Distribution Of Phenotypes Research Articles

Surveillance of multi-drug resistance phenotypes in Staphylococcus aureus in Japan and correlation with whole-genome sequence findings

Antimicrobial resistance in Staphylococcus aureus imposes a high disease burden. Both phenotypic and genotypic monitoring are key to understanding and containing emerging resistant strains. Phenotypic monitoring of emerging resistance in S.aureus and correlation of priority strain phenotypes with whole-genome sequencing (WGS) findings. Antimicrobial susceptibility test results of >40,000 isolates from 213 participating hospitals from 2011 to 2019 were exported from the national Japan Nosocomial Infections Surveillance (JANIS) database. Longitudinal and geographic distribution and prevalence of distinct multi-drug resistance phenotypes ('resistance profiles') of S.aureus were examined among hospitals and prefectures. We further conducted a genome sequence analysis of strains with specific resistance profiles of concern. The overall prevalence of meticillin-resistant S.aureus (MRSA) decreased from 40.3% to 35.1% from 2011 to 2019. However, among dozens of S.aureus resistance profiles, only one profile of a type of MRSA, exhibited a statistically significant increase in inpatient frequency, exceeding 10% during the nine years. This MRSA profile showed resistance to oxacillin, erythromycin and levofloxacin. Analysis of WGS results of S.aureus isolates with this phenotype revealed that most belonged to clonal complex 8, and all carried SCCmec IV, typical of community-acquired MRSA. Tracking distinct resistance profiles deepened our understanding of the overall decrease in MRSA and led to recognition of the emergence of a new resistance phenotype. This study provides a model for future epidemiological research on antimicrobial resistance correlating multi-drug resistance phenotypes with selective genome sequencing, which can be applied to other bacterial species.

Clinical value of positive BET and pelvic floor dyssynergia in Chinese patients with functional defecation disorder

Background Functional defecation disorder (FDD) is a common subtype of functional constipation (FC). Balloon expulsion test (BET) and high resolution anorectal manometry (HR-ARM) are significant tools but their results are not always consistent. Aims To investigate the characteristics of patients with positive BET and pelvic floor dyssynergia (PFD) and explore the value of both positive results in FDD diagnosis. Methods We retrospectively diagnosed FC subtypes and enrolled FDD patients based on Rome-IV criteria. They underwent HR-ARM, BET and CTT tests. Then they were classified to two groups and further stratified by FDD subtypes. Validated questionnaires were applied to investigate patients’ constipation, anxiety/depression and quality of life. Results 335 FDD patients were finally enrolled. They were classified into two groups according to whether BET and PFD were both positive (consistent or not). 84.48% showed consistent results. These patients had significantly higher anal residual pressure, lower anal relaxation rate, manometric defecation index (MDI) and a more negative rectoanal pressure gradient (RAPG) (Ps < .05). The specific distribution of FDD phenotypes in two groups showed significant difference (p = .021). Males suffered a more negative RAPG (p < .001) and age was correlated with anal relaxation rate (p < .001). A subset (177 individuals) was investigated with validated questionnaires. Scores for Defecation Symptoms, Physical Discomfort and GAD-7 score were significantly high in Consistent Group (Ps < .05). GAD-7 score was associated with Defecation Symptoms (p < .001) while anal residual pressure, GAD-7 and Defecation Symptoms score were linked to Physical Discomfort (Ps < .05). The diagnostic specificity and PPV for FDD rose significantly with positive BET and PFD. Conclusion FDD patients with positive BET and PFD suffered from severe defecation symptoms, anxiety and impaired QOL. Positive BET and PFD could be an ideal tool for screening FDD.

Latent CMV makes older adults less naïve.

There is a widespread general consensus that protective immunity against infectious disease in older people is less effective than in younger adults, due to “immunosenescence”.1 There has been considerable controversy as to whether latent infection with human herpesviruses (HHV), particularly HHV5 (cytomegalovirus, CMV), seminally contributes to this state of immunosenescence. While it is clear that CMV-infected-vs-non-infected individuals display markedly different distributions of diverse immune cell phenotypes in the blood, the clinical implications of these findings remain unclear.

Abstract P3-19-29: Polygenic risk scores predict toxicities in racially diverse breast cancer patients following radiotherapy

Abstract Purpose: Fatigue, fibrosis, and breast asymmetry are the most common side effects of radiotherapy, experienced in up to 40% of survivors long term. Due to the prevalence of these toxicities, a number of patient, tumor, and treatment-related characteristics have been studied in an attempt to identify at risk individuals. Additionally, several single nucleotide polymorphisms (SNPs) such as those that reside in gene TGFB1 have been associated with long-term breast fibrosis following radiotherapy by genome-wide association studies (GWAS). However, these findings are often not consistently replicated in various cohorts, particularly those with racially diverse patients, indicating that these significant SNPs (with p &amp;lt; 5e-8) or clinical factors alone may not provide enough information to determine individual risk for radiation-related toxicities. We hypothesized that the Polygenic Risk Scores (PRS) derived from the GWAS summary statistics of a larger number of potentially significant SNPs (e.g. with p-values &amp;lt; 0.05) have the potential to improve risk prediction, especially by using GWAS data of a racially diverse cohort. Methods: We conducted three prospective, longitudinal studies of breast cancer patients treated with whole breast radiotherapy with or without regional nodal irradiation. In all studies, fatigue, skin thickening, and breast asymmetry were assessed before and 12-18 months post radiotherapy using the following identical measures: percentage breast retraction assessment (pBRA) calculated from digital photographs, skin thickening objectively measured on ultrasound images (STRA), and fatigue assessed by the Multidimensional Fatigue Symptom Inventory (MFI) 20-item scale. We profiled genome-wide SNP data from peripheral blood samples of enrolled patients (n=176; 44% African Ancestry; 56% European Ancestry) by Affymetrix arrays and then imputed these genotyped SNPs to 1000 Genome Phase III reference panel. Genotyped or imputed SNPs with imputation R2&amp;gt;0.3 with minor allele frequency (MAF) &amp;gt; 5% (~10M) were analyzed in our GWAS with baseline, post radiotherapy, and changes in pBRA, STRA, and MFI. GWAS was first conducted separately in African and European ancestry samples, and then combined by meta-analysis for baseline and post radiotherapy measurements. Joint GWAS was conducted on all samples for the change phenotypes as we observed no heterogeneous phenotype distribution for samples of different ancestries. PRS was derived using the GWAS summary statistics for each phenotype. Results: Twelve independent significant SNPs were identified for baseline and post radiotherapy measurements in pBRA, STRA, and MFI, all of which were identified only in patients of African and not European ancestry due to low MAF &amp;lt; 5%. All post radiotherapy PRS were significantly correlated with the corresponding baseline (r&amp;gt;0.29, p &amp;lt; 0.05) and change PRS (r&amp;gt;0.19, p &amp;lt;0.05). Importantly, PRS accounted for 76%, 73%, and 79% of the variance of changes in pBRA, STRA, and MFI after radiation. When clinical (e.g. breast volume and age) and treatment-related factors (e.g. radiation dose, chemotherapy treatment) were added as additional covariates to the respective PRS, the prediction R2 increased to 92%, 96%, and 96% for changes in pBRA, STRA, and MFI, respectively. Conclusions: Our findings indicate that over 70% of the variation in fatigue, skin thickening and breast asymmetry changes experienced by breast cancer patients after radiotherapy may be explained by PRS, which can be derived from our GWAS summary statistics and SNP data profiled from blood samples prior to radiotherapy. Genome-wide significant risk SNPs of baseline and post radiotherapy measurements of pBRA, STRA, and MFI were found only in samples of patients of African ancestry. Future studies aimed at replicating our findings in larger cohorts are needed. Citation Format: Mylin Ann Torres, Tian Liu, Boran Zhou, Xiaofeng Yang, Gabrielle Brown, India Green, Jolinta Lin, Andrew H Miller, Jingjing Yang. Polygenic risk scores predict toxicities in racially diverse breast cancer patients following radiotherapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-29.

Sex-Specific Impact of Different Obesity/Metabolic Phenotypes on Long-Term Cardiovascular Outcomes in Acute Coronary Syndrome Patients.

Obesity, a major risk factor for acute coronary syndrome (ACS), is a multifaceted disease with different metabolic phenotypes and sex-specific features. Here, we evaluated the long-term cardiovascular risk by different obesity/metabolic phenotypes and by sex in ACS patients. The occurrence of the composite outcome of death, nonfatal reinfarction with or without PCI and/or stroke was evaluated in 674 patients (504 men; 170 women), consecutively hospitalized for ACS and followed-up for 7 years, who were stratified in metabolically healthy (MHNW) and unhealthy normal weight (MUNW), and in metabolically healthy (MHO) and unhealthy obese (MUO) groups. At baseline, 54.6% of patients were included in the MHNW group, 26.4% in the MUNW, 5.9% in the MHO and 13.1% in the MUO, with no sex-differences in the distribution of phenotypes. The overall rate of major outcome (100 person-years) in the reference group (MHNW) was higher in men than in women (RR: 1.19 vs. 0.6). The Kaplan–Meier curves for cumulative survival free from cardiovascular events according to obesity/metabolic status diverged significantly according to sex (log rank test, p = 0.006), this effect being more prominent in men (log 11.20; p = 0.011), than in women (log 7.98; p = 0.047). Compared to MHNW, the risk increased in obese men (RR: 2.2; 95% 1.11–1.54 in MUO group), whereas in women the risk was confined to metabolically unhealthy subjects (RR: 3.2; 95% CI 1.23–9.98, MUNW group). Our data show a sex-specific impact of obesity phenotypes on long-term cardiovascular risk in patients hospitalized for ACS.

Recruitment of IL-1β-producing intermediate monocytes enhanced by C5a contributes to the development of malignant pleural effusion.

BackgroundMonocytes are involved in tumor growth and metastasis, but the distribution of monocyte phenotypes and their role in the development of malignant pleural effusion (MPE) remains unknown.MethodsA total of 94 MPE patients (76 diagnosed with adenocarcinoma lung cancer and 18 with squamous cell lung cancer) and 102 volunteers for health examination in Xiangya Hospital from December 2016 to December 2019 were included in the study.ResultsThe distribution of monocyte subtypes identified by the expression of CD14 and CD16 were analyzed by flow cytometry. The proportion of CD14++CD16+ intermediate monocytes were significantly increased in pleural effusion of MPE patients. The complement system components were assayed by immunohistochemistry and ELISA, and higher expression of the classical and alternative pathways were detected in malignant pleural tissue. Transwell assay further revealed that C5a enhanced the infiltration of intermediate monocytes into the pleural cavity by promoting CCL2 production in pleural mesothelial cells (PMCs). In addition, C5a promoted the secretion of IL‐1β by intermediate monocytes. Furthermore, C5a activated in intermediate monocytes and IL‐1β released after C5a stimulation by monocytes promoted the proliferation, migration, adhesion, and epithelial‐to‐mesenchymal transition (EMT) of tumor cells, and attenuated tumor cell apoptosis.ConclusionsC5a, activated by the classical and alternative pathways of the complement system, not only mediated the infiltration of intermediate monocytes by enhancing CCL2 production in PMCs but also induced IL‐1β release from the recruited monocytes in MPE. The consequence of C5a activation and the subsequent IL‐1β overexpression in intermediate monocytes contributed to MPE progression.

Predicting the genomic resolution of bulk segregant analysis.

Bulk segregant analysis is a technique for identifying the genetic loci that underlie phenotypic trait differences. The basic approach is to compare two pools of individuals from the opposing tails of the phenotypic distribution, sampled from an interbred population. Each pool is sequenced and scanned for alleles that show divergent frequencies between the pools, indicating potential association with the observed trait differences. Bulk segregant analysis has already been successfully applied to the mapping of various quantitative trait loci in organisms ranging from yeast to maize. However, these studies have typically suffered from rather low mapping resolution, and we still lack a detailed understanding of how this resolution is affected by experimental parameters. Here, we use coalescence theory to calculate the expected genomic resolution of bulk segregant analysis for a simple monogenic trait. We first show that in an idealized interbreeding population of infinite size, the expected length of the mapped region is inversely proportional to the recombination rate, the number of generations of interbreeding, and the number of genomes sampled, as intuitively expected. In a finite population, coalescence events in the genealogy of the sample reduce the number of potentially informative recombination events during interbreeding, thereby increasing the length of the mapped region. This is incorporated into our model by an effective population size parameter that specifies the pairwise coalescence rate of the interbreeding population. The mapping resolution predicted by our calculations closely matches numerical simulations and is surprisingly robust to moderate levels of contamination of the segregant pools with alternative alleles. Furthermore, we show that the approach can easily be extended to modifications of the crossing scheme. Our framework will allow researchers to predict the expected power of their mapping experiments, and to evaluate how their experimental design could be tuned to optimize mapping resolution.

New genomic regions associated with white mold resistance in dry bean using a MAGIC population.

Dry bean (Phaseolus vulgaris L.) production in many regions is threatened by white mold (WM) [Sclerotinia sclerotiorum (Lib.) de Bary]. Seed yield losses can be up to 100% under conditions favorable for the pathogen. The low heritability, polygenic inheritance, and cumbersome screening protocols make it difficult to breed for improved genetic resistance. Some progress in understanding genetic resistance and germplasm improvement has been accomplished, but cultivars with high levels of resistance are yet to be released. A WM multiparent advanced generation inter-cross (MAGIC) population (n = 1060) was developed to facilitate mapping and breeding efforts. A seedling straw test screening method provided a quick assay to phenotype the population for response to WM isolate 1980. Nineteen MAGIC lines were identified with improved resistance. For genome-wide association studies (GWAS), the data was transformed into three phenotypic distributions-quantitative, polynomial, and binomial-and coupled with ∼52,000 single-nucleotide polymorphisms (SNPs). The three phenotypic distributions identified 30 significant genomic intervals [-log10 (P value) ≥ 3.0]. However, across distributions, four new genomic regions as well as two regions previously reported were found to be associated with resistance. Cumulative R2 values were 57% for binomial distribution using 13 genomic intervals, 41% for polynomial using eight intervals, and 40% for quantitative using 11 intervals. New resistant germplasm as well as new genomic regions associated with resistance are now available for further investigation.

Recommendations for COPD management in Central and Eastern Europe

ABSTRACT Introduction The Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy report provides guidance on effective management of chronic obstructive pulmonary disease (COPD) according to local healthcare systems. However, COPD is a heterogenous disease and certain aspects, including prevalence, disease–time course and phenotype distribution, can differ between countries. Moreover, features of clinical practice and healthcare systems for patients with COPD can vary widely, even in geographically close and economically similar countries. Areas covered Based on an initial workshop of respiratory physicians from eleven countries across Central and Eastern Europe (CEE) in December 2018 and subsequent discussions, this article offers region-specific insights from clinical practice and healthcare systems in CEE. Taking recommendations from the GOLD 2022 report into account, we suggest approaches to adapt these into national clinical guidelines for COPD management in CEE. Expert opinion Several factors should be considered when optimizing management of COPD in CEE compared with other regions, including differences in smoking status, vaccination uptake, prevalence of tuberculosis and nontuberculous mycobacteria, and variations in healthcare systems. We provide guidance and algorithms for pharmacologic and non-pharmacologic management of COPD for the following scenarios: initial and follow-up treatment, treatment of patients with frequent exacerbations, and withdrawal of inhaled corticosteroids where appropriate.

Targeting of the alphav beta3 integrin complex by CAR-T cells leads to rapid regression of diffuse intrinsic pontine glioma and glioblastoma

BackgroundDiffuse intrinsic pontine glioma (DIPG) and glioblastoma (GBM) are two highly aggressive and generally incurable gliomas with little therapeutic advancements made in the past several decades. Despite immense initial success...

From dietary adaptation in the past to drug metabolism of today: An example of NAT genes in the Croatian Roma

AbstractObjectivesThe evolutionary mechanisms that shape the genetic structure of a population left their mark on genes that metabolize drugs. The Roma are an example of a population in which the migrations, isolation, and multiple founder effects have affected its genetic structure. In this study, we investigated NAT1 and NAT2 genes, members of the xenobiotic‐metabolizing NAT gene family in three Roma groups from Croatia to explore the specificities of the Roma population in relation to other populations.Materials and MethodsSeven SNPs in the NAT1 gene and seven in the NAT2 gene were genotyped in 439 Roma from Croatia, members of three socio‐culturally different and geographically distant groups (two groups of Vlax/Bayash Roma and one Balkan Roma group). Intra‐ and inter‐population variation was assessed in the Roma and 2504 individuals from the 1000 Genomes project database.ResultsThe distribution of haplotypes differed significantly between the Roma groups for NAT2, but not for NAT1. Translation of NAT2 diplotypes into acetylation phenotypes showed significant differences between populations. The Roma from Balkan had the highest frequency of slow acetylators among the studied populations. In the overall worldwide sample, population differentiation was higher for NAT2 than for NAT1 haplotypes consistent with pairwise genetic distances that were smaller for NAT1 than for NAT2. The Ewens–Watterson test results suggest that NAT1 is subjected to directional selection, while NAT2 is evolving neutrally.ConclusionThe distribution of variations within NAT genes in the Croatian Roma population is similar to that in the surrounding European populations. The significantly different distribution of NAT2 gene haplotypes and consequent phenotypes between the three investigated Roma groups is probably the result of genetic drift due to different demographic history and socio‐cultural isolation. The highest frequency of slow acetylators in Balkan Roma compared to the world populations makes them more prone to develop a NAT gene‐related adverse drug reaction than other populations.

Distribution characteristics of antibiotic resistance bacteria and related genes in urban recreational lakes replenished by different supplementary water source.

The distribution characteristics of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in urban recreational water from different water-supply sources might be different. In this study, water samples were collected to detect the antibiotic resistance of heterotrophic bacteria to five antibiotics, and the content, phenotype, gene type and species distribution of resistant bacteria were analyzed. The results showed that the changes of bacteria resistance rate in two lakes to five kinds of antibiotics were synchronous with time, and it would reach its maximum in autumn. The detection of ARGs and int I in 80 resistance strains showed that the detection rate of tetG, tetA and int I was high. Here, 51.25% of the bacteria were doubly resistant to AMP-CTX. The 80 isolate strains were of nine genera and 19 species, among which Bacillus cereus, Escherichia coli, Aeromonas veronii, Aeromonas caviae and Raoultella ornithinolytica were the common ARB species in two lakes. Correlation analysis showed that the water temperature was significantly correlated with the content of ARB in sulfamethoxazole (SMZ) and cefotaxime (CTX) (p < 0.05), and the total phosphorus (TP) in FQ lake was significantly correlated with the content of AMP-resistant bacteria (p < 0.05), while there were no other correlations between the changes of other water quality indexes and the content of ARB (p > 0.05).

Breast cancer stem cell population in different molecular subtypes of breast cancer.

Breast cancer heterogeneity is well documented and to some extent is attributed to the presence of cancer stem cells (CSCs). Breast cancer stem cells are identified by the presence of cell surface molecule CD44 and absence of CD24. In the present study a flowcytometric analysis was done to study the expression distribution of CSC phenotype of CD44+/CD24-/low, among different molecular subtypes of breast cancer and to find a correlation with clinicopathological features. CSCs were observed in all the molecular subtypes of breast cancer. The highest population of CSCs was noted in luminal B (3.4%), followed by TNBC (1.7%), and Her-2 subtype (1.6%). The least number of CD44+/CD24- cells were seen in Luminal A subgroup (1.3%). Existence of cancer stem cells in all the subtypes may suggest the possibility of failure of current therapies in treatment of patients.

Ethnical Differences in Knee Phenotypes Indicate the Need for a More Individualized Approach in Knee Arthroplasty: A Comparison of 80 Asian Knees with 308 Caucasian Knees.

The purpose of this study was to determine the distribution of functional knee phenotypes in a non-osteoarthritic Asian population. The Stryker Orthopaedic Modeling and Analytics (SOMA) database was searched for CT scans of the lower limb meeting the following inclusion criteria: patient age at time of image >18 and <46 years, no signs of fractures and/or previous surgery and/or degenerative changes, Asian ethnicity. A total of 80 CT scans of 40 patients were included (24 males, 16 females). The hip-knee-ankle angle (HKA), femoral mechanical angle (FMA) and tibial mechanical angle (TMA) were measured. Based on these measurements, each limb was phenotyped according to the previously introduced functional knee phenotype concept. All angles and phenotypes of the present study were compared with previously published data of a non-osteoarthritic Caucasian population (308 legs of 160 patients, 102 males, 58 females). Asian knees had a significantly lower TMA (both genders p < 0.001) but a higher FMA (males p < 0.05, females p < 0.001) than Caucasian knees but showed no difference in the HKA. Asian knees differed significantly with regard to femoral and tibial phenotypes (p < 0.01), but not with regard to limb phenotypes. The high variability of all coronal alignment parameters highlights the importance of a detailed analysis prior to TKA. Ethnical differences underline the need for a more individualized approach in TKA.

Phylogeography and population genetics reveal ring species patterns in a highly polymorphic California lily

AbstractAimNatural selection typically results in the homogenization of reproductive traits, reducing natural variation within populations; thus, highly polymorphic species present unresolved questions regarding the mechanisms that shape and maintain gene flow given a diversity of phenotypes. We used an integrative framework to characterize phenotypic diversity and assess how evolutionary history and population genetics affect the highly polymorphic nature of a California endemic lily.LocationCalifornia, United States.TaxonButterfly mariposa lily, Calochortus venustus (Liliaceae).MethodsWe summarized phenotypic diversity at both metapopulation and subpopulation scales to explore spatial phenotypic distributions. We sampled 174 individuals across the species range representing multiple samples for each population and each phenotype. We used restriction‐site‐associated DNA sequencing (RAD‐Seq) to detect population clusters, gene flow between phenotypes and between populations, infer haplotype networks, and reconstruct ancestral range evolution to infer historical migration and range expansion.ResultsPolymorphic floral traits within the species such as petal pigmentation and distal spots are geographically structured, and inferred evolutionary history is consistent with a ring species pattern involving a complex of populations having experienced sequential change in genetic and phenotypic variation from the founding population. Populations remain interconnected yet have differentiated from each other along a bifurcating south‐to‐north range expansion, consequently indicating parallel evolution towards the white morphotype in the northern range. Thus, our phylogeographical analyses reveal morphological convergence with population genetic cohesion irrespective of phenotypic diversity.Main conclusionsPhenotypic variation in the highly polymorphic Calochortus venustus is not due to genetic differentiation between phenotypes; rather there is genetic cohesion within six geographically defined populations, some of which maintain a high level of within‐population phenotypic diversity. Our results demonstrate that analyses of polymorphic taxa greatly benefit from disentangling phenotype from genotype at various spatial scales. We discuss results in light of ring species concepts and the need to determine the adaptive significance of the patterns we report.

Prevalence, phenotypic distribution, and clinical characteristics of polycystic ovary syndrome in Egyptian women with type 1 diabetes mellitus

BackgroundType 1 diabetes mellitus (T1DM) has shown a steady increase in prevalence in most parts of the world. Polycystic ovary syndrome (PCOS) frequently occurs in 15–20% of women in their reproductive age. It is associated with subfertility, ovulatory dysfunction, dysregulated androgen biosynthesis, and increased risk of insulin resistance. This study aims to assess the prevalence, phenotypic distribution, and clinical characteristics of PCOS in a sample of Egyptian women with T1DM.Patients and methodsA total of 100 Egyptian women in their reproductive age (18–42 years old) previously diagnosed as having T1DM were recruited in the study. They were screened for symptoms and signs of PCOS by clinical, laboratory, and radiological investigations.ResultsOverall, 28% of our women with T1DM had PCOS and 61% had metabolic syndrome. Frank PCOS was the most common PCOS phenotype (47%). When women with T1DM with and without PCOS were compared, BMI, waist circumference, systolic blood pressure, and fasting blood sugar were statistically higher in the PCOS group, whereas high-density lipoprotein cholesterol was statistically lower (P < 0.05). Follicular-stimulating hormone (FSH) and sex hormone-binding globulin were also statistically lower and luteinizing hormone (LH), LH/FSH ratio, and total testosterone (TT) were statistically higher (P < 0.01) in the PCOS than in the non-PCOS group. In women with T1DM, LH, LH/FSH ratio, and TT were positively correlated with BMI and waist circumference, whereas LH/FSH ratio and TT were negatively correlated with high-density lipoprotein cholesterol.ConclusionThe prevalence of PCOS among women with T1DM in our sample of Egyptian patients revealed that PCOS and its associated traits are common findings. Thus, current T1DM management guidelines should include screening tests for PCOS and androgen excess as these patients have a high incidence of metabolic syndrome.

An integrative taxonomic study of the genus Theromyzon (Hirudinea: Glossiphoniidae), with description of a new North American species

Theromyzon Philippi, 1867 is a genus of sanguivorous, freshwater leeches in the family Glossiphoniidae. The genus is broadly distributed across the globe, possibly due to the frequent feeding in the nasopharyngeal cavities of migratory waterfowl that may allow for long distance dispersal. The genus has a history of taxonomic confusion resulting from mischaracterisations of key morphological features of type specimens that have produced several re-descriptions and synonyms. Here, we bring partial order to this confusion through robust morphological investigations of newly collected North American (and a single South American) specimens, representing most of the known species diversity from this continent. We also produce the first species-level phylogeny for Theromyzon and attempt to understand species boundaries regarding both morphology and genetics. Our results demonstrate that there are at least five species of Theromyzon present in North America (T. bifarium, T. tessulatum, T. rude, T. trizonare, and a clade that needs further investigation), and a hitherto undescribed taxon that does not conform to any previously published description, and represents a unique lineage in the phylogeny; we describe this new species under the name Theromyzon tigris sp. nov. This study sheds light on the discriminatory power of select morphological characters and the distribution of phenotypes within the genus. We also provide a comprehensive classification framework for the known species within the genus designed to facilitate identification and minimise future taxonomic confusion.

Quantile-Specific Heritability of Inflammatory and Oxidative Stress Biomarkers Linked to Cardiovascular Disease.

PurposeHeritability (h2, the proportion of the phenotypic variance attributable to additive genetic effects) is traditionally assumed to be constant throughout the distribution of the phenotype. However, the heritabilities of circulating C-reactive protein, interleukin-6, plasminogen activator inhibitor type-1 (PAI-1), and monocyte chemoattractant protein-1 (MCP-1) concentrations depend upon whether the phenotype is high or low relative to their distributions (quantile-dependent expressivity), which may account for apparent gene–environment interactions. Whether the heritabilities of other inflammatory biomarkers linked to cardiovascular disease are quantile-dependent remain to be determined.Patients and MethodsQuantile-specific offspring-parent (βOP) and full-sib regression slopes (βFS) were estimated by applying quantile regression to the age- and sex-adjusted phenotypes of families surveyed as part of the Framingham Heart Study. Quantile-specific heritabilities were calculated as: h2=2βOP/(1+rspouse) and h2={(1+8rspouseβFS)0.5–1}/(2rspouse).ResultsHeritability (h2 ± SE) of lipoprotein-associated phospholipase A2 (Lp-PLA2) mass concentrations increased from 0.11 ± 0.03 at the 10th percentile, 0.08 ± 0.03 at the 25th, 0.12 ± 0.03 at the 50th, 0.20 ± 0.04 at the 75th, and 0.26 ± 0.06 at the 90th percentile, or 0.0023 ± 0.0006 per each one-percent increase in the phenotype distribution (Plinear trend= 0.0004). Similarly, h2 increased 0.0029 ± 0.0011 (Plinear trend= 0.01) for sP-selectin, 0.0032 ± 0.0009 (Plinear trend= 0.0001) for soluble intercellular adhesion molecule 1 (sICAM-1), and 0.0026 ± 0.0006 for tumor necrosis factor receptor 2 (TNFR2) (Plinear trend= 5.0 × 10−6) per each one-percent increase in their distributions when estimated from βOP. Osteoprotegerin and soluble ST2 heritability also increased significantly with increasing percentiles of their distributions when estimated from βFS. Lp-PLA2 activity, CD40 ligand, TNFα, interleukin-18, and myeloperoxidase heritability showed no significant quantile-dependence.ConclusionThe heritabilities of circulating Lp-PLA2-mass, sP-selectin, sICAM-1, TNFR2, osteoprotegerin and soluble ST2 concentrations are quantile-dependent, which may contribute to purported genetic modulations of: 1) sP-selectin’s relationships to venous thrombosis, pulmonary hypertension, type 2 diabetes and atorvastatin treatment; 2) sICAM-I’s relationships to brain abscess and atorvastatin treatment; and 3) Lp-PLA2’s relationships to myocardial infarction and preeclampsia.

Does Haptoglobin Phenotype Impact Infection Mortality?

Introduction: The physiological status of a subject and the pathophysiology in some diseases might be under the influence of haptoglobin phenotype. The objective of this work was to determine the relationship between mortality from HIV/AIDS infection and haptoglobin phenotype in a black population in Côte d’Ivoire. Methods: The study was conducted from a retrospective panel of 933 sera/plasma from the previous workup of the ANRS 12136 TEMPRANO trial at month 0 of patients in deferred-ART arms. For each subject, we determined the serum haptoglobin concentration, haptoglobin phenotype, and other variables from patient files from the TEMPRANO trial database. Statistical tests used were Chi-2, Fischer, and Kruskal-Wallis tests for non-gaussian distribution. We used the Kaplan-Meier method for survival analysis. Results: The distributions of the haptoglobin phenotypes were 32.3% for Hp 1-1, 39.5% for Hp 2-1 and 27.2% for Hp 2-2. The blood haptoglobin concentration seemed to be associated with haptoglobin phenotypes (p-value > 5%). The survival rate at M30 and for an extended follow-up up to 6 years was independent of haptoglobin phenotype (p-value > 5%). Besides, the haptoglobin phenotypes do not appear to be associated with CD4+ T-cell count and with hemoglobin concentration. Conclusion: Haptoglobin phenotype seems to not impact the mortality of HIV/AIDS infection. However, given the antioxidant and immunomodulatory properties of some haptoglobin phenotypes, it would be relevant to seek out possible confounding factors indirectly associated with haptoglobin phenotypes and clinical or biological infection variables.

ВЛИЯНИЕ ВАРИКОЗНОЙ БОЛЕЗНИ ВЕН НИЖНИХ КОНЕЧНОСТЕЙ НА КАЧЕСТВО ЖИЗНИ И ИНДИВИДУАЛЬНЫЕ ОСОБЕННОСТИ ГЕМОДИНАМИКИ АМБУЛАТОРНЫХ ПАЦИЕНТОВ С АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИЕЙ

The purpose of the study is to study the effect of varicose veins of the lower extremities (VVLE) on the quality of life (QoL) and individual hemodynamic characteristics of outpatients with arterial hypertension (AH). The object of the study were outpatients from a number of polyclinics in Minsk with AH of 1 and 2 degrees and in combination with VVLE with chronic venous insufficiency (CVI) of 0—1 degree. QoL was studied using the Russian-language general RAND-36 questionnaire; hemodynamic phenotypes were assessed by BP parameters using the method for analyzing quantitative relationships of BP parameters (AQRBPP). In the course of the study, it was found that AH of 1—2 degrees negatively affects all spheres of life of patients, moderately reducing QOL indicators on all scales of the RAND-36 questionnaire. LEVV with minimal CVI significantly reduces such QoL indicators as SF (social functioning), BP (bodily pain) and HH (compared to the previous year), which requires appropriate correction. At the same time, VVLE with CVI grade 0—1 does not significantly affect the distribution of hemodynamic phenotypes in patients with AH. The study showed that the use of a set of indicators, including, along with traditional methods of research, the determination of QoL and the functional state of blood circulation according to AQRBPP allows you to better objectify the condition of patients with isolated hypertension and in combination with VVLE, conduct dynamic monitoring on an outpatient basis, individualize and optimize the process of treating these patients.