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1.
Biomed Opt Express ; 15(2): 1021-1037, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38404321

ABSTRACT

We present a fully automatic montage pipeline for adaptive optics SLO retinal images. It contains a flexible module to estimate the translation between pairwise images. The user can change modules to accommodate the alignment of the dataset using the most appropriate alignment technique, provided that it estimates the translation between image pairs and provides a quantitative confidence metric for the match between 0 and 1. We use these pairwise comparisons and associated metrics to construct a graph where nodes represent frames and edges represent the overlap relations. We use a small diameter spanning tree to determine the best pairwise alignment for each image based on the entire set of image relations. The final stage of the pipeline is a blending module that uses dynamic programming to improve the smoothness of the transition between frames. Data sets ranging from 26 to 119 images were obtained from individuals aged 24 to 81 years with a mix of visually normal control eyes and eyes with glaucoma or diabetes. The resulting automatically generated montages were qualitatively and quantitatively compared to results from semi-automated alignment. Data sets were specifically chosen to include both high quality and medium quality data. The results obtained from the automatic method are comparable or better than results obtained by an experienced operator performing semi-automated montaging. For the plug-in pairwise alignment module, we tested a technique that utilizes SIFT + RANSAC, Normalized cross-correlation (NCC) and a combination of the two. This pipeline produces consistent results not only on outer retinal layers, but also on inner retinal layers such as a nerve fiber layer or images of the vascular complexes, even when images are not of excellent quality.

2.
Transl Vis Sci Technol ; 12(11): 16, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37962539

ABSTRACT

Purpose: Adaptive optics scanning laser ophthalmoscopy (AOSLO) enables the visualization and measurement of the retinal microvasculature structure in humans. We investigated the hypothesis that diabetes mellitus (DM) induces remodeling to the wall structure in small retinal arterioles. These alterations may allow better understanding of vascular remodeling in DM. Methods: We imaged retinal arterioles in one eye of 48 participants (26 with DM and 22 healthy controls) with an AOSLO. Structural metrics of 274 arteriole segments (203 with DM and 71 healthy controls) ≤ 50 µm in outer diameter (OD) were quantified and we compared differences in wall thickness (WT), wall-to-lumen ratio (WLR), inner diameter (ID), OD, and arteriolar index ratio (AIR) between controls and participants with DM. We also compared the individual AIR (iAIR) in groups of individuals. Results: The WLR, WT, and AIRs were significantly different in the arteriole segments of DM participants (P < 0.001). The iAIR was significantly deviated in the DM group (P < 0.001) and further division of the participants with DM into groups revealed that there was an effect of the presence of diabetic retinopathy (DR) on the iAIR (P < 0.001). Conclusions: DM induces remodeling of wall structure in small retinal arterioles and in groups of individuals. The use of AIR allows us to assess remodeling independently of vessel size in the retina and to compute an index for each individual subject. Translational Relevance: High-resolution retinal imaging allows noninvasive assessment of small retinal vessel remodeling in DM that can improve our understanding of DM and DR in living humans.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Humans , Arterioles/diagnostic imaging , Retina , Retinal Vessels/diagnostic imaging , Diabetic Retinopathy/diagnostic imaging , Ophthalmoscopy
3.
Biomed Opt Express ; 14(10): 5267-5281, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37854570

ABSTRACT

The trabecular meshwork (TM), located within the iridocorneal angle, is a target for many glaucoma treatments aimed at controlling intraocular pressure. However, structural variations between individuals are poorly understood. We propose a newly designed gonioscopic lens optimized for high-resolution imaging to image fine structures of the human TM in vivo. The body of the new lens is index-matched to the human cornea and includes a choice of two gonioscopic mirrors (59° and 63°) and matching air-spaced doublets placed on the anterior surface of the goniolens. The new design allows a diffraction-limited image plane at the iridocorneal angle structures. The goniolens design was built and then placed on the subjects eyes coupled to the cornea with goniogel and a 3D adjustable mount. Images were obtained using a commercially available OCT device (Heidelberg Spectralis). The optical resolution was measured in a model eye as 40.32 and 45.25 cy/mm respectively for each mirror angle. In humans, dense OCT scans with minimum spacing oriented tangential to the iris and ICA were performed on 7 healthy subjects (23-73 yrs). The TM was successfully imaged in all subjects. The custom goniolens improved the contrast of the uveoscleral meshwork structures and corneoscleral meshwork revealing limbus parallel striations, not visible with previous goniolens designs. Transverse OCT images were constructed along the segmentation line, providing an enface image of the TM structures including corneoscleral beams, previously only imaged in vivo using custom adaptive optics systems.

4.
BMC Med Educ ; 23(1): 463, 2023 Jun 21.
Article in English | MEDLINE | ID: mdl-37344832

ABSTRACT

Anxiety levels in medical students have been reported as higher than the aged-matched general population, yet medical students are less likely to seek care for mental health issues. Medical students carry high levels of self-stigma about their own mental health and fear the negative consequences of seeking care. The purpose of this study was to examine the student population at the University of South Carolina School of Medicine Greenville (UofSC SOMG) for anxiety levels and determine the self-stigma attitudes this population carries. UofSC SOMG students were surveyed using the GAD7, questions about mental health stigma, and open-ended questions on barriers to mental health care in medical students. Anxiety levels were compared to student responses. 31% of students reported moderate-severe anxiety levels. Stigma was the most frequently listed barrier to care, however, students with moderate-severe anxiety were more likely to report cost as a barrier to care than students with minimal anxiety levels. Despite free and accessible mental health care, medical students at UofSC SOMG still have anxiety at rates higher than the general population. Future work should help to provide interventions to the barriers of care, so medical students can better utilize mental health care resources.


Subject(s)
Anxiety , Health Services Accessibility , Patient Acceptance of Health Care , Students, Medical , Female , Humans , Male , Anxiety/epidemiology , Anxiety/psychology , Anxiety/therapy , Health Care Surveys , Patient Acceptance of Health Care/psychology , Patient Acceptance of Health Care/statistics & numerical data , Schools, Medical , Self Concept , South Carolina/epidemiology , Stereotyping , Students, Medical/psychology , Students, Medical/statistics & numerical data
5.
Biomed Opt Express ; 13(9): 4652-4667, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-36187241

ABSTRACT

Intraocular pressure (IOP) is the only modifiable risk factor for glaucoma progression, and many treatments target the trabecular meshwork (TM). Imaging this region in vivo is challenging due to optical limitations of imaging through the cornea at high angles. We propose a gonioscopic OCT approach using a custom goniolens and a commercially available OCT device to improve imaging of the TM, Schlemm's canal (SC) and adjacent structures within the iridocorneal angle (ICA). The goniolens is modified with a plano-convex focusing lens and placed on the eye optically mated with goniogel and aided by a 3D adjustable mount. Gonioscopic OCT volume scans are acquired to image SC. Transverse enface images allowed measurements of SC over a 45° section of the ICA for the first time and revealed locations of SC narrowing. The band of extracanalicular limbal lamina and corneoscleral bands were imaged in most subjects and these bands were confirmed using exterior OCT imaging. The polarization dependence of the visibility of these structures is studied by polarization rotation the OCT beam with a half-wave plate, allowing increased contrast of SC. Gonioscopic OCT has successfully been used to image the human ICA in 3D in vivo. This approach provides more detailed characterization of the TM and SC, enhancing their contrast against their birefringent backgrounds.

6.
Front Med (Lausanne) ; 9: 826643, 2022.
Article in English | MEDLINE | ID: mdl-35372411

ABSTRACT

Purpose: Cones in diabetic patients are at risk due to metabolic and vascular changes. By imaging retinal vessel modeling at high magnification, we reduced its impact on cone distribution measurements. The retinal vessel images and retinal thickness measurements provided information about cone microenvironment. Methods: We compared cone data in 10 diabetic subjects (28-78 yr) to our published norms from 36 younger and 10 older controls. All subjects were consented and tested in a manner approved by the Indiana University Institutional Review Board, which adhered to the Declaration of Helsinki. Custom adaptive optics scanning laser ophthalmoscopy (AOSLO) was used to image cones and retinal microcirculation. We counted cones in a montage of foveal and temporal retina, using four non-contiguous samples within 0.9-7 deg that were selected for best visibility of cones and least pathology. The data were fit with a two parameter exponential model: ln(cone density) = a * microns eccentricity + b. These results were compared to retinal thickness measurements from SDOCT. Results: Diabetic cone maps were more variable than in controls and included patches, or unusually bright and dark cones, centrally and more peripherally. Model parameters and total cones within the central 14 deg of the macula differed across diabetic patients. Total cones fell into two groups: similar to normal for 5 vs. less than normal for 2 of 2 younger diabetic subjects and 3 older subjects, low but not outside the confidence limits. Diabetic subjects had all retinal vascular remodeling to varying degrees: microaneurysms; capillary thickening, thinning, or bends; and vessel elongation including capillary loops, tangles, and collaterals. Yet SD-OCT showed that no diabetic subject had a Total Retinal Thickness in any quadrant that fell outside the confidence limits for controls. Conclusions: AOSLO images pinpointed widespread retinal vascular remodeling in all diabetic eyes, but the SDOCT showed no increased retinal thickness. Cone reflectivity changes were found in all diabetic patients, but significantly low cone density in only some. These results are consistent with early changes to neural, glial, or vascular components of the retinal without significant retinal thickening due to exudation.

7.
Adv Ther ; 38(7): 3973-3985, 2021 07.
Article in English | MEDLINE | ID: mdl-34101144

ABSTRACT

INTRODUCTION: Anacetrapib is a novel, powerful cholesteryl ester transfer protein (CETP) inhibitor with bidirectional lipid regulation, which was developed for dyslipidemia. The aim of this study is to evaluate the single- and multiple-dose pharmacokinetics (PK), safety and tolerability of anacetrapib in healthy Chinese subjects and assess the PK difference between Chinese and other populations. METHODS: Forty subjects were enrolled in an open-label study consisting of three panels (50 mg single dose; 100 mg single dose followed by 100 mg once-daily multiple doses for 10 days; a 200 mg single dose). Safety and tolerability were evaluated by monitoring adverse events, laboratory safety tests, ECGs, vital signs and physical examination. PK were evaluated and compared with historical data in black and white subjects. RESULTS: Anacetrapib was absorbed after administration of a single oral dose, with a median Tmax of 3.0-5.0 h and elimination half-life of 105.3-122.3 h. The AUC and Cmax of anacetrapib increased in a slightly less than dose-proportional manner over a dose range of 50-200 mg. Once-daily administration of 100 mg of anacetrapib for 10 days resulted in a median Tmax of 5.0 h with an apparent half-life of 193.7 h on Day 10 of multiple dosing. Anacetrapib accumulation ratios (Day 10 of multiple dosing/Day 1) were 1.39 (AUC0-24 h), 1.11 (Cmax) and 2.57 (C24 h). CONCLUSION: The PK properties of anacetrapib in Chinese subjects are comparable to those observed in the black population and in white subjects. Single and once-daily administration of anacetrapib was generally well tolerated in healthy Chinese subjects observed in this study. TRIAL REGISTRATION: chinadrugtrials.org.cn identifier number CTR20130983.


Subject(s)
Cholesterol Ester Transfer Proteins , Oxazolidinones , Area Under Curve , China , Dose-Response Relationship, Drug , Double-Blind Method , Humans , Oxazolidinones/adverse effects
8.
Opt Lett ; 46(4): 753-756, 2021 Feb 15.
Article in English | MEDLINE | ID: mdl-33577506

ABSTRACT

Scanning imaging systems are susceptible to image warping in the presence of target motion occurring within the time required to acquire an individual image frame. In this Letter, we introduce the use of a dual raster scanning approach to correct for motion distortion without the need for prior knowledge of the undistorted image. In the dual scanning approach, the target is imaged simultaneously with two imaging beams from the same imaging system. The two imaging beams share a common pupil but have a spatial shift between the beams on the imaging plane. The spatial shift can be used to measure high speed events, because it measures an identical region at two different times within the time required for acquisition of a single frame. In addition, it provides accurate spatial information, since two different regions on the target are imaged simultaneously, providing an undistorted estimate of the spatial relation between regions. These spatial and temporal relations accurately measure target motion. Data from adaptive optics scanning laser ophthalmoscope (AOSLO) imaging of the human retina are used to demonstrate this technique. We apply the technique to correct the shearing of retinal images produced by eye motion. Three control subjects were measured while imaging different retinal layers and retinal locations to qualify the effectiveness of the algorithm. Since the time shift between channels is readily adjustable, this method can be tuned to match different imaging situations. The major requirement is the need to separate the two images; in our case, we used different near infrared spectral regions and dichroic filters.


Subject(s)
Eye/diagnostic imaging , Movement , Ophthalmoscopes , Adult , Humans
9.
Womens Health (Lond) ; 16: 1745506520922760, 2020.
Article in English | MEDLINE | ID: mdl-32459136

ABSTRACT

BACKGROUND: Clinical factors associated with exclusion from recombinant tissue plasminogen activator in both men and women are not completely understood. The aim of this study is to determine whether there is a gender difference in clinical risk factors that excluded ischemic stroke patients with a history of smoking from recombinant tissue plasminogen activator. METHODS: Retrospective data from a stroke registry were analyzed, and multivariable linear regression models were used to determine gender differences. Logistic regression models determined exclusion clinical risk factors for thrombolysis in male and female acute ischemic stroke patients with a history of smoking, while sequentially adjusting for sociodemographic, clinical, and stroke-related variables. The Kaplan-Meier survival analysis was used to determine the exclusion probabilities of men and women with a history of smoking within the stroke population. RESULTS: Of the 1,446 acute ischemic stroke patients eligible for recombinant tissue plasminogen activator, 379 patients with a history of smoking were examined, of which 181 received recombinant tissue plasminogen activator while 198 were excluded from receiving recombinant tissue plasminogen activator. Of the 198 patients, 75 females and 123 males were excluded from receiving recombinant tissue plasminogen activator. After multivariable adjustment for age, National Institutes of Health scores, and stroke-related factors, females who present with weakness/paresis on initial examination (OR = 0.117, 95% CI, 0.025-0.548) and men who present with a history of previous transient ischemic attack (OR = 0.169, 95% CI, 0.044-0.655), antiplatelet medication use (OR = 0.456, 95% CI, 0.230-0.906), and weakness/paresis on initial examination (OR = 0.171, 95% CI, 0.056-0.521) were less likely to be excluded from recombinant tissue plasminogen activator (thrombolysis therapy). CONCLUSIONS: In an ischemic stroke population with a history of smoking, female smokers are more likely to be excluded from thrombolysis therapy in comparison to men, even after adjustment for confounding variables.


Subject(s)
Brain Ischemia/drug therapy , Smoking/epidemiology , Stroke/epidemiology , Thrombolytic Therapy , Aged , Aged, 80 and over , Female , Fibrinolytic Agents/therapeutic use , Humans , Incidence , Logistic Models , Male , Middle Aged , Registries , Retrospective Studies , Risk Factors , Sex Factors , Stroke/drug therapy , Tissue Plasminogen Activator/therapeutic use
10.
Clin Transl Sci ; 12(5): 545-555, 2019 09.
Article in English | MEDLINE | ID: mdl-31215755

ABSTRACT

ß-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is required for the production of ß-amyloid peptides, which are implicated in the etiology of Alzheimer's disease. The safety and pharmacokinetics of the BACE1 inhibitor verubecestat have previously been studied in young adults aged 19-45 years. In this randomized, placebo-controlled, phase I study (protocol MK-8931-006), we investigated the safety, tolerability, and pharmacokinetics of a single dose (100 mg) or multiple doses (30, 80, and 120 mg) once daily for 28 days of verubecestat in healthy elderly subjects. Safety end points were assessed at baseline and during the duration of the study period and indicated that verubecestat was generally well tolerated. Verubecestat pharmacokinetics were similar between healthy elderly male and female subjects and similar to those reported in healthy young males in previous studies. These data supported subsequent studies to assess the potential efficacy of verubecestat in subjects with Alzheimer's disease.


Subject(s)
Amyloid Precursor Protein Secretases/antagonists & inhibitors , Aspartic Acid Endopeptidases/antagonists & inhibitors , Cyclic S-Oxides/adverse effects , Cyclic S-Oxides/pharmacokinetics , Thiadiazines/adverse effects , Thiadiazines/pharmacokinetics , Administration, Oral , Aged , Amyloid Precursor Protein Secretases/metabolism , Aspartic Acid Endopeptidases/metabolism , Cyclic S-Oxides/administration & dosage , Cyclic S-Oxides/blood , Dose-Response Relationship, Drug , Female , Humans , Male , Thiadiazines/administration & dosage , Thiadiazines/blood
11.
Neurol Sci ; 40(9): 1829-1839, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31049791

ABSTRACT

OBJECTIVE: To investigate clinical risk factors that were associated with gender differences in thrombolysis therapy in stroke patients with incidence of obesity. METHOD: Retrospective data of obese acute ischemic stroke patients were extracted from a stroke registry between January 2010 and June 2016. Gender differences in exclusion from rtPA or thrombolysis therapy were determined following an adjustment for differences in demographics, clinical risk factors using multiple regression analysis. Significant interactions between variables in the regression models were determined using variance inflation factors. RESULTS: A total of 1105 obese stroke patients were admitted, 549 were excluded from rtPA of which 51.7% were males and 48.3% were females. Among obese male stroke patients, age > 80 years (OR = 1.029, 95% CI, 1.005-1.054, P = 0.016), a history of peripheral vascular disease (OR = 3.008, 95% CI, 0.989-9.153, P = 0.052), and an elevated diastolic blood pressure (OR = 1.018, 95% CI, 1.001-1.035, P = 0.038) were associated with exclusion from rtPA therapy. In obese female stroke patients, coronary artery disease was associated with exclusion from rtPA (OR = 2.478, 95% CI, 1.270-4.836, P = 0.008) while antihypertensive therapy was associated with inclusion for rtPA (OR = 0.326, 95% CI, 0.139-0.764). CONCLUSION: Elderly obese male stroke patients with elevated diastolic blood pressure, history of peripheral vascular disease, and obese female stroke patients with a history of coronary artery disease were more likely to be excluded from rtPA.


Subject(s)
Brain Ischemia/drug therapy , Coronary Artery Disease , Fibrinolytic Agents/therapeutic use , Hypertension , Obesity , Peripheral Vascular Diseases , Registries , Stroke/drug therapy , Thrombolytic Therapy/statistics & numerical data , Tissue Plasminogen Activator/therapeutic use , Aged , Aged, 80 and over , Antihypertensive Agents/therapeutic use , Brain Ischemia/epidemiology , Comorbidity , Coronary Artery Disease/epidemiology , Female , Humans , Hypertension/epidemiology , Incidence , Male , Middle Aged , Obesity/epidemiology , Peripheral Vascular Diseases/epidemiology , Retrospective Studies , Risk Factors , Sex Factors , Stroke/epidemiology
12.
J Am Chem Soc ; 141(7): 2838-2842, 2019 02 20.
Article in English | MEDLINE | ID: mdl-30698426

ABSTRACT

We describe the 3-iodopropyl acetal moiety as a simple cleavable unit that undergoes acid catalyzed hydrolysis to liberate HI (p Ka ∼ -10) and acrolein stoichiometrically. Integrating this unit into linear and network polymers gives a class of macromolecules that undergo a new mechanism of degradation with an acid amplified, sigmoidal rate. This trigger-responsive self-amplified degradable polymer undergoes accelerated rate of degradation and agent release.

13.
BMC Womens Health ; 19(1): 11, 2019 01 16.
Article in English | MEDLINE | ID: mdl-30651099

ABSTRACT

BACKGROUND: When untreated, dyslipidemia is a higher risk factor for stroke and stroke-related mortality in men than in women. However, when dyslipidemia is treated the risk reduction is the same, but men benefited from mortality reduction more than women. Whether there is a gender difference in exclusion criteria for the use of recombinant tissue plasminogen activator (rtPA) or thrombolysis therapy in an acute ischemic stroke subpopulation with dyslipidemia is yet to be investigated. METHOD: In a dyslipidemic stroke population obtained from a stroke registry, gender differences in exclusion risk factors were determined using clinical and demographic variables. Univariate analysis compared the recombinant tissue plasminogen activator (rtPA) group and the no rtPA group. Multiple regression analysis was used to determine demographic and clinical factors associated with inclusion and exclusion for rtPA in the total dyslipidemic stroke population and the subsets of the male and female population. The regression model was tested using the Hosmer-Lemeshow test, for the overall correct classification percentage. Significant interactions and multicollinearity between independent variables were examined using variance inflation factors. RESULTS: A total of 769 patients presented with acute ischemic stroke with incidence dyslipidemia; 325 received rtPA while 444 were excluded from rtPA. Of those excluded from rtPA, 54.30% were female and 45.72% were male. In an adjusted analysis, female patients with increased age (OR = 1.024, 95% CI, 1.001-1.047, P < 0.05), with a history of carotid artery stenosis (OR = 7.063, 95% CI, 1.506-33.134, P < 0.05), and previous stroke (OR = 1.978, 95% CI, 1.136-3.442, P < 0.05) were more likely to be excluded from rtPA. Male patients with atrial fibrillation (OR = 2.053, 95% CI, 1.059-3.978, P = 0.033), carotid artery stenosis (OR = 2.400, 95% CI, 1.062-5.424, P = 0.035), and previous stroke (OR = 1.785, 95% CI, 1.063-2.998, P = 0.028) were more likely to be excluded from rtPA. CONCLUSION: Although there are some similarities in the clinical risk factors for exclusion in both male and female stroke patients with incidence of dyslipidemia, there are differences as well. Elderly female stroke patients with incidence of dyslipidemia are more likely to be excluded from rtPA, even after adjustment for the effect of confounding variables. Further research should focus on how identified clinical risk factors can be targeted and managed to improve the use of rtPA in elderly female acute ischemic stroke population with incidence of dyslipidemia.


Subject(s)
Dyslipidemias/epidemiology , Dyslipidemias/therapy , Fibrinolytic Agents/therapeutic use , Stroke/therapy , Tissue Plasminogen Activator/therapeutic use , Aged , Aged, 80 and over , Dyslipidemias/complications , Female , Humans , Incidence , Male , Middle Aged , Multivariate Analysis , Registries , Risk Factors , Sex Factors , Stroke/complications , Thrombolytic Therapy/methods
14.
J Clin Pharmacol ; 59(5): 646-653, 2019 05.
Article in English | MEDLINE | ID: mdl-30536420

ABSTRACT

In patients with renal insufficiency, dose adjustments based on creatinine clearance and body weight have been a component of imipenem dosage instructions. The objective of the current analysis was to provide revised dosing recommendations by evaluating the impact of creatinine clearance and body weight on the pharmacokinetics of imipenem. A population pharmacokinetics model was developed with data from 465 patients and 3300 pharmacokinetic samples. Simulations provided data to support revision of the dosing recommendations to remove body weight-adjusted dosing, and the analysis formed the basis for updates that are reflected on the current imipenem label for both the United States and Europe. The optimized regimen provided an advantage in terms of improved target attainment at breakpoint minimum inhibitory concentration values of 1 and 2 µg/mL, as low-body-weight patients maintained >90% probability of target attainment compared to <90% probability of target attainment achieved with the previously approved regimen. It was concluded that additional dose adjustments for body weight were not necessary and the new scheme would simplify dosing while maintaining patient safety and efficacy.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Body Weight/drug effects , Imipenem/administration & dosage , Imipenem/pharmacokinetics , Renal Insufficiency/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Creatinine/blood , Dose-Response Relationship, Drug , Female , Humans , Infusions, Intravenous , Male , Microbial Sensitivity Tests , Middle Aged , Monte Carlo Method , Young Adult
15.
Anat Rec (Hoboken) ; 301(12): 2095-2102, 2018 12.
Article in English | MEDLINE | ID: mdl-30312532

ABSTRACT

Enteropathogenic Escherichia coli (EPEC), Salmonella typhimurium, and Listeria monocytogenes usurp the actin cytoskeleton for their attachment, internalization and transport within and amongst infected cells. To try to gain a greater understanding of the molecular components utilized by these microbes during their infections we previously concentrated actin-rich structures generated during EPEC infections (called pedestals) and identified the heat shock cognate 70 protein (Hsc70) as a potential candidate. This multifunctional protein classically acts as a chaperone for the proper folding of a variety of proteins and is involved in uncoating clathrin from coated pits. Here we demonstrated that Hsc70 is recruited to actin structures generated during EPEC, Listeria and Salmonella infections, but not to the same location as clathrin. Anat Rec, 301:2095-2102, 2018. © 2018 Wiley Periodicals, Inc.


Subject(s)
Actins/metabolism , HSC70 Heat-Shock Proteins/metabolism , Listeria monocytogenes/metabolism , Actins/analysis , Animals , HSC70 Heat-Shock Proteins/analysis , HeLa Cells , Humans , Listeria monocytogenes/chemistry
16.
Anat Rec (Hoboken) ; 301(12): 2103-2111, 2018 12.
Article in English | MEDLINE | ID: mdl-30312538

ABSTRACT

The ingestion of enteropathogenic Escherichia coli (EPEC), Listeria monocytogenes, or Salmonella enterica serovar Typhimurium leads to their colonization of the intestinal lumen, which ultimately causes an array of ailments ranging from diarrhea to bacteremia. Once in the intestines, these microbes generate various actin-rich structures to attach, invade, or move within the host intestinal epithelial cells. Although an assortment of actin-associated proteins has been identified to varying degrees at these structures, the localization of many actin stabilizing proteins have yet to be analyzed. Here, we examined the recruitment of the actin-associated proteins, calponin 1 and 2 at EPEC pedestals, L. monocytogenes actin clouds, comet tails and listeriopods, and S. Typhimurium membrane ruffles. In other systems, calponins are known to bind to and stabilize actin filaments. In EPEC pedestals, calponin 1 was recruited uniformly throughout the structures while calponin 2 was enriched at the apical tip. During L. monocytogenes infections, calponin 1 was found through all the actin-rich structures generated by the bacteria, while calponin 2 was only present within actin-rich structures formed by L. monocytogenes near the host cell membrane. Finally, both calponins were found within S. Typhimurium-generated membrane ruffles. Taken together, we have shown that although calponin 1 is recruited to actin-rich structures formed by the three bacteria, calponin 2 is specifically recruited to only membrane-bound actin-rich structures formed by the bacteria. Thus, our findings suggest that calponin 2 is a novel marker for membrane-bound actin structures formed by pathogenic bacteria. Anat Rec, 301:2103-2111, 2018. © 2018 Wiley Periodicals, Inc.


Subject(s)
Actins/metabolism , Calcium-Binding Proteins/metabolism , Enteropathogenic Escherichia coli/metabolism , Listeria monocytogenes/metabolism , Microfilament Proteins/metabolism , Salmonella enterica/metabolism , Actins/analysis , Caco-2 Cells , Calcium-Binding Proteins/analysis , Cell Membrane/chemistry , Cell Membrane/metabolism , Cell Membrane/ultrastructure , Enteropathogenic Escherichia coli/chemistry , Humans , Listeria monocytogenes/chemistry , Microfilament Proteins/analysis , Salmonella enterica/chemistry , Calponins
17.
J Community Health ; 43(2): 328-337, 2018 04.
Article in English | MEDLINE | ID: mdl-28929402

ABSTRACT

Laws across the globe require healthcare providers to disclose patient health information to public health entities for surveillance and intervention purposes. Physicians play a unique role in such mandatory reporting regimes. However, research reveals consistent under-reporting and points to limited knowledge of mandates, perceived burdens of reporting, misaligned incentives and penalties, and a lack of streamlined processes as significant reporting barriers. These barriers suggest that how legal mandates are structured may impact compliance; yet little research systematically examines their characteristics. Law-based reporting requirements differ across jurisdictions. Thus, we conducted a case study in the U.S. State of Nevada to characterize its physician mandatory reporting laws using legal mapping methodology. Nevada is a useful case study because it has few local jurisdictions and its legislature meets biennially. First, we searched key terms to find relevant state mandates and screened them using inclusion criteria. We then scanned near included provisions for additional requirements and incorporated requirements known a priori. We also searched relevant local regulations. Next, we analyzed all included provisions. Our findings indicate wide, intra-jurisdictional variation in reporting requirements across conditions. Variability extends to physician discretion, information reported, timing, recipient agencies, reporting processes, and implications of non-compliance. Local-level variation adds further complexity. Some relevant state requirements apply only to physicians and nearly one-third were absent from our searches. Our findings support exploring the hypothesis that reporting requirements' characteristics may impact compliance and call for empirically testing such relationships to enhance compliance and public health surveillance and intervention efforts.


Subject(s)
Disease Notification/legislation & jurisprudence , Mandatory Reporting , Physicians/legislation & jurisprudence , Public Health Surveillance , Humans , Nevada
18.
Invest Ophthalmol Vis Sci ; 58(9): 3395-3403, 2017 07 01.
Article in English | MEDLINE | ID: mdl-28687853

ABSTRACT

Purpose: We measured localized changes occurring in the foveal cone photoreceptors and related defects in the cone mosaic to alterations in the nearby retinal vasculature. Methods: The central 4° of the retina of 54 diabetic (53.7 ± 12.5 years) and 85 control (35.8 ± 15.2 years) participants were imaged with the Indiana adaptive optics scanning laser ophthalmoscope. Foveal cones and overlying retinal capillaries were imaged and infrared scanning laser ophthalmoscopy (IR SLO) images and optical coherence tomography (OCT) B-scans were obtained. Follow-up imaging sessions were performed with intervals from 4 to 50 months for 22 of the 54 diabetic participants. Results: The foveal cone mosaics of 49 of 54 diabetic participants were of sufficient quality to assess the absence or presence of small localized defects in the cone mosaic. In 13 of these 49 diabetic participants we found localized defects, visualized as sharp-edged areas of cones with diminished reflectivity. These small, localized areas ranged in size from 10 × 10 µm to 75 × 30 µm. Of these 13 participants with cone defects, 11 were imaged over periods from 4 to 50 months and the defects remained relatively stable. These dark regions were not shadows of overlying retinal vessels, but all participants with these localized defects had alterations in the juxtafoveal capillary network. Conclusions: The foveal cone mosaic can show localized areas of dark cones that persist over time, that apparently correspond to either missing or nonreflecting cones, and may be related to local retinal ischemia.


Subject(s)
Diabetes Mellitus/pathology , Fovea Centralis/pathology , Retinal Cone Photoreceptor Cells/pathology , Adult , Aged , Case-Control Studies , Female , Humans , Male , Microscopy, Confocal , Middle Aged , Ophthalmoscopy/methods , Retinal Vessels/pathology , Tomography, Optical Coherence/methods , Young Adult
19.
J Matern Fetal Neonatal Med ; 25(9): 1544-8, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22233403

ABSTRACT

OBJECTIVE: To determine factors influencing separation and infectious type wound complications (WCs) in morbidly obese women undergoing primary cesarean delivery (CD). METHODS: Retrospective cohort study evaluating infectious and separation WC in morbidly obese (body mass index [BMI] > 35 kg/m(2)) women undergoing primary CD between January 1994 and December 2008. Chi-square, Fisher's exact and Student's t tests used to assess associated factors; backward logistic regression to determine unadjusted and adjusted odds ratios. RESULTS: Of 623 women, low transverse skin incisions were performed in 588 (94.4%), vertical in 35 (7%). Overall WC rate was 13.5%, which varied by incision type (vertical 45.7% vs. 11.6% transverse; p < 0.01), but not BMI class. Incision type and unscheduled CD were associated with infection risk, while incision type, BMI, race and drain use were associated with wound separation. CONCLUSION: In morbidly obese women both infectious and separation type WC are more common in vertical than low transverse incisions; therefore transverse should be preferred.


Subject(s)
Cesarean Section/adverse effects , Obesity, Morbid/surgery , Postoperative Complications/etiology , Pregnancy Complications/surgery , Adult , Cesarean Section/rehabilitation , Cesarean Section/statistics & numerical data , Cohort Studies , Female , Humans , Infant, Newborn , Obesity, Morbid/complications , Obesity, Morbid/epidemiology , Parity , Postoperative Complications/epidemiology , Pregnancy , Pregnancy Complications/epidemiology , Retrospective Studies , Risk Factors , Surgical Wound Dehiscence/epidemiology , Surgical Wound Dehiscence/etiology , Surgical Wound Infection/epidemiology , Surgical Wound Infection/etiology , Young Adult
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