Skin Cancer in the Incarcerated Population-A Single-Center Study.

BACKGROUND: The incarcerated population may have variable access to specialty care that may affect the detection and diagnosis of skin cancer. OBJECTIVE: The purpose of the study was to characterize skin cancers in the incarcerated population and determine time to treatment initiation (TTI) after biopsy. METHODS: A retrospective cohort study was performed using data from a single-center referral hospital of incarcerated patients with biopsy-proven basal cell carcinoma (BCC), squamous cell carcinoma (SCC), or melanoma between January 2009 and December 2019. The main outcome measured was TTI after biopsy. RESULTS: One hundred thirteen patients, majority men (96.5%) and of Caucasian race (89.4%), were diagnosed and/or treated for 191 skin cancers. Of these 191 skin cancers, 118 were BCC (61.8%), 58 were SCC (30.4%), and 15 were melanomas (7.9%). The average TTI after biopsy for melanoma was 57 days (range: 21-136, median: 51, 95% confidence interval: 39.89-74.10) with an average Breslow depth of 1.57 mm. CONCLUSION: The average TTI of melanoma in the incarcerated population in this study was greater than 30 days, which may have increased mortality risk.

Rest-Activity Pattern Alterations in Idiopathic REM Sleep Behavior Disorder.

OBJECTIVE: The purpose of this study was to investigate the differences in actigraphy-measured rest-activity patterns (eg, sleep-wake cycle, circadian rest-activity rhythm, and physical activity) across different stages of α-synucleinopathy. METHODS: We compared alterations in 7-day actigraphy-measured rest-activity patterns among patients with clinically diagnosed α-synucleinopathies (n = 44), and their age-, sex-, and body mass index (BMI)-matched patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD, n = 88), and non-rapid eye movement (REM) sleep behavior disorder (RBD) controls (n = 44) in a case-control study (study 1) and between convertors (n = 22) and their age-, sex-, BMI-, iRBD-duration, and follow-up duration-matched non-convertors (n = 66) in a prospective nested case-control study (study 2). RESULTS: In study 1, there were significant increases (all p values were adjusted by false discovery rate < 0.01) in probable napping behaviors (percentage, duration, and episodes), activity fragmentation (estimated by kAR ), and physical inactivity during active periods across controls, and iRBD, to clinically diagnosed α-synucleinopathies. In study 2, higher levels (all p values were adjusted by false discovery rate < 0.05) of baseline objective probable napping, activity fragmentation, and physical inactivity during active periods were associated with the conversion of patients with iRBD into clinically diagnosed α-synucleinopathies at 2 years of follow-up with medium to large effect sizes (Cohen's d: 0.56 to 0.80). These findings were further supported by functional linear modeling analyses. INTERPRETATION: Rest-activity pattern alterations, mainly objective probable napping behaviors, activity fragmentation, and physical inactivity during active period, emerge as early as at the stage of iRBD, which serves as early and robust prodromal markers of the conversion of iRBD into clinically diagnosed α-synucleinopathies. ANN NEUROL 2020;88:817-829.

Dual-specificity phosphatase (DUSP) genetic variants predict pulmonary hypertension in patients with bronchopulmonary dysplasia.

BACKGROUND: Pulmonary hypertension (PH) in patients with bronchopulmonary dysplasia (BPD) results from vasoconstriction and/or vascular remodeling, which can be regulated by mitogen-activated protein kinases (MAPKs). MAPKs are deactivated by dual-specificity phosphatases (DUSPs). We hypothesized that single-nucleotide polymorphisms (SNPs) in DUSP genes could be used to predict PH in BPD. METHODS: Preterm infants diagnosed with BPD (n = 188) were studied. PH was defined by echocardiographic criteria. Genomic DNA isolated from patient blood samples was analyzed for 31 SNPs in DUSP genes. Clinical characteristics and minor allele frequencies were compared between BPD-PH (cases) and BPD-without PH (control) groups. Biomarker models to predict PH in BPD using clinical and SNP data were tested by calculations of area under the ROC curve. RESULTS: In our BPD cohort, 32% (n = 61) had PH. Of the DUSP SNPs evaluated, DUSP1 SNP rs322351 was less common, and DUSP5 SNPs rs1042606 and rs3793892 were more common in cases than in controls. The best fit biomarker model combines clinical and DUSP genetic data with an area under the ROC curve of 0.76. CONCLUSION: We identified three DUSP SNPs as potential BPD-PH biomarkers. Combining clinical and DUSP genetic data yields the most robust predictor for PH in BPD.

Implementation of hormonal contraceptive furnishing in San Francisco community pharmacies.

BACKGROUND: In 2013, California passed Senate Bill 493, which allowed pharmacists to furnish hormonal contraceptives without a physician's prescription. Despite this expanded scope of practice, only 11% of the pharmacies reported furnishing hormonal contraception over the following 6 years. OBJECTIVES: Our study objectives were to determine the extent of hormonal contraceptive furnishing and identify the factors that led to successful implementation in San Francisco community pharmacies. METHODS: Backspace we conducted a cross-sectional survey to identify community pharmacies furnishing hormonal contraception in San Francisco. Interviews were coded inductively to identify consistent themes. Semistructured interviews with pharmacists at the locations that furnished contraception identified the factors that had led to successful implementation in local community pharmacies, as well as assessing changes in practice during the coronavirus disease (COVID-19) pandemic. RESULTS: San Francisco had 113 operational community pharmacies in April 2020. Of these, 21 locations reported that they furnished hormonal contraception (19%), and we interviewed pharmacists at 12 of those locations. We identified 3 key factors that drove implementation at the pharmacy level: administrative support, advertising, and pharmacist engagement. Additional drivers of implementation involved the nature of the community. The respondents also reported on barriers that continued to slow adoption, including consultation fees, time constraints, and patient privacy. Changes in demand for services owing to COVID-19 risks were inconsistent. CONCLUSION: Our findings suggest strategies that community pharmacies can use to expand their scope of practice and improve quality and continuity of care for patients.

Characterization of reactive nitrogen species in allergic asthma.

OBJECTIVE: To investigate the molecular mechanism of reactive nitrogen species (RNS) in the pathogenesis of asthma and examine the use of fractional exhaled nitric oxide (FENO) measurements in close conjunction with standard clinical assessments of asthma. DATA SOURCES: Through PubMed, Google Scholar, and Medline databases, a broad medical literature review was performed in the following areas of asthma pathobiology and management: allergic asthma, RNS, nitric oxide (NO), airway inflammation, and FENO. STUDY SELECTIONS: Studies were selected based on the physiologic and pathophysiologic roles of RNS in relation to allergic asthma. Current evaluations on clinical applications of FENO in asthma treatment also were selected. RESULTS: At the onset of an asthma attack, an enhanced production of NO strongly correlates with increase inducible NO synthase (NOS) activity, whereas endothelial NOS and neuronal NOS regulate primarily normal metabolic functions in the central and peripheral airways. During allergic inflammatory responses, NO and superoxide form peroxynitrite, which has deleterious effects in the respiratory tract. RNS directly accentuates airway inflammation and cytotoxicity through nitrosative stress. Moreover, the use of FENO to monitor eosinophilic-mediated airway inflammation is a potentially valuable assessment that supplements standard procedures to monitor the progression of asthma. CONCLUSION: This review examines recent evidence implicating the molecular mechanisms of NO and NO-derived RNS in the pathobiology of asthma and suggests that monitoring FENO may markedly contribute to asthma diagnosis.

Clinical Validation of a Handheld Deep Learning Tool for Identification of Glaucoma Medications.

Purpose: To validate a convolutional neural network (CNN)-based smartphone application for the identification of glaucoma eye drop medications in patients with normal and impaired vision. Methods: Sixty-eight patients with visual acuity (VA) of 20/70 or worse in at least one eye who presented to an academic glaucoma clinic from January 2021 through August 2022 were included. Non-English-speaking patients were excluded. Enrolled subjects participated in an activity in which they identified a predetermined and preordered set of six topical glaucoma medications, first without the CNN and then with the CNN for a total of six sequential measurements per subject. Responses to a standardized survey were collected during and after the activity. Primary quantitative outcomes were medication identification accuracy and time. Primary qualitative outcomes were subjective ratings of ease of smartphone application use. Results: Topical glaucoma medication identification accuracy (OR = 12.005, P < 0.001) and time (OR = 0.007, P < 0.001) both independently improved with CNN use. CNN use significantly improved medication accuracy in patients with glaucoma (OR = 4.771, P = 0.036) or VA ≤ 20/70 in at least one eye (OR = 4.463, P = 0.013) and medication identification time in patients with glaucoma (OR = 0.065, P = 0.017). CNN use had a significant positive association with subject-reported ease of medication identification (X2(1) = 66.117, P < 0.001). Conclusion: Our CNN-based smartphone application is efficacious at improving glaucoma eye drop identification accuracy and time. This tool can be used in the outpatient setting to avert preventable vision loss by improving medication adherence in patients with glaucoma.

Metastatic melanoma of unknown origin mimicking neurofibromatosis.

We present an unusual case of metastatic melanoma in a young patient with imaging appearance resembling neurofibromatosis. A 36-year-old-man with a history of cervical radiculopathy presented with cauda equina syndrome. An MRI was performed for further evaluation demonstrating multiple intradural, extramedullary enhancing lesions in the thoracic and lumbar spine, as well as extra-axial enhancing lesions with involvement of the lateral ventricles and posterior fossa. Bilateral pulmonary masses were found on chest CT. Lung lesions were biopsied and positive for metastatic melanoma. Melanoma is the third most common primary neoplasm to produce brain metastasis and should be considered on the differential as a cause of newly detected intracranial and intraspinal masses in young patients.

A Novel Epidemiological Approach to Geographically Mapping Population Dry Eye Disease in the United States Through Google Trends.

PURPOSE: Our study fills the spatiotemporal gaps in dry eye disease (DED) epidemiology by using Google Trends as a novel epidemiological tool for geographically mapping DED in relation to environmental risk factors. METHODS: We used Google Trends to extract DED-related queries estimating users' intent from 2004 to 2019 in the United States. We incorporated national climate data to generate heat maps comparing geographic, temporal, and environmental relationships of DED. Multivariable regression models were constructed to generate quadratic forecasts predicting DED and control searches. RESULTS: Our results illustrated the upward trend, seasonal pattern, environmental influence, and spatial relationship of DED search volume across the US geography. Localized patches of DED interest were visualized in urban areas. There was no significant difference in DED queries across the US census regions (P = 0.3543). Regression model 1 predicted DED queries per state (R2 = 0.61), with the significant predictor being urban population [r = 0.56, adjusted (adj.) P < 0.001, n = 50]; model 2 predicted DED searches over time (R2 = 0.97), with significant predictors being control queries (r = 0.85, adj. P = 0.0169, n = 190), time (r = 0.96, adj. P < 0.001, n = 190), time2 (r = 0.97, adj. P < 0.001, n = 190), and seasonality (winter r = -0.04, adj. P = 0.0196, n = 190; spring r = 0.10, adj. P < 0.001, n = 190). CONCLUSIONS: Our study used Google Trends as a novel epidemiologic approach to geographically mapping the US DED. Importantly, urban population and seasonality were stronger risk factors of DED searches than temperature, humidity, sunshine, pollution, or region. Our work paves the way for future exploration of geographic information systems for locating DED and other diseases through online population metrics.

Immune thrombocytopenia in 2 healthy young women after the Pfizer-BioNTech BNT16B2b2 messenger RNA coronavirus disease 2019 vaccination.

Immune thrombocytopenic purpura (ITP) is a rare complication associated with vaccines targeting various diseases, including influenza, measles-mumps-rubella, hepatitis B, and diphtheria-tetanus-pertussis. We report 2 cases of ITP in healthy 20-year-old and 21-year-old women presenting to Emory University in Atlanta, GA, 2 days after the second dose and 11 days after the first dose (respectively) of the Pfizer-BioNTech messenger RNA severe acute respiratory syndrome coronavirus 2 vaccine. Both patients recovered quickly. With more than a billion doses of coronavirus disease 2019 vaccines safely administered worldwide as of May 2021, discussions with patients should put into perspective the low risks of vaccination against the enormous societal benefit of the coronavirus disease 2019 vaccine.

Src-inducible association of CrkL with procaspase-8 promotes cell migration.

Procaspase-8, the zymogen form of the apoptosis-initiator caspase-8, undergoes phosphorylation following integrin-mediated cell attachment to an extracellular matrix substrate. Concordant with cell attachment to fibronectin, a population of procaspase-8 becomes associated with a peripheral insoluble compartment that includes focal complexes and lamellar microfilaments. Phosphorylation of procaspase-8 both impairs its maturation to the proapoptotic form and can promote cell migration. Here we show that the cytoskeletal adaptor protein CrkL promotes caspase-8 recruitment to the peripheral spreading edge of cells, and that the catalytic domain of caspase-8 directly interacts with the SH2 domain of CrkL. We show that the interaction is abolished by shRNA-mediated silencing of Src, in Src-deficient MEFs, and by pharmacologic inhibitors of the kinase. The results provide insight into how tyrosine kinases may act to coordinate the suppression caspase-8 mediated apoptosis, while promoting cell invasion.