Wisconsin Disability Association

ABSTRACTObjectiveAlexander disease (AxD) is a severe neurodegenerative disorder caused by gain‐of‐function mutations in the gene for GFAP, which lead to protein aggregation and a primary astrocytopathy. Symptoms vary, but failure to thrive (FTT) and frequent emesis are common and cause significant morbidity. Here we investigate GDF15, a member of the TGFβ superfamily, which regulates energy balance and appetite, as a potential mediator of FTT in AxD.MethodsIn this study, we use the Gfap+/R237H rat model (R237H), in which pups fail to gain weight after weaning and become frail and impaired as they mature, to assess muscle atrophy, energy expenditure, and feeding behavior in AxD. We measure GDF15 in brain and cerebrospinal fluid (CSF), assess activation of its receptor GFRAL in area postrema neurons, and use GFAP suppression to correlate FTT phenotypes with GDF15 expression. Finally, we measure GDF15 in patients with AxD.ResultsR237H rats show reduced lean and fat mass and muscle atrophy despite reduced energy expenditure, and at an early age exhibit pica and anorexia. GDF15 is expressed by R237H rat astrocytes and is elevated in brainstem and CSF, but not in plasma. Neurons expressing GFRAL, a mediator of GDF15‐induced appetite suppression, are activated in the area postrema. Suppression of GFAP using antisense oligonucleotides normalizes weight gain and GDF15 levels in brainstem and CSF. In human AxD, GDF15 is elevated in CSF, but not in blood.InterpretationGDF15 is associated with FTT in AxD and provides both a target and useful biomarker for the development of future therapeutics.

ABSTRACTAn increasing number of physically active adults are taking the mTOR inhibitor rapamycin off label with the goal of extending healthspan. However, frequent rapamycin dosing disrupts metabolic health during sedentary conditions and abates the anabolic response to exercise. Intermittent once‐weekly rapamycin dosing minimizes many negative metabolic side effects of frequent rapamycin in sedentary mice. However, it remains unknown how different rapamycin dosing schedules impact metabolic, physical, and skeletal muscle adaptations to voluntary exercise training. Therefore, we tested the hypothesis that intermittent rapamycin (2 mg/kg; 1×/week) would avoid detrimental effects on adaptations to 8 weeks of progressive weighted wheel running (PoWeR) in adult female mice (5‐month‐old) by evading the sustained inhibitory effects on mTOR signaling by more frequent dosing schedules (2 mg/kg; 3×/week). PoWeR improved maximal exercise capacity, absolute grip strength, and myofiber hypertrophy with no differences between vehicle or rapamycin‐treated mice despite greater voluntary running volume with intermittent rapamycin treatment. Conversely, frequent and intermittent rapamycin‐treated mice had impaired glucose tolerance and insulin sensitivity compared to vehicle‐treated mice after PoWeR; however, intermittent rapamycin reduced the impact on glucose intolerance versus frequent rapamycin. Collectively, these data in adult female mice suggest that (1) rapamycin is largely compatible with the physical and skeletal muscle benefits of PoWeR and (2) the detrimental effects of rapamycin on glucose metabolism in the context of voluntary exercise may be reduced by intermittent dosing.

BackgroundPrader-Willi syndrome (PWS) is a complex genetic neurodevelopmental condition characterised by a range of debilitating and lifelong symptoms. The many physical and behavioural challenges that arise with adults with PWS often necessitate full-time (i.e., 24-hour) professional care support. However, despite the fact that many clinicians regard full-time PWS-specific care to represent best practice, relatively few studies have directly examined the benefits of such services. The purpose of this paper is to use archival data to investigate the impact of full-time care services on people with PWS, and to assemble a large statistical dataset on which robust analyses of improvements in weight, BMI, and behavioural outcomes can be based.MethodsInformation collated by the International PWS Organisation (IPWSO), an international non-profit membership organisation supporting national PWS associations around the world, was combined into a single anonymised dataset for statistical analysis. Data were supplied by service-providers from several countries who provide full-time support to people with PWS. The dataset included details on the specific services provided, basic demographic information on service recipients, including weight, body mass index (BMI), and observational records relating to behaviours of concern (BOC; consisting of temper outbursts, skin-picking, egocentrism, inflexibility, and striving for dominance).ResultsA total of 193 people with PWS (ranging in age from < 10 yrs to > 50 yrs; 93% of whom were > 18 yrs), residing in 11 services across 6 countries, were represented in the dataset. On average, people with PWS showed significant reductions in weight and BMI after joining a full-time care service, with improvements within one year of entering, which were cumulative over time and independent of age or initial weight at entry. Similar cumulative improvements over time were seen for BOC within one year and were unrelated to age or severity of BOC at entry. The degree to which services are specialised for residents with PWS appeared to confer particular benefits, with people living in PWS-exclusive services showing the greatest improvements in weight, BMI, and BOC. Reductions in BOC were associated with greater, rather than less, social contact, suggesting that these improvements were not achieved at the expense of broader freedoms, such as the opportunity to meet with families and friends.ConclusionsWe conclude that full-time care services have a high likelihood of enhancing the lives of people with PWS within one year with long-lasting benefits, especially if those services are exclusive and specialised around the particular needs of PWS.

The American Association on Intellectual and Developmental Disabilities (AAIDD) and The Arc of the United States (The Arc) have a long history of taking jointly held positions on matters of public policy that affect people with intellectual and developmental disabilities (IDD). This article describes the methods used to develop and evaluate the understandability and fidelity of written plain language summaries of the organizations' joint position statements for an audience of people with IDD who read. Implications for adapting source material for nonreading audiences are discussed.

Small-scale farming of edible insects could help combat public health challenges such as protein energy malnutrition and anemia, but reliable low-cost feeds for insects are needed. In resource-limited contexts, where grains such as maize are prohibitively costly for use as insect feed, the feasibility of insect farming may depend on finding alternatives. Here, we explore the potential to modify plentiful maize crop residue with edible mushroom mycelium to generate a low-cost feed adjunct for the farmed two-spotted cricket, Gryllus bimaculatus. Mushroom farming, like insect agriculture, is versatile; it can yield nutritious food while increasing system circularity by utilizing lignocellulosic residues from row crops as inputs. Pleurotus ostreatus, is an edible basidiomycete capable of being cultivated on corn stover (Zea mays). Mushroom harvest results in abundant “spent” substrate, which we investigated as a candidate feed ingredient. We created six cricket feeds containing fermented Pleurotus substrate plus an unfermented control, measuring cricket mass, mortality, and maturation weekly to evaluate cricket growth performance impacts of both fungal fermentation duration and mushroom formation. Pasteurized corn stover was inoculated with P. ostreatus mycelium and fermented for 0, 2, 3, 4, or 8 weeks. Some 4 and 8-week substrates were induced to produce mushrooms through manipulations of temperature, humidity, and light conditions. Dried fermented stover (40%) was added to a 1:1 corn/soy grain mix and fed to crickets ad libitum for 44 days. The unfermented control group showed higher survivorship compared to several fermented diets. Control group mass yield was higher for 2 out of 6 fermented diets. Little variation in cricket iron content was observed via ICP-spectrometry across feeds, averaging 2.46 mg/100 g. To determine bioavailability, we conducted in vitro Caco-2 human colon epithelial cell absorption assays, showing that iron in crickets fed fruiting-induced substrates was more bioavailable than in unfruited groups. Despite more bioavailable iron in crickets reared on post-fruiting substrates, we conclude that Pleurotus-fermented stover is an unsuitable feed ingredient for G. bimaculatus due to high mortality, variability in growth responses within treatments, and low mass yield.

Food cellars, otherwise referred to as ice or meat cellars, (lednik in Russian, k’aetyran in Chukchi, siġļuaq in Iñupiaq, and siqlugaq in Yupik) are a natural form of refrigeration in permafrost or seasonally frozen ground used to preserve, age, and ferment foods harvested for subsistence, including marine mammals, birds, fish, and plants. Indigenous peoples throughout the Arctic have constructed cellars in frozen ground for millennia. This paper focuses on cellars in Russian and American coastal and island communities of the Bering Strait, the region otherwise known as Beringia. This area has a unique, culturally rich, and politically dynamic history. Many traditions associated with cellars are threatened in Chukchi communities in Russia because of the impacts of climate change, relocation, dietary changes, and industrial development. However, even with warmer temperatures, cellars still provide a means to age and ferment food stuffs following traditional methods. In cooperation with local stakeholders, we measured internal temperatures of 18 cellars in 13 communities throughout the Bering Strait region and northern Alaska. Though cellars are widely used in permafrost regions, their structure, usage, and maintenance methods differ and exhibit influences of local climates, traditions, and economic activities. Monitoring internal temperatures and recording structural descriptions of cellars is important in the face of climate change to better understand the variety and resilience of living adaptations in different cold regions.

Three deliberate teaching practices can help students strengthen multiple connections to a unifying concept.

The James Bay Treaty-Treaty No. 9 was unique among the numbered treaties of Canada in that there was a need for the concurrence of the Province of Ontario. Last-minute negotiations by the Dominion of Canada to gain said concurrence led to an agreement with the Province of Ontario, and this agreement became part of the Treaty No. 9 package at Ontario’s insistence. However, since the agreement was not executed until after the Treaty No. 9 expedition had left for the field, an incomplete Treaty No. 9 package that lacked the agreement was presented to and signed by the First Nation groups in 1905. Furthermore, spaces had been left in the vellum copies of Treaty No. 9 and the agreement to add in the date of the agreement when fully executed. In the spaces that were left for this purpose, the date of the agreement was backdated to 3 July. This act of deception was suggested by the Treasurer of the Government of Ontario, A. Matheson in order to date of the agreement earlier than the date in the Treaty. Thus, the common law legality of the Treaty No. 9 package must be questioned, especially since officials of the Governments of Canada and Ontario left documentation of their deception. Without the agreement being attached as specified in the Treaty No. 9 document that left Ottawa in 1905, consideration of the terms of the agreement by the First Nation signatories of the treaty could not have occurred prior to signing. It follows that there exists a question of whether the land south of the Albany River was ever ceded in Treaty No. 9 from a common law perspective, unless documentation can be presented indicating that the complete Treaty No. 9 package was presented to the First Nation signatories; the written record indicates otherwise. In the end, the courts will have to decide the legality of Treaty No. 9 from a common law perspective.