Bacteriophage Crosstalk: Coordination of Prophage Induction by Trans-Acting Antirepressors

Many species of bacteria harbor multiple prophages in their genomes. Prophages often carry genes that confer a selective advantage to the bacterium, typically during host colonization. Prophages can convert to infectious viruses through a process known as induction, which is relevant to the spread of bacterial virulence genes. The paradigm of prophage induction, as set by the phage Lambda model, sees the process initiated by the RecA-stimulated self-proteolysis of the phage repressor. Here we show that a large family of lambdoid prophages found in Salmonella genomes employs an alternative induction strategy. The repressors of these phages are not cleaved upon induction; rather, they are inactivated by the binding of small antirepressor proteins. Formation of the complex causes the repressor to dissociate from DNA. The antirepressor genes lie outside the immunity region and are under direct control of the LexA repressor, thus plugging prophage induction directly into the SOS response. GfoA and GfhA, the antirepressors of Salmonella prophages Gifsy-1 and Gifsy-3, each target both of these phages' repressors, GfoR and GfhR, even though the latter proteins recognize different operator sites and the two phages are heteroimmune. In contrast, the Gifsy-2 phage repressor, GtgR, is insensitive to GfoA and GfhA, but is inactivated by an antirepressor from the unrelated Fels-1 prophage (FsoA). This response is all the more surprising as FsoA is under the control of the Fels-1 repressor, not LexA, and plays no apparent role in Fels-1 induction, which occurs via a Lambda CI-like repressor cleavage mechanism. The ability of antirepressors to recognize non-cognate repressors allows coordination of induction of multiple prophages in polylysogenic strains. Identification of non-cleavable gfoR/gtgR homologues in a large variety of bacterial genomes (including most Escherichia coli genomes in the DNA database) suggests that antirepression-mediated induction is far more common than previously recognized

Identifying Cardiac Amyloid in Aortic Stenosis: ECV Quantification by CT in TAVR Patients.

OBJECTIVES: The purpose of this study was to validate computed tomography measured ECV (ECVCT) as part of routine evaluation for the detection of cardiac amyloid in patients with aortic stenosis (AS)-amyloid. BACKGROUND: AS-amyloid affects 1 in 7 elderly patients referred for transcatheter aortic valve replacement (TAVR). Bone scintigraphy with exclusion of a plasma cell dyscrasia can diagnose transthyretin-related cardiac amyloid noninvasively, for which novel treatments are emerging. Amyloid interstitial expansion increases the myocardial extracellular volume (ECV). METHODS: Patients with severe AS underwent bone scintigraphy (Perugini grade 0, negative; Perugini grades 1 to 3, increasingly positive) and routine TAVR evaluation CT imaging with ECVCT using 3- and 5-min post-contrast acquisitions. Twenty non-AS control patients also had ECVCT performed using the 5-min post-contrast acquisition. RESULTS: A total of 109 patients (43% male; mean age 86 ± 5 years) with severe AS and 20 control subjects were recruited. Sixteen (15%) had AS-amyloid on bone scintigraphy (grade 1, n = 5; grade 2, n = 11). ECVCT was 32 ± 3%, 34 ± 4%, and 43 ± 6% in Perugini grades 0, 1, and 2, respectively (p < 0.001 for trend) with control subjects lower than lone AS (28 ± 2%; p < 0.001). ECVCT accuracy for AS-amyloid detection versus lone AS was 0.87 (0.95 for 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid Perugini grade 2 only), outperforming conventional electrocardiogram and echocardiography parameters. One composite parameter, the voltage/mass ratio, had utility (similar AUC of 0.87 for any cardiac amyloid detection), although in one-third of patients, this could not be calculated due to bundle branch block or ventricular paced rhythm. CONCLUSIONS: ECVCT during routine CT TAVR evaluation can reliably detect AS-amyloid, and the measured ECVCT tracks the degree of infiltration. Another measure of interstitial expansion, the voltage/mass ratio, also performed well

New mobile gene cassettes containing an aminoglycoside resistance gene, aacA7, and a chloramphenicol resistance gene, catB3, in an integron in pBWH301.

The multidrug resistance plasmid pBWH301 was shown to contain a sull-associated integron with five inserted gene cassettes, aacA7-catB3-aadB-oxa2-orfD, all of which can be mobilized by the integron-encoded DNA integrase. The aadB, oxa2, and orfD cassettes are identical to known cassettes. The aacA7 gene encodes a protein that is a member of one of the three known families of aminoglycoside acetyltransferases classified as AAC(6')-I. The chloramphenicol acetyltransferase encoded by the catB3 gene is closely related to members of a recently identified family of chloramphenicol acetyltransferases. The catB3 gene displays a relatively high degree of sequence identity to a chromosomally located open reading frame in Pseudomonas aeruginosa, and this may represent evidence for the acquisition by a cassette of a chromosomal gene

Feasibility, Usability and Acceptability of a mHealth Intervention to Reduce Cardiovascular Risk in Rural Hispanic Adults: Descriptive Study

BackgroundMobile health (mHealth) technology using apps or devices to self-manage health behaviors is an effective strategy to improve lifestyle-related health problems such as hypertension, obesity, and diabetes. However, few studies have tested an mHealth intervention with Hispanic/Latino adults, and no studies were found testing mHealth with rural Hispanic/Latino adults, the fastest-growing population in rural areas. ObjectiveThe purpose of this study was to evaluate the feasibility, usability, and acceptability of an mHealth cardiovascular risk self-management intervention with rural Hispanic/Latino adults. MethodsA descriptive study using quantitative and qualitative methods was used to evaluate the feasibility, usability, and acceptability of delivering a 12-week mHealth self-management intervention to reduce cardiovascular risk with rural Hispanic/Latino adults who were randomized to 1 of 2 groups. Both groups were asked to use MyFitnessPal to self-monitor daily steps, weight, and calories. The intervention group received support to download, initiate, and troubleshoot technology challenges with MyFitnessPal (Under Armour) and a smart scale, while the enhanced usual care group received only a general recommendation to use MyFitnessPal to support healthy behaviors. The usability of MyFitnessPal and the smart scale was measured using an adapted Health Information Technology Usability EvaluationScale (Health-ITUES). Adherence data in the intervention group (daily steps, weight, and calories) were downloaded from MyFitnessPal. Acceptability was evaluated using semistructured interviews in a subsample (n=5) of intervention group participants. ResultsA sample of 70 eligible participants (enhanced usual care group n=34; intervention group n=36) were enrolled between May and December 2019. The overall attrition was 28% at 12 weeks and 54% at 24 weeks. mHealth usability in the intervention group increased at each time point (6, 12, and 24 weeks). Adherence to self-monitoring using mHealth in the intervention group after week 1 was 55% for steps, 39% for calories, and 35% for weights; at the end of the 12-week intervention, the adherence to self-monitoring was 31% for steps, 11% for weight, and 8% for calories. Spikes in adherence coincided with scheduled in-person study visits. Structured interviews identified common technology challenges including scale and steps not syncing with the app and the need for additional technology support for those with limited mHealth experience. ConclusionsRecruitment of rural Hispanic/Latino adults into the mHealth study was feasible using provider and participant referrals. The use of MyFitnessPal, the smart scale, and SMS text messages to self-monitor daily steps, weights, and calories was acceptable and feasible if technology support was provided. Future research should evaluate and support participants’ baseline technology skill level, provide training if needed, and use a phone call or SMS text message follow-ups as a strategy to minimize attrition. A wearable device, separate from the smartphone app, is recommended for activity tracking

Exercise Oscillatory Ventilation: Interreviewer Agreement and a Novel Determination

INTRODUCTION: Determination of exercise oscillatory ventilation (EOV) is subjective, and the interreviewer agreement has not been reported. The purposes of this study were, among patients with heart failure (HF), as follows: 1) to determine the interreviewer agreement for EOV and 2) to describe a novel, objective, and quantifiable measure of EOV. METHODS: This was a secondary analysis of the HEART Camp: Promoting Adherence to Exercise in Patients with Heart Failure study. EOV was determined through a blinded review by six individuals on the basis of their interpretation of the EOV literature. Interreviewer agreement was assessed using Fleiss kappa (κ). Final determination of EOV was based on agreement by four of the six reviewers. A new measure (ventilation dispersion index; VDI) was calculated for each test, and its ability to predict EOV was assessed with the receiver operator characteristics curve. RESULTS: Among 243 patients with HF (age, 60 ± 12 yr; 45% women), the interreviewer agreement for EOV was fair (κ = 0.303) with 10-s discrete data averages and significantly better, but only moderate (κ = 0.429) with 30-s rolling data averages. Prevalence rates of positive and indeterminate EOVs were 18% and 30% with the 10-s discrete averages and 14% and 13% with the 30-s rolling averages, respectively. VDI was strongly associated with EOV, with areas under the receiver operator characteristics curve of 0.852 to 0.890. CONCLUSIONS: Interreviewer agreement for EOV in patients with HF is fair to moderate, which can negatively affect risk stratification. VDI has strong predictive validity with EOV; as such, it might be a useful measure of prognosis in patients with HF

Effects of the HEART Camp Trial on Adherence to Exercise in Patients With Heart Failure

BACKGROUND: Few exercise training studies in patients with heart failure (HF) report adherence to guideline-recommended 150 minutes of moderate-intensity exercise per week, and no studies have focused on a primary outcome of adherence. METHODS AND RESULTS: This randomized controlled trial evaluated the effect of a multicomponent intervention, Heart Failure Exercise and Resistance Training (HEART) Camp, on adherence to exercise (after 6, 12, and 18 months) compared with an enhanced usual care (EUC) group. Patients (n = 204) were 55.4% male, overall average age was 60.4 years, and 47.5% were nonwhite. The HEART Camp group had significantly greater adherence at 12 (42%) and 18 (35%) months compared with the EUC group (28% and 19%, respectively). No significant difference (P \u3e .05) was found at 6 months. The treatment effect did not differ based on patient\u27s age, race, gender, marital status, type of HF (preserved or reduced ejection fraction) or New York Heart Association functional class. Left ventricular ejection fraction (LVEF) significantly moderated the treatment effect, with greater adherence at higher LVEF. CONCLUSIONS: The multicomponent HEART Camp intervention showed efficacy with significant effects at 12 months and 18 months. Adherence levels remained modest, indicating a need for additional research to address methods and strategies to promote adherence to exercise in patients with HF