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Aim: A novel design for non-reversible as well as reversible parity generator and detector in Quantum-dot Cellular Automata (QCA) technology is presented in this research article. Parity generator and detector circuits are reliable error-checking components of a nano-communication system. Objective: The main focus of this research is to design an ultra-low-power fault-tolerant reversible gate implementation of the parity logic function in QCA. An efficient QCA design layout with minimal area, less latency and the least energy dissipation is desired. Methods: The proposed designs are developed using Quantum-dot Cellular Automata (QCA) technology. The circuits are optimized using majority gate reduction and clock zone reduction techniques. Also, the cell-cell interaction technique is employed to further optimize the QCA circuit. To increase the fault tolerance and ultra-low power operation, reversible QCA circuits are designed using cascaded Feynman gates. Results Conclusion: The efficiency of the parity generator and detector is calculated to be more than 25% compared to existing QCA layouts. It is demonstrated in this paper that the proposed circuits perform exceptionally well on every design parameter. The design parameters under consideration are cell count, cell area, complexity, crossover count, latency and energy dissipation. Conclusion: Using reversible logic, a fault-tolerant and defect-sensitive circuit are developed for parity generation and detection.

Objectives The study aimed to (i) compare the maladaptive domains and facets according to the Alternative Model of Personality Disorders (AMPD) Criterion B in patients with a type II bipolar disorder (BD-II) or major depressive disorder (MDD) with healthy controls (HCs), and (ii) investigating the relationship between affective temperaments and these domains and facets in the total sample. Methods Outpatients diagnosed with current BD-II (n = 37; female 62.2%) or MDD (n = 17; female 82.4%) based on the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria and community HCs (n = 177; female 62.1%) in Kermanshah from July to October 2020 included this case-control study. All participants completed the Personality Inventory for DSM-5 (PID-5), the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A), and the second version of the Beck Depression Inventory (BDI-II). Data were analyzed using analysis of variance (ANOVA), Pearson correlation, and multiple regression. Results The score of patients with BD-II in all five domains and those with MDD in three domains including negative affectivity, detachment, and disinhibition are significantly higher than the HCs (p Conclusions Two unique profiles are proposed, including three domains of negative affectivity, detachment, and disinhibition associated with the depressive temperament for MDD, and two domains of antagonism and psychoticism related to cyclothymic temperament for BD-II.

BackgroundEnvironmental pollution and infertility are two modern global challenges that agonize personal and public health. The causal relationship between these two deserves scientific efforts to intervene. It is believed that melatonin maintains antioxidant properties and may be utilized to protect the testicular tissue from oxidant effects caused by toxic materials.MethodsA systematic literature search was conducted in PubMed, Scopus, and Web of Science to identify the animal trial studies that evaluated melatonin therapy’s effects on rodents’ testicular tissue against oxidative stress caused by heavy metal and non-heavy metal environmental pollutants. Data were pooled, and standardized mean difference and 95% confidence intervals were estimated using the random-effect model. Also, the risk of bias was assessed using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool. (PROSPERO: CRD42022369872)ResultsOut of 10039 records, 38 studies were eligible for the review, of which 31 were included in the meta-analysis. Most of them showed beneficial effects of melatonin therapy on testicular tissue histopathology. [20 toxic materials were evaluated in this review, including arsenic, lead, hexavalent chromium, cadmium, potassium dichromate, sodium fluoride, cigarette smoke, formaldehyde, carbon tetrachloride (CCl4), 2-Bromopropane, bisphenol A, thioacetamide, bisphenol S, ochratoxin A, nicotine, diazinon, Bis(2-ethylhexyl) phthalate (DEHP), Chlorpyrifos (CPF), nonylphenol, and acetamiprid.] The pooled results showed that melatonin therapy increased sperm count, motility, viability and body and testicular weights, germinal epithelial height, Johnsen's biopsy score, epididymis weight, seminiferous tubular diameter, serum testosterone, and luteinizing hormone levels, testicular tissue Malondialdehyde, glutathione peroxidase, superoxide dismutase, and glutathione levels. On the other hand, abnormal sperm morphology, apoptotic index, and testicular tissue nitric oxide were lower in the melatonin therapy arms. The included studies presented a high risk of bias in most SYRCLE domains.ConclusionIn conclusion, our study demonstrated amelioration of testicular histopathological characteristics, reproductive hormonal panel, and tissue markers of oxidative stress. Melatonin deserves scientific attention as a potential therapeutic agent for male infertility.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42022369872.

PurposeTo present a case of periorbital and orbital necrotizing fasciitis (PONF) from an odontogenic source with a distinct microbiologic profile and highlight the need for emergent multidisciplinary management.ObservationsA 39-year-old man presented with periorbital swelling, pain, and erythema following facial trauma. Imaging revealed peri-dental collections, accompanying maxillary sinusitis, and pre- and post-septal involvement. Immediate surgical debridement of necrotic tissue along with broad-spectrum antibiotics were pursued for management. Cultures grew multiple organisms, most notably Streptococcus milleri group and Staphylococcus lugdunensis.Conclusions and importancePONF is a rare yet potentially fatal disease. Streptococcus milleri group and a fulminant course are to be suspected when the source is odontogenic. Timely multidisciplinary surgical debridement and medical management with intravenous antibiotics is critical for best outcomes.

Despite advancement in the surgical instrumentation and techniques, proliferative vitreoretinopathy (PVR) remains the most common cause for failure of rhegmatogenous retinal detachment (RRD) repair. This review discusses ongoing translational and clinical advancements in PVR.PVR represents an exaggerated and protracted scarring process that can occur after RRD. The primary cell types involved are retinal pigment epithelium, glial, and inflammatory cells. They interact with growth factors and cytokines derived from the breakdown of the blood-retinal barrier that trigger a cascade of cellular processes, such as epithelial-mesenchymal transition, cell migration, chemotaxis, proliferation, elaboration of basement membrane and collagen and cellular contraction, leading to overt retinal pathology. Although there are currently no medical therapies proven to be effective against PVR in humans, increased understanding of the risks factors and pathophysiology have helped guide investigations for molecular targets of PVR. The leading therapeutic candidates are drugs that mitigate growth factors, inflammation, and proliferation are the leading therapeutic candidates.Although multiple molecular targets have been investigated to prevent and treat PVR, none have yet demonstrated substantial evidence of clinical benefit in humans though some show promise. Advancements in our understanding of the pathophysiology of PVR may help develop a multipronged approach for this condition.

The COVID-19 pandemic caused a significant change in traffic operations and safety. For instance, various U.S. states reported an increase in the rate of fatal and severe injury crashes over this duration. In April and May of 2020, comprehensive stay-at-home orders were issued across the country, including in Maine. These orders resulted in drastic reductions in traffic volume. Additionally, there is anecdotal evidence that speed enforcement had been reduced during pandemic. Drivers responded to these changes by increasing their speed. More importantly, data show that speeding continues to occur, even one year after the onset of the pandemic. This study develops statistical models to quantify the impact of the pandemic on speeding in Maine. We developed models for three rural facility types (i.e., major collectors, minor arterials, and principal arterials) using a mixed effect Binomial regression model and short duration speed and traffic count data collected at continuous count stations in Maine. Our results show that the odds of speeding by more than 15 mph increased by 34% for rural major collectors, 32% for rural minor arterials, and 51% for rural principal arterials (non-Interstates) during the stay-at-home order in April and May of 2020 compared to the same months in 2019. In addition, the odds of speeding by more than 15 mph, in April and May of 2021, one year after the order, were still 27% higher on rural major collectors and 17% higher on rural principal arterials compared to the same months in 2019.

We report a case of a 47-year-old female who experienced periorbital swelling while descending from a Himalayan mountain climb and was found to have bilateral superior ophthalmic vein thromboses (SOVT). Infectious, autoimmune, and hypercoagulability work-up were negative with no cavernous sinus involvement. Symptoms resolved upon initiation of anticoagulation and oral steroids. SOVT is a rare but serious condition and has a risk of extending into the cavernous sinus if not treated early. Although infection is the most common etiology, venous thrombosis can be precipitated under high altitude and low oxygen pressure environments. We present a case of superior ophthalmic vein thrombosis associated with high-altitude conditions.

Purpose To compare fluid detection of autosegmented en face to 12-line radial spectral domain optical coherence tomography scan patterns in neovascular age-related macular degeneration. Methods Retrospective observational case series. Sixty-seven patients (94 eyes) with neovascular age-related macular degeneration underwent autosegmented en face optical coherence tomography (with associated 304-line raster scan) and 12-line radial scan patterns. Sensitivity and specificity of fluid detection for en face scan and 12-line radial scans were determined by combining radial and 304-line raster scans as a gold standard. Results Two hundred and fifty-eight en face and 12-line radial spectral domain optical coherence tomography scans were interpreted. Seventy-five scans (58.1%) had fluid, whereas 54 scans (41.9%) did not. En face scan pattern fluid detection sensitivity and specificity was 89.3% and 61.1%, respectively. Twelve-line radial scan pattern fluid detection sensitivity and specificity was 97.3% and 100%, respectively. The difference in fluid detection between scan patterns was statistically significant (P = 0.01). Decreased central macular thickness was associated with false-positive (P = 0.035) and false-negative (P = 0.01) fluid detection on en face scans. Conclusion En face optical coherence tomography alone is not as sensitive or specific as the 12-line radial scan pattern in detecting fluid in neovascular age-related macular degeneration. En face scans should be corroborated with other optical coherence tomography protocols to guide clinical decision making.

Convincing clinical evidence exists to support early surgical decompression in the setting of cervical spinal cord injury (SCI). However, clinical evidence on the effect of early surgery in patients with thoracic and thoracolumbar (from T1 to L1 [T1–L1]) SCI is lacking and a critical knowledge gap remains. This randomized controlled trial (RCT) sought to evaluate the safety and efficacy of early (

BackgroundAspartate β-hydroxylase (ASPH) is an embryonic transmembrane protein aberrantly upregulated in cancer cells, associated with malignant transformation and, in some reports, with poor clinical prognosis.ObjectiveTo report the expression patterns of ASPH in acute myeloid leukemia (AML).MethodsCell surface expression of ASPH was measured via 8-color multiparameter flow cytometry in 41 AML patient samples (31 bone marrow, 10 blood) using fluorescein isothiocyanate (FITC)-conjugated anti-ASPH antibody, SNS-622. A mean fluorescent intensity (MFI) of 10 was used as a cutoff for ASPH surface expression positivity. Data regarding patient and disease characteristics were collected.ResultsASPH surface expression was found on AML blasts in 16 samples (39%). Higher ASPH expression was seen in myeloblasts of African American patients (p=0.02), but no correlation was found between ASPH expression and other patient or disease characteristics. No association was found between ASPH status and CR rate (p=0.53), EFS (p=0.87), or OS (p=0.17).ConclusionsASPH is expressed on blasts in approximately 40% of AML cases, and may serve as a new therapeutically targetable leukemia-associated antigen.

Purpose To report the imaging findings of a single case of paracentral acute middle maculopathy associated with bilateral Purtscher-like retinopathy in the setting of recent viral illness. Methods Case report, multimodal imaging. Results A 21-year-old woman who awoke with sudden-onset bilateral finger count vision in the setting of a recent viral illness. Initial examination and imaging was consistent with a bilateral Purtscher-like retinopathy with evidence of paracentral acute middle maculopathy and ellipsoid zone thickening and hyperreflectivity on spectral domain optical coherence tomography (OCT). Baseline fluorescein angiography and OCT angiography revealed normal perfusion and flow, respectively. All laboratory investigation was negative for possible causative etiology. The patient was followed for 6 months with steady visual improvement to 20/20 in both eyes. En face OCT demonstrated near-complete restoration of the ellipsoid layer. The patient still noted bilateral scotomas which were mapped out on microperimetry and found to correlate to en face OCT findings. Conclusion Purtscher-like retinopathy in the setting of recent viral illness is a rare cause of vision loss that may be associated with the finding of paracentral acute middle maculopathy on spectral domain OCT. Despite poor presenting vision, in the presence of normal perfusion near total visual recovery is possible.

PurposeTo examine the effect of low-dose, oral isotretinoin in lowering the risk of proliferative vitreoretinopathy (PVR) following rhegmatogenous retinal detachment (RRD) repair.MethodsProspective, open label, dual-cohort study with pathology-matched historical controls. The prospective experimental arms included two cohorts, composed of 51 eyes with recurrent PVR-related RRD and 58 eyes with primary RRD associated with high-risk features for developing PVR. Eyes in the experimental arms received 20 mg of isotretinoin by mouth once daily for 12 weeks starting the day after surgical repair. The primary outcome measure was single surgery anatomical success rate at 3 months following the study surgery.ResultsThe single surgery anatomic success rate was 78.4% versus 70.0% (p=0.358) in eyes with recurrent PVR-related retinal detachment exposed to isotretinoin versus historical controls, respectively. In eyes with RRD at high risk for developing PVR, the single surgery success rate was 84.5% versus 61.1% (p=0.005) for eyes exposed to isotretinoin versus historical controls, respectively. For eyes enrolled in the experimental arms, the most common isotretinoin-related side effects were dry skin/mucus membranes in 106 patients (97.2%), abnormal sleep/dreams in 4 patients (3.7%) and fatigue in 3 patients (2.8%).ConclusionThe management and prevention of PVR is challenging and complex. At the dose and duration given in this study, oral istotretinoin may reduce the risk of PVR-associated recurrent retinal detachment in eyes with primary RRD at high risk of developing PVR.

Background: Due to the increased resistance against existing antibiotics, research is essential to discover new and alternative ways to control infections induced by resistant pathogens. Objective: The goal of the current scrutinization was to enrich the dissolution rate and antibacterial property of cefixime (CEF) orally. Methods: To achieve the desired results, chitosan nanoparticles (NPs) containing CEF were fabricated using the ionic gelation method. Central Composite design has been applied to get the optimal formulation for the delivery of CEF. The effect of three variables, such as the concentration of chitosan, tripolyphosphate, and tween 80, on the characteristics of NPs was evaluated. Results: The optimized NPs involved a relatively monodispersed size distribution with an average diameter of 193 nm and a zeta potential of about 11 mV. The scanning tunneling microscope confirmed the size of NPs. The surface morphology of NPs was observed by scanning electron microscopy. The calorimetric analysis indicated the amorphous state of cefixime in the formulation. The dissolution rate of NPs in aqueous media was acceptable and the model of release kinetics for CEF from NPs followed the Peppas model. The potency of CEF in NPs against various types of bacteria was hopefully efficient. The ex-vivo release study demonstrated higher penetration of NPs from the rat intestine compared to free drug. The cell culture study showed the safety of the optimized formulation. Conclusion: Chitosan NPs could be considered a significant system for the controlled delivery of CEF due to its antibacterial effectiveness.

Convincing clinical evidence exists to support early surgical decompression in the setting of cervical spinal cord injury (SCI). However, clinical evidence on the effect of early surgery in patients with thoracic and thoracolumbar (from T1 to L1 [T1-L1]) SCI is lacking and a critical knowledge gap remains. This randomized controlled trial (RCT) sought to evaluate the safety and efficacy of early (

To evaluate the safety and effects of oral eplerenone in chronic central serous chorioretinopathy.Prospective, randomized, double-blind, placebo-control study at a tertiary referral academic private practice. For a diagnosis of chronic central serous chorioretinopathy, patients must have had at least 3 months clinical follow-up demonstrating persistent symptoms, subfoveal fluid on spectral-domain optical coherence tomography, and50% reduction in fluid thickness. Patients were randomized 2:1 (treatment:placebo) to receive eplerenone (25 mg daily for 1 week, then up to 50 mg daily for 8 weeks) or placebo once daily.Fifteen patients completed the study. Ten patients (15 eyes) were randomized into the eplerenone treatment arm, while the remaining 5 patients (6 eyes) received placebo. After 9 weeks of eplerenone therapy, mean logarithm of the minimal angle of resolution visual acuity improved from 0.394 (Snellen equivalent: 20/50) to 0.330 (20/43, P = 0.04). In the placebo group, the mean logarithm of the minimal angle of resolution visual acuity slightly decreased from 0.313 (20/41) to 0.342 (20/44) during the same period (P = 0.21). With respect to anatomic changes, mean maximal subretinal fluid height in the eplerenone group improved from 139.3 μm at baseline to 51.8 μm (P = 0.02), mean subfoveal fluid height improved from 121.4 μm to 29.4 μm (P = 0.01), and mean central subfield thickness improved from 366.2 μm to 283.7 μm (P = 0.02). In comparison with the placebo group, mean maximal subretinal fluid height worsened from 135.9 μm to 172.3 μm (P = 0.32), mean subfoveal fluid height worsened from 92.1 μm to 134.0 μm (P = 0.54), and mean central subfield thickness worsened from 345.0 μm to 380.0 μm (P = 0.37). No patients in either group experienced serious adverse events to result in treatment discontinuation.These findings suggest that oral eplerenone therapy is safe and potentially effective in the treatment of chronic central serous chorioretinopathy with persistent subretinal fluid.

Purpose: To investigate how the optical density ratio (ODR) of subretinal fluid (SRF) obtained by optical coherence tomography (OCT) in eyes with chronic central serous retinopathy (CSR), defined as symptoms >3 months, treated with eplerenone correlates with treatment response and visual outcomes. Methods: This retrospective, single-center observational study included patients with chronic CSR treated with eplerenone who had at least 6 weeks of follow-up. Eyes with poor-quality OCT scans, shallow SRF precluding sampling of optical density (OD), and macular pathology other than CSR were excluded. Optical density of the vitreous and SRF was measured using ImageJ and used to calculate ODR (ODR = ODSRF/ODVIT). Peak SRF height, foveal SRF height, central macular thickness (CMT), and Snellen visual acuity (VA) were measured. The Mann-Whitney U test was used to compare continuous variables. Pearson correlation coefficient was used to determine the statistical significance of applied linear regressions. Results: Twenty-three eyes of 23 patients met the inclusion criteria. Six (26%) eyes had complete resolution of foveal SRF (resolvers) with eplerenone treatment, and the remainder of patients had worsening or incomplete resolution (nonresolvers). Resolvers had significantly lower baseline logarithm of the minimum angle of resolution (logMAR) VA ( P < .01) than nonresolvers. There was a positive linear correlation between ODR and logMAR VA at baseline ( R2 = 0.208; P = .03) and follow-up ( R2 = 0.206; P = .03). A significant correlation between ODR and percentage change in CMT was found ( R2 = 0.263; P = .01). Linear correlations were not found between ODR and age, peak SRF height, and foveal SRF height (all P > .125). Conclusion: Lower baseline ODR was associated with improved percentage change in CMT and VA in patients treated with eplerenone for chronic CSR. Optical density ratio may represent a novel prognostic biomarker that may help determine which eyes with chronic CSR may respond better to eplerenone.

As folic acid receptors are overexpressed in various cancers including the colon, therefore, nanoparticles of folic acid-polyethylene glycol -poly lactic-co-glycolic acid were fabricated and loaded with irinotecan by emulsification/solvent evaporation technique to target the folic acid receptors in colorectal tumors. The chemical structure of synthesized polymer was examined by 1H NMR, and Box-Behnken design was utilized to determine the combined impact of independent variables for choosing the appropriate formulation. Dynamic light scattering, scanning electron microscope and differential scanning calorimetry (DSC) were utilized to scrutinize irinotecan in nanoparticles. The Box-Behnken design indicated a reasonable correlation between the predicted and experimented values which proves the efficiency of the selected statistical model. The optimized nanoparticles had an acceptable size and morphology. DSC analysis exhibited that irinotecan in nanoparticles is in an amorphous state. The optimized formulation exhibited a prolonged release profile. In addition, the higher drug release from nanoparticles in acidic pH indicates that they can be used to target the extracellular pH of the tumor. The activity of targeted nanoparticles against tumors was higher than the irinotecan and simple nanoparticles. Evaluation of folic acid decorated nanoparticles containing irinotecan confirmed their suitability for targeted delivery of irinotecan in folate positive cancers.

Purpose To evaluate the usefulness of the video indirect ophthalmoscope (VIO) to improve resident ophthalmologist skill with indirect ophthalmoscopy (IO) and scleral depression (SD). Design Prospective, randomized, double-arm interventional study. Participants Ten ophthalmology residents were enrolled in an educational program using the Heine Video Omega 2C VIO (Heine USA Ltd, Dover, NH) and served as the study group. Ten other experience-matched ophthalmology residents functioned as the control group. Methods At baseline, all study and control residents completed surveys assessing their subjective comfort and skill with IO. Each resident also completed a standardized full IO examination with SD that was recorded using the VIO. Each resident in the study group received 3 monthly 1-hour teaching sessions using the VIO. Surveys and recorded standardized examinations were repeated for all residents after the 3-month period. Both baseline and final examination videos were graded using a standardized grading scale by 3 independent retina faculty members masked to the identities of the residents and timing of the examination. Main Outcome Measures Improved visualization of the peripheral retina (ora serrata) as evaluated by masked graders was the primary outcome measure. Improved examination efficiency grade was the secondary outcome measure. Results Both the study group and the control group had significant improvement in ability to examine the peripheral retina and ora serrata compared with baseline ( P = 0.02 and P = 0.03, respectively). The study group also showed significantly improved examination efficiency compared with baseline, which was not noted in the control group ( P = 0.01 and P = 0.53, respectively). The study group self-reported significantly improved confidence in the ability to identify retinal tears, whereas the control group did not ( P = 0.003 and P = 0.08, respectively). Study group participants also reported significantly improved ability to recognize retinal holes ( P = 0.003), subretinal fluid ( P = 0.02), and vitreoretinal tufts ( P = 0.02), whereas the control group did not. Conclusions This novel educational study suggests that VIO as part of a structured teaching program may improve resident ophthalmologist confidence and ability with identifying retinal pathologic features using IO with SD.

Purpose: To characterize and quantify the pre- and postoperative foveal structural and functional patterns in full-thickness macular holes. Methods: Subjects presenting with a full-thickness macular hole that had pre- and postoperative imaging were included. En face optical coherence tomography (OCT) and OCT angiography (OCTA) was performed. Foveal avascular zone (FAZ) area, macular hole size, number and size of perifoveal cysts were measured. Results: Five eyes from 5 patients were included in the study. The hole was closed in all eyes after the initial surgery. OCTA showed enlargement of the FAZ and delineation of the holes within the FAZ. Mean preoperative FAZ area was 0.41 ± 0.104 mm2. Visual acuity was improved and mean FAZ area was reduced to 0.27 ± 0.098 mm2 postoperatively (P

Purpose To quantify foveal avascular zone (FAZ) area and macular vascular density objectively using optical coherence tomography angiography (OCTA) and to examine correlations with visual acuity in eyes with diabetic retinopathy (DR) in the absence of diabetic macular edema. Design Retrospective observational case series. Participants Eighty-four eyes from 55 patients with DR and 34 control eyes from 27 age-matched healthy participants. Methods All eyes underwent OCTA (RTVue-XR Avanti; Optovue, Inc, Fremont, CA). Integrated automated algorithms were used to quantify FAZ area and macular vascular density. Main Outcome Measures FAZ area, vessel area density (VAD), vessel length density (VLD), and visual acuity. Results In each study eye, DR was classified as mild nonproliferative DR (NPDR; n = 32 [38%]), moderate-to-severe NPDR (n = 31 [37%]), or proliferative DR (n = 21 [25%]). Mean FAZ area was greater in diabetic eyes compared with control eyes both in the superficial (0.427 mm 2 vs. 0.275 mm 2 ; P 2 vs. 0.372 mm 2 ; P P P −1 vs. 21.55 mm −1 ; P −1 vs. 24.38 mm −1 ; P P P P P Conclusions Automated quantitative algorithms allow for objective assessment of retinal vascular changes in eyes with DR that are correlated to visual acuity. These methods may prove useful in monitoring disease progression and identifying parameters that affect visual function.

Loss to follow-up (LTFU) after anti-vascular endothelial growth factor (anti-VEGF) injections increases the risk of vision loss among patients with neovascular age-related macular degeneration (nAMD).To report rates of LTFU among patients with nAMD after anti-VEGF injections and to identify risk factors associated with LTFU in this population.This retrospective cohort study of data from 9007 patients who received anti-VEGF injections for treatment of nAMD was performed at an urban, private retina practice with multiple locations from April 1, 2012, to January 12, 2016.Rates of LTFU after anti-VEGF injections. Loss to follow-up was defined as receipt of 1 or more injections with no subsequent follow-up visit within 12 months.Among the 9007 patients (mean [SD] age, 81.2 [8.8] years; 5917 [65.7%] female; 7905 [87.8%] white), 2003 (22.2%) were LTFU. Odds of LTFU were greater among patients 81 to 85 years of age (odds ratio [OR], 1.58; 95% CI, 1.38-1.82; P .001), 86 to 90 years of age (OR, 2.29; 95% CI, 2.00-2.62; P .001), and more than 90 years of age (OR, 3.31; 95% CI, 2.83-3.86; P .001) compared with patients 80 years of age and younger. Odds of LTFU among African American patients (OR, 1.47; 95% CI, 1.00-2.16; P = .05), Asian patients (OR, 2.63; 95% CI, 1.71-4.03; P .001), patients of other race (OR, 3.07; 95% CI, 1.38-6.82; P = .006), and patients of unreported race (OR, 2.29; 95% CI, 1.96-2.68; P .001) were greater than odds of LTFU among white patients. Odds of LTFU were greater among patients with regional adjusted gross income of $50 000 or less (OR, 1.52; 95% CI, 1.30-1.79; P .001), $51 000 to $75 000 (OR, 1.35; 95% CI, 1.17-1.56; P .001), and $76 000 to $100 000 (OR, 1.28; 95% CI, 1.08-1.50; P = .004) compared with patients with incomes greater than $100 000. Odds of LTFU for patients living 21 to 30 miles (OR, 1.33; 95% CI, 1.05-1.69; P = .02) and more than 30 miles (OR, 1.55; 95% CI, 1.28-1.88; P .001) from clinic were greater compared with patients who lived 10 miles or less from the clinic. Odds of LTFU were greater among patients who received unilateral injections (OR, 1.44; 95% CI, 1.28-1.61; P .001) than among patients who received bilateral injections.We found a high rate of LTFU after anti-VEGF injections among patients with nAMD and identified multiple risk factors associated with LTFU among this population. Although our results may not be generalizable, data on LTFU in a clinical practice setting are needed to understand the scope of the problem so that interventions may be designed to improve outcomes.

To describe the clinical features and management of six patients with ocular complications associated with direct oral anticoagulants (DOACs).The medical records of all adult patients known to be taking a DOAC and with an unusual bleeding event at a large tertiary referral center over a one-year period were reviewed. Patients with less than one-month follow-up were excluded. Data collection included relevant clinic notes, operative reports, surgical videos, and clinical images (fundus photography, optical coherence tomography, B-scan ultrasonography, and fluorescein angiography).Six eyes in six patients were identified with an unusual bleeding event associated with DOAC use. One patient was taking apixaban, two patients were taking dabigatran, and three patients were taking rivaroxaban. Two patients had large submacular hemorrhage (including one with vitreous hemorrhage breakthrough), three patients had vitreous hemorrhage, and one patient had recurrent hyphema. Presenting visual acuity ranged from 20/40 to light perception. Three individuals required therapeutic and/or diagnostic pars plana vitrectomy for vitreous hemorrhage. Final visual acuity ranged from 20/25 to count finger vision. The associated DOAC was permanently discontinued in two of the six cases. Follow-up was one to four months from onset of identified DOAC-related complication.DOAC use may be associated with ocular bleeding. Ophthalmologists should be aware of potential hemorrhagic complications and obtain consultation with primary providers regarding DOAC cessation guidelines.

To quantify density of macular vascular networks over regions of interest in healthy subjects using optical coherence tomography angiography (OCTA).Prospective cross-sectional study.Setting was the Retina and Oncology Services of Wills Eye Hospital. Subjects with no known systemic disease and without retinal pathology were included. OCTA was performed on a 3 × 3-mm region centered on the macula and en face angiograms of the superficial and deep vascular networks were acquired. Vascular density was calculated using an automated image thresholding method over regions of interest. Foveal and parafoveal vascular density were calculated. The differences between vascular networks, sexes, and fellow eyes and correlation between vascular density, signal strength, and age, as well as reproducibility of measurements, were evaluated.A total of 198 healthy eyes were imaged, from which 163 eyes of 122 subjects were included based on image quality criteria. In the parafoveal region, deep vascular density was significantly higher than the superficial (52% ± 2.4% vs 46% ± 2.2%; P.001), whereas the opposite was found in the foveal region (27% ± 5.2% vs 32% ± 3.2%; P.001). All vascular density measurements were statistically similar in fellow eyes and there was no sex difference (P.05). There was a negative correlation between vascular density and age that persisted upon adjusting for signal strength. Vascular density measurements were highly correlated between separate imaging sessions with intraclass correlation coefficients of over 0.85 for all assessments.Calculation of vascular density using OCTA is a reproducible and noninvasive method to quantitate individual networks within the macula. Understanding normal values and their correlations could affect clinical evaluation of the macula in healthy patients and disease states.

Aims To quantify the change in drusen volume over time and identify its prognostic value for individual risk assessment. Methods A prospective observational study over a minimum of 3 years and maximum of 5 years and follow-up examination every 3 months was conducted at the ophthalmology department of the Medical University of Vienna. 109 patients presenting early and intermediate age-related macular degeneration (AMD) were included, of which 30 patients concluded a regular follow-up for at least 3 years. 50 eyes of 30 patients were imaged every 3 months using spectral-domain and polarisation-sensitive optical coherence tomography (OCT). Drusen volume was measured using an automated algorithm. Data of a 6-month follow-up were segmented manually by expert graders. Results Gradings from 24 000 individual B-scans showed solid correlation between manual and automated segmentation with an initial mean drusen volume of 0.17 mm 3 . The increase in drusen volume was shown to be comparable among all eyes, and a model for long-term drusen volume development could be fitted as a cubic polynomial function and an R 2 =0.955. Spontaneous drusen regression was observed in 22 of 50 eyes. In this group, four eyes developed choroidal neovascularisation and three geographic atrophy. Conclusions Drusen volume increase over time can be described by a cubic function. Spontaneous regression appears to precede conversion to advanced AMD. OCT might be a promising tool for predicting the individual risk of progression of AMD.

The authors describe a case of para-central acute middle maculopathy (PAMM) in a 75-year-old man who had recently undergone cardiac catheterization. Imaging with simultaneous en face optical coherence tomography (OCT) and OCT angiography (OCTA) revealed signal abnormalities localized to the deep capillary plexus. This case highlights the ability of OCTA to image and localize retinal disease by vascular distribution, previously difficult with conventional fluorescein angiography, and lends evidence to the belief that PAMM is caused by vascular injury to the intermediate and deep capillary plexus. [ Ophthalmic Surg Lasers Imaging Retina . 2015;46:972–975.]

BACKGROUND AND OBJECTIVE: This study evaluated the residual subfoveal fluid (SFF) immediately after rhegmatogenous retinal detachment (RRD) repair using intraoperative optical coherence tomography (iOCT). PATIENTS AND METHODS: This retrospective cohort study assessed fovea-involving RRD repaired by pars plana vitrectomy (PPV) using different drainage techniques. iOCT images were acquired through the fovea at the start of the case prior to initiating vitrectomy and then again immediately prior to introduction of tamponade. RESULTS: Ten eyes (32.3%) received perfluoro-n-octane (PFO), 12 (38.7%) underwent a posterior drainage retinotomy, and nine (29.0%) had drainage through the retinal break. There was no significant difference in the mean SFF thickness between eyes in either group ( P = .85). There was no significant association between SFF thickness on iOCT and functional or anatomic outcomes ( P > .05). CONCLUSION: There is no difference in the amount of residual SFF as measured on iOCT during RRD repair with pars plana vitrectomy using either direct drainage, drainage retinotomy, or PFO. [ Ophthalmic Surg Lasers Imaging Retina . 2019;50:497–503.]

To compare fluid detection of autosegmented en face to 12-line radial spectral domain optical coherence tomography scan patterns in neovascular age-related macular degeneration.Retrospective observational case series. Sixty-seven patients (94 eyes) with neovascular age-related macular degeneration underwent autosegmented en face optical coherence tomography (with associated 304-line raster scan) and 12-line radial scan patterns. Sensitivity and specificity of fluid detection for en face scan and 12-line radial scans were determined by combining radial and 304-line raster scans as a gold standard.Two hundred and fifty-eight en face and 12-line radial spectral domain optical coherence tomography scans were interpreted. Seventy-five scans (58.1%) had fluid, whereas 54 scans (41.9%) did not. En face scan pattern fluid detection sensitivity and specificity was 89.3% and 61.1%, respectively. Twelve-line radial scan pattern fluid detection sensitivity and specificity was 97.3% and 100%, respectively. The difference in fluid detection between scan patterns was statistically significant (P = 0.01). Decreased central macular thickness was associated with false-positive (P = 0.035) and false-negative (P = 0.01) fluid detection on en face scans.En face optical coherence tomography alone is not as sensitive or specific as the 12-line radial scan pattern in detecting fluid in neovascular age-related macular degeneration. En face scans should be corroborated with other optical coherence tomography protocols to guide clinical decision making.

PURPOSE To report a prospective, randomized comparative study assessing clinical outcomes of plain gut versus polyglactin 910 (PG910) sutures for sclerotomy closure after 23-gauge pars plana vitrectomy. METHODS A single-masked, randomized, prospective study was undertaken with 49 eyes of 49 patients undergoing 23-gauge pars plana vitrectomy randomized to sclerotomy closure with either plain gut suture, PG910 (Vicryl) suture or a combination of the two. Assessment was based on both a postoperative pain scale and a standardized assessment of scleral inflammation at each suture site. RESULTS No wound leakage was noted postoperatively in any patient. Across all groups, scleral inflammation was significantly higher at the PG910 suture sites compared with the plain gut suture sites at both the 1-week (P = 0.04) and 1-month postoperative visits (P < 0.001). Patients with PG910 sutures reported greater pain at the 1-month postoperative visit than those with plain gut sutures (P = 0.018). CONCLUSION This prospective study suggests improved tolerability and reduced inflammation using plain gut suture compared with an 8-0 PG910 suture to close 23-gauge sclerotomies.

The aim of this study was investigation of green marketing and its impacts on consumer behavior in sports shops in East Azerbaijan province of Iran. The present study is functionalized by objectives and done by field. The study statistical society was sports shops in East Azerbaijan and 210 samples were chosen randomly according to Morgan sampling method and 196 questionnaires were collected finally. The author-prepared questionnaire’s validity was approved by some experts in sport management and marketing. Field and the reliability were assessed by pilot study using Chronbach’s Alpha (α= 819%) which showed that the tool was reliable. The questionnaire had 30 items rated by Lakers scale. Questionnaire introduction contained demographic pieces information of age, income and education degree. Results shows that a significant relationship between green products features, green promotion, green pricing and green distributing with consumer green behavior; and education, income, and age, but not marital status, gender had a moderating effect on consumer green sports behavior.

Immune cells utilize the IDO enzymatic conversion of trp to kyn to determine T-cell activation vs. anergy/apoptosis. In prior studies, urine IDO levels were higher in rejecting renal allografts than in stable state. However, urine IDO levels in healthy subjects or children are unknown. As a corollary to a larger longitudinal and prospective study of serum and urine IDO levels for transplant immune monitoring, here, we analyzed the difference between urine IDO levels in stable post-transplant vs. healthy children. IDO levels were measured by tandem mass spectrometry and expressed as kyn/trp ratios. We compared one-time urine samples, from 34 well children at general pediatric clinics, to the first-month post-transplant urine samples from 18 children, while in stable state (no acute rejection or major infection event in next 30 days). Urine kyn/trp ratios were significantly higher in stable children in first-month post-kidney transplant (median 16.6, range 3.9-44.0) vs. healthy children (median 9.2, range 3.51-17.0; p = 0.0057 by nonparametric Mann-Whitney test). Higher urine IDO levels even with stable transplant suggest a continuous ongoing low-grade allorecognition/inflammatory process. Our data also provide baseline urine IDO levels in healthy subjects for use in future studies.

PURPOSE To describe the utility of microperimetry testing in the diagnosis of a bilateral occipital stroke. METHODS Retrospective case report. RESULTS A 57-year-old male with hypertension presented with complaints of bilateral blurred central vision and bilateral hypertensive retinopathy with cotton-wool spots. Automated perimetry demonstrated a central scotoma in both eyes that did not respect the vertical midline; however, microperimetry testing revealed a bilateral homonymous hemianopia that suggested cerebrovascular disease which was subsequently confirmed with magnetic resonance imaging. DISCUSSION In cases of unexplained central visual loss, microperimetry testing may be a useful ancillary test for the diagnosis of cerebrovascular disease.

Purpose: To report a single case of paracentral acute middle maculopathy in association with retinal artery occlusion in the setting of ipsilateral facial cosmetic filler injection. Methods: Case report. Patient: A 35-year-old woman presenting with sudden vision loss to finger count vision immediately after left nasal fat pad cosmetic filler injection. Results: Dilated funduscopic examination revealed a swollen optic disc with multiple branch arterial occlusions with visible embolic material. Fluorescein angiography confirmed multiple branch arterial occlusions in addition to a focal choroidal infarction in the macula. Spectral-domain optical coherence tomography revealed middle retinal hyperreflectivity in the superotemporal macula consistent with paracentral acute middle maculopathy. En face optical coherence tomography demonstrated a superotemporal area of whitening at the level of the deep capillary plexus corresponding to the paracentral acute middle maculopathy lesion seen on spectral-domain optical coherence tomography. On twelve-month follow-up, final visual acuity was 20/100 due to optic neuropathy. Conclusion: Emboli from cosmetic facial filler injections may rarely result in ipsilateral arterial occlusions and now have a novel association with paracentral acute middle maculopathy likely due to deep capillary plexus feeder vessel occlusion.

To describe a surgical technique for fluorescein-assisted subretinal tissue plasminogen activator delivery during pars plana vitrectomy for submacular hemorrhage. Retrospective, interventional, consecutive case series. Six eyes of 6 patients were reviewed. Etiology of submacular hemorrhage was age-related macular degeneration in 2 eyes and polypoidal choroidal vasculopathy in 4 eyes. Twenty-three-gauge pars plana vitrectomy was performed and fluorescein-stained tissue plasminogen activator was injected in the subretinal space through a 41-gauge cannula in all eyes. Sulfur hexafluoride (SF6) gas (n = 5 eyes) or air (n = 1 eye) tamponade was instilled at the conclusion of surgery. Successful displacement of submacular hemorrhage was achieved in all eyes. Mean visual acuity improved from 20/693 preoperatively to 20/224 postoperatively (P = 0.14) at mean follow-up of 560 ± 464 days. No intraoperative or postoperative complications were encountered. Fluorescein-assisted subretinal delivery of tissue plasminogen activator was well tolerated and allowed for improved visualization of subretinal bleb formation during pars plana vitrectomy for submacular hemorrhage.

Introduction Despite recent advances in treatment, acute myeloid leukemia (AML) remains difficult to cure with high rates of relapse. Relapsed/refractory AML patients who are elderly or unfit for cytotoxic chemotherapy and whose disease fails to respond to hypomethylating agents represent an unmet need, and new safe and effective treatment options are needed for this patient population. Aspartate β-hydroxylase (ASPH) is a transmembrane protein that hydroxylates aspartyl and asparaginyl residues of epidermal growth factor (EGF)-like protein domains, and promotes cellular motility, migration, and adhesion. ASPH is highly expressed during fetal development and in placental trophoblasts, but not in any other healthy adult human tissue. ASPH is uniquely upregulated in cancer cells and is reported to be overexpressed in over 20 different solid neoplasms, in which it propagates a malignant phenotype, and is associated with increased cell proliferation, invasiveness, and poor prognosis. ASPH is therapeutically targetable via a fully human monoclonal antibody against ASPH, SNS-622. Subsequently, SNS-622 antibody-drug conjugates (ADCs) and a vaccine have been developed and are under current preclinical and clinical testing, respectively. We have previously demonstrated ASPH overexpression on the MOLM-14 AML cell line and effective in vitro killing of these cells using SNS-622 ADCs. In an effort to further characterize ASPH as a therapeutic target in AML, we report here the first study of ASPH expression patterns in AML patient samples. Methods Bone marrow (BM) aspirate and peripheral blood (PB) samples were collected from AML patients during 2014-2018 on a University of Maryland Greenebaum Comprehensive Cancer Center (UMGCCC) tissue banking protocol. Mononuclear cells were isolated by density centrifugation and were viably cryopreserved at -80ᵒC. Samples were analyzed using 8-color multiparameter flow cytometry to assess cell surface expression of ASPH, using fluorescein isothiocyanate (FITC)-conjugated SNS-622. The remainder of the fluorophores were labeled with standard lineage-specific markers. Expression of ASPH was measured via FITC fluorescence for each cell population and analyzed by two blinded, independent reviewers using FlowLogicTM software. Statistical analysis of ASPH expression was conducted using IBM® SPSS® Statistics for Windows, release 25.0.0 (IBM Corp., Armonk, N.Y., USA). Cohen's kappa (κ) was used to quantify the inter-observer agreement between two independent observers. Visual inspection of the expression data for the whole patient population showed a bimodal distribution, which was used to identify a robust cut-point separating high (i.e. positive) from low (i.e. negative) ASPH expression. Results Forty-two AML patient samples were evaluated (32 BM, 10 PB). Median patient age was 66 years, 48% (n=20) were female, 69% Caucasian and 21% African American. Disease status was 52% untreated de novo, 19% untreated secondary from antecedent MDS or MPN, and 29% relapsed/refractory. Samples were cytogenetically and molecularly diverse - with 50% exhibiting normal and 14% complex karyotype; 38% FLT3-ITD or FLT3-TKD, 29% NPM1, 19% IDH1/2, and 10% TP53 mutations. Full patient characteristics are shown in Table 1. Myeloblast expression of ASPH was found in 38% of samples (n=16; 14 BM, 2 PB) with a mean fluorescent intensity (MFI) of 10 as a cutoff for ASPH surface expression positivity. ASPH expression was not seen on other non-neoplastic cells including CD34+ hematopoietic stem cells, B- or T-lymphocytes, and monocytes. A blinded, independent review of the data revealed a Cohen's kappa (κ) of 0.74 with standard error of the estimate of ± 0.11. Patients with AML with ASPH expression were clinically heterogeneous, with no correlation between ASPH expression and AML subtype, karyotype or mutation status (Table 1). Conclusion ASPH is overexpressed in approximately 40% of patients with AML and serves as a promising therapeutic target. An ASPH nanoparticle vaccine is currently under clinical investigation and has shown promising results in solid tumors. We plan to expand clinical testing of targeting ASPH to AML. The ASPH positivity cutoff established via this work will serve as the eligibility criterion for the planned phase Ib/IIa of anti-ASPH vaccination in AML. . Disclosures Lebowitz: Sensei Biotherapeutics: Employment. Malhotra:Sensei Biotherapeutics: Employment. Fuller:Sensei Biotherapeutics: Employment. Shahlaee:Sensei Biotherapeutics: Equity Ownership; Sensei Biotherapeutics: Consultancy. Ghanbari:Sensei Biotherapeutics: Employment; Sensei Biotherapeutics: Equity Ownership. Emadi:NewLink Genetics: Research Funding.

Background Both acute rejection (AR) and major infection events (MIE) can reduce long-term allograft survival. We assessed the simultaneous efficacy of serum and urine biomarker indoleamine 2,3-dioxygenase (IDO) enzyme activity and peripheral blood CD4-ATP levels for AR and MIE association, respectively. Methods We prospectively tested 217 blood and 167 urine serial samples, collected monthly for 12 months after transplantation from 29 consecutive children receiving a kidney transplant. The indoleamine 2,3-dioxygenase activity was assessed by mass spectrometry assays using the ratio of product L-kynurenine (kyn) to substrate tryptophan (trp). Kyn/trp ratios and blood CD4 T-cell ATP levels were correlated with AR, MIE, or stable group (no events) in the next 30 days. Results Using absolute cutoffs and allocating to samples to AR, MIE, or stable group, mean serum kyn/trp ratios were significantly elevated in the group that experienced AR (P=0.0007). Similarly, peripheral blood CD4-ATP levels were significantly lower in the group experiencing MIE (P=0.0351). Urine kyn/trp ratios and blood tacrolimus levels were not different between AR and stable groups. Within-subject analyses, accounting for repeated measures in subjects, also showed that, over time, serum kyn/trp ratios were higher before AR (P=0.031) and blood CD4-ATP levels were lower before MIE (P=0.008). Conclusions These results from our pilot discovery group suggest that a panel of biomarkers together can predict overimmunosuppression or underimmunosuppression. Further independent validation in a multicenter cohort is suggested.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology with a complex pathogenesis involving multiple genetic and environmental contributions. Single-nucleotide polymorphisms (SNPs) in cytokine genes are associated with higher or lower cytokine activity, which can alter the susceptibility to certain diseases or their clinical outcomes. We investigated SNPs of the IL-1 family in Iranian SLE patients and normal individuals. We obtained blood samples from 207 SLE patients and 213 healthy controls. Cytokine genotyping was performed by polymerase chain reaction with sequence-specific primers. The following SNPs were assessed: IL-1A rs1800587, IL-1B rs16944 and rs1143634, IL-1R1 rs2234650 and IL-1RN rs315952. The frequency of the IL-1RN rs315952 CT genotype was significantly lower among patients with SLE compared with healthy controls (OR = 0.63, 95 % CI = 0.42–0.95; P

Objective: Coronary Artery Disease (CAD) would continue to concern medical society in the foreseeable future. Determining the extent of coronary luminal stenosis is a key factor in management of CAD. Methods presently used are costly and pose certain dangers, ranging from nephrotoxicity to death. Long Pentraxin or Pentraxin-3 (PTX3) has been used to predict survival or atherosclerotic process, but not to identify coronary stenosis. Calcium Score has been used to this end with some success. Methods: Individuals with chronic stable angina, without evidence of Myocardial Infarction (MI), who were categorized as intermediate-risk after completing a treadmill exercise test, according to Duke Protocol, underwent cardiac catheterization. In addition, blood samples were drawn for coronary sinus PTX3, and also PTX3, uric acid, high-sensitivity C-reactive protein (hs-CRP), cholesterol, glucose and High-Density Lipo-protein (HDL) in peripheral circulation. Calcium Scores were calculated using Agatston Score and non-contrast multi-slice CT scan. Participants were divided according to the number of stenotic coronary arteries (patent, one-, two-and three-vessel disease). Results: We found that PTX3 levels in coronary sinus and femoral vein correlated with each other, after log-transforming the values. Also we found that PTX3 levels and Calcium Scores differed among individuals with triple-vessel involvement and individuals without significant stenosis in any of coronary arteries. No significant differences were observed, regarding hs-CRP levels. Conclusion: PTX3 levels in periphery correlate with those in coronary arteries, and this variable can be measured with a less invasive procedure. In addition to Calcium Score, PTX3 levels are different in our four groups. The combined contribution of PTX3 and calcium score may help us identify individuals with significant coronary artery stenosis without needing to perform cardiac catheterization in a select group of patients.

BACKGROUND: We aimed to compare pain relief and safety of two doses of morphine in adult emergency department (ED) patients with acute limb trauma pain. METHODS: A total of 200 adult ED patients over 20 years of age requiring opioid analgesia were randomly allocated to two groups. Following a first dose of intravenous morphine sulfate at 0.10 mg/kg, a randomized double-blind placebo-controlled trial of intravenous morphine sulfate at 0.05 mg/kg versus the same amount of placebo was performed. Measurement of visual analogue scale pain intensity and assessment of adverse effects were performed at baseline (before morphine at 0.10 mg/kg), 30 minutes from baseline (just before study drug administration), and at 60 minutes from baseline (30 minutes after study drug). RESULTS: No significant difference was found between groups at 30 minutes from baseline. There was significant reduction in final pain after 1 hour in the 0.15 mg/kg compared to 0.10 mg/kg group (p

The ability to make informed benefit-risk assessments for potentially cardiotoxic new compounds is of considerable interest and importance at the public health, drug development, and individual patient levels. Cardiac imaging approaches in the evaluation of drug-induced myocardial dysfunction will likely play an increasing role. However, the optimal choice of myocardial imaging modality and the recommended frequency of monitoring are undefined. These decisions are complicated by the array of imaging techniques, which have varying sensitivities, specificities, availabilities, local expertise, safety, and costs, and by the variable time-course of tissue damage, functional myocardial depression, or recovery of function. This White Paper summarizes scientific discussions of members of the Cardiac Safety Research Consortium on the main factors to consider when selecting nonclinical and clinical cardiac function imaging techniques in drug development. We focus on 3 commonly used imaging modalities in the evaluation of cardiac function: echocardiography, magnetic resonance imaging, and radionuclide (nuclear) imaging and highlight areas for future research.