The molecular clockwork of mammalian cells.

Most organisms contain self-sustained circadian clocks. These clocks can be synchronized by environmental stimuli, but can also oscillate indefinitely in isolation. In mammals this is true at the molecular level for the majority of cell types that have been examined. A core set of "clock genes" form a transcriptional/translational feedback loop (TTFL) which repeats with a period of approximately 24 h. The exact mechanism of the TTFL differs slightly in various cell types, but all involve similar family members of the core cohort of clock genes. The clock has many outputs which are unique for different tissues. Cells in diverse tissues will convert the timing signals provided by the TTFL into uniquely orchestrated transcriptional oscillations of many clock-controlled genes and cellular processes.

The effect of mandatory post-call relief on sleep and wellness in ophthalmology residents.

BACKGROUND: Multiple duty hour reforms have been implemented to optimize resident wellness through increasing opportunities for sleep recovery, but few studies have recorded objectively measured sleep or shown direct sleep and wellness benefits from such interventions. This study seeks to determine whether mandatory post-call relief policies with a partial night float system improved resident sleep, activity, and burnout among ophthalmology residents taking home call. METHODS: We conducted a two group cohort study of ophthalmology residents at the University Washington comparing post graduate year-2 (PGY-2) resident sleep, activity, and burnout between the optional post-call relief group from July 1, 2017 to June 30, 2019 to the mandatory post-call relief group from July 1, 2019 to June 30, 2021. RESULTS: Of twenty total residents participating in the survey portion, 18 residents participated in the sleep and activity tracking portion of the study, 9 in in the optional post-call relief cohort, and 9 in the mandatory post-call relief cohort. The mandatory post-call relief group recorded longer total sleep on call than the optional post-call relief group (p < 0.001). There was no difference in overnight sleep recorded on call (median 3.4 h), but residents recorded more time napping in the mandatory post-call relief cohort (p < 0.001). There was no significant difference between cohorts in amount of sleep while not on call. Residents in the mandatory post-call relief cohort recorded higher average daily steps, higher exercise time, and lower sedentary time than residents in the optional post-call relief cohort (p < 0.001). They also recorded lower median emotional exhaustion on the Maslach Burnout Inventory and lower stress in the Depression and Anxiety Stress Scale in the mandatory post-call relief cohort (p = 0.008). CONCLUSIONS: Implementation of mandatory post-call relief policies with a partial night-float system among PGY-2 residents was associated with more post-call naps with more overall physical activity, lower emotional exhaustion scores, and lower stress scores, despite no changes to overnight sleep on call or total sleep. Although sample size limits interpretation of data, implementation of mandatory post call relief could be considered to improve post-call sleep in programs with home call.

Using Deep Learning to Automate Goldmann Applanation Tonometry Readings.

PURPOSE: To develop an objective and automated method for measuring intraocular pressure using deep learning and fixed-force Goldmann applanation tonometry (GAT) techniques. DESIGN: Prospective cross-sectional study. PARTICIPANTS: Patients from an academic glaucoma practice. METHODS: Intraocular pressure was estimated by analyzing videos recorded using a standard slit-lamp microscope and fixed-force GAT. Video frames were labeled to identify the outline of the reference tonometer and the applanation mires. A deep learning model was trained to localize and segment the tonometer and mires. Intraocular pressure values were calculated from the deep learning-predicted tonometer and mire diameters using the Imbert-Fick formula. A separate test set was collected prospectively in which standard and automated GAT measurements were collected in random order by 2 independent masked observers to assess the deep learning model as well as interobserver variability. MAIN OUTCOME MEASURES: Intraocular pressure measurements between standard and automated methods were compared. RESULTS: Two hundred sixty-three eyes of 135 patients were included in the training and validation videos. For the test set, 50 eyes from 25 participants were included. Each eye was measured by 2 observers, resulting in 100 videos. Within the test set, the mean difference between automated and standard GAT results was -0.9 mmHg (95% limits of agreement [LoA], -5.4 to 3.6 mmHg). Mean difference between the 2 observers using standard GAT was 0.09 mmHg (LoA,-3.8 to 4.0 mmHg). Mean difference between the 2 observers using automated GAT videos was -0.3 mmHg (LoA, -4.1 to 3.5 mmHg). The coefficients of repeatability for automated and standard GAT were 3.8 and 3.9 mmHg, respectively. The bias for even-numbered measurements was reduced when using automated GAT. CONCLUSIONS: Preliminary measurements using deep learning to automate GAT demonstrate results comparable with those of standard GAT. Automated GAT has the potential to improve on our current GAT measurement standards significantly by reducing bias and improving repeatability. In addition, ocular pulse amplitudes could be observed using this technique.

Characterisation and diagnosis of ulcers in inpatient dermatology consultation services: A multi-centre study.

Accurate and prompt diagnosis of skin ulcers is critical to optimise management; however, studies in hospitalised patients are limited. This retrospective review of dermatologic consultations included 272 inpatients with skin ulcers between July 2015 and July 2018 in four U.S. academic hospitals. The median age was 54 years and 45% were male. In 49.3% of the patients, skin ulcers were considered the primary reason for admission. Ulcers of 62% were chronic and 49.6% were located on the lower extremities. Pyoderma gangrenosum (17.3%), infection (12.5%), and exogenous causes (11.8%) were the leading aetiologies; 12% remained diagnostically inconclusive after consultation. Diagnostic agreements pre-dermatology and post-dermatology consult ranged from 0.104 (n = 77, 95% CI 0.051-0.194) to 0.553 (n = 76, 95% CI 0.440-0.659), indicating poor-modest agreement. This study highlights the diagnostic complexity and relative incidences of skin ulcers in the inpatient setting.

Performance of Generative Large Language Models on Ophthalmology Board-Style Questions.

PURPOSE: To investigate the ability of generative artificial intelligence models to answer ophthalmology board-style questions. DESIGN: Experimental study. METHODS: This study evaluated 3 large language models (LLMs) with chat interfaces, Bing Chat (Microsoft) and ChatGPT 3.5 and 4.0 (OpenAI), using 250 questions from the Basic Science and Clinical Science Self-Assessment Program. Although ChatGPT is trained on information last updated in 2021, Bing Chat incorporates a more recently indexed internet search to generate its answers. Performance was compared with human respondents. Questions were categorized by complexity and patient care phase, and instances of information fabrication or nonlogical reasoning were documented. MAIN OUTCOME MEASURES: Primary outcome was response accuracy. Secondary outcomes were performance in question subcategories and hallucination frequency. RESULTS: Human respondents had an average accuracy of 72.2%. ChatGPT-3.5 scored the lowest (58.8%), whereas ChatGPT-4.0 (71.6%) and Bing Chat (71.2%) performed comparably. ChatGPT-4.0 excelled in workup-type questions (odds ratio [OR], 3.89, 95% CI, 1.19-14.73, P = .03) compared with diagnostic questions, but struggled with image interpretation (OR, 0.14, 95% CI, 0.05-0.33, P < .01) when compared with single-step reasoning questions. Against single-step questions, Bing Chat also faced difficulties with image interpretation (OR, 0.18, 95% CI, 0.08-0.44, P < .01) and multi-step reasoning (OR, 0.30, 95% CI, 0.11-0.84, P = .02). ChatGPT-3.5 had the highest rate of hallucinations and nonlogical reasoning (42.4%), followed by ChatGPT-4.0 (18.0%) and Bing Chat (25.6%). CONCLUSIONS: LLMs (particularly ChatGPT-4.0 and Bing Chat) can perform similarly with human respondents answering questions from the Basic Science and Clinical Science Self-Assessment Program. The frequency of hallucinations and nonlogical reasoning suggests room for improvement in the performance of conversational agents in the medical domain.

Topical adapalene for the treatment of follicular conjunctivitis due to periocular molluscum contagiosum in children.

PURPOSE: Periocular molluscum contagiosum can cause a chronic secondary follicular conjunctivitis or keratoconjunctivitis that rarely leads to corneal scarring and visual impairment. We describe two cases of follicular conjunctivitis due to periocular molluscum contagiosum that were successfully treated with topical adapalene 0.1%. OBSERVATIONS: Case 1 is a 9-year old female with a history of leg molluscum contagiosum who presented with three 1mm flesh-colored umbilicated papules on the periocular skin of the right eye with associated follicular conjunctivitis and diffuse corneal punctate epithelial erosions. Ocular symptoms were persistent for 6 months. Case 2 is a 4-year old female with a 3-month history of right periocular bumps and one month of conjunctival redness with eyelid edema. Examination revealed umbilicated flesh colored nodules on the right upper and lower eyelids with associated trace conjunctival injection. Both patients experienced rapid resolution of both eyelid involvement and conjunctivitis following the use of twice daily topical adapalene 0.1% to the eyelid lesions, with no reported side effects. CONCLUSIONS AND IMPORTANCE: Topical adapalene 0.1% is a cost-effective, convenient, and non-toxic over-the-counter retinoid cream that should be considered for first-line therapy in the treatment of periocular molluscum contagiosum and any associated conjunctivitis.

Relationships Between Sleep, Activity, and Burnout in Ophthalmology Residents.

OBJECTIVE: To objectively measure sleep and activity levels and examine their relationship to burnout, depression, anxiety, and stress in ophthalmology residents. DESIGN: A cohort study of ophthalmology residents at the University of Washington from July 1, 2017 to June 30, 2018. SETTING: Single-center academic institution. PARTICIPANTS: Fourteen ophthalmology residents at the University of Washington enrolled between July 1, 2017 and June 30, 2018. RESULTS: Data were collected from 14 residents, ages 27 to 34. Wrist actigraphy allowed for objective measurement of resident sleep and activity, though adherence to wrist actigraphy usage dropped significantly over time. Residents recorded significantly less sleep on call compared to when they were off call, with mean (SD) 3.6 (2.0) hours on primary call, 5.6 (1.8) hours on secondary call, and 6.7 (1.4) hours off call. Lower average sleep on call was associated with higher emotional exhaustion (r = -0.69, p = 0.04), lower personal accomplishment (r = 0.82, p = 0.007), higher anxiety (r = -0.90, p = 0.001), and higher stress (r = -0.75, p = 0.02). Higher daily activity was associated with higher sense of personal accomplishment (r = 0.57, p = 0.04). Average nightly sleep, average sleep while not on call, and daily sedentary time was not associated with any subset of burnout. CONCLUSIONS: The association between objectively measured sleep while on call and burnout, depression, and anxiety are consistent with findings from prior studies which relied on subjective measures of sleep. The direction of causality - whether poor sleep caused burnout, burnout caused poor sleep, or both - could not be assessed in the present study. However, these results are consistent with the hypothesis that poor sleep on call contributes to resident burnout and that physical activity may reduce aspects of burnout. The use of wrist actigraphy to objectively measure sleep and activity patterns may help focus and evaluate interventions aimed at decreasing resident burnout.

Monitoring changes in knee surface morphology after anterior cruciate ligament reconstruction surgery using 3Dsurface scanning.

STUDY DESIGN: Prospective case series. BACKGROUND: After surgical reconstruction of the anterior cruciate ligament, recovery to pre-injury levels of knee function is challenging. Postoperative edema and muscle atrophy are common roadblocks to full function and are evident in changes to the surface morphology of the knee. There are currently few accessible objective tools to accurately track these morphological changes. OBJECTIVES: We aimed to determine if 3D surface scanning can be used to monitor changes in the external shape of the knee after surgery and throughout the rehabilitation process. METHODS: Thirty participants had 3D surface scans taken of their knee, along with questionnaire-based functional outcomes prior to surgery (baseline), and at two-week, six-week, 12-week, and 26-week timepoints post-surgery. Volumetric changes relative to pre-op were assessed using generalized linear growth models for key anatomical regions and correlated with functional outcomes. RESULTS: Significant swelling of the patella region compared to baseline was evident immediately after surgery (14%, p < 0.001), before returning to pre-operative levels. Changes in volume at this region were significantly associated with patient-reported functional outcomes. Reductions in volume of the regions corresponding to the vastus medialis and lateralis muscles were significant at 12 weeks post-surgery (p = 0.018 and 0.01 respectively) but returned to baseline levels at six months. CONCLUSION: We demonstrate the use of 3D surface scanning as a method for capturing detailed measurements of knee surface morphology after surgery. Significant changes in external morphology are evident during the rehabilitation process.