Periodontal Status and High‐Sensitivity C‐Reactive Protein Levels in Polycystic Ovary Syndrome With and Without Medical Treatment

Background: Recently, some studies have revealed the effect of polycystic ovary syndrome (PCOS) on gingival inflammation. This cross‐sectional study attempts to assess the periodontal status and systemic inflammation of women receiving medical treatment for PCOS and women newly diagnosed with PCOS. Methods: A total of 126 participants comprising 41 newly diagnosed patients with PCOS (PCOS‐N), 45 patients with PCOS on medical treatment (PCOS‐MT), and 40 systemically healthy controls (control group [CG]) were examined. Periodontal parameters, anthropometric parameters, and serum levels of high‐sensitivity C‐reactive protein (hsCRP) were recorded. Results: Women with newly diagnosed PCOS had increased sites with bleeding on probing (BOP), probing depth, clinical attachment level (CAL), waist circumference (WC), hsCRP, and prevalence of periodontitis compared with control and PCOS‐MT groups (P ≤0.05). On partial correlation analysis after controlling for confounders, BOP and CAL correlated positively and significantly with hsCRP (P = 0.01 and P = 0.005). Multivariate linear regression analysis revealed that BOP and CAL (dependent variable) (P = 0.009/R² = 0.05 and P = 0.005/R² = 0.07, respectively) had significant association with hsCRP. Furthermore, hsCRP, when considered as outcome, also exhibited association with CAL and WC (P = 0.002/R² = 0.07 and P = 0.04/R² = 0.106). Logistic regression analysis demonstrated that the PCOS‐N group had 2.88 times increased likelihood of having moderate periodontitis (adjusted odds ratio 2.88, 95% confidence interval 1.18 to 6.98). Conclusions: Women with newly diagnosed PCOS may have increased prevalence and likelihood for periodontitis, with higher measures of periodontal inflammation and breakdown than those on medical treatment for PCOS and systemically healthy females. Furthermore, periodontal breakdown might depend on systemic inflammation and vice versa.     

Nucleotide deletion in RHCE*cE (907delC) is responsible for a D- - haplotype in Hispanics

BACKGROUND: Lack of Cc and Ee expression is associated with either hybrid alleles in which regions of RHCE are replaced by RHD or nucleotide deletion(s) in RHCE. The former have been found as D– – phenotypes, and the latter as Rh_null when accompanied by deletion of RHD. We investigated RH in eight samples, three presenting as D– –, whose c–E– red blood cell (RBC) typing was discordant with the RHCE genotype that predicted c+E+. STUDY DESIGN AND METHODS: Serologic and molecular testing was performed by standard methods. CASES AND RESULTS: RBCs from Patient 1 were D+C?E?c+e+^w but DNA testing predicted E+. RBCs from Patients 2, 3, and 4 typed as D+C?E?c?e? but DNA testing predicted c+E+. All had alloantibodies strongly reactive with all RBCs tested except D– – and Rh_null. Patient 5 had anti‐c and anti‐E but DNA testing predicted she was c+E+. RBCs from three donors typed D+C+E?c?e+ with DNA testing predicting c+E+. All had RHCE*cE with deletion of nucleotide 907C in Exon 6 predicted to cause a premature stop codon at Amino Acid 303 (Leu303Stop). HphI polymerase chain reaction–restriction fragment length polymorphism was used to confirm the deletion and to screen 100 Hispanic, 100 Caucasian, and 100 African American donor samples. One additional example was found. CONCLUSIONS: A novel allele, RHCE*cE 907delC (ISBT provisional designation RHCE*03N.02), silences c and E and in the homozygous state resulted in a D– – phenotype and production of anti‐Rh17. All eight probands were Hispanic. The allele is associated with discrepant molecular typing, with an approximate frequency of 0.005 in Hispanics.     

Structural and Binding Studies of SAP-1 Protein With Heparin

SAP-1 is a low molecular weight cysteine protease inhibitor (CPI) which belongs to type-2 cystatins family. SAP-1 protein purified from human seminal plasma (HuSP) has been shown to inhibit cysteine and serine proteases and exhibit interesting biological properties, including high temperature and pH stability. Heparin is a naturally occurring glycosaminoglycan (with varied chain length) which interacts with a number of proteins and regulates multiple steps in different biological processes. As an anticoagulant, heparin enhances inhibition of thrombin by the serpin antithrombin III. Therefore, we have employed surface plasmon resonance (SPR) to improve our understanding of the binding interaction between heparin and SAP-1 (protease inhibitor). SPR data suggest that SAP-1 binds to heparin with a significant affinity (K_D = 158 nm ). SPR solution competition studies using heparin oligosaccharides showed that the binding of SAP-1 to heparin is dependent on chain length. Large oligosaccharides show strong binding affinity for SAP-1. Further to get insight into the structural aspect of interactions between SAP-1 and heparin, we used modelled structure of the SAP-1 and docked with heparin and heparin-derived polysaccharides. The results suggest that a positively charged residue lysine plays important role in these interactions. Such information should improve our understanding of how heparin, present in the reproductive tract, regulates cystatins activity.     

Genomic and Functional Portrait of a Highly Virulent,CTX-M-15-Producing H30-Rx Subclone of Escherichia coli Sequence Type 131

Escherichia coli sequence type 131 (ST131) is a pandemic clone associated with multidrug-resistant, extraintestinal infections, attributable to the presence of the CTX-M-15 extended-spectrum β-lactamase gene and mutations entailing fluoroquinolone resistance. Studies on subclones within E. coli ST131 are critically required for targeting and implementation of successful control efforts. Our study comprehensively analyzed the genomic and functional attributes of the H30-Rx subclonal strains NA097 and NA114, belonging to the ST131 lineage. We carried out whole-genome sequencing, comparative analysis, phenotypic virulence assays, and profiling of the antibacterial responses of THP1 cells infected with these subclones. Phylogenomic analysis suggested that the strains were clonal in nature and confined entirely to a single clade. Comparative genomic analysis revealed that the virulence and resistance repertoires were comparable among the H30-Rx ST131 strains except for the commensal ST131 strain SE15. Similarly, seven phage-specific regions were found to be strongly associated with the H30-Rx strains but were largely absent in the genome of SE15. Phenotypic analysis confirmed the virulence and resistance similarities between the two strains. However, NA097 was found to be more robust than NA114 in terms of virulence gene carriage (dra operon), invasion ability (P < 0.05), and antimicrobial resistance (streptomycin resistance). RT² gene expression profiling revealed generic upregulation of key proinflammatory responses in THP1 cells, irrespective of ST131 lineage status. In conclusion, our study provides comprehensive, genome-inferred insights into the biology and immunological properties of ST131 strains and suggests clonal diversification of genomic and phenotypic features within the H30-Rx subclone of E. coli ST131.     

Entrustment and Mapping of Observable Practice Activities for Resident Assessment

Entrustable Professional Activities (EPAs) and the Next Accreditation System reporting milestones reduce general competencies into smaller evaluable parts. However, some EPAs and reporting milestones may be too broad to use as direct assessment tools. We describe our internal medicine residency curriculum and assessment system, which uses entrustment and mapping of observable practice activities (OPAs) for resident assessment. We created discrete OPAs for each resident rotation and learning experience. In combination, these serve as curricular foundation and tools for assessment. OPA performance is measured via a 5-point entrustment scale, and mapped to milestones and EPAs. Entrustment ratings of OPAs provide an opportunity for immediate structured feedback of specific clinical skills, and mapping OPAs to milestones and EPAs can be used for longitudinal assessment, promotion decisions, and reporting. Direct assessment and demonstration of progressive entrustment of trainee skill over time are important goals for all training programs. Systems that use OPAs mapped to milestones and EPAs provide the opportunity for achieving both, but require validation.     

Psychosocial Correlates of Monocyte Activation and HIV Persistence in Methamphetamine Users

This cross-sectional study investigated the associations of psychosocial factors relevant to recovery from substance use disorders with monocyte activation and HIV persistence in a sample of 84 HIV-positive, methamphetamine-using sexual minority men with undetectable HIV viral load (<40 copies/mL). We examined if psychosocial factors were associated with decreased soluble CD14 (sCD14) and lower proviral HIV DNA. Multiple linear regression models adjusted for age, anti-retroviral therapy regimen, and CD4+ T-cell count. Time on ART was also included in models examining proviral HIV DNA. Greater self-efficacy for managing methamphetamine triggers and higher social support for abstinence were independently associated with lower sCD14. Greater social support for abstinence was also independently associated with lower proviral HIV DNA. Psychosocial factors relevant to recovery from substance use disorders are associated with lower monocyte activation and decreased proviral HIV DNA. Findings underscore the need for longitudinal research to identify plausible mechanisms linking psychosocial factors and substance use with biological processes relevant to HIV pathogenesis.