Divergent Gut Microbiota: Archaeal and Bacterial Signatures Unveil Unique Patterns in Colombian Cyclists Compared to Weightlifters and Non-Athletes.

Engagement in physical activity, across various sports, promotes a diverse microbiota in active individuals. This study examines the gut microbiota of Colombian athletes, specifically weightlifters (n = 16) and road cyclists (n = 13), compared to non-athletes (n = 15). Using Kruskal-Wallis tests, the physical activity level of a group of non-athletic individuals and the sports experience of a group of professional athletes is analyzed. The median age of participants is 24 years, comprising 25 men and 19 women. The microbiota is collected using fecal samples. Participants provided these samples during their pre-competitive stage, specifically during the concentration phase occurring two weeks prior to national competitions. This timing is chosen to capture the microbial composition during a period of heightened physical preparation. Questionnaire responses and microbial composition assessments identify disparities among groups. Microbial composition analysis explores core microbiome, abundance, and taxonomy using Pavian, MicrobiomeAnalyst 2.0, and GraPhlAn. ANCOM-BC2 reveals differentially abundant species. Road cyclists exhibit decreased Bacteria and increased Archaea abundance. Phylum-level variations included Planctomycetes, Acidobacteria, and Proteobacteria, while Bacteroidetes prevailed. Key families influencing gut microbiota are Bacteroidaceae, Muribaculaceae, and Selenomonadaceae. Weightlifters exhibit unique viral and archaeal community connections, while cyclists showed specialized microbial interplay influenced by endurance exercise. Correlation network analysis emphasizes distinctive microbial interactions within athlete groups, shedding light on the impact of physical activities on gut microbiota and athlete health.

Recent advances with alkaline phosphatase isoenzymes and their inhibitors.

Alkaline phosphatases are found in different living species and play crucial roles in various significant functions, such as hydrolyzing a variable spectrum of phosphate-containing physiological compounds, contributing to DNA synthesis, bone calcification, and attenuation of inflammation. They are homodimeric enzymes; each subunit contains one magnesium ion and two zinc ions crucial for the catalytic activity of the enzyme. Alkaline phosphatases exist in four distinct isoenzymes (placental, intestinal, germ cell, and tissue nonspecific alkaline phosphatases), which are expressed by four different genes; each one of them has distinguished functions. Any disturbance in the gene expression of alkaline phosphatase eventually induces serious disease conditions. Thus, the need to explore new lead inhibitors has increased recently. In this literature review, we aim to investigate the role of alkaline phosphatase in different diseases and physiological conditions and to study the structure-activity relationships of recently reported inhibitors. We focused on the lead compounds reported in the last 5 years (between 2015 and 2019).

Finding of Agr Phase Variants in Staphylococcus aureus.

Staphylococcus aureus is an important human pathogen whose success is largely attributed to its vast arsenal of virulence factors that facilitate its invasion into, and survival within, the human host. The expression of these virulence factors is controlled by the quorum sensing accessory gene regulator (Agr) system. However, a large proportion of clinical S. aureus isolates are consistently found to have a mutationally inactivated Agr system. These mutants have a survival advantage in the host but are considered irreversible mutants. Here we show, for the first time, that a fraction of Agr-negative mutants can revert their Agr activity. By serially passaging Agr-negative strains and screening for phenotypic reversion of hemolysis and subsequent sequencing, we identified two mutational events responsible for reversion: a genetic duplication plus inversion event and a poly(A) tract alteration. Additionally, we demonstrate that one clinical Agr-negative methicillin-resistant S. aureus (MRSA) isolate could reproducibly generate Agr-revertant colonies with a poly(A) tract genetic mechanism. We also show that these revertants activate their Agr system upon phagocytosis. We propose a model in which a minor fraction of Agr-negative S. aureus strains are phase variants that can revert their Agr activity and may act as a cryptic insurance strategy against host-mediated stress.IMPORTANCEStaphylococcus aureus is responsible for a broad range of infections. This pathogen has a vast arsenal of virulence factors at its disposal, but avirulent strains are frequently isolated as the cause of clinical infections. These isolates have a mutated agr locus and have been believed to have no evolutionary future. Here we show that a fraction of Agr-negative strains can repair their mutated agr locus with mechanisms resembling phase variation. The agr revertants sustain an Agr OFF state as long as they exist as a minority but can activate their Agr system upon phagocytosis. These revertant cells might function as a cryptic insurance strategy to survive immune-mediated host stress that arises during infection.

Efficacy of live attenuated vaccine derived from the Streptococcus agalactiae on the immune responses of Oreochromis niloticus.

Streptococcus agalactiae species have been recognized as the main pathogen causing high mortality in fish leading to significant worldwide economical losses to the aquaculture industries. Vaccine development has become a priority in combating multidrug resistance in bacteria; however, there is a lack of commercial live attenuated vaccine (LAV) against S. agalactiae in Malaysia. The aim of this study is to compare two methods using attenuated bacteria as live vaccine and to evaluate the efficacy of selected LAV on the immune responses and resistance of Oreochromis niloticus (tilapia) against S. agalactiae. The LAV derived from S. agalactiae had been weakened using the chemical agent Acriflavine dye (LAV1), whereas the second vaccine was weakened using serial passages of bacteria on broth media (LAV2). Initial immunization was carried out only on day one, given twice-in the morning and evening, for the 42 day period. Serum samples were collected to determine the systemic antibody (IgM) responses and lysozymal (LSZ) activity using ELISA. On day 43 after immunization, the fish were injected intraperitoneally (i.p) with 0.1 mL of S. agalactiae at LD50 = 1.5 × 105 (CFU)/fish. Fish were monitored daily for 10 days. Clinical signs, mortality and the relative percent of survival (RPS) were recorded. Trial 1 results showed a significant increased (P < 0.05) in serum IgM titers and LSZ activity as compared to LAV2 and the control group (unvaccinated fish). The efficacy of LAV1 was proven effective as determined by the RPS values, LAV1 at 81.58% as compared to LAV2 at 65.79%. Trial 2 of LAV1 and control group were further determined by administering primary and booster doses revealed a RPS value for LAV1 of 82.05%, with the significant enhancement on the immune responses of tilapia as compared to control group. In conclusion, LAV revealed to elevate antibody IgM levels, LSZ activity and provide long-term protection when added to feed. LAV is a low-cost vaccine shown to rapidly increase the immune response of fish and increase survival rates of fish against S. agalactiae infection.

Association of African Ancestry With Electrocardiographic Voltage and Concentric Left Ventricular Hypertrophy: The Dallas Heart Study.

Importance: Compared with white individuals, black individuals have increased electrocardiographic voltage and an increased prevalence of concentric left ventricular (LV) hypertrophy. Whether environmental or genetic factors lead to these racial differences is unknown. Objective: To determine whether proportion of genetically determined African ancestry among self-reported black individuals is associated with increased electrocardiographic voltage and concentric LV hypertrophy (LVH). Design, Setting, and Participants: The Dallas Heart Study is a probability-based cohort study of English- or Spanish-speaking Dallas County, Texas, residents, with deliberate oversampling of black individuals. Participants underwent extensive phenotyping, which included electrocardiography (ECG), cardiac magnetic resonance imaging (CMR), and dual-energy radiography absorptiometry (DEXA) at a single center. Participants aged 18 to 65 years who enrolled in the Dallas Heart Study between July 2000 and December 2002, self-identified as black (n = 1251) or white (n = 826), and had ECG, CMR, and DEXA data were included in this analysis. Data were analyzed from June 2017 to September 2018. Exposures: Proportion of African ancestry. Main Outcomes and Measures: Electrocardiographic voltage (12-lead and 9-lead) and markers of concentric LVH as assessed by CMR (LV concentricity0.67 [LV mass/end-diastolic volume0.67], LV wall thickness [LVWT], and prevalent LVH [defined by LV mass/height2.7]). Results: Of the 2077 participants included in the study, 1138 (54.8%) were women, and the mean (SD) age was 45.2 (9.9) years. Black race and African ancestry were individually associated with increased ECG voltage, LV concentricity0.67, LVWT, and prevalent LVH in multivariable analyses adjusting for age, sex, systolic blood pressure, antihypertensive medication use, and body composition. When African ancestry and black race were entered together into multivariable models, African ancestry but not black race remained associated with ECG voltage, LVWT, LV concentricity0.67, and prevalent LVH. Among black participants, African ancestry remained associated with these 4 phenotypes (12-lead voltage: ß, 0.05; P = .04; LVWT: ß, 0.05; P = .02; LV concentricty0.67: ß, 0.05; P = .045; prevalent LVH: odds ratio, 1.2; 95% CI, 1.03-1.4; P = .02). Conclusions and Relevance: Genetically determined African ancestry was associated with electrocardiographic voltage, measures of concentric LV remodeling, and prevalent LVH. These data support a genetic basis related to African ancestry for the increased prevalence of these cardiovascular traits in black individuals.

Contemporary Use of Laser During Percutaneous Coronary Interventions: Insights from the Laser Veterans Affairs (LAVA) Multicenter Registry.

BACKGROUND: The contemporary use and outcomes of excimer laser coronary atherectomy (ELCA) in percutaneous coronary intervention (PCI) are not well described. METHODS: We examined the baseline clinical and angiographic characteristics and procedural outcomes of 130 target lesions in 121 consecutive PCIs (n = 116 patients) in which ELCA was performed at three United States Department of Veterans Affairs (VA) medical centers between 2008 and 2016. RESULTS: Mean age was 68.5 ± 9 years and 97% of the patients were men. Patients had high prevalence of diabetes mellitus (63%), prior coronary artery bypass graft surgery (41%), and prior myocardial infarction (60%). The most common target vessel was the left anterior descending (32%), followed by the right coronary artery (30%), circumflex artery (20%), and saphenous vein graft (12%). The target lesions were highly complex, with moderate/severe calcification in 62% and in-stent restenosis in 37%. The most common indication for ELCA was balloon-uncrossable lesions (43.8%), followed by balloon-undilatable lesions (40.8%) and thrombotic lesions (12.3%). Use of ELCA was associated with high technical success rate (90.0%) and procedural success rate (88.8%), and low major adverse cardiac event (MACE) rate (3.45%). Mean procedure time was 120 min (interquartile range [IQR], 81-191 min), air kerma radiation dose was 2.76 Gy (IQR, 1.32-5.01 Gy), and contrast volume was 273 mL (IQR, 201-362 mL). CONCLUSION: In a contemporary multicenter United States registry, ELCA was commonly used in highly complex lesions and was associated with high technical and procedural success rates and low incidence of MACE.

Radiation-associated lens changes in the cardiac catheterization laboratory: Results from the IC-CATARACT (CATaracts Attributed to RAdiation in the CaTh lab) study.

OBJECTIVE: To examine the relationship between occupational exposure to ionizing radiation and the prevalence of lens changes in interventional cardiologists (ICs) and catheterization laboratory ("cath-lab") staff. BACKGROUND: Exposure to ionizing radiation is associated with the development of lens opacities. ICs and cath-lab staff can receive high doses of ionizing radiation without protection, and may thus be at risk for lens opacity formation. METHODS: We conducted a cross-sectional study at an interventional cardiology conference. Study participants completed a questionnaire pertaining to occupational exposure to radiation and potential confounders for the development of cataracts, followed by slit-lamp examination and grading of lens findings. RESULTS: A total of 117 attendees participated in the study, including 99 (85%; 49 ± 11 years-old; 82% male) with occupational exposure to ionizing radiation and 18 (15%; 39 ± 12 years-old; 61% male) unexposed controls. The prevalence of overall cortical and posterior subcapsular lens changes (including subclinical findings) was higher in exposed participants compared with controls (47 vs. 17%, P = 0.015). Occupational exposure and age over 60 were independent predictors of lens changes (odds ratio [95% CI]: 6.07 [1.38-43.45] and 7.72 [1.60-43.34], respectively). The prevalence of frank opacities was low and similar between the two groups (14 vs. 6%, P = 0.461). Most lens findings consisted of subclinical changes in the periphery of the lens without impact on visual acuity. CONCLUSIONS: Compared with unexposed controls, ICs and cath-lab staff had a higher prevalence of lens changes that may be attributable to ionizing radiation exposure. While most of these changes were subclinical, they are important due to the potential to progress to clinical symptoms, highlighting the importance of minimizing staff radiation exposure.

Sodium Polyanethol Sulfonate Modulates Natural Transformation of SigH-Expressing Staphylococcus aureus.

Expression of genes required for natural genetic competence in Staphylococcus aureus is controlled by an alternative transcription sigma factor, SigH. However, even in the SigH-expressing cells, the DNA transformation efficiency varies depending on culture conditions. We report here that cells grown in the competence-inducing medium (CS2 medium) exhibit enlarged morphology with disintegrated cell walls. Notably, an autolysis inhibitor, Sodium Polyanethol Sulfonate (SPS), facilitated transformation in CS2 medium in a dose-dependent manner, suggesting the involvement of the cell wall metabolism in transformation. However, the transformation efficiency of cells grown in TSB was not improved by physical or enzymatic damage on the cell walls.

Adjacent-possible ecological niche: growth of Lactobacillus species co-cultured with Escherichia coli in a synthetic minimal medium.

In certain conditions, members of the Lactobacillus genus are auxotrophs that have fastidious requirements for growth. Notably, Lactobacillus cannot grow in M9 medium, a minimal synthetic medium used for Escherichia coli. However, we found that some Lactobacillus strains can be grown in M9 when co-cultured with E. coli K-12. In the co-culture, L. casei proliferates exponentially, reaching cell densities of 108 CFU (colony-forming unit) ml-1 in 6 h and dominating E. coli in the late growth phase. Spent medium from E. coli grown overnight lacked this growth-promoting effect on L. casei. Similarly, the effect was not observed when the species were separated by a 0.4-µm membrane. Microscopic observations showed that L. casei are embedded in the micro-scale clusters of E. coli in the early growth phase. This study describes for the first time the ability of a Lactobacillus species to grow in minimal medium when in close proximity with co-cultured bacteria.

The Impact of Proximal Vessel Tortuosity on the Outcomes of Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From a Contemporary Multicenter Registry.

INTRODUCTION: We examined the impact of proximal vessel tortuosity on the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: The baseline clinical and angiographic characteristics and procedural outcomes of 1618 consecutive CTO-PCIs performed between 2012 and 2016 at 14 United States centers in 1589 patients were reviewed. RESULTS: Mean patient age was 65.3 ± 10.0 years and 85% were men. Moderate/severe proximal vessel tortuosity was present in 35.7% of target lesions. Compared with non-tortuous lesions, tortuous lesions had longer length (30 mm [interquartile range, 20-50 mm] vs 28 mm [interquartile range, 16-40 mm]; P<.001), more proximal cap ambiguity (36% vs 28%; P<.01), and more frequent utilization of the retrograde approach (52% vs 37%; P<.001). Moderate/severe proximal vessel tortuosity was associated with lower technical success rates (84.1% vs 91.3%; P<.001) and procedural success rates (82.3% vs 89.9%; P<.001), but similar incidence of major cardiac adverse events (3.0% vs 2.5%; P=.59). Moderate/severe tortuosity was associated with longer procedure time and fluoroscopy time, higher air kerma radiation dose, and larger contrast volume. CONCLUSION: In a contemporary multicenter registry, moderate/severe proximal vessel tortuosity was present in approximately one-third of target CTO lesions and was associated with more frequent use of the retrograde approach and lower success rates, but similar complication rates.

Comparison of the American College of Cardiology/American Heart Association and the European Society of Cardiology Guidelines for the Management of Patients With Valvular Heart Disease.

BACKGROUND: The American College of Cardiology/American Heart Association (ACC/AHA) and the European Society of Cardiology (ESC) have developed guidelines to assist clinicians in making evidence-based decisions. This study compares the ACC/AHA and ESC guidelines for the management of patients with valvular heart disease (VHD). METHODS: The current ACC/AHA and ESC guidelines for VHD, last updated in 2014 and 2012, respectively, were compared by class of recommendation (COR), level of evidence (LOE), and content. RESULTS: The ACC/AHA and ESC VHD guidelines contain 229 and 85 recommendations, respectively. The COR distributions of the ACC/AHA and ESC VHD guidelines were 47.6% vs 44.7% class I [P=.65]; 46.3% vs 55.3% class II [P=.16]; and 6.1% vs 0.0% class III [P=.01], respectively. The LOE distributions were 3.1% vs 0.0% LOE A [P=.20]; 47.2% vs 10.6% LOE B [P<.001]; and 49.8% vs 89.4% LOE C [P<.001], respectively. The recommendation type distributions were 31.0% vs 2.4% diagnostic [P<.001]; 23.1% vs 16.5% medical therapy [P=.20]; and 45.9% vs 81.2% interventional/surgical recommendations [P<.001], respectively. The content of the guidelines was similar, with only minor differences in a few recommendations. CONCLUSIONS: The ACC/AHA VHD guidelines contain significantly more recommendations. The distribution of COR was similar, but the ACC/AHA guidelines included more LOE B recommendations and fewer LOE C recommendations, suggesting that the ACC/AHA guidelines place greater emphasis on published data than expert opinion. Overall, the ACC/AHA and ESC guidelines provide similar recommendations, suggesting consistency in practice; however, the relative paucity of LOE A recommendations highlights the need for additional research.

Comparison of the American College of Cardiology/American Heart Association and the European Society of Cardiology guidelines for the management of patients with non-ST-segment elevation acute coronary syndromes.

INTRODUCTION: The American College of Cardiology (ACC), the American Heart Association (AHA), and the European Society of Cardiology (ESC) have been developing guidelines to assist clinicians in making evidence-based decisions. MATERIALS AND METHODS: The current ACC/AHA and ESC guidelines for non-ST-segment elevation acute coronary syndromes (NSTE-ACS) that were updated in 2014 and 2015, respectively, were compared to assess the number of recommendations on the basis of class of recommendation and level of evidence (LOE), the sources cited, and the content. RESULTS: The total number of recommendations in the ACC/AHA and ESC guidelines was 182 and 147, respectively. The recommendation class distribution of the ACC/AHA guidelines was 61.0% class I (compared with 61.9% in the ESC guidelines, P=0.865), 29.7% class II (compared with 32.0% in the ESC guidelines, P=0.653), and 9.3% class III (compared with 6.1% in the ESC guidelines, P=0.282). The LOE distribution among ACC/AHA guidelines was 15.9% LOE A (compared with 27.9% in the ESC guidelines, P=0.008), 50.0% LOE B (compared with 33.3% in the ESC guidelines, P=0.002), and 34.1% LOE C (compared with 38.8% in the ESC guidelines, P=0.377). The ACC/AHA guidelines cited 827 publications and the ESC guidelines cited 551 publications, 124 of which were shared by both sets of guidelines. The guidelines' approaches to NSTE-ACS were consistent, with minor differences in diagnostic and medical therapy recommendations. CONCLUSION: Overall, the ACC/AHA and ESC guidelines contain a comparable number of recommendations and provide similar guidance for the management of patients with NSTE-ACS.

Saphenous vein graft near-infrared spectroscopy imaging insights from the lipid core plaque association with clinical events near-infrared spectroscopy (ORACLE-NIRS) registry.

OBJECTIVES: We sought to examine near-infrared spectroscopy (NIRS) imaging findings of aortocoronary saphenous vein grafts (SVGs). BACKGROUND: SVGs are prone to develop atherosclerosis similar to native coronary arteries. They have received little study using NIRS. METHODS: We examined the clinical characteristics and imaging findings from 43 patients who underwent NIRS imaging of 45 SVGs at our institution between 2009 and 2016. RESULTS: The mean patient age was 67 ± 7 years and 98% were men, with high prevalence of diabetes mellitus (56%), hypertension (95%), and dyslipidemia (95%). Mean SVG age was 7 ± 7 years, mean SVG lipid core burden index (LCBI) was 53 ± 60 and mean maxLCBI4 mm was 194 ± 234. Twelve SVGs (27%) had lipid core plaques (2 yellow blocks on the block chemogram), with a higher prevalence in SVGs older than 5 years (46% vs. 5%, P = 0.002). Older SVG age was associated with higher LCBI (r = 0.480, P < 0.001) and higher maxLCBI4 mm (r = 0.567, P < 0.001). On univariate analysis, greater annual total cholesterol exposure was associated with higher SVG LCBI (r = 0.30, P = 0.042) and annual LDL-cholesterol and triglyceride exposure were associated with higher SVG maxLCBI4 mm (LDL-C: r = 0.41, P = 0.020; triglycerides: r = 0.36, P = 0.043). On multivariate analysis, the only independent predictor of SVG LCBI and maxLCBI4mm was SVG age. SVG percutaneous coronary intervention was performed in 63% of the patients. An embolic protection device was used in 96% of SVG PCIs. Periprocedural myocardial infarction occurred in one patient. CONCLUSIONS: Older SVG age and greater lipid exposure are associated with higher SVG lipid burden. © 2016 Wiley Periodicals, Inc.

Prevalence, indications and management of balloon uncrossable chronic total occlusions: Insights from a contemporary multicenter US registry.

BACKGROUND: Balloon uncrossable lesions can be challenging to treat, requiring specialized techniques and equipment. METHODS: We examined the prevalence, clinical and angiographic characteristics, management and procedural outcomes of balloon uncrossable lesions in a multicenter chronic total occlusion (CTO) percutaneous coronary intervention (PCI) registry. RESULTS: Between 2012 and 2016, 718 CTO PCIs (in which the occlusion was successfully crossed with a guidewire) were performed in 701 patients at 11 US centers. Mean age was 65.6 ± 10 years and 84% of the patients were men. Balloon uncrossable lesions represented 9% of all CTOs. Balloon uncrossable CTOs had more moderate/severe calcification (82% vs. 52%, P < 0.0001), moderate/severe tortuosity (61% vs. 35% P < 0.0001) and higher J-CTO score (2.95 ± 1.32 vs. 2.43 ± 1.23, P = 0.005) as compared with the remaining lesions. Technical and procedural success was significantly lower for balloon uncrossable lesions (90.5% vs. 98.3%, P < 0.0001 and 88.9% vs. 96.6% P = 0.004), respectively, but the incidence of major adverse events was similar (1.6% vs. 2.2%, P = 0.751). Balloon uncrossable lesions required longer procedure (208 [interquartile range: 135, 258] vs. 135 [94, 194] min, P < 0.0001) and fluoroscopy (77 [52, 100] vs. 45 min [27, 75], P < 0.0001) time. Techniques used to treat balloon uncrossable lesions included balloon-assisted microdissection (23%), excimer laser atherectomy (18%), and rotational atherectomy (16%). Excimer laser atherectomy and balloon-assisted microdissection were associated with the highest technical and procedural success rates. CONCLUSIONS: Balloon uncrossable CTOs are common, are associated with high rates of technical failure, and require specialized techniques for successful treatment. © 2016 Wiley Periodicals, Inc.

Comparison of various scores for predicting success of chronic total occlusion percutaneous coronary intervention.

BACKGROUND: Various scoring systems have been developed to predict the technical outcome and procedural efficiency of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We examined the predictive capacity of 3 CTO PCI scores (Clinical and Lesion-related [CL], Multicenter CTO registry in Japan [J-CTO] and Prospective Global Registry for the Study of Chronic Total Occlusion Intervention [PROGRESS CTO] scores) in 664 CTO PCIs performed between 2012 and 2016 at 13 US centers. RESULTS: Technical success was 88% and the retrograde approach was utilized in 41%. Mean CL, J-CTO and PROGRESS CTO scores were 3.9±1.9, 2.6±1.2 and 1.4±1.0, respectively. All scores were inversely associated with technical success (p<0.001 for all) and had moderate discriminatory capacity (area under the curve 0.691 for the CL score, 0.682 for the J-CTO score and 0.647 for the PROGRESS CTO score [p=non-significant for pairwise comparisons]). The difference in technical success between the minimum and maximum CL score strata was the highest (32%, vs. 15% for J-CTO and 18% for PROGRESS CTO scores). All scores tended to perform better in antegrade-only procedures and correlated significantly with procedure time and fluoroscopy dose; the CL score also correlated significantly with contrast utilization. CONCLUSIONS: CL, J-CTO and PROGRESS CTO scores perform moderately in predicting technical outcome of CTO PCI, with better performance for antegrade-only procedures. All scores correlate with procedure time and fluoroscopy dose, and the CL score also correlates with contrast utilization.

Effect of Lesion Age on Outcomes of Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From a Contemporary US Multicenter Registry.

BACKGROUND: We sought to determine the effect of lesion age on procedural techniques and outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We examined the characteristics and outcomes of 394 CTO PCIs with data on lesion age, performed between 2012 and 2016 at 11 experienced US centres. RESULTS: Mean patient age was 66 ± 10 years and 85.6% of the patients were men. Overall technical and procedural success rates were 90.1% and 87.5%, respectively. A major adverse cardiovascular event (MACE) occurred in 16 patients (4.1%). Mean and median lesion ages were 43 ± 62 months and 12 months (interquartile range, 3-64 months), respectively. Patients were stratified into tertiles according to lesion age (3-5, 5-36.3, and > 36.3 months). Older lesion age was associated with older patient age (68 ± 8 vs 65 ± 10 vs 64 ± 11 years; P = 0.009), previous coronary artery bypass grafting (62% vs 42% vs 30%; P < 0.001), and moderate/severe calcification (75% vs 53% vs 59%; P = 0.001). Older lesions more often required use of the retrograde approach and antegrade dissection/re-entry for successful lesion crossing. There was no difference in technical (87.8% vs 89.6% vs 93.0%; P = 0.37) or procedural (86.3% vs 87.4% vs 89.0%; P = 0.80) success, or the incidence of MACE (3.1% vs 3.0% vs 6.3%; P = 0.31) for older vs younger occlusions. CONCLUSIONS: Older CTO lesions exhibit angiographic complexity and more frequently necessitate the retrograde approach or antegrade dissection/re-entry. Older CTOs can be recanalized with high technical and procedural success and acceptable MACE rates. Lesion age appears unlikely to be a significant determinant of CTO PCI success.

Expression of a cryptic secondary sigma factor gene unveils natural competence for DNA transformation in Staphylococcus aureus.

It has long been a question whether Staphylococcus aureus, a major human pathogen, is able to develop natural competence for transformation by DNA. We previously showed that a novel staphylococcal secondary sigma factor, SigH, was a likely key component for competence development, but the corresponding gene appeared to be cryptic as its expression could not be detected during growth under standard laboratory conditions. Here, we have uncovered two distinct mechanisms allowing activation of SigH production in a minor fraction of the bacterial cell population. The first is a chromosomal gene duplication rearrangement occurring spontaneously at a low frequency [≤10(-5)], generating expression of a new chimeric sigH gene. The second involves post-transcriptional regulation through an upstream inverted repeat sequence, effectively suppressing expression of the sigH gene. Importantly, we have demonstrated for the first time that S. aureus cells producing active SigH become competent for transformation by plasmid or chromosomal DNA, which requires the expression of SigH-controlled competence genes. Additionally, using DNA from the N315 MRSA strain, we successfully transferred the full length SCCmecII element through natural transformation to a methicillin-sensitive strain, conferring methicillin resistance to the resulting S. aureus transformants. Taken together, we propose a unique model for staphylococcal competence regulation by SigH that could help explain the acquisition of antibiotic resistance genes through horizontal gene transfer in this important pathogen.