A multidisciplinary approach and consensus statement to establish standards of care for Angelman syndrome.

BACKGROUND: Angelman syndrome (AS) is a rare neurogenetic disorder present in approximately 1/12,000 individuals and characterized by developmental delay, cognitive impairment, motor dysfunction, seizures, gastrointestinal concerns, and abnormal electroencephalographic background. AS is caused by absent expression of the paternally imprinted gene UBE3A in the central nervous system. Disparities in the management of AS are a major problem in preparing for precision therapies and occur even in patients with access to experts and recognized clinics. AS patients receive care based on collective provider experience due to limited evidence-based literature. We present a consensus statement and comprehensive literature review that proposes a standard of care practices for the management of AS at a critical time when therapeutics to alter the natural history of the disease are on the horizon. METHODS: We compiled the key recognized clinical features of AS based on consensus from a team of specialists managing patients with AS. Working groups were established to address each focus area with committees comprised of providers who manage >5 individuals. Committees developed management guidelines for their area of expertise. These were compiled into a final document to provide a framework for standardizing management. Evidence from the medical literature was also comprehensively reviewed. RESULTS: Areas covered by working groups in the consensus document include genetics, developmental medicine, psychology, general health concerns, neurology (including movement disorders), sleep, psychiatry, orthopedics, ophthalmology, communication, early intervention and therapies, and caregiver health. Working groups created frameworks, including flowcharts and tables, to help with quick access for providers. Data from the literature were incorporated to ensure providers had review of experiential versus evidence-based care guidelines. CONCLUSION: Standards of care in the management of AS are keys to ensure optimal care at a critical time when new disease-modifying therapies are emerging. This document is a framework for providers of all familiarity levels.

Comparison of Two Photoscreeners in a Population of Syrian Refugee Children.

PURPOSE: To evaluate children in the Za'atari refugee camp in Jordan to better understand the prevalence of ocular pathology and to compare two photoscreening devices to evaluate their utility. METHODS: Families at the Syrian American Medical Society Clinic were offered vision screening for children aged 1 to 18 years. Participants were offered visual acuity measurement and photoscreening with two devices approved for use in the United States. If visual acuity in either eye was worse than 20/40 or either photoscreening device indicated possible pathology, a complete eye examination was performed with cycloplegic refraction and dilated examination. RESULTS: Ninety-one participants completed the screening protocol. The average age of participants who completed the study was 7.8 years (range: 1 to 16 years). Twenty-eight participants (30.8%) failed at least one screening component. In this population, the following pathology was identified: astigmatism (12.1%), esotropia (9.9%), amblyopia (9.9%), hyperopia (7.7%), exotropia (3.3%), and myopia (1.1%). The Plusoptix vision screener (Plusoptix) had a sensitivity of 100% for the identification of amblyopia and 85% specificity. The GoCheck Kids application (Gobiquity) had a sensitivity of 66.67% for the identification of amblyopia and 94% specificity. The positive predictive value for the Plusoptix vision screener and the GoCheck Kids application for the detection of amblyopia risk factors was 77% for both. CONCLUSIONS: The high rate of ophthalmic pathology identified in this study reinforces the urgent need for proper vision screening and intervention in this population. [J Pediatr Ophthalmol Strabismus. 2021;58(6):396-400.].

Cell Phone Selfies: Clinching the Diagnosis of Iris Microhemangiomatosis.

Four patients presented with a history of "blood" or a "dark spot" in the eye captured on cell phone photos. These episodes prompted presentation to an ophthalmologist where they all had normal slit lamp exams without a hyphema at initial evaluation. With evidence of a spontaneous hyphema seen on photos, further testing was performed including iris fluorescein angiography which revealed hyperfluorescent iris margin vascular tufts, confirming the diagnosis of iris microhemangiomatosis in each patient. All cases were managed conservatively, and only 1 needed topical antihypertensives. Without these patient-initiated photos, the diagnosis of iris microhemangiomatosis would likely remain elusive as slit lamp exam was normal at the time of initial examination in all 4 cases. Ophthalmologists should be aware of this rare diagnosis in the event a patient comes with a cell phone selfie documenting a spontaneous hyphema, especially when emanating from pupillary border.

Clinical and demographic differences between idiopathic intracranial hypertension patients with mild and severe papilledema.

PURPOSE: The purpose of this study was to evaluate whether papilledema severity is associated with specific demographic or clinical factors in patients with idiopathic intracranial hypertension (IIH). MATERIALS AND METHODS: A retrospective cohort study of consecutive IIH patients seen at one tertiary care institution between 1989 and March 31, 2017 was performed. IIH patients were classified as mild (Frisén Grade 1 or 2) or severe (Frisén Grade 4 or 5) based on grading of fundus photographs obtained at first presentation. Demographic and clinical variables including age, body mass index (BMI), gender, visual acuity, Humphrey visual field mean deviation, and cerebrospinal fluid (CSF) opening pressure were extracted from patient medical records for statistical analyses. RESULTS: A total of 239 patients were included in the study: 152 with mild papilledema and 87 with severe papilledema. There was no difference in age, race, BMI, or male gender between the mild and severe papilledema groups. CSF opening pressure was significantly higher in the severe papilledema group (41.89 cm of water vs. 33.69, 95% confidence interval [CI]: -10.79--5.62, P < 0.0001). There was a significant difference in the Humphrey mean deviation (-6.38 dB compared to - 3.25 dB, 95% CI: -4.82--1.44 dB, P < 0.001) and average logarithm of the minimum angle of resolution visual acuity at final follow-up (0.21 vs. 0.045, 95% CI: -0.299--0.040 , P = 0.01). CONCLUSION: Age, race, sex, and BMI were similar in IIH patients with mild versus severe papilledema, emphasizing the importance of a dilated fundus examination to reliably stratify patients. Patients with severe papilledema are at higher risk of visual acuity and visual field loss at final follow-up.

Addition of arabinoxylan and mixed linkage glucans in porcine diets affects the large intestinal bacterial populations.

PURPOSE: To investigate the effects of two cereal soluble dietary fibres (SDF), wheat arabinoxylan (AX) and oat-mixed linkage glucans (MLG), on fermentative end-products and bacterial community profiles of the porcine caecum (Cae) and distal colon (DC). We hypothesised that feeding pigs these SDF would stimulate Cae and DC carbohydrate fermentation, resulting in a modification of the resident bacterial communities. METHODS: Five groups of six pigs were each fed one diet based on wheat starch (WS) only, or treatment diets in which some WS was replaced by 10 % AX, or 10 % MLG, a combination of 5 % AX:5 % MLG (AXMLG), or completely replaced with ground whole wheat. Post-euthanasia, Cae and DC digesta were collected for analysis of fermentative end-products, and bacterial community profiles were determined by 16S rRNA gene amplicon 454 pyrosequencing. RESULTS: Across all the SDF-containing diets, predominantly in the proximal region of the large intestine, Prevotella, Lactobacillus, Mitsuokella and Streptococcus were most significantly influenced (P < 0.05), while notable changes were observed for the Ruminococcaceae and Lachnospiraceae families in the Cae and DC. The addition of MLG or AXMLG had the greatest effect of influencing bacterial profiles, reducing sequence proportions assigned to the genus Clostridium, considered detrimental to gut health, with associated increases in short-chain fatty acid and reduced ammonia concentrations. CONCLUSIONS: This study demonstrated how the cereal SDF AX and MLG altered the large intestinal bacterial community composition, particularly proximally, further giving insights into how diets rich in specific complex carbohydrates shift the bacterial population, by increasing abundance and promoting greater diversity of those bacteria considered beneficial to gut health.

Comparing distance visual acuity measurement with a novel eye chart and the Landolt C chart in a population of children aged 6-18 years.

PURPOSE: The Handy Eye Chart™ is designed to assist in evaluating the visual acuity of patients with non-standard communication styles. The Handy Eye Chart™ has been previously validated against the early treatment diabetic retinopathy study (ETDRS) chart. The aim of this research is to compare visual acuity outcomes with The Handy Eye Chart™ against the international gold standard, the Landolt C chart, in a population of children. METHODS: Sixty participants between the ages of 6 and 18 were recruited at the Pediatric Section of the Department of Ophthalmology at the Emory Eye Center. Visual acuity was evaluated using The Handy Eye Chart™ and the Landolt C Chart, altering the order of administration between charts. The visual acuity data were compared using t test, linear regression, and Bland-Altman analysis. RESULTS: The mean difference in visual acuity was 0.02 logMAR (CI 0.009-0.04, p = 0.002). The correlation coefficient was 0.98. The Bland-Altman analysis shows the 95% limits of agreement between the charts to be -0.14 to 0.09 logMAR. CONCLUSIONS: The Handy Eye Chart™ is a valid measure of visual acuity when compared with the international gold standard, the Landolt C Chart.

Retinoinvasive Uveal Melanoma: Report of 2 Cases and Review of the Literature.

PURPOSE: To describe the clinical history and histopathologic findings of 2 cases of retinoinvasive uveal melanoma. METHODS: The medical records and pathology specimens of 2 patients with retinoinvasive uveal melanoma were reviewed. RESULTS: The first patient had an iris/ciliary body melanoma that was treated and the second patient had suspected iridocorneal endothelial syndrome. Both patients developed a blind, painful eye; the first patient's right eye was enucleated and the left eye of the second patient underwent evisceration. Histopathologic examination of the enucleated eye showed a tumor composed of minimally pigmented spindle-shaped cells with fusiform nuclei and prominent nucleoli and round cells with prominent nucleoli. The tumor cells invaded into the retina where they formed perivascular aggregates. Examination of the evisceration specimen showed a proliferation of pigmented tumor cells within the stroma of one iris leaflet. The tumor cells extended onto the ciliary body and vitreous base and invaded the retina. The pathologic diagnosis in both patients was retinoinvasive uveal melanoma. CONCLUSIONS: Careful funduscopic and imaging examination should be performed in eyes with unilateral glaucoma with iris/ciliary body lesions, and enucleation, rather than evisceration, should be performed, as retinoinvasive melanoma is in the differential diagnosis.

Comparison of the Handy Eye Chart and the Lea Symbols Chart in a population of deaf children aged 7-18 years.

PURPOSE: To compare the results of visual acuity testing in a population of deaf children using the Handy Eye Chart versus the Lea Symbols Chart and to compare testability and preference between charts. METHODS: A total of 24 participants were recruited at the Atlanta Area School for the Deaf. Visual Acuity was evaluated using the Handy Eye Chart and the Lea Symbols Chart. Patient preference and duration of testing were measured. RESULTS: The mean difference between the visual acuity as measured by each chart was -0.02 logMAR (95% CI, -0.06 to 0.03). Testing with the Handy Eye Chart was an average of 13.79 seconds faster than testing with the Lea Symbols Chart (95% CI, 1.1-26.47; P = 0.03). Of the 24 participants, 17 (71%) preferred the Handy Eye Chart (95% CI: 49%-87%; P = 0.07). CONCLUSIONS: The Handy Eye Chart is a fast, valid, and useful tool for measuring visual acuity in deaf children age 7-18 years. Additional research is needed to evaluate the utility of the Handy Eye Chart in younger children and deaf adults.

Intactness of cell wall structure controls the in vitro digestion of starch in legumes.

Increasing the level of starch that is not digested by the end of the small intestine and therefore enters the colon ('resistant starch') is a major opportunity for improving the nutritional profile of foods. One mechanism that has been shown to be successful is entrapment of starch within an intact plant tissue structure. However, the level of tissue intactness required for resistance to amylase digestion has not been defined. In this study, intact cells were isolated from a range of legumes after thermal treatment at 60 °C (starch not gelatinised) or 95 °C (starch gelatinised) followed by hydrolysis using pancreatic alpha amylase. It was found that intact cells, isolated at either temperature, were impervious to amylase. However, application of mechanical force damaged the cell wall and made starch accessible to digestive enzymes. This shows that the access of enzymes to the entrapped swollen starch is the rate limiting step controlling hydrolysis of starch in cooked legumes. The results suggest that a single cell wall could be sufficient to provide an effective delivery of starch to the large intestine with consequent nutritional benefits, provided that mechanical damage during digestion is avoided.

Reliability of ion accumulation and growth components for selecting salt tolerant lines in large populations of rice.

Ion accumulation and growth under salt stress was studied in two experiments in a rice mapping population derived from parents CO39 and Moroberekan with 4-fold differences in shoot Na+ accumulation. The 120 recombinant inbred lines (RILs) had differences up to 100-fold in Na+. Measurement of 'salt tolerance' (biomass production of the RILs in 100mM NaCl relative to controls) after 42 days showed a 2-fold variation in 'salt tolerance' between parents, with five RILs being more tolerant than the more tolerant parent CO39. The reliability of various traits for selecting salt tolerance in large populations was explored by measuring Na+, K+ and K+/Na+ ratios in leaf blades and sheaths after 7 or 21 days of exposure to 100mM NaCl, and their correlation with various growth components and with leaf injury. The highest correlations were found for Na+ in the leaf blade on day 21 with injury at day 42 in both experiments (r=0.7). Earlier measurements of Na+ or of injury had lower correlations. The most sensitive growth components were tiller number plant-1 and shoot water content (g water g-1 dry weight), and these were correlated significantly with Na+ and, to a lesser extent, with K+/Na+. These studies showed that exposure for at least 42 days may be needed to clearly demonstrate the beneficial effect of the trait for Na+ exclusion on growth under salinity.

The utilization of bicycles in the delivery of emergency medical services : A preliminary report

Introductions: Bicycles may be useful in the delivery of out-of-hospital emergency medical services. The use of bicycles in providing emergency medical services was investigated by surveying currently existing bicycles systems. Methods: Two questionnaires were developed to again information on service areas, injuries, gear used, missions and specific data from bicycles-medic response. Results: Of 210 surveys mailed to bicycle-medics, 21 (10

) were completed and returned by the pre-established deadline. Of returned by the pre-established deadline. Of 11 surveys mailed to bicyvle-medics supervisors, four (36

) were returned. Preliminary results showed that 76

of respondents are career providers and the remainder serve as volunteers. Conclusion: This survey begins to characterize the utilization of bicycles as a tool to gain patient access in specialized situations. The use of bicycle-medics may be cost-effective, may help to improve employee marale, and possibly reducee employee health-care costs. Further study is needed to determine the impact of bicycle-medics on patient outcomes and response times (AU)

Changes of water-relation characteristics and levels of organic cytoplasmic solutes during salinity induced transition of Mesembryanthemum crystallinum from C3-photosynthesis to crassulacean acid metabolism.

NaCl was added to the nutrient solution of 4-6-week old Mesembryanthemum crystallinum plants so that the concentration rose by 50 mM per day. Ten to fifteen days after a concentration of 400 mM was reached, pronounced diurnal oscillations of malate levels indicated that plants had changed from C3-photosynthesis to crassulacean acid metabolism (CAM). Due to the NaCl-treatment the solute potential (Ψs) decreased from about -6 bar to -25 bar, and the water potential (Ψ) changed from about -5 bar to -23 bar on average. Ψ showed small diurnal oscillations both in controls and NaCl-treated plants, with an amplitude of 1 to 3 bar, the value at the end of the dark phase being less negative than that at the end of the light phase. Changes of ion levels due to the NaCl-treatment were average increases in Na+ and Cl- from 10-20 to 370-470 mmol kg-1 FW and from below 10 to 280-325 mmol kg-1 FW, respectively, and a decrease in K+ from 70-80 to 25 mmol kg-1 FW. These changes of ion levels corresponded very closely to an increase of dry weight in per cent of fresh weight observed during the NaCl-treatment (e.g. a change of 2% in one experiment), and osmotically they matched the measured change in Ψs (e.g. about 18-20 bar in one experiment).Most of the organic solutes analysed did not show any significant changes as a result of the NaCl-treatment. The following compounds were identified within the respective ranges of concentrations: mannitol (0.2 to 0.5 mmol kg-1 FW), sum of quaternary ammonium compounds (60 to 140 mg kg-1 FW), choline (0.1 to 0.4 mmol kg-1 FW), betaine (0.3 to 0.7 mmol kg-1 FW), hexoses (2-9 mmol kg-1 FW), pentoses (1-5 mmol kg-1 FW) and sucrose (2-4 mmol kg-1 FW). The levels of proline and of total amino acids minus proline rose during the NaCl-treatment from 0.1-1 mmol kg-1 FW to 2.5-5 mmol kg-1 FW and from 2.5-4 mmol kg-1 FW to 6-8 mmol kg-1 FW, respectively.The changes of Ψs and Ψ, and of Na+- and Cl--levels were complete, and new steady levels were attained by the time 400 mM NaCl was reached in the nutrient solution, i.e. many days before pronounced diurnal malate oscillations indicated that the change from C3-photosynthesis to CAM had occurred. The attainment of new steady levels of proline and K+, however, was much slower and coincided with the onset of CAM.