Positive Impacts of Adolescent Involvement in Health Research: An Umbrella Review.

Despite an increased recognition of the right of adolescents to be involved in decisions that affect them, young people continue to be under-involved in health research. One of the reasons is a lack of awareness among researchers on the current evidence base around the benefits of involving adolescents. To address this, we conducted an umbrella review to synthesize the evidence on the positive impacts of adolescent involvement in health research. This umbrella review was preregistered with PROSPERO (CRD42021287467). We searched 11 databases, Google Scholar, PROSPERO, reference lists, 10 journals, websites of 472 organizations, and sought input from experts. Ultimately, we included 99 review articles. We found that adolescent involvement has many positive impacts on young people, including increased knowledge and skills; personal development; financial benefits; career and academic growth; enhanced relationships; and valuing their experience. The positive impacts of adolescent involvement on the research itself include increased relevance of the study to adolescents, improved recruitment, development of more adolescent-friendly materials, enhanced data collection and analysis, and more effective dissemination. Researchers also benefited from adolescents' involvement through increased knowledge, skills, and a shift in their attitudes. The evidence supporting the positive impacts of adolescent involvement in research is substantial but limited by a lack of rigorous evaluation, inconsistent reporting, and unclear evaluation methods.

Involving adolescents in the design, implementation, evaluation and dissemination of health research: an umbrella review protocol.

INTRODUCTION: A lack of awareness on how to engage adolescents in research has been reported as one of the barriers to meaningful youth involvement in health research. Currently, available guidelines on youth involvement are limited in terms of the scope (e.g., focused on limited health research areas), content (e.g., include broad principles) and context (e.g., most guidelines are from high-income countries) for which the guidelines are applicable. To address this, we will develop a set of comprehensive guidelines based on consolidated evidence on youth involvement in health research. To inform these guidelines, we are first conducting an umbrella review to (1) summarise and synthesise findings from reviews on involving adolescents in health research, (2) consolidate the challenges experienced in youth involvement and the recommendations to mitigate these challenges, (3) identify best practices and (4) identify gaps and methodological weaknesses in the extant literature on involving adolescents in health research. METHODS AND ANALYSIS: We will include review articles exploring adolescents' involvement in studies aiming to improve their physical or mental health. Databases to be searched include Cochrane Database of Systematic Reviews, Medical Literature Analysis and Retrieval System Online (MEDLINE), Scopus, Embase, PsycINFO, PsycArticles, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Epistemonikos and Health Systems Evidence. A grey literature search will be conducted in Web of Science, ProQuest, Google Scholar and PROSPERO, supplemented by a handsearch of the reference lists of eligible reviews, relevant journals, websites of related organisations and input from experts. Data will be analysed using narrative synthesis. ETHICS AND DISSEMINATION: Ethical approval is not required as we are not collecting participant data as part of this review. The findings of this umbrella review will be disseminated through peer-reviewed publications, participatory workshops and academic conferences. PROSPERO REGISTRATION NUMBER: CRD42021287467.

A Comprehensive Study of the Retinal Phenotype of Rpe65-Deficient Dogs.

The Rpe65-deficient dog has been important for development of translational therapies of Leber congenital amaurosis type 2 (LCA2). The purpose of this study was to provide a comprehensive report of the natural history of retinal changes in this dog model. Rpe65-deficient dogs from 2 months to 10 years of age were assessed by fundus imaging, electroretinography (ERG) and vision testing (VT). Changes in retinal layer thickness were assessed by optical coherence tomography and on plastic retinal sections. ERG showed marked loss of retinal sensitivity, with amplitudes declining with age. Retinal thinning initially developed in the area centralis, with a slower thinning of the outer retina in other areas starting with the inferior retina. VT showed that dogs of all ages performed well in bright light, while at lower light levels they were blind. Retinal pigment epithelial (RPE) inclusions developed and in younger dogs and increased in size with age. The loss of photoreceptors was mirrored by a decline in ERG amplitudes. The slow degeneration meant that sufficient photoreceptors, albeit very desensitized, remained to allow for residual bright light vision in older dogs. This study shows the natural history of the Rpe65-deficient dog model of LCA2.

Sildenafil Administration in Dogs Heterozygous for a Functional Null Mutation in Pde6a: Suppressed Rod-Mediated ERG Responses and Apparent Retinal Outer Nuclear Layer Thinning.

This study was designed to assess risk for retinal toxicity associated with administration of high-dose sildenafil citrate to dogs heterozygous for a functionally null mutation in Pde6a over a 4-month period. Three Pde6a +/- dogs were administered 14.3 mg/kg sildenafil per os and two Pde6a +/- dogs placebo once daily for 16 weeks. Three Pde6a +/+ dogs were administered sildenafil for 7 days. Ophthalmic examination, vision testing, and electroretinography (ERG) were regularly performed. At study termination, dogs were euthanized and globes collected. Retinal layer thickness and photoreceptor nuclei counts were determined from plastic sections. In both Pde6a +/- and Pde6a +/+ sildenafil-treated (ST) dogs, elevation of dark-adapted b-wave threshold and unmasking of the scotopic threshold response (STR) were observed. Sildenafil treated Pde6a +/- dogs had significantly thinner ONL (24.90 +/-1.88 µm, p = 0.004) and lower photoreceptor nuclei counts (273.6 +/- 29.3 cells/100 µm, p = 0.008) compared to measurements (35.90 +/- 1.63 µm) and counts (391.5 +/-27.0 cells/100 µm) from archived untreated Pde6a +/- dogs.

An association between systemic cyclosporine administration and development of acute bullous keratopathy in cats.

OBJECTIVE: To determine whether any association exists between the onset of feline acute bullous keratopathy (ABK) and administration of systemic corticosteroid or immunosuppressive therapy. ANIMALS STUDIED: Medical records of cats diagnosed with ABK between the years of 2000 and 2008 were retrospectively reviewed. Breed, age at diagnosis, weight, systemic disease status, eye affected, ophthalmic examination findings, systemic and topical therapy instituted, dosage and duration of therapy, visual outcome and histopathological analyses were recorded in cases meeting the inclusion criteria. RESULTS: A total of 12 cats of a surveyed population of 70 167 met the inclusion criteria with 17/24 eyes affected by ABK. Medical and/or surgical therapy was utilized for management of ABK with 13/17 eyes remaining sighted at the time of last follow-up. In a subset of cases corneal cytology, aerobic bacterial culture, FHV-1 PCR, virus isolation and/or histopathology were performed; no infectious organisms were identified. A rupture in Descemet's membrane of the cornea was identified histologically in two globes. A total of 10 of 12 cats had been previously diagnosed with ongoing systemic disease. A total of 10 of 12 cats were receiving systemic therapy, and a significant association (P < 0.001) was noted between systemic administration of corticosteroids and/or cyclosporine A and the development of ABK. A total of 8 of 10 cats were administered oral prednisolone at doses between 1-2 mg/kg every 12-24 h. A total of 5 of 8 cats receiving oral prednisolone were concurrently administered oral cyclosporine at doses of 1.5-7 mg/kg every 12-24 h. Systemic cyclosporine therapy was found to be a significant risk factor (P < 0.001) for ABK development, while systemic prednisolone was not significant (P = 0.10). CONCLUSIONS: Systemic cyclosporine administration appears to be a risk factor for development of ABK in the population of cats studied.

Improving sexual health communication between older women and their providers: how the integrative model of behavioral prediction can help.

Talking about sexual health can be a challenge for some older women. This project was initiated to identify key factors that improve communication between aging women and their primary care providers. A sample of women (aged 60+) completed an online survey regarding their intent to communicate with a provider about sexual health. Using the integrative model of behavioral prediction as a guide, the survey instrument captured data on attitudes, perceived norms, self-efficacy, and intent to communicate with a provider about sexual health. Data were analyzed using structural equation modeling. Self-efficacy and perceived norms were the most important factors predicting intent to communicate for this sample of women. Intent did not vary with race, but mean scores of the predictors of intent varied for African American and White women. Results can guide practice and intervention with ethnically diverse older women who may be struggling to communicate about their sexual health concerns.

Successful gene therapy in older Rpe65-deficient dogs following subretinal injection of an adeno-associated vector expressing RPE65.

Young Rpe65-deficient dogs have been used as a model for human RPE65 Leber congenital amaurosis (RPE65-LCA) in proof-of-concept trials of recombinant adeno-associated virus (rAAV) gene therapy. However, there are relatively few reports of the outcome of rAAV gene therapy in Rpe65-deficient dogs older than 2 years of age. The purpose of this study was to investigate the success of this therapy in older Rpe65-deficient dogs. Thirteen eyes were treated in dogs between 2 and 6 years old. An rAAV2 vector expressing the human RPE65 cDNA driven by the human RPE65 promoter was delivered by subretinal injection. Twelve of the 13 eyes had improved retinal function as assessed by electroretinography, and all showed improvement in vision at low lighting intensities. Histologic examination of five of the eyes was performed but found no correlation between electroretinogram (ERG) rescue and numbers of remaining photoreceptors. We conclude that functional rescue is still possible in older dogs and that the use of older Rpe65-deficient dogs, rather than young Rpe65-deficient dogs that have very little loss of photoreceptors, more accurately models the situation when treating human RPE65-LCA patients.

Analysis of a survey database of pet food-induced poisoning in North America.

Following the outbreak of pet food-induced nephrotoxicity in March 2007, a voluntary online survey of all AAVLD-accredited laboratories, commercial laboratories, and veterinary clinics across North America was conducted. There was no information on toxicity of melamine or factors affecting the disease outcome following exposure to melamine in pets. Data were collected from affected pets to learn about the disease outcome and the affected pet population. The web-based electronic survey used the online tool, Survey Monkey™. Data were collected between April 5 and October 31, 2007. Four hundred fifty-one cases of 586 reported cases met the criteria for inclusion in the study. Most reported cases were from California, Texas, Michigan, Florida, and Ontario. Of the 451 cases, 424 were reported as affected. Of these, 278 cases (65.6%) were cats and 146 (34.4%) were dogs. A total of 278 pets (171 cats and 107 dogs) were reported to have died (a ratio of 1.6:1). However, within species, there was a higher percentage of deceased dogs (73.3%) than cats (61.5%). Of the affected pet population, older male cats with preexisting disease conditions were more likely to be deceased. Analysis of the pets in this large database of naturally affected pets yielded interesting findings. It showed that more cats than dogs were affected and also that preexisting renal diseases and old age predicted the most severe outcome (death or euthanasia) than any other factors.

Re-expansion pulmonary oedema and circulatory shock in a 20-year-old man.

Re-expansion pulmonary oedema is a well-recognized rare complication of the treatment of spontaneous pneumothorax. It has been associated with death in 20% of cases. A fit 20-year-old man who had returned from holiday 2 days previously presented with a large left-sided pneumothorax of 10 days' duration. He had exhibited symptoms of chest pain and shortness of breath during the return flight. He showed no signs of respiratory distress at presentation to the Accident and Emergency Department, but after treatment with a chest tube in the ensuing 90 min developed severe unilateral re-expansion pulmonary oedema and circulatory collapse. Factors in the aetiology of the condition and prevention are considered.

Use of middle infrared radiation to estimate the leaf area index of a boreal forest.

The leaf area index (LAI) of boreal forest can be estimated using reflected radiation recorded by satellite sensors. Measurements of visible and near infrared radiation are commonly used in the normalized difference vegetation index (NDVI) to estimate LAI. However, research, mainly in tropical forest, has demonstrated that LAI is related more closely to radiation of middle infrared wavelengths than of visible wavelengths. This paper derives a vegetation index, VI3, based on radiation from vegetation recorded at near and middle infrared wavelengths. For a boreal forest canopy, the relationship between VI3 and LAI was observed to be much stronger than that between NDVI and LAI. In addition, the LAI estimated using VI3 accounted for about 76% of the variation in field estimates of LAI, compared with about 46% when using the NDVI. We conclude that information provided by middle infrared radiation should be considered when estimating the leaf area index of boreal forest.

The potential of a monocyte cell surface marker as an indicator of endotoxin exposure.

Endotoxin is common in workplaces such as farms, grain processing plants and cotton mills, and exposure can lead to a wide variety of respiratory symptoms including organic toxic dust syndrome and chronic bronchitis. We developed an in vitro model to enable us to determine the use of lipopolysaccharide receptor (CD14) expression to act as a biomarker of endotoxin exposure. Whole blood was incubated with endotoxin, human serum albumin (HSA) or phosphate buffered saline (PBS) at 37 C to determine the time course of CD14 expression following in vitro stimulus. Fluorescent-labelled antibodies were used to label CD14 on monocytes, and CD45 on monocytes and lymphocytes. Levels of CD14 and CD45 expression were measured by flow cytometry. Levels of expression were determined on eight different samples at the optimum time point and concentration of endotoxin. CD14 expression on monocytes was upregulated in response to endotoxin exposure (p < 0 0001) and could be measured easily in whole blood samples using flow cytometry 4 h afterexposure. CD45 upregulation in response to endotoxin was monocytespecific (p < 0 0001), there was no significant difference in expression of CD45 on lymphocytes between the PBS and HSA controls and endotoxin-exposed cells (p= 0 6). We have shown that the expression of cell surface CD14 and CD45 was significantly increased following in vitro exposure to endotoxin, and that this response was specific for monocytes. We suggest that the measurement of CD14 on monocytes by flow cytometry may be a useful biomarkerof endotoxin exposure.

Exploring the relationship between reflectance red edge and chlorophyll content in slash pine.

Chlorophyll is a key indicator of the physiological status of a forest canopy. However, its distribution may vary greatly in time and space, so that the estimation of chlorophyll content of canopies or branches by extrapolation from leaf values obtained by destructive sampling is labor intensive and potentially inaccurate. Chlorophyll content is related positively to the point of maximum slope in vegetation reflectance spectra which occurs at wavelengths between 690-740 nm and is known as the "red edge." The red edge of needles on individual slash pine (Pinus elliottii Engelm.) branches and in whole forest canopies was measured with a spectroradiometer. Branches were measured on the ground against a spectrally flat reflectance target and canopies were measured from observation towers against a spectrally variable understory and forest floor. There was a linear relationship between red edge and chlorophyll content of branches (R(2) = 0.91). Measurements of the red edge and this relationship were used to estimate the chlorophyll content of other branches with an error that was lower than that associated with the calorimetric (laboratory) method. There was no relationship between the red edge and the chlorophyll content of whole canopies. This can be explained by the overriding influence of the understory and forest floor, an influence that was illustrated by spectral mixture modeling. The results suggest that the red edge could be used to estimate the chlorophyll content in branches, but it is unlikely to be of value for the estimation of chlorophyll content in canopies unless the canopy cover is high.