Mycobacterial RNase E cleaves with a distinct sequence preference and controls the degradation rates of most Mycolicibacterium smegmatis mRNAs.

The mechanisms and regulation of RNA degradation in mycobacteria have been subject to increased interest following the identification of interplay between RNA metabolism and drug resistance. Mycobacteria encode multiple ribonucleases predicted to participate in mRNA degradation and/or processing of stable RNAs. RNase E is hypothesized to play a major role in mRNA degradation because of its essentiality in mycobacteria and its role in mRNA degradation in gram-negative bacteria. Here, we defined the impact of RNase E on mRNA degradation rates transcriptome-wide in the nonpathogenic model Mycolicibacterium smegmatis. RNase E played a rate-limiting role in degradation of the transcripts encoded by at least 89% of protein-coding genes, with leadered transcripts often being more affected by RNase E repression than leaderless transcripts. There was an apparent global slowing of transcription in response to knockdown of RNase E, suggesting that M. smegmatis regulates transcription in responses to changes in mRNA degradation. This compensation was incomplete, as the abundance of most transcripts increased upon RNase E knockdown. We assessed the sequence preferences for cleavage by RNase E transcriptome-wide in M. smegmatis and Mycobacterium tuberculosis and found a consistent bias for cleavage in C-rich regions. Purified RNase E had a clear preference for cleavage immediately upstream of cytidines, distinct from the sequence preferences of RNase E in gram-negative bacteria. We furthermore report a high-resolution map of mRNA cleavage sites in M. tuberculosis, which occur primarily within the RNase E-preferred sequence context, confirming that RNase E has a broad impact on the M. tuberculosis transcriptome.

Continuing Education Evaluations of an Internal Medicine and a Pediatric Podcast.

INTRODUCTION: This study aimed to characterize practitioners who use podcasts as a form of continuing education (CE), evaluate attitudes regarding podcasting as a medium for CE, and assess intended practice change after listening to podcasts for CE. METHODS: We examined CE data from a mandatory postpodcast evaluation collected between February 2021 and August 2021 for two free podcasts. We analyzed linked episode data containing podcast downloads. RESULTS: Listeners downloaded 972,691 episodes and claimed 8182 CE credits (less than 1% of total downloads) over 7 months. CE credit was claimed by physicians, physician assistants, nurses, and pharmacists. Most listeners claiming CE credit were not affiliated with an academic institution. Motivation for listening to episodes included a topic of interest, relevance to a patient, and a topic of less comfort. Of individuals obtaining CE, 98% intended to implement change after listening. DISCUSSION: Although only a small number of podcast listeners claim CE credit, those who claim credit represent a diverse and interprofessional audience. Listeners select podcasts to fill self-identified learning needs. Overwhelmingly, listeners report podcast CE changes intended practice. Podcasts may be an effective modality for CE and practice change; further research should focus on facilitators and barriers to CE uptake and on patient health outcomes.

Changes in Pediatricians' Child Passenger Safety Counseling With Initiation of a Booster Seat Program.

Booster seats reduce injury in motor vehicle crashes, yet they are used less frequently than car seats and seat belts. Primary care providers are well positioned to educate and encourage families to use booster seats. We aimed to assess how a booster seat distribution program affected the documentation of restraint usage and anticipatory guidance at well-child visits at a pediatric primary care practice. We performed a retrospective chart review of patients aged 4 to 12 years from June to December in 2019 and 2020, representing before and after a booster seat program. The most frequently documented restraints in 2019 and 2020 were seat belts (51% vs 30%), booster seats (25% vs 27%), and not documented/unclear (17% vs 25%) (P < .001). The program significantly increased referrals for booster seats (P < .001). Despite significant differences in the proportion of children in each restraint category, overall booster seat use was similar between years.

Cardiopulmonary Resuscitation Training in Select Rhode Island High Schools: A Descriptive Study.

Fewer than 15% of people who have out-of-hospital cardiac arrests survive, but chances of survival can be tripled with effective bystander cardiopulmonary resuscitation (CPR). The majority of states, including Rhode Island, require high school CPR training, yet the impact of this is not well studied. A 33-question REDCap survey regarding cardiac arrest preparedness, CPR education, and barriers to CPR training was emailed to high school staff in Rhode Island. There were 62 responses; 26% reported their school taught CPR and 94% felt it was important for students to have CPR certification. Barriers included time (85%), budget (82%), and materials (79%). Over 80% felt students would not be able to perform high-quality CPR or properly use a defibrillator. Despite laws requiring CPR training and the belief by school staff of the importance of CPR training, the majority of students are not receiving CPR training. Staff report students do not have the ability to perform effective CPR or use a defibrillator.

Learning Through Listening: A Scoping Review of Podcast Use in Medical Education.

PURPOSE: To improve understanding of podcast use in medical education by examining current research on descriptive attributes and educational outcomes, highlighting implications of the current evidence base for educational practices, and identifying research gaps to guide future investigation. METHOD: The authors conducted a scoping review, searching PubMed and Embase databases in June-July 2020 for English-language studies of audio-only medical education podcast use in undergraduate, graduate, and continuing medical education. The authors excluded studies without original data or with nonphysician data that could not be separated from physician data. From included studies, the authors extracted data regarding descriptive outcomes (e.g., podcast use, content areas, structure) and educational outcomes (classified using Kirkpatrick's 4 levels of evaluation). RESULTS: Of 491 unique articles, 62 met inclusion criteria. Descriptive outcomes were reported in 44 studies. Analysis of these studies revealed podcast use has increased over time, podcasts are a top resource for resident education, and podcasts are being incorporated into formal medical curricula. Educational outcomes were reported in 38 studies. The 29 studies that assessed learner reaction and attitudes to podcasts (Kirkpatrick level 1) showed learners value podcasts for their portability, efficiency, and combined educational and entertainment value. The 10 studies that assessed knowledge retention (Kirkpatrick level 2) showed podcasts to be noninferior to traditional teaching methods. The 11 studies that assessed behavior change (Kirkpatrick level 3) showed improved documentation skills in medical students and self-reported practice change in residents and practicing physicians after listening to podcasts. None of the studies reported system change or patient outcomes (Kirkpatrick level 4). CONCLUSIONS: Future research should focus on the optimal structure of podcasts for learning, higher-level outcomes of podcasts, and the implementation of podcasts into formal curricula. Podcasts may prove to be essential tools for disseminating and implementing the most current, evidence-based practices.

Changes in Sick Visits at an Academic Pediatric Primary Care Practice due to the COVID-19 Pandemic.

BACKGROUND/OBJECTIVE: The COVID-19 pandemic decreased pediatric patient volumes; however, details regarding patterns of use within primary care sick visits are not well understood. METHODS: We performed a retrospective chart review of sick visits in an academic primary care clinic from March-August 2019 and 2020 and recorded demographics and visit diagnoses. Descriptive statistics, Chi-square, and Fisher's exact tests were used to compare the two time periods. RESULTS: Patient age, gender, and insurance type were similar across years. In 2020, there were 1,868 sick visits (247 telehealth, 4%-36% of monthly visits) compared to 4,007 (0 telehealth) in 2019. The proportion of infectious diagnoses decreased (35% vs 48%); non-infectious diagnoses increased, including dermatological (25% vs 19%) and genitourinary/reproductive (9% vs. 6%) diagnoses.  Conclusion: Similar to pediatric emergency departments, we found decreased primary care sick visits. Telehealth increased in 2020 and varied with COVID-19 community prevalence. Visits for contagious illnesses decreased in 2020, likely related to mitigation measures.

Visits for Possible COVID-19 in a Pediatric Primary Care Practice Early in the Pandemic.

BACKGROUND: Children with COVID-19 usually present with mild symptoms. We characterize visits with respect to symptoms and testing in the outpatient setting. METHODS: A retrospective chart review of sick visits in a pediatric academic primary care clinic April-August 2020. We included possible COVID-19 cases, or "persons under investigation" (PUIs), recording symptoms, positive contacts, and COVID-19 testing. Descriptive statistics and Chi-square or Fisher's exact tests for comparisons were used. RESULTS: 32% (476/1,474) of sick visits were PUIs; 20% were telehealth. Symptoms most commonly reported were fever, congestion/rhinorrhea and cough. 76% of PUIs were tested for COVID-19. Only presence of COVID-19 contacts and loss of taste/smell were significantly associated with positive tests (p<0.001). CONCLUSION: Nearly a third of sick visits in an academic pediatric practice were seen for possible COVID-19 symptoms and most were tested. The majority with and without COVID-19 had fever, congestion and/or cough. Our findings suggest low thresholds for testing in children.

Polyethylene glycol-b-poly(lactic acid) polymersomes as vehicles for enzyme replacement therapy.

AIM: Polymersomes are created to deliver an enzyme-based therapy to the brain in lysosomal storage disease patients. MATERIALS & METHODS: Polymersomes are formed via the injection method using poly(ethylene glycol)-b-poly(lactic acid) (PEGPLA) and bound to apolipoprotein E, to create a brain-targeted delivery vehicle. RESULTS: Polymersomes have a smallest average diameter of 145 ± 21 nm and encapsulate ß-galactosidase at 72.0 ± 12.2% efficiency. PEGPLA polymersomes demonstrate limited release at physiologic pH (7.4), with a burst release at the acidic pH (4.8) of the lysosome. PEGPLA polymersomes facilitate delivery of active ß-galactosidase to an in vitro model of GM1 gangliosidosis. CONCLUSION: The foundation has been laid for testing of PEGPLA polymersomes to deliver enzymatic treatments to the brain in lysosomal storage disorders for the first time.

Emerging therapies for neuropathic lysosomal storage disorders.

Approximately 1 in 5000-8000 children are born annually with a lysosomal storage disease (LSD), which affects their cells' ability to break down naturally occurring substrates. Accumulation, or "storage," of undegraded substrates leads to a wide variety of clinical symptoms, and early mortality. Currently, for LSDs with central nervous system (CNS) involvement, there is no available treatment. Four methods of treatment are being explored in clinical trials and preclinical settings: enzyme replacement therapy, ex vivo gene therapy, in vivo gene therapy, and nanoparticle-based therapy. In general, each therapeutic approach has been hindered by an inability to cross the blood-brain barrier (BBB) without invasive intracranial surgeries. Also, once the treatment has entered the brain, it is difficult to ensure therapeutic levels of enzyme distributed evenly throughout the entire parenchyma. Enzyme replacement therapy (ERT) is the current standard of care for lysosomal diseases without CNS involvement. However, with the recent advent of nanoparticle-based therapy, direct targeting of either gene therapy or ERT to the brain has become plausible. Ex vivo gene therapy, in vivo gene therapy, ERT and nanoparticle-based therapies are explained, while synthesizing and analyzing their potential as clinical treatments targeted to the CNS. While difficulties in treating the entire brain remain, preclinical studies demonstrate profound therapeutic benefit in animal models and generate hope for successful translation to humans.

Recent developments in home sleep-monitoring devices.

Improving our understanding of sleep physiology and pathophysiology is an important goal for both medical and general wellness reasons. Although the gold standard for assessing sleep remains the laboratory polysomnogram, there is an increasing interest in portable monitoring devices that provide the opportunity for assessing sleep in real-world environments such as the home. Portable devices allow repeated measurements, evaluation of temporal patterns, and self-experimentation. We review recent developments in devices designed to monitor sleep-wake activity, as well as monitors designed for other purposes that could in principle be applied in the field of sleep (such as cardiac or respiratory sensing). As the body of supporting validation data grows, these devices hold promise for a variety of health and wellness goals. From a clinical and research standpoint, the capacity to obtain longitudinal sleep-wake data may improve disease phenotyping, individualized treatment decisions, and individualized health optimization. From a wellness standpoint, commercially available devices may allow individuals to track their own sleep with the goal of finding patterns and correlations with modifiable behaviors such as exercise, diet, and sleep aids.

Mammalian sleep genetics.

Mammalian sleep is a complex phenomenon governed by the interplay of neural circuits and signaling systems. The impact of genetic manipulations on sleep-wake dynamics provides important insights into this complex behavior. Here we review the sleep-related phenotypes of over 50 transgenic animal models spanning a variety of signaling systems. This heterogeneous literature includes outcomes spanning motor activity patterns, sleep-wake stage architecture, responses to sleep deprivation, circadian rhythmicity, and other perturbations such as food restriction, temperature challenge, and infection exposure. Insights from these animal experiments hold potential to converge with the well-known sleep-wake neurocircuitry as well as the increasingly available human genetic information, especially in patient populations exhibiting sleep-wake pathology.

Sleep telemedicine: a survey study of patient preferences.

Telemedicine is an increasingly recognized option for cost-effective management of chronic conditions. We surveyed Sleep Clinic patients about their experiences and preferences regarding different forms of telemedicine. Adult Sleep Clinic patients seen between 2009 and 2011 received a brief survey either by postal mail (n = 156) or, for those with an available email address, electronically (n = 282). The overall response rate was 28.1% (n = 123 responses), with email response rates being higher than postal mail responses. The most commonly reported barriers to in-person physician visits were parking cost (44%), time away from work/school (34%), and cost of gas (26%). Whereas 89% of respondents indicated using telephone and 55% of respondents indicated using email to communicate with providers, none reported experience with video telemedicine. Despite this lack of experience, over 60% reported feeling comfortable or willing to try it. Of those who were uncomfortable about video telemedicine, the two main reasons were that in-person visits feel more natural (48%) and that the doctor might need to perform an examination (24%). More than half of respondents reported willingness to pay a copay for a video visit. Video telemedicine represents a feasible option for chronic sleep disorders management.