Role of Drosophila IKK gamma in a toll-independent antibacterial immune response

We have generated, by ethylmethane sulfonate mutagenesis, loss-of-function mutants in the Drosophila homolog of the mammalian I-kappa B kinase (IKK) complex component IKK gamma (also called NEMO). Our data show that Drosophila IKK gamma is required for the Relish-dependent immune induction of the genes encoding antibacterial peptides and for resistance to infections by Escherichia coli. However, it is not required for the Toll-DIF-dependent antifungal host defense. The results indicate distinct control mechanisms of the Rel-like transactivators DIF and Relish in the Drosophila innate immune response and show that Drosophila Toll does not signal through a IKK gamma-dependent signaling complex. Thus, in contrast to the vertebrate inflammatory response, IKK gamma is required for the activation of only one immune signaling pathway in Drosophila.     

Functional magnetic resonance imaging evidence for binocular interactions in human visual cortex

Using functional magnetic resonance imaging (fMRI), we explored the binocular interactions occurring when subjects viewed dichoptically presented checkerboard stimuli. A flickering radial checkerboard was presented to each eye of the subject, while T2*-weighted images were acquired over the visual cortex with gradient-echo, echoplanar sequences. We compared responses in striate and extrastriate visual cortex under four conditions: both eyes were stimulated at the same time (binocular condition), each eye was stimulated in alternation (monocular condition) or first the one eye then the other eye was stimulated (left eye first - right eye trailing, or vice versa). The results indicate that only the striate area, in and near the calcarine fissure, shows significant differences for these stimulation conditions. These differences are not evident in more remote extrastriate or associational visual areas, although the BOLD response in the stimulation-rest comparison was robust. These results suggest that the effect could be related to inhibitory interactions across ocular dominance columns in striate visual cortex.     

Users' Perceptions of the Impact of Electronic Aids to Daily Living Throughout the Acquisition Process

This study investigated the experience of seven new users of a particular type of assistive technology through the stages of anticipating, acquiring, and using an electronic aid to daily living. A mixed methods research approach was used to explore each of these stages. The Psychosocial Impact of Assistive Devices Scale was used to measure the perceived impact of the new assistive technology on users' quality of life, and findings were further explored and developed through open-ended questioning of the participants. Results indicated that preacquisition of the device, users predicted that the electronic aid to daily living would have a positive impact on their feelings of competence and confidence and that the device would enable them in a positive way. One month after acquiring the device a reduced, yet still positive, impact was observed. By 3 and 6 months after acquisition, perceived impact returned to the same positive high level as preacquisition. It is suggested that prior to receiving the device, potential users have positive expectations for the device that are not based in experience. At the early acquisition time, users adjust expectations of the role of the assistive technology in their lives and strive to balance expectations with reality. Three to 6 months after acquiring an electronic aid to daily living, the participants have a high positive view of how the device impacts on their lives based in experience and reality. A model illustrating the electronic aids to daily living acquisition process is proposed, and suggestions for future study are provided.     

Changes in exertion-related symptoms in adults and youth who have sustained a sport-related concussion

ObjectivesTo identify the symptoms responsible for cessation of exercise testing and evaluate changes in post-concussion symptom scores on the Post-Concussion Symptom Scale (PCSS) from the Sport-Concussion Assessment Tool (SCAT5) immediately, 1–4 h, and 6–12 h following completion of the Buffalo Concussion Treadmill Test (BCTT) in youth and adults who have sustained a sport-related concussion.DesignProspective case-series.MethodsIndividuals who were diagnosed with a sport-related concussion and self-reported difficulties with exertion were referred to perform an exertional treadmill test. Individuals were recruited from a university sports medicine clinic. Change in PCSS symptom severity scores were operationally defined as a change ≥4 points.ResultsForty-five individuals aged 13–57 years consented to participate. A total of 14/24 (58.3%) female and 13/21 (61.9%) male participants reported an increase in symptom severity scores immediately following the BCTT. At 1–4 h, 5/10 (50.0%) males and 5/14 (35.7%) females who completed the PCSS had elevated symptom severity scores compared to pre-exertion. Only 24.2% (3/17 males and 5/16 females) of participants completing the PCSS at 6–12 h reported increased symptom severity scores.ConclusionExertional testing is an important component of a multifaceted assessment following concussion; however, previous research evaluating symptom responses to exertion is limited. This study provides evidence to suggest individuals who experience an exacerbation of concussion-associated symptoms after exertion are likely to return to pre-exertion levels within the same day. Future research monitoring symptoms following exertion and throughout recovery should be performed in tandem with physiological measures to better understand the source of symptoms.     

Disruption of copper homeostasis due to a mutation of Atp7a delays the onset of prion disease

Copper influences the pathogenesis of prion disease, but whether it is beneficial or detrimental remains controversial. Copper homeostasis is also essential for normal physiology, as highlighted by the spectrum of diseases caused by disruption of the copper transporting enzymes ATP7A and ATP7B. Here, by using a forward genetics approach in mice, we describe the isolation of three alleles of Atp7a, each with different phenotypic consequences. The mildest of the three, Atp7a(brown), was insufficient to cause lethality in hemizygotes or mottling of the coat in heterozygotes, but did lead to coat hypopigmentation and reduced copper content in the brains of hemizygous males. When challenged with Rocky Mountain Laboratory scrapie, the onset of prion disease was delayed in Atp7a(brown) mice, and significantly less proteinase-resistant prion protein was found in the brains of moribund Atp7a(brown) mice compared with WT littermates. Our results establish that ATP7A-mediated copper homeostasis is important for the formation of pathogenic proteinase-resistant prion protein.     

One Size Does Not Fit All: Choosing Practical Cognitive Screening Tools for Your Practice

Every year, millions of patients worldwide undergo cognitive testing. Unfortunately, new barriers to the use of free open access cognitive screening tools have arisen over time, making accessibility of tools unstable. This article is in follow-up to an editorial discussing alternative cognitive screening tools for those who cannot afford the costs of the Mini-Mental State Examination and Montreal Cognitive Assessment (see www.dementiascreen.ca ). The current article outlines an emerging disruptive “free-to-fee” cycle where free open access cognitive screening tools are integrated into clinical practice and guidelines, where fees are then levied for the use of the tools, resulting in clinicians moving on to other tools. This article provides recommendations on means to break this cycle, including the development of tool kits of valid cognitive screening tools that authors have contracted not to charge for (i.e., have agreed to keep free open access). The PRACTICAL.1 Criteria ( PRACTI cing C linician A ccessibility and L ogistical Criteria Version 1 ) are introduced to help clinicians select from validated cognitive screening tools, considering barriers and facilitators, such as whether the cognitive screening tools are easy to score and free of cost. It is suggested that future systematic reviews embed the PRACTICAL.1 criteria, or refined future versions, as part of the standard of review. Methodological issues, the need for open access training to insure proper use of cognitive screening tools, and the need to anticipate growing ethnolinguistic diversity by developing tools that are less sensitive to educational, cultural, and linguistic bias are discussed in this opinion piece. J Am Geriatr Soc 68:2207–2213, 2020.