numbers increased, loss of NKp30+ NK cells, especially in the CD56dim subpopulation, was found. Perforin levels were decreased in these cells. Decreased expression of the NKp30 C isoform and overexpression of soluble B7H6 was found in cervical cancer patients when compared against healthy subjects. PBMCs from healthy subjects downregulated NKp30 isoforms after co-culture with B7H6-expressing tumour cells. Taken together, these findings describe a unique down-modulation or non-fitness status of the immune response in cervical cancer, the understanding of which will be important for the design of novel immunotherapies against this disease.

Low-diversity microbiota and an increased metabolism of arginine and aromatic amino acids: a hallmark of hepatic encephalopathy in western Mexican patients with alcohol-associated cirrhosis.

AIMS: To evaluate the composition and functions of the gut microbiota in patients with decompensated alcohol-associated cirrhosis, with and without hepatic encephalopathy (HE). METHODS AND RESULTS: Faecal samples from 31 inpatients (20 with HE, 11 without HE), and from 18 age-balanced healthy controls (HC), were included. Microbial composition was determined by 16S rRNA amplicon sequencing and analysed using QIIME2. Metabolic pathways were inferred by PICRUSt2, and short-chain fatty acids (SCFAs) quantification was performed by gas chromatography. The gut microbiota of patients with HE was characterized by a diminished α-diversity, compared to no-HE (P < 0.01) and HC (P < 0.001) groups; ß-diversity also differed between HE vs no-HE patients (P < 0.05), and between HE vs HC (P < 0.001). In patients with HE, Escherichia/Shigella, Burkholderiales and Lactobacillales taxa predominated. In contrast, patients without HE were characterized by Veillonella and Bacteroides. Reduced levels of faecal SCFAs in both groups correlated with a depletion of beneficial taxa, such as Ruminococcus or Faecalibacterium. PICRUSt2 analysis showed both an enhanced catabolism of arginine through ammonia-producing pathways and chorismate biosynthesis in HE patients, a key precursor of aromatic amino acids. CONCLUSIONS: The gut microbiota of HE patients exhibits a proinflammatory dysbiotic profile, plus metabolic pathways that produce potentially neurotoxic byproducts.

Nanoparticles Formulation Improves the Antifibrogenic Effect of Quercetin on an Adenine-Induced Model of Chronic Kidney Disease.

Renal fibrosis is the final stage of chronic kidney injury characterized by glomerulosclerosis and tubulointerstitial fibrosis with parenchymal destruction. Quercetin belongs to the most studied flavonoids with antioxidant, anti-inflammatory, antifibrogenic, and antitumor activity. It modifies the TGF-ß/Smad signaling pathway, decreasing profibrogenic expression molecules and inducing the expression of antioxidant, anti-inflammatory, and antifibrogenic molecules. However, quercetin exhibits poor water solubility and low absorption and bioavailability. This limitation was solved by developing a nanoparticles formulation that improves the solubility and bioavailability of several bioactive compounds. Therefore, we aimed to investigate the in vivo antifibrogenic effect of a quercetin nanoparticles formulation. Male C57BL/6 mice were induced into chronic renal failure with 50 mg/kg of adenine for four weeks. The animals were randomly grouped and treated with 25, 50, or 100 mg/kg of quercetin, either macroparticles or nanoparticles formulation. We performed biochemical, histological, and molecular analyses to evaluate and compare the effect of macroparticles versus nanoparticles formulation on kidney damage. Here, we demonstrated that smaller doses of nanoparticles exhibited the same beneficial effect as larger doses of macroparticles on preventing kidney damage. This finding translates into less quercetin consumption reaching the desired therapeutic effect.

Estimation of Pollutant Emissions in Real Driving Conditions Based on Data from OBD and Machine Learning.

This article proposes a methodology for the estimation of emissions in real driving conditions, based on board diagnostics data and machine learning, since it has been detected that there are no models for estimating pollutants without large measurement campaigns. For this purpose, driving data are obtained by means of a data logger and emissions through a portable emissions measurement system in a real driving emissions test. The data obtained are used to train artificial neural networks that estimate emissions, having previously estimated the relative importance of variables through random forest techniques. Then, by the application of the K-means algorithm, labels are obtained to implement a classification tree and thereby determine the selected gear by the driver. These models were loaded with a data set generated covering 1218.19 km of driving. The results generated were compared to the ones obtained by applying the international vehicle emissions model and with the results of the real driving emissions test, showing evidence of similar results. The main contribution of this article is that the generated model is stronger in different traffic conditions and presents good results at the speed interval with small differences at low average driving speeds because more than half of the vehicle's trip occurs in urban areas, in completely random driving conditions. These results can be useful for the estimation of emission factors with potential application in vehicular homologation processes and the estimation of vehicular emission inventories.

Positive staining of the immunoligand B7-H6 in abnormal/transformed keratinocytes consistently accompanies the progression of cervical cancer.

BACKGROUND: B7-H6 has been revealed as an endogenous immunoligand expressed in a variety of tumors, but not expressed in healthy tissues. Heretofore, no studies have been reported describing B7-H6 in women with cervical cancer. To investigate this question, our present study was conducted. RESULTS: This retrospective study comprised a total of 62 paraffinized cervical biopsies, which were distributed in five groups: low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), squamous cervical carcinoma (SCC), uterine cervical adenocarcinoma (UCAC), and a group of cervicitis (as a control for non-abnormal/non-transformed cells). Cervical sections were stained by immunohistochemistry to explore the expression of B7-H6, which was reported according to the immunoreactive score (IRS) system. We observed a complete lack of B7-H6 in LSIL abnormal epithelial cells. Interestingly, B7-H6 began to be seen in HSIL abnormal epithelial cells; more than half of this group had B7-H6 positive cells, with staining characterized by a cytoplasmic and membranous pattern. B7-H6 in the SCC group was also seen in the majority of the sections, showing the same cytoplasmic and membranous pattern. Strong evidence of B7-H6 was notably found in UCAC tumor columnar cells (in 100% of the specimens, also with cytoplasmic and membranous pattern). Moreover, consistent B7-H6 staining was observed in infiltrating plasma cells in all groups. CONCLUSIONS: B7-H6 IRS positively correlated with disease stage in the development of cervical cancer; additionally, B7-H6 scores were found to be even higher in the more aggressive uterine cervical adenocarcinoma, suggesting a possible future therapeutic target for this cancer type.

B7-H6, an immunoligand for the natural killer cell activating receptor NKp30, reveals inhibitory effects on cell proliferation and migration, but not apoptosis, in cervical cancer derived-cell lines.

BACKGROUND: Although great progress has been made in treatment regimens, cervical cancer remains as one of the most common cancer in women worldwide. Studies focusing on molecules that regulate carcinogenesis may provide potential therapeutic strategies for cervical cancer. B7-H6, an activating immunoligand expressed by several tumor cells, is known to activate NK cell-mediated cytotoxicity once engaged with its natural receptor NKp30. However, the opposite, that is, the effects in the tumor cell triggered by B7-H6 after interacting with NKp30 has not yet been well explored. METHODS: In this study, we evaluated the surface expression of B7-H6 by flow cytometry. Later, we stimulated B7-H6 positive cervical cancer derived-cell lines (HeLa and SiHa) with recombinant soluble NKp30 (sNKp30) protein and evaluated biological effects using the impedance RTCA system for cell proliferation, the scratch method for cell migration, and flow cytometry for apoptosis. Cellular localization of B7-H6 was determined using confocal microscopy. RESULTS: Notably, we observed that the addition of sNKp30 to the cervical cancer cell lines decreased tumor cell proliferation and migration rate, but had no effect on apoptosis. We also found that B7-H6 is selectively maintained in tumor cell lines, and that efforts to sort and purify B7-H6 negative or positive cells were futile, as negative cells, when cultured, regained the expression of B7-H6 and B7-H6 positive cells, when sorted and cultivated, lost a percentage of B7-H6 expression. CONCLUSIONS: Our results suggest that B7-H6 has an important, as of yet undescribed, role in the biology of the cervical tumor cells themselves, suggesting that this protein might be a promising target for anti-tumor therapy in the future.

Serological and molecular study of Hepatitis E virus in pediatric patients in Mexico.

INTRODUCTION AND OBJECTIVES: Cases of viral hepatitis reported in Mexico are typically identified as hepatitis A, B and C. However, unspecified cases are reported annually. Hepatitis E virus (HEV) is an emergent agent that causes a self-limiting infection that can evolve to chronic in immunosuppressed individuals. In Mexico, HEV genotype 2 is considered endemic, though it's the prevalence is not well known. Therefore, the present study was designed to determine the prevalence of HEV among patients at the "Hospital Infantil de Mexico Federico Gomez". MATERIALS AND METHODS: The study included 99 patients, anti-HEV antibody (IgG and IgM) were detected by indirect ELISA and viral genome was identified using RT-PCR technique. Two PCR products of positive cases were sequenced. RESULTS: ELISA results were positive in 3% and 6%, for IgG and IgM respectively, 54.5% prevalence was found by PCR. Low lymphocyte count (p<0.05) and malnutrition (p<0.005) were significant factors for high PCR prevalence and could increase the possibility of infection. Two samples were sequenced and confirmed the presence of HEV genotype 3. CONCLUSIONS: This report reveals the incidence of HEV in pediatric patients in Mexico. Moreover, the identification of HEV genotype 3 in human samples suggests a potential zoonotic risk that requires further research.

Biological and toxicological evaluation of Rhus trilobata Nutt. (Anacardiaceae) used traditionally in mexico against cancer.

BACKGROUND: Rhus trilobata Nutt. (Anacardiaceae) (RHTR) is a plant of Mexico that is traditionally used as an alternative treatment for several types of cancer. However, the phytochemical composition and potential toxicity of this plant have not been evaluated to support its therapeutic use. Therefore, this study aimed to evaluate the biological activity of RHTR against colorectal adenocarcinoma cells, determine its possible acute toxicity, and analyze its phytochemical composition. METHODS: The traditional preparation was performed by decoction of stems in distilled water (aqueous extract, AE), and flavonoids were concentrated with C18-cartridges and ethyl acetate (flavonoid fraction, FF). The biological activity was evaluated by MTT viability curves and the TUNEL assay in colorectal adenocarcinoma (CACO-2), ovarian epithelium (CHO-K1) and lung/bronchus epithelium (BEAS-2B) cells. The toxicological effect was determined in female BALB/c mice after 24 h and 14 days of intraperitoneal administration of 200 mg/kg AE and FF, respectively. Later, the animals were sacrificed for histopathological observation of organs and sera obtained by retro-orbital bleeding for biochemical marker analysis. Finally, the phytochemical characterization of AE and FF was conducted by UPLC-MSE. RESULTS: In the MTT assays, AE and FF at 5 and 18 µg/mL decreased the viability of CACO-2 cells compared with cells treated with vehicle or normal cells (p ≤ 0.05, ANOVA), with changes in cell morphology and the induction of apoptosis. Anatomical and histological analysis of organs did not reveal important pathological lesions at the time of assessment. Additionally, biochemical markers remained normal and showed no differences from those of the control group after 24 h and 14 days of treatment (p ≤ 0.05, ANOVA). Finally, UPLC-MSE analysis revealed 173 compounds in AE-RHTR, primarily flavonoids, fatty acids and phenolic acids. The most abundant compounds in AE and FF were quercetin and myricetin derivates (glycosides), methyl gallate, epigallocatechin-3-cinnamate, ß-PGG, fisetin and margaric acid, which might be related to the anticancer properties of RHTR. CONCLUSION: RHTR exhibits biological activity against cancer cells and does not present adverse toxicological effects during its in vivo administration, supporting its traditional use.

An uncommon inheritance pattern in Niemann-Pick disease type C: identification of probable paternal germline mosaicism in a Mexican family.

BACKGROUND: Niemann-Pick disease type C (NP-C) is a fatal lysosomal neurodegenerative and neurovisceral disease. It is caused by defects in intracellular lipid trafficking, which lead to the accumulation of lipids and glycosphingolipids within the endosomes and lysosomes of affected individuals. Pathogenic variants of the NPC1 or NPC2 genes yield highly variable phenotypes with a time course that ranges from fetal onset (i.e., hydrops fetalis) to progressive dementia in adults. NP-C is typically inherited in an autosomal-recessive manner. To our knowledge, no previous report has identified germline mosaicism as an inheritance mechanism in NP-C. CASE PRESENTATION: We report the case of a male Mexican patient with "variant" filipin staining and a juvenile form of NP-C attributed to compound heterozygosity for two previously reported pathogenic variants of NPC1: c.[1042C>T];[2780C>T] or p.[Arg348*];[Ala927Val]. The proband's mother and healthy sister were heterozygous carriers of the c.2780C > T (exon 18) and c.1042C > T (exon 8) variants, respectively. However, direct sequencing of exons 8 and 18 of NPC1 revealed no mutation in genomic DNA obtained from the father's peripheral blood. DNA profiling ruled out the possibility of non-paternity. We were unable to obtain a sperm sample to demonstrate paternal gonadal mosaicism. NPC1 haplotype analysis using 20 linked single nucleotide variants failed to yield sufficient information to document a p.(Arg348*) NPC1 pathogenic variant-associated haplotype in the family. CONCLUSIONS: We propose that this case of NP-C involves paternal germline mosaicism. To the best of our knowledge, this has not previously been reported in NP-C.

Liver fibrosis in bile duct-ligated rats correlates with increased hepatic IL-17 and TGF-ß2 expression.

UNLABELLED: BACKGROUND AND RATIONALE FOR THE STUDY: IL-17, TGF-ß1/2 are cytokines involved in the development of kidney, pulmonary and liver fibrosis. However, their expression kinetics in the pathogenesis of cholestatic liver fibrosis have not yet been fully explored. The aim of the study was to analyze the expression of IL-17, RORγt, NKp46, TGF-ß1, and TGF-ß2 in the liver of rats with bile duct ligation (BDL). RESULTS: Hepatic IL-17A gene expression analyzed by qRT-PCR showed a dramatic increase of 350 and 10 fold, at 8 and 30 days post BDL, respectively. TGFß1 and TGFß2 gene expression significantly increased throughout the whole fibrotic process. At the protein level in liver homogenates, IL-17, TGF-ß1, and RORγt significantly increased at 8 and 30 days after BDL. Interestingly, a significant increase in the protein levels of TGF-ß2 and decrease of NKp46 was observed only 30 days after BDL. Unexpectedly, TGF-ß2 exhibited stronger signals than TGF-ß1 at the gene expression and protein levels. Histological analysis showed bile duct proliferation and collagen deposition. CONCLUSIONS: Our results suggest that pro-fibrogenic cytokines IL-17, TGF-ß1 and, strikingly, TGF-ß2 might be important players of liver damage in the pathogenesis of early and advanced experimental cholestatic fibrosis. Th17 cells might represent an important source of IL-17, while NK cell depletion may account for the perpetuation of liver damage in the BDL model.

Identification of novel gene targets and putative regulators of arsenic-associated DNA methylation in human urothelial cells and bladder cancer.

There is strong epidemiologic evidence linking chronic exposure to inorganic arsenic (iAs) to myriad adverse health effects, including cancer of the bladder. We set out to identify DNA methylation patterns associated with arsenic and its metabolites in exfoliated urothelial cells (EUCs) that originate primarily from the urinary bladder, one of the targets of arsenic-induced carcinogenesis. Genome-wide, gene-specific promoter DNA methylation levels were assessed in EUCs from 46 residents of Chihuahua, Mexico, and the relationship was examined between promoter methylation profiles and the intracellular concentrations of total arsenic and arsenic species. A set of 49 differentially methylated genes was identified with increased promoter methylation associated with EUC tAs, iAs, and/or monomethylated As (MMAs) enriched for their roles in metabolic disease and cancer. Notably, no genes had differential methylation associated with EUC dimethylated As (DMAs), suggesting that DMAs may influence DNA methylation-mediated urothelial cell responses to a lesser extent than iAs or MMAs. Further analysis showed that 22 of the 49 arsenic-associated genes (45%) are also differentially methylated in bladder cancer tissue identified using The Cancer Genome Atlas repository. Both the arsenic- and cancer-associated genes are enriched for the binding sites of common transcription factors known to play roles in carcinogenesis, demonstrating a novel potential mechanistic link between iAs exposure and bladder cancer.

An approach to the immunophenotypic features of circulating CD4⁺NKG2D⁺ T cells in invasive cervical carcinoma.

BACKGROUND: NKG2D, an activating immunoreceptor, is primarily restricted to NK cells and CD8(+) T cells. The existence of an atypical cytotoxic CD4(+)NKG2D(+) T cell population has also been found in patients with autoimmune dysfunctions. Nonetheless, contradictory evidence has categorized this population with a regulatory rather than cytotoxic role in other situations. These confounding data have led to the proposal that two distinct CD4(+)NKG2D(+) T cell subsets might exist. The immune response elicited in cervical cancer has been characterized by apparent contradictions concerning the role that T cells, in particular T-helper cells, might be playing in the control of the tumor growth. Interestingly, we recently reported a substantial increase in the frequency of CD4(+)NKG2D(+) T cells in patients with cervical intraepithelial neoplasia grade-1. However, whether this particular population is also found in patients with more advanced cervical lesions or whether they express a distinctive phenotype remains still to be clarified. In this urgent study, we focused our attention on the immunophenotypic characterization of CD4(+)NKG2D(+) T cells in patients with well-established cervical carcinoma and revealed the existence of at least two separate CD4(+)NKG2D(+) T cell subsets defined by the co-expression or absence of CD28. RESULTS: Patients with diagnosis of invasive cervical carcinoma were enrolled in the study. A group of healthy individuals was also included. Multicolor flow cytometry was used for exploration of TCR alpha/beta, CD28, CD158b, CD45RO, HLA-DR, CD161, and CD107a. A Luminex-based cytokine kit was used to quantify the levels of pro- and anti-inflammatory cytokines. We found an increased percentage of CD4(+)NKG2D(+) T cells in patients with cervical cancer when compared with controls. Accordingly with an increase of CD4(+)NKG2D(+) T cells, we found decreased CD28 expression. The activating or degranulation markers HLA-DR, CD161, and CD107a were heterogeneously expressed. The levels of IL-1beta, IL-2, TNF-alpha, and IL-10 were negatively correlated with the percentages of CD4(+)NKG2D(+) T cells in patients with cervical carcinoma. CONCLUSIONS: Taken together, our results reveal the existence of two separate CD4(+)NKG2D(+) T cell subsets defined by the co-expression or absence of CD28, the latter more likely to be present in patients with cervical cancer.

Quantitative structure-activity relationship of molecules constituent of different essential oils with antimycobacterial activity against Mycobacterium tuberculosis and Mycobacterium bovis.

BACKGROUND: Essential oils and their constituents are commonly known for their antibacterial, antifungal and antiparasitic activity, and there are also reports on the antimycobacterial properties, but more experimental data are needed for the description of the mechanism of action or structural (and molecular) properties related to the antimicrobial activity. METHODS: Twenty-five constituents of essential oils were evaluated against Mycobacterium tuberculosis H37Rv and Mycobacterium bovis AN5 by the Alamar Blue technique. Twenty compounds were modeled using in silico techniques descriptor generation and subsequent QSAR model building using genetic algorithms. The p-cymene, menthol, carvacrol and thymol were studied at the quantum mechanical level through the mapping of HOMO and LUMO orbitals. The cytotoxic activity against macrophages (J774A) was also evaluated for these four compounds using the Alamar Blue technique. RESULTS: All compounds tested showed to be active antimicrobials against M. tuberculosis. Carvacrol and thymol were the most active terpenes, with MIC values of 2.02 and 0.78 µg/mL respectively. Cinnamaldehyde and cinnamic acid were the most active phenylpropanes with MIC values of 3.12 and 8.16 µg/mL respectively. The QSAR models included the octanol-water partition (LogP) ratio as the molecular property that contributes the most to the antimycobacterial activity and the phenolic group (nArOH) as the major structural element. CONCLUSIONS: The description of the molecular properties and the structural characteristics responsible for antimycobacterial activity of the compounds tested, were used for the development of mathematical models that describe structure-activity relationship. The identification of molecular and structural descriptors provide insight into the mechanisms of action of the active molecules, and all this information can be used for the design of new structures that could be synthetized as potential new antimycobacterial agents.

Tailored nutrition education and food assistance improve adherence to HIV antiretroviral therapy: evidence from Honduras.

Food insecurity and malnutrition negatively affect adherence to antiretroviral therapy (ART) and are associated with poor HIV clinical outcomes. We examined the effect of providing household food assistance and nutrition education on ART adherence. A 12-month prospective clinical trial compared the effect of a monthly household food basket (FB) plus nutrition education (NE) versus NE alone on ART adherence on 400 HIV patients at four clinics in Honduras. Participants had been receiving ART for an average of 3.7 years and were selected because they had suboptimal adherence. Primary outcome measures were missed clinic appointments, delayed prescription refills, and self-reported missed doses of ART. These three adherence measures improved for both groups over 12 months (p < 0.01), mostly within 6 months. On-time prescription refills improved for the FB plus NE group by 19.6 % more than the group receiving NE alone after 6 months (p < 0.01), with no further change at 12 months. Change in missed appointments and self-reported missed ART doses did not significantly differ by intervention group.

Agave-Laurate-Bioconjugated Fructans Decrease Hyperinsulinemia and Insulin Resistance, Whilst Increasing IL-10 in Rats with Metabolic Syndrome Induced by a High-Fat Diet.

Metabolic syndrome (MetS) comprises a cluster of metabolic risk factors, which include obesity, hypertriglyceridemia, high blood pressure, and insulin resistance. The purpose of this study was to evaluate the effects of laurate-bioconjugated fructans on pro- and anti-inflammatory cytokines in Wistar rats with MetS induced by a high-fat diet. Laurate-bioconjugated fructans were synthesized with agave fructans, immobilized lipase B, and vinyl laureate as the acylant. Groups were fed a standard diet (NORMAL), a high-fat diet (HFD), or a high-fat diet plus laurate-bioconjugated fructans (FL PREV) for 9 weeks. A fourth group received a high-fat diet for 6 weeks, followed by simultaneous exposure to a high-fat diet and laurate-bioconjugated fructans for 3 additional weeks (FL REV). The dose of laurate-bioconjugated fructans was 130 mg/kg. Laurate-bioconjugated fructans reduced food and energy intake, body weight, body mass index, abdominal circumference, adipose tissue, adipocyte area, serum triglycerides, insulin, insulin resistance, and C-reactive protein but they increased IL-10 protein serum levels and mRNA expression. The impact of laurate-bioconjugated fructans on zoometric and metabolic parameters supports their potential as therapeutic agents to improve obesity, obesity comorbidities, insulin resistance, type 2 diabetes mellitus, and MetS.

Acute pulmonary artery dissection in an adult with chronic pulmonary hypertension secondary to congenital heart disease: a case report.

Background: D-Transposition of the great arteries (d-TGA) is characterized by the aorta positioned above the right ventricle and the pulmonary artery above the left ventricle. Acute pulmonary artery dissection (PAD) is a rare and often lethal condition. We present a case report of acute PAD in an adult with d-TGA and pulmonary hypertension. Case summary: A 49-year-old male with history of d-TGA palliated with an atrial switch (Mustard) operation, pulmonary venous baffle stenosis treated percutaneously, chronic pulmonary hypertension (mixed group 1 and 2), and severe dilatation of pulmonary arteries (pulmonary trunk of 75 mm) presented to the emergency department with chest pain and acute respiratory failure. Blood pressure was 106/78 mmHg, heart rate 93 b.p.m., and oxygen saturation 88% on room air. A computed tomography (CT) scan showed acute right PAD. He was not considered suitable for surgery nor percutaneous procedure. Epoprostenol was initiated to reduce parietal stress, but after initial stabilization, pulmonary venous stent baffle gradient increased and acute pulmonary oedema occurred. Epoprostenol was withdrawn, and furosemide was initiated, with good clinical response. A follow-up CT scan showed dissection morphological stabilization and false lumen thrombosis, and the patient was discharged. Discussion: Pulmonary hypertension and previous pulmonary artery dilatation are reported as the main underlying conditions leading to PAD. No previous cases of PAD are described in patients with history of d-TGA and atrial switch procedure. Evidence regarding the best treatment of PAD is lacking, but it seems reasonable to reduce parietal stress using pulmonary vasodilators. Nevertheless, in patients with post-capillary pulmonary hypertension, pulmonary vasodilatation may cause important pulmonary congestion.

Oxidative and Fibrinolytic Mechanisms: Two Important Processes to Consider in Platelet Storage

Objective: Platelet-rich plasma (PRP) is used in multiple coagulation disorders. Its therapeutic effectiveness relies on technical procedures related to PRP procurement and preservation because free radicals induce platelet activation and aging. This work aims to elucidate the oxidative mechanisms involved in activation of platelets obtained from PRP during storage. Materials and Methods: One hundred ten PRP batches were obtained from healthy donors and kept under stirring at a temperature of 20-24 °C. Protein extraction was performed from platelet homogenates and plasma at different times of storage from day 1 to 20. The activities of antioxidant markers such as catalase (CAT), superoxide dismutase, and ceruloplasmin, as well as fibrinolytic protein activity metalloproteases 2 and 3, plasmin, and urokinase plasminogen activator, were analyzed by zymography assays. Oxidized proteins were also determined. Results: Significant activity of antioxidant enzymes and fibrinolytic molecules was observed on day 5 of storage in PRP homogenates, which increased over time and was concomitantly correlated with oxidized protein levels. Reverse enzymatic activity patterns were observed in plasma, except for CAT, which remained unchanged. Conclusion: Storage conditions of platelets from PRP for up to 5 days induced in vitro platelet activation by oxidative damage and proteolysis. This finding confirms the need for proper management of these blood products to preserve their viability and functionality.

Human TIMP1 Is a Growth Factor That Improves Oocyte Developmental Competence.

Oocyte developmental competence is the ability of a mature oocyte to be fertilized and subsequently support embryonic development. Such competence is gained during folliculogenesis and is facilitated by the bidirectional communication into a compacted cumulus-oocyte complex (COC). Human tissue inhibitor of metalloproteinases-1 (TIMP1) participates in biological processes, including cell growth, differentiation, and apoptosis. This study aimed to evaluate the influence of TIMP1 as a growth factor on the in vitro maturation (IVM) culture of bovine COCs to improve oocyte developmental competence. All TIMP1 treatments (50, 100, and 150 ng/mL) favored the COCs' compaction structure (p < 0.05). TIMP1 at 150 ng/mL produced more oocytes in metaphase II compared to the other treatments (p < 0.05). The 150 ng/mL TIMP1 generated oocytes with the most (p < 0.05) cortical granules below the plasma membrane (pattern I). In a parthenogenesis assay, oocyte IVM in 50 ng/mL of TIMP1 produced the most blastocyst compared to the other treatments (p < 0.05). The Principal Component Analysis (PCA) showed that 50 ng/mL of TIMP1 was the best condition to develop oocyte competence because it was associated with the COC compact and cortical granule pattern I. TIMP1 influences the development of oocyte competence when added to the IVM culture medium of COCs.

Pregnancy-related aortic complications in women with bicuspid aortic valve.

OBJECTIVES: To describe the aortic-related risks associated with pregnancy in women with bicuspid aortic valve (BAV) and to evaluate changes in aortic diameter in pregnancy. METHODS: Prospective observational study of patients with BAV from a single-site registry of pregnant women with structural heart disease between 2013 and 2020. Cardiac, obstetric and neonatal outcomes were studied. An assessment of aortic dimensions was performed during pregnancy by two-dimensional echocardiography. Aortic diameters were measured at the annulus, root, sinotubular junction and maximum ascending aorta diameter, and the largest diameter was used. Measurements of the aorta were made using the end-diastolic leading edge-to-leading edge convention. RESULTS: Forty-three women (32.9 years, IQR 29.6-35.3) with BAV were included: 9 (20.9%) had repaired aortic coarctation; 23 (53.5%) had moderate or severe aortic valve disease; 5 (11.6%) had a bioprosthetic aortic valve; and 2 (4.7%) had a mechanical prosthetic aortic valve. Twenty (47.0%) were nulliparous. The mean aortic diameter in the first trimester was 38.5 (SD 4.9) mm, and that in the third trimester was 38.4 (SD 4.8) mm. Forty (93.0%) women had an aortic diameter of <45 mm; 3 (7.0%) had 45-50 mm; and none had >50 mm. Three women (6.9%) with BAV presented cardiovascular complications during pregnancy or the postpartum period (two prosthetic thrombosis and one heart failure). No aortic complications were reported. There was a small but significant increase in aortic diameter during pregnancy (third trimester vs first trimester, 0.52 (SD 1.08) mm; p=0.03). Obstetric complications appeared in seven (16.3%) of pregnancies, and there were no maternal deaths. Vaginal non-instrumental delivery was performed in 21 (51.2%) out of 41 cases. There were no neonatal deaths, and the mean newborn weight was 3130 g (95% CI 2652 to 3380). CONCLUSIONS: Pregnancy in BAV women had a low rate of cardiac complications with no aortic complications observed in a small study group. Neither aortic dissection nor need for aortic surgery was reported. A low but significant aortic growth was observed during pregnancy. Although requiring follow-up, the risk of aortic complications in pregnant women with BAV and aortic diameters of <45 mm at baseline is low.