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The limited ability of newborn piglets to produce cytokines may influence lymphocyte development and response to antigen exposure. As a result, colostrum intake is crucial because it contains nutrients that contribute to immune system development in piglets. Our goal was to investigate the effect of sow parity on the transfer of maternal cytokines to nursing piglets. Sixty piglets from nine sows were divided into six groups: piglets from gilts or sows kept with their dams and allowed to suckle normally; piglets from gilts or sows having their dams exchanged and then allowed to suckle normally; piglets from gilts or sows isolated from their dams and bottle-fed a commercial milk replacer formula for pigs. All piglets remained in the diet groups for 24 hours after birth. Concentrations of cytokines in colostrum and serum of gilt/ sows and serum of piglets were then evaluated. The 13 evaluated cytokines had higher concentrations in colostrum and serum of sows than in gilts. Concentrations of GM-CSF, IFNγ, IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL-18, and TNFα were higher in piglets suckling sows. Piglets that received commercial formula showed higher concentrations of the cytokines IL1-RA and IL-8 than piglets fed colostrum. This outcome can influence piglets’ development into adulthood. In short, our findings demonstrated that maternal parity influenced colostrum cytokine composition and its maternal transfer patterns.

Biallelic mutations in the RCBTB1 gene cause retinal dystrophy. Here, we characterized the effects of RCBTB1 gene deficiency in retinal pigment epithelial (RPE) cells derived from a patient with RCBTB1‐associated retinopathy and restored RCBTB1 expression in these cells using adeno‐associated viral (AAV) vectors. Induced pluripotent stem cells derived from a patient with compound heterozygous RCBTB1 mutations (c.170delG and c.707delA) and healthy control subjects were differentiated into RPE cells. RPE cells were treated with AAV vectors carrying a RCBTB1 transgene. Patient‐derived RPE cells showed reduced expression of RCBTB1. Expression of NFE2L2 showed a non‐significant reduction in patient RPE cells compared with controls, while expression of its target genes (RXRA, IDH1 and SLC25A25) was significantly reduced. Trans‐epithelial electrical resistance, surface microvillus densities and primary cilium lengths were reduced in patient‐derived RPE cells, compared with controls. Treatment of patient RPE with AAV vectors significantly increased RCBTB1, NFE2L2 and RXRA expression and cilium lengths. Our study provides the first report examining the phenotype of RPE cells derived from a patient with RCBTB1‐associated retinopathy. Furthermore, treatment of patient‐derived RPE with AAV‐RCBTB1 vectors corrected deficits in gene expression and RPE ultrastructure, supporting the use of gene replacement therapy for treating this inherited retinal disease.

Background: Inflammation is a risk factor for chronic physical illnesses. Evidence is building that inflammation is also a risk factor for mental illnesses making inflammation a common mechanism which could explain the high comorbidity between mental and physical illnesses. Methods: Based on a systematic search, a review on factors associated with inflammation in the depressed chronically ill has been conducted. Relevant articles have been selected according to the methodological considerations (scope, sample size, type of analysis and bias). Results: Five categories of factors mediate the association between chronic physical and mental illnesses: (1) social–demographic factors, (2) social–economic background, (3) adverse health behaviours, (4) psychological stress and (5) genetics. Psychological therapies and medication also moderate this association. A theoretical model of the interplay between inflammation, depression and chronic physical illness is then presented. Discussion: Inflammation contribute to both chronic physical and mental illnesses. These conclusions support future advances in clinical and research practice, as well as training and education.

Light activation of the classical light-sensing retinal neurons, the photoreceptors, results in a graded change in membrane potential that ultimately leads to a reduction in neurotransmitter release to the post-synaptic retinal neurons. Photoreceptors show striking powers of adaptation, and for visual processing to function optimally, they must adjust their gain to remain responsive to different levels of ambient light intensity. The presence of a tightly controlled balance of inward and outward currents modulated by several different types of ion channels is what gives photoreceptors their remarkably dynamic operating range. Part of the resetting and modulation of this operating range is controlled by potassium and calcium voltage-gated channels, which are involved in setting the dark resting potential and synapse signal processing, respectively. Their essential contribution to visual processing is further confirmed in patients suffering from cone dystrophy with supernormal rod response (CDSRR) and congenital stationary night blindness type 2 (CSNB2), both conditions that lead to irreversible vision loss. This review will discuss these two types of voltage-gated ion channels present in photoreceptors, focussing on their structure and physiology, and their role in visual processing. It will also discuss the use and benefits of knockout mouse models to further study the function of these channels and what routes to potential treatments could be applied for CDSRR and CSNB2.

We surveyed Canadian critical care physicians who may care for patients who are potential organ donors to understand their attitudes and knowledge of legislation governing the deceased organ donation system. We used a web-based, self-administered survey that included questions related to opt-out consent and mandatory referral legislation. Potential participants were identified through membership lists of professional societies and manual searches. We designed our survey using standardized methods and administered it in February and March 2018. Fifty percent (263/529) of potential participants completed the questionnaire. A majority (61%; 144/235) supported a change towards an opt-out consent model, and 77% (181/235) stated they believe it would increase donation rates. Asked if opt-out consent would change their practices, 71% (166/235) stated an opt-out model would not change how or if they approach families to discuss donation. Fifty-six percent (139/249) supported mandatory referral laws, while only 42% (93/219) of those working in provinces with mandatory referral correctly stated that such laws exist in their province. Respondents gave variable responses on who should be accountable when patients are not referred, and 16% (40/249) believed no one should be held accountable. While a majority of critical care physicians supported opt-out consent and mandatory referral, many were neutral or against it. Many were unaware of existing laws and had variable opinions on how to ensure accountability. Efforts to increase understanding of how legislative models influence practice are required for any law to achieve its desired effect.

Objective To explore whether anxiety and depression are associated with clinical measures of disease for adolescent patients with juvenile idiopathic arthritis (JIA) and whether anxiety and depression are associated with increased peripheral proinflammatory cytokine levels in adolescent patients with JIA and in healthy adolescent controls. Methods A total of 136 patients with JIA and 88 healthy controls ages 13-18 years completed questionnaires on anxiety and depressive symptoms. For patients with JIA, pain, disability, physician global assessment (using a visual analog scale [VAS]), and number of joints with active inflammation (active joint count) were recorded. In a subsample, we assessed lipopolysaccharide-stimulated interleukin 6 (IL-6) production from peripheral blood mononuclear cells, serum IL-6, cortisol, and C-reactive protein levels. Data were analyzed by linear regression analysis. Results Levels of anxiety and depressive symptoms in patients with JIA were not significantly different than those in healthy controls. For patients with JIA, anxiety was significantly associated with disability (β = 0.009, P = 0.002), pain (β = 0.029, P = 0.011), and physician global assessment VAS (β = 0.019, P = 0.012), but not with active joint count (β = 0.014, P = 0.120). Anxiety was not associated with any laboratory measures of inflammation for JIA patients. These relationships were also true for depressive symptoms. For healthy controls, there was a trend toward an association of anxiety (but not depressive symptoms) with stimulated IL-6 (β = 0.004, P = 0.052). Conclusion Adolescent patients with JIA experience equivalent levels of anxiety and depressive symptoms as healthy adolescents. For adolescent patients with JIA, anxiety and depressive symptoms are associated with pain, disability, and physician global assessment VAS, but not with inflammation.

Inherited retinal diseases (IRDs) are a heterogeneous group of blinding disorders, which result in dysfunction or death of the light-sensing cone and rod photoreceptors. Despite individual IRDs being rare, collectively, they affect up to 1:2000 people worldwide, causing a significant socioeconomic burden, especially when cone-mediated central vision is affected. This study uses the Pde6ccpfl1 mouse model of achromatopsia, a cone-specific vision loss IRD, to investigate the potential gene-independent therapeutic benefits of a histone demethylase inhibitor GSK-J4 on cone cell survival. We investigated the effects of GSK-J4 treatment on cone cell survival in vivo and ex vivo and changes in cone-specific gene expression via single-cell RNA sequencing. A single intravitreal GSK-J4 injection led to transcriptional changes in pathways involved in mitochondrial dysfunction, endoplasmic reticulum stress, among other key epigenetic pathways, highlighting the complex interplay between methylation and acetylation in healthy and diseased cones. Furthermore, continuous administration of GSK-J4 in retinal explants increased cone survival. Our results suggest that IRD-affected cones respond positively to epigenetic modulation of histones, indicating the potential of this approach in the development of a broad class of novel therapies to slow cone degeneration.

Photoreceptor cell transplantation into the mouse retina has been shown to result in the transfer of cytoplasmic material between donor and host photoreceptors. Recently it has been found that this inter-photoreceptor material transfer process is likely to be mediated by nanotube-like structures connecting donor and host photoreceptors. By leveraging cone-specific reporter mice and super-resolution microscopy we provide evidence for the transfer of cytoplasmic material also from endogenous cones to endogenous rod photoreceptors and the existence of nanotube-like cell-cell connections possibly mediating this process in the adult mouse retina, together with preliminary data indicating that horizontal material transfer may also occur in the human retina.

Submitted by Ana Livia de Carvalho Bovolato (alc.bovolato@unesp.br) on 2021-11-08T07:47:30Z No. of bitstreams: 1 tese-versão final Ana Livia C Bovolato.pdf: 4571444 bytes, checksum: 4a90b3202bf7b7e3bf9cbf51b2e6fd98 (MD5) Approved for entry into archive by Elida Daniele de Antonio null (elida_daniele@btu.unesp.br) on 2021-11-08T14:10:00Z (GMT) No. of bitstreams: 1 bovolato_alc_dr_bot.pdf: 4571444 bytes, checksum: 4a90b3202bf7b7e3bf9cbf51b2e6fd98 (MD5) Made available in DSpace on 2021-11-08T14:10:00Z (GMT). No. of bitstreams: 1 bovolato_alc_dr_bot.pdf: 4571444 bytes, checksum: 4a90b3202bf7b7e3bf9cbf51b2e6fd98 (MD5) Previous issue date: 2021-10-07 A doença de Alzheimer (DA) é a uma doença neurodegenerativa complexa, responsável pela maioria dos casos de comprometimento cognitivo progressivo em pacientes idosos. O processo degenerativo pode iniciar 20 anos antes da manifestação clínica da doença. O diagnóstico precoce e preciso da DA continua laborioso e quase sempre interfaceado com o diagnóstico de exclusão. Neste projeto é proposto o desenvolvimento de um biossensor para a detecção da doença de Alzheimer baseado na detecção de autoanticorpos anti-ATP-sintase subunidade Beta e anti-FRMD8 presentes em amostra periféricas, soro, e em LCR (líquido cefalorraquidiano) de pacientes com a doença de Alzheimer. Para tal foi construído dois sistemas baseados em imunoensaios: 1) imobilizou-se ATP-Sintase subunidade Beta em lâmina de ouro modificadas com 11-MUA e Quitosana e 2) imobilizou-se o peptídeo FRMD8 associado ao lipossomo de DPPG em superfície de ouro modificada com 11-MUA e PEI. Em ambos os casos se quantificou os respectivos anticorpos comerciais diluídos nas proporções não diluído, 0,01mg/mL (puro), 1:10 (0,001mg/mL), 1:100 (0,0001mg/mL), 1:1000 (10ng/mL) e 1:10000 (1ng/mL), com o intuito de gerar uma curva de calibração. Para realizar as medidas foi feita a técnica de SERS (Espectroscopia Raman Aprimorada por Superfície) usando sondas SERS de nanopartículas de ouro modificadas com Anti-IgG porção Fc. Como análise comparativa, ambos os resultados foram comparados com amostras de indivíduos não portadores de DA (como controle Alzheimer, CA) e com anti-HIV p17 como controle experimental (CE). Os sensores foram hábeis de gerar curvas de calibração na qual o biossensor baseado em FRMD8 foi capaz de detectar até 1ng/mL e o biossensor baseado em ATP-Sintase foi capaz de detectar até 10ng/mL. Na validação, apenas o biossensor baseado em ATP Sintase se demostrou eficaz na semi-quatificação e diferenciação entre controles e amostras e através de análise de PCA foi estabelecer e criar um Score SERS e correlacionar com o Score MEEM. Um ponto extremamente importante a se destacar nesse trabalho é que não há biomarcador “perfeito” para a DA devido ao seu múltiplo interfaceamento, sendo, a melhor alternativa, uma análise de múltiplos marcadores. Alzheimer's disease (AD) is a complex neurodegenerative disease, responsible for most cases of progressive cognitive impairment in elderly patients. The degenerative process can start 20 years before the clinical manifestation of the disease. The early and accurate diagnosis of AD remains laborious and is almost always intertwined with diagnoses of exclusion. This project proposes the development of a biosensor for the detection of Alzheimer's disease based on the detection of antiATP-synthase Beta and anti-FRMD8 autoantibodies present in peripheral samples, serum, and in CSF (cerebrospinal fluid) from patients with Alzheimer's disease. For this purpose, two systems based on immunoassays were constructed: 1) ATP-Synthase Beta subunit was immobilized on gold plate modified with 11-MUA and Chitosan and 2) FRMD8 peptide associated with DPPG liposome was immobilized on a modified gold surface with 11-MUA and PEI. In both cases, the respective commercial antibodies were quantified in the proportions undiluted, 0.01mg/mL (pure), 1:10 (0.001mg/mL), 1:100 (0.0001mg/mL), 1:1000 (1ng/mL) and 1:10000 (1ng/mL), to generate a calibration curve. The SERS (Surface Enhanced Raman Spectroscopy) technique was performed using SERS probes of gold nanoparticles modified with Anti-IgG Fc portion. As a comparative analysis, both results were compared with samples from individuals without AD (as control Alzheimer, CA) and with anti-HIV p17 as experimental control (EC). The sensors were able to generate calibration curves in which the FRMD8-based biosensor was able to detect up to 1ng/mL and the ATP-Synthase-based biosensor was able to detect up to 10ng/mL. In the validation test, only the ATP Synthase-based biosensor proved to be effective in semi-qualification and differentiation between controls and samples, and, through PCA analysis, it was established and created SERS Score and correlated with the MEEM Score. An extremely important point to be highlighted in this work is that there is no “perfect” biomarker for AD due to its multiple interfacing, the best alternative being an analysis of multiple markers.

Depression frequently co-occurs with coronary heart disease (CHD), worsening clinical outcomes of both, and inflammation has been proposed as a biological link between these two disorders. The aim of the present study was to investigate the role of inflammation in the development of depression in CHD patients during a 3-year follow-up. We examined the inflammatory biomarker, high-sensitivity C-reactive protein (hsCRP), measured at baseline, as a potential predictor of later onset of depression. We recruited 89 CHD patients, who were assessed at baseline and then every 6 months, for three years. The sample included, at baseline, 25 depressed and 64 non-depressed CHD patients, as confirmed by Clinical Interview Schedule Revised (CIS-R). Depressive symptoms were assessed at baseline and all follow-up points by the Patient Health Questionnaire-9 (PHQ-9). In all CHD patients (n = 89), we found a significant positive correlation between hsCRP levels and the severity of depressive symptoms at baseline (PHQ-9, r = 0.23, p = 0.032). During follow-up, n = 21 patients (of the 64 non-depressed at baseline) developed depression, defined as being PHQ-9 positive (a score ≥ 10) in at least one follow-up assessment. Of these, n = 9 subjects were defined as developing clinically-significant depression, that is, having a positive PHQ-9 in at least 3 of the 6 follow-up assessments, implying a duration of symptoms of at least one year. We found that increased hsCRP values at baseline predicted future onset of depression. Specifically, baseline hsCRP values were higher in patients who later developed clinically-significant depression (mean ± SD; 6.76 ± 6.52 mg/L) compared with never-depressed (2.77 ± 3.13 mg/L; F(1,48) = 7.29, p = 0.010), even after controlling for baseline PHQ-9 scores. In conclusion, inflammation in CHD patients is associated with future development of clinically-significant depression. HsCRP, a reliable and ready-to-use biological marker of inflammation, may help to identify depression high-risk phenotypes even among CHD patients, who already have high baseline inflammation. Our study conveys important preliminary findings that will require further replication but that have the potential to affect the mental and physical health of a vulnerable group of individuals.

Trust in the deceased organ donation process relies on the expectation that the diagnosis of death by neurologic criteria (DNC) is accurate and reliable. The objective of this study was to assess the perceptions and approaches to DNC diagnosis among Canadian intensivists.We conducted a self-administered, online, cross-sectional survey of Canadian intensivists. Our sampling frame included all intensivists practicing in Canadian institutions. Results are reported using descriptive statistics.Among 550 identified intensivists, 249 (45%) completed the survey. Respondents indicated they would be comfortable diagnosing DNC based on clinical criteria alone in cases where there is movement in response to stimulation (119/248; 48%); inability to evaluate upper/lower extremity responses (84/249; 34%); spontaneous peripheral movement (76/249; 31%); inability to evaluate both oculocephalic and oculo-caloric reflexes (40/249; 16%); presence of high cervical spinal cord injury (40/249; 16%); and within 24 hr of hypoxemic-ischemic brain injury (38/247; 15%). Most respondents agreed that an ancillary test should always be conducted when a complete clinical evaluation is impossible (225/241; 93%); when there is possibility of a residual sedative effect (216/242; 89%); when the mechanism for brain injury is unclear (172/241; 71%); and if isolated brainstem injury is suspected (142/242; 59%). Sixty-six percent (158/241) believed that ancillary tests are sensitive and 55% (132/241) that they are specific for DNC. Respondents considered the following ancillary tests useful for DNC: four-vessel conventional angiography (211/241; 88%), nuclear imaging (179/240; 75%), computed tomography (CT) angiography (156/240; 65%), and CT perfusion (134/240; 56%).There is variability in perceptions and approaches to DNC diagnosis among Canadian intensivists, and some practices are inconsistent with national recommendations.RéSUMé: OBJECTIF: La confiance dans le processus de don d’organes de donneurs décédés repose sur l’attente que le diagnostic de décès déterminé par des critères neurologiques (DDN) soit précis et fiable. L’objectif de cette étude était d’évaluer les perceptions et les approches du diagnostic de DDN chez les intensivistes canadiens. MéTHODE: Nous avons mené un sondage transversal auto-administré et en ligne auprès des intensivistes canadiens. Notre base d’échantillonnage comprenait tous les intensivistes exerçant dans des établissements canadiens. Les résultats sont présentés à l’aide de statistiques descriptives. RéSULTATS: Parmi les 550 intensivistes identifiés, 249 (45 %) ont répondu au sondage. Les répondants ont indiqué qu’ils seraient à l’aise de diagnostiquer un DDN en fonction de critères cliniques seulement dans les cas où il y a : un mouvement en réponse à une stimulation (119/248; 48 %); une incapacité à évaluer les réponses des membres supérieurs et inférieurs (84/249; 34 %); un mouvement périphérique spontané (76/249; 31 %); une incapacité à évaluer à la fois les réflexes oculo-céphaliques et vestibulo-oculaires (40/249; 16 %); la présence de lésions médullaires cervicales hautes (40/249; 16 %); et dans les 24 heures suivant une lésion cérébrale hypoxémique-ischémique (38/247; 15 %). La plupart des répondants étaient d’accord pour dire qu’un test auxiliaire devrait toujours être réalisé lorsqu’une évaluation clinique complète est impossible (225/241; 93 %); lorsqu’il y a possibilité d’un effet sédatif résiduel (216/242; 89 %); lorsque le mécanisme de la lésion cérébrale n’est pas clair (172/241; 71 %); et si une lésion isolée du tronc cérébral est suspectée (142/242; 59 %). Soixante-six pour cent (158/241) des répondants étaient d’avis que les tests auxiliaires étaient sensibles et 55 % (132/241) qu’ils étaient spécifiques pour le DDN. Les répondants ont jugé utiles les tests auxiliaires suivants pour le DDN : l’angiographie conventionnelle des quatre vaisseaux (211/241; 88 %), l’imagerie nucléaire (179/240; 75 %), l’angiographie par tomodensitométrie (TDM) (156/240; 65 %) et la perfusion en TDM (134/240; 56 %). CONCLUSION: Les perceptions et les approches du diagnostic de DDN varient parmi les intensivistes canadiens, et certaines pratiques ne sont pas conformes aux recommandations nationales.

Cone Dystrophy with Supernormal Rod Response (CDSRR) is a rare autosomal recessive disorder leading to severe visual impairment in humans, but little is known about its unique pathophysiology. We have previously shown that CDSRR is caused by mutations in the KCNV2 (Potassium Voltage-Gated Channel Modifier Subfamily V Member 2) gene encoding the Kv8.2 subunit, a modulatory subunit of voltage-gated potassium (Kv) channels. In a recent study, we validated a novel mouse model of Kv8.2 deficiency at a late stage of the disease and showed that it replicates the human electroretinogram (ERG) phenotype. In this current study, we focused our investigation on young adult retinas to look for early markers of disease and evaluate their effect on retinal morphology, electrophysiology and immune response in both the Kv8.2 knockout (KO) mouse and in the Kv2.1 KO mouse, the obligate partner of Kv8.2 in functional retinal Kv channels. By evaluating the severity of retinal dystrophy in these KO models, we demonstrated that retinas of Kv KO mice have significantly higher apoptotic cells, a thinner outer nuclear cell layer and increased activated microglia cells in the subretinal space. Our results indicate that in the murine retina, the loss of Kv8.2 subunits contributes to early cellular and physiological changes leading to retinal dysfunction. These results could have potential implications in the early management of CDSRR despite its relatively nonprogressive nature in humans.

Light activation of the classical light-sensing retinal neurons, the photoreceptors, results in a graded change in membrane potential that ultimately leads to a reduction in neurotransmitter release to the post-synaptic retinal neurons. Photoreceptors show striking powers of adaptation, and for visual processing to function optimally, they must adjust their gain to remain responsive to different levels of ambient light intensity. The presence of a tightly controlled balance of inward and outward currents modulated by several different types of ion channels is what gives photoreceptors their remarkably dynamic operating range. Part of the resetting and modulation of this operating range is controlled by potassium and calcium voltage-gated channels, which are involved in setting the dark resting potential and synapse signal processing, respectively. Their essential contribution to visual processing is further confirmed in patients suffering from cone dystrophy with supernormal rod response (CDSRR) and congenital stationary night blindness type 2 (CSNB2), both conditions that lead to irreversible vision loss. This review will discuss these two types of voltage-gated ion channels present in photoreceptors, focussing on their structure and physiology, and their role in visual processing. It will also discuss the use and benefits of knockout mouse models to further study the function of these channels and what routes to potential treatments could be applied for CDSRR and CSNB2.

Inherited retinal diseases (IRDs) comprise a clinically and genetically heterogeneous group of disorders that can ultimately result in photoreceptor dysfunction/death and vision loss. With over 270 genes known to be involved in IRDs, translation of treatment strategies into clinical applications has been historically difficult. However, in recent years there have been significant advances in basic research findings as well as translational studies, culminating in an increasing number of clinical trials with the ultimate goal of reducing vision loss and associated morbidities. The recent approval of Luxturna® (voretigene neparvovec-rzyl) for Leber congenital amaurosis type 2 (LCA2) prompts a review of the current clinical trials for IRDs, with a particular focus on the importance of adeno-associated virus (AAV)-based gene therapies. The present article reviews the current state of AAV use in gene therapy clinical trials for IRDs, with a brief background on AAV and the reasons behind its dominance in ocular gene therapy. It will also discuss pre-clinical progress in AAV-based therapies aimed at treating other ocular conditions that can have hereditable links, and what alternative technologies are progressing in the same therapeutic space.

While comorbidity between coronary heart disease (CHD) and depression is evident, it is unclear whether the two diseases have shared underlying mechanisms. We performed a range of analyses in 367,703 unrelated middle-aged participants of European ancestry from UK Biobank, a population-based cohort study, to assess whether comorbidity is primarily due to genetic or environmental factors, and to test whether cardiovascular risk factors and CHD are likely to be causally related to depression using Mendelian randomization. We showed family history of heart disease was associated with a 20% increase in depression risk (95% confidence interval [CI] 16–24%, p

Background Typically, people with Parkinson’s Disease (PD) progress to develop a gait pattern that is characterized by quick, short and shuffling steps. Gait cycle is altered and lacks definition and fluidity. Gait training combined with a variety of feedback modalities for PD are usually based on non-immediate and externally-based cues but none of these provide real-time feedback on gait quality and acquired gains tend to abate shortly after rehabilitation. Based on principals of motor learning, our team has developed the Heel2Toe sensor to provide real-time auditory feedback during gait training. Research question Is a short-term training using the Heel2Toe sensor feasible and efficient to improve gait in people with PD? Our objectives are to identify the extent of the immediate response to the feedback within the same session and the carry-over response to training and; 2) to identify patients’ perceived effects, pleasures and challenges of using the Heel2Toe. Methods Single-arm, proof-of-concept study. Six people received five sessions of gait training over a 2–3-week period using the Heel2Toe augmented with mobility exercises as an adjunct to gait training. The main outcomes were technically assessed gait parameters collected over a 2-minute walk test, without and with feedback. Heel2Toe signals were analyzed to extract angular velocity(AV), percentage of good steps, average cadence, and AV coefficient of variation(CV). Results An immediate response to the Heel2Toe use and a carry-over response to the short-term training with the sensor were observed: an increase in AV with a reduction in CV (better heel strike and gait regularity); an increase in %good steps; and a near-optimal and homogeneous cadence (∼100 steps/min), which is equivalent to a moderate-intensity walking. Significance Gait training using the Heel2Toe sensor is feasible and potentially effective for improving gait quality in people with PD. A definitive trial is a logical next step.

Usher syndrome is a genetic disorder causing neurosensory hearing loss and blindness from retinitis pigmentosa (RP). Adaptive techniques such as braille, digital and optical magnifiers, mobility training, cochlear implants, or other assistive listening devices are indispensable for reducing disability. However, there is currently no treatment to reduce or arrest sensory cell degeneration. There are several classes of treatments for Usher syndrome being investigated. The present article reviews the progress this research has made towards delivering commercial options for patients with Usher syndrome.

Age-related macular degeneration (AMD) is a progressive degenerative disease that is the leading cause of vision loss in the elderly population. Degeneration/dysregulation of the retinal pigment epithelium (RPE), a supportive monolayer of cells underlying the photoreceptors is commonly seen in patients with AMD. While treatment exists for the neovascular/wet form of AMD, there is currently no cure for the non-exudative/dry form of AMD, making it imperative to understand the pathogenesis of this disease. Although our understanding of the aetiology of AMD has increased over the years, the underlying disease mechanism has not yet been identified, mainly due to the multifactorial nature of this disease. Herein, we review some of the commonly proposed degeneration pathways of RPE cells and their role in the pathogenesis of AMD; including activation of the complement cascade, oxidative stress-induced cell death mechanisms, dysfunctional mitochondria and the role of crystallins in AMD disease progression. This article is protected by copyright. All rights reserved.

We surveyed Canadian critical care physicians who may care for patients who are potential organ donors to understand their attitudes and knowledge of legislation governing the deceased organ donation system.We used a web-based, self-administered survey that included questions related to opt-out consent and mandatory referral legislation. Potential participants were identified through membership lists of professional societies and manual searches. We designed our survey using standardized methods and administered it in February and March 2018.Fifty percent (263/529) of potential participants completed the questionnaire. A majority (61%; 144/235) supported a change towards an opt-out consent model, and 77% (181/235) stated they believe it would increase donation rates. Asked if opt-out consent would change their practices, 71% (166/235) stated an opt-out model would not change how or if they approach families to discuss donation. Fifty-six percent (139/249) supported mandatory referral laws, while only 42% (93/219) of those working in provinces with mandatory referral correctly stated that such laws exist in their province. Respondents gave variable responses on who should be accountable when patients are not referred, and 16% (40/249) believed no one should be held accountable.While a majority of critical care physicians supported opt-out consent and mandatory referral, many were neutral or against it. Many were unaware of existing laws and had variable opinions on how to ensure accountability. Efforts to increase understanding of how legislative models influence practice are required for any law to achieve its desired effect.RéSUMé: OBJECTIF: Nous avons étudié les intensivistes canadiens qui prennent soin de patients potentiellement donneurs d’organes afin de comprendre leurs attitudes et connaissances quant aux lois régissant le système de don d’organes de donneurs décédés. MéTHODE: Nous avons utilisé un sondage électronique auto-administré incluant des questions liées au consentement implicite avec option de retrait et à la législation de référence obligatoire. Les participants potentiels ont été identifiés grâce aux listes des sociétés professionnelles et par des recherches manuelles. Nous avons conçu notre sondage à l’aide de méthodes standardisées et l’avons administré en février et mars 2018. RéSULTATS: Cinquante pour cent (263/529) des participants potentiels ont complété le questionnaire. La majorité (61 %; 144/235) était en faveur d’un changement vers un modèle de consentement avec option de retrait, et 77 % (181/235) ont déclaré penser que cela augmenterait les taux de don. Lorsqu’il leur a été demandé si l’option de consentement avec option de retrait modifierait leur pratique, 71 % (166/235) ont affirmé qu’un modèle avec possibilité de retrait ne modifierait pas leur façon ou leur intention d’approcher les familles pour parler de don d’organes. Cinquante-six pour cent (139/249) étaient en faveur de lois concernant la référence obligatoire, alors que seulement 42 % (93/219) des intensivistes travaillant dans des provinces où la référence était obligatoire ont correctement déclaré que de telles lois existaient dans leur province. Les répondants ont donné des réponses variables quant à l’imputabilité lors de la non-référence des patient, et 16 % (40/249) étaient d’avis que personne ne devrait être tenu responsable. CONCLUSION: Alors que la majorité des intensivistes était en faveur du consentement avec option de retrait et de la référence obligatoire, bon nombre n’avaient pas d’avis sur la question ou étaient contre. De nombreux intensivistes ne connaissaient pas bien les lois existantes et avaient des opinions variables sur la façon de garantir l’imputabilité. Des efforts sont nécessaires pour augmenter la compréhension de la manière dont les modèles législatifs influencent la pratique afin qu’une loi, quelle qu’elle soit, ait l’effet désiré.

Inherited retinal diseases (IRDs) are a leading cause of blindness. To date, 260 disease-causing genes have been identified, but there is currently a lack of available and effective treatment options. Cone photoreceptors are responsible for daylight vision but are highly susceptible to disease progression, the loss of cone-mediated vision having the highest impact on the quality of life of IRD patients. Cone degeneration can occur either directly via mutations in cone-specific genes (primary cone death), or indirectly via the primary degeneration of rods followed by subsequent degeneration of cones (secondary cone death). How cones degenerate as a result of pathological mutations remains unclear, hindering the development of effective therapies for IRDs. This review aims to highlight similarities and differences between primary and secondary cone cell death in inherited retinal diseases in order to better define cone death mechanisms and further identify potential treatment options.

Objective: To investigate the influence of single and dual sensory impairments prospectively on cognition in adults aged ⩾50 years. Method: Community-dwelling English adults ( n = 4,621) were followed up from 2008 to 2014. Self-reported hearing and vision were collected in 2008. Change in cognitive performance on working memory and executive function between 2008 and 2014 was evaluated. Results: Compared with good hearing and good vision, respectively, poor hearing and poor vision were associated with worse cognitive function (hearing: unstandardized coefficient B = 0.83, 95% Confidence Interval [CI] = [0.29, 1.37]; vision: B = 1.61, 95% CI = [0.92, 2.29] adjusted for age, sex, baseline cognition). Compared with no sensory impairment, dual sensory impairment was associated with worse cognition ( B = 2.30, 95% CI = [1.21, 3.39] adjusted for age, sex, baseline cognition). All associations remained after further adjustment for sociodemographic characteristics, lifestyle factors, chronic conditions, falls, mobility, depression, and lack of companionship. Discussion: The findings are important as age-related sensory impairments are often preventable or modifiable, which may prevent or delay cognitive impairment.

To determine the occurrence of diarrhea and associated factors in critically ill patients with traumatic brain injury (TBI) in use of nutritional therapy. Prospective cohort study conducted in an Intensive Care Unit (ICU) of a General Hospital reference in trauma. We evaluated TBI patients who stayed less than 72 h in the ICU, who were using EN for at least 48 h. Definition of diarrhea it was considered three or more episodes of liquid stools or semi-liquid at 24 h. For analysis were evaluated demographic, epidemiological, clinical and nutritional data. Twenty-three patients were evaluated, being 86.9% male, median 33 years old (IQR = 25-52 years) and 16-day ICU stay (IQR = 10-26 days). Diarrhea occurred in 69.6% of the patients and they had a longer time in the ICU (p = 0.007). All patients who used combination prokinetic therapy (metoclopramide and erythromycin) and used antibiotics for more than 8 days had diarrhea (p = 0.057 and p = 0.007, respectively). The incidence of diarrhea was high in TBI patients with enteral nutrition and was associated with the use of antibiotics for more than one week.

Resumo O pseudoaneurisma da artéria esplênica é uma entidade rara, com pouco mais de 150 casos descritos na literatura. A pancreatite é a etiologia mais comum, seguida do trauma. Em contraposição ao aneurisma verdadeiro, esse pseudoaneurisma é frequentemente sintomático, com risco de ruptura de 47% e mortalidade de 90%, quando não tratado. Descrevemos o caso de uma paciente de 48 anos que apresentou hemorragia gastrointestinal associada a pancreatite crônica agudizada. Durante investigação, a endoscopia evidenciou sinais de sangramento recente, e a angiorressonância de abdome observou volumoso pseudoaneurisma da artéria esplênica. Foi submetida a tratamento endovascular com embolização com micromolas, não apresentando novos episódios de sangramento. Atualmente, o tratamento endovascular é efetivo com baixa morbimortalidade e taxas de sucesso de 79-100%, sendo uma técnica viável para pacientes com processo inflamatório abdominal em franca atividade. Realizamos uma revisão das técnicas endovasculares e agentes embolizantes usados para o tratamento dessa patologia.

First Place Award Submission - CA147Category: Clinical ApplicationManagement of obesity after spinal cord injury: a systematic reviewMir Hatef Shojaei1, Mohammad Alavinia1, B. Catharine Craven1,21N...

High visual acuity and the ability to identify colours is solely dependent upon healthy cone photoreceptors in the retina. Little is known about cone migration mechanisms during postmitotic retinal maturation which, if it occurs erroneously, can result in non-functional cells and altered vision. This review provides an overview of neuronal and cone somal migration mechanisms and the potential molecular partners and nuclear structures driving this process. Furthermore, it will also review foveal formation and how that differs from peripheral cone migration in the human retina.

IntroductionIn Canada, deceased organ donation provides over 80% of transplanted organs. At the time of death, families, friends or others assume responsibility as substitute decision-makers (SDMs) to consent to organ donation. Despite their central role in this process, little is known about what barriers, enablers and beliefs influence decision-making among SDMs. This study aims to explore the experiences and perspectives of SDMs involved in making decisions around the withdrawal of life-sustaining therapies, end-of-life care and deceased organ donation.Methods and analysisSDMs of 60 patients admitted to intensive care units will be enrolled for this study. Ten hospitals across five provinces in Canada in a prospective multicentre qualitative cohort study. We will conduct semistructured telephone interviews in English or French with SDMs between 6 and 8 weeks after the patient’s death. Our sampling frame will stratify SDMs into three groups: SDMs who were not approached for organ donation; SDMs who were approached and consented to donate and SDMs who were approached but did not consent to donate. We will use two complementary theoretical frameworks—the Common-Sense Self-Regulation Model and the Theoretical Domains Framework— to inform our interview guide. Interview data will be analysed using deductive directed content analysis and inductive thematic analysis.Ethics and disseminationThis study has been approved by the Centre Hospitalier de l’Université de Montréal Research Ethics Board. The findings from this study will help identify key factors affecting substitute decision-making in deceased organ donation, reasons for non-consent and barriers to achieve congruency between SDM and patient wishes. Ultimately, these data will contribute to the development and evaluation of tools and training for healthcare providers to support SDMs in making decisions about organ donation.Trial registration numberNCT03850847.

Integrated production systems have been used with various crops, and their use in floriculture is innovative. The effects of green fertilization in floriculture and the appropriate fertilization levels are still unknown. The aim was to identify the best dose of chemical fertilizer, with or without green fertilization, for integrated production of ‘Carola’ roses. The treatments consisted of 4 doses of the chemical fertilization recommended for rose bushes, (25%, 50%, 75%, and 100%), with or without green fertilization (calopo). Plants that were not treated with 100% (or complete) of chemical fertilization were supplemented monthly with Bokashi (16 g/plant, via the soil) and biofertilizer (5% via the leaves). The assessments were conducted 3 times per week for a year. The use of less chemical fertilizer did not affect rose production or quality, whereas the use of green fertilization did not provide a satisfactory outcome. The analyses, biometric, accumulation and nutrient content, and chemical characteristics of the soil, indicated that green fertilization with calopo was not beneficial. Moreover, with the exception of nitrogen and magnesium, there is the possibility of using 75% of the recommended chemical fertilization in rose bushes. Resumo O sistema de produção integrada vem sendo utilizado em várias culturas, sendo inovador o seu uso em floricultura. Nessa atividade ainda são desconhecidos os efeitos de adubação verde ainda como os níveis de adubação fornecidos não são precisos. O objetivo foi identificar a melhor dose de adubo químico associado ou não à adubação verde, em produção integrada de rosas ‘Carola’. Os tratamentos consistiram de quatro porcentagens de adubação química, segundo a recomendação para Minas Gerais, (25%, 50%, 75% e 100%) associado ou não à adubação verde (calopogônio). Plantas que não receberam 100% da adubação química receberam a complementação de Bokashi (16 g/planta, via solo) e biofertilizante (5% foliar), em aplicações mensais. As avaliações foram realizadas três vezes por semana em um ano. A redução da adubação química não prejudicou a produção e qualidade das rosas, mas o adubo verde não foi benéfico. Os resultados das análises biométricas, de acúmulo, teor de nutrientes e características químicas do solo indicam que a adubação verde com calopogônio não é eficiente e, exceto para nitrogênio e magnésio, há possibilidade de utilização de até 75% da adubação química recomendada.