Serogroup B meningococcal disease in persons previously vaccinated with a serogroup B meningococcal vaccine - United States, 2014-2019.

Since serogroup B meningococcal (MenB) vaccines became available in the United States, six serogroup B meningococcal disease cases have been reported in MenB-4C (n = 4) or MenB-FHbp (n = 2) recipients. Cases were identified and characterized through surveillance and health record review. All five available isolates were characterized using whole genome sequencing; four isolates (from MenB-4C recipients) were further characterized using flow cytometry, MenB-4C-induced serum bactericidal activity (SBA), and genetic Meningococcal Antigen Typing System (gMATS). Three patients were at increased meningococcal disease risk because of an outbreak or underlying medical conditions, and only four of the six patients had completed a full 2-dose MenB series. Isolates were available from 5 patients, and all contained sub-family A FHbp. The four isolates from MenB-4C recipients expressed NhbA but were mismatched for the other MenB-4C vaccine antigens. These four isolates were relatively resistant to MenB-4C-induced SBA, but predicted by gMATS to be covered. Overall, patient risk factors, incomplete vaccine series completion, waning immunity, and strain resistance to SBA likely contributed to disease in these six patients.

Receptiveness and Responsiveness Toward Using Social Media for Safe Firearm Storage Outreach: Mixed Methods Study.

BACKGROUND: Childhood and adolescent firearm injury and death rates have increased over the past decade and remain major public health concerns in the United States. Safe firearm storage has proven to be an effective measure to prevent firearm injury and death among youth. Social media has been used as an avenue to promote safe firearm storage, but perceptions of this tool remain unknown. OBJECTIVE: The aim of this study was to determine receptiveness and responsiveness in promoting firearm lock box and trigger lock giveaway events on social media, and to describe the characteristics of participants who learned of these events through social media. METHODS: We performed a mixed methods study combining a content analysis of Facebook event post comments, quantitative analysis of positive and negative feedback on social media, and a descriptive analysis of event participant characteristics. Through a qualitative content analysis approach, we thematically coded comments from each event's social media page posting. Interrater reliability and κ statistics were calculated. We calculated the prevalence of positive and negative feedback data. Further, we calculated descriptive statistics for demographic characteristics gathered from day-of-event intake surveys. Differences between collected measures were analyzed with χ2 and t tests according to how the participant found out about the event (social media vs other means). Using concurrent analysis, we synthesized the results from both the qualitative and quantitative aims. RESULTS: Through qualitative content analysis, 414 comments from 13 events were coded. Seven themes emerged through the comment coding process with the most common being "positive receptiveness" (294/414, 71.0%). From quantitative analysis of the social media content, we found higher levels of positive feedback compared to negative feedback. The average number of event post "likes" was 1271.3 per event, whereas the average count in which "hide post" was clicked was 72.3 times per event. Overall, 35.9% (1457/4054) of participants found out about the event through social media. The participants who learned about the event through social media were on average significantly younger than those who learned about the event through other means (-6.4 years, 95% CI -5.5 to -7.3). Among the group that learned of the event through social media, 43.9% (629/1433) identified as female, whereas 35.5% (860/2420) identified as female among the group that learned of the event through other means. CONCLUSIONS: There was overall positive receptiveness and responsiveness toward firearm lock box and trigger lock giveaway events when promoted on social media. Compared with other promotional tools, social media has the ability to reach those who are younger and those who identify as female. Future studies should extend this research to determine whether there is a difference between rural and urban settings, and consider other social media platforms in the analysis.

Risks of preterm birth and growth restriction in second births after a first-born male infant.

PURPOSE: A first-born male infant may lead to an exaggerated immune response in the mother in subsequent pregnancies, increasing the risk of preterm birth (PTB) and growth restriction. This study investigated whether risks of PTB and growth restriction are greater among infants preceded by a first-born male infant and evaluated if the associations differ by paternity change or the second-born's sex. METHODS: We conducted a population-based cohort study using 2003-2014 Washington State birth certificate data and included mothers and birth year frequency-matched second live-born infants preceded by a first-born male (n = 58,704) or by a first-born female infant (n = 58,704). Using stratified analyses, we estimated adjusted relative risks (RRs) of PTB, low birthweight (LBW), and small for gestational age (SGA). RESULTS: Second-born infants preceded by a first-born male had greater risks of PTB (RR = 1.14; 95% CI: 1.09-1.19), LBW (RR = 1.17; 1.10-1.24), and SGA (RR = 1.13; 1.08-1.18). The RR was elevated for indicated PTB (RR = 1.19; 1.10-1.29), preterm premature rupture of membranes (RR = 1.15; 1.01-1.32), and spontaneous PTB (RR = 1.12; 1.05-1.20). Associations did not differ by second-born infant's sex or paternity change. CONCLUSION: Having a first-born male infant was associated with a greater risk of PTB, LBW, and SGA in the second-born infant.

Cardiac remodelling in a swine model of chronic thromboembolic pulmonary hypertension: comparison of right vs. left ventricle.

KEY POINTS: Right ventricle (RV) function is the most important determinant of survival and quality of life in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The changes in right and left ventricle gene expression that contribute to ventricular remodelling are incompletely investigated. RV remodelling in our CTEPH swine model is associated with increased expression of the genes involved in inflammation (TGFß), oxidative stress (ROCK2, NOX1 and NOX4), and apoptosis (BCL2 and caspase-3). Alterations in ROCK2 expression correlated inversely with RV contractile reserve during exercise. Since ROCK2 has been shown to be involved in hypertrophy, oxidative stress, fibrosis and endothelial dysfunction, ROCK2 inhibition may present a viable therapeutic target in CTEPH. ABSTRACT: Right ventricle (RV) function is the most important determinant of survival and quality of life in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The present study investigated whether the increased cardiac afterload is associated with (i) cardiac remodelling and hypertrophic signalling; (ii) changes in angiogenic factors and capillary density; and (iii) inflammatory changes associated with oxidative stress and interstitial fibrosis. CTEPH was induced in eight chronically instrumented swine by chronic nitric oxide synthase inhibition and up to five weekly pulmonary embolizations. Nine healthy swine served as a control. After 9 weeks, RV function was assessed by single beat analysis of RV-pulmonary artery (PA) coupling at rest and during exercise, as well as by cardiac magnetic resonance imaging. Subsequently, the heart was excised and RV and left ventricle (LV) tissues were processed for molecular and histological analyses. Swine with CTEPH exhibited significant RV hypertrophy in response to the elevated PA pressure. RV-PA coupling was significantly reduced, correlated inversely with pulmonary vascular resistance and did not increase during exercise in CTEPH swine. Expression of genes associated with hypertrophy (BNP), inflammation (TGFß), oxidative stress (ROCK2, NOX1 and NOX4), apoptosis (BCL2 and caspase-3) and angiogenesis (VEGFA) were increased in the RV of CTEPH swine and correlated inversely with RV-PA coupling during exercise. In the LV, only significant changes in ROCK2 gene-expression occurred. In conclusion, RV remodelling in our CTEPH swine model is associated with increased expression of genes involved in inflammation and oxidative stress, suggesting that these processes contribute to RV remodelling and dysfunction in CTEPH and hence represent potential therapeutic targets.

Perspectives on Smartphone Ownership and Use by Early Adolescents.

PURPOSE: Increasing numbers of youth are becoming smartphone owners as early adolescents (EAs). Understanding how EAs receive and use their initial smartphones is important towards informing provider counseling and parental guidance. The purpose of this qualitative study was to understand EA perspectives and experiences with smartphone ownership. METHODS: Focus groups were conducted with EAs ages 10-14years in Washington State. We utilized purposeful sampling to represent different communities and health status. During focus groups, trained facilitators used a semi-structured facilitator guide to prompt discussion about EAs' smartphone ownership and use. RESULTS: A total of 45 EAs with average age 11.2 (SD=0.77), 51.1% female, 64.4% white and 20% rural, participated in 12 focus groups. Of 3 major themes, the first was Maturity, which included EAs' views that they should achieve milestones rather than an age for smartphone ownership. The second theme was Deference to Parents, which included EAs' interest in engaging with parents to establish rules for smartphone use. The final theme was Accountability, as EAs described the importance of responsibility and cost-sharing. Two minor themes arose which included the role of EAs asking for phones and the individuality of phone use. CONCLUSIONS: Early adolescents supported timing of a first smartphone tied to meaningful milestones, and wanted parent engagement in developing rules to support them in initial smartphone ownership. Findings can be used to empower parent involvement in EA smartphone use to promote safe and productive behavior.

Natural selection retains overrepresented out-of-frame stop codons against frameshift peptides in prokaryotes.

BACKGROUND: Out-of-frame stop codons (OSCs) occur naturally in coding sequences of all organisms, providing a mechanism of early termination of translation in incorrect reading frame so that the metabolic cost associated with frameshift events can be reduced. Given such a functional significance, we expect statistically overrepresented OSCs in coding sequences as a result of a widespread selection. Accordingly, we examined available prokaryotic genomes to look for evidence of this selection. RESULTS: The complete genome sequences of 990 prokaryotes were obtained from NCBI GenBank. We found that low G+C content coding sequences contain significantly more OSCs and G+C content at specific codon positions were the principal determinants of OSC usage bias in the different reading frames. To investigate if there is overrepresentation of OSCs, we modeled the trinucleotide and hexanucleotide biases of the coding sequences using Markov models, and calculated the expected OSC frequencies for each organism using a Monte Carlo approach. More than 93% of 342 phylogenetically representative prokaryotic genomes contain excess OSCs. Interestingly the degree of OSC overrepresentation correlates positively with G+C content, which may represent a compensatory mechanism for the negative correlation of OSC frequency with G+C content. We extended the analysis using additional compositional bias models and showed that lower-order bias like codon usage and dipeptide bias could not explain the OSC overrepresentation. The degree of OSC overrepresentation was found to correlate negatively with the optimal growth temperature of the organism after correcting for the G+C% and AT skew of the coding sequence. CONCLUSIONS: The present study uses approaches with statistical rigor to show that OSC overrepresentation is a widespread phenomenon among prokaryotes. Our results support the hypothesis that OSCs carry functional significance and have been selected in the course of genome evolution to act against unintended frameshift occurrences. Some results also hint that OSC overrepresentation being a compensatory mechanism to make up for the decrease in OSCs in high G+C organisms, thus revealing the interplay between two different determinants of OSC frequency.