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Preprocedural coronary computed tomography angiography (CCTA) can be useful in procedural planning for chronic total occlusion (CTO) percutaneous coronary intervention (PCI).We examined the clinical, angiographic and procedural characteristics and outcomes of cases with vs. without preprocedural CCTA in PROGRESS-CTO (NCT02061436). Multivariable logistic regression was used to adjust for confounding factors.Of 7034 CTO PCI cases, preprocedural CCTA was used in 375 (5.3%) with increasing frequency over time. Patients with preprocedural CCTA had a higher prevalence of prior coronary artery bypass graft surgery (39% vs. 27%, p 0.001) and angiographically unfavorable characteristics including higher prevalence of proximal cap ambiguity (52% vs. 33%, p 0.001) and moderate/severe calcification (59% vs. 41%, p 0.001) compared with those without CCTA. CCTA helped resolve proximal cap ambiguity in 27%, identified significant calcium not seen on diagnostic angiography in 18%, changed estimated CTO length by5 mm in 10%, and was performed as part of initial coronary artery disease work up in 19%. CCTA cases had higher J-CTO (2.6 ± 1.2 vs. 2.3 ± 1.3, p 0.001) and PROGRESS-CTO (1.3 ± 1.0 vs. 1.2 ± 1.0 p = 0.027) scores. After adjusting for potential confounders, cases with preprocedural CCTA had similar technical success (odds ratio [OR]: 1.18, 95% confidence interval [CI], 0.83-1.67) and incidence of major adverse cardiovascular events (OR: 1.47, 95% CI, 0.72-3.00).Preprocedural CCTA was used in ~5% of CTO PCI cases. While CCTA may help with procedural planning, especially in complex cases, technical success and MACE were similar with or without CCTA.

TheGardnerellagenus, now made up of more than 13 species, is associated with the polymicrobial disorder bacterial vaginosis (BV). However, the details of BV pathogenesis are poorly defined, and the contributions made by individual species are largely unknown. We report here that colony phenotypes characterized by size (large and small) and opacity (opaque and translucent) are phase variable and are conserved among all testedGardnerellastrains, representing at least ten different species. With the hypothesis that these different variants could be an important missing piece to the enigma of how BV develops in vivo, we characterized their differences. Beyond increased colony size, large colony variants (Lg) showed reduced vaginolysin secretion and faster growth rate relative to small colony variants (Sm). The ability to inhibit growth ofNeisseria gonorrhoeaeand commensal lactobacillus species varied by strain and in some instances differed between variants. Proteomics analyses indicate that 127-173 proteins are differentially expressed between variants. Further, whole genome sequencing analyses revealed an abundance of genes associated with variable poly-guanine tracts, implicating slipped strand mispairing inGardnerellaphase variation, and illuminating the potential for previously unrecognized variability within clonal populations. Collectively, these results suggest that colony variants may be primed to serve different roles in BV pathogenesis.

The hybrid algorithm was designed to assist with initial and subsequent crossing strategy selection in chronic total occlusion (CTO) percutaneous coronary interventions (PCIs). However, the success of the initially selected strategy has received limited study.We examined the impact of adherence to the hybrid algorithm recommendation for initial CTO crossing technique selection in 4178 CTO PCIs from a large multicenter registry.The initial crossing strategy was concordant with the hybrid algorithm recommendation in 1833 interventions (44%). Patients in the concordant group had a similar age to those in the discordant group but a lower mean J-CTO score (2.0 ± 1.4 vs 2.8 ± 1.1; P .01). The concordant group showed higher technical success with the first crossing strategy (68% vs 48%; P .01) and higher overall technical success (88% vs 83%; P .01) with no difference in the incidence of in-hospital major adverse events (1.8% vs 2.3%; P = .26). In multivariable analysis, after adjustment for age, prior myocardial infarction, prior PCI, prior coronary artery bypass grafting, J-CTO score, and scheduled CTO PCI, nonadherence to the hybrid algorithm was independently associated with lower technical success of the initial crossing strategy (odds ratio, 0.55; 95% confidence interval, 0.48-0.64; P .01).Adherence to the hybrid algorithm for initial crossing strategy selection is associated with higher CTO PCI success but similar in-hospital major adverse cardiac events.

Resumen Introduccion y objetivos El algoritmo hibrido se diseno para ayudar en la seleccion de las estrategias de cruce inicial y siguientes en la intervencion coronaria percutanea (ICP) para la oclusion cronica total (OTC); sin embargo, el exito de la estrategia de inicio seleccionada se ha estudiado poco hasta ahora. Metodos Se estudio el impacto de la adherencia a la recomendacion del algoritmo hibrido para la seleccion de la tecnica de cruce inicial en 4.178 ICP de OTC en un registro multicentrico de gran tamano. Resultados La estrategia de cruce inicial coincidio con la recomendacion del algoritmo hibrido en 1.833 casos (44%). Los pacientes en el grupo concordante tuvieron una edad similar, pero un indice J-OTC menor (2,0 ± 1,4 frente a 2,8 ± 1,1; p Conclusiones La adherencia al algoritmo hibrido para la seleccion de la estrategia inicial de cruce se asocio con mayor exito de la ICP para la OTC y similar tasa de eventos cardiovasculares hospitalarios graves.

The prevalence and outcomes of patients who presented with an acute coronary syndrome (ACS) and underwent chronic total occlusion (CTO) percutaneous coronary intervention (PCI) have received limited study.We examined the clinical characteristics and procedural outcomes of ACS patients who underwent CTO-PCI in the Prospective Global Registry for the Study of CTO Intervention (PROGRESS-CTO; NCT02061436).Of the 8826 patients who underwent CTO-PCI between 2012 and 2022 at 38 centers, 558 (6.3%) presented with ACS. ACS presentation was with non-ST-segment elevation myocardial infarction (MI) in 54%, unstable angina in 33%, and ST-segment elevation MI in 6.5%. ACS patients were older (66 ± 11 years vs 64 ± 10 years; P.001) and had higher prevalence of comorbidities such as diabetes mellitus (48% vs 42%; P=.02), prior MI (52% vs 45%; P.01), and lower left ventricular ejection fraction (49 ± 14% vs 51 ± 13%; P.01). While the PROGRESS-CTO score (1.4 ± 1.0 vs 1.2 ± 1.0; P.001) was higher in the ACS group, the J-CTO score was comparable (2.3 ± 1.2 vs 2.4 ± 1.3; P=.68). Technical success (88% vs 86%; P=.12) and the incidence of in-hospital major adverse cardiovascular event (MACE) (0.9% vs 2.1%; P=.06) and adverse events at 3-month follow-up (3.4% vs 7.2%; Kaplan-Meier log-rank P=.16) were similar between ACS and non-ACS patients, respectively.Approximately 6% of patients who underwent CTO-PCI presented with an ACS. Technical success, in-hospital MACE, and the incidence of adverse events up to 3 months were similar between patients who presented with vs without an ACS.

Chronic diseases are disproportionately high among African Americans, often caused by social determinants of health (e.g., access to physical activity opportunities), as stated by the Centers for Disease Control and Prevention. Several studies have examined practices and policies of shared-use in school-based and other settings. There is still a gap in the literature regarding how faith-based shared-use programs, practices, and policies are implemented in a virtual or hybrid setting. This evaluation reviewed program activities and partnerships and assessed program needs for quality improvement. Focus groups ( n = 2) were conducted with program participants and site coordinators from five faith-based shared-use sites. A 12-question discussion guide was developed based on topics of interest predetermined by the project team to understand participant perceptions about participation, satisfaction, and recommendations. Focus group audio recordings were transcribed verbatim and reviewed using thematic analysis. The evaluators reviewed transcripts separately to confirm final coding and ensured intercoder reliability. The analysis yielded six themes and eight subthemes. Findings indicated that the program was rewarding and achievable, with suggestions for improvement. Social support was developed as a result of the program, health improvements were observed by participants, and networked partnerships were formed to promote health and wellness. The virtual platform presented limited access; therefore, adopting a hybrid approach could offer greater flexibility and reach broader audiences. It may be helpful for public health agencies to partner with faith-based organizations to jointly open their facilities. Agencies, like local health departments, may consider establishing agreements to expand shared-use to local faith-based settings.

The diversity and dominant bacterial taxa in the vagina are reported to be influenced by multiple intrinsic and extrinsic factors, including but not limited to pregnancy, contraceptive use, pathogenic states, socioeconomic status, and ancestry. However, the extent to which host genetic factors influence variation in the vaginal microbiota is unclear. We used a biometrical genetic approach to determine whether host genetic factors contribute to inter-individual differences in taxa from a sample of 332 twins who self-identified as being of African (44 pairs) or European ancestry (122 pairs). Lactobacillus crispatus, a major determinant of vaginal health, was identified as heritable among European American women (narrow-sense heritability = 34.7%, P-value = 0.018). Heritability of L. crispatus is consistent with the reduced prevalence of adverse reproductive disorders, including bacterial vaginosis and preterm birth, among women of European ancestry., Wright et al. apply biometric genetic approach to identify the extent to which host genetic factors influence species-level variation in the vaginal microbiota. Their study suggests that Lactobacillus crispatus, a major determinant of vaginal health, is heritable among European American women, consistent with the reduced prevalence of adverse reproductive disorders in them.

Gardnerella spp. are the most frequent organisms found in bacterial vaginosis (BV). However, colonization by Gardnerella spp. does not always lead to BV. Developments in molecular genetics have shed new light on the diversity of the genus Gardnerella, leading to an emended description of Gardnerella vaginalis and, for the first time, the inclusion of more species of Gardnerella, namely, Gardnerella leopoldii, Gardnerella piotii, and Gardnerella swidsinskii. While no association had been made between the novel Gardnerella species and virulence potential, there is genomic evidence of a higher prevalence of some genotypes in BV cases, as compared with colonization in women in whom BV has been clinically ruled out. Gardnerella vaginalis has been considered a pivotal player in the progression of bacterial vaginosis (BV), a condition associated with serious health complications. However, G. vaginalis is also commonly found in asymptomatic or BV-negative women. This has generated interest in the question of whether genetic differences among isolates might distinguish pathogenic from commensal isolates. G. vaginalis was the only recognized species in its genus for four decades, but recently an emended description of G. vaginalis and descriptions of three new species Gardnerella leopoldii, Gardnerella piotii, and Gardnerella swidsinskii have been proposed. This review provides background on the heterogeneity and diversity within the genus Gardnerella, highlighting the main features that distinguish species and clades, and how these features may impact BV development., J.C. and N.C. acknowledge the projects PTDC/BIA-MIC/28271/2017 (POCI-01-0145-FEDER-028271), and the strategic funding of unit UID/BIO/04469/2019, supported by the Portuguese Foundation for Science and Technology., info:eu-repo/semantics/publishedVersion

The aim of this study was to examine the use of saphenous vein grafts (SVGs) for retrograde crossing during chronic total occlusion (CTO) percutaneous coronary intervention (PCI).The use of SVGs for retrograde crossing during CTO PCI has received limited study.A total of 1,615 retrograde CTO PCIs performed between 2012 and 2019 at 25 centers were examined. Clinical, angiographic, and technical characteristics and procedural outcomes were compared among retrograde cases via SVGs (SVG group) versus other collateral vessels (non-SVG group).Retrograde CTO PCI via SVGs was performed in 189 cases (12%). Patients in the SVG group were older (mean age 70 ± 9 years vs. 64 ± 10 years; p 0.01) and had higher rates of prior myocardial infarction (62% vs. 51%; p 0.01) and prior PCI (81% vs. 70%; p 0.01). They were more likely to have moderate or severe calcification (81% vs. 65%; p 0.01) and moderate or severe tortuosity (53% vs. 44%; p = 0.02) and had similar J-CTO (Multicenter CTO Registry in Japan) scores (3.2 ± 1.0 vs. 3.1 ± 1.1; p = 0.13) but higher PROGRESS-CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) scores (4.7 ± 1.7 vs. 3.1 ± 1.1; p 0.01). Technical (85% vs. 78%; p = 0.04) and procedural (81% vs. 74%; p = 0.04) success rates were higher in the SVG group, with no difference in in-hospital major adverse events (6.4% vs. 4.4%; p = 0.22). Contrast volume was lower in the SVG group (225 ml [173 to 325 ml] vs. 292 ml [202 to 400 ml]; p 0.01).Use of SVGs for retrograde crossing is associated with higher rates of technical and procedural success and similar rates of in-hospital major adverse cardiac events compared with retrograde CTO PCI via other collateral vessels.

The prevalence, treatment, and outcomes of balloon undilatable lesions encountered in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) have received limited study.We examined the clinical characteristics and procedural outcomes of balloon undilatable lesions in the Prospective Global Registry for the Study of CTO Intervention (PROGRESS-CTO, NCT02061436).Of 6535 CTO PCIs performed between 2012 and 2022, 558 (8.5%) lesions were balloon undilatable. In this subset, patients were older (mean age 67 ± 10 vs. 64 ± 10, p 0.001) and had higher prevalence of comorbidities: diabetes mellitus (54% vs. 40%, p 0.001), prior PCI (71% vs. 59%, p 0.001), prior myocardial infarction (52% vs. 45%, p = 0.003), and prior coronary artery bypass graft surgery (44% vs. 25%, p 0.001). The CTO lesion length was estimated to be 34 ± 23 mm, mean J-CTO score was 2.9 ± 1.1 and mean PROGRESS-CTO score was 1.4 ± 1.0. A cutting balloon was used in 27%, a scoring balloon in 15%, laser in 14%, rotational atherectomy in 28%, orbital atherectomy in 10%, intravascular lithotripsy in 1% and other modalities/approaches in 5%. Balloon undilatable lesions had lower technical success (90.9% vs. 93.8%, p = 0.007) and higher incidence of major adverse cardiovascular events (MACE) (composite of in-hospital death, acute myocardial infarction, stroke, re-PCI, emergency CABG, and pericardiocentesis) (5.0% versus 1.3%, p 0.001).Approximately 1 in 12 CTO (8.5%) lesions are balloon undilatable. Treatment of balloon undilatable lesions is associated with lower technical success and higher in-hospital MACE.

Background: The relationship between left ventricular ejection fraction (LVEF) and the success and safety of coronary chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. Methods: We examined the clinical characteristics and outcomes of CTO PCI in the Prospective Global Registry for the Study of CTO Intervention (PROGRESS-CTO) after stratifying patients by LVEF (≤35%, 36%–49%, and ≥50%). Results: A total of 7827 CTO PCI procedures with LVEF data were included. Mean age was 64 ± 10 years, 81% were men, 43% had diabetes mellitus, 61% had prior PCI, 45% had prior myocardial infarction, and 29% had prior coronary artery bypass graft surgery. Technical success was similar in the three LVEF strata: 85%, 86%, and 87%, p = 0.391 for LVEF ≤35%, 36%–49%, and ≥50%, respectively. In-hospital mortality was higher in lower LVEF patients (1.1%, 0.4%, and 0.3%, respectively, p = 0.001). In-hospital major adverse cardiovascular events (MACE) were numerically higher in lower EF patients (2.7%, 2.1%, and 1.9%, p = 0.271). At a median follow-up of 2 months (interquartile range: 19-350 days), patients with lower LVEF continued to have higher mortality (4.9%, 3.2%, and 1.4%, p < 0.001) while the MACE rates were similar (9.3%, 9.6%, and 7.4%, p = 0.172). Conclusion: CTO PCI can be performed with high technical success in patients with reduced LVEF but is associated with higher in-hospital and post-discharge mortality.

The composition of the human vaginal microbiome has been extensively studied and is known to influence reproductive health. However, the functional roles of individual taxa and their contributions to negative health outcomes have yet to be well characterized. Here, we examine two vaginal bacterial taxa grouped within the genus Megasphaera that have been previously associated with bacterial vaginosis (BV) and pregnancy complications. Phylogenetic analyses support the classification of these taxa as two distinct species. These two phylotypes, Megasphaera phylotype 1 (MP1) and Megasphaera phylotype 2 (MP2), differ in genomic structure and metabolic potential, suggestive of differential roles within the vaginal environment. Further, these vaginal taxa show evidence of genome reduction and changes in DNA base composition, which may be common features of host dependence and/or adaptation to the vaginal environment. In a cohort of 3870 women, we observed that MP1 has a stronger positive association with bacterial vaginosis whereas MP2 was positively associated with trichomoniasis. MP1, in contrast to MP2 and other common BV-associated organisms, was not significantly excluded in pregnancy. In a cohort of 52 pregnant women, MP1 was both present and transcriptionally active in 75.4 % of vaginal samples. Conversely, MP2 was largely absent in the pregnant cohort. This study provides insight into the evolutionary history, genomic potential and predicted functional role of two clinically relevant vaginal microbial taxa.

Objective The aim of this study was to evaluate the differences between the vaginal microbiome of reproductive-aged women with overweight and obesity (Ow/Ob) compared with healthy weight (HW). Methods In this case-control study, a cohort of 367 nonpregnant women (18 to 40 years) with Ow/Ob (BMI ≥25 kg/m2 ) was case-matched with 367 women with HW (BMI 18.0 to 24.9 kg/m2 ). The study was a secondary analysis of 16S rRNA vaginal microbiome surveys through the Vaginal Human Microbiome Study (VaHMP). Groups were matched on age, race/ethnicity, income, and nulliparity status. Results Mean age and BMI of Ow/Ob and HW groups were 26.8 versus 26.7 years and 37.0 versus 22.1 kg/m2 , respectively. The overall vaginal microbiome composition differed between groups (PERMANOVA, p = 0.035). Women with Ow/Ob had higher alpha diversity compared with women with HW (Wilcoxon test, Shannon index p = 0.025; inverse Simpson index p = 0.026). Lactobacillus dominance (≥30% proportional abundance) was observed in a greater proportion of women with HW (48.7%) compared with Ow/Ob (40.1%; p = 0.026). Conclusions The vaginal microbiome differs in reproductive-aged women with Ow/Ob compared with women with HW, with increased alpha diversity and decreased predominance of Lactobacillus. Observed differences in the vaginal microbiome may partially explain differences in preterm birth and bacterial vaginosis risk between these populations.

The outcomes of distal radial access (dRA) in chronic total occlusion percutaneous coronary intervention (CTO-PCI) have received limited study.We compared the clinical, angiographic, and procedural characteristics of 120 CTO-PCIs performed via dRA access with 2625 CTO-PCIs performed via proximal radial access (pRA) in a large, multicenter registry.The dRA group had lower mean PROGRESS-CTO score than the pRA group (1.0 ± 1 vs 1.2 ± 1, respectively; P=.05), while J-CTO score (2.4 ± 1.2 vs 2.3 ± 1.3; P=.43) and PROGRESS-CTO Complications score (2.8 ± 1.8 vs 2.6 ± 1.9; P=.16) were similar in the dRA vs pRA groups, respectively. Technical success was similar in the 2 groups (90% dRA vs 86% pRA; P=.14). Concomitant use of femoral access did not alter procedural success. The incidence of major periprocedural adverse cardiac events was similar in the 2 groups (0.8% dRA vs 2.4% pRA; P=.26), whereas the incidence of tamponade requiring pericardiocentesis was lower with dRA (0% dRA vs 4.69% pRA; P.001), as was air kerma radiation dose (median, 1.7 Gy; interquartile range [IQR], 0.97-2.63 Gy in the dRA group vs median, 2.27 Gy; IQR, 1.2-3.9 Gy in the pRA group; P.001).Use of dRA in CTO-PCI is associated with similar procedural success and risk of complications as compared with pRA.

The incidence of preterm birth exceeds 10% worldwide. There are significant disparities in the frequency of preterm birth among populations within countries, and women of African ancestry disproportionately bear the burden of risk in the United States. In the present study, we report a community resource that includes 'omics' data from approximately 12,000 samples as part of the integrative Human Microbiome Project. Longitudinal analyses of 16S ribosomal RNA, metagenomic, metatranscriptomic and cytokine profiles from 45 preterm and 90 term birth controls identified harbingers of preterm birth in this cohort of women predominantly of African ancestry. Women who delivered preterm exhibited significantly lower vaginal levels of Lactobacillus crispatus and higher levels of BVAB1, Sneathia amnii, TM7-H1, a group of Prevotella species and nine additional taxa. The first representative genomes of BVAB1 and TM7-H1 are described. Preterm-birth-associated taxa were correlated with proinflammatory cytokines in vaginal fluid. These findings highlight new opportunities for assessment of the risk of preterm birth.

Background Health care workers routinely contaminate skin and clothing when doffing personal protective equipment (PPE). Alternative doffing strategies, such as hand hygiene on gloved hands and double gloving, have been suggested but not validated by comparison against the standard Centers for Disease Control and Prevention procedures. Methods Participants were assigned to doff PPE following 1 of 4 specific strategies. Prior to doffing, PPE was “contaminated” with Glo Germ and fluorescing Staphylococcus epidermidis at the recommended level of 1.5 × 108 colony forming units/mL. After doffing, areas of self-contamination were detected using a black light. Cultures were taken from these areas using cotton swabs, inoculated onto blood agar plates, and incubated for 48hours. Each participant completed a survey regarding usability. The Fisher exact test and the Kruskal-Wallis test were used for data analysis with SAS 9.4. Results There were 51 participants who completed the study. Breaches in PPE were observed in only 5 of 51 doffs (10%). However, 46 of 51 (90%) had areas of self-contamination that was apparent by transfer of Glo Germ to skin or clothing. A subset (16%) of these sites also grew fluorescing S epidermidis. Assigned doffing strategy was associated with bacterial contamination (P = .0151), but not usability (P = .2372). Conclusions Participants experienced self-contamination when doffing PPE with both a surrogate marker and live bacteria. Close attention to doffing technique is necessary for optimal results, and one-step procedures may be more effective.

There is limited data on the use of atherectomy during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We compared the clinical and procedural characteristics and outcomes of CTO PCIs performed with or without atherectomy in a contemporary multicenter CTO PCI registry. Between 2012 and 2018, 3,607 CTO PCIs were performed at 21 participating centers. Atherectomy was used in 117 (3.2%) cases: rotational atherectomy in 105 cases, orbital atherectomy in 8, and both in 4 cases. Patients in whom atherectomy was used, were older (68 ± 8 vs 64 ± 10 years, p0.0001) and had higher Japan-chronic total occlusion score (3.0 ± 1.2 vs 2.4 ± 1.3, p0.0001). CTO PCI cases in which atherectomy was used had similar technical (91% vs 87%, p = 0.240) and procedural (90% vs 85%, p = 0.159) success and in-hospital major adverse cardiac event (4% vs 3%, p = 0.382) rates. However, atherectomy cases were associated with higher rates of donor vessel injury (4% vs 1%, p = 0.031), tamponade requiring pericardiocentesis (2.6% vs 0.4%, p = 0.012) and more often required use of a left ventricular assist device (9% vs 5%, p = 0.031). Atherectomy cases were associated with longer procedural duration (196 [141, 247] vs 119 [76, 180] minutes, p0.0001), and higher patient air kerma radiation dose (3.6 [2.5, 5.6] vs 2.8 [1.6, 4.7] Gray, p = 0.001). In conclusion, atherectomy is currently performed in approximately 3% of CTO PCI cases and is associated with similar technical and procedural success and overall major adverse cardiac event rates, but higher risk for donor vessel injury and tamponade.

Objectives This study examined the frequency and outcomes of radial access for chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Background Radial access improves the safety of PCI, but its role in CTO PCI remains controversial. Methods We compared the clinical, angiographic, and procedural characteristics of 3,790 CTO interventions performed between 2012 and 2018 via radial-only access (RA) (n = 747) radial-femoral access (RFA) (n = 844) and femoral-only access (n = 2,199) access at 23 centers in the United States, Europe, and Russia. Results Patients’ mean age was 65 ± 10 years, and 85% were men. Transradial access (RA and RFA) was used in 42% of CTO interventions and significantly increased over time from 11% in 2012 to 67% in 2018 (p Conclusions Transradial access is increasingly being used for CTO PCI and is associated with similar technical and procedural success and lower major bleeding rates compared with femoral-only access interventions. (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention [PROGRESS CTO]; NCT02061436)

ObjectiveEvaluate differences between the vaginal microbiome of reproductive-aged women with overweight and obesity (Ow/Ob) compared with healthy weight (HW).MethodsA cohort of 367 non-pregnant women (18-40 years) with Ow/Ob (body mass index [BMI] ≥25 kg/m2) was case-matched with 367 women with HW (BMI 18.0-24.9 kg/m2). The study was a secondary analysis of 16S rRNA vaginal microbiome surveys through the Vaginal Human Microbiome Study (VaHMP). Groups were matched on age, race/ethnicity, income, and nulliparity status.ResultsMean age and BMI of Ow/Ob and HW groups were 26.8 versus 26.7 years and 37.0 versus 22.1 kg/m2, respectively. The overall vaginal microbiome composition differed between groups (PERMANOVA, p=0.035). Women with Ow/Ob had higher alpha-diversity compared with women with HW (Wilcoxon test, Shannon index p=0.025; Inverse Simpson index p=0.026). Lactobacillus dominance (≥30% proportional abundance) was observed in a greater proportion of women with HW (48.7%) compared with Ow/Ob (40.1%; p=0.026).ConclusionsThe vaginal microbiome differs in reproductive-aged women with Ow/Ob compared with women with HW, with increased alpha-diversity and decreased predominance of Lactobacillus. Observed differences in vaginal microbiome may partially explain differences in preterm birth and bacterial vaginosis risk between these populations.

Gardnerella vaginalis has recently been split into 13 distinct species. In this study, we tested the hypotheses that species-specific variations in the vaginolysin (VLY) amino acid sequence could influence the interaction between the toxin and vaginal epithelial cells and that VLY variation may be one factor that distinguishes less virulent or commensal strains from more virulent strains. This was assessed by bioinformatic analyses of publicly available Gardnerella spp. sequences and quantification of cytotoxicity and cytokine production from purified, recombinantly produced versions of VLY. After identifying conserved differences that could distinguish distinct VLY types, we analyzed metagenomic data from a cohort of female subjects from the Vaginal Human Microbiome Project to investigate whether these different VLY types exhibited any significant associations with symptoms or Gardnerella spp.-relative abundance in vaginal swab samples. While Type 1 VLY was most prevalent among the subjects and may be associated with increased reports of symptoms, subjects with Type 2 VLY dominant profiles exhibited increased relative Gardnerella spp. abundance. Our findings suggest that amino acid differences alter the interaction of VLY with vaginal keratinocytes, which may potentiate differences in bacterial vaginosis (BV) immunopathology in vivo.

Introduction: Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has been advancing due to improvement of equipment, operator experience, and techniques. Methods: We examined contemporary outcomes of CTO PCI by analyzing the clinical, angiographic, and procedural characteristics of 7,031 CTO interventions performed in 6,984 patients at 35 participating centers between 2012 and 2020. Results: Mean age was 64.5 ± 10 years and 82% of the patients were men. The patients had high prevalence of comorbidities, such as diabetes (42%), prior coronary artery bypass graft surgery (29%), prior myocardial infarction (45%), and prior heart failure (29%). The most common CTO target vessel was the right coronary artery (53%), followed by the left anterior descending artery (26%), and left circumflex artery (20%). The mean J-CTO and PROGRESS scores were 2.41 ± 1.28 and 1.09 ± 1.01, respectively. The overall technical and procedural success rates were 85.9% and 83.8% and the rate of in-hospital major cardiac adverse events (MACE) was 2.06%. Technical success and procedural success rates were lower for higher values of J-CTO and PROGRESS scores, and MACE rate was higher ( Figure 1 ). The final successful crossing strategy was antegrade wire escalation in 53.7%, retrograde in 19.9%, and antegrade dissection reentry in 14.6%. The overall median air kerma radiation dose, contrast volume, procedure and fluoroscopy time were 2.30 (1.30, 3.90) Gray, 225 (160, 305) ml, 115 (75, 170) and 43 (26, 70) minutes, respectively. Conclusions: Using a combination of crossing strategies, high success and acceptable complication rates can be achieved in CTO PCI among various centers and patient populations.

The composition of the human vaginal microbiome has been extensively studied and is known to influence reproductive health. However, the functional roles of individual taxa and their contributions to negative health outcomes have yet to be well characterized. Here, we examine two vaginal bacterial taxa grouped within the genus Megasphaera that have been previously associated with bacterial vaginosis (BV) and pregnancy complications. Phylogenetic analyses support the classification of these taxa as two distinct species. These two phylotypes, Megasphaera phylotype 1 (MP1) and Megasphaera phylotype 2 (MP2), differ in genomic structure and metabolic potential, suggestive of differential roles within the vaginal environment. Further, these vaginal taxa show evidence of genome reduction and changes in DNA base composition, which may be common features of host dependence and/or adaptation to the vaginal environment. In a cohort of 3,870 women, we observed that MP1 has a stronger positive association with bacterial vaginosis whereas MP2 was positively associated with trichomoniasis. MP1, in contrast to MP2 and other common BV-associated organisms, was not significantly excluded in pregnancy. In a cohort of 52 pregnant women, MP1 was both present and transcriptionally active in 75.4% of vaginal samples. Conversely, MP2 was largely absent in the pregnant cohort. This study provides insight into the evolutionary history, genomic potential and predicted functional role of two clinically relevant vaginal microbial taxa.

The impact of intravascular ultrasound (IVUS) utilization for stent optimization on the long-term outcomes in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study.We examined the outcomes of CTO-PCI with and without IVUS use for stent optimization in 922 CTO-PCIs performed between 2012 and 2019 at 12 United States centers. Major adverse cardiac event (MACE) was defined as the composite of cardiac death, acute coronary syndrome, and target-vessel revascularization.IVUS was used in 344 procedures (37%) for stent optimization. Mean patient age was 65 ± 10 years and 83% were men. Patients in the IVUS group were less likely to have a prior myocardial infarction (39% vs 50%; P.01), more likely to undergo right coronary artery CTO-PCI (49% vs 55%; P=.01), and had higher mean J-CTO score (2.6 ± 1.1 vs 2.4 ± 1.2; P=.04). The final crossing strategy in patients in the IVUS group was less likely to be antegrade wire escalation (54% vs 57%) and more likely to be retrograde (29% vs 21%; P.01). Median follow-up was 141 days (interquartile range, 30-365 days). The incidence of 12-month MACE was similar in the IVUS and no-IVUS groups (20.3% vs 18.3%; log-rank P=.67).IVUS was used for stent optimization in approximately one-third of CTO-PCIs. Despite higher lesion complexity in the IVUS group, the incidence of MACE was similar during follow-up.

Sneathia amnii is a poorly characterized emerging pathogen that has been implicated in amnionitis and urethritis. We found that S. amnii damages fetal membranes, and we identified and purified a cytotoxic exotoxin that lyses human red blood cells and damages cells from fetal membranes. The gene appears to be cotranscribed with a second gene that encodes a protein with identity to two-partner system transporters, suggesting that it is the “A,” or secreted component of a type Vb system. The toxin is 1,881 amino acids with a molecular weight of approximately 200 kDa. It binds to red blood cell membranes and forms pores with a diameter of 2.0 to 3.0 nm, resulting in osmolysis. Because it appears to be the “A” or passenger component of a two-partner system, we propose to name this novel cytotoxin/hemolysin CptA for cytopathogenic toxin component A. IMPORTANCE Sneathia amnii is a very poorly characterized emerging pathogen that can affect pregnancy outcome and cause urethritis and other infections. To date, nothing is known about its virulence factors or pathogenesis. We have identified and isolated a cytotoxin, named CptA for cytopathogenic toxin, component A, that is produced by S. amnii. CptA is capable of permeabilizing chorionic trophoblasts and lysing human red blood cells and, thus, may play a role in virulence. Except for small domains conserved among two-partner secretion system passenger proteins, the cytotoxin exhibits little amino acid sequence homology to known toxins. In this study, we demonstrate the pore-forming activity of this novel toxin.

Summary Background Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications. Methods In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov , NCT02439749 . Findings From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was −3·9 mm Hg (Bayesian 95% credible interval −6·2 to −1·6) and for office systolic blood pressure the difference was −6·5 mm Hg (−9·6 to −3·5). No major device-related or procedural-related safety events occurred up to 3 months. Interpretation SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications. Funding Medtronic.

Writing is considered a very important skill in language learning yet a very challenging task for students to master it. It is also a required skill for students to score good grades in their academics. Inappropriate use of words, incorrect, and illogical sentence structures and grammatical mistakes while writing, reflect poorly on the language proficiency of learners. This also creates issues later in their professional life. Addressing these challenges at the tertiary level has been an area of concern to English language teachers. The prime aim of this study is to explore the challenges and problems encountered by teachers in teaching writing skills to learners in the ESL classroom. This chapter also proposes a process-product based effective pedagogic practice which was experimented in the ESL classroom while teaching writing. The approach employed facilitated learners to overcome issues by making learners use the language in context rather than merely based on grammar structure.