Healing Spaces: Feasibility of a Multisensory Experience for Older Adults with Advanced Dementia and their Caregivers

Healing Spaces proposes a new approach to multisensory interventions that show potential in ameliorating the behavioral and psychological symptoms of advanced dementia in older adults. Using smart technology, the project combines both digital and physical components to transform spaces and create unified, curated sensory experiences that provide meaningful context for interaction, and are easy for caregivers to deliver. A usability study was conducted for the Healing Spaces app followed by a feasibility evaluation of the full experience in a memory care facility recruiting caregivers, and residents in advanced stages of dementia. The feasibility evaluation successfully illuminated strengths as well as areas for improvement for the Healing Spaces experience in a memory care setting with older adults with advanced dementia. Caregivers and facility managers expressed interest in continuing to use Healing Spaces with the residents of the facility. Lessons learned about the technical and logistical implementation of Healing Spaces are discussed, as well as future directions for study design and potential therapeutic value of the experience.Comment: PETRA 20: Proceedings of the 13th ACM International Conference on PErvasive Technologies Related to Assistive Environments. June 2020. Article No 24. Pages 1 to

Acute panuveitis with hypopyon in Crohn's disease secondary to medical therapy: a case report

<p>Abstract</p> <p>Background</p> <p>A case report to highlight the association between rifabutin and hypopyon</p> <p>Methods</p> <p>A 56 year old male presented with a one day history of blurred vision in his right eye. He had an established diagnosis of Crohn's disease which was in remission following treatment with rifabutin and clarithromycin. A brisk anterior uveitis with hypopyon and a mild vitritis was detected in the right eye. The acute inflammatory episode resolved following treatment with topical corticosteroids and withdrawal of rifabutin.</p> <p>Results</p> <p>The presence of hypopyon is atypical in uveitis associated with inflammatory bowel disease. The association between rifabutin treatment and hypopyon uveitis is well recognised in Mycobacterium avium paratuberculosis. However, use of rifabutin in the management of Crohn's disease is controversial and not widely known to an ophthalmic readership.</p> <p>Conclusion</p> <p>This report highlights the importance of keeping abreast of novel therapeutic developments in systemic conditions likely to be encountered in ophthalmology.</p

Birdshot chorioretinopathy: current knowledge and new concepts in pathophysiology, diagnosis, monitoring and treatment

Birdshot chorioretinopathy (BCR) is a rare form of chronic, bilateral, posterior uveitis with a distinctive clinical phenotype, and a strong association with HLA-A29. It predominantly affects people in middle age. Given its rarity, patients often encounter delays in diagnosis leading to delays in adequate treatment, and thus risking significant visual loss. Recent advances have helped increase our understanding of the underlying autoimmune mechanisms involved in disease pathogenesis, and new diagnostic approaches such as multimodality imaging have improved our ability to both diagnose and monitor disease activity. Whilst traditional immunosuppressants may be effective in BCR, increased understanding of immune pathways is enabling development of newer treatment modalities, offering the potential for targeted modulation of immune mediators. In this review, we will discuss current understanding of BCR and explore recent developments in diagnosis, monitoring and treatment of this disease. Synonyms for BCR: Birdshot chorioretinopathy, Birdshot retinochoroiditis, Birdshot retino-choroidopathy, Vitiliginous choroiditis. Orphanet number: ORPHA179 OMIM: 605808

Choriocapillaris and Choroidal Microvasculature Imaging with Ultrahigh Speed OCT Angiography

We demonstrate in vivo choriocapillaris and choroidal microvasculature imaging in normal human subjects using optical coherence tomography (OCT). An ultrahigh speed swept source OCT prototype at 1060 nm wavelengths with a 400 kHz A-scan rate is developed for three-dimensional ultrahigh speed imaging of the posterior eye. OCT angiography is used to image three-dimensional vascular structure without the need for exogenous fluorophores by detecting erythrocyte motion contrast between OCT intensity cross-sectional images acquired rapidly and repeatedly from the same location on the retina. En face OCT angiograms of the choriocapillaris and choroidal vasculature are visualized by acquiring cross-sectional OCT angiograms volumetrically via raster scanning and segmenting the three-dimensional angiographic data at multiple depths below the retinal pigment epithelium (RPE). Fine microvasculature of the choriocapillaris, as well as tightly packed networks of feeding arterioles and draining venules, can be visualized at different en face depths. Panoramic ultra-wide field stitched OCT angiograms of the choriocapillaris spanning ~32 mm on the retina show distinct vascular structures at different fundus locations. Isolated smaller fields at the central fovea and ~6 mm nasal to the fovea at the depths of the choriocapillaris and Sattler's layer show vasculature structures consistent with established architectural morphology from histological and electron micrograph corrosion casting studies. Choriocapillaris imaging was performed in eight healthy volunteers with OCT angiograms successfully acquired from all subjects. These results demonstrate the feasibility of ultrahigh speed OCT for in vivo dye-free choriocapillaris and choroidal vasculature imaging, in addition to conventional structural imaging.National Institutes of Health (U.S.) (NIH R01-EY011289-27)National Institutes of Health (U.S.) (NIH R01-EY013178-12)National Institutes of Health (U.S.) (NIH R44-EY022864-01)National Institutes of Health (U.S.) (NIH R01-CA075289-16)United States. Air Force Office of Scientific Research (AFOSR FA9550-10-1-0551)United States. Air Force Office of Scientific Research (AFOSR FA9550-12-1-0499

Targeting the histone methyltransferase G9a activates imprinted genes and improves survival of a mouse model of Prader–Willi syndrome

Prader–Willi syndrome (PWS) is an imprinting disorder caused by a deficiency of paternally expressed gene(s) in the 15q11–q13 chromosomal region. The regulation of imprinted gene expression in this region is coordinated by an imprinting center (PWS-IC). In individuals with PWS, genes responsible for PWS on the maternal chromosome are present, but repressed epigenetically, which provides an opportunity for the use of epigenetic therapy to restore expression from the maternal copies of PWS-associated genes. Through a high-content screen (HCS) of >9,000 small molecules, we discovered that UNC0638 and UNC0642—two selective inhibitors of euchromatic histone lysine N-methyltransferase-2 (EHMT2, also known as G9a)—activated the maternal (m) copy of candidate genes underlying PWS, including the SnoRNA cluster SNORD116, in cells from humans with PWS and also from a mouse model of PWS carrying a paternal (p) deletion from small nuclear ribonucleoprotein N (Snrpn (S)) to ubiquitin protein ligase E3A (Ube3a (U)) (mouse model referred to hereafter as m+/pΔS−U). Both UNC0642 and UNC0638 caused a selective reduction of the dimethylation of histone H3 lysine 9 (H3K9me2) at PWS-IC, without changing DNA methylation, when analyzed by bisulfite genomic sequencing. This indicates that histone modification is essential for the imprinting of candidate genes underlying PWS. UNC0642 displayed therapeutic effects in the PWS mouse model by improving the survival and the growth of m+/pΔS−U newborn pups. This study provides the first proof of principle for an epigenetics-based therapy for PWS

The Related Transcriptional Enhancer Factor-1 Isoform, TEAD4216, Can Repress Vascular Endothelial Growth Factor Expression in Mammalian Cells

Increased cellular production of vascular endothelial growth factor (VEGF) is responsible for the development and progression of multiple cancers and other neovascular conditions, and therapies targeting post-translational VEGF products are used in the treatment of these diseases. Development of methods to control and modify the transcription of the VEGF gene is an alternative approach that may have therapeutic potential. We have previously shown that isoforms of the transcriptional enhancer factor 1-related (TEAD4) protein can enhance the production of VEGF. In this study we describe a new TEAD4 isoform, TEAD4216, which represses VEGF promoter activity. The TEAD4216 isoform inhibits human VEGF promoter activity and does not require the presence of the hypoxia responsive element (HRE), which is the sequence critical to hypoxia inducible factor (HIF)-mediated effects. The TEAD4216 protein is localized to the cytoplasm, whereas the enhancer isoforms are found within the nucleus. The TEAD4216 isoform can competitively repress the stimulatory activity of the TEAD4434 and TEAD4148 enhancers. Synthesis of the native VEGF165 protein and cellular proliferation is suppressed by the TEAD4216 isoform. Mutational analysis indicates that nuclear or cytoplasmic localization of any isoform determines whether it acts as an enhancer or repressor, respectively. The TEAD4216 isoform appears to inhibit VEGF production independently of the HRE required activity by HIF, suggesting that this alternatively spliced isoform of TEAD4 may provide a novel approach to treat VEGF-dependent diseases

Illness meanings and experiences for pre-ulcer and ulcer conditions of Buruli ulcer in the Ga-West and Ga-South Municipalities of Ghana

ABSTRACT: BACKGROUND: Ghana is a Buruli ulcer (BU) endemic country yet there is paucity of socio-cultural research on BU. Examining distinctive experiences and meanings for pre-ulcers and ulcers of BU may clarify the disease burden, illness experience and local perceptions of causes and spread, and environmental features of BU, which are useful to guide public health programmes and future research. This study aimed to explain local meanings and experiences of BU for persons with pre-ulcers and ulcers in the Ga-West and Ga-South municipalities in Accra. METHODS: Semi-structured interviews based on the Explanatory Model Interview Catalogue framework were administered to 181 respondents comprising 15 respondents with pre-ulcers and 166 respondents with ulcers. The Wilcoxon rank-sum test was used to compare categories of illness experiences (PD) and perceived causes (PC) among respondents with pre-ulcer and ulcer conditions. The Fisher's exact test was used to compare the most troubling PD and the most important PC variables. Qualitative phenomenological analysis of respondents' narratives clarified illness experiences and meanings with reference to PC and PD variables. RESULTS: Families of respondents with pre-ulcers and the respondents themselves were often anxious about disease progression, while families of respondents with ulcers, who had to give care, worried about income loss and disruption of school attendance. Respondents with pre-ulcers frequently reported swimming in ponds and rivers as a perceived cause and considered it as the most important PC (53.3%). Respondents with ulcers frequently attributed their BU illness to witchcraft (64.5%) and respondents who claimed they had no water contact, questioned the credibility of health messages CONCLUSIONS: Affected persons with pre-ulcers are likely to delay treatment because of social and financial constraints and the absence of pain. Scepticism on the role of water in disease contagion and prolonged healin is perceived to make ideas of witchcraft as a PC more credible, among respondents with ulcers. Health messages should address issues of locally perceived risk and vulnerability. Guided by study findings, further research on the role of environmental, socio-cultural and genetic factors in BU contagion, is also needed to clarify and formulate health messages and strengthen public health initiative

Branch Retinal Vein Occlusion: Pathogenesis, Visual Prognosis, and Treatment Modalities

In branch retinal vein occlusion (BRVO), abnormal arteriovenous crossing with vein compression, degenerative changes of the vessel wall and abnormal hematological factors constitute the primary mechanism of vessel occlusion. In general, BRVO has a good prognosis: 50–60% of eyes are reported to have a final visual acuity (VA) of 20/40 or better even without treatment. One important prognostic factor for final VA appears to be the initial VA. Grid laser photocoagulation is an established treatment for macular edema in a particular group of patients with BRVO, while promising results for this condition are shown by intravitreal application of steroids or new vascular endothelial growth factor inhibitors. Vitrectomy with or without arteriovenous sheathotomy combined with removal of the internal limiting membrane may improve vision in eyes with macular edema which are unresponsive to or ineligible for laser treatment