Post-transcriptional regulation of satellite cell quiescence by TTP-mediated mRNA decay.

Skeletal muscle satellite cells in their niche are quiescent and upon muscle injury, exit quiescence, proliferate to repair muscle tissue, and self-renew to replenish the satellite cell population. To understand the mechanisms involved in maintaining satellite cell quiescence, we identified gene transcripts that were differentially expressed during satellite cell activation following muscle injury. Transcripts encoding RNA binding proteins were among the most significantly changed and included the mRNA decay factor Tristetraprolin. Tristetraprolin promotes the decay of MyoD mRNA, which encodes a transcriptional regulator of myogenic commitment, via binding to the MyoD mRNA 3' untranslated region. Upon satellite cell activation, p38α/β MAPK phosphorylates MAPKAP2 and inactivates Tristetraprolin, stabilizing MyoD mRNA. Satellite cell specific knockdown of Tristetraprolin precociously activates satellite cells in vivo, enabling MyoD accumulation, differentiation and cell fusion into myofibers. Regulation of mRNAs by Tristetraprolin appears to function as one of several critical post-transcriptional regulatory mechanisms controlling satellite cell homeostasis

Messages to Motivate Human Papillomavirus Vaccination: National Studies of Parents and Physicians

Physician communication about human papillomavirus (HPV) vaccine is a key determinant of uptake. To support physician communication, we sought to identify messages that would motivate HPV vaccination

Announcements Versus Conversations to Improve HPV Vaccination Coverage: A Randomized Trial

Improving provider recommendations is critical to addressing low human papillomavirus (HPV) vaccination coverage. Thus, we sought to determine the effectiveness of training providers to improve their recommendations using either presumptive “announcements” or participatory “conversations.

The disordered N-terminal tail of SARS-CoV-2 Nucleocapsid protein forms a dynamic complex with RNA

The SARS-CoV-2 Nucleocapsid (N) protein is responsible for condensation of the viral genome. Characterizing the mechanisms controlling nucleic acid binding is a key step in understanding how condensation is realized. Here, we focus on the role of the RNA binding domain (RBD) and its flanking disordered N-terminal domain (NTD) tail, using single-molecule Förster Resonance Energy Transfer and coarse-grained simulations. We quantified contact site size and binding affinity for nucleic acids and concomitant conformational changes occurring in the disordered region. We found that the disordered NTD increases the affinity of the RBD for RNA by about 50-fold. Binding of both nonspecific and specific RNA results in a modulation of the tail configurations, which respond in an RNA length-dependent manner. Not only does the disordered NTD increase affinity for RNA, but mutations that occur in the Omicron variant modulate the interactions, indicating a functional role of the disordered tail. Finally, we found that the NTD-RBD preferentially interacts with single-stranded RNA and that the resulting protein:RNA complexes are flexible and dynamic. We speculate that this mechanism of interaction enables the Nucleocapsid protein to search the viral genome for and bind to high-affinity motifs

Trending anti-E7 serology predicts mortality and recurrence of HPV-associated cancers of the oropharynx

High-risk human papillomavirus (HPV) is among the most common causes of head and neck cancer (HNC) with increasing incidence. HPV-associated HNC patients\u27 clinical response to treatment varies drastically, which has made treatment de-escalation clinical trials challenging. To address the need for noninvasive biomarkers that differentiate patient outcomes, serum antibodies to E7 oncoprotein levels were evaluated in serial serum specimens from HPV-positive HNC patients

Practice guidelines for clinical microbiology laboratories: Mycobacteria

Mycobacteria are the causative organisms for diseases such as tuberculosis (TB), leprosy, Buruli ulcer, and pulmonary nontuberculous mycobacterial disease, to name the most important ones. In 2015, globally, almost 10 million people developed TB, and almost half a million patients suffered from its multidrug-resistant form. In 2016, a total of 9,287 new TB cases were reported in the United States. In 2015, there were 174,608 new case of leprosy worldwide. India, Brazil, and Indonesia reported the most leprosy cases. In 2015, the World Health Organization reported 2,037 new cases of Buruli ulcer, with most cases being reported in Africa. Pulmonary nontuberculous mycobacterial disease is an emerging public health challenge. The U.S. National Institutes of Health reported an increase from 20 to 47 cases/100,000 persons (or 8.2% per year) of pulmonary nontuberculous mycobacterial disease among adults aged 65 years or older throughout the United States, with 181,037 national annual cases estimated in 2014. This review describes contemporary methods for the laboratory diagnosis of mycobacterial diseases. Furthermore, the review considers the ever-changing health care delivery system and stresses the laboratory’s need to adjust and embrace molecular technologies to provide shorter turnaround times and a higher quality of care for the patients who we serve

Practice Change in Community Pharmacy: A Case Study of Multiple Stakeholders' Perspectives

Objective: To obtain a multi-stakeholder perspective of community pharmacy practice change. Design: Qualitative study. Setting: Community pharmacy in rural Mississippi. Participants: Fourteen key stakeholders of the patient care practice including pharmacists (n=4), support staff (n=2), collaborating providers (n=4), patients (n=3), and a payer (n=1). Intervention: Semi-structured interviews and participant-observation techniques were used. Main outcome measures: Description of the community pharmacy's practice and business model and identification of practice change facilitators. Results: Change facilitators for this practice included: a positive reputation in the community, forming solid relationships with providers, and convenience of patient services. Communication in and outside of the practice, adequate reimbursement, and resource allocation were identified as challenges. Conclusions: This case study is a multi-stakeholder examination of community pharmacy practice change and readers are provided with a real-world example of a community pharmacy's successful establishment of a patient care practice.   Type: Case Stud

Why is announcement training more effective than conversation training for introducing HPV vaccination? A theory-based investigation

Abstract Background Improving healthcare providers’ communication about HPV vaccination is critical to increasing uptake. We previously demonstrated that training providers to use presumptive announcements to introduce HPV vaccination improved uptake, whereas training them to use participatory conversations had no effect. To understand how communication training changed provider perceptions and communication practices, we evaluated intermediate outcomes and process measures from our randomized clinical trial, with a particular focus on identifying mechanisms that might explain the announcement training’s impact. Methods In 2015, a physician educator delivered 1-h in-clinic HPV vaccination recommendation trainings at 20 primary care clinics in North Carolina serving 11,578 patients age 11 or 12. Clinics were randomized to receive training to use “announcements” that presume parents are ready to vaccinate or “conversations” that invite dialog about vaccination. Training participants were 83 HPV vaccine providers. Pre- and post-training surveys assessed constructs from the theory of planned behavior (TPB), including providers’ attitudes and subjective norms about HPV vaccination and their perceived behavioral control to recommend HPV vaccination. Surveys also assessed providers’ perceptions of the announcement and conversation communication strategies. Results Both trainings improved TPB-related constructs, including providers’ positive attitudes toward HPV vaccination, subjective norms, and perceived behavioral control to recommend the vaccine (all p < .001, Cohen’s d = .62–.90). Furthermore, in both trainings, the amount of time providers reported needing to discuss HPV vaccination with parents decreased from pre-training to 1-month follow-up (mean = 3.8 vs. 3.2 min, p = .01, d = .28). However, announcement trainings outperformed conversation trainings on other measures. For example, providers who received announcement training more often reported that the communication strategy saved them time, was easy to use, helped them promote HPV vaccination as routine care, and increased HPV vaccination coverage in their clinics (all p < .05; d = .44–.60). Conclusions Both announcement and conversation trainings improved providers’ HPV vaccine-related perceptions. However, providers viewed announcements as easier to use and more effective, which may help to explain the success of this training approach. Future provider communication interventions should consider implementation outcomes, including acceptability, alongside more traditional TPB constructs. Trial registration clinicaltrials.gov, NCT02377843 . Registered on February 27, 2015

Quality of Physician Communication about Human Papillomavirus Vaccine: Findings from a National Survey

Improving the quality of physicians’ recommendations for human papillomavirus (HPV) vaccination is critical to addressing low coverage. Thus, we sought to describe HPV vaccine communication practices among primary care physicians