Metformin Inhibits Zika Virus Infection in Trophoblast Cell Line.

Zika virus (ZIKV) infections have been associated with severe clinical outcomes, which may include neurological manifestations, especially in newborns with intrauterine infection. However, licensed vaccines and specific antiviral agents are not yet available. Therefore, a safe and low-cost therapy is required, especially for pregnant women. In this regard, metformin, an FDA-approved drug used to treat gestational diabetes, has previously exhibited an anti-ZIKA effect in vitro in HUVEC cells by activating AMPK. In this study, we evaluated metformin treatment during ZIKV infection in vitro in a JEG3-permissive trophoblast cell line. Our results demonstrate that metformin affects viral replication and protein synthesis and reverses cytoskeletal changes promoted by ZIKV infection. In addition, it reduces lipid droplet formation, which is associated with lipogenic activation of infection. Taken together, our results indicate that metformin has potential as an antiviral agent against ZIKV infection in vitro in trophoblast cells.

Production and Immunogenicity Assessment of LTp50: An Escherichia coli-Made Chimeric Antigen Targeting S1- and S2-Epitopes from the SARS-CoV-2/BA.5 Spike Protein.

Subunit vaccines stand as a leading approach to expanding the current portfolio of vaccines to fight against COVID-19, seeking not only to lower costs but to achieve long-term immunity against variants of concern and have the main attributes that could overcome the limitations of the current vaccines. Herein a chimeric protein targeting S1 and S2 epitopes, called LTp50, was designed as a convenient approach to induce humoral responses against SARS-CoV-2. LTp50 was produced in recombinant Escherichia coli using a conventional pET vector, recovering the expected antigen in the insoluble fraction. LTp50 was purified by chromatography (purity > 90%). The solubilization and refolding stages helped to obtain a stable protein amenable for vaccine formulation. LTp50 was adsorbed onto alum, resulting in a stable formulation whose immunogenic properties were assessed in BALB/c mice. Significant humoral responses against the S protein (BA.5 variant) were detected in mice subjected to three subcutaneous doses (10 µg) of the LTp50/alum formulation. This study opens the path for the vaccine formulation optimization using additional adjuvants to advance in the development of a highly effective anti-COVID-19 vaccine directed against the antigenic regions of the S protein, which are less prone to mutations.

Follicular Dynamics and Pregnancy Rates during Foal Heat in Colombian Paso Fino Mares Bred under Permanent Grazing.

No studies have evaluated the peripartum follicular dynamics resulting in foal heat under tropical environments. We aimed to assess retrospectively the peripartum follicular dynamics in Colombian Paso Fino mares that were inseminated at the foal heat, becoming pregnant or not. Records including follicular dynamics of pregnant mares prepartum and from foaling until foal heat ovulation were assessed in Colombian Paso Fino mares (CPF, n = 24) bred under permanent grazing in a tropical herd in Colombia. The number of ovarian follicles >10 mm before foaling and the largest follicle (F1) growth rate (mm/day) from foaling until the F1 reached the largest diameter (pre-ovulatory size) at the foal heat were assessed. Mares were inseminated at foal heat with 20 mL of semen (at least 500 million live spermatozoa) with >75% motility and 80% viability from a stallion of proven fertility. Ovulation was confirmed the day after follicles had reached the largest diameter. Quantitative data from follicular growth, the day at ovulation, from mares that became pregnant (PM) or not (NPM) at 16 days post-insemination were compared by one-way ANOVA, repeated measures ANOVA (follicle growth rate data) or Chi-square test (edema and cytology scores data). Epidemiological data, gestation length, and the number of follicles on third prepartum days did not significantly differ between PM and NPM (p > 0.05). Seventy-one percent of mares (17/24) got pregnant. Ovulatory follicles grew faster in the NPM group (n = 7), which ovulated between the seventh and ninth postpartum days, compared to PM (n = 17), which ovulated between the 11th and 13th postpartum days. Pre-ovulatory follicle diameter in PM (48.57 ± 0.8 mm) was significantly larger than in NPM (42.99 ± 1.0 mm) (p < 0.05). In addition, the PM edema score (2.93 ± 0.32 mm) on ovulation day was significantly lower (p < 0.05) than NPM (4.47 ± 0.05 mm). First postpartum ovulation occurred at 12.6 ± 0.3 and 8.5 ± 0.4 days (p < 0.05) in PM and NPM, respectively. Colombian Paso Fino mares bred under permanent grazing under tropical rainforest conditions with no foaling or postpartum complications showed a 71% gestation rate when inseminated at foal heat when ovulation occurs between the second and third postpartum week.

Adaptation to Living at High Altitude in Patients with COPD. Comparative Study of Exercise Capacity and Ventilatory Variables between Patients Residing at High and Low Altitudes in the Andes.

González-García, Mauricio and Luis Ernesto Téllez. Adaptation to living at high altitude in patients with COPD. Comparative study of exercise capacity and ventilatory variables between patients residing at high and low altitudes in the Andes. High Alt Med Biol. 00:000-000, 2024. Introduction: Although some variables related to oxygen transport and utilization such as ventilation, pulmonary vascular responses to hypoxia, heart rate (HR), cardiac output, hemoglobin (Hb), and oxygen saturation (SpO2) are used to compare adaptation to altitude between populations, peak oxygen consumption (VO2) constitutes an integrative measure of total oxygen transport that may reflect successful adaptation to altitude. We designed this study to make a direct comparison of VO2 in a cardiopulmonary exercise test (CPET) between chronic obstructive pulmonary disease (COPD) patients residing at high altitude (Bogotá, Colombia: 2,640 m) (COPD-HA) and those living at low altitude (Bucaramanga, Colombia: 959 m) (COPD-LA). Methods: All patients performed a CPET with measurements of VO2, minute ventilation (VE), HR, oxygen pulse (VO2/HR), ventilatory equivalents (VE/VCO2), and SpO2. Unpaired T-test or Mann-Whitney U test were used for comparisons between COPD-HA and COPD-LA. Results: We included 71 patients with COPD, 53 COPD-HA, and 18 COPD-LA. There were no differences between groups in age, sex, or forced expiratory volume in 1 second. The means ± SD of Hb, g/dl was slightly higher in COPD-HA (15.9 ± 1.9 vs. 14.7 ± 1.8, p = 0.048), without differences in VO2, % pred (71.6 ± 17.9 vs. 69.0 ± 17.0, p = 0.584), VO2/HR, % pred (92.1 ± 22.0 vs. 89.7 ± 19.8, p = 0.733) or VE/MVV, % (75.5 ± 14.1 vs. 76.5 ± 14.3, p = 0.790) at peak exercise between groups. Median (IQR) of VE/VCO2 nadir [38.0 (37.0-42.0) vs. 32.5 (31.0-39.0), p = 0.005] was significantly higher, and SpO2, % at rest [88.0 (86.0-91.0) vs. 95.0 (94.0-96.0), p < 0.001] and at peak exercise [84.0 (77.0-90.0) vs. 93.0 (92.0-95.0), p < 0.001] were significantly lower in COPD-HA. Conclusions: Despite higher desaturation at rest and during exercise in COPD-HA, there were no differences in VO2 peak between COPD-HA and COPD-LA, suggesting a potential altitude adaptation in those patients chronically exposed to hypoxia.

Changes in wider field swept-source OCT angiography vascular metrics with anti-vascular endothelial growth factor therapy in central retinal vein occlusion.

PURPOSE: To investigate the impact of anti-VEGF therapy on vascular metrics in eyes with macular edema secondary to central retinal vein occlusion (CRVO) using wider field swept-source OCT angiography (WF SS-OCTA). METHODS: We included 23 eyes with macular edema associated with non-ischemic CRVO from 22 patients treated with anti-VEGF therapy (median number of injections: 5 [2-9]). Changes in vessel density (VD), vessel skeletonized density (VSD), and foveal avascular zone (FAZ) parameters were measured using WF SS-OCTA. Visual acuity (VA) and central subfield thickness (CST) were also measured. RESULTS: Median CST decreased significantly from 369 µm (305-531) to 267 µm (243-300, p < 0.001). VD and VSD parameters in 12 × 12 mm images showed significant reductions. For instance, VSD in the whole retina decreased from a median of 13.37 (11.22-13.74) to 11.29 (9.36-12.97, p = 0.013). Additionally, a significant increase in FAZ circularity was found, suggesting improved microvascular integrity. Significant inverse correlations were found between the number of anti-VEGF injections and all VSD and VD parameters on the 12 × 12 mm images (p < 0.05). Notably, the reductions in VSD and VD on 12 × 12 mm angiograms in the deep capillary plexus (DCP) after each injection significantly correlated with increased logMAR VA (worse VA). CONCLUSION: Anti-VEGF therapy in CRVO patients not only mitigates macular edema but also alters the overall microvascular morphology and functionality as revealed by WF SS-OCTA.

Twisted Intramolecular Charge-Transfer State Addition to Electron-Poor Olefins.

When electron-rich arylpyrrolinium salts are irradiated with ultraviolet light in the presence of Michael acceptors, the pyrrolinyl and aryl fragments add to the activated and polarized double bond in a regioselective manner, forming two C-C bonds and fragmenting the substrate. In this paper, we present a model for this intriguing reaction, supported by spectroscopy and computational analyses, and provide evidence for rectifying previously misassigned structures. We postulate that the photochemical reaction is inefficient because the reaction between the twisted intramolecular charge-transfer state and the olefin competes with fluorescence from this state upon photon absorption. We also discuss the practical advantages of performing this photochemical reaction in a continuous flow setup. Additionally, we explore several subsequent reactions that allow us to further modify the products of the photochemical step, ultimately leading to the creation of new chemical structures.

Quantitative Contrast Sensitivity Function and the Effect of Aging in Healthy Adult Eyes: A Normative Database.

BACKGROUND AND OBJECTIVE: We sought to establish normative quantitative contrast sensitivity function (qCSF) values in healthy adult eyes and investigate the effect of age on qCSF. PATIENTS AND METHODS: Healthy eyes underwent qCSF testing (adaptive sensory technology) and Snellen's visual acuity (VA). Descriptive statistics and mixed-effects multivariable linear regressions were evaluated. RESULTS: A total of 334 eyes (290 patients) with median age 61 years (range 21 to 88) had qCSF values as follows: area under the log contrast sensitivity function curve: 1.18; contrast acuity: 1.32; contrast sensitivity (CS) at 1 cycle per degree (cpd): 1.32; CS at 1.5 cpd: 1.37; CS at 3 cpd: 1.38; CS at 6 cpd: 1.20; CS at 12 cpd: 0.69; CS at 18 cpd: 0.22. Linear reductions in qCSF values per decade of age ranged from -0.02 to -0.07 vs 0.01 for visual acuity (VA). Age had a greater effect on the majority of qCSF values than VA (beta standardized regression coefficient ranged from -0.309 to -0.141 for qCSF values vs 0.177 for VA). CONCLUSIONS: We herein establish a normative database for qCSF and quantify the effect of age on qCSF values, adding evidence towards the validation of qCSF as a clinical endpoint. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Sputum Biomarkers in Wood and Tobacco Smoke Etiotypes of Chronic Obstructive Pulmonary Disease.

Introduction: There is a need to better understand the etiotypes of chronic obstructive pulmonary disease (COPD) beyond the tobacco-smoke (TS-COPD). Wood smoke COPD (WS-COPD) is characterized by greater airway compromise, milder emphysema, and slower rate of lung function decline than TS-COPD. However, it is unclear if these two etiotypes of COPD have differences in sputum biomarker concentrations. Objective was to compare sputum levels of selected sputum biomarkers between WS-COPD and TS-COPD, and healthy controls. Methods: Eighty-eight women (69±12 years) were recruited and classified into: WS-COPD (n=31), TS-COPD (n=29) and controls (n=28). Using ELISA, we determined induced sputum levels of metalloproteinase 9 (MMP-9), chemokine ligand 5 (CCL5), interleukin-8 (IL-8), chemokine ligand 16 (CCL16/HCC-4) and vascular endothelial growth factor (VEGF-1). Differences were analyzed by Kruskal-Wallis and Mann-Whitney-U tests and correlation between airflow limitation and biomarkers by Spearman's test. Results: At similar degree of airflow obstruction, anthropometrics and medications use, the level of sputum CCL5 was higher in TS-COPD than WS-COPD (p=0.03) without differences in MMP-9, IL-8, CCL16/HCC-4, and VEGF-1. Women with WS-COPD and TS-COPD showed significantly higher sputum levels of MMP-9, IL-8 and CCL5 compared with controls (p<0.001). FEV1% predicted correlated negatively with levels of MMP-9 (rho:-0.26; P=0.016), CCL5 (rho:-0.37; P=0.001), IL-8 (rho:-0.42; P<0.001) and VEGF (rho:-0.22; P=0.04). Conclusion: While sputum concentrations of MMP-9, IL-8, and CCL5 were higher in COPD women compared with controls, women with TS-COPD had higher levels of CCL5 compared with those with WS-COPD. Whether this finding relates to differences in pathobiological pathways remains to be determined.

Tropical high altitude and severe asthma in adults: house dust mite sensitization and phenotypic distribution.

BACKGROUND: There is a lack of information on house dust mite (HDM) sensitization and phenotype distribution in patients with severe asthma (SA) living permanently at high-altitude (HA) in tropical regions, which may be different. OBJECTIVE: The aim of this study was to characterize adults with SA in a tropical high altitude city (2,640 m): Bogotá, Colombia. MATERIAL AND METHODS: This observational cross-sectional study included severe asthmatic outpatients (n = 129) referred to the ASMAIRE program of the Fundación Neumológica Colombiana in Bogotá (2,640 m). Clinical history, spirometry, total IgE, blood eosinophils, and skin prick test (SPT), including HDM allergens, were performed. Phenotype definitions: Allergic/atopic (AA): IgE ≥100 IU/mL and/or at least one positive SPT; eosinophilic (EOS): blood eosinophils ≥300 cells/µL; type 2-high: AA and/or EOS phenotype; type 2-low: non-AA/non-EOS phenotype (IgE <100 IU/mL, negative SPT, and blood eosinophils <300 cells/µL). RESULTS: A total of 129 adults with SA were included, 79.8% female. Phenotype distribution: AA: 61.2%; EOS: 37.2%; type 2-high: 72.1%; type 2-low: 27.9%. Among AA patients, HDM sensitization was present in 87% and 34.9% were non-eosinophilic. There was a significant overlap between the phenotypes. CONCLUSIONS: In contrast to non-tropical high-altitude regions, we found a high frequency of HDM sensitization in patients with AA phenotype living in a tropical high-altitude city. We also found a discrete lower frequency of EOS phenotype with no other significant differences in the phenotypic distribution compared to that described at low altitudes. We propose that tropical location may modify the effect of high altitude on HDM concentrations and allergenicity.

Core Cariology Curriculum Framework in Spanish for Latin American dental schools: development and consensus.

The aim of this study was to develop and achieve consensus on a cariology teaching framework for dental schools in Latin American Spanish-speaking countries. The Delphi process, with a ≥8 0% pre-defined participants' agreement, included three phases and a Coordinating Group. During the Preparation phase three panels of experts were selected and invited to participate: a) Regional academic/professional Dental Associations (Associations-Panel): n = 12; b) Regional Dental Schools (Dental-Schools-Panel): existing dental schools (n = 263) from the 19 Spanish-speaking regional countries; c) International academic/professional associations Peer Experts (Peer-Panel): n = 4. Based on consensus documents from Europe, Colombia, the Caribbean, USA, Chile and Spain, and updated scientific evidence, the Coordinating Group developed a baseline framework proposal of domains, main competencies (MC) and specific competencies (SC). The Consultation-Agreement and Consensus phases included three rounds of questionnaires with a step-wise sharing of the MC updated version of the consensus framework with the Dental-Schools-Panel and including SC with the Associations-Panel. Diverse communication strategies were used ( e.g ., independent google-form questionnaires and workshops). Consensus was reached after an on-site Associations-Panel workshop and secret voting, followed by an online meeting with the Peers-Panel. A total of 127 academic/professional institutions participated (Associations-Panel: 11, 91.6%; Dental-Schools-Panel: 112, 42.6%, all countries; Peers-Panel: 4, 100%). The baseline Cariology teaching framework of 5 domains, 10 MC and 92 SC underwent modifications after agreements for a final consensus framework consisting of 5 domains, 10 MC and 85 SC. A Core Cariology curriculum framework in Spanish for Latin American Dental Schools was successfully developed and agreed upon with regional dental academic and professional institutions.

Modulation of the Altered Intestinal Microbiota by Use of Antibiotics with a Novel Synbiotic on Wistar Rats.

The use of antibiotics unbalances the intestinal microbiota. Probiotics, prebiotics, and synbiotics are alternatives for these unbalances. The effects of a new synbiotic composed of probiotic Saccharomyces boulardii CNCM I-745 and fructans from Agave salmiana (fAs) as prebiotics were assessed to modulate the intestinal microbiota. Two probiotic presentations, the commercial probiotic (CP) and the microencapsulated probiotic (MP) to improve those effects, were used to prepare the synbiotics and feed Wistar rats subjected to antibiotics (AB). Eight groups were studied, including five controls and three groups to modulate the microbiota after the use of antibiotics: G5: AB + MP-synbiotic, G6: AB + CP-synbiotic, and G8: AB + fAs. All treatments were administered daily for 7 days. On days 7 and 21, euthanasia was performed, cecum tissue was recovered and used to evaluate histological analysis and to study microphotograph by TEM, and finally, bacterial DNA was extracted and 16S rRNA gene metabarcode sequencing was performed. Histological analysis showed less epithelial damage and more abundance of the intestinal microbiota in the groups G5, G6, and G8 in comparison with the AB control group after 7 days. Microphotograph of the cecum at 2 weeks post treatment showed that G5 and G6 presented beneficial effects in epithelial reconstruction. Interestingly, in the groups that used the synbiotic without AB (G3 and G4) in addition to contributing to the recovery of the autochthonous microbiota, it promotes the development of beneficial microorganisms; those results were also achieved in the groups that used the synbiotic with AB enhancing the bacterial diversity and regulating the impact of AB.

A saurischian (Archosauria, Dinosauria) ilium from the Upper Triassic of southern Brazil and the rise of Herrerasauria.

The Carnian (Upper Triassic) rocks of the Candelária Sequence present a rich record of dinosaurs, including some of the oldest known dinosaurs worldwide. In this contribution we describe the first unequivocal dinosaur from the Pivetta site, located in the Restinga Sêca municipality, Southern Brazil. The specimen CAPPA/UFSM 0373 is an isolated but well-preserved left ilium. A thorough examination of the specimen's anatomy and a phylogenetic analysis provides evidence that CAPPA/UFSM 0373 belongs to the Herrerasauria. We were able to identify several similarities with potential non-herrerasaurid herrerasaurians (e.g., Tawa hallae, "Caseosaurus crosbyensis"), which were previously only known from North American deposits. In contrast, herrerasaurids (e.g., Herrerasaurus ischigualastensis) are almost exclusively known from South America. Our results support the nesting of CAPPA/UFSM 0373 as an early-diverging herrerasaurian. Furthermore, this is potentially the first record of a non-herrerasaurid herrerasaurian in unambiguous Carnian beds, suggesting a hidden diversity of dinosaurs in the Carnian rocks of the Candelária Sequence, which can be revealed even by fragmentary specimens.

Knowledge of Vaccination Against Influenza and Pneumococcus in Patients with Chronic Obstructive Pulmonary Disease in an Integrated Care Program.

Purpose: To compare the level of knowledge in vaccination against influenza and pneumococcus of patients with chronic obstructive pulmonary disease (COPD) who are managed in an Integrated Care Program (ICP) with those who receive usual care (UC). Methods: A telephone survey of patients diagnosed with COPD registered in public care networks or private institutions was done. A descriptive and comparative analysis of the characteristics of the ICP and UC groups was carried out. The relationship between belonging to an ICP and the level of knowledge about vaccination was evaluated using Propensity Score Matching (PSM) and multivariate logistic and ordinal regression models. Results: Of 674 study participants, 27.2% were from the ICP group. ICP patients were older, more frequently men, from a higher socioeconomic stratum and a higher educational level (p<0.05). 75.5% of the patients in the ICP group had a high level of vaccination knowledge compared to 42.7% in the UC group (p<0.001). In the multivariate analysis, adjusting for sociodemographic variables, years of COPD diagnosis, and comorbidities, belonging to the ICP was associated with a higher probability of answering questions about vaccination correctly and having a high level of knowledge (OR 3.397, IC 95% 2.058-5.608, p<0.001). Conclusion: Patients with COPD managed in an ICP have a higher level of knowledge in vaccination against influenza and pneumococcus, compared to patients in usual care.

Desenlaces maternos y neonatales en gestantes con cardiopatía con evaluación única vs. evaluación semiestructurada por un equipo cardio-obstétrico / Maternal and neonatal outcomes in pregnant women with heart disease with single evaluation vs. semi-structured evaluation by a cardio-obstetric team

Resumen Introducción: Las enfermedades cardiovasculares en las gestantes son desafiantes, con alta morbimortalidad materna y perinatal, por lo que se recomienda un equipo cardio-obstétrico para su atención. Aun así, pocos datos evalúan el impacto de estos equipos. Por lo tanto, el presente estudio tiene como objetivo comparar los resultados obstétricos, maternos y neonatales del seguimiento semiestructurado (SSE) en una clínica cardio-obstétrica con respecto a un seguimiento usual o seguimiento no estructurado (SNE) en gestantes con enfermedad cardiaca. Métodos: Se realizó un registro prospectivo de gestantes con cardiopatías. Se compararon las pacientes con SSE por un equipo cardio-obstétrico, contra aquellas con evaluación única o SNE. Se calculó el riesgo de eventos según la clasificación de la Organización Mundial de la Salud modificado (OMSm) y la escala del Cardiac Disease in Pregnancy Study II (CARPREG-II) y se evaluaron los desenlaces cardiacos, obstétricos y neonatales. Resultados: Se evaluaron 168 pacientes, 37 con SSE y 131 con evaluación única (SNE). Los principales diagnósticos fueron cardiopatía congénita, arritmias y valvulopatías. La media del CARPREG-II en pacientes de SNE fue 2.48 (DE: 2.3) y en pacientes de SSE fue 3.37 (DE: 2.45; p = 0.041). La media de la OMSm en pacientes de SNE fue 2.1 (DE: 1.6) y con SSE fue 2.65 (DE: 0.95; p = 0.0052). No hubo diferencias significativas en los desenlaces cardiacos primarios (13.8% en SNE vs. 5.4% en SSE; p = 0.134), cardiacos secundarios (5.3 en SNE vs. 2.7 en SSE; p = 0.410), obstétricos (10% en SNE vs. 16.2% en SSE; p = 0.253) y neonatales (35.9% en SNE y 40.5% en SSE; p = 0.486) a pesar de que las pacientes con SSE tenían un riesgo mayor que las pacientes con SNE según las escalas de la OMSm y el CARPREG-II. Conclusiones: En gestantes con cardiopatía, un SSE comparado con un SNE por un equipo cardio-obstétrico no mostró diferencias estadísticamente significativas en los desenlaces cardiovasculares, obstétricos y neonatales, a pesar de que las pacientes con SSE tenían un riesgo significativamente más alto de desenlaces adversos por las escalas de la OMSm y el CARPREG-II. Esto sugiere que el SSE logra al menos equiparar los desenlaces a pesar del mayor riesgo de eventos adversos que tenían las pacientes de este grupo.

Abstract Introduction: Cardiovascular diseases in pregnant women are challenging, with high maternal and perinatal morbidity and mortality, so a cardio-obstetric team is recommended for their care. Even so, little data evaluates the impact of these teams. Therefore, the present study aims to compare the obstetric, maternal, and neonatal outcomes of semi-structured follow-up (SSF) in a Cardio-obstetric clinic concerning regular or unstructured follow-up (USF) in pregnant women with heart disease. Methods: A prospective registry of pregnant women with heart disease was carried out. Patients with SSF by a cardio-obstetric team were compared with those with single evaluation or USF. The risk of events was calculated according to the modified World Health Organization (mWHO) classification and the CARPREG-II scale, and cardiac, obstetric, and neonatal outcomes were evaluated. Results: One hundred sixty-eight patients were evaluated, 37 with SSF and 131 with single evaluation (USF). The primary diagnoses were congenital heart disease, arrhythmias, and valve disease. The average CARPREG-II in USF patients was 2.48 (SD 2.3); in SSF patients, it was 3.37 (SD 2.45; p = 0.041). The average of the mWHO in patients with USF was 2.1 (SD 1.6), and with SSF, it was 2.65 (SD 0.95; p = 0.0052). There were no significant differences in primary cardiac outcomes (13.8% in USF vs. 5.4% in SSF; p = 0.134), secondary cardiac (5.3% in USF vs. 2.7% in SSF; p = 0.410), obstetric (10% in USF vs. 16.2% in SSF; p = 0.253) and neonatal (35.9% in USF and 40.5% in SSF; p = 0.486) even though patients with SSF had a higher risk than patients with USF according to the mWHO and CARPREG-II scales. Conclusions: In pregnant women with heart disease, an SSF compared with a USF by a cardio-obstetric team did not show statistically significant differences in cardiovascular, obstetric, and neonatal outcomes. However, patients with SSF had a significantly higher risk of adverse outcomes due to the mWHO and CARPREG-II scales. This result suggests that the SSF achieves at least equal outcomes despite the higher risk of adverse events that patients in this group had.

New reptile shows dinosaurs and pterosaurs evolved among diverse precursors.

Dinosaurs and pterosaurs have remarkable diversity and disparity through most of the Mesozoic Era1-3. Soon after their origins, these reptiles diversified into a number of long-lived lineages, evolved unprecedented ecologies (for example, flying, large herbivorous forms) and spread across Pangaea4,5. Recent discoveries of dinosaur and pterosaur precursors6-10 demonstrated that these animals were also speciose and widespread, but those precursors have few if any well-preserved skulls, hands and associated skeletons11,12. Here we present a well-preserved partial skeleton (Upper Triassic, Brazil) of the new lagerpetid Venetoraptor gassenae gen. et sp. nov. that offers a more comprehensive look into the skull and ecology of one of these precursors. Its skull has a sharp, raptorial-like beak, preceding that of dinosaurs by around 80 million years, and a large hand with long, trenchant claws that firmly establishes the loss of obligatory quadrupedalism in these precursor lineages. Combining anatomical information of the new species with other dinosaur and pterosaur precursors shows that morphological disparity of precursors resembles that of Triassic pterosaurs and exceeds that of Triassic dinosaurs. Thus, the 'success' of pterosaurs and dinosaurs was a result of differential survival among a broader pool of ecomorphological variation. Our results show that the morphological diversity of ornithodirans started to flourish among early-diverging lineages and not only after the origins of dinosaurs and pterosaurs.

Maternal and neonatal outcomes in pregnant women with heart disease with single evaluation vs. semi-structured evaluation by a cardio-obstetric team.

INTRODUCTION: Cardiovascular diseases in pregnant women are challenging, with high maternal and perinatal morbidity and mortality, so a cardio-obstetric team is recommended for their care. Even so, little data evaluates the impact of these teams. Therefore, the present study aims to compare the obstetric, maternal, and neonatal outcomes of semi-structured follow-up (SSF) in a Cardio-obstetric clinic concerning regular or unstructured follow-up (USF) in pregnant women with heart disease. METHODS: A prospective registry of pregnant women with heart disease was carried out. Patients with SSF by a cardio-obstetric team were compared with those with single evaluation or USF. The risk of events was calculated according to the modified World Health Organization (mWHO) classification and the CARPREG-II scale, and cardiac, obstetric, and neonatal outcomes were evaluated. RESULTS: One hundred sixty-eight patients were evaluated, 37 with SSF and 131 with single evaluation (USF). The primary diagnoses were congenital heart disease, arrhythmias, and valve disease. The average CARPREG-II in USF patients was 2.48 (SD 2.3); in SSF patients, it was 3.37 (SD 2.45; p = 0.041). The average of the mWHO in patients with USF was 2.1 (SD 1.6), and with SSF, it was 2.65 (SD 0.95; p = 0.0052). There were no significant differences in primary cardiac outcomes (13.8% in USF vs. 5.4% in SSF; p = 0.134), secondary cardiac (5.3% in USF vs. 2.7% in SSF; p = 0.410), obstetric (10% in USF vs. 16.2% in SSF; p = 0.253) and neonatal (35.9% in USF and 40.5% in SSF; p = 0.486) even though patients with SSF had a higher risk than patients with USF according to the mWHO and CARPREG-II scales. CONCLUSIONS: In pregnant women with heart disease, an SSF compared with a USF by a cardio-obstetric team did not show statistically significant differences in cardiovascular, obstetric, and neonatal outcomes. However, patients with SSF had a significantly higher risk of adverse outcomes due to the mWHO and CARPREG-II scales. This result suggests that the SSF achieves at least equal outcomes despite the higher risk of adverse events that patients in this group had.

INTRODUCCIÓN: Las enfermedades cardiovasculares en las gestantes son desafiantes, con alta morbimortalidad materna y perinatal, por lo que se recomienda un equipo cardio-obstétrico para su atención. Aun así, pocos datos evalúan el impacto de estos equipos. Por lo tanto, el presente estudio tiene como objetivo comparar los resultados obstétricos, maternos y neonatales del seguimiento semiestructurado (SSE) en una clínica cardio-obstétrica con respecto a un seguimiento usual o seguimiento no estructurado (SNE) en gestantes con enfermedad cardiaca. MÉTODOS: Se realizó un registro prospectivo de gestantes con cardiopatías. Se compararon las pacientes con SSE por un equipo cardio-obstétrico, contra aquellas con evaluación única o SNE. Se calculó el riesgo de eventos según la clasificación de la Organización Mundial de la Salud modificado (OMSm) y la escala del Cardiac Disease in Pregnancy Study II (CARPREG-II) y se evaluaron los desenlaces cardiacos, obstétricos y neonatales. RESULTADOS: Se evaluaron 168 pacientes, 37 con SSE y 131 con evaluación única (SNE). Los principales diagnósticos fueron cardiopatía congénita, arritmias y valvulopatías. La media del CARPREG-II en pacientes de SNE fue 2.48 (DE: 2.3) y en pacientes de SSE fue 3.37 (DE: 2.45; p = 0.041). La media de la OMSm en pacientes de SNE fue 2.1 (DE: 1.6) y con SSE fue 2.65 (DE: 0.95; p = 0.0052). No hubo diferencias significativas en los desenlaces cardiacos primarios (13.8% en SNE vs. 5.4% en SSE; p = 0.134), cardiacos secundarios (5.3 en SNE vs. 2.7 en SSE; p = 0.410), obstétricos (10% en SNE vs. 16.2% en SSE; p = 0.253) y neonatales (35.9% en SNE y 40.5% en SSE; p = 0.486) a pesar de que las pacientes con SSE tenían un riesgo mayor que las pacientes con SNE según las escalas de la OMSm y el CARPREG-II. CONCLUSIONES: En gestantes con cardiopatía, un SSE comparado con un SNE por un equipo cardio-obstétrico no mostró diferencias estadísticamente significativas en los desenlaces cardiovasculares, obstétricos y neonatales, a pesar de que las pacientes con SSE tenían un riesgo significativamente más alto de desenlaces adversos por las escalas de la OMSm y el CARPREG-II. Esto sugiere que el SSE logra al menos equiparar los desenlaces a pesar del mayor riesgo de eventos adversos que tenían las pacientes de este grupo.

Ultrastructural and Functional Characterization of Mitochondrial Dynamics Induced by Human Respiratory Syncytial Virus Infection in HEp-2 Cells.

Human respiratory syncytial virus (hRSV) is the leading cause of acute lower respiratory tract infections in children under five years of age and older adults worldwide. During hRSV infection, host cells undergo changes in endomembrane organelles, including mitochondria. This organelle is responsible for energy production in the cell and plays an important role in the antiviral response. The present study focuses on characterizing the ultrastructural and functional changes during hRSV infection using thin-section transmission electron microscopy and RT-qPCR. Here we report that hRSV infection alters mitochondrial morphodynamics by regulating the expression of key genes in the antiviral response process, such as Mfn1, VDAC2, and PINK1. Our results suggest that hRSV alters mitochondrial morphology during infection, producing a mitochondrial phenotype with shortened cristae, swollen matrix, and damaged membrane. We also observed that hRSV infection modulates the expression of the aforementioned genes, possibly as an evasion mechanism in the face of cellular antiviral response. Taken together, these results advance our knowledge of the ultrastructural alterations associated with hRSV infection and might guide future therapeutic efforts to develop effective antiviral drugs for hRSV treatment.

On a skeletally immature individual of Unaysaurus tolentinoi (Dinosauria: Sauropodomorpha) from the upper Triassic of southern Brazil.

The lineage of sauropodomorph dinosaurs raised some of the most impressive animals that ever walked on Earth. However, the massive titans of the Mesozoic Era originated from far smaller dinosaurs. The Triassic beds from Brazil yielded the earliest part of this evolutionary history. Despite the diverse fossil record of early sauropodomorphs, juvenile specimens, as well as certain species are poorly sampled. This is the case for Unaysaurus tolentinoi, an unaysaurid sauropodomorph from Caturrita Formation (ca. 225 Ma; early Norian, Late Triassic). The holotype and only specimen of U. tolentinoi was excavated from the Água Negra Locality (São Martinho da Serra, Rio Grande do Sul, Brazil) in 1998. More than two decades later, no other fossil vertebrates have been reported from the same fossiliferous site. Here we describe a skeletally immature specimen which was found in association with the holotype of U. tolentinoi. The specimen was discovered after a first-hand examination of the holotype and comprises some isolated vertebrae and elements from the posterior autopodium. According to linear regressions, its metatarsal I is approximately 41.7 mm in length, compared to approximately 75.9 mm in the holotype. The repeated elements and reduced size indicates that it does not belong to the elements originally used to erect U. tolentinoi. Rather, the specimen is assigned to U. tolentinoi by topotypy and shared morphology. In addition to the reduced size, distinct lines of evidence (e.g., neurocentral sutures; bone texture) support its assignment to a skeletally immature individual. In sum, the new material expands the record of U. tolentinoi, and represents an additional juvenile dinosaur from the Caturrita Formation.

Prevalence of genetic mutations in alpha-1 antitrypsin deficiency (aatd) in patients with chronic obstructive pulmonary disease in Colombia.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is an underrecognized genetic disorder associated mainly with pulmonary emphysema and Chronic Obstructive Pulmonary Disease (COPD). All individuals with COPD regardless of age or ethnicity should be tested for AATD, but in Colombia its prevalence in unknown. MAIN OBJECTIVE: To determine the prevalence of the genetic mutations, present in AATD in adult patients with COPD in Colombia, using a genotyping test on cells from the oral mucosa. METHODS: This was a multicentre, observational, cross-sectional study which included adult patients attending seven COPD care centres in Colombia. Demographic data, medical history, including history of exposure to smoking and biomass smoke, most recent spirometry, pharmacological and non-pharmacological treatment received, serum AAT levels, and mutations detected by the genotyping test were recorded for all the recruited patients. For the comparison of variables between the groups with and without mutation, we used the X2 test for the qualitative variables and the Student's t-test or Mann-Whitney U test according to their distribution. MAIN FINDINGS: We collected a sample of 1,107 patients, the median age was 73.8 years (87.6-79.9). Mutations were documented in 144 patients (13.01%), the majority had the M/S mutation (78.50%), followed by M/Z (9.72%). One patient had a ZZ mutation and two patients had null alleles. In total, 23 patients had mutations associated with serum AAT deficiency (levels below 60 mg/dl). CONCLUSIONS: Genetic mutations were documented in 13.01% of patients with COPD in Colombia and 2.07% were AATD-related, showing that there is a significant number of underdiagnosed patients.

A new silesaurid from Carnian beds of Brazil fills a gap in the radiation of avian line archosaurs.

Comprising the oldest unequivocal dinosauromorphs in the fossil record, silesaurs play an important role in the Triassic radiation of dinosaurs. These reptiles provide the main source of information regarding the ancestral body plan of dinosaurs, as well as the basis for biogeographic models. Nevertheless, the co-occurrence of silesaurs and the oldest unequivocal dinosaurs is rare, which hampers reliable ecological inferences. Here we present the first species of silesaur from the oldest unequivocal dinosaur-bearing beds from Brazil. Amanasaurus nesbitti gen. et sp. nov. possesses a unique set of femoral traits among silesaurs, including the oldest occurrence of an anterior trochanter separated by the femoral shaft by a marked cleft. Its femoral length indicates that the new species rivals in size with most coeval dinosaurs. This find challenges the assumption that in faunas where silesaurs and unambiguous dinosaurs co-occurred, silesaurs were relatively smaller. Moreover, the presence of dinosaur-sized silesaurs within ecosystems with lagerpetids, sauropodomorphs and herrerasaurids reinforces the complex scenario regarding the early radiation of Pan-Aves. Silesaurs-independent of their phylogenetic position-persisted during most of the Triassic Period, with its plesiomorphic body size advancing through the dawn of dinosaurs, instead of silesaur lineages decrease in body size through time.