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1.
JAMA Netw Open ; 7(5): e249831, 2024 May 01.
Article En | MEDLINE | ID: mdl-38700859

Importance: Patients with inequitable access to patient portals frequently present to emergency departments (EDs) for care. Little is known about portal use patterns among ED patients. Objectives: To describe real-time patient portal usage trends among ED patients and compare demographic and clinical characteristics between portal users and nonusers. Design, Setting, and Participants: In this cross-sectional study of 12 teaching and 24 academic-affiliated EDs from 8 health systems in California, Connecticut, Massachusetts, Ohio, Tennessee, Texas, and Washington, patient portal access and usage data were evaluated for all ED patients 18 years or older between April 5, 2021, and April 4, 2022. Exposure: Use of the patient portal during ED visit. Main Outcomes and Measures: The primary outcomes were the weekly proportions of ED patients who logged into the portal, viewed test results, and viewed clinical notes in real time. Pooled random-effects models were used to evaluate temporal trends and demographic and clinical characteristics associated with real-time portal use. Results: The study included 1 280 924 unique patient encounters (53.5% female; 0.6% American Indian or Alaska Native, 3.7% Asian, 18.0% Black, 10.7% Hispanic, 0.4% Native Hawaiian or Pacific Islander, 66.5% White, 10.0% other race, and 4.0% with missing race or ethnicity; 91.2% English-speaking patients; mean [SD] age, 51.9 [19.2] years). During the study, 17.4% of patients logged into the portal while in the ED, whereas 14.1% viewed test results and 2.5% viewed clinical notes. The odds of accessing the portal (odds ratio [OR], 1.36; 95% CI, 1.19-1.56), viewing test results (OR, 1.63; 95% CI, 1.30-2.04), and viewing clinical notes (OR, 1.60; 95% CI, 1.19-2.15) were higher at the end of the study vs the beginning. Patients with active portal accounts at ED arrival had a higher odds of logging into the portal (OR, 17.73; 95% CI, 9.37-33.56), viewing test results (OR, 18.50; 95% CI, 9.62-35.57), and viewing clinical notes (OR, 18.40; 95% CI, 10.31-32.86). Patients who were male, Black, or without commercial insurance had lower odds of logging into the portal, viewing results, and viewing clinical notes. Conclusions and Relevance: These findings suggest that real-time patient portal use during ED encounters has increased over time, but disparities exist in portal access that mirror trends in portal usage more generally. Given emergency medicine's role in caring for medically underserved patients, there are opportunities for EDs to enroll and train patients in using patient portals to promote engagement during and after their visits.


Emergency Service, Hospital , Patient Portals , Humans , Female , Emergency Service, Hospital/statistics & numerical data , Male , Patient Portals/statistics & numerical data , Cross-Sectional Studies , Middle Aged , Adult , United States , Aged , Young Adult
2.
Cornea ; 2024 Apr 02.
Article En | MEDLINE | ID: mdl-38561842

PURPOSE: The purpose of this study was to compare changes in the posterior curvature and the posterior-anterior radii ratio of the cornea, 1 year postoperatively in laser in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), and small incision lenticule extraction (SMILE). METHODS: This retrospective study was performed at a single surgical center. 199 eyes were included in the study from 119 patients with manifest refraction spherical equivalents from -7.61 to -2.54 D. 67 eyes underwent LASIK, 89 underwent PRK, and 43 underwent SMILE. Both preoperative and 1-year postoperative front and back sagittal keratometry were measured at 4- to 6-mm zones around the corneal vertex. Corneal asphericity (Q-value) was measured at an 8-mm zone around the corneal vertex. RESULTS: The average change in the posterior-anterior radii ratio after LASIK, PRK, and SMILE did not differ between surgery groups at 4 mm (LASIK: -0.075, PRK: -0.073, SMILE: -0.072, P = 0.720), 5 mm (LASIK: -0.072, PRK: -0.068, SMILE: -0.068, P = 0.531), or 6 mm (LASIK: -0.075, PRK: -0.071, SMILE: -0.072, P = 0.456) zones. Anterior Q-value significantly positively increased after all 3 surgeries (P < 0.001). The posterior Q-value also significantly positively increased after LASIK (P < 0.001) and SMILE (P < 0.001), but not after PRK (P = 0.227). Both anterior and posterior keratometric power decreased significantly after LASIK, PRK, and SMILE for all diameters. CONCLUSIONS: The change in the posterior-anterior radii ratio was not influenced by the type of refractive surgery performed, as indicated by statistically identical preoperative, postoperative, and delta values. In addition, the posterior cornea exhibited paracentral flattening after LASIK, SMILE, and PRK and increased oblateness after LASIK and SMILE.

3.
Clin Ophthalmol ; 18: 377-392, 2024.
Article En | MEDLINE | ID: mdl-38343904

Purpose: We assess the relationship between preoperative myopic sphere, astigmatism, and spherical equivalent and effective optical zone (EOZ) size, shape, and decentration within individual populations of post-LASIK, PRK, and SMILE patients. Patients and Methods: A retrospective chart review was conducted with 118 LASIK, 144 PRK, and 41 SMILE eyes from 179 total patients that underwent compound myopic ablation. One-year postoperative Pentacam tangential difference maps were used for EOZ data measurements. Correlational analysis between compound myopic measures [sphere, cylinder, manifest refractive spherical equivalent (MRSE)] and EOZ parameters was performed, and differences between groups of myopic sphere and cylinder within each surgery type were assessed. Results: An increase in absolute myopic sphere (and subsequent MRSE) is associated with a smaller EOZ area in SMILE (r=0.454, p=0.003) and a more circular EOZ shape in LASIK (r=0.396, p<0.001) and PRK (r=0.563, p<0.001). An increase in absolute myopic cylinder is associated with an increased EOZ area in all three surgery types [LASIK (r=-0.459, p<0.001), PRK (r=-0.716, p<0.001), SMILE (r=-0.429, p=0.005)] and a more elliptical EOZ in LASIK (r=-0.491, p<0.001) and PRK (r=-0.538, p<0.001). Conclusion: While astigmatism may be correlated to EOZ size within all three refractive surgery types, myopic sphere alone is insufficient to estimate EOZ size differences for procedures with a large blend zone of ablation like LASIK or PRK. Shape is just as important a factor as size to consider when examining corneal EOZ differences; reported correlative findings likely result from inherent differences in surgical technique and abruptness of planned surgical ablation borders.

4.
J Refract Surg ; 39(11): 741-750, 2023 Nov.
Article En | MEDLINE | ID: mdl-37937754

PURPOSE: To explore size, decentration, and eccentricity of effective optical zones (EOZs) in laser in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), and small incision lenticule extraction (SMILE) and correlate them to higher order aberrations (HOAs). METHODS: This was a retrospective chart review of 188 eyes that underwent refractive surgery for compound myopia (61 LASIK, 84 PRK, 43 SMILE). EOZ measurements were determined using 1-year postoperative Pentacam (Oculus Optikgeräte GmbH) tangential difference maps. HOA data were measured using Pentacam wavefront aberration Zernike polynomials. Correlations between EOZs and HOAs were analyzed. RESULTS: The EOZs of LASIK and PRK are smaller than SMILE at 19.54 ± 1.44, 19.39 ± 1.66, and 22.18 ± 2.61 mm2, respectively (P < .001). No difference existed in absolute decentration from corneal vertex (P = .078) or pupil center (P = .131), but horizontal and vertical components differed significantly (P < .001). Smaller EOZ areas were correlated with greater spherical aberration induction (rLASIK = -0.378, rPRK = -0.555, rSMILE = -0.501) and total HOA induction in all groups. Absolute decentration from corneal vertex positively correlated with total HOA (rLASIK = 0.396, rPRK = 0.463, rSMILE = 0.399) and directional vertical coma induction negatively correlated with vertical decentration from the corneal vertex (rLASIK = -0.776, rPRK = -0.665, rSMILE = -0.576) in all groups. CONCLUSIONS: SMILE results in a larger EOZ than LASIK and PRK, and absolute decentration remains comparable regardless of surgical reference center, despite horizontal/vertical differences. Surgical planning to ensure adequate EOZ size and centration may reduce induction of HOAs, including spherical aberrations and vertical coma. [J Refract Surg. 2023;39(11):741-750.].


Corneal Wavefront Aberration , Keratomileusis, Laser In Situ , Myopia , Photorefractive Keratectomy , Humans , Keratomileusis, Laser In Situ/methods , Visual Acuity , Retrospective Studies , Coma/surgery , Corneal Topography , Corneal Wavefront Aberration/surgery , Lasers, Excimer/therapeutic use , Myopia/surgery
5.
Clin Ophthalmol ; 17: 3307-3322, 2023.
Article En | MEDLINE | ID: mdl-37933328

Purpose: To provide a comprehensive guide of all implantable collamer lens (ICL) sizing nomograms and the respective preoperative diagnostic devices that are required. This guide would help clinicians in choosing the appropriate ICL size for myopic patients to optimize postoperative vault height. Methods: A literature search of peer-reviewed journals describing methods and postoperative outcomes of ICL sizing was conducted. Research articles containing ICL nomograms or formulas were identified from this search. Preoperative variables necessary for these nomograms and the required diagnostic devices to measure these parameters such as topography, biometry, or ultrasound biomicroscopy (UBM) were noted. An additional search was conducted to identify artificial intelligence (AI) or machine learning (ML)-derived nomograms. Results: Eighteen ICL sizing nomograms were identified through literature search. Five of these nomograms are available for use and require topography or biometry devices. Of these, four include the manufacturer's, optimized white-to-white (WTW), Kang, Kim, and Rocamora Nomograms. Eight of the 18 nomograms available for use require UBM. Eight of these include the Kojima, Nakamura, KS, ZZ, Dougherty, Parkhurst, Russo, and Reinstein Nomograms. Four of the 18 nomograms are ML-derived including Shen, Rocamora, Russo, and Kang Nomograms. Conclusion: ICL nomograms are a vital tool in helping clinicians select the right ICL size for myopic patients to optimize postoperative vault reducing risk of postoperative complications. Based on available diagnostic devices such as topography, biometry, or UBM clinicians can integrate specific nomograms into practice.

7.
Drug Metab Dispos ; 51(12): 1607-1614, 2023 Dec.
Article En | MEDLINE | ID: mdl-37684056

Pomotrelvir is an orally bioavailable, target antiviral inhibitor of the main protease (Mpro) of coronaviruses, including severe acute respiratory syndrome coronavirus 2, the etiological agent of Coronavirus Disease 2019. The pharmacokinetics, metabolism and elimination of two [14C]-labeled microtracers of 5 µCi/700 mg pomotrelvir with separate labeling positions (isotopomers), [lactam carbonyl-14C-pomotelvir] and [benzene ring-U-14C-pomotrelvir], following a single oral dose in healthy adult males was evaluated in two separate cohorts. Pomotrelvir was rapidly absorbed and eliminated primarily through metabolism and subsequently excreted via urine and feces. There were no differences in pomotrelvir pharmacokinetics between the two cohorts. The mean total radioactive dose recovered was 93.8% (n = 8) in the lactam cohort (58% in urine and 36% in feces) and 94.2% (n = 8) in the benzene cohort (75% in urine and 19% in feces), with ≥80% of [14C] recovered within 96 hours after dosing. About 5% and 3% of the intact pomotrelvir was recovered in feces and urine, respectively. Eleven major metabolites were detected and characterized using liquid chromatography-accelerator mass spectrometry and liquid chromatography tandem mass spectrometry methods, with three and six different metabolites elucidated in the samples collected from lactam and benzene cohorts, respectively, and two metabolites observed in both cohorts. The major metabolism pathway of pomotrelvir is through hydrolysis of its peptide bonds followed by phase II conjugations. These results support that the application of two radiolabeled isotopomers provided a comprehensive metabolite profiling analysis and was a successful approach in identifying the major disposition pathways of pomotrelvir that has complex routes of metabolism. SIGNIFICANCE STATEMENT: An unconventional approach using two differentially labeled [14C] microtracers, [lactam carbonyl-14C-pomotrelvir] and [benzene ring-U-14C-pomotrelvir] evaluated the mass balance of orally administered pomotrelvir in healthy adult males in two separate cohorts. The radioactive dose recovered in excreta was about 94% for both cohorts. While the two isotopomers of the radiolabeled-pomotrelvir showed no major differences in pharmacokinetics overall, they allowed for differential detection of their radiolabeled metabolites and appropriate characterization of their plasma exposure and excretion in urine and feces.


Benzene , Lactams , Adult , Humans , Male , Chromatography, High Pressure Liquid/methods , Benzene/analysis , Chromatography, Liquid , Biotransformation , Feces/chemistry , Lactams/analysis , Administration, Oral , Carbon Radioisotopes/analysis
8.
Clin Ophthalmol ; 17: 2563-2573, 2023.
Article En | MEDLINE | ID: mdl-37662649

Purpose: To compare 3 of the most common corneal refractive procedures; PRK, LASIK, and SMILE assessing ΔK/ΔSEQ ratio and its correlation with preoperative demographics including age, keratometry, pachymetry, cylinder value, and attempted myopic correction. The goal was to analyze the relative strength of each preoperative parameter in accounting for changes in ∆K/∆SEQ. Patients and Methods: A total of 370 eyes from 102 male and 97 female patients (173 eyes PRK, 153 LASIK, and 44 SMILE) with ages ranging from 20 to 51 underwent refractive surgery for myopia between -0.25 and -7.71 D manifest refraction spherical equivalent (MRSE). All surgeries were performed at a single surgery center in Draper, Utah. The Pentacam was used for all optical measurements and data were gathered pre-operatively and then again 1-year post-operatively. Only patients who achieved emmetropia at a visual acuity of 20/25 or better were included. Results: The mean ΔK/ΔSEQ ratio for LASIK (0.839 ± 0.020) was significantly greater than that of PRK (0.775 ± 0.022) and SMILE (0.709 ± 0.046). Age was found to negatively correlate with ΔK/ΔSEQ for both LASIK (r = -0.177) and SMILE (r = -0.451) procedures. Pre-op keratometry was found to negatively correlate with ΔK/ΔSEQ for LASIK (r = -0.202) but not for PRK or SMILE. Pre-op pachymetry was not correlated with ΔK/ΔSEQ for any of the procedures. Attempted myopic spherical equivalent (SEQ) correction was positively correlated with ΔK/ΔSEQ for LASIK (r = 0.236), PRK (r = 0.459), and SMILE (r = 0.304). Lastly, pre-op cylinder value was found to be correlated to ΔK/ΔSEQ in SMILE (r = -0.367), but not in LASIK or PRK. Conclusion: The ΔK/ΔSEQ ratio not only differs depending on the procedure being done but also by pre-operative factors such as age, keratometry, attempted correction, and cylinder value. Multiple linear regression analysis revealed that the attempted correction had the greatest effect on ∆K/∆SEQ out of all parameters in LASIK and PRK. For SMILE, age had the greatest predictive value of the change in ∆K/∆SEQ. While the exact effect of these parameters will vary by surgeon, all of these should be factored into a refractive surgeon's nomograms in order to achieve optimal visual outcomes for their patients.

9.
CPT Pharmacometrics Syst Pharmacol ; 12(10): 1553-1564, 2023 10.
Article En | MEDLINE | ID: mdl-37614073

Pomotrelvir is a new chemical entity and potent direct-acting antiviral inhibitor of the main protease of coronaviruses. Here the cytochrome P450 (CYP)-mediated drug-drug interaction (DDI) potential of pomotrelvir was evaluated for major CYP isoforms, starting with in vitro assays followed by the basic static model assessment. The identified CYP3A4-mediated potential DDIs were evaluated clinically at a supratherapeutic dose of 1050 mg twice daily (b.i.d.) of pomotrelvir, including pomotrelvir coadministration with ritonavir (strong inhibitor of CYP3A4) or midazolam (sensitive substrate of CYP3A4). Furthermore, a physiologically-based pharmacokinetic (PBPK) model was developed within the Simcyp Population-based Simulator using in vitro and in vivo information and validated with available human pharmacokinetic (PK) data. The PBPK model was simulated to assess the DDI potential for CYP isoforms that pomotrelvir has shown a weak to moderate DDI in vitro and for CYP3A4 at the therapeutic dose of 700 mg b.i.d. To support the use of pomotrelvir in women of childbearing potential, the impact of pomotrelvir on the exposure of the representative oral hormonal contraceptive drugs ethinyl estradiol and levonorgestrel was assessed using the PBPK model. The overall assessment suggested weak inhibition of pomotrelvir on CYP3A4 and minimal impact of a strong CYP3A4 inducer or inhibitor on pomotrelvir PK. Therefore, pomotrelvir is not anticipated to have clinically meaningful DDIs at the clinical dose. These comprehensive in vitro, in clinic, and in silico efforts indicate that the DDI potential of pomotrelvir is minimal, so excluding patients on concomitant medicines in clinical studies would not be required.


Cytochrome P-450 CYP3A , Hepatitis C, Chronic , Humans , Female , Antiviral Agents/pharmacology , Cytochrome P-450 Enzyme System , Drug Interactions , Protein Isoforms , Models, Biological , Cytochrome P-450 CYP3A Inhibitors/pharmacology , Computer Simulation
10.
J Clin Med ; 12(13)2023 Jul 07.
Article En | MEDLINE | ID: mdl-37445571

The ratio of posterior-to-anterior curvature radii of the cornea (P/A ratio) is an important element in determining corneal refractive power. P/A ratio has been well studied in patients prior to undergoing refractive surgery, but its postoperative value remains less so. We aimed to examine the value of preoperative characteristics of refractive surgery patients in predicting the 1-year postoperative P/A ratio in LASIK, PRK, and SMILE using both linear and multivariate regression analyses. This was a retrospective study that included patients with manifest refraction spherical equivalents (MRSE) from -7.71D to -0.25D. In total, 164 eyes underwent LASIK, 183 underwent PRK, and 46 underwent SMILE. All patients had preoperative and 1-year postoperative front sagittal and back sagittal keratometry measurements at 4, 5, and 6 mm around the corneal vertex. Postoperative P/A after LASIK, PRK, and SMILE was found to be significantly correlated with MRSE and preoperative P/A. Stepwise variable selection in multivariate regression revealed that spherical equivalent was the most significant predictor of postoperative P/A. When coupled with other preoperative characteristics, including P/A, age, asphericity, and keratometry, the multivariate regressions were able to produce models with high predictive value in LASIK (adjusted R2: 0.957), PRK (adjusted R2: 0.934), and SMILE (adjusted R2: 0.894).

11.
Cureus ; 13(3): e13787, 2021 Mar 09.
Article En | MEDLINE | ID: mdl-33842161

Statins are among the most frequently prescribed drugs as they effectively lower cardiovascular mortality. Atherosclerotic plaques are stabilized and lipid levels are lowered, as statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Patients placed on these drugs frequently report muscle aches, but true myositis that would call for discontinuance of the drug is actually uncommon. Workup for statin-induced myositis would require ruling out other causes of myositis and muscular dystrophies, and this can often be perplexing for the primary care physician to whom these patients initially present. This case report and recommendations may serve as a helpful guide.

12.
Glia ; 68(10): 1987-2000, 2020 10.
Article En | MEDLINE | ID: mdl-32173924

Tanycytes are radial glial cells located in the mediobasal hypothalamus. Recent studies have proposed that tanycytes play an important role in hypothalamic control of energy homeostasis, although this has not been directly tested. Here, we report the phenotype of mice in which tanycytes of the arcuate nucleus and median eminence were conditionally ablated in adult mice. Although the cerebrospinal fluid-hypothalamic barrier was rendered more permeable following tanycyte ablation, neither the blood-hypothalamic barrier nor leptin-induced pSTAT3 activation in hypothalamic parenchyma were affected. We observed a significant increase in visceral fat distribution accompanying insulin insensitivity in male mice, without significant effect on either body weight or food intake. A high-fat diet tended to accelerate overall body weight gain in tanycyte-ablated mice, but the development of visceral adiposity and insulin insensitivity was comparable to wildtype. Thermoneutral housing exacerbated fat accumulation and produced a shift away from fat oxidation in tanycyte-ablated mice. These results clarify the extent to which tanycytes regulate energy balance, and demonstrate a role for tanycytes in regulating fat metabolism.


Adipose Tissue/metabolism , Arcuate Nucleus of Hypothalamus/metabolism , Ependymoglial Cells/metabolism , Gene Deletion , Median Eminence/metabolism , Obesity/metabolism , Animals , Arcuate Nucleus of Hypothalamus/chemistry , Energy Metabolism/physiology , Ependymoglial Cells/chemistry , Male , Median Eminence/chemistry , Mice , Mice, Inbred C57BL , Mice, Transgenic , Obesity/genetics
13.
Proc Natl Acad Sci U S A ; 116(28): 14290-14299, 2019 07 09.
Article En | MEDLINE | ID: mdl-31235582

Animal models of central nervous system (CNS) demyelination, including toxin-induced focal demyelination and immune-mediated demyelination through experimental autoimmune encephalomyelitis (EAE), have provided valuable insights into the mechanisms of neuroinflammation and CNS remyelination. However, the ability to track changes in transcripts, proteins, and metabolites, as well as cellular populations during the evolution of a focal lesion, has remained challenging. Here, we developed a method to label CNS demyelinating lesions by the intraperitoneal injection of a vital dye, neutral red (NR), into mice before killing. We demonstrate that NR-labeled lesions can be easily identified on the intact spinal cord in both lysolecithin- and EAE-mediated demyelination models. Using fluorescence microscopy, we detected NR in activated macrophages/microglia and astrocytes, but not in oligodendrocytes present in lesions. Importantly, we successfully performed RT-qPCR, Western blot, flow cytometry, and mass spectrometry analysis of precisely dissected NR-labeled lesions at 5, 10, and 20 d postlesion (dpl) and found differential changes in transcripts, proteins, cell populations, and metabolites in lesions over the course of remyelination. Therefore, NR administration is a simple and powerful method to track and analyze the detailed molecular, cellular, and metabolic changes that occur within the lesion microenvironment over time following CNS injury. Furthermore, this method can be used to identify molecular and metabolic pathways that regulate neuroinflammation and remyelination and facilitate the development of therapies to promote repair in demyelinating disorders such as multiple sclerosis.


Central Nervous System/diagnostic imaging , Microglia/drug effects , Multiple Sclerosis/diagnostic imaging , Nervous System Diseases/diagnostic imaging , Animals , Astrocytes/drug effects , Astrocytes/pathology , Astrocytes/ultrastructure , Cellular Microenvironment/drug effects , Central Nervous System/drug effects , Demyelinating Diseases/diagnostic imaging , Demyelinating Diseases/metabolism , Demyelinating Diseases/pathology , Disease Models, Animal , Flow Cytometry , Humans , Lysophosphatidylcholines/toxicity , Mice , Microglia/metabolism , Microglia/pathology , Microglia/ultrastructure , Multiple Sclerosis/metabolism , Multiple Sclerosis/pathology , Myelin Sheath/drug effects , Myelin Sheath/pathology , Myelin Sheath/ultrastructure , Nerve Regeneration/drug effects , Nervous System Diseases/metabolism , Nervous System Diseases/pathology , Neutral Red/pharmacology , Oligodendroglia/metabolism , Oligodendroglia/pathology , Remyelination/drug effects , Spinal Cord Injuries/diagnostic imaging , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/pathology
14.
Front Neurosci ; 13: 240, 2019.
Article En | MEDLINE | ID: mdl-30941008

Leptin is secreted by adipocytes to regulate appetite and body weight. Recent studies have reported that tanycytes actively transport circulating leptin across the brain barrier into the hypothalamus, and are required for normal levels of hypothalamic leptin signaling. However, direct evidence for leptin receptor (LepR) expression is lacking, and the effect of tanycyte-specific deletion of LepR has not been investigated. In this study, we analyze the expression and function of the tanycytic LepR in mice. Using single-molecule fluorescent in situ hybridization (smfISH), RT-qPCR, single-cell RNA sequencing (scRNA-Seq), and selective deletion of the LepR in tanycytes, we are unable to detect expression of LepR in the tanycytes. Tanycyte-specific deletion of LepR likewise did not affect leptin-induced pSTAT3 expression in hypothalamic neurons, regardless of whether leptin was delivered by intraperitoneal or intracerebroventricular injection. Finally, we use activity-regulated scRNA-Seq (act-Seq) to comprehensively profile leptin-induced changes in gene expression in all cell types in mediobasal hypothalamus. Clear evidence for leptin signaling is only seen in endothelial cells and subsets of neurons, although virtually all cell types show leptin-induced changes in gene expression. We thus conclude that LepR expression in tanycytes is either absent or undetectably low, that tanycytes do not directly regulate hypothalamic leptin signaling through a LepR-dependent mechanism, and that leptin regulates gene expression in diverse hypothalamic cell types through both direct and indirect mechanisms.

16.
Cardiol Young ; 28(3): 351-353, 2018 Mar.
Article En | MEDLINE | ID: mdl-29151383

Inflammatory bowel disease is closely associated with an increased risk for thrombotic events. Thrombosis mostly occurs in the extremities, lungs, and liver; but it can also occur in the ventricles of the heart. The primary goal of this article is to increase awareness of the risk for ventricular thrombosis in this patient population among healthcare professionals and, thus, appropriate prompt use of thromboprophylaxis therapy for these patients during acute flare-ups. Early diagnosis and intervention are critical for ventricular thrombosis to prevent systemic embolisation of the thrombus. Concisely, inflammatory bowel disease predisposes to the development of thrombi. A low threshold for the use of imaging studies to detect such thrombi is warranted.


Heart Diseases/complications , Inflammatory Bowel Diseases/complications , Thrombosis/complications , Cardiac Imaging Techniques , Early Diagnosis , Heart Diseases/diagnostic imaging , Heart Ventricles/diagnostic imaging , Humans , Thrombosis/diagnostic imaging
17.
PeerJ ; 5: e3951, 2017.
Article En | MEDLINE | ID: mdl-29109912

BACKGROUND: Currently, there is limited knowledge about the genetics underlying pigmentary traits in East Asian populations. Here, we report the results of the first genome-wide association study of pigmentary traits (skin and iris color) in individuals of East Asian ancestry. METHODS: We obtained quantitative skin pigmentation measures (M-index) in the inner upper arm of the participants using a portable reflectometer (N = 305). Quantitative measures of iris color (expressed as L*, a* and b* CIELab coordinates) were extracted from high-resolution iris pictures (N = 342). We also measured the color differences between the pupillary and ciliary regions of the iris (e.g., iris heterochromia). DNA samples were genotyped with Illumina's Infinium Multi-Ethnic Global Array (MEGA) and imputed using the 1000 Genomes Phase 3 samples as reference haplotypes. RESULTS: For skin pigmentation, we did not observe any genome-wide significant signal. We followed-up in three independent Chinese samples the lead SNPs of five regions showing multiple common markers (minor allele frequency ≥ 5%) with good imputation scores and suggestive evidence of association (p-values < 10-5). One of these markers, rs2373391, which is located in an intron of the ZNF804B gene on chromosome 7, was replicated in one of the Chinese samples (p = 0.003). For iris color, we observed genome-wide signals in the OCA2 region on chromosome 15. This signal is driven by the non-synonymous rs1800414 variant, which explains 11.9%, 10.4% and 6% of the variation observed in the b*, a* and L* coordinates in our sample, respectively. However, the OCA2 region was not associated with iris heterochromia. DISCUSSION: Additional genome-wide association studies in East Asian samples will be necessary to further disentangle the genetic architecture of pigmentary traits in East Asian populations.

18.
Cureus ; 9(8): e1588, 2017 Aug 21.
Article En | MEDLINE | ID: mdl-29062620

Ludwig's angina is a diffuse cellulitis in the submandibular, sublingual, and submental spaces, characterized by its propensity to spread rapidly to the surrounding tissues. Early recognition and treatment for Ludwig's angina are of paramount importance due to the myriad of complications that can occur in association with Ludwig's angina. Known complications of Ludwig's angina include carotid arterial rupture or sheath abscess, thrombophlebitis of the internal jugular vein, mediastinitis, empyema, pericardial effusion, osteomyelitis of the mandible, subphrenic abscess, aspiration pneumonia, and pleural effusion. By reporting a case of Ludwig's angina, we hope to raise the awareness in our medical community for this rare clinical entity. This case describes a 54-year-old woman with Ludwig's angina that evolved from a chronic odontogenic infection. She presented with perioral swelling with the involvement of bilateral submandibular and sublingual areas, accompanied by excruciating pain, chills, fever, and vomiting. She was treated with clindamycin and cefoxitin for infection and vigorously hydrated. This case is exemplary for the successful management of this potentially lethal clinical condition. Our early recognition and aggressive treatment helped to prevent complications from Ludwig's angina.

19.
R Soc Open Sci ; 3(1): 150424, 2016 Jan.
Article En | MEDLINE | ID: mdl-26909168

There are many textural elements that can be found in the human eye, including Fuchs' crypts, Wolfflin nodules, pigment spots, contraction furrows and conjunctival melanosis. Although iris surface features have been well-studied in populations of European ancestry, the worldwide distribution of these traits is poorly understood. In this paper, we develop a new method of characterizing iris features from photographs of the iris. We then apply this method to a diverse sample of East Asian, European and South Asian ancestry. All five iris features showed significant differences in frequency between the three populations, indicating that iris features are largely population dependent. Although none of the features were correlated with each other in the East and South Asian groups, Fuchs' crypts were significantly correlated with contraction furrows and pigment spots and contraction furrows were significantly associated with pigment spots in the European group. The genetic marker SEMA3A rs10235789 was significantly associated with Fuchs' crypt grade in the European, East Asian and South Asian samples and a borderline association between TRAF3IP1 rs3739070 and contraction furrow grade was found in the European sample. The study of iris surface features in diverse populations may provide valuable information of forensic, biomedical and ophthalmological interest.

20.
Pigment Cell Melanoma Res ; 29(2): 141-62, 2016 Mar.
Article En | MEDLINE | ID: mdl-26547379

In this study, we present a new quantitative method to measure iris colour based on high-resolution photographs. We applied this method to analyse iris colour variation in a sample of individuals of East Asian, European and South Asian ancestry. We show that measuring iris colour using the coordinates of the CIELAB colour space uncovers a significant amount of variation that is not captured using conventional categorical classifications, such as 'brown', 'blue' or 'green'. We tested the association of a selected panel of polymorphisms with iris colour in each population group. Six markers showed significant associations with iris colour in the European sample, three in the South Asian sample and two in the East Asian sample. We also observed that the marker HERC2 rs12913832, which is the main determinant of 'blue' versus 'brown' iris colour in European populations, is also significantly associated with central heterochromia in the European sample.


Asian People/genetics , Eye Color/genetics , Guanine Nucleotide Exchange Factors/genetics , Iris , Polymorphism, Genetic , Quantitative Trait, Heritable , White People/genetics , Adolescent , Adult , Female , Humans , Iris Diseases/genetics , Male , Pigmentation Disorders/genetics , Ubiquitin-Protein Ligases
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