Optimizing Provider Preexposure Prophylaxis (PrEP) Training: A Cross-Sectional Analysis of Recommendations from Providers Across the PrEP Implementation Cascade.

Expanding PrEP access necessitates training that supports healthcare providers' progression along the PrEP implementation cascade, moving from PrEP awareness to prescription. We surveyed 359 USA providers about PrEP training content and format recommendations. We examined the association between cascade location and training recommendations. Most providers were aware of PrEP (100%), willing to prescribe PrEP (97.2%), had discussed PrEP with patients (92.2%), and had prescribed PrEP (79.9%). Latent class regression analysis revealed that cascade location was associated with training recommendations. Although all providers recommended PrEP-specific content (e.g., patient eligibility), providers who were located further along the cascade also recommended more comprehensive content, including sexual history-taking and sexual and gender minority competence training. Providers further along the cascade were also more likely to recommend interactive training formats (e.g., role-playing). These insights from providers furthest along the cascade indicate the importance of including comprehensive content and interactive formats in future PrEP training initiatives.

Scanning Electron Microscopic Hair Shaft Analysis in Ectodermal Dysplasia Syndromes.

OBJECTIVES: The objective of the current study was to catalog hair shaft abnormalities in individuals with ectodermal dysplasia (ED) syndromes using scanning electron microscopy (SEM) and to compare the findings with those in unaffected controls. This is the second of a two-part study, the first of which used light microscopy as the modality and was previously published. METHODS: Scanning electron microscopy was performed in a blinded manner on hair shafts from 65 subjects with seven types of ED syndromes and 41 unaffected control subjects. Assessment was performed along the length of the shaft and in cross section. SETTING: Hair donations were collected at the 28th Annual National Family Conference held by the National Foundation for Ectodermal Dysplasia. Control subjects were recruited from a private dermatology practice and an academic children's hospital outpatient dermatology clinic. RESULTS: SEM identified various pathologic hair shaft abnormalities in each type of ED and in control patients. When hairs with all types of ED were grouped together and compared with those of control patients, the difference in the presence of small diameter and shallow and deep grooves was statistically significant (p < 0.05). When the EDs were separated according to subtype, statistically significant findings were also seen. CONCLUSION: SEM is a possible adjuvant tool in the diagnosis of ED syndromes. There are significant differences, with high specificity, between the hairs of individuals with ED and those of control subjects and between subtypes.

Recurrent skin and soft tissue infections (SSTIs) in three family members caused by methicillin-resistant Staphylococcus aureus (MRSA) with Panton-Valentine leukocidin (PVL) exotoxin.

Three family members attended their general practice and emergency department over a 3-month period with recurrent skin and soft tissue infections (SSTIs) such as paronychia, submandibular carbuncle and groin and gluteal abscess requiring surgical drainage. Only when two family members were concurrently admitted with abscesses requiring drainage under general anaesthetic was the definitive diagnosis reached. The wound swabs identified methicillin-resistant Staphylococcus aureus (MRSA) and subsequent identification of the exotoxin Panton-Valentine leukocidin (PVL). Following MRSA decolonisation therapy with mupirocin and octenidine, only one family member has had one recurrence of an SSTI with MRSA isolated from the wound. When patients present with a history of recurrent SSTIs or a family all have had similar presentations, the clinician should consider MRSA with PVL exotoxin infection. Then patients must be referred for confirmation to ensure management is effective for the SSTI and prescribe MRSA decolonisation therapy concurrently to reduce recurrence.

Perceived Threat of Disaster, Efficacy, and Psychological Distress Among Individuals with a Physical Disability: A Longitudinal Model.

OBJECTIVE: Individuals with physical disabilities experience distress when faced with the threat of human-made and natural disasters, yet little is known about how to reduce that distress. This study used Protection Motivation Theory to longitudinally test the relationships between psychological distress and disaster-related cognitive appraisals, including perceived threat, emergency preparedness self-efficacy, and response efficacy, in a sample of individuals with physical disabilities. METHODS: A nationwide convenience sample of 106 adults completed 2 surveys approximately 5 years apart. Structural equation modeling was used to assess effects of perceived threat, self-efficacy, and response efficacy on psychological distress across the 2 waves. RESULTS: Our results suggest that the associations of proximal perceived threat and self-efficacy with psychological distress remain stable across time, while the effect of response efficacy is variable and may be more context-specific. Importantly, individuals who reported an increase in self-efficacy over time also reported (on average) a decrease in psychological distress. CONCLUSIONS: In addition to broadening our understanding of factors related to psychological distress, these results have potentially important intervention implications; for example, to the extent that self-efficacy is a malleable construct, one way of reducing disaster-related psychological distress may be to increase an individual's self-efficacy.

Interactions of amyloidogenic proteins with mitochondrial protein import machinery in aging-related neurodegenerative diseases.

Most mitochondrial proteins are targeted to the organelle by N-terminal mitochondrial targeting sequences (MTSs, or "presequences") that are recognized by the import machinery and subsequently cleaved to yield the mature protein. MTSs do not have conserved amino acid compositions, but share common physicochemical properties, including the ability to form amphipathic α-helical structures enriched with basic and hydrophobic residues on alternating faces. The lack of strict sequence conservation implies that some polypeptides can be mistargeted to mitochondria, especially under cellular stress. The pathogenic accumulation of proteins within mitochondria is implicated in many aging-related neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's diseases. Mechanistically, these diseases may originate in part from mitochondrial interactions with amyloid-ß precursor protein (APP) or its cleavage product amyloid-ß (Aß), α-synuclein (α-syn), and mutant forms of huntingtin (mHtt), respectively, that are mediated in part through their associations with the mitochondrial protein import machinery. Emerging evidence suggests that these amyloidogenic proteins may present cryptic targeting signals that act as MTS mimetics and can be recognized by mitochondrial import receptors and transported into different mitochondrial compartments. Accumulation of these mistargeted proteins could overwhelm the import machinery and its associated quality control mechanisms, thereby contributing to neurological disease progression. Alternatively, the uptake of amyloidogenic proteins into mitochondria may be part of a protein quality control mechanism for clearance of cytotoxic proteins. Here we review the pathomechanisms of these diseases as they relate to mitochondrial protein import and effects on mitochondrial function, what features of APP/Aß, α-syn and mHtt make them suitable substrates for the import machinery, and how this information can be leveraged for the development of therapeutic interventions.

Using Live Cell STED Imaging to Visualize Mitochondrial Inner Membrane Ultrastructure in Neuronal Cell Models.

Mitochondria play many essential roles in the cell, including energy production, regulation of Ca2+ homeostasis, lipid biosynthesis, and production of reactive oxygen species (ROS). These mitochondria-mediated processes take on specialized roles in neurons, coordinating aerobic metabolism to meet the high energy demands of these cells, modulating Ca2+ signaling, providing lipids for axon growth and regeneration, and tuning ROS production for neuronal development and function. Mitochondrial dysfunction is therefore a central driver in neurodegenerative diseases. Mitochondrial structure and function are inextricably linked. The morphologically complex inner membrane with structural infolds called cristae harbors many molecular systems that perform the signature processes of the mitochondrion. The architectural features of the inner membrane are ultrastructural and therefore, too small to be visualized by traditional diffraction-limited resolved microscopy. Thus, most insights on mitochondrial ultrastructure have come from electron microscopy on fixed samples. However, emerging technologies in super-resolution fluorescence microscopy now provide resolution down to tens of nanometers, allowing visualization of ultrastructural features in live cells. Super-resolution imaging therefore offers an unprecedented ability to directly image fine details of mitochondrial structure, nanoscale protein distributions, and cristae dynamics, providing fundamental new insights that link mitochondria to human health and disease. This protocol presents the use of stimulated emission depletion (STED) super-resolution microscopy to visualize the mitochondrial ultrastructure of live human neuroblastoma cells and primary rat neurons. This procedure is organized into five sections: (1) growth and differentiation of the SH-SY5Y cell line, (2) isolation, plating, and growth of primary rat hippocampal neurons, (3) procedures for staining cells for live STED imaging, (4) procedures for live cell STED experiments using a STED microscope for reference, and (5) guidance for segmentation and image processing using examples to measure and quantify morphological features of the inner membrane.

Retrospective Study of Healthcare Resources Developed for Patients by Interprofessional Teams.

Wayne State University (WSU) emphasizes the importance of interdisciplinary education by having students participate in an Interprofessional Team Visit (IPTV) program. A 60-minute virtual visit is conducted to assess adults aged over 50 years within the Detroit Metropolitan Area (Metro Detroit) community. This project was designed to prepare healthcare students in evaluating the mental, physical, and social health aspects of assigned patients based on specific disciplinary assessments. Upon completion of assessments, the interdisciplinary team provided the patient with resources based on the team and the patient's agreed-upon area of concern. Twenty-eight IPTV teams, consisting of a medical and occupational therapy student and a healthcare professional student from another discipline studying at WSU, were randomly created. The IPTV resource guides created by each team were reviewed and sorted into two categories based on the health or social need of the individual patient. The data identified three main areas of interest, which included medication management, diet and exercise plans, and the use of technology to stay connected to medical professionals, friends, and family. The purpose of this report is to assess the IPTV program's findings and analyze patients' concerns based on health or social needs and the resources presented to them.

Bacteriophages Isolated From Turkeys Infecting Diverse Salmonella Serovars.

Salmonella is one of the leading causes of foodborne illnesses worldwide. The rapid emergence of multidrug-resistant Salmonella strains has increased global concern for salmonellosis. Recent studies have shown that bacteriophages (phages) are novel and the most promising antibacterial agents for biocontrol in foods because phages specifically kill target bacteria without affecting other bacteria, do not alter organoleptic properties or nutritional quality of foods, and are safe and environmentally friendly. Due to the vast variation in Salmonella serotypes, large numbers of different and highly virulent Salmonella phages with broad host ranges are needed. This study isolated 14 Salmonella phages from turkey fecal and cecal samples. Six phages (Φ205, Φ206, Φ207, ΦEnt, ΦMont, and Φ13314) were selected for characterization. These phages were from all three families in the Caudovirales order. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed that each phage had a unique structural protein profile. Each phage had a distinct host range. Φ207 and ΦEnt are both siphophages. They shared eight hosts, including seven different Salmonella serovars and one Shigella sonnei strain. These two phages showed different restriction banding patterns generated through EcoRI or HindIII digestion, but shared three bands from EcoRI digestion. ΦEnt displayed the broadest and very unusual host range infecting 11 Salmonella strains from nine serovars and three Shigella strains from two species, and thus was further characterized. The one-step growth curve revealed that ΦEnt had a short latent period (10 min) and relatively large burst size (100 PFU/infected cell). ΦEnt and its host showed better thermal stabilities in tryptic soy broth than in saline at 63 or 72°C. In the model food system (cucumber juice or beef broth), ΦEnt infection [regardless of the multiplicity of infections (MOIs) of 1, 10, and 100] resulted in more than 5-log10 reduction in Salmonella concentration within 4 or 5 h. Such high lytic activity combined with its remarkably broad and unusual host range and good thermal stability suggested that ΦEnt is a novel Salmonella phage with great potential to be used as an effective biocontrol agent against diverse Salmonella serovars in foods.

A model of giant vacuole dynamics in human Schlemm's canal endothelial cells.

Aqueous humour transport across the inner wall endothelium of Schlemm's canal likely involves flow through giant vacuoles and pores, but the mechanics of how these structures form and how they influence the regulation of intraocular pressure (IOP) are not well understood. In this study, we developed an in vitro model of giant vacuole formation in human Schlemm's canal endothelial cells (HSCECs) perfused in the basal-to-apical direction (i.e., the direction that flow crosses the inner wall in vivo) under controlled pressure drops (2 or 6 mmHg). The system was mounted on a confocal microscope for time-lapse en face imaging, and cells were stained with calcein, a fluorescent vital dye. At the onset of perfusion, elliptical void regions appeared within an otherwise uniformly stained cytoplasm, and 3-dimensional reconstructions revealed that these voids were dome-like outpouchings of the cell to form giant vacuole-like structures or GVLs that reproduced the classic "signet ring" appearance of true giant vacuoles. Increasing pressure drop from 2 to 6 mmHg increased GVL height (14 ± 4 vs. 21 ± 7 µm, p < 0.0001) and endothelial hydraulic conductivity (1.15 ± 0.04 vs. 2.11 ± 0.49 µl min⁻¹ mmHg⁻¹ cm⁻²; p < 0.001), but there was significant variability in the GVL response to pressure between cell lines isolated from different donors. During perfusion, GVLs were observed "migrating" and agglomerating about the cell layer and often collapsed despite maintaining the same pressure drop. GVL formation was also observed in human umbilical vein and porcine aortic endothelial cells, suggesting that giant vacuole formation is not a unique property of Schlemm's canal cells. However, in these other cell types, GVLs were rarely observed "migrating" or contracting during perfusion, suggesting that Schlemm's canal endothelial cells may be better adapted to withstand basal-to-apical directed pressure gradients. In conclusion, we have established an in vitro model system to study giant vacuole dynamics, and we have demonstrated that this system reproduces key aspects of giant vacuole morphology and behaviour. This model offers promising opportunities to investigate the role of endothelial cell biomechanics in the regulation of intraocular pressure in normal and glaucomatous eyes.

Management of non-traumatic epistaxis in adults in the emergency department.

BACKGROUND/AIMS: Despite epistaxis being a common presentation to emergency departments there is a lack of guidelines, both nationally and internationally, for its management. The authors reviewed the current management of epistaxis and then introduced a new pathway for management to see if care could be improved. The aims were to evaluate the impact of the pathway on reduction of emergency department breaches, emergency ambulance transfers and hospital admissions. METHODS: The study was an interrupted time series analysis over 29 months and included 903 participants. A pathway for the management of adults with non-traumatic epistaxis was designed and implemented in a university teaching hospital with an emergency department annual attendance rate of 105 495 in 2019-20. RESULTS: The pathway led to a 14-minute longer stay in the emergency department, a 5% increase in emergency department breaches, an 8.2% reduction in admissions, a 3.6% reduction in emergency ambulance transfers, a 14.1% increase in nasal cautery and a 3.2% reduction in nasal packing. CONCLUSIONS: The authors calculate that these results equate to roughly 56 hospital bed days saved, providing better care closer to home for patients, in addition to beneficial knock-on effects for other emergency department and admitted patients.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for the prevention of migraines.

OBJECTIVE: To evaluate the literature examining the efficacy of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) for migraine prophylaxis. DATA SOURCES: MEDLINE (1966-October 2009) and International Pharmaceutical Abstracts were searched using the terms migraine, headache, renin-angiotensin system, angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, aldosterone antagonist, and the individual agents in these classes. STUDY SELECTION AND DATA EXTRACTION: English-language human clinical trials, case reports, and systematic reviews were evaluated for efficacy and safety data. The references of reviewed articles were examined to identify additional sources. DATA SYNTHESIS: Preventative trials evaluating ACE inhibitors consist of a case series, 2 open-label trials, and a placebo-controlled trial. Lisinopril reduced headache hours 20%, headache days 17%, and migraine days 21% versus placebo in the controlled trial (p < 0.05). Clinically significant (>50%) reductions in migraine measures were more common (52-66%) in open-label ACE inhibitor trials than in the controlled (32-36%) trial. Preventive trials evaluating ARBs consist of a meta-analysis, an open-label trial, and 2 placebo-controlled trials. Candesartan reduced headache hours 31%, headache days 26%, and migraine days 28% versus placebo in the first controlled trial (p < or = 0.001). Telmisartan did not reduce any prespecified primary or secondary outcome measures in the second controlled trial. Clinically significant reductions (>50%) in migraine measures were more common (54-88%) in open-label ARB trials than in the controlled (26-38%) trials. A prescription database review found that ACE inhibitor or ARB therapy halved the use of abortive migraine agents compared to diuretic therapy. CONCLUSIONS: ACE inhibitors and ARBs have migraine prophylaxis activity similar to that of some currently utilized agents. Low-dose lisinopril or candesartan may be reasonable second- or third-line agents, particularly in patients with other indications for ACE inhibitor or ARB therapy. Further controlled clinical trials are needed to delineate the role of these agents in migraine prevention.

Iatrogenic pneumothorax in a 4-week-old girl: new diagnosis of congenital lobar emphysema.

A 4-week-old female patient presented with severe respiratory distress, hypoxia and apnoeic episodes on a background of a few-day history of coryza and cough. There was significantly reduced air entry on the left side and a displacement of the apex beat to the right of the chest. The examination findings with oxygen desaturations and a right-sided mediastinal shift on chest X-ray led to a diagnosis of tension pneumothorax following which a needle thoracentesis was undertaken. This appeared to worsen the patient's clinical condition; hence, a chest drain was inserted with unsatisfactory clinical improvement. In view of the presentation and lack of clinical improvement after chest drain insertion, the case was transferred to the paediatric respiratory team in a tertiary centre where the diagnosis was revised to congenital lobar emphysema based on chest computer tomography findings. She subsequently benefited from a left upper lobectomy and lingulectomy and was discharged home 4 days after surgery.

Suprasternal Approach to Transcatheter Aortic Valve Replacement in a Complex Congenital Pediatric Patient Presenting With Cardiogenic Shock.

Transcatheter aortic valve replacement (TAVR) offers well established benefit for adults with severe aortic stenosis, although applications in the pediatric population remain limited. We describe a case of a 15-year-old male with complex congenital heart disease presenting with cardiogenic shock in the setting of mixed severe aortic stenosis (AS) and severe aortic insufficiency (AI). Self-expanding TAVR was performed via suprasternal approach with robust clinical improvement. At one month follow up, he had resolution of clinical heart failure with improvement in ejection fraction and no symptoms of valvulopathy. To our knowledge, there have been no described cases of suprasternal TAVR in a pediatric patient.

Return-to-play probabilities following new versus recurrent ankle sprains in high school athletes.

OBJECTIVES: Although ankle sprains have the highest recurrence rate of any musculoskeletal injury, objective estimates of when an athlete is likely to return-to-play (RTP) are unknown. The purpose was to compare time to return-to-play probability timelines for new and recurrent ankle sprains in interscholastic athletes. DESIGN: Observational. METHODS: Ankle sprain data were collected at seven high schools during the 2007-2008 and 2008-2009 academic years. Ankle sprains were categorized by time lost from participation (same day return, next-day return, 3-day return, 7-day return, 10-day return, >22-day return, no return [censored data]). Time-to-event analyses were used to determine the influence of ankle injury history on return-to-play after an ankle sprain. RESULTS: 204 ankle sprains occurred during 479,668 athlete-exposures, 163 were new (4 censored) and 35 recurrent (1 censored). There was no significant difference (p=0.89) between the time-to-event curves for new and recurrent ankle sprains. The median (inter-quartile rage) time to return-to-play for new sprains (inter-quartile range)=3 days (same day to 7 day return); recurrent sprains=next day return (next day to 7 day return). Noteworthy probabilities [95% CIs] include: same day return (new=25.2[18.7, 31.9], recurrent=17.1[6.6, 30.3]); next-day return (new=43.6[35.3, 52.7], recurrent=51.4[32.5, 67.5]); and 7-day return (new=85.9[73.8, 94.4], recurrent=94.3[47.8, 99.5]). CONCLUSIONS: Previous injury history did not affect time until return-to-play probabilities for ankle sprains. Time until return-to-play analyses that describe the likelihood of return-to-play are useful to clinicians by providing prognostic guidelines and can be used for educating athletes, coaches, and parents about the likely timeframe of being withheld from play.

Trends in concussion return-to-play timelines among high school athletes from 2007 through 2009.

CONTEXT: Whereas guidelines about return-to-play (RTP) after concussion have been published, actual prognoses remain elusive. OBJECTIVE: To develop probability estimates for time until RTP after sport-related concussion. DESIGN: Descriptive epidemiology study. SETTING: High school. PATIENTS OR OTHER PARTICIPANTS: Injured high school varsity, junior varsity, or freshman athletes who participated in 1 of 13 interscholastic sports at 7 area high schools during the 2007-2009 academic years. INTERVENTION(S): Athletic trainers employed at each school collected concussion data. The athletic trainer or physician on site determined the presence of a concussion. Athlete-exposures for practices and games also were captured. MAIN OUTCOME MEASURE(S): Documented concussions were categorized by time missed from participation using severity outcome intervals (same-day return, 1- to 2-day return, 3- to 6-day return, 7- to 9-day return, 10- to 21-day return, >21-day return, no return [censored data]). We calculated Kaplan-Meier time-to-event probabilities that included censored data to determine the probability of RTP at each of these time intervals. RESULTS: A total of 81 new concussions were documented in 478 775 athlete-exposures during the study period. After a new concussion, the probability of RTP (95% confidence interval) was 2.5% (95% confidence interval = 0.3, 6.9) for a 1- to 2-day return, 71.3% (95% confidence interval = 59.0, 82.9) for a 7- to 9-day return, and 88.8% (95% confidence interval = 72.0, 97.2) for a 10- to 21-day return. CONCLUSIONS: For high school athletes, RTP within the first 2 days after concussion was unlikely. After 1 week, the probability of return rose substantially (approximately 71%). Prognostic indicators are used to educate patients about the likely course of disease. Whereas individual symptoms and recovery times vary, prognostic time-to-event probabilities allow clinicians to provide coaches, parents, and athletes with a prediction of the likelihood of RTP within certain timeframes after a concussion.