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Competing Interests: The authors report no conflicts of interest.

Background: Age-related distance esotropia (ARDE), is an acquired, small, comitant esodeviation that is greater at distance than at near. It occurs in older adult patients without a history of neurological event or prior strabismus. It has been observed more frequently in White adults than in other racial groups. The purpose of this study was to assess the demographic and clinical characteristics of patients with ARDE presenting at a tertiary neuro-ophthalmology clinic., Methods: In this retrospective study, ICD-9/10 (ICD-9 378.85 and ICD-10 H51.8) codes were used to identify all patients with ARDE from 2005 to 2020 seen in a single tertiary neuro-ophthalmology clinic. ARDE was defined as esotropia greater at distance than near with associated clinical signs of adnexal tissue laxity. Patients with history or findings compatible with other etiologies of strabismus, such as thyroid eye disease, neuromuscular disorders, sensory deviations, sudden onset of diplopia, and high myopia, as well as those with prior strabismus surgery, were excluded., Results: A total of 89 patients (59 females [66%]) met inclusion criteria. Mean patient age was 76.6 years. All patients were White except for a single patient of African descent. Mean follow-up time was 25.2 months. Mean esodeviation at distance on presentation was 6.6 Δ . Of the 87 patients electing nonsurgical treatment, 80 achieved remission of diplopia symptoms with prism therapy alone. Of the 89 patients, 59 had no neuroimaging., Conclusions: ARDE in our neuro-ophthalmology clinic population was diagnosed almost exclusively in older White adults. Prism therapy was effective for a majority of our patients., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: To evaluate the accuracy and safety of oral fluorescein angiography (OFA) in differentiating papilledema from pseudopapilledema in pediatric patients., Design: Retrospective evaluation of a diagnostic test., Methods: We retrospectively reviewed medical records of all children ≤18 years of age who presented to the Arkansas Children's Hospital between May 2018 and August 2021 with suspected optic disc (OD) swelling that had OFA and images >30 minutes after oral ingestion. Two masked specialists interpreted the images as either OD leakage, no leakage, or borderline leakage. Optic disc swelling was graded clinically according to the Frisen grading scale (0-5). We compared OFA images to the final clinical diagnosis and calculated the accuracy of the test as follows: (number of eyes correctly identified as papilledema [true positive] + number of eyes correctly identified as pseudopapilledema [true negative]) / (total number of eyes) × 100%., Results: Forty-five patients (90 eyes) were included, 11 patients with papilledema and 34 with pseudopapilledema. The mean age was 14.1 ± 3.5 years; 66.7% were female. The accuracy of OFA was 62% for reviewer 1 and 69% for reviewer 2. No ocular or systemic side effects after OFA were observed. There was substantial agreement (k = 0.779) between both reviewers in grading the OFA images., Conclusion: OFA cannot definitively distinguish papilledema from pseudopapilledema in children and should be interpreted in conjunction with other clinical findings., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The evaluation and management of vertical strabismus is more challenging and nuanced than that of horizontal strabismus. Vertical strabismus often results from a variety of restrictive or paretic causes, which can be further characterized as either acquired or congenital. In some cases, identifying the correct etiology of the strabismus can mean uncovering a potentially life-threatening condition, such as a brain tumor or stroke. The keys to identifying the correct diagnosis are, first and foremost, a careful history, and secondly, a detailed examination. The characteristics, etiologies, and evaluation of vertical strabismus will be reviewed here.

Competing Interests: The authors report no conflicts of interest.

Purpose: To determine a safe timeframe and parameters for performing cataract surgery after diagnosis and treatment of giant cell arteritis (GCA)., Setting: Single institution in the United States., Design: Retrospective chart review., Methods: This retrospective study used ICD-9/10 and Current Procedural Terminology codes to identify all patients with biopsy-proven GCA who underwent cataract surgery from 2005 to 2019 at a single institution. Excluded from the study were patients whose date of biopsy diagnosis or dose of corticosteroids at the time of cataract surgery was unknown., Results: Chart review identified 15 eyes of 10 patients that met inclusion criteria; 80% of patients were women, and mean age was 74.4 years. Two patients had a history of arteritic ischemic optic neuropathy. There were no perioperative or postoperative complications in the 15 eyes that underwent cataract surgery with varying doses of prednisone at the time of surgery (1 to 25 mg daily prednisone ± 10 to 25 mg weekly methotrexate; median prednisone dose of 10.75 mg) and varying time from biopsy diagnosis of GCA to surgery of at least 7 months (median 13.75 months)., Conclusions: Cataract surgery seemed safe for patients with GCA on varying doses of prednisone at the time of surgery at least 7 months from time of biopsy diagnosis. There is a need for a larger cohort of data from neuro-ophthalmologists and cataract surgeons nationally to establish guidelines for safe cataract surgery in patients with GCA., (Copyright © 2020 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Motivation deficits are a prominent feature of schizophrenia and have substantial consequences for functional outcome. The impact of amotivation on exploratory behaviour has not been extensively assessed by entirely objective means. This study evaluated deficits in exploratory behaviour in an open-field setting using wireless motion capture. Twenty-one stable adult outpatients with schizophrenia and twenty matched healthy controls completed the Novelty Exploration Task, in which participants explored a novel environment containing familiar and uncommon objects. Objective motion data were used to index participants' locomotor activity and tendency for visual and tactile object exploration. Clinical assessments of positive and negative symptoms, apathy, cognition, depression, medication side-effects, and community functioning were also administered. Relationships between task performance and clinical measures were evaluated using Spearman correlations, and group differences were evaluated using multivariate analysis of covariance tests. Although locomotor activity and tactile exploration were similar between the schizophrenia and healthy control groups, schizophrenia participants exhibited reduced visual object exploration (F(2,35)=3.40, p=0.045). Further, schizophrenia participants' geometric pattern of locomotion, visual exploration, and tactile exploration were correlated with overall negative symptoms (|ρ|=0.46-0.64, p<=0.039) and apathy (|ρ|=0.49-0.62, p<=0.028), and both visual and tactile exploration were also correlated with community functioning (|ρ|=0.46-0.48, p<=0.043). The Novelty Exploration Task may be a valuable tool to quantify exploratory behaviour beyond what is captured through standard clinical instruments and human observer ratings. Findings from this initial study suggest that locomotor activity and object interaction tendencies are impacted by motivation, and reveal deficits specifically in visual exploration in schizophrenia., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Nasopharyngeal carcinoma (NPC) is a common viral-associated neoplasm in which multiple signaling cascades are interfered with by Epstein-Bar virus (EBV) latent proteins and various genetic alterations. Aside from the previously reported PIK3CA amplification, we examined the role of INPP4B, a negative regulator of the PI3K/AKT signaling pathway in the development of NPC. By RT-PCR and Western blotting, we revealed that the expression of INPP4B was down-regulated in all five established EBV-positive tumor lines. While INPP4B was consistently expressed in normal nasopharyngeal epithelial cells, downregulation of INPP4B was found in 32/65 (49.2%) of primary tumors by immunohistochemistry. Furthermore, our study also demonstrated the hypermethylation of the 5'CpG island of INPP4B in the tumors in which INPP4B transcription was downregulated. Notably, the re-expression of INPP4B was detected in the NPC cells treated with the demethylation agent (5-aza-2'deoxycytidine). Our study showed that promoter hypermethylation was the major mechanism for transcriptional silencing of INPP4B in NPC. Furthermore, restoration of INPP4B expression significantly suppressed PI3K/AKT downstream signals in the NPC C666-1 cells. In vivo growth inhibition was clearly demonstrated in the tumor cells stably expressing INPP4B. The findings indicate that epigenetic inactivation of INPP4B is one of the key mechanisms in activating PI3K/AKT signaling cascade and playing a role in the tumorigenesis of NPC.

As a distinct type of head and neck cancer, non-keratinizing nasopharyngeal carcinoma (NPC) is closely associated with EBV infection and massive lymphoid infiltration. The unique histological features suggest that local inflammation plays an important role in NPC tumourigenesis. We comprehensively characterized NF-κB signalling, a key inflammatory pathway which might contribute to the tumourigenesis of this EBV-associated cancer. By EMSA, western blotting, and immunohistochemical staining, constitutive activation of distinct NF-κB complexes, either p50/p50/Bcl3 or p50/RelB, was found in almost all EBV-positive NPC tumours. siRNA or chemical inhibition of NF-κB signalling significantly inhibited the growth of EBV-positive NPC cells C666-1. Gene expression profiling identified a number of NF-κB target genes involved in cell proliferation, apoptosis, immune response, and transcription. We further confirmed that p50 signals modulate the expression of multiple oncogenes (MYB, BCL2), chemokines, and chemokine receptors (CXCL9, CXCL10, CX3CL1, and CCL20). The findings support a crucial role of these constitutively activated NF-κB signals in NPC tumourigenesis and local inflammation. In addition to expression of the viral oncoprotein LMP1, genetic alteration of several NF-κB regulators (eg TRAF3, TRAF2, NFKBIA, A20) also contributes to the aberrant NF-κB activation in EBV-associated NPC. Except for LMP1-expressing C15 cells, all NPC tumour lines harbour at least one of these genetic alterations. Importantly, missense mutations of TRAF3, TRAF2, and A20 were also detected in 3/33 (9.1%) primary tumours. Taken together with the reported LTBR amplification in 7.3% of primary NPCs, genetic alterations in NF-κB pathways occurred in at least 16% of cases of this cancer. The findings indicate that distinct NF-κB signals are constitutively activated in EBV-positive NPC cells by either multiple genetic changes or EBV latent genes., (Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Background and Purpose: RSA can be used for early detection of unstable implants. We assessed the micromotion of the Mobility Total Ankle System over 2 years, to evaluate the stability of the bone-implant interface using radiostereometric analysis measurements of longitudinal migration and inducible displacement., Patients and Methods: 23 patients were implanted with the Mobility system. Median age was 62 (28-75) years and median BMI was 28.8 (26.0-34.5). Supine radiostereometric analysis examinations were done from postoperatively to the 2-year follow-up. Standing examinations were taken from the 3-month to the 2-year follow-up. Migrations and displacements were assessed using model-based RSA software (v. 3.2)., Results: The median maximum total point motion (MTPM) for the implants at 2 years was 1.19 (0.39-1.95) mm for the talar component and 0.90 (0.17-2.28) mm for the spherical tip of the tibial component. The general pattern for all patients was that the slope of the migration curves decreased over time. The main direction of motion for both components was that of subsidence. The median 2-year MTPM inducible displacement for the talar component was 0.49 (0.27-1.15) mm, and it was 0.07 (0.03-0.68) mm for the tibial component tip., Interpretation: The implants subside into the bone over time and under load. This corresponds to the direction of primary loading during standing or walking. This statistically significant motion may become a clinically significant finding that would correspond with premature implant failure.

Objectives: To find out and explore the knowledge and opinion of Chinese people on cardiovascular disease and awareness of cardiac rehabilitation., Design: A cross-sectional study using 14-item bilingual (Chinese and English) questionnaires that include information on demographics, health status, cardiovascular disease related knowledge and perception, and awareness and understanding of the cardiac rehabilitation programme., Setting: Chinese community groups in the Midlands, UK from January to April 2008., Participants: 436 questionnaires from Chinese adults over 18 were obtained., Main Outcome Measures: Current knowledge and attitude towards cardiovascular disease and awareness of cardiac rehabilitation., Results: Obesity was the most common risk factor identified by 80.7% of participants. Those originated from China had significantly less knowledge compared with subjects from other countries (p<0.001). People who have had exposure or experience of cardiac disease rated a higher risk of cardiac disease for Chinese living in the UK than people without experience. A majority (81.7%) used orthodox medicine and perceived it to be most effective against cardiac disease. Only 30% of participants were aware of cardiac rehabilitation., Conclusion: The coronary artery disease (CAD) risk factors of Chinese population have increased significantly in the last decade. Cardiac rehabilitation awareness was poor among the sample population of this study and language barrier is still a problem. More large studies on Chinese population assessing CAD risk should be done to provide more evidence on CAD prevention for this growing population in the Western world.

Background: The goal of this study was to design a RSA marker insertion protocol to evaluate the stability of the bone-implant interface of a TAA prosthesis, and to validate that this marker insertion protocol can be combined with MBRSA technology to provide clinically adequate precision in assessing the micromotion of the TAA prosthesis., Methods: The Mobility™ Total Ankle System was used in this study. A marker placement protocol was developed with a Phantom Protocol. The Improved Marker Placement Protocol was used in 20 patients. Postoperative RSA double exams were taken. Condition Numbers (CN) were used to assess the marker distribution. The system precision was defined as the standard deviation of the double exams (MTE, MRE). MBRSA software was used to evaluate the double exams., Results: The RSA marker insertion technique for the 20 {\it in vivo} cases provided satisfactory results. CNs in all subjects but one were below 50 mm(-1) and implied a desirable marker configuration. The tibial sphere MTE was 0.07 mm and the talar was 0.09 mm. The talar MRE was 0.51 degrees., Conclusion: The system precision for these {\it in vivo} TAA implants was within the normal range identified by RSA studies, and comparable to the existing TAA RSA studies. This study demonstrated a reliable RSA marker insertion technique in both the tibia and talus. The study confirms that the insertion and MBRSA technique allows the typical high precision demonstrated in other RSA studies (standard deviation less than or equal to 0.25 mm or 0.6 degrees)., Clinical Relevance: This method may allow more accurate assessment of prosthetic subsidence clinically.

The Physiological and Operative Severity Score for enUmeration of Mortality and morbidity (POSSUM) scoring systems have been designed for comparative audit and have been well validated in general and vascular surgery. The Portsmouth predictor equation (P-POSSUM) was highly predictive of mortality in a study of elective craniotomies for neurosurgery but has yet to be validated in spinal, peripheral nerve or acute cranial neurosurgery. The West Australian Categorisation of Operative Severity (WA classification) was created for all neurosurgical procedures. Case notes and laboratory results of 531 consecutive patients undergoing neurosurgery were reviewed retrospectively. All POSSUM variables were collected and the POSSUM and P-POSSUM mortality equations were applied. The observed mortality rate was 4.52% and the WA P-POSSUM predicted mortality rate was 4.58% (p>0.951). The WA P-POSSUM rate was more predictive than either the WA POSSUM rate (10.9%, p<0.0001) or the previously proposed elective craniotomy P-POSSUM classification (5.8%, p<0.198). We concluded that the P-POSSUM model with WA classification has the potential to be used in mortality audits for general neurosurgery. By quantifying preoperative risk, P-POSSUM might provide a useful denominator to observed death rates for meaningful comparison of individual neurosurgeons and between departments.

The hydrogen belts of membranes are defined as the regions consisting of hydrogen bond acceptors, i.e., the C=O groups of glycero- and sphingolipids, and hydrogen bond donors, i.e., cholesterol-OH, sphingolipid-OH, proteins, and water. Lipid-lipid hydrogen bonding in these belts has been suggested. The connection of such hypothetical bonding with the condensation effect, i.e., the apparent reduction of surface area occupied by phospholipids in mixed monolayers with cholesterol, has been tested with lipids possissing and lacking C=O groups: diester, diether, and dialkyl phosphatidylcholine, and analogous polyoxyethylene diglycerides. Condensation by cholesterol was observed for all lipids. Consequently, the hypothetical lipid-C=O-cholesterol hydrogen bonding is not a prerequisite for the condensation effect.

Three different sieve size fractions of ergot-containing biodegradable microcapsules were examined both in vitro and in vivo. The sieve sizes and average particle diameter, (micron), were: less than 45-75 (mean = 30); 75-106 (mean = 79); 106-177 (mean = 130). These microcapsules contained ca. 9% drug and were produced from 50:50 poly(DL-lactide-co-glycolide). The objective was to determine the effect of particle size on in vivo and in vitro degradation rates. The microcapsules were injected into rat gastrocnemius muscle and excised and examined at various time points up to 70 days. Initially a minimal tissue response was noted which was characterized by a sharply localized acute inflammatory reaction. Following this, connective tissue and foreign body giant cells engulfed the microcapsules at 20-30 days. Only vestiges of the microcapsules were found surrounded by minimal connective tissue and foreign body giant cells after 60-70 days. The tissue reaction was a minimal, sharply localized foreign body giant cell and connective tissue process for all three size groups of microcapsules. The largest microcapsules (mean = 130 microns) exhibited a slightly greater tendency to undergo in vivo and in vitro degradation relative to the other groups. However, it can be concluded that over the microcapsule size ranges examined minimal differences in the degradation properties of the polymeric matrices and consequently those of the microcapsules were noted.

The biodegradation of the copolymer 50:50 poly(DL-lactide-co-glycolide)-lypressin microcapsules was studied by light and electron microscopic methods and 14C release. Intramuscular injection sites of microcapsules in rats were studied by dissecting and conventional light microscopy as well as scanning (SEM) and transmission electron microscopy. A minimal localized acute myositis was seen initially at the injection sites. By Day 4, a few small foreign body giant cells were present participating in the minimal foreign body response. Later the inflammatory cells decreased and the individual microcapsules were walled off by immature fibrous connective tissue and large syncytial foreign body giant cells. By Day 35, definitive changes in some microcapsules, consisting of a granular and slightly eroded appearance of the internal matrix, were seen by SEM. By Day 42, the outer rims of the microcapsules were extensively eroded. At Day 56, the inflammatory and connective tissue reactions were almost completely resolved and biodegradation continued so that only remnant pieces of the microcapsules were present at Day 63. The morphologic picture correlated well with loss of 14C radioactivity, which could no longer be detected at the injection sites on Day 56. Phagocytosis did not seem to be an important factor in the biodegradation.