Enhancing Perspective in Global Health: A Case Study on an International Ophthalmology Partnership.

Introduction: Global ophthalmology opportunities are becoming increasingly popular, and international partnerships are becoming more common among academic training institutions in the United States. There is need for training in the complex relational, motivational, ethical, and logistical issues that may arise in these partnerships.

Methods: We developed a 3-hour case-based session featuring four characters in a fictitious international ophthalmology partnership scenario.

A Randomized Phase 1 Evaluation of Deupirfenidone, a Novel Deuterium-Containing Drug Candidate for Interstitial Lung Disease and Other Inflammatory and Fibrotic Diseases.

LYT-100 (deupirfenidone) is a selectively deuterated form of pirfenidone under development for the treatment of inflammatory and fibrotic diseases, including interstitial lung disease. Adverse events associated with antifibrotics can be a barrier to adoption and persistence in patients with interstitial lung diseases, most of whom are not on standard-of-care therapy. LYT-100 is designed to have a differentiated pharmacokinetic (PK) profile from pirfenidone and could offer a differentiated safety profile compared to current standard-of-care drugs while retaining the biochemical potency and specificity of pirfenidone.

Physician Compliance to Choosing Wisely® Initiative in Radiographic Imaging of Low Risk Prostate Cancer in an Integrated Health Care System.

Introduction: We evaluated the adherence of urologists within an integrated health care system to Choosing Wisely®, an initiative aimed at avoiding unnecessary medical tests. In urology, 2 of the guidelines state bone scans and pelvic computerized tomography scans are unnecessary in low risk prostate cancer.

Methods: We performed a retrospective study on patients diagnosed with low risk prostate cancer between January 1, 2010 and December 31, 2017 at Kaiser Permanente Southern California.

Characteristics Associated With New Patient Appointment No-Shows at an Academic Ophthalmology Department in the United States.

Purpose: This study aimed to identify patient and appointment characteristics associated with no-shows to new patient appointments at a US academic ophthalmology department.

Design: Cross-sectional study.

Methods: This was a study of all adult patients with new patient appointments scheduled with an attending ophthalmologist at Penn State Eye Center between January 1 and December 31 of 2019.

Corneal bee sting: improvement in the acute stage in the absence of treatment.

Bee sting injuries to the eye are relatively uncommon. The outcomes of corneal bee sting injuries are highly variable, and there is no consensus on the management at the time of initial presentation. We report a case of a 17-year-old male with a corneal bee sting injury that significantly improved in the acute stage without any treatment, which to the best of our knowledge is the first report in the literature documenting the natural history of a corneal bee sting injury in the acute stage.

Sex Differences in Academic Rank, Scholarly Productivity, National Institutes of Health Funding, and Industry Ties Among Academic Cornea Specialists in the United States.

Purpose: This study analyzed sex differences among cornea specialists with regards to academic rank, scholarly productivity, National Institutes of Health (NIH) funding, and industry partnerships.

Design: Cross-sectional study.

Methods: This was a study of faculty at 113 US academic programs.

Neoadjuvant Leuprolide Therapy with Radical Prostatectomy: Long-term Effects on Health-related Quality of Life.

Background: Neoadjuvant androgen ablation (neoadjuvant androgen deprivation therapy [NADT]) is used prior to radical prostatectomy, contrary to guidelines, but its long-term effects on quality of life is unknown.

Objective: To determine the effect of NADT on patient's long-term recovery following surgery.

Design, Setting, And Participants: From March 2011 to August 2013, 5808 men with newly diagnosed prostate were followed up to 24 mo.

A Layered Control Architecture of Sleep and Arousal.

Sleep and wakefulness are promoted not by a single neural pathway but via wake or sleep-promoting nodes distributed across layers of the brain. We equate each layer with a brain region in proposing a layered subsumption model for arousal based on a computational architecture. Beyond the brainstem the layers include the diencephalon (hypothalamus, thalamus), basal ganglia, and cortex.

International experiences during United States ophthalmology residency training: Current structure of international experiences and perspectives of faculty mentors at United States training institutions.

Background: There is a high level of interest in international experiences during United States (U.S.) ophthalmology residency training among both program directors and trainees.

How Should Mission Trips Be Administered?

Opportunities to study and practice health-related professions internationally offer transformative benefits for patients, educators, and students. Institutions and educators should model ethical behavior and set examples for global health trainees. Toward this end, it is imperative that universities engaging in international immersion experiences ensure that principles of respect, beneficence, and justice are upheld.

Nigrostriatal and mesolimbic control of sleep-wake behavior in rat.

The midbrain dopamine system via the dorsal and ventral striatum regulates a wide range of behaviors. To dissect the role of dopaminergic projections to the dorsal striatum (nigrostriatal projection) and ventral striatum (mesolimbic projection) in sleep-wake behavior, we selectively chemogenetically stimulated nigrostriatal or mesolimbic projections and examined the resulting effects on sleep in rats. Stimulation of nigrostriatal pathways increased sleep and EEG delta power, while stimulation of mesolimbic pathways decreased sleep and reduced cortical EEG power.

Synergy Testing of Antiamoebic Agents for Acanthamoeba: Antagonistic Effect of Voriconazole.

Purpose: To determine whether combinations of commonly used antiamoebic agents display synergy in their ability to kill Acanthamoeba cysts in vitro.

Methods: Synergy testing was performed with a microdilution checkerboard assay on 10 clinical Acanthamoeba keratitis isolates collected at the Proctor Foundation from 2008 to 2012. Each isolate was exposed to pairwise combinations of chlorhexidine, propamidine, and voriconazole.

RNA G-quadruplex is resolved by repetitive and ATP-dependent mechanism of DHX36.

DHX36 is a DEAH-box helicase that resolves parallel G-quadruplex structures formed in DNA and RNA. The recent co-crystal structure of DHX36 bound G4-DNA revealed an intimate contact, but did not address the role of ATP hydrolysis in G4 resolving activity. Here, we demonstrate that unlike on G4-DNA, DHX36 displays ATP-independent unfolding of G4-RNA followed by ATP-dependent refolding, generating a highly asymmetric pattern of activity.

Protein and RNA dynamical fingerprinting.

Protein structural vibrations impact biology by steering the structure to functional intermediate states; enhancing tunneling events; and optimizing energy transfer. Strong water absorption and a broad continuous vibrational density of states have prevented optical identification of these vibrations. Recently spectroscopic signatures that change with functional state were measured using anisotropic terahertz microscopy.

The National Sleep Foundation's Sleep Satisfaction Tool.

Objectives: The National Sleep Foundation (NSF) sought to test, refine, and add statistical rigor to its previously described provisional Sleep Satisfaction Tool (SST). The tool assesses the general population's sleep satisfaction.

Design: In 2017, NSF created a provisional tool through systematic literature review and an expert consensus panel process.

Structural basis of G-quadruplex unfolding by the DEAH/RHA helicase DHX36.

Guanine-rich nucleic acid sequences challenge the replication, transcription, and translation machinery by spontaneously folding into G-quadruplexes, the unfolding of which requires forces greater than most polymerases can exert. Eukaryotic cells contain numerous helicases that can unfold G-quadruplexes . The molecular basis of the recognition and unfolding of G-quadruplexes by helicases remains poorly understood.

Diversity of Chlamydia trachomatis in Trachoma-Hyperendemic Communities Treated With Azithromycin.

Prior studies have theorized that low chlamydial genetic diversity following mass azithromycin treatments for trachoma may create a population bottleneck that prevents the return of infection, but little empirical evidence exists to support this hypothesis. In this study, a single mass azithromycin distribution was administered to 21 communities in the Gurage Zone of Ethiopia in 2003. All children aged 1-5 years had conjunctival swabs performed before treatment and 2 and 6 months after treatment.

A provisional tool for the measurement of sleep satisfaction.

Objectives: The goal of this project was to provisionally identify the basic elements of sleep satisfaction within the general population.

Methods: The National Sleep Foundation conducted a systematic literature review and identified 495 published articles evaluating potential indicators of sleep satisfaction. The National Sleep Foundation then convened an expert panel ("Panel"), provided full-text articles and summaries, and used a modified RAND appropriateness method with three total rounds of voting to determine the appropriateness of indicators for sleep satisfaction.

Corneal transplantation at Tenwek Hospital, Kenya, East Africa: Analysis of outcomes and associated patient socioeconomic characteristics.

Purpose: To review the graft survival rate, visual outcomes, and patient demographics of primary penetrating keratoplasty performed at Tenwek Hospital, a mission hospital in rural Kenya.

Methods: A retrospective review was performed of the clinical records of patients who underwent primary penetrating keratoplasty for optical purposes from January 2012 to October 2014. The graft survival rates were constructed using the Kaplan-Meier method, and the effect of clinical and socioeconomic characteristics on time to graft failure were examined using Cox regression models.

Targeted disruption of supraspinal motor circuitry reveals a distributed network underlying Restless Legs Syndrome (RLS)-like movements in the rat.

In this study we uncovered, through targeted ablation, a potential role for corticospinal, cerebello-rubro-spinal, and hypothalamic A11 dopaminergic systems in the development of restless legs syndrome (RLS)-like movements during sleep. Targeted lesions in select basal ganglia (BG) structures also revealed a major role for nigrostriatal dopamine, the striatum, and the external globus pallidus (GPe) in regulating RLS-like movements, in particular pallidocortical projections from the GPe to the motor cortex. We further showed that pramipexiole, a dopamine agonist used to treat human RLS, reduced RLS-like movements.

Ventral medullary control of rapid eye movement sleep and atonia.

Discrete populations of neurons at multiple levels of the brainstem control rapid eye movement (REM) sleep and the accompanying loss of postural muscle tone, or atonia. The specific contributions of these brainstem cell populations to REM sleep control remains incompletely understood. Here we show in rats that viral vector-based lesions of the ventromedial medulla at a level rostral to the inferior olive (pSOM) produced violent myoclonic twitches and abnormal electromyographic spikes, but not complete loss of tonic atonia, during REM sleep.

Stimulation of the Pontine Parabrachial Nucleus Promotes Wakefulness via Extra-thalamic Forebrain Circuit Nodes.

Human and animal studies have identified an especially critical role for the brainstem parabrachial (PB) complex in regulating electrocortical (electroencephalogram [EEG]) and behavioral arousal: lesions of the PB complex produce a monotonous high-voltage, slow-wave EEG and eliminate spontaneous behaviors. We report here that targeted chemogenetic activation of the PB complex produces sustained EEG and behavioral arousal in the rat. We further establish, using viral-mediated retrograde activation, that PB projections to the preoptic-basal forebrain and lateral hypothalamus, but not to the thalamus, mediate PB-driven wakefulness.

The anatomical, cellular and synaptic basis of motor atonia during rapid eye movement sleep.

Rapid eye movement (REM) sleep is a recurring part of the sleep-wake cycle characterized by fast, desynchronized rhythms in the electroencephalogram (EEG), hippocampal theta activity, rapid eye movements, autonomic activation and loss of postural muscle tone (atonia). The brain circuitry governing REM sleep is located in the pontine and medullary brainstem and includes ascending and descending projections that regulate the EEG and motor components of REM sleep. The descending signal for postural muscle atonia during REM sleep is thought to originate from glutamatergic neurons of the sublaterodorsal nucleus (SLD), which in turn activate glycinergic pre-motor neurons in the spinal cord and/or ventromedial medulla to inhibit motor neurons.

Anterior Insula Regulates Multiscale Temporal Organization of Sleep and Wake Activity.

The role of specific cortical regions in sleep-regulating circuits is unclear. The anterior insula (AI) has strong reciprocal connectivity with wake and sleep-promoting hypothalamic and brainstem regions, and we hypothesized that the AI regulates patterns of sleep and wakefulness. To test this hypothesis, we lesioned the AI in rats (n = 8) and compared sleep, wake, and activity regulation in these animals with nonlesioned controls (n = 8) with 24-h sleep recordings and chronic infrared activity monitoring.

Dermatological Adverse Events Associated with Topical Brimonidine Gel 0.33% in Subjects with Erythema of Rosacea: A Retrospective Review of Clinical Studies.

Background: The topical α2 adrenergic receptor agonist brimonidine gel 0.33% is an effective and safe pharmacological treatment for the facial erythema of rosacea. However, adverse events of worsened redness have occasionally been reported with its use.