Discordant Perception of Disease Activity Between Providers and Adolescents with Systemic Lupus Erythematosus: A Cohort Study.

Discordance in perception of disease activity between adolescent patients with lupus and their providers may influence disease outcomes. We found that patients endorsed higher perceptions of disease activity than providers. Discordance was present at all levels of disease activity, particularly in patients with high activity, nephritis, and/or taking corticosteroids or mycophenolate mofetil.

Exon capture museomics deciphers the nine-banded armadillo species complex and identifies a new species endemic to the Guiana Shield.

The nine-banded armadillo (Dasypus novemcinctus) is the most widespread xenarthran species across the Americas. Recent studies have suggested it is composed of four morphologically and genetically distinct lineages of uncertain taxonomic status. To address this issue, we used a museomic approach to sequence 80 complete mitogenomes and capture 997 nuclear loci for 71 Dasypus individuals sampled across the entire distribution. We carefully cleaned up potential genotyping errors and cross contaminations that could blur species boundaries by mimicking gene flow. Our results unambiguously support four distinct lineages within the D. novemcinctus complex. We found cases of mito-nuclear phylogenetic discordance but only limited contemporary gene flow confined to the margins of the lineage distributions. All available evidence including the restricted gene flow, phylogenetic reconstructions based on both mitogenomes and nuclear loci, and phylogenetic delimitation methods consistently supported the four lineages within D. novemcinctus as four distinct species. Comparable genetic differentiation values to other recognized Dasypus species further reinforced their status as valid species. Considering congruent morphological results from previous studies, we provide an integrative taxonomic view to recognise four species within the D. novemcinctus complex: D. novemcinctus, D. fenestratus, D. mexicanus, and D. guianensis sp. nov., a new species endemic of the Guiana Shield that we describe here. The two available individuals of D. mazzai and D. sabanicola were consistently nested within D. novemcinctus lineage and their status remains to be assessed. The present work offers a case study illustrating the power of museomics to reveal cryptic species diversity within a widely distributed and emblematic species of mammals.

Clinical, pathological and gene expression profiling of estrogen receptor discordance in breast cancer.

BACKGROUND: Breast cancer (BC) is the world's largest tumor species in which hormone receptor-positive patients have relatively good prognosis. However, majority of patients will develop late resistance, one of the important factors is due to the loss of the original estrogen receptor (ER) expression. METHODS: We conducted this study in 115 patients with BC who experienced second biopsy at Jiangsu Province Hospital (JSPH) and divided patients into two subgroups ER + to - and ER + to + . First, clinicopathological characteristics between two groups were evaluated. Second, we explored candidate genes related to BC ER intratumor heterogeneity by applying next-generation sequencing (NGS) in 42 patients. Multi-omics integrative analysis of tumor transcriptomic, cancer-related pathway, diagnostic and prognostic value and immune profile were conducted. Besides, preliminary assay were also used to evaluate the correlation between KMT2C and ERα (ESR1) expression. The CCK-8, 5-Ethynyl-2'-deoxyuridine (EdU) assays, Transwell assays and the wound scratch tests were applied to explore the cellular interactions between KMT2C and BC. RESULTS: We find the histological type (p = 0.008) and disease-free survival (DFS) (p = 0.004) were significantly different in two subgroups. In Cox survival analysis, metastasis (Hazard ratio (HR) > 1, p = 0.007) and neo-adjuvant (HR < 1, p < 0.001) are independent prognostic factors of DFS. Besides, by analyzing NGS results, we found four genes KMT2C, FGFR19, FGF1 and FGF4 were highly mutated genes in ER + to - subgroup. Furthermore, the gene KMT2C displayed significant diagnostic value and prognostic value in BC and pan-cancer. In addition, a positive correlation between KMT2C expression and immune infiltrating levels of T cell CD4 + , macrophage and neutrophil was found. In the end, Western blot and RT-qPCR assay were used and found KMT2C and ERα (ESR1) expressions are strongly positive correlated in mRNA and protein level. Inhibition of KMT2C significantly reduced proliferation, invasion, and migration of MCF7 cells. CONCLUSION: People in two cohorts from JSPH presented different clinical characteristics and prognosis. The gene KMT2C may affect the progression of BC by regulating the molecular, epigenetic activity and immune infiltration. It may also serve as a novel prognostic biomarker for BC patients who underwent ER status converted from positive to negative.

Range-wide phylogenomics of the Great Horned Owl (Bubo virginianus) reveals deep north-south divergence in northern Peru.

The Great Horned Owl (Bubo virginianus) inhabits myriad habitats throughout the Americas and shows complex patterns of individual and geographic morphological variation. The owl family Strigidae is known to follow ecogeographic rules, such as Gloger's rule. Although untested at the species level, these ecogeographic rules may affect B. virginianus plumage coloration and body size. Previous studies have indicated that, despite this species' morphological variability, little genetic differentiation exists across parts of their range. This study uses reduced representation genome-wide nuclear and complete mitochondrial DNA sequence data to assess range-wide relationships among B. virginianus populations and the disputed species status of B. v. magellanicus (Magellanic or Lesser Horned Owl) of the central and southern Andes. We found shallow phylogenetic relationships generally structured latitudinally to the north of the central Andes, and a deep divergence between a southern and northern clade close to the Marañón Valley in the central Andes, a common biogeographic barrier. We identify evidence of gene flow between B. v. magellanicus and other subspecies based on mitonuclear discordance and F-branch statistics. Overall differences in morphology, plumage coloration, voice, and genomic divergence support species status for B. v. magellanicus.

Disparities in Postoperative Communication Patterns Among Spanish-speaking Pediatric Patients with Hydrocephalus.

OBJECTIVE: To determine if differences exist in postoperative communication patterns or healthcare use among English-speaking patients (ESPs) and Spanish-speaking patients (SSPs) with childhood hydrocephalus. STUDY DESIGN: A single-institution, retrospective cohort study was conducted. Through simple random sampling, 50 ESPs and 50 SSPs (<18 years old) who underwent a ventriculoperitoneal shunt or endoscopic third ventriculostomy were identified. Demographics, communication with clinic (eg, number of calls or messages postoperatively), and healthcare use were collected. Multiple linear regressions assessed the significance of predictors on communication frequency and use. RESULTS: SSPs were more likely to have a comorbidity and ventriculoperitoneal shunt than ESPs. SSPs had longer median postoperative length of stay (P < .01) and 30-day readmission rate (P < .01) than ESPs. Only 18% of SSPs communicated with clinic; 11 total calls or messages were from SSPs vs 57 from ESPs (P < .01). The most common reason for outreach among both cohorts was a new symptom. ESP outreach most frequently resulted in reassurance or medical course changes on an outpatient basis (30% ESPs vs 0% SSPs; P = .04), whereas SSP outreach most frequently resulted in guidance to present to the emergency department (3% ESPs vs 36% SSPs; P < .01). Language remained a significant predictor for number of calls or messages, even after adjusting for comorbidity, operation type, and insurance (P < .01). CONCLUSIONS: Despite having more complex disease, only 18% of SSPs communicated with the neurosurgical team postoperatively and were more frequently sent to the emergency department for management. Future research will explore communication barriers and preferences to ensure postoperative care is timely and patient centered.

CardIAP: calcium transients confocal image analysis tool.

One of the main topics of cardiovascular research is the study of calcium (Ca2+) handling, as even small changes in Ca2+ concentration can alter cell functionality (Bers, Annu Rev Physiol, 2014, 76, 107-127). Ionic calcium (Ca2+) plays the role of a second messenger in eukaryotic cells, associated with cellular functions such as cell cycle regulation, transport, motility, gene expression, and regulation. The use of fluorometric techniques in isolated cells loaded with Ca2+-sensitive fluorescent probes allows quantitative measurement of dynamic events occurring in living, functioning cells. The Cardiomyocytes Images Analyzer Python (CardIAP) application addresses the need to analyze and retrieve information from confocal microscopy images systematically, accurately, and rapidly. Here we present CardIAP, an open-source tool developed entirely in Python, freely available and useable in an interactive web application. In addition, CardIAP can be used as a standalone Python library and freely installed via PIP, making it easy to integrate into biomedical imaging pipelines. The images that can be generated in the study of the heart have the particularity of requiring both spatial and temporal analysis. CardIAP aims to open the field of cardiomyocytes and intact hearts image processing. The improvement in the extraction of information from the images will allow optimizing the usage of resources and animals. With CardIAP, users can run the analysis to both, the complete image, and portions of it in an easy way, and replicate it on a series of images. This analysis provides users with information on the spatial and temporal changes in calcium releases and characterizes them. The web application also allows users to extract calcium dynamics data in downloadable tables, simplifying the calculation of alternation and discordance indices and their classification. CardIAP aims to provide a tool that could assist biomedical researchers in studying the underlying mechanisms of anomalous calcium release phenomena.

Revisiting phylogeny, systematics, and biogeography of a Pleistocene radiation.

PREMISE: Pilosocereus (Cactaceae) is an important dry forest element in all subregions and transitional zones of the neotropics, with the highest diversity in eastern Brazil. The genus is subdivided into informal taxonomic groups; however, most of these are not supported by recent molecular phylogenetic inferences. This lack of confidence is probably due to the use of an insufficient number of loci and the complexity of cactus diversification. Here, we explored the species relationships in Pilosocereus in more detail, integrating multilocus phylogenetic approaches with the assessment of the ancestral range and the effect of geography on diversification shifts. METHODS: We used 28 nuclear, plastid, and mitochondrial loci from 54 plant samples of 31 Pilosocereus species for phylogenetic analyses. We used concatenated and coalescent phylogenetic trees and Bayesian models to estimate the most likely ancestral range and diversification shifts. RESULTS: All Pilosocereus species were clustered in the same branch, except P. bohlei. The phylogenetic relationships were more associated with the geographic distribution than taxonomic affinities among taxa. The genus began diversifying during the Plio-Pleistocene transition in the Caatinga domain and experienced an increased diversification rate during the Calabrian age. CONCLUSIONS: We recovered a well-supported multispecies coalescent phylogeny. Our results refine the pattern of rapid diversification of Pilosocereus species across neotropical drylands during the Pleistocene and highlight the need for taxonomic rearrangements in the genus. We recovered a pulse of diversification during the Pleistocene that was likely driven by multiple dispersal and vicariance events within and among the Caatinga, Cerrado, and Atlantic Forest domains.

Phylogenomics of the world's otters.

Comparative whole-genome analyses hold great power to illuminate commonalities and differences in the evolution of related species that share similar ecologies. The mustelid subfamily Lutrinae includes 13 currently recognized extant species of otters,1-5 a semiaquatic group whose evolutionary history is incompletely understood. We assembled a dataset comprising 24 genomes from all living otter species, 14 of which were newly sequenced. We used this dataset to infer phylogenetic relationships and divergence times, to characterize patterns of genome-wide genealogical discordance, and to investigate demographic history and current genomic diversity. We found that genera Lutra, Aonyx, Amblonyx, and Lutrogale form a coherent clade that should be synonymized under Lutra, simplifying the taxonomic structure of the subfamily. The poorly known tropical African Aonyx congicus and the more widespread Aonyx capensis were found to be reciprocally monophyletic (having diverged 440,000 years ago), supporting the validity of the former as a distinct species. We observed variable changes in effective population sizes over time among otters within and among continents, although several species showed similar trends of expansions and declines during the last 100,000 years. This has led to different levels of genomic diversity assessed by overall heterozygosity, genome-wide SNV density, and run of homozygosity burden. Interestingly, there were cases in which diversity metrics were consistent with the current threat status (mostly based on census size), highlighting the potential of genomic data for conservation assessment. Overall, our results shed light on otter evolutionary history and provide a framework for further in-depth comparative genomic studies targeting this group.

Incomplete lineage sorting and reticulate evolution mask species relationships in Brunelliaceae, an Andean family with rapid, recent diversification.

PREMISE: To date, phylogenetic relationships within the monogeneric Brunelliaceae have been based on morphological evidence, which does not provide sufficient phylogenetic resolution. Here we use target-enriched nuclear data to improve our understanding of phylogenetic relationships in the family. METHODS: We used the Angiosperms353 toolkit for targeted recovery of exonic regions and supercontigs (exons + introns) from low copy nuclear genes from 53 of 70 species in Brunellia, and several outgroup taxa. We removed loci that indicated biased inference of relationships and applied concatenated and coalescent methods to infer Brunellia phylogeny. We identified conflicts among gene trees that may reflect hybridization or incomplete lineage sorting events and assessed their impact on phylogenetic inference. Finally, we performed ancestral-state reconstructions of morphological traits and assessed the homology of character states used to define sections and subsections in Brunellia. RESULTS: Brunellia comprises two major clades and several subclades. Most of these clades/subclades do not correspond to previous infrageneric taxa. There is high topological incongruence among the subclades across analyses. CONCLUSIONS: Phylogenetic reconstructions point to rapid species diversification in Brunelliaceae, reflected in very short branches between successive species splits. The removal of putatively biased loci slightly improves phylogenetic support for individual clades. Reticulate evolution due to hybridization and/or incomplete lineage sorting likely both contribute to gene-tree discordance. Morphological characters used to define taxa in current classification schemes are homoplastic in the ancestral character-state reconstructions. While target enrichment data allows us to broaden our understanding of diversification in Brunellia, the relationships among subclades remain incompletely understood.

Localized Phylogenetic Discordance Among Nuclear Loci Due to Incomplete Lineage Sorting and Introgression in the Family of Cotton and Cacao (Malvaceae).

The economically important cotton and cacao family (Malvaceae sensu lato) have long been recognized as a monophyletic group. However, the relationships among some subfamilies are still unclear as discordant phylogenetic hypotheses keep arising when different sources of molecular data are analyzed. Phylogenetic discordance has previously been hypothesized to be the result of both introgression and incomplete lineage sorting (ILS), but the extent and source of discordance have not yet been evaluated in the context of loci derived from massive sequencing strategies and for a wide representation of the family. Furthermore, no formal methods have been applied to evaluate if the detected phylogenetic discordance among phylogenomic datasets influences phylogenetic dating estimates of the concordant relationships. The objective of this research was to generate a phylogenetic hypothesis of Malvaceae from nuclear genes, specifically we aimed to (1) investigate the presence of major discordance among hundreds of nuclear gene histories of Malvaceae; (2) evaluate the potential source of discordance; and (3) examine whether discordance and loci heterogeneity influence on time estimates of the origin and diversification of subfamilies. Our study is based on a comprehensive dataset representing 96 genera of the nine subfamilies and 268 nuclear loci. Both concatenated and coalescence-based approaches were followed for phylogenetic inference. Using branch lengths and topology, we located the placement of introgression events to directly evaluate whether discordance is due to introgression rather than ILS. To estimate divergence times, concordance and molecular rate were considered. We filtered loci based on congruence with the species tree and then obtained the molecular rate of each locus to distribute them into three different sets corresponding to shared molecular rate ranges. Bayesian dating was performed for each of the different sets of loci with the same parameters and calibrations. Phylogenomic discordance was detected between methods, as well as gene histories. At deep coalescent times, we found discordance in the position of five subclades probably due to ILS and a relatively small proportion of introgression. Divergence time estimation with each set of loci generated overlapping clade ages, indicating that, even with different molecular rate and gene histories, calibrations generally provide a strong prior.

Discordant Ca2+ release in cardiac myocytes: characterization and susceptibility to pharmacological RyR2 modulation.

Systolic Ca2+ transients are shaped by the concerted summation of Ca2+ sparks across cardiomyocytes. At high pacing rates, alterations of excitation-contraction coupling manifest as pro-arrhythmic Ca2+ alternans that can be classified as concordant or discordant. Discordance is ascribed to out-of-phase alternation of local Ca2+ release across the cell, although the triggers and consequences of this phenomenon remain unclear. Rat ventricular cardiomyocytes were paced at increasing rates. A discordance index (SD of local alternans ratios) was developed to quantify discordance in confocal recordings of Ca2+ transients. Index values were significantly increased by rapid pacing, and negatively correlated with Ca2+ transient amplitude change, indicating that discordance is an important contributor to the negative Ca2+ transient-frequency relationship. In addition, the largest local calcium transient in two consecutive transients was measured to build a potential "best release" profile, which quantitatively confirmed discordance-induced Ca2+ release impairment (DICRI). Diastolic Ca2+ homeostasis was also observed to be disrupted by discordance, as late Ca2+ release events elicited instability of resting Ca2+ levels. Finally, the effects of two RyR2 inhibitors (VK-II-86 and dantrolene) were tested. While both compounds inhibited Ca2+ wave generation, only VK-II-86 augmented subcellular discordance. Discordant Ca2+ release is a quantifiable phenomenon, sensitive to pacing frequency, and impairs both systolic and diastolic Ca2+ homeostasis. Interestingly, RyR2 inhibition can induce discordance, which should be considered when evaluating pharmacological RyR2 modulators for clinical use.

Fetal Genotype-Phenotype Sex Discordance: A Case of 5-Alpha-Reductase Deficiency.

OBJECTIVE: To describe the prenatal and postnatal diagnostic workup leading to the diagnosis of 5-alpha-reductase type 2 deficiency (5AR2D) in a case of 46,XY disorder of sex development (DSD). CASE REPORT: A first-trimester noninvasive prenatal test (NIPT) on maternal blood revealed a male fetus with a low risk of aneuploidy. However, a female fetus was identified at the second-trimester scan. A repeat sample revealed similar results and ruled out the possibility of both a sample swap or a vanishing twin. At birth, phenotypically female external genitalia were evident, with testes noted in the labioscrotal area. Neonatal blood confirmed a 46,XY complement and a 46,XY DSD genetic panel revealed a 5AR2D. CONCLUSION: Our case and others described in the literature demonstrate that fetal sex discordance detected by a combination of NIPT and subsequent ultrasound examination can be associated with several biological conditions, with DSD being the most significant.

The association between maternal and foetal factors with birth weight discordance in twins from Yucatan, Mexico.

Birth weight discordance (BWD) is not an uncommon event in twin pregnancies and can be associated with maternal and newborn characteristics. We aimed to analyse the association between maternal sociodemographic and newborn characteristics with BWD in twin infants born in Yucatan, Mexico, during 2008-2017 (n = 2091 pairs). BWD was calculated as the percentage of birth weight of the heavier twin. We defined three categories of BWD: concordant twins: <15%, mild-discordant: 15-24%, and severe discordant: ≥25%. A multinomial logistic regression model was used to analyse the association between maternal sociodemographic and newborn characteristics with BWD. Seventy-four percent (n = 1547) of twin pairs were classified as concordant, 17% (n = 356) met the criteria for mild-discordance and 9% (n = 188) for severe discordance. The odds for mild-discordance were significantly lower for mothers with medium level of education and in the highest quartile of total twin birth weight (TBW). Opposite-sex twin pairs showed increased odds for mild-discordance compared with same-sex pairs. The odds for severe discordance increased as mothers were in older age groups and decreased as TBW increased. Our rates of BWD are similar to those reported in populations from wealthier countries and maternal age and education, infants' sex, and TBW are associated with BWD.

Prevalence of Genetically Complex Leishmania Strains With Hybrid and Mito-Nuclear Discordance.

Approximately 20 Leishmania species are known to cause cutaneous, mucocutaneous, and visceral disorders in humans. Identification of the causative species in infected individuals is important for appropriate treatment and a favorable prognosis because infecting species are known to be the major determinant of clinical manifestations and may affect treatments for leishmaniasis. Although Leishmania species have been conventionally identified by multilocus enzyme electrophoresis, genetic analysis targeting kinetoplast and nuclear DNA (kDNA and nDNA, respectively) is now widely used for this purpose. Recently, we conducted countrywide epidemiological studies of leishmaniasis in Ecuador and Peru to reveal prevalent species using PCR-RFLP targeting nDNA, and identified unknown hybrid parasites in these countries together with species reported previously. Furthermore, comparative analyses of kDNA and nDNA revealed the distribution of parasites with mismatches between these genes, representing the first report of mito-nuclear discordance in protozoa. The prevalence of an unexpectedly high rate (~10%) of genetically complex strains including hybrid strains, in conjunction with the observation of mito-nuclear discordance, suggests that genetic exchange may occur more frequently than previously thought in natural Leishmania populations. Hybrid Leishmania strains resulting from genetic exchanges are suggested to cause more severe clinical symptoms when compared with parental strains, and to have increased transmissibility by vectors of the parental parasite species. Therefore, it is important to clarify how such genetic exchange influences disease progression and transmissibility by sand flies in nature. In addition, our aim was to identify where and how the genetic exchange resulting in the formation of hybrid and mito-nuclear discordance occurs.

Joint Associations of Maternal-Fetal APOL1 Genotypes and Maternal Country of Origin With Preeclampsia Risk.

RATIONALE & OBJECTIVES: Preeclampsia, which disproportionately affects Black women, is a leading cause of preterm delivery and risk for future hypertension and chronic kidney disease (CKD). Apolipoprotein L1 (APOL1) kidney risk alleles, common among Black individuals, contribute substantially to CKD disparities. Given the strong link between preeclampsia and CKD, we investigated whether maternal and fetal APOL1 risk alleles can jointly influence preeclampsia risk, and explored potential modifiers of the association between APOL1 and preeclampsia. STUDY DESIGN: Nested case-control study. SETTING & PARTICIPANTS: 426 Black mother-infant pairs (275 African Americans and 151 Haitians) from the Boston Birth Cohort. EXPOSURE: Maternal and fetal APOL1 risk alleles. OUTCOMES: Preeclampsia. ANALYTICAL APPROACH: Logistic regression models with adjustment for demographic characteristics were applied to analyze associations between fetal and maternal APOL1 risk alleles and risk of preeclampsia and to investigate the effects of modification by maternal country of origin. RESULTS: Fetal APOL1 risk alleles tended to be associated with an increased risk of preeclampsia, which was not statistically significant in the total genotyped population. However, this association was modified by maternal country of origin (P<0.05 for interaction tests): fetal APOL1 risk alleles were significantly associated with an increased risk of preeclampsia among African Americans under recessive (odds ratio [OR], 3.6 [95% CI, 1.3-9.7]; P=0.01) and additive (OR, 1.7 [95% CI, 1.1-2.6]; P=0.01) genetic models but not in Haitian Americans. Also, maternal-fetal genotype discordance at the APOL1 locus was associated with a 2.6-fold higher risk of preeclampsia (P<0.001) in African Americans. LIMITATIONS: Limited sample size in stratified analyses; self-reported maternal country of origin; pre-pregnancy estimated glomerular filtration rate (eGFR) and proteinuria data in mothers were not collected; unmeasured confounding social and/or environmental factors; no replication study. CONCLUSIONS: This study supports the hypothesis that fetal APOL1 kidney risk alleles are associated with increased risk for preeclampsia in a recessive mode of inheritance in African Americans and suggests that maternal-fetal genotype discordance is also associated with this risk. These conclusions underscore the need to better understand maternal-fetal interaction and their genetic and environmental factors as contributors to ethnic disparities in preeclampsia.

Finding complexity in complexes: Assessing the causes of mitonuclear discordance in a problematic species complex of Mesoamerican toads.

Mitonuclear discordance is a frequently encountered pattern in phylogeographic studies and occurs when mitochondrial and nuclear DNA display conflicting signals. Discordance among these genetic markers can be caused by several factors including confounded taxonomies, gene flow, and incomplete lineage sorting. In this study, we present a strong case of mitonuclear discordance in a species complex of toads (Bufonidae: Incilius coccifer complex) found in the Chortís Block of Central America. To determine the cause of mitonuclear discordance in this complex, we used spatially explicit genetic data to test species limits and relationships, characterize demographic history, and quantify gene flow. We found extensive mitonuclear discordance among the three recognized species within this group, especially in populations within the Chortís Highlands of Honduras. Our data reveal nuclear introgression within the Chortís Highlands populations that was most probably driven by cyclical range expansions due to climatic fluctuations. Though we determined introgression occurred within the nuclear genome, our data suggest that it is not the key factor in driving mitonuclear discordance in the entire species complex. Rather, due to a lack of discernible geographic pattern between mitochondrial and nuclear DNA, as well as a relatively recent divergence time of this complex, we concluded that mitonuclear discordance has been caused by incomplete lineage sorting. Our study provides a framework to test sources of mitonuclear discordance and highlights the importance of using multiple marker types to test species boundaries in cryptic species.

Discordance of Low-Density Lipoprotein Cholestrol and Non-High-Density Lipoprotein Cholestrol and Coronary Artery Disease Severity / Discordância entre Colesterol LDL e Não-HDL e Gravidade da Doença Arterial Coronária

Abstract Background: A sizeable proportion of patients have discordant low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). Objectives: We assessed the relationship between discordance of LDL-C and non-HDL-C and coronary artery disease (CAD) severity. Methods: We retrospectively evaluated the data of 574 consecutive patients who underwent coronary angiography. Fasting serum lipid profiles were recorded, SYNTAX and Gensini scores were calculated to establish CAD complexity and severity. We determined the medians for LDL-C and non-HDL-C to examine the discordance between LDL-C and non-HDL-C. Discordance was defined as LDL-C greater than or equal to the median and non-HDL-C less than median; or LDL-C less than median and non-HDL-C greater than or equal to median. A p value < 0.05 was accepted as statistically significant. Results: LDL-C levels were strongly and positively correlated with non-HDL-C levels (r = 0.865, p < 0.001) but 15% of patients had discordance between LDL-C and non-HDL-C. The percentage of patients with a Gensini score of zero or SYNTAX score of zero did not differ between discordant or concordant groups (p = 0.837, p = 0.821, respectively). Mean Gensini and SYNTAX scores, percentage of patients with Gensini score ≥20 and SYNTAX score >22 were not different from group to group (p = 0.635, p = 0.733, p = 0.799, p = 0.891, respectively). Also, there was no statistically significant correlation between LDL-C and Gensini or SYNTAX scores in any of the discordant or concordant groups. Additionally, no correlation was found between non-HDL-C and Gensini or SYNTAX score. Conclusions: While there was discordance between LDL-C and non-HDL-C (15% of patients), there is no difference regarding CAD severity and complexity between discordant and concordant groups.

Resumo Fundamento: Uma proporção considerável de pacientes apresenta níveis discordantes de colesterol de lipoproteína de baixa densidade (LDL) e de não alta densidade (não HDL). Objetivos: Avaliar a relação da discordância entre colesterol LDL e não HDL com a gravidade da doença arterial coronariana (DAC). Métodos: Avaliamos retrospectivamente os dados de 574 pacientes submetidos consecutivamente à angiografia coronariana. Foram registrados os perfis lipídicos séricos em jejum, e depois foram calculados os escores SYNTAX e Gensini para estabelecer a complexidade e a gravidade da DAC. Determinamos as medianas para colesterol LDL e não-HDL para examinar a discordância entre ambos. Discordância foi definida como LDL maior ou igual à mediana e não-HDL menor que mediana; ou LDL menor que a mediana e não-HDL maior ou igual à mediana. Valor de p < 0,05 foi aceito como estatisticamente significante. Resultados: Os níveis de colesterol LDL estiveram forte e positivamente correlacionados com os níveis de colesterol não-HDL (r = 0,865, p < 0,001), mas 15% dos pacientes apresentaram discordância entre LDL e não-HDL. A porcentagem de pacientes com escore Gensini ou SYNTAX zero não diferiu entre os grupos discordantes ou concordantes (p = 0,837, p = 0,821, respectivamente). Escores médios de Gensini e SYNTAX, porcentagem de pacientes com escore Gensini ≥ 20 e SYNTAX > 22 não foram diferentes de grupo para grupo (p = 0,635, p = 0,733, p = 0,799, p = 0,891, respectivamente). Além disso, não houve correlação estatisticamente significativa entre os escores de cholesterol LDL e Gensini ou SYNTAX em nenhum dos grupos discordantes ou concordantes. Também não foi encontrada correlação entre cholesterol não HDL e escore Gensini ou SYNTAX. Conclusões: Embora tenha havido discordância entre colesterol LDL e não-HDL (15% dos pacientes), não há diferença quanto à gravidade e complexidade da DAC entre os grupos discordantes e concordantes.

Cerebrospinal fluid pleocytosis as a predictive factor for CSF and plasma HIV RNA discordance and escape.

The aims of this study were to investigate the frequency of HIV-1 RNA level discordance between the cerebrospinal fluid (CSF) and plasma and of CSF viral escape (CVE) in patients with HIV-1 subtype C on antiretroviral therapy, and evaluate the CSF white blood cell (WBC) performance characteristics in predicting CSF discordance in HIV+ group and the frequency of cognitive impairment in individuals with CSF HIV discordance or escape. HIV-1 RNA levels were assessed in plasma and CSF samples from 68 HIV+ participants without opportunistic infection. CSF discordance was found in 7.4% and CVE in 10%, with comparable frequencies between HIV-1B and C. Twenty samples (29%) showed increased CSF WBC counts. This group had higher CSF and plasma HIV-1 RNA levels than the group with normal WBC counts (p < 0.0001 and 0.006, respectively). The odds of CSF discordance were 18 times higher for a person with CSF WBC count of > 5 cells/mm3 than the group with normal CSF WBC count. CSF WBC counts (cut-off of 15 cells/mm3) showed high-performance characteristics as a predictive biomarker of CSF discordance (AUC the ROC curve 0.98). The frequency of cognitive impairment for CSF escape or discordance was 83% and 80%. The odds of cognitive impairment in these groups were 19 and 15 times higher than those for an HIV(-) person. Viral discordance or escape in the CNS occurs at a comparable frequency for HIV-1C and HIV-1B. The CSF WBC count was effective as a predictive biomarker of CSF and plasma discordance.

The roles of vicariance and dispersal in the differentiation of two species of the Rhinella marina species complex.

The high levels of Neotropical biodiversity are commonly associated with the intense Neogene-Quaternary geological events and climate dynamics. Here, we investigate the evolutionary history of two species of Neotropical closely related amphibians (R. horribilis and R. marina). We combine published data with new mitochondrial DNA sequences and multiple nuclear markers, including 12 microsatellites. The phylogenetic analyses showed support for grouping the samples in two main clades; R. horribilis (Central America and Mexico) and R. marina (South America east of the Andes). However, the phylogenetic inferences also show an evident mito-nuclear discordance. We use Approximate Bayesian Computation (ABC) to test the role of different events in the diversification between the two groups recovered. We found that both species were affected primarily by a recent Pleistocene divergence, which was similar to the divergence estimate revealed by the Isolation-with-Migration model, under persistent bidirectional gene flow through time. We provide the first evidence that R. horribilis is differentiated from the South American R. marina at the nuclear level supporting the taxonomic status of R. horribilis, which has been controversial for more than a century.

Parity and gonotrophic discordance of females of Aedes aegypti and Aedes albopictus (Diptera: Culicidae) in the city of São Paulo, SP, Brazil.

The objective of this study was to assess the parity, presence of blood in the stomach, and the gonotrophic discordance of females of Aedes aegypti and Aedes albopictus captured in two areas of the city of São Paulo. The captures were undertaken monthly, by aspiration, in the period from January, 2015 to August, 2017. All the females of the two species had their midguts and ovaries dissected to determine the presence of blood and the parity/stage of maturation. With regard to parity, 27% and 34% of the females of Ae. aegypti and Ae. albopictus, respectively, were parous or were in advanced stages of the development of their ovaries (33% and 27%, respectively). The larger part of the females of Ae. aegypti and Ae. albopictus contained blood in their stomachs (77% and 60%, respectively), beyond which 36% and 27% of the females of Ae. aegypti and Ae. albopictus, respectively, were in gonotrophic discordance. Our results indicate favorable conditions in the study areas because of the presence of parous females. Moreover, this frequent and multiple contact of Ae. aegypti and Ae. albopictus females with vertebrate hosts, such as humans, increases the possibility of transmitting the viruses they may be carrying.