Leaf Endophytes Relationship with Host Metabolome Expression in Tropical Gymnosperms.

Plant-microbe interactions play a pivotal role in shaping host fitness, especially concerning chemical defense mechanisms. In cycads, establishing direct correlations between specific endophytic microbes and the synthesis of highly toxic defensive phytochemicals has been challenging. Our research delves into the intricate relationship between plant-microbe associations and the variation of secondary metabolite production in two closely related Zamia species that grow in distinct habitats; terrestrial and epiphytic. Employing an integrated approach, we combined microbial metabarcoding, which characterize the leaf endophytic bacterial and fungal communities, with untargeted metabolomics to test if the relative abundances of specific microbial taxa in these two Zamia species were associated with different metabolome profiles. The two species studied shared approximately 90% of the metabolites spanning diverse biosynthetic pathways: alkaloids, amino acids, carbohydrates, fatty acids, polyketides, shikimates, phenylpropanoids, and terpenoids. Co-occurrence networks revealed positive associations among metabolites from different pathways, underscoring the complexity of their interactions. Our integrated analysis demonstrated to some degree that the intraspecific variation in metabolome profiles of the two host species was associated with the abundance of bacterial orders Acidobacteriales and Frankiales, as well as the fungal endophytes belonging to the orders Chaetothyriales, Glomerellales, Heliotiales, Hypocreales, and Sordariales. We further associate individual metabolic similarity with four specific fungal endophyte members of the core microbiota, but no specific bacterial taxa associations were identified. This study represents a pioneering investigation to characterize leaf endophytes and their association with metabolomes in tropical gymnosperms, laying the groundwork for deeper inquiries into this complex domain.

In vitro evaluation of methanol extracts of edible fungi Pleurotus ostreatus and Lentinula edodes against Rhyssomatus nigerrimus Fahraeus.

The study aimed to evaluate the insecticidal activity of extracts of edible mushrooms Pleurotus ostreatus and Lentinula edodes against Rhyssomatus nigerrimus. Methanol:water extracts (70:30) of P. ostreatus and L. edodes were made and evaluated in two in vitro tests (exposure and immersion toxic effect) against R. nigerrimus. Subsequently, the toxicity test of the extracts against Artemia salina was evaluated. These extracts were subjected to colorimetric tests and gas chromatography-mass spectrometry. The results showed a mortality effect against R. nigerrimus of 50% for the P. ostreatus 2 extracts at a concentration of 20% in the immersion test. Likewise, in the toxic effect test, 90% mortality was observed after five days of exposure to a concentration of 10%. On the other hand, for the toxicity test, the extract that showed the values with the highest mortality against A. salina was P. ostreatus, starting with 80% mortality at 100µg/mL. The functional groups present in the extracts were saponins, coumarins, and alkaloids. Furthermore, the presence of more than 7 compounds in the mushroom extracts evaluated is reported. This study demonstrates the insecticidal activity of P. ostreatus and L. edodes fungal extracts and indicates the importance of using different in vitro tests to elucidate the mechanism of action for future studies.

Comprehensive phylogenomic time tree of bryophytes reveals deep relationships and uncovers gene incongruences in the last 500 million years of diversification.

PREMISE: Bryophytes form a major component of terrestrial plant biomass, structuring ecological communities in all biomes. Our understanding of the evolutionary history of hornworts, liverworts, and mosses has been significantly reshaped by inferences from molecular data, which have highlighted extensive homoplasy in various traits and repeated bursts of diversification. However, the timing of key events in the phylogeny, patterns, and processes of diversification across bryophytes remain unclear. METHODS: Using the GoFlag probe set, we sequenced 405 exons representing 228 nuclear genes for 531 species from 52 of the 54 orders of bryophytes. We inferred the species phylogeny from gene tree analyses using concatenated and coalescence approaches, assessed gene conflict, and estimated the timing of divergences based on 29 fossil calibrations. RESULTS: The phylogeny resolves many relationships across the bryophytes, enabling us to resurrect five liverwort orders and recognize three more and propose 10 new orders of mosses. Most orders originated in the Jurassic and diversified in the Cretaceous or later. The phylogenomic data also highlight topological conflict in parts of the tree, suggesting complex processes of diversification that cannot be adequately captured in a single gene-tree topology. CONCLUSIONS: We sampled hundreds of loci across a broad phylogenetic spectrum spanning at least 450 Ma of evolution; these data resolved many of the critical nodes of the diversification of bryophytes. The data also highlight the need to explore the mechanisms underlying the phylogenetic ambiguity at specific nodes. The phylogenomic data provide an expandable framework toward reconstructing a comprehensive phylogeny of this important group of plants.

Acute fetal cardiovascular adaptation to artificial placenta in sheep model.

OBJECTIVE: To describe the acute cardiovascular adaptation of the fetus after connection to an artificial placenta (AP) in a sheep model, using ultrasound and invasive and non-invasive hemodynamic assessment. METHODS: This was an experimental study of 12 fetal sheep that were transferred to an AP system, consisting of a pumpless circuit with umbilical cord connection, at 109-117 days' gestation. The study was designed to collect in-utero and postcannulation measurements in all the animals. The first six consecutive fetuses were fitted with intravascular catheters and perivascular probes to obtain invasive physiological data, including arterial and venous intravascular pressures and perivascular blood flows, with measurements taken in utero and at 5 and 30 min after cannulation. These experiments were designed with a survival goal of 1-3 h. The second set of six fetuses were not fitted with catheters, and experiments were aimed at 3-24 h of survival. Echocardiographic assessment of cardiac anatomy and function, as well as measurements of blood flow and pre- and postmembrane pressures recorded by circuit sensors in the AP system, were available for most of the fetuses. These data were acquired in utero and at 30 and 180 min after cannulation. RESULTS: Compared with in-utero conditions, the pulsatility index at 30 and 180 min after connection to the AP system was reduced in the umbilical artery (median, 1.36 (interquartile range (IQR), 1.06-1.50) vs 0.38 (IQR, 0.31-0.50) vs 0.36 (IQR, 0.29-0.41); P < 0.001 for extreme timepoints) and the ductus venosus (median, 0.50 (IQR, 0.41-0.67) vs 0.29 (IQR, 0.22-0.33) vs 0.36 (IQR, 0.22-0.41); P = 0.011 for extreme timepoints), whereas umbilical venous peak velocity increased (median, 20 cm/s (IQR, 18-22 cm/s) vs 39 cm/s (IQR, 31-43 cm/s) vs 43 cm/s (IQR, 34-54 cm/s); P < 0.001 for extreme timepoints) and flow became more pulsatile. Intravascular monitoring showed that arterial and venous pressures increased transiently after connection, with median values for mean arterial pressure at baseline, 5 min and 30 min of 43 mmHg (IQR, 35-54 mmHg), 72 mmHg (IQR, 61-77 mmHg) and 58 mmHg (IQR, 50-64 mmHg), respectively (P = 0.02 for baseline vs 5 min). Echocardiography showed a similar transient elevation of fetal heart rate at 30 and 180 min after connection compared with in utero (median, 145 bpm (IQR, 142-156 bpm) vs 188 bpm (IQR, 171-209 bpm) vs 175 bpm (IQR, 165-190 bpm); P = 0.001 for extreme timepoints). Fetal cardiac structure and function were mainly preserved; median values for right fractional area change were 36% (IQR, 34-41%) in utero, 38% (IQR, 30-40%) at 30 min and 37% (IQR, 33-40%) at 180 min (P = 0.807 for extreme timepoints). CONCLUSIONS: Connection to an AP system resulted in a transient fetal hemodynamic response that tended to normalize over hours. In this short-term evaluation, cardiac structure and function were preserved. However, the system resulted in non-physiologically elevated venous pressure and pulsatile flow, which should be corrected to avoid later impairment of cardiac function. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Halo sign in fetal cytomegalovirus infection: cerebral imaging abnormalities and postmortem histopathology in 35 infected fetuses.

OBJECTIVE: To evaluate the correlation of periventricular echogenic halo (halo sign) with histopathological findings and its association with other brain imaging abnormalities in fetuses with cytomegalovirus (CMV) infection. METHODS: This was a retrospective study of fetuses diagnosed with severe CMV infection based on central nervous system (CNS) abnormalities seen on ultrasound, which had termination of pregnancy (TOP) or fetal demise at a single center from 2006 to 2021. All included cases had been evaluated by conventional complete fetal autopsy. A maternal-fetal medicine expert reanalyzed the images from the transabdominal and transvaginal neurosonography scans, blinded to the histological findings. The halo sign was defined as the presence of homogeneous periventricular echogenicity observed in all three fetal brain orthogonal planes (axial, parasagittal and coronal). Cases were classified according to whether the halo sign was the only CNS finding (isolated halo sign) or concomitant CNS anomalies were present (non-isolated halo sign). An expert fetal radiologist reanalyzed magnetic resonance imaging (MRI) examinations when available, blinded to the ultrasound and histological results. Hematoxylin-eosin-stained histologic slides were reviewed independently by two experienced pathologists blinded to the neuroimaging results. Ventriculitis was classified into four grades (Grades 0-3) according to the presence and extent of inflammation. Brain damage was categorized into two stages (Stage I, mild; Stage II, severe) according to the histopathological severity and progression of brain lesions. RESULTS: Thirty-five CMV-infected fetuses were included in the study, of which 25 were diagnosed in the second and 10 in the third trimester. One fetus underwent intrauterine demise and TOP was carried out in 34 cases. The halo sign was detected on ultrasound in 32 (91%) fetuses (23 in the second trimester and nine in the third), and it was an isolated sonographic finding in six of these cases, all in the second trimester. The median gestational age at ultrasound diagnosis of the halo sign was similar between fetuses in which this was an isolated and those in which it was a non-isolated CNS finding (22.6 vs 24.4 weeks; P = 0.10). In fetuses with a non-isolated halo sign, the severity of additional ultrasound findings was not associated with the trimester at diagnosis, except for microencephaly, which was more frequent in the second compared with the third trimester (10/18 (56%) vs 1/8 (13%); P = 0.04). With respect to histopathological findings, ventriculitis was observed in all fetuses with an isolated halo sign, but this was mild (Grade 1) in the majority of cases (4/6 (67%)). Extensive ventriculitis (Grade 2 or 3) was more frequent in fetuses with a non-isolated halo sign (21/26 (81%)) and those without a periventricular echogenic halo (2/3 (67%); P = 0.032). All fetuses with an isolated halo sign were classified as histopathological Stage I with no signs of brain calcifications, white-matter necrosis or cortical injury. On the other hand, 25/26 fetuses with a non-isolated halo sign and all three fetuses without a periventricular echogenic halo showed severe brain lesions and were categorized as histopathological Stage II. Among fetuses with a non-isolated halo, histological brain lesions did not progress with gestational age, although white-matter necrosis was more frequent, albeit non-significantly, in fetuses diagnosed in the second vs the third trimester (10/15 (67%) vs 3/11 (27%); P = 0.06). CONCLUSIONS: In CMV-infected fetuses, an isolated periventricular echogenic halo was observed only in the second trimester and was associated with mild ventriculitis without signs of white-matter calcifications or necrosis. When considering pregnancy continuation, detailed neurosonographic follow-up complemented by MRI examination in the early third trimester is indicated. The prognostic significance of the halo sign as an isolated finding is still to be determined. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Brain cortical maturation assessed by magnetic resonance imaging in unaffected or mildly affected fetuses with cytomegalovirus infection.

OBJECTIVES: To assess by magnetic resonance imaging (MRI) the cortical maturation pattern in fetuses with cytomegalovirus (CMV) infection with mild or no abnormalities on ultrasound (US) and MRI, and to establish possible differences compared with healthy controls. METHODS: This was a retrospective case-control study of consecutive pregnancies with a CMV-infected fetus undergoing prenatal MRI as a complementary diagnostic tool in two centers, and a control group of singleton low-risk pregnancies without fetal structural abnormalities, with normal fetal growth and with healthy newborns. CMV infection was confirmed by extraction of CMV-DNA from fetal and neonatal samples. Only fetuses with mild (mildly affected) or no (unaffected) neuroimaging abnormalities on US and MRI were included. MRI measurements of fetal parieto-occipital sulcus, cingulate sulcus and calcarine sulcus depth, Sylvian fissure depth and Sylvian fissure angles were performed and cortical development grading of specific cortical areas and sulci were assessed by one operator who was blinded to CMV infection status. Data were compared between controls and fetuses with CMV infection, using linear regression and non-parametric trend analysis. RESULTS: Twenty-four CMV-infected fetuses (seven unaffected and 17 mildly affected) and 24 healthy controls that underwent fetal MRI between 27 and 36 weeks' gestation were included. Compared with controls, CMV-infected fetuses showed significantly larger median lateral ventricular width (right side, 7.8 (interquartile range (IQR), 5.9-9.9) mm vs 3.9 (IQR, 2.6-5.3) mm; left side, 7.5 (IQR, 6.0-10.9) mm vs 4.2 (IQR, 3.2-5.3) mm), significantly decreased parieto-occipital sulcus depth (right side, 12.6 (IQR, 11.3-13.5) mm vs 15.9 (IQR, 13.5-17.3) mm; left side, 12.3 (IQR, 10.6-13.5) mm vs 16.0 (IQR, 13.3-17.5) mm) and calcarine sulcus depth (right side, 15.4 (IQR, 14.4-16.3) mm vs 17.5 (IQR, 16.1-18.7) mm; left side, 14.6 (IQR, 14.1-15.6) mm vs 16.7 (IQR, 15.6-18.9) mm) (P < 0.001 for all). Compared with controls, CMV-infected fetuses also had significantly smaller upper (right side, 42.8° (IQR, 35.8-45.8°) vs 48.9° (IQR, 38.4-64.7°); left side, 40.9° (IQR, 34.2-45.8°) vs 48.2° (IQR, 41.9-60.7°)) and lower (right side, 41.6° (IQR, 34.4-49.2°) vs 48.9° (IQR, 40.6-60.9°); left side, 42.2° (IQR, 38.8-46.9°) vs 48.9° (IQR, 39.5-57.5°)) Sylvian fissure angles (P < 0.05 for all). In addition, the mildly affected CMV-infected fetuses had a significantly lower cortical development grading in the temporal and parietal areas, and the parieto-occipital and calcarine sulci compared with healthy fetuses (P < 0.05). These differences persisted when adjusting for gestational age, ipsilateral atrium width, fetal gender and when considering small-for-gestational age as a confounding factor. CONCLUSIONS: Unaffected and mildly affected CMV-infected fetuses showed delayed cortical maturation compared with healthy controls. These results suggest that congenital CMV infection, even in non-severely affected fetuses that are typically considered of good prognosis, could be associated with altered brain cortical structure. Further research is warranted to better elucidate the correlation of these findings with neurodevelopmental outcomes. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

New data on efficacy of valacyclovir in secondary prevention of maternal-fetal transmission of cytomegalovirus.

OBJECTIVE: Congenital cytomegalovirus (CMV) infection is the leading cause of non-genetic hearing and neurological deficits. The aim of our study was to evaluate the efficacy and safety of valacyclovir (VCV) treatment in preventing CMV transmission to the fetus after maternal primary infection. METHODS: This was a retrospective, multicenter study evaluating the rate of maternal-fetal CMV transmission in pregnancies with maternal primary CMV infection treated with VCV at a dosage of 8 g per day (VCV group) compared with a control group of untreated women. Each case underwent virological testing to confirm maternal primary infection and to provide accurate dating of onset of infection. The primary outcome was the presence of congenital CMV infection at birth diagnosed based on polymerase chain reaction analysis of saliva, urine and/or blood samples. The efficacy of VCV treatment was assessed using logistic regression analysis adjusted for a propensity score. RESULTS: In total, 143 patients were included in the final analysis, of whom 59 were in the VCV group and 84 were in the untreated control group. On propensity-score-adjusted analysis, VCV treatment was significantly associated with an overall reduction in the rate of maternal-fetal CMV transmission (odds ratio, 0.40 (95% CI, 0.18-0.90); P = 0.029). The rate of maternal-fetal CMV transmission, determined at birth, in the VCV vs control group was 7% (1/14) vs 10% (1/10) after periconceptional maternal primary infection (P = 1.00), 22% (8/36) vs 41% (19/46) after first-trimester maternal primary infection (P = 0.068) and 25% (2/8) vs 52% (14/27) after second-trimester maternal primary infection (P = 0.244). When analyzing the efficacy of VCV treatment according to maternal viremia at treatment initiation, there was a trend towards greater efficacy when patients were viremia-positive (21% vs 43%; P = 0.072) compared with when they were viremia-negative (22% vs 17%; P = 0.659). Maternal side effects associated with VCV were mild and non-specific in most cases. CONCLUSION: Our findings indicate that VCV treatment of pregnant women with primary CMV infection reduces the risk of maternal-fetal transmission of CMV and may be effective in cases with primary infection in the first and second trimesters. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Nematicidal activity of leaf extract of Moringa oleifera Lam. against Haemonchus contortus and Nacobbus aberrans.

In the present study, the nematicidal activity of a Moringa oleifera ethyl acetate leaf extract against the eggs and larvae of Haemonchus contortus and Nacobbus aberrans, nematodes of agricultural importance, was evaluated. The experimental design for the evaluation of the effects against both nematodes consisted of eight treatments (n = 4). Distilled water, Tween (4%) and a commercial anthelmintic agent (ivermectin, 5 mg/mL) were used as controls, and for treatments 4-8, the concentrations of the extract were 20, 10, 5, 2.5 and 1.25 mg/mL, respectively. Readings were taken at 12 h and 24 h for N. aberrans and 48 h and 72 h for H. contortus post-treatment under an optical microscope (10× and 40×). The data obtained were analysed by analysis of variance through a completely randomized factorial design using the SAS V9 program. The results show that, for H. contortus egg hatching, 85.88% inhibition was obtained at a concentration of 20 mg/mL at 48 h, while for third-stage larva (L3) mortality, the highest percentage was 68.19% at 1.25 mg/mL at 72 h. In the case of N. aberrans, the greatest inhibition of egg hatching was 90.69% at 5 mg/mL at 12 h post-treatment, and for larval mortality, it was 100% at 10 mg/mL at 24 h post-treatment. The main major compounds identified by qualitative analysis and by gas chromatography coupled to mass spectrometry were 9,12,15-octadecatrienoic acid, (Z,Z,Z)-, n-hexadecanoic acid and 2,4-di-tert-butylphenol, and the minor compounds included phytol, γ-sitosterol and α-tocopheryl acetate. It was demonstrated that the ethyl acetate leaf extract of M. oleifera Lam. shows great potential for combating agricultural nematodes.

A novel thylakoid-less isolate fills a billion-year gap in the evolution of Cyanobacteria.

Cyanobacteria have played pivotal roles in Earth's geological history, especially during the rise of atmospheric oxygen. However, our ability to infer the early transitions in Cyanobacteria evolution has been limited by their extremely lopsided tree of life-the vast majority of extant diversity belongs to Phycobacteria (or "crown Cyanobacteria"), while its sister lineage, Gloeobacteria, is depauperate and contains only two closely related species of Gloeobacter and a metagenome-assembled genome. Here, we describe a new cultured member of Gloeobacteria, Anthocerotibacter panamensis, isolated from a tropical hornwort. Anthocerotibacter diverged from Gloeobacter over 1.4 Ga ago and has low 16S rDNA identities with environmental samples. Our ultrastructural, physiological, and genomic analyses revealed that this species possesses a unique combination of traits that are exclusively shared with either Gloeobacteria or Phycobacteria. For example, similar to Gloeobacter, it lacks thylakoids and circadian clock genes, but the carotenoid biosynthesis pathway is typical of Phycobacteria. Furthermore, Anthocerotibacter has one of the most reduced gene sets for photosystems and phycobilisomes among Cyanobacteria. Despite this, Anthocerotibacter is capable of oxygenic photosynthesis under a wide range of light intensities, albeit with much less efficiency. Given its key phylogenetic position, distinct trait combination, and availability as a culture, Anthocerotibacter opens a new window to further illuminate the dawn of oxygenic photosynthesis.

Intrathecal Administration of an Anti-nociceptive Non-CpG Oligodeoxynucleotide Reduces Glial Activation and Central Sensitization.

Inflammatory pain associates with spinal glial activation and central sensitization. Systemic administration of IMT504, a non-CpG oligodeoxynucleotide originally designed as an immunomodulator, exerts remarkable anti-allodynic effects in rats with complete Freund´s adjuvant (CFA)-induced hindpaw inflammation. However, the anti-nociceptive mechanisms of IMT504 remain unknown. Here we evaluated whether IMT504 blocks inflammatory pain-like behavior by modulation of spinal glia and central sensitization. The study was performed in Sprague Dawley rats with intraplantar CFA, and a single lumbosacral intrathecal (i.t.) administration of IMT504 or vehicle was chosen to address if changes in glial activation and spinal sensitization relate to the pain-like behavior reducing effects of the ODN. Naïve rats were also included. Von Frey and Randall-Selitto tests, respectively, exposed significant reductions in allodynia and mechanical hypersensitivity, lasting at least 24 h after i.t. IMT504. Analysis of electromyographic responses to electrical stimulation of C fibers showed progressive reductions in wind-up responses. Accordingly, IMT504 significantly downregulated spinal glial activation, as shown by reductions in the protein expression of glial fibrillary acidic protein, CD11b/c, Toll-like receptor 4 (TLR4) and the phosphorylated p65 subunit of NFκB, evaluated by immunohistochemistry and western blot. In vitro experiments using early post-natal cortical glial cultures provided further support to in vivo data and demonstrated IMT504 internalization into microglia and astrocytes. Altogether, our study provides new evidence on the central mechanisms of anti-nociception by IMT504 upon intrathecal application, and further supports its value as a novel anti-inflammatory ODN with actions upon glial cells and the TLR4/NFκB pathway. Intrathecal administration of the non-CpG ODN IMT504 fully blocks CFA-induced mechanical allodynia and hypersensitivity, in association with reduced spinal sensitization. Administration of the ODN also results in downregulated gliosis and reduced TLR4-NF-κB pathway activation. IMT504 uptake into astrocytes and microglia support the concept of direct modulation of CFA-induced glial activation.

Population genomics of a reindeer lichen species from North American lichen woodlands.

PREMISE: Lichens are one of the main structural components of plant communities in the North American boreal biome. They play a pivotal role in lichen woodlands, a large ecosystem situated north of the closed-crown forest zone, and south of the forest-tundra zone. In Eastern Canada (Quebec), there is a remnant LW found 500 km south of its usual distribution range, in the Parc National des Grands-Jardins, originated mainly because of wildfires. We inferred the origin of the lichen Cladonia stellaris from this LW and assessed its genetic diversity in a postfire succession. METHODS: We genotyped 122 individuals collected across a latitudinal gradient in Quebec. Using the software Stacks, we compared four different approaches of locus selection and single-nucleotide polymorphism calling. We identified the best fitting approach to investigate population structure and estimate genetic diversity of C. stellaris. RESULTS: Populations in southern Quebec are not genetically different from those of northern LWs. The species consists of at least four phylogenetic lineages with elevated levels of genetic diversity and low co-ancestry. In Parc National des Grands-Jardins, we reported high values of genetic diversity not related with time since fire disturbance and low genetic differentiation among populations with different fire histories. CONCLUSIONS: This first population genomic study of C. stellaris is an important step forward to understand the origin and biogeographic patterns of lichen woodlands in North America. Our findings also contribute to the understanding of the effect of postfire succession on the genetic structure of the species.

Trend of in-hospital deaths by pulmonary embolism in Ecuador. Findings from 2011-2018 national reports.

BACKGROUND: Pulmonary embolism (PE) is a potentially fatal disease related to venous thromboembolism. Information regarding this pathology in the Ecuadorian population is limited. This study aims to present the PE hospital mortality rates (HMR) in Ecuador, analyze its trend and risk factors. METHODS: An epidemiological, descriptive and cross-sectional study based on the reporting and trend analysis of pulmonary embolism HMR in the Ecuadorian population from 2011 to 2018 through the governmental database of the Ecuadorian National Statistics and Census Institute, was conducted. RESULTS: In Ecuador, PE hospital discharges (HD) varied from 358 in 2011 to 424 in 2018. More than 60% of patients were older than 60 years. Also, the frequency of PE with acute cor pulmonale increased from 3.07% in 2011 to 16.98% in 2018 (P<0.05). The HMR by 100 HD increased between 2011 (12.85/100 HD) and 2018 (17.02/100 HD) (P<0.05), with the highest rate reported in 2017 (21.52/100 HD). In the period studied, 505 in-hospital deaths were reported in patients with PE, the average age in this group was 64.3 years, 58.42% were female, and 10.89% had acute cor pulmonale (ICD-10 I26.0). Risk factors associated with PE in-hospital death were acute cor pulmonale (OR 1.63, 95% CI: 1.18 to 2.25, P<0.01) and 60 years or more (OR 1.73, 95% CI 1.40-2.15, P<0.01). CONCLUSION: A significant increase in PE HMR in Ecuador was found. Also, acute cor pulmonale and age of 60 years or more may be potential risk factors for in-hospital death in patients with PE.

Population Genomics and Phylogeography of a Clonal Bryophyte With Spatially Separated Sexes and Extreme Sex Ratios.

The southern Appalachian (SA) is one of the most biodiversity-rich areas in North America and has been considered a refugium for many disjunct plant species, from the last glacial period to the present. Our study focuses on the SA clonal hornwort, Nothoceros aenigmaticus J. C. Villarreal & K. D. McFarland. This hornwort was described from North Carolina and is widespread in the SA, growing on rocks near or submerged in streams in six and one watersheds of the Tennessee (TR) and Alabama (AR) Rivers, respectively. Males and female populations occur in different watersheds, except in the Little Tennessee (TN) River where an isolated male population exists ca. 48 km upstream from the female populations. The sex ratio of 1:0 seems extreme in each population. In this study, we use nuclear and organellar microsatellites from 250 individuals from six watersheds (seven populations) in the SA region and two populations from Mexico (23 individuals). We, then, selected 86 individuals from seven populations and used genotyping by sequencing to sample over 600 bi-allelic markers. Our results suggest that the SA N. aenigmaticus and Mexican plants are a nested within a clade of sexual tropical populations. In the US populations, we confirm an extreme sex ratio and only contiguous US watersheds share genotypes. The phylogenetic analysis of SNP data resolves four clusters: Mexican populations, male plants (Little Pigeon and Pigeon river watersheds) and two clusters of female plants; one from the Little Tennessee and Hiwassee Rivers (TR) and the other from the Ocoee (TR) and Coosa (AR) Rivers. All clusters are highly differentiated (Fst values over 0.9). In addition, our individual assignment analyses and PCAs reflect the phylogenetic results grouping the SA samples in three clades and recovering males and female plants with high genetic differentiation (Fst values between 0.5 and 0.9 using microsatellites and bi-allelic markers). Our results point to Pleistocene events shaping the biogeographical pattern seen in US populations. The extreme sex ratio reflects isolation and highlights the high vulnerability of the populations in the SA.

Immunopathogenesis of canine chronic ulcerative stomatitis.

Canine Chronic Ulcerative Stomatitis is a spontaneously occurring inflammatory disease of the oral mucosa. An immune-mediated pathogenesis is suspected though not yet proven. We have recently reported on the clinical and histologic features, and identification of select leukocyte cell populations within the lesion. A clinical and histologic similarity to oral lichen planus of people was proposed. In the present study, these initial observations are extended by examining lesions from 24 dogs with clinical evidence of chronic ulcerative stomatitis. Because dogs with chronic ulcerative stomatitis often have concurrent periodontal disease, we wondered if dental plaque/biofilm may be a common instigator of inflammation in both lesions. We hypothesized that dogs with chronic ulcerative stomatitis would exhibit a spectrum of pathologic changes and phenotype of infiltrating leukocytes that would inform lesion pathogenesis and that these changes would differ from inflammatory phenotypes in periodontitis. Previously we identified chronic ulcerative stomatitis lesions to be rich in FoxP3+ and IL17+ cells. As such, we suspect that these leukocytes play an important role in lesion pathogenesis. The current study confirms the presence of moderate to large numbers of FoxP3+ T cells and IL17+ cells in all ulcerative stomatitis lesions using confocal immunofluorescence. Interestingly, the majority of IL17+ cells were determined to be non-T cells and IL17+ cell frequencies were negatively correlated with severity on the clinical scoring system. Three histologic subtypes of ulcerative stomatitis were determined; lichenoid, deep stomatitis and granulomatous. Periodontitis lesions, like stomatitis lesions, were B cell and plasma cell rich, but otherwise differed from the stomatitis lesions. Direct immunofluorescence results did not support an autoantibody-mediated autoimmune disease process. This investigation contributes to the body of literature regarding leukocyte involvement in canine idiopathic inflammatory disease pathogenesis.

La práctica oftalmológica en México del siglo xviii / The practice of ophthalmology in Mexico in the 18th century

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Effect of omega-3 fatty acids supplementation during pregnancy on lung function in preschoolers: a clinical trial.

RATIONALE: Prenatal omega-3 fatty acids improve alveolarization, diminish inflammation, and improve pulmonary growth, but it is unclear whether these outcomes translate into improved postnatal lung function. OBJECTIVE: We assessed the effect of prenatal supplementation with docosahexaenoic acid (DHA) on offspring lung function through 60 months of age. METHODS: We included a cohort of 772 Mexican preschoolers whose mothers participated in a clinical trial (NCT00646360) of supplementation with DHA or a placebo from week 18-22 of gestation through delivery. MEASUREMENTS: The children were followed after birth and anthropometric measurements and forced oscillation tests were performed at 36, 48, and 60 months of age. The effect of DHA was tested using a longitudinal mixed effect models. RESULTS: Overall, mean (Standard Deviation) of the measurements of respiratory system resistance and respiratory system reactance at 6, 8, and 10 Hz during follow up period were 11.3 (2.4), 11.1 (2.4), 10.3 (2.2) and -5.2 (1.6), -4.8 (1.7), -4.6 (1.6), respectively. There were no significant differences in pulmonary function by treatment group. DHA did not affect the average lung function or the trajectories through 60 months. CONCLUSIONS: Prenatal DHA supplementation did not influence pulmonary function in this cohort of Mexican preschoolers.

Added value of chromosomal microarray analysis over conventional karyotyping in stillbirth work-up: systematic review and meta-analysis.

OBJECTIVE: To assess the added value of chromosomal microarray analysis (CMA) over conventional karyotyping to assess the genetic causes in stillbirth. METHODS: To identify relevant studies, published in English or Spanish and without publication time restrictions, we performed a systematic search of PubMed, SCOPUS and ISI Web of Science databases, The Cochrane Library and the PROSPERO register of systematic reviews, for case series of fetal loss ≥ 20 weeks of gestation, with normal or suspected normal karyotype, undergoing CMA and with at least five subjects analyzed. To investigate quality, two reviewers evaluated independently the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. For the meta-analysis, the incremental yield of CMA over karyotyping was assessed by single-proportion analysis using a random-effects model (weighting by inverse variance). We assessed heterogeneity between studies and performed a sensitivity analysis and a subgroup analysis of structurally abnormal (malformed or growth-restricted) and normal fetuses. RESULTS: Included in the meta-analysis were seven studies involving 903 stillborn fetuses which had normal karyotype. The test success rate achieved by conventional cytogenetic analysis was 75%, while that for CMA was 90%. The incremental yield of CMA over conventional karyotyping based on the random-effects model was 4% (95% CI, 3-5%) for pathogenic copy-number variants (pCNVs) and 8% (95% CI, 4-17%) for variants of unknown significance. Subgroup analysis showed a 6% (95% CI, 4-10%) incremental yield of CMA for pCNVs in structurally abnormal fetuses and 3% (95% CI, 1-5%) incremental yield for those in structurally normal fetuses. The pCNV found most commonly was del22q11.21. CONCLUSIONS: CMA, incorporated into the stillbirth work-up, improves both the test success rate and the detection of genetic anomalies compared with conventional karyotyping. To achieve a genetic diagnosis in stillbirth is particularly relevant for the purpose of counseling regarding future pregnancies. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Valor añadido del análisis de microarrays cromosómicos sobre el cariotipado convencional en el estudio de éxitus fetal: revisión sistemática y metaanálisis OBJETIVO: Evaluar el valor añadido del análisis de microarrays cromosómicos (AMC) sobre el cariotipado convencional para evaluar las causas genéticas en el éxitus fetal. MÉTODOS: Para identificar estudios relevantes, publicados en inglés o español y sin restricciones de tiempo de la publicación, se realizó una búsqueda sistemática en las bases de datos PubMed, SCOPUS e ISI Web of Science, The Cochrane Library y el registro de revisiones sistemáticas PROSPERO, para series de casos de pérdida fetal ≥ 20 semanas de gestación, con cariotipo normal o presuntamente normal, sometidos a AMC y con al menos cinco sujetos analizados. Para investigar la calidad, dos revisores evaluaron de forma independiente el riesgo de sesgo mediante la herramienta Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Para el metaanálisis, se evaluó el rendimiento incremental del AMC sobre el cariotipado mediante un análisis de proporción única que empleó un modelo de efectos aleatorios (ponderación por varianza inversa). Se evaluó la heterogeneidad entre los estudios y se realizó un análisis de sensibilidad y un análisis de subgrupos de fetos estructuralmente anómalos (con malformación o con restricción del crecimiento) y normales. RESULTADOS: En el metaanálisis se incluyó siete estudios que comprendían 903 casos de éxitus fetal con cariotipo normal. La tasa de éxito de la prueba alcanzada mediante el análisis citogenético convencional fue del 75%, mientras que la del AMC fue del 90%. El rendimiento incremental del AMC sobre el cariotipado convencional en el modelo de efectos aleatorios fue del 4% (IC 95%, 3-5%) para las variantes patógenas del número de copias (VNCp) y del 8% (IC 95%, 4-17%) para las variantes de significancia desconocida. El análisis de subgrupos mostró un rendimiento incremental del AMC del 6% (IC 95%, 4-10%) para los fetos estructuralmente anormales y del 3% (IC 95%, 1-5%) para los fetos estructuralmente normales. La VNCp encontrada más comúnmente fue del22q11.21. CONCLUSIONES: El AMC, incorporado en el estudio del éxitus fetal, mejora tanto la tasa de éxito de las pruebas como la detección de anomalías genéticas en comparación con el cariotipado convencional. El diagnóstico genético en el éxitus fetal es especialmente relevante para el asesoramiento en futuros embarazos.

Genome-wide organellar analyses from the hornwort Leiosporoceros dussii show low frequency of RNA editing.

Because hornworts occupy a pivotal position in early land colonization as sister to other bryophytes, sister to tracheophytes, or sister to all other land plants, a renewed interest has arisen in their phylogenetic diversity, morphology, and genomes. To date, only five organellar genome sequences are available for hornworts. We sequenced the plastome (155,956 bp) and mitogenome (212,153 bp) of the hornwort Leiosporoceros dussii, the sister taxon to all hornworts. The Leiosporoceros organellar genomes show conserved gene structure and order with respect to the other hornworts and other bryophytes. Additionally, using RNA-seq data we quantified the frequency of RNA-editing events (the canonical C-to-U and the reverse editing U-to-C) in both organellar genomes. In total, 109 sites were found in the plastome and 108 in the mitogenome, respectively. The proportion of edited sites corresponds to 0.06% of the plastome and 0.05% of the mitogenome (in reference to the total genome size), in contrast to 0.58% of edited sites in the plastome of Anthoceros angustus (161,162 bp). All edited sites in the plastome and 88 of 108 sites in the mitogenome are C-to-U conversions. Twenty reverse edited sites (U-to-C conversions) were found in the mitogenome (17.8%) and none in the plastome. The low frequency of RNA editing in Leiosporoceros, which is nearly 88% less than in the plastome of Anthoceros and the mitogenome of Nothoceros, indicates that the frequency of RNA editing has fluctuated during hornwort diversification. Hornworts are a pivotal land plant group to unravel the genomic implications of RNA editing and its maintenance despite the evident evolutionary disadvantages.