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\u3cem\u3eBacillus subtilis\u3c/em\u3e-Derived Peptides Disrupt Quorum Sensing and Biofilm Assembly in Multidrug-Resistant Staphylococcus Aureus
Multidrug-resistant Staphylococcus aureus is one of the most clinically important pathogens in the world, with infections leading to high rates of morbidity and mortality in both humans and animals. The ability of S. aureus to form biofilms protects cells from antibiotics and promotes the transfer of antibiotic resistance genes; therefore, new strategies aimed at inhibiting biofilm growth are urgently needed. Probiotic species, including Bacillus subtilis, are gaining interest as potential therapies against S. aureus for their ability to reduce S. aureus colonization and virulence. Here, we search for strains and microbially derived compounds with strong antibiofilm activity against multidrug-resistant S. aureus by isolating and screening Bacillus strains from a variety of agricultural environments. From a total of 1,123 environmental isolates, we identify a single strain B. subtilis 6D1, with a potent ability to inhibit biofilm growth, disassemble mature biofilm, and improve antibiotic sensitivity of S. aureus biofilms through an Agr quorum sensing interference mechanism. Biochemical and molecular networking analysis of an active organic fraction revealed multiple surfactin isoforms, and an uncharacterized peptide was driving this antibiofilm activity. Compared with commercial high-performance liquid chromatography grade surfactin obtained from B. subtilis, we show these B. subtilis 6D1 peptides are significantly better at inhibiting biofilm formation in all four S. aureus Agr backgrounds and preventing S. aureus-induced cytotoxicity when applied to HT29 human intestinal cells. Our study illustrates the potential of exploring microbial strain diversity to discover novel antibiofilm agents that may help combat multidrug-resistant S. aureus infections and enhance antibiotic efficacy in clinical and veterinary settings
Childhood Maltreatment and Amygdala-Mediated Anxiety and Posttraumatic Stress Following Adult Trauma
Background
Childhood abuse (physical, emotional, and sexual) is associated with aberrant connectivity of the amygdala, a key threat-processing region. Heightened amygdala activity also predicts adult anxiety and posttraumatic stress disorder (PTSD) symptoms, as do experiences of childhood abuse. The current study explored whether amygdala resting-state functional connectivity may explain the relationship between childhood abuse and anxiety and PTSD symptoms following trauma exposure in adults. Methods
Two weeks posttrauma, adult trauma survivors (n = 152, mean age [SD] = 32.61 [10.35] years; women = 57.2%) completed the Childhood Trauma Questionnaire and underwent resting-state functional magnetic resonance imaging. PTSD and anxiety symptoms were assessed 6 months posttrauma. Seed-to-voxel analyses evaluated the association between childhood abuse and amygdala resting-state functional connectivity. A mediation model evaluated the potential mediating role of amygdala connectivity in the relationship between childhood abuse and posttrauma anxiety and PTSD. Results
Childhood abuse was associated with increased amygdala connectivity with the precuneus while covarying for age, gender, childhood neglect, and baseline PTSD symptoms. Amygdala-precuneus resting-state functional connectivity was a significant mediator of the effect of childhood abuse on anxiety symptoms 6 months posttrauma (B = 0.065; 95% CI, 0.013–0.130; SE = 0.030), but not PTSD. A secondary mediation analysis investigating depression as an outcome was not significant. Conclusions
Amygdala-precuneus connectivity may be an underlying neural mechanism by which childhood abuse increases risk for anxiety following adult trauma. Specifically, this heightened connectivity may reflect attentional vigilance for threat or a tendency toward negative self-referential thoughts. Findings suggest that childhood abuse may contribute to longstanding upregulation of attentional vigilance circuits, which makes one vulnerable to anxiety-related symptoms in adulthood
The Feasibility and Acceptability of a Diabetes Survival Skills Intervention for Persons Transitioning from Prison to the Community
Community evidenced-based diabetes self-management education (DSME) models have not been examined for feasibility, acceptability, or effectiveness among persons transitioning from prison to the community to independent diabetes self-management (DSM). In a non-equivalent control group design with repeated measures, we examined the feasibility, acceptability, and preliminary effect of a 6-week, 1-h per week Diabetes Survival Skills (DSS) intervention on diabetes knowledge, distress, self-efficacy, and outcome expectancy for transitioning incarcerated males. Of the 92 participants (84% T2D, 83% using insulin, 40% Black, 20% White, 30% Latino, 66% high school or less, mean age 47.3 years, 84% length of incarceration ≤4 years ), 41 completed the study (22 control/19 intervention [TX]). One-way repeated measures ANOVAs revealed significant changes in diabetes knowledge within each group (C, p = .002; TX, p = .027) at all time points; however, a two-way repeated measures ANOVA showed no differences between groups. Additionally, both groups showed improvement in diabetes-related distress and outcome expectancy with the treatment group experiencing greater and sustained improvement at the 12-week time point. Analysis of focus group data (Krippendorf) revealed acceptance of and enthusiasm for the DSS training and low literacy education materials, the need for skill demonstration, and ongoing support throughout incarceration and before release. Our results highlight the complexity of working with incarcerated populations. After most of the sessions, we observed some information sharing between the intervention and the control groups on what they did in their respective sessions. Due to high attrition, the power to detect effects was limited. Yet, results suggest that the intervention is feasible and acceptable with an increased sample size and refined recruitment procedure
Intensive Postpartum Antihypertensive Treatment (IPAT) and Healthy Lifestyle Education: Study Protocol for a Pilot Randomized Controlled Trial for Patients with Hypertensive Disorders of Pregnancy
Background
Hypertensive disorders of pregnancy (HDP) complicate about 10% of pregnancies and lead to postpartum hospital readmissions and cardiovascular complications. Following HDP, vascular dysfunction could persist and accelerate the trajectory of cardiovascular disease risk. The benefits of intensive blood pressure (BP) control following HDP have not been adequately investigated. Therefore, no standard guidelines exist to guide the management of mild-to-moderate hypertension in the postpartum period, leading to a wide variation in clinical practice. The present study will investigate the effect of intensive BP control and healthy lifestyle education on maternal cardiovascular health (CVH) and vascular function following HDP.
Methods
The Intensive Postpartum Antihypertensive Treatment (IPAT) study is a randomized controlled, two-arm, single-site, pilot trial where 60 postpartum HDP patients will be randomized 1:1 to one of two groups: 1) Intensive postpartum BP control – nifedipine initiation at BP ≥140/90 mmHg to maintain BP \u3c 140/90 mmHg; or 2) Less intensive postpartum BP control – nifedipine initiation at BP ≥150/100 mmHg to maintain BP \u3c 150/100 mmHg. All participants will also undergo vascular function assessments and receive healthy lifestyle education. The study will primarily test feasibility of all study procedures. It will secondarily examine changes in BP and CVH scores from baseline to 12 months postpartum.
Conclusion
This pilot trial will study whether the BP threshold of 140/90 is superior to 150/100 for initiation of pharmacotherapy and evaluate feasibility to ultimately conduct a trial capable of generating robust evidence to standardize clinical practice and guidelines in postpartum HDP management
Legislative Redistricting and the Partisan Distribution of Transportation Expenditure
I show that a state representative’s political party determines transportation expenditure in the area she represents. Previous studies of this topic consider party changes through election outcomes, which may be correlated with unobservable determinants of expenditure. To overcome this issue, I identify my estimates using Ohio’s 2012 state legislative redistricting, which moved many geographic areas into districts with opposite party incumbents. The Republican party controlled the state legislature and governorship over the period I study. I find that areas moving from governing party Republican to minority party Democratic districts received $3.4M (0.18 standard deviations) less annual highway construction funding than areas remaining in Republican districts. Areas moving from a Democratic to a Republican district, on the other hand, experienced no increase in expenditure—the negative effect of moving to a different representative’s district appears to outweigh the positive effect of a majority party representative. Descriptive evidence suggests that changing representative’s party through redistricting had a different effect on construction funding than changing through an election, underlining the importance of my identification strategy
VoiceAttack: Fingerprinting Voice Command on VPN-protected Smart Home Speakers
Recently, there are growing security and privacy concerns regarding smart voice speakers, such as Amazon Alexa and Google Home. Extensive prior research has shown that it is surprisingly easy to infer Amazon Alexa voice commands over their network traffic data. To prevent these traffic analytics (TA)-based inference attacks, smart home owners are considering deploying virtual private networks (VPNs) to safeguard their smart speakers. In this work, we design a new machine learning (ML) and deep learning (DL)-powered attack framework---VoiceAttack that could still accurately fingerprint voice commands on VPN-encrypted voice speaker network traffic. We evaluate VoiceAttack under 5 different real-world settings using Amazon Alexa and Google Home. Our results show that VoiceAttack could correctly infer voice command sentences with a Matthews Correlation Coefficient (MCC) of 0.68 in a closed-world setting and infer voice command categories with an MCC of 0.84 in an open-world setting by eavesdropping VPN-encrypted network traffic rates. This presents a significant risk to user privacy and security, as it suggests that external on-path attackers could still potentially intercept and decipher users\u27 voice commands despite the VPN encryption. We then further examine the sensitivity of voice speaker commands to VoiceAttack. We find that 134 voice speaker commands are highly vulnerable to VoiceAttack and 3 commands are less sensitive. We also present a proof-of-concept defense approach---VoiceDefense, which could effectively mitigate TA attack accuracy on Amazon Echo and Google Home by ~50%
Coupling and Decoupling of Ancestral Linkages and Current Cross-Border Economic Activities: Genetics and Policy
This paper studies the potential link between the biological evolution of populations and present-day economic interactions by estimating the correlation of shared ancestry among populations with cross-border capital and human flows. To this end, we employ the new concept of genetic distance, based on (dis)similarity of neutral gene alleles, to quantify shared ancestry. We then incorporate the genetic distance measure into an augmented gravity model, traditionally used to analyze the effect of geographical distance on bilateral exchange. Our analysis focuses on bilateral foreign direct investment (FDI) and migration across 135 countries and we use both linear regression techniques as well as the Poisson Pseudo-Maximum Likelihood Estimator to account for any non-linearities in the model. Our results show that a 1% increase in genetic distance reduces FDI flows by 0.08% while controlling for other distance constructs and factors associated with global capital and human movement. Genetic distance also has a negative effect on migration, where a 1% increase in genetic distance reduces migration flows by 0.22%, with all other things remaining constant. Our study, therefore, links shared ancestry with economic behavior, showing how historical connections are associated with current economic exchanges among nations. Additionally, recognizing that ancestral ties are outside human control, we examine policy measures that help nations overcome such distance barriers. Our findings show that strengthening a nation’s institutional quality and adherence to the rule of law can effectively mitigate any negative correlation of distance constructs with economic exchanges. These insights suggest that prudent policies to foster a stable business environment are essential for any nation to attract FDI and human capital, even from geographically or genetically distant nations
Effect of Surface Finish and Resin Cement on the Bond Strength to CAD-CAM Ceramics for Interim Resin-bonded Prostheses
Statement of problem
Resin-bonded prostheses, including interim resin-bonded prostheses, are effective in preserving tooth structure compared with other types of fixed dental prostheses for the replacement of missing teeth. However, loss of retention remains a notable concern with these types of prostheses. Purpose
The purpose of this in vitro study was to investigate the influence of glass-ceramic type, resin type, and surface finish on the shear bond strength (SBS) to the CAD-CAM ceramics used to fabricate interim resin-bonded prostheses. Material and methods
Eighty 10×2-mm glass-ceramic disks were fabricated by using a diamond saw (IsoMet 1000), 40 from feldspathic porcelain blocks (Vita Mark II) and 40 from lithium disilicate blocks (IPS e.max CAD). Half of the specimens in each group were left with a dull or matte surface finish after cutting, while the other half were glazed with an add-on glaze (VitaAkzento Plus Glaze Spray and IPS e.max CAD Glaze Spray, respectively). The disks were mounted in acrylic, and each group was subdivided into 2, with 1 receiving a photopolymerized resin cement (RelyX Veneer) and the other receiving a flowable composite resin (Filtek Supreme Ultimate Flow) to form 2.38×2-mm cylinders. SBS was determined using a universal testing machine (Instron 4411) in accordance with the International Organization for Standardization (ISO) 29022:2013 standard, and failure modes were analyzed by using a stereomicroscope with ×40 magnification. The data were analyzed with a 3-way analysis of variance and Tukey post hoc analysis. The chi-squared test was used to analyze the failure mode (α=.05 for all tests). Results
Ceramic type, resin type, and surface finish significantly impacted SBS (P\u3c .001, P=.003, P\u3c .001, respectively). Lithium disilicate showed higher SBS than feldspathic porcelain, and flowable composite resin exhibited higher SBS than resin cement. Glazed surfaces displayed lower SBS compared with the dull or matte surfaces. The combinations among the 3 materials also impacted SBS (P=.03). In addition, the combinations between ceramic type and surface finish affected SBS (P\u3c .001), regardless of resin cement type. No other combinations affected the SBS (P\u3e.05). The mode of failure was different among the groups (P\u3c .001). In comparison with all other groups, cohesive failures were most prevalent in feldspathic porcelain with a dull or matte surface finish, regardless of the resin type used. Conclusions
The SBS to glass-ceramics was influenced by ceramic material, resin cement type, and surface finish. Flowable composite resin showed higher SBS than resin cement. A dull or matte surface finish exhibited greater bond strength than a glazed surface. Lithium disilicate had higher SBS than feldspathic porcelain