Characterization of Protein Involved in Hemolysis Expressed by Sneathia amnii, a Pathogen of the Female Urogenital Tract

Sneathia amnii is a poorly characterized gram-negative anaerobe that commonly colonizes the vagina. It has been linked to many obstetric disorders, including preterm labor, preeclampsia, and chorioamnionitis. S. amnii lyses human red blood cells, and we aimed to identify the hemolysin. We identified two genes that appear to encode transporter and effector components of a two-partner secretion system. The putative effector, which we refer to as SaFHA, contains a domain with amino acid similarity to the filamentous hemagglutinin (FHA) of Bordetella pertussis and its predicted structure suggests it may form a transmembrane channel or pore. Thus, we hypothesized that SaFHA would be secreted by S. amnii and that it would play a role in hemoglobbin release. To test this, a portion of the gene encoding the SaFHA protein in S. amnii was expressed in E. coli and used as an immunogen in rabbits. Western analysis using anti-SaFHA revealed that the protein is secreted and localizes to the bacterial surface. Pre-treatment of S. amnii with anti-SaFHA blocked the hemolytic activity whereas antiserum against an irrelevant protein had no effect. We partially purified SaFHA from S. amnii using cation exchange chromatography and the partially purified protein mediated hemoglobin release from human RBC, supporting our hypothesis. Further characterization of SaFHA will help provide more insight on the virulence of S. amnii, and perhaps shed light on the etiology of Sneathia-associated vaginal conditions, as well as future treatment options.https://scholarscompass.vcu.edu/gradposters/1046/thumbnail.jp

Hyperactivity in the Gunn rat model of neonatal jaundice: age-related attenuation and emergence of gait deficits

Background Neonatal jaundice resulting from elevated unconjugated bilirubin (UCB) occurs in 60–80% of newborn infants. Although mild jaundice is generally considered harmless, little is known about its long-term consequences. Recent studies have linked mild bilirubin-induced neurological dysfunction (BIND) with a range of neurological syndromes, including attention deficit-hyperactivity disorder. The goal of this study was to measure BIND across the lifespan in the Gunn rat model of BIND. Methods Using a sensitive force plate actometer, we measured locomotor activity and gait in jaundiced (jj) Gunn rats versus their non-jaundiced (Nj) littermates. Data were analyzed for young adult (3–4 months), early middle-aged (9–10 months), and late middle-aged (17–20 months) male rats. Results jj rats exhibited lower body weights at all ages and a hyperactivity that resolved at 17–20 months of age. Increased propulsive force and gait velocity accompanied hyperactivity during locomotor bouts at 9–10 months in jj rats. Stride length did not differ between the two groups at this age. Hyperactivity normalized and gait deficits, including decreased stride length, propulsive force, and gait velocity, emerged in the 17–20-month-old jj rats. Conclusions These results demonstrate that, in aging, hyperactivity decreases with the onset of gait deficits in the Gunn rat model of BIND

Algorithm Development and Validation of CDOM Properties for Estuarine and Continental Shelf Waters Along the Northeastern U.S. Coast

An extensive set of field measurements have been collected throughout the continental margin of the northeastern U.S. from 2004 to 2011 to develop and validate ocean color satellite algorithms for the retrieval of the absorption coefficient of chromophoric dissolved organic matter (aCDOM) and CDOM spectral slopes for the 275:295 nm and 300:600 nm spectral range (S275:295 and S300:600). Remote sensing reflectance (Rrs) measurements computed from in-water radiometry profiles along with aCDOM() data are applied to develop several types of algorithms for the SeaWiFS and MODIS-Aqua ocean color satellite sensors, which involve least squares linear regression of aCDOM() with (1) Rrs band ratios, (2) quasi-analytical algorithm-based (QAA based) products of total absorption coefficients, (3) multiple Rrs bands within a multiple linear regression (MLR) analysis, and (4) diffuse attenuation coefficient (Kd). The relative error (mean absolute percent difference; MAPD) for the MLR retrievals of aCDOM(275), aCDOM(355), aCDOM(380), aCDOM(412) and aCDOM(443) for our study region range from 20.4-23.9 for MODIS-Aqua and 27.3-30 for SeaWiFS. Because of the narrower range of CDOM spectral slope values, the MAPD for the MLR S275:295 and QAA-based S300:600 algorithms are much lower ranging from 9.9 and 8.3 for SeaWiFS, respectively, and 8.7 and 6.3 for MODIS, respectively. Seasonal and spatial MODIS-Aqua and SeaWiFS distributions of aCDOM, S275:295 and S300:600 processed with these algorithms are consistent with field measurements and the processes that impact CDOM levels along the continental shelf of the northeastern U.S. Several satellite data processing factors correlate with higher uncertainty in satellite retrievals of aCDOM, S275:295 and S300:600 within the coastal ocean, including solar zenith angle, sensor viewing angle, and atmospheric products applied for atmospheric corrections. Algorithms that include ultraviolet Rrs bands provide a better fit to field measurements than algorithms without the ultraviolet Rrs bands. This suggests that satellite sensors with ultraviolet capability could provide better retrievals of CDOM. Because of the strong correlations between CDOM parameters and DOM constituents in the coastal ocean, satellite observations of CDOM parameters can be applied to study the distributions, sources and sinks of DOM, which are relevant for understanding the carbon cycle, modeling the Earth system, and to discern how the Earth is changing

SAEM Response to the National Institutes of Health request for information: Future directions in violence against women research

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Genome-wide association of familial prostate cancer cases identifies evidence for a rare segregating haplotype at 8q24.21

Previous genome-wide association studies (GWAS) of prostate cancer risk focused on cases unselected for family history and have reported over 100 significant associations. The International Consortium for Prostate Cancer Genetics (ICPCG) has now performed a GWAS of 2511 (unrelated) familial prostate cancer cases and 1382 unaffected controls from 12 member sites. All samples were genotyped on the Illumina 5M+exome single nucleotide polymorphism (SNP) platform. The GWAS identified a significant evidence for association for SNPs in six regions previously associated with prostate cancer in population-based cohorts, including 3q26.2, 6q25.3, 8q24.21, 10q11.23, 11q13.3, and 17q12. Of note, SNP rs138042437 (p = 1.7e−8) at 8q24.21 achieved a large estimated effect size in this cohort (odds ratio = 13.3). 116 previously sampled affected relatives of 62 risk-allele carriers from the GWAS cohort were genotyped for this SNP, identifying 78 additional affected carriers in 62 pedigrees. A test for an excess number of affected carriers among relatives exhibited strong evidence for co-segregation of the variant with disease (p = 8.5e−11). The majority (92 %) of risk-allele carriers at rs138042437 had a consistent estimated haplotype spanning approximately 100 kb of 8q24.21 that contained the minor alleles of three rare SNPs (dosage minor allele frequencies <1.7 %), rs183373024 (PRNCR1), previously associated SNP rs188140481, and rs138042437 (CASC19). Strong evidence for co-segregation of a SNP on the haplotype further characterizes the haplotype as a prostate cancer pre-disposition locus

Development and Psychometric Validation of the Pandemic-Related Traumatic Stress Scale for Children and Adults

To assess the public health impact of the COVID-19 pandemic on mental health, investigators from the National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) research program developed the Pandemic-Related Traumatic Stress Scale (PTSS). Based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) acute stress disorder symptom criteria, the PTSS is designed for adolescent (13–21 years) and adult self-report and caregiver-report on 3–12-year-olds. To evaluate psychometric properties, we used PTSS data collected between April 2020 and August 2021 from non-pregnant adult caregivers (n = 11,483), pregnant/postpartum individuals (n = 1,656), adolescents (n = 1,795), and caregivers reporting on 3–12-year-olds (n = 2,896). We used Mokken scale analysis to examine unidimensionality and reliability, Pearson correlations to evaluate relationships with other relevant variables, and analyses of variance to identify regional, age, and sex differences. Mokken analysis resulted in a moderately strong, unidimensional scale that retained nine of the original 10 items. We detected small to moderate positive associations with depression, anxiety, and general stress, and negative associations with life satisfaction. Adult caregivers had the highest PTSS scores, followed by adolescents, pregnant/postpartum individuals, and children. Caregivers of younger children, females, and older youth had higher PTSS scores compared to caregivers of older children, males, and younger youth, respectively

Height, selected genetic markers and prostate cancer risk:Results from the PRACTICAL consortium

Background: Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer. Methods: We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases and 6016 controls and a subset of high grade cases (2480 cases). We explored height, polymorphisms in genes related to growth processes as main effects and their possible interactions. Results: The results suggest that height is associated with high-grade prostate cancer risk. Men with height 4180cm are at a 22% increased risk as compared to men with height o173cm (OR 1.22, 95% CI 1.01–1.48). Genetic variants in the growth pathway gene showed an association with prostate cancer risk. The aggregate scores of the selected variants identified a significantly increased risk of overall prostate cancer and high-grade prostate cancer by 13% and 15%, respectively, in the highest score group as compared to lowest score group. Conclusions: There was no evidence of gene-environment interaction between height and the selected candidate SNPs. Our findings suggest a role of height in high-grade prostate cancer. The effect of genetic variants in the genes related to growth is seen in all cases and high-grade prostate cancer. There is no interaction between these two exposures.</p

The development of a web- and a print-based decision aid for prostate cancer screening

Background Whether early detection and treatment of prostate cancer (PCa) will reduce disease-related mortality remains uncertain. As a result, tools are needed to facilitate informed decision making. While there have been several decision aids (DAs) developed and tested, very few have included an exercise to help men clarify their values and preferences about PCa screening. Further, only one DA has utilized an interactive web-based format, which allows for an expansion and customization of the material. We describe the development of two DAs, a booklet and an interactive website, each with a values clarification component and designed for use in diverse settings. Methods We conducted two feasibility studies to assess men\u27s (45-70 years) Internet access and their willingness to use a web- vs. a print-based tool. The booklet was adapted from two previous versions evaluated in randomized controlled trials (RCTs) and the website was created to closely match the content of the revised booklet. Usability testing was conducted to obtain feedback regarding draft versions of the materials. The tools were also reviewed by a plain language expert and the interdisciplinary research team. Feedback on the content and presentation led to iterative modifications of the tools. Results The feasibility studies confirmed that the Internet was a viable medium, as the majority of men used a computer, had access to the Internet, and Internet use increased over time. Feedback from the usability testing on the length, presentation, and content of the materials was incorporated into the final versions of the booklet and website. Both the feasibility studies and the usability testing highlighted the need to address men\u27s informed decision making regarding screening. Conclusions Informed decision making for PCa screening is crucial at present and may be important for some time, particularly if a definitive recommendation either for or against screening does not emerge from ongoing prostate cancer screening trials. We have detailed our efforts at developing print- and web-based DAs to assist men in determining how to best meet their PCa screening preferences. Following completion of our ongoing RCT designed to test these materials, our goal will be to develop a dissemination project for the more effective tool

Association analysis of 9,560 prostate cancer cases from the International Consortium of Prostate Cancer Genetics confirms the role of reported prostate cancer associated SNPs for familial disease

Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case-control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial prostate cancer cases and the subset of aggressive cases. For the familial prostate cancer phenotype, 20 of the 25 SNPs were at least nominally associated with prostate cancer and 16 remained significant after multiple testing correction (p≤1E−3) occurring on chromosomal bands 6q25, 7p15, 8q24, 10q11, 11q13, 17q12, 17q24, and Xp11. For aggressive disease, 16 of the SNPs had at least nominal evidence and 8 were statistically significant including 2p15. The results indicate that the majority of common, low-risk alleles identified in GWAS studies for all prostate cancer also contribute risk for familial prostate cancer, and that some may be contribute risk to aggressive disease