Activation of TnSmu1, an integrative and conjugative element, by an ImmR-like transcriptional regulator in Streptococcus mutans.

Integrative and conjugative elements (ICEs) are chromosomally encoded mobile genetic elements that can transfer DNA between bacterial strains. Recently, as part of efforts to determine hypothetical gene functions, we have discovered an important regulatory module encoded on an ICE known as TnSmu1 on the Streptococcus mutans chromosome. The regulatory module consists of a cI-like repressor with a helix-turn-helix DNA binding domain immR Smu (immunity repressor) and a metalloprotease immA Smu (anti-repressor). It is not possible to create an in-frame deletion mutant of immR Smu and repression of immR Smu with CRISPRi (CRISPR interference) causes substantial cell defects. We used a bypass of essentiality (BoE) screen to discover genes that allow deletion of the regulatory module. This revealed that conjugation genes, located within TnSmu1, can restore the viability of an immR Smu mutant. Deletion of immR Smu also leads to production of a circular intermediate form of TnSmu1, which is also inducible by the genotoxic agent mitomycin C. To gain further insights into potential regulation of TnSmu1 by ImmRSmu and broader effects on S. mutans UA159 physiology, we used CRISPRi and RNA-seq. Strongly induced genes included all the TnSmu1 mobile element, genes involved in amino acid metabolism, transport systems and a type I-C CRISPR-Cas system. Lastly, bioinformatic analysis shows that the TnSmu1 mobile element and its associated genes are well distributed across S. mutans isolates. Taken together, our results show that activation of TnSmu1 is controlled by the immRA Smu module, and that activation is deleterious to S. mutans, highlighting the complex interplay between mobile elements and their host.

Glycoprotein IIb/IIIa inhibitors: The resurgence of tirofiban.

Glycoprotein (GP) IIb/IIIa inhibitors block platelet aggregation, reducing thrombotic events in acute coronary syndrome. They are most often utilized in patients who likely have an intracoronary thrombus. Tirofiban, eptifibatide, and abciximab are the three GP IIb/IIIa inhibitors approved for use in the United States. Each agent has unique pharmacological properties. They all have a rapid onset and are most often utilized in conjunction with heparin. Tirofiban, in particular, fell out of favor due to inferior dosing with its original Food and Drug Administration (FDA) approved indication, but has re-emerged in the market with a high-dose bolus regimen that is considered equally as effective as the FDA approved dosing regimens of other GP IIb/IIIa inhibitors. This review looks at pharmacological properties of all three agents, significant clinical trials associated with their use, and their place in current guidelines.

Functions of social support and self-verification in association with loneliness, depression, and stress.

This study investigated the influence of social support and self-verification on loneliness, depression, and stress among 477 college students. The authors propose and test a theoretical model using structural equation modeling. The results indicated empirical support for the model, with self-verification mediating the relation between social support and health outcomes. The results have implications for social support and self-verification research, which are discussed along with directions for future research and limitations of the study.

Communication competence, social support, and depression among college students: a model of facebook and face-to-face support network influence.

This study examined the influence of the social networking site Facebook and face-to-face support networks on depression among (N = 361) college students. The authors used the Relational Health Communication Competence Model as a framework for examining the influence of communication competence on social support network satisfaction and depression. Moreover, they examined the influence of interpersonal and social integrative motives as exogenous variables. On the basis of previous work, the authors propose and test a theoretical model using structural equation modeling. The results indicated empirical support for the model, with interpersonal motives predicting increased face-to-face and computer-mediated competence, increased social support satisfaction with face-to-face and Facebook support, and lower depression scores. The implications of the findings for theory, key limitations, and directions for future research are discussed.

Evaluation of a standardized protocol using lepirudin or argatroban for heparin-induced thrombocytopenia.

STUDY OBJECTIVE: To evaluate the effectiveness of our institutions heparin-induced thrombocytopenia (HIT) protocol in achieving a therapeutic activated partial thromboplastin time (aPTT) and to evaluate patient outcomes related to bleeding and thrombotic events before and after protocol implementation. DESIGN: Retrospective, single-center, pre- and post- assessment of a protocol previously approved at our institution. SETTING: 400-bed community hospital serving surrounding rural populations with emphasis in cardiothoracic surgery. PATIENTS: Retrospective chart review based on drug charge data identified 29 patients that received either argatroban or lepirudin for greater than 24 hours. Nineteen patients received either argatroban or lepirudin prior to HIT-protocol implementation, while the remaining ten received either drug after the HIT protocol was implemented. INTERVENTION: Implementation of HIT protocol occurred in March 2009. Patients were divided into pre-protocol and post-protocol groups. RESULTS: Primary outcome was to evaluate the number of therapeutic, subtherapeutic, and supratherapeutic aPTTs between two groups. In the pre-protocol group, aPTTs were therapeutic, subtherapeutic, and supratherapeutic 48.5% (164/338), 14.2% (48/338), and 37.2% (126/338) of the time, respectively. Meanwhile aPTTs in the post-protocol group were therapeutic, subtherapeutic, and supratherapeutic 46.6% (89/191), 22% (42/191), and 31.4% (60/191) of the time, respectively. The number of subtherapeutic aPTTs was statistically higher in the post-protocol group compared to the pre-protocol group. Secondary endpoints included the number of bleeding events and number of thrombotic events. None of the secondary endpoints reached statistical significance. Time to therapeutic aPTT was also evaluated: in the pre-protocol group median time (range) was 15 hours (2-108.6) compared to 8.1 hours (2.3-94.2) in the post-protocol group. CONCLUSIONS: Adoption and implementation of HIT protocol at our institution resulted in significantly more subtherapeutic aPTTs as compared to time prior to protocol. Although not statistically significant, the time required to obtain therapeutic aPTT was reduced by almost 50% after protocol implementation, which could be of clinical importance. Larger studies are needed to continue to assess if standardized protocols are effective in treatment of HIT.

In their own words: participants' perceptions of the impact of adult day services.

Despite the growth in the number of adult day services programs providing long-term care in the United States, researchers have struggled to consistently identify the benefits of the services to older adult participants. Instead of identifying participant outcomes driven by administrative databases, funding requirements or accreditation expectations, this study attempted to identify outcomes through the lived experiences of the older adult participants through one-on-one interviews after 3 months of attendance. The purpose of this qualitative study was to gain an understanding of the experiences of older adult participants and to build theoretical understandings that connect experiences with outcomes. Twenty-eight semistructured interviews were conducted with older adults attending 4 day health programs administered by 1 organization in a large mid-west City. Three main program experiences were identified: social connections with participants, empowering relationships with staff, and participation and enjoyment of activities and services. These experiences seemed to be associated with perceived improvements in psychosocial well-being and a perceived decrease in burden or dependence on the caregiver. The findings provide theoretical connections that are helpful for exploring the impact of adult day services based on participant perspectives. Results suggest a need for further examination of the role social workers play in supporting psychosocial services within adult day programs.