Miracle-dz/UniFAR-FTUs huggingface dataset:
Subjective Blur Limits for Higher Order Aberrations

Purpose. We compared subjective blur limits for defocus and the higher-order aberrations of coma, trefoil, and spherical aberration. Methods. Spherical aberration was presented in both Zernike and Seidel forms. Black letter targets (0.1, 0.35, and 0.6 logMAR) on white backgrounds were blurred using an adaptive optics system for six subjects under cycloplegia with 5 mm artificial pupils. Three blur criteria of just noticeable, just troublesome, and just objectionable were used. Results. When expressed as wave aberration coefficients, the just noticeable blur limits for coma and trefoil were similar to those for defocus, whereas the just noticeable limits for Zernike spherical aberration and Seidel spherical aberration (the latter given as an “rms equivalent”) were considerably smaller and larger, respectively, than defocus limits. Conclusions. Blur limits increased more quickly for the higher order aberrations than for defocus as the criterion changed from just noticeable to just troublesome and then to just objectionable.
Pharmacodynamics, pharmacokinetics and clinical efficacy of telavancin in the treatment of pneumonia

ABSTRACT Introduction: Telavancin is a novel lipoglycopeptide derivative of vancomycin that has activity against Gram-positive aerobic and anerobic bacteria, for the treatment of serious infections, including complicated skin and skin structure infections (cSSSI) and pneumonia. Areas covered: This article was compiled through searches on telavancin up to December 2015 in the PubMed and the clinicaltrials.gov databases; the FDA and European Medicine Agency (EMA) websites. In our review, particular attention was paid to those articles that reviewed the pharmacokinetic characteristics of the drug and animal models of infection. We also searched for evidence of the efficacy of telavancin as demonstrated in clinical trials, safety and tolerability data and have compiled a summary of clinical trials on telavancin in pneumonia. Expert opinion: Telavancin is approved in Europe and the USA for the treatment of nosocomial pneumonia caused by methicillin resistant Staphylococcus aureus when other alternatives are not suitable.
Induction of cytochrome promotes liver injury in ob/ob mice

Cytochrome P450 2E1 (CYP2E1) activates several hepatotoxins and contributes to alcoholic liver damage. Obesity is a growing health problem in the United States. The aim of the present study was to evaluate whether acetone‐ or pyrazole‐mediated induction of CYP2E1 can potentiate liver injury in obesity. CYP2E1 protein and activity were elevated in acetone‐ or pyrazole‐treated obese and lean mice. Acetone or pyrazole induced distinct histological changes in liver and significantly higher aminotransferase enzymes in obese mice compared to obese controls or acetone‐ or pyrazole‐treated lean mice. Higher caspase‐3 activity and numerous apoptotic hepatocytes were observed in the acetone‐ or pyrazole‐treated obese mice. Increased protein carbonyls, malondialdehyde, 4‐hydroxynonenal‐protein adducts, elevated levels of inducible nitric oxide synthase, and higher 3‐nitrotyrosine protein adducts were found in livers of acetone‐ or pyrazole‐treated obese animals, suggesting elevated oxidative and nitrosative stress. Liver tumor necrosis factor α levels were higher in pyrazole‐treated animals. The CYP2E1 inhibitor chlormethiazole and iNOS inhibitor N‐(3‐(aminomethyl)‐benzyl) acetamidine abrogated the toxicity and the oxidative/nitrosative stress elicited by the induction of CYP2E1. Conclusion: These results show that obesity contributes to oxidative stress and liver injury and that induction of CYP2E1 enhances these effects. (HEPATOLOGY 2007;45:1355–1365.)
Eccentric Gaze Direction in Patients with Central Field Loss

Purpose. This study describes the binocular eccentric gaze direction (EGD) of 434 patients with binocular central field loss and presents a comparison with other studies on eccentric gaze behavior. Methods. We reviewed the records of 434 patients with bilateral central scotomas. Eligible patients had not received eccentric viewing training and demonstrated a spontaneously developed eccentric gaze behavior. Data were collected on monocular and binocular EGD, visual acuity, and underlying ocular pathology. Findings concerning the EGD were compared with other studies that evaluated gaze behavior in patients with central field loss. Results. In the group of 434 patients, age-related macular disease was the most frequent pathology (77%). The majority of these patients demonstrated a binocular EGD (bEGD) to the right (50%). In 25% of the patients, a superior bEGD was found. Less often, a bEGD to the left (14%) and to inferior (11%) were encountered. Review of the literature indicates that the majority of patients developed a monocular EGD in the superior direction. Conclusions. This is a study on bEGD behavior in a large population of patients with bilateral central scotomas. The bEGD was guided by the gaze of the better-seeing eye. The preference for a bEGD to the right differs from findings of previous studies. Review of the literature suggests that not only the ocular pathology but also the method of investigation is most likely to influence the observed EGD. Most studies evaluated the location of the preferred retinal locus using a monocular technique; this may not reflect an individual's actual binocular behavior as it relates to activities of daily living.
Khat chewing increases the risk for developing chronic liver disease: A hospital‐based case–control study

The chewing of the leaves of Catha edulis (khat) has been implicated in the development of liver disease, but no controlled observations have been undertaken. The objective of the present study was to determine whether khat chewing is associated with development of chronic liver disease (CLD). A case–control study was conducted at two public hospitals in Harar, Ethiopia, between April 2015 and April 2016. A consecutive sample of 150 adult hospital attendees with CLD were included as cases, and 300 adult hospital attendees without clinical or laboratory evidence of CLD were included as controls. Khat consumption was quantified in “khat years”; 1 khat year was defined as daily use of 200 g of fresh khat for 1 year. A logistic regression model was used to control for confounders. There was a significant association between chewing khat and the risk for developing CLD (crude odds ratio, 2.64; 95% confidence interval [CI], 1.56‐4.58). In men, this risk, following adjustment for age, alcohol use, and chronic hepatitis B/C infection, increased with increasing khat exposure; thus, compared to never users the adjusted odds ratios were for low khat exposure 3.58 (95% CI 1.05‐12.21), moderate khat exposure 5.90 (95% CI 1.79‐19.44), and high khat exposure 13.03 (95% CI 3.61‐47.02). The findings were robust in a post hoc sensitivity analysis in which individuals with identifiable risk factors for CLD were excluded. Conclusion: A significant association was observed between chewing khat and the risk for developing CLD, and in men the association was strong and dose‐dependent, suggesting a causal relationship; as the prevalence of khat chewing is increasing worldwide, these findings have major public health implications. (Hepatology 2018;68:248‐257).
Effect of Prophylactic Antibiotic Drops on Ocular Microbiota and Physiology during Silicone Hydrogel Lens Wear

Purpose. Bacterial contamination of the contact lens surface has been demonstrated to cause corneal infiltrative events. A reduction in the rate of bacterially driven corneal infiltrative events associated with lens wear is one of the major goals of the contact lens industry. There is a concern over the potential of any antimicrobial strategy that there will be unwanted changes to the ocular microbiota or the development of resistance to the antimicrobial. The aim of this study was to investigate the effect of prophylactic topical antibiotic instillation during continuous wear of silicone hydrogel lenses on the normal ocular microbiota, the throat microbiota, and the ocular physiology. Methods. Forty-two male subjects were dispensed with lotrafilcon A silicone hydrogel contact lenses for a 3-month, 30 night continuous wear, monthly replacement trial. Subjects were randomized into either tobramycin 0.3% (test) or saline (control) drop group. Two drops were instilled into each eye on waking and before sleep. At monthly visits, lenses were collected aseptically, and ocular and throat swabs were performed, followed by standard microbial recovery and identifications. Any corneal infiltrative event at scheduled or unscheduled visits was recorded. Results. Numbers of microbes recovered from eye swabs from the tobramycin (test) group were significantly lower than the control (p = 0.01). Gram-positive cocci were recovered less frequently from the test group (p = 0.001). There were no significant differences in the numbers and types of microbes recovered from lens samples, or the contamination rate of the lenses between the two groups. There were no changes in the numbers of fungi or bacteria from throat swabs. There was no evidence of changes to resistance profile of microbes in the throat. More eye swabs from the test group (68.5%) were culture-negative than swabs from control (46.5%; p = 0.002). The test group had less corneal staining superiorly (0.0 ± 0.0 vs. 0.3 ± 0.4; p = 0.025) but increased bulbar redness (2.2 ± 0.5 vs. 1.5 ± 0.4; p < 0.001) at the 3-month visit only, compared with control group. Conclusions. Overall, there appeared to be a minimal safety risk with 3-month's prophylactic antibiotic drop use during continuous wear of silicone hydrogel lenses. Clinically, antibiotic drop use induced a mild to moderate increase in bulbar redness by the 3-month time-point. Antibiotic use reduced microbiota on lids but did not affect the microbiota of the throat or change resistance to tobramycin.
Fluorescent peptide highlights micronodules in murine hepatocellular carcinoma models and humans in vitro

Early detection and clear delineation of microscopic lesions during surgery are critical to the prognosis and survival of patients with hepatocellular carcinoma (HCC), a devastating malignancy without effective treatments except for resection. Tools to specifically identify and differentiate micronodules from normal tissue in HCC patients can have a positive impact on survival. Here, we discovered a peptide that preferentially binds to HCC cells through phage display. Significant accumulation of the fluorescence‐labeled peptide in tumor from ectopic and orthotopic HCC mice was observed within 2 hours of systemic injection. Contrast between tumor and surrounding liver is up to 6.5‐fold, and useful contrast lasts for 30 hours. Micronodules (0.03 cm in diameter) in liver and lung can clearly be distinguished from normal tissue with this fluorescence‐labeled peptide in orthotopic HCC mice and HCC patients. Compared to indocyanine green, a Food and Drug Administration–approved imaging contrast agent, an up to 8.7‐fold higher differentiation ratio of tumor to fibrosis is achieved with this fluorescence‐labeled peptide. Importantly, this peptide enables up to 10‐fold differentiation between HCC and peritumoral tissue in human tissues and the complete removal of tumor in HCC mice with surgical navigation. No abnormalities in behavior or activity are observed after systemic treatment, indicating the absence of overt toxicity. The peptide is metabolized with a half‐life of approximately 4 hours in serum. Conclusion: Our findings demonstrate that micronodules can be specifically differentiated with high sensitivity from surrounding tissue with this molecule, opening clinical possibilities for early detection and precise surgery of HCC. (Hepatology 2018).
Foveal Localization in Non-Exudative AMD Using Scanning Laser Polarimetry

Purpose. To determine whether custom scanning laser polarimetry (SLP) images, differing in polarization content, can be used to accurately localize the fovea in the presence of non-exudative age-related macular degeneration (AMD). To determine whether alterations to the foveal structure in non-exudative AMD significantly disrupts the birefringent Henle fiber layer, responsible for the macular cross pattern in some SLP images. To determine whether phase retardation information, specifically color-coded information representing its magnitude and axis, allow better foveal localization than images including retardation amplitude only. Methods. SLP images were acquired in 25 AMD subjects and 25 age-matched controls. Raw data were used to generate five custom image types differing in polarization content. The foveal location was marked by three graders in each image type for each subject. The difference in variability was compared between the AMD subjects and matched controls. We further determined whether the orientation of Henle fiber layer phase retardation improved localization in 10 subjects with the highest variability in images including only phase retardation amplitude. Results. Images that differed in polarization content led to strikingly different visualizations of AMD pathology. The Henle fiber layer remained sufficiently intact to assist in fovea localization in all subjects but with more variability in the AMD group. For both the AMD and matched control group, images containing birefringence amplitude and orientation information reduced the amount of intragrader, intergrader, and interimage variability for estimating foveal location. Conclusions. The disruption in Henle fiber birefringence was evident in the eyes with AMD but nevertheless was sufficient to help in foveal localization despite macular pathology. Phase retardation amplitude and axis of orientation can be a useful tool in foveal localization in patients with AMD.
Measuring Changes in Ciliary Muscle Thickness with Accommodation in Young Adults

Purpose. To develop a measurement protocol for changes in the shape and size of the ciliary muscle with accommodation using the Zeiss Visante™ anterior segment optical coherence tomography (AS-OCT) and to determine the test-retest repeatability of these measurements. Methods. Subjects were 25 adults aged 23 to 28 years. The ciliary muscle was imaged at two visits with the Visante™ while accommodative response was monitored during imaging using the PowerRefractor. Ciliary muscle thickness (CMT) was measured at 1 mm (CMT1), 2 mm (CMT2), and 3 mm (CMT3) posterior to the scleral spur and at the point of maximal thickness (CMTMAX). Thickness was measured at these locations while subjects viewed a target at distance and at a 4.00 D accommodative stimulus. Outcome measures were the change in thickness between distance and the 4.00 D stimulus and the change in thickness per diopter of accommodative response (PowerRefractor). Finally, the repeatability measurements between visit 1 and visit 2 were determined with a Bland-Altman analysis. Results. The statistically significant modeled changes in CMT were as follows: CMTMAX = 69.2 &mgr;m (4.00 D stimulus) and 18.1 &mgr;m (per diopter of accommodation); CMT1 = 45.2 &mgr;m (4.00 D stimulus) and 12.3 &mgr;m (per diopter of accommodation); and CMT3 = −45.9 &mgr;m (4.00 D stimulus) and −12.0 &mgr;m (per diopter of accommodation); p < 0.0001 for all. Conclusions. The combination of the Visante™ and the PowerRefractor is a feasible tool for measuring thickening of ciliary muscle at more anterior locations and thinning at more posterior locations during accommodation. We noted a wide range of accommodative responses during the time of image capture in this study indicating that the most accurate estimates of the change in ciliary muscle dimensions with accommodation may be obtained by using accommodative response rather than stimulus values and by using measurements taken simultaneously with image capture.
Cerebral perfusion monitoring in acute care surgery: current and perspective use

ABSTRACT Introduction: The technology near infrared spectroscopy (NIRS) has been utilized extensively in several clinical settings and one of which is in cerebral oximetry. This review will provide information on the technology, clinical applications and algorithm to follow when desaturation occurs. Areas covered: The review will cover the technology of near infrared spectroscopy, cerebral oximetry and the utilization of cerebral oximetry in each clinical setting. Expert commentary: Cerebral oximetry provides a noninvasive measure of cerebral oxygenation, which when persistently declining, can serve as a warning sign of hemodynamic or metabolic compromise intraoperatively or a predictor of postoperative cognitive dysfunction. Although useful, the cerebral oximetry readings must be interpreted in the context of other clinical information. When cerebral desaturation is confirmed, an algorithm should be followed in an attempt to increase oxygen delivery to the brain and/or decrease cerebral metabolic rate of oxygen.
Evaluation of the MiStent sustained sirolimus eluting biodegradable polymer coated stent for the treatment of coronary artery disease: does uniform sustained abluminal drug release result in earlier strut coverage and better safety profile?

ABSTRACT Introduction: Treatment of coronary artery disease has made strides over the last decades. Development of drug eluting stents (DES), coated with a polymer layer and an anti-proliferative drug to reduce neointimal hyperplasia, has reduced the incidence of in-stent-restenosis relative to treatment with bare metal stents. Patients treated with first generation DES more likely suffer from (very) late events which can be cause by the permanent presence of a polymer. Therefore second generation DES with more biocompatible coatings, and third generation DES, with very thin struts coated with biodegradable polymers, were developed. Areas covered: The MiStent SES is one of these third generation DES and is designed to limit the duration of polymer exposure, optimize coronary vessel healing and more precisely and consistently control drug elution to improve safety and clinical outcomes. This review provides a detailed description of the technique behind the MiStent SES, and describes the pre-clinical and clinical trials conducted with this device to date. Expert commentary: Recent clinical trials have shown non-inferiority of very thin strut biodegradable polymer coated DES compared to durable polymer coated DES, whilst maintaining an excellent safety profile. Longer follow-up, to see the real potential benefits of these devices, is mandatory however.
Healthcare Cost and Utilization in Nonalcoholic Fatty Liver Disease: Real‐World Data From a Large U.S. Claims Database

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing. The health care burden resulting from the multidisciplinary management of this complex disease is unknown. We assessed the total health care cost and resource utilization associated with a new NAFLD diagnosis, compared with controls with similar comorbidities. We used OptumLabs Data Warehouse, a large national administrative claims database with longitudinal health data of over 100 million individuals enrolled in private and Medicare Advantage health plans. We identified 152,064 adults with a first claim for NAFLD between 2010 and 2014, of which 108,420 were matched 1:1 by age, sex, metabolic comorbidities, length of follow‐up, year of diagnosis, race, geographic region, and insurance type to non‐NAFLD contemporary controls from the OptumLabs Data Warehouse database. Median follow‐up time was 2.6 (range 1‐6.5) years. The final study cohort consisted of 216,840 people with median age 55 (range 18‐86) years, 53% female, 78% white. The total annual cost of care per NAFLD patient with private insurance was $7,804 (interquartile range [IQR] $3,068‐$18,688) for a new diagnosis and $3,789 (IQR $1,176‐$10,539) for long‐term management. These costs are significantly higher than the total annual costs of $2,298 (IQR $681‐$6,580) per matched control with similar metabolic comorbidities but without NAFLD. The largest increases in health care utilization that may account for the increased costs in NAFLD compared with controls are represented by liver biopsies (relative risk [RR] = 55.00, 95% confidence interval [CI] 24.48‐123.59), imaging (RR = 3.95, 95% CI 3.77‐4.15), and hospitalizations (RR = 1.87, 95% CI 1.73‐2.02). Conclusion: The costs associated with the care for NAFLD independent of its metabolic comorbidities are very high, especially at first diagnosis. Research efforts shouldfocus on identification of underlying determinants of use, sources of excess cost, and development of cost‐effective diagnostic tests.
Sensory systems and ionocytes are targets for silver nanoparticle effects in fish

Abstract Some nanoparticles (NPs) may induce adverse health effects in exposed organisms, but to date the evidence for this in wildlife is very limited. Silver nanoparticles (AgNPs) can be toxic to aquatic organisms, including fish, at concentrations relevant for some environmental exposures. We applied whole mount in-situ hybridisation (WISH) in zebrafish embryos and larvae for a suite of genes involved with detoxifying processes and oxidative stress, including metallothionein (mt2), glutathionine S-transferase pi (gstp), glutathionine S-transferase mu (gstm1), haem oxygenase (hmox1) and ferritin heavy chain 1 (fth1) to identify potential target tissues and effect mechanisms of AgNPs compared with a bulk counterpart and ionic silver (AgNO3). AgNPs caused upregulation in the expression of mt2, gstp and gstm1 and down regulation of expression of both hmox1 and fth1 and there were both life stage and tissue-specific responses. Responding tissues included olfactory bulbs, lateral line neuromasts and ionocytes in the skin with the potential for effects on olfaction, behaviour and maintenance of ion balance. Silver ions induced similar gene responses and affected the same target tissues as AgNPs. AgNPs invoked levels of target gene responses more similar to silver treatments compared to coated AgNPs indicating the responses seen were due to released silver ions. In the Nrf2 zebrafish mutant, expression of mt2 (24 hpf) and gstp (3 dpf) were either non-detectable or were at lower levels compared with wild type zebrafish for exposures to AgNPs, indicating that these gene responses are controlled through the Nrf2-Keap pathway.
The Utility of MR Elastography to Differentiate Nodular Regenerative Hyperplasia from Cirrhosis

Nodular regenerative hyperplasia (NRH) is characterized by diffuse parenchymal nodularity of the liver with small regenerative nodules, leading to possible portal hypertension. Differentiating NRH from cirrhosis on standard imaging is difficult. We evaluated the potential utility of MRI and MR Elastography (MRE) in differentiating NRH and cirrhosis. This article is protected by copyright. All rights reserved.