Respiratory Management of Patients with ALS in Northern New England

Background: • Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease caused by the degeneration of brain and spinal cord motor neurons, leading to steady loss of voluntary muscle function and early death from respiratory failure. •The incidence of ALS is 1?2/100,000 population, the prevalence is 5?6/100,000 and approximately 30,000 people are living with ALS in the United States. • Currently there is no cure for ALS; treatment is focused on symptomatic care and improving the quality of life. • Most ALS patients in the United States are treated either at multidisciplinary ALS centers/clinics in academic institutions or by community?based physicians/ neurology practices. • It is unclear if outcomes in patients with ALS are different among those followed in multidisciplinary clinics(MDC) versus community based physicians/ neurology practices (CP). • The goal of this project was to compare the type of respiratory education and care received by patients with ALS from Northern New England at MDC’s (Fletcher Allen and Dartmouth Medical Center) versus CP.https://scholarworks.uvm.edu/comphp_gallery/1029/thumbnail.jp

Nigrostriatal overabundance of α-synuclein leads to decreased vesicle density and deficits in dopamine release that correlate with reduced motor activity

α-Synuclein (α-syn) is a presynaptic protein present at most nerve terminals, but its function remains largely unknown. The familial forms of Parkinson's disease associated with multiplications of the α-syn gene locus indicate that overabundance of this protein might have a detrimental effect on dopaminergic transmission. To investigate this hypothesis, we use adeno-associated viral (AAV) vectors to overexpress human α-syn in the rat substantia nigra. Moderate overexpression of either wild-type (WT) or A30P α-syn differs in the motor phenotypes induced, with only the WT form generating hemiparkinsonian impairments. Wild-type α-syn causes a reduction of dopamine release in the striatum that exceeds the loss of dopaminergic neurons, axonal fibers, and the reduction in total dopamine. At the ultrastructural level, the reduced dopamine release corresponds to a decreased density of dopaminergic vesicles and synaptic contacts in striatal terminals. Interestingly, the membrane-binding-deficient A30P mutant does neither notably reduce dopamine release nor it cause ultrastructural changes in dopaminergic axons, showing that α-syn's membrane-binding properties are critically involved in the presynaptic defects. To further determine if the affinity of the protein for membranes determines the extent of motor defects, we compare three forms of α-syn in conditions leading to pronounced degeneration. While membrane-binding α-syns (wild-type and A53T) induce severe motor impairments, an N-terminal deleted form with attenuated affinity for membranes is inefficient in inducing motor defects. Overall, these results demonstrate that α-syn overabundance is detrimental to dopamine neurotransmission at early stages of the degeneration of nigrostriatal dopaminergic axon

Nigrostriatal overabundance of alpha-synuclein leads to decreased vesicle density and deficits in dopamine release that correlate with reduced motor activity

alpha-Synuclein (alpha-syn) is a presynaptic protein present at most nerve terminals, but its function remains largely unknown. The familial forms of Parkinson's disease associated with multiplications of the alpha-syn gene locus indicate that overabundance of this protein might have a detrimental effect on dopaminergic transmission. To investigate this hypothesis, we use adeno-associated viral (AAV) vectors to overexpress human alpha-syn in the rat substantia nigra. Moderate overexpression of either wild-type (WT) or A30P alpha-syn differs in the motor phenotypes induced, with only the WT form generating hemiparkinsonian impairments. Wild-type alpha-syn causes a reduction of dopamine release in the striatum that exceeds the loss of dopaminergic neurons, axonal fibers, and the reduction in total dopamine. At the ultrastructural level, the reduced dopamine release corresponds to a decreased density of dopaminergic vesicles and synaptic contacts in striatal terminals. Interestingly, the membrane-binding-deficient A30P mutant does neither notably reduce dopamine release nor it cause ultrastructural changes in dopaminergic axons, showing that alpha-syn's membrane-binding properties are critically involved in the presynaptic defects. To further determine if the affinity of the protein for membranes determines the extent of motor defects, we compare three forms of alpha-syn in conditions leading to pronounced degeneration. While membrane-binding alpha-syns (wild-type and A53T) induce severe motor impairments, an N-terminal deleted form with attenuated affinity for membranes is inefficient in inducing motor defects. Overall, these results demonstrate that alpha-syn overabundance is detrimental to dopamine neurotransmission at early stages of the degeneration of nigrostriatal dopaminergic axons

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Retinal Causes of a Neurologic-Type Visual Field Defect

Power point of case presentation of 47 year old female with history of breast cancer with new onset temporal visual field defect and photopsias. Differential diagnosis of homonymous hemianopia discussed; retinal causes of neurologic-type visual field defects reviewed including: white dot syndrome (multiple evanescent white dot syndrome), cancer- associated retinopathy, tamoxifen retinopathy, autoimmune retinopath

Validity and Acceptance of Color Vision Testing on Smartphones

Background: Ishihara color plates (ICP) are the most commonly used color vision test (CVT) worldwide. With the advent of new technologies, attempts have been made to streamline the process of CVT. As hardware and software evolve, smartphone-based testing modalities may aid ophthalmologists in performing more efficient ophthalmic examinations. We assess the validity of smartphone color vision testing (CVT) by comparing results using the Eye Handbook (EHB) CVT application with standard Ishihara color plates (ICP). Methods: Prospective case-control study of subjects 18 years and older with visual acuity of 20/100 or better at 14 inches. The study group included patients with any ocular pathology. The color vision deficient (CVD) group was patients who failed more than 2 plates. The control group had no known ocular pathology. CVT was performed with both ICP and EHB under standardized background illuminance. Eleven plates were tested with each modality. Validity of EHB CVT and acceptance of EHB CVT were analyzed. Statistical analyses were performed using Bland-Altman plot with limits of agreement (LOA) at the 95th percentile of differences in score, independent samples t tests with 95% confidence interval (CI), and Pearson χ tests. Results: The Bland-Altman plot showed agreement between correct number of plates in EHB and ICP for the study subjects (bias, -0.25; LOA, -1.92 to 1.42). Agreement was also observed between the correct number of plates in EHB and ICP for the controls (bias, -0.01; LOA, -0.61 to 0.59) and CVD (bias, -0.50; LOA, -4.64 to 3.64) subjects. The sensitivity of EHB was 0.92 (95% CI 0.76-1.07) and the specificity of EHB was 1.00 (95% CI 1.00-1.00). Fifty-nine percent preferred EHB, 12% preferred ICP, and 29% had no preference. Conclusions: In healthy controls and patients with ocular pathology, there was an agreement of CVT results comparing EHB with ICP. Overall, the majority preferred EHB to ICP. These findings demonstrate that further testing is required to understand and improve the validity of smartphone CVT in subjects with ocular pathology

Neuromyelitis Optica

Power point of case presentation of female with bilateral, sequential atypical optic neuritis. MRI Brain normal with no demyelination; MRI Spine shows enhancement at multiple levels and NMO antibody positive, confirming diagnosis of neuromyelitis optica (NMO). History of NMO discussed, diagnostic criteria, prognosis, and treatment options

Non-Organic Visual Loss

Power point of case presentation of 12 year old girl with recurrent monocular visual loss. Examination is normal. Differential diagnosis discussed, including non-organic visual loss. Diagnostic testing for non-organic visual loss reviewed. Slide 4: Figure 1: Table of exam findings Slide 5: Figure 2: Table of exam findings continued Slide 16: Figure 3: Diagram of visual angle (Taken from http://wiki.bethanycrane.com/introducingtheeye) Slide 17: Figure 4: Menace reflex - blinking in response to threat Slide 18: Figure 5: Signature testing Slide 19: Fig 6 (top): Proprioception testing ; Figure 7 (bottom): Optokinetic drum testing Slide 20: Fig 8: Fogging test with a phoropter (Taken from: Chen CS, Lee AW, Karagiannis A, Crompton JL, Selva D. Practical clinical approaches to functional visual loss. J Clin Neurosci. 2007 Jan;14(1):1-7.) Slide 21: Fig 9: Worth 4-dot fusional testing (Taken from: http://foresighteyes.com/productdepth.html) Slide 22: Fig 10: Stereoscopic testing (Taken from: http://www.starophthalmic.com/store/shop/index.php?cPath=80_157) Slide 23: Fig 11: Diplopia testing with prisms for non-organic visual loss (Taken from: Chen CS, Lee AW, Karagiannis A, Crompton JL, Selva D. Practical clinical approaches to functional visual loss. J Clin Neurosci. 2007 Jan;14(1):1-7.

Infraorbital dark circles: A review of the pathogenesis, evaluation and treatment

Infraorbital dark circles represent a common and multifactorial challenge in the world of aesthetic medicine and are the result of a variety of factors including deep facial anatomy, soft tissue changes, as well as contributions from the skin. A variety of treatment options exist, and a customised management strategy can be developed for the particular anatomic changes present. A literature search using MEDLINE and non-MEDLINE sources was performed utilising keywords including: 'Dark circles' 'infraorbital dark circles', 'infraorbital pigment', 'under-eye circles' and 'lower eyelid bags'. A comprehensive review of the literature was performed and the data were assimilated with evidence from our practice. This review provides a detailed discussion of the aetiology, pathogenesis, evaluation and management of infraorbital dark circles. An understanding of the deep and superficial anatomy is crucial to the management of this complex entity. The armamentarium for treatment includes minimally invasive interventions such as makeup and cosmeceuticals, a variety of laser and chemical treatments, fillers and fat transfer, as well as more invasive surgical manoeuvres

Prevalence and severity of ocular surface Neoplasia in African nations and need for early interventions

Ocular surface squamous neoplasia (OSSN) is a common ocular surface tumor with an increased incidence in African countries (3.4 and 3.0 cases/year/100,000). Despite its potential for vision loss and death, OSSN remains largely neglected by both eye and HIV care programs in Africa. The purpose of this review is to identify the barriers to timely diagnosis and early interventions for OSSN in Africa. PubMed searches were conducted targeting previous use of topical chemotherapy (interferon alpha 2b, Mitomycin-C, 5-Fluorouracil) and Human papillomavirus (HPV) vaccination in Africa. We found that OSSN is a significant vision and life-threatening health problem in Africa leading to significant loss of vision, as well as facial disfigurement and social stigma. We did not find any reports on the use of topical interferon, Mitomycin-C or HPV vaccination for OSSN in Africa. One report on the use of topical 5-FU for OSSN in Africa was found. Common barriers to early detection and management of OSSN in Africa include lack of sufficient laboratory infrastructure, lack of trained healthcare personnel, lack of compliance with follow-up visits, cost of topical chemotherapies, and cultural preferences for traditional medicines. In conclusion, OSSN is a significant vision and life-threatening health problem in Africa. There is not much literature on prevention or treatment options for early stages of OSSN in Africa. The use of topical chemotherapy as early interventions and judicious use of smart phone Apps to help with remote diagnosis of early OSSN should be further explored