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Two new high-performance insulation materials (HPIM) for the usage in buildings are presented. We show how to use and apply the upcoming aerogel products and give examples for structural details. While both materials achieve very low lambda values due to Knudsen-Effect of aerogels, they differ clearly in other key characteristics. SLENTEX® is a slim, mechanically flexible, non-combustible aerogel mat. It is open for water vapor diffusion but water-repellent. It is suitable for applications with strict fire regulations since it is a purely mineral-based product. SLENTITE® is a homogeneous polyurethane-based aerogel insulation board without lamination or encapsulation layers and also vapor open. Its surface adheres to almost any organic or inorganic binder. It can be processed very much like conventional insulation boards. While their handling and application are very similar to other insulation materials, aerogels are however no general-purpose insulation products: due to their sophisticated production process, and thus higher price compared to conventional insulation products, HPIM are best applied as problem solvers. In well-motivated situations, e.g. where space is limited or particular aesthetic requirements apply, they offer cost effective alternatives to standard solutions.

We present two recent test case application examples of a new high-performance insulation panel with product name SLENTITE® used as core element of a rendered internal wall insulation system. The first case study refers to the 18th-century building Alte Schäfflerei now the Fraunhofer Centre for Conservation and Energy Performance of Historic Buildings, at the monastery Benediktbeuern, southern Germany, where SLENTITE® was applied in 11/2017. The second test case was installed in 04/2019 in a heritage building situated in the historic center of Luxembourg. In Benediktbeuern, a single layer of insulation material was chosen, in Luxembourg we applied two layers of insulation. In both cases, detail work around the windows was a main task and we gained experience on product processing under real conditions. In terms of indoor room usage, the object in Benediktbeuern is used as exhibition hall with rare traffic and well controlled climate, whereas the object in Luxembourg is used as meeting room without climate control. Measured data of 20 months from the object in Benediktbeuern and first impressions of the performance in Luxembourg are discussed.

Aims: The aggregation and deposition of amyloid-β (Aβ) peptides in the brain is thought to be the initial driver in the pathogenesis of Alzheimer's disease (AD). Aside from full-length Aβ peptides starting with an aspartate residue in position 1, both N-terminally truncated and elongated Aβ peptides are produced by various proteases from the amyloid precursor protein (APP) and have been detected in brain tissues and body fluids. Recently, we demonstrated that the particularly abundant N-terminally truncated Aβ4-x peptides are generated by ADAMTS4, a secreted metalloprotease that is exclusively expressed in the oligodendrocyte cell population. In this study, we investigated whether ADAMTS4 might also be involved in the generation of N-terminally elongated Aβ peptides., Methods: We used cell-free and cell-based assays in combination with matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF) and electrochemiluminescence sandwich immunoassays to identify and quantify N-terminally elongated Aβ peptide variants. Antibodies against these Aβ variants were characterised by peptide microarrays and employed for the immunohistochemical analyses of human brain samples., Results: In this study, we discovered additional ADAMTS4 cleavage sites in APP. These were located N-terminal to Asp-(1) in the Aβ peptide sequence between residues Glu-(-7) and Ile-(-6) as well as Glu-(-4) and Val-(-3), resulting in the release of N-terminally elongated Aβ-6-x and Aβ-3-x peptides, of which the latter serve as a component in a promising Aβ-based plasma biomarker. Aβ-6/-3-40 peptides were detected in supernatants of various cell lines and in the cerebrospinal fluid (CSF), and ADAMTS4 enzyme activity promoted the release of Aβ-6/-3-x peptides. Furthermore, by immunohistochemistry, a subset of AD cases displayed evidence of extracellular and vascular localization of N-terminally elongated Aβ-6/-3-x peptides., Discussion: The current findings implicate ADAMTS4 in both the pathological process of Aβ peptide aggregation and in the early detection of amyloid pathology in AD., (© 2024 The Author(s). Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.)

Background: In Canada, disparities between Indigenous and non-Indigenous Peoples continue to exist in health and education because of the past and current harms of racism and colonization. One step towards closing health gaps is clinicians who can provide health and social care services that are free of racism and mistrust. Indigenous health providers are in the best position to provide this culturally relevant and safe care to their own communities. Therefore, more Indigenous students graduating from health professional programs are required to meet these needs. Indigenous identity support can be a facilitator for Indigenous student academic success but developing one's Indigenous identity can be challenging in post-secondary education environments. We explored how Indigenous rehabilitation students expressed, and wanted to be supported in their identity and academic success., Methods: Using a narrative inquiry approach, we conducted interviews with seven students from the occupational, physical, and respiratory therapy programs of a Canadian university. Students were asked to tell their story of learning about, applying to, and being in their rehabilitation program and how their Indigenous identity impacted these experiences. Data analysis was conducted by Indigenous and non-Indigenous team members, analyzing the stories on interaction of the participant with (1) themselves and others, (2) time, and (3) situation or place., Results: The researchers developed seven mini-stories, one for each participant, to illustrate the variation between participant experiences in the development of their Indigenous and professional identity, before and during their rehabilitation program. The students appreciated the opportunities afforded to them by being admitted to their programs in a Indigenous Peoples category, including identity affirmation. However, for most students, being in this category came with feared and/or experienced stigma. The work to develop a health professional identity brought even more complexity to the already complex work of developing and maintaining an Indigenous identity in the colonized university environment., Conclusion: This study highlights the complexity of developing a rehabilitation professional identity as an Indigenous student. The participant stories call for universities to transform into an environment where Indigenous students can be fully accepted for their unique gifts and the identities given to them at birth., (© 2024. The Author(s).)

The patients' fear of the dentist plays an important role in the everyday life of a dentist. The anxiety level of children in relation to dental treatment/visits and to their parents' dental fear was evaluated in three different centers. Assessments of a modified CFSS-DS (mCFSS-DS) were performed by questionnaire with 60 children and their parents. Children's dmft/DMFT scores, age and gender were evaluated in relation to the parents' perception of their child's anxiety levels. For statistical evaluation, Kruskal-Wallis and Wilcoxon tests as well as Spearman's correlation coefficient (Spearman) were used. The significance level was set at 0.05. There were no significant differences regarding children's mCFSS-DS between the three centers ( p = 0.398, Kruskal-Wallis). The parents' mCFSS-DS scores correlated significantly with their children's mCFSS-DS scores ( p = 0.004, Spearman). However, the mean mCFSS-DS score of the children was significantly higher than the mean score of parents' perception of their child's anxiety ( p = 0.000, Wilcoxon). The age of the child had an influence on the mCFSS-DS score ( p = 0.02, Kruskal-Wallis) but neither the children's gender ( p = 0.170, Kruskal-Wallis), nor the dmft/DMFT showed an impact ( p < 0.725, Spearman). Although a positive correlation was found between the results of the children's and parents' questionnaire, many parents underestimated the anxiety level of their children.

Senile plaques consisting of amyloid-beta (Aβ) peptides are a major pathological hallmark of Alzheimer's disease (AD). Aβ peptides are heterogeneous regarding the exact length of their amino- and carboxy-termini. Aβ1-40 and Aβ1-42 are often considered to represent canonical "full-length" Aβ species. Using immunohistochemistry, we analyzed the distribution of Aβ1-x, Aβx-42 and Aβ4-x species in amyloid deposits in the subiculum, hippocampus and cortex in 5XFAD mice during aging. Overall plaque load increased in all three brain regions, with the subiculum being the area with the strongest relative plaque coverage. In the subiculum, but not in the other brain regions, the Aβ1-x load peaked at an age of five months and decreased thereafter. In contrast, the density of plaques positive for N-terminally truncated Aβ4-x species increased continuously over time. We hypothesize that ongoing plaque remodeling takes place, leading to a conversion of deposited Aβ1-x peptides into Aβ4-x peptides in brain regions with a high Aβ plaque burden.

Background: Physiotherapists are often important figures in the lives of people with physical disabilities and chronic conditions, yet gaps in understanding remain regarding how therapists promote physical activity and leverage existing community-based recreation programs., Purpose: We used qualitative methods to explore experiences of physiotherapists as well as individuals with disabilities and chronic conditions receiving physiotherapy, with a focus on strategies to promote physical activity and the extent that therapists leverage community-based resources and programs., Methods: Semi-structured interviews were completed with nine physiotherapists (six American and three Canadian) and eight individuals with a physical disability (all Americans)., Results: Participants reflected on the salience of physical activity promotion throughout physiotherapy but also highlighted barriers. Three themes explored idealized and problematic experiences with physical activity promotion in therapy: 1) individualized promotion of physical activity; 2) increasing physical activity options for patients via engagement with the community; and 3) options for physical activity in the community. Differences were also noted between therapist and patient participants and when contrasting across countries (i.e. funding models). For instance, physiotherapists in publicly funded contexts relied more heavily on engagement with accessible community-based programming than privately funded counterparts., Conclusion: Therapists should further integrate patient perspectives when considering physical activity promotion. Additional research is needed to explore how therapists incorporate community-based programs into health promotion while further understanding the extent that these strategies align with the scope of physiotherapy practice in varying contexts.

Introduction: Racism exists in the healthcare system and is a root cause of health inequities among Indigenous Peoples. When microaggressions of racism are carried out by healthcare providers, therapeutic trust may be broken and quality of care may be impacted. Anti-racism response training is considered best practice in recognizing and addressing racism. The objective of this study was to evaluate the impact of a virtual (synchronous) anti-racism response training workshop among a group of rehabilitation therapists from across Canada., Methods: A 90-minute virtual anti-racism simulation workshop for rehabilitation therapists was developed and delivered virtually four times across Canada between 2020 and 2021. Following an introduction and pre-briefing, role-playing among participants was used to address microaggressive Indigenous-specific racism, followed by an in-depth debriefing with trained facilitators. A post-workshop survey was conducted to evaluate this anti-racism simulation workshop and assess the impact on participating occupational therapists (OTs) and physiotherapists (PTs). Following each simulation workshop, participants were invited to complete an anonymous post-activity survey ( n  = 20; 50% OTs, 45% PTs). Open text responses were analyzed thematically from the perspective of critical race theory., Results: The majority of the participants self-identified as women (95%); white (90%); mid-career (52%); and had never personally experienced racism (70%). All participants agreed that the workshop gave them ideas on how to start dismantling racism in their workplace. Thematic analysis resulted in four themes: so much to unlearn, remain humble, resist the silence, and discomfort is okay., Discussion: Despite feelings of discomfort, OTs and PTs appreciated anti-racism skills-based training and recognized the importance of taking action on racism in the workplace. Findings from this study support online (synchronous) anti-racism training as a viable and effective means of creating space for rehabilitation professionals to lean into brave conversations that are necessary for developing strategies to address racial microaggressions impacting Indigenous persons in the workplace. We believe that these small steps of preparing and practicing anti-racism strategies among rehabilitation therapists are essential to achieving a collective goal of dismantling racism in the health system., Competing Interests: AB was employed by Community Therapy Services Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Fricke, Beach Ducharme, Beavis, Flett and Oosman.)

Background: Following the onset of the COVID-19 pandemic, telerehabilitation (TR) has been expanding to address the challenges and risks of in-person delivery. It is likely that a level of TR delivery will continue after the pandemic because of its advantages, such as reducing geographical barriers to service. Many pandemic-related TR initiatives were put in place quickly. Therefore, we have little understanding of current TR delivery, barriers and facilitators, and how therapists anticipate integrating TR into current practice. Knowing this information will allow the incorporation of competencies specifically related to the use and provision of TR into professional profiles and entry-to-practice education, thereby promoting high-quality TR care., Objective: This study aimed to obtain a descriptive overview of current TR practice among rehabilitation therapists in Canada and the Netherlands and identify perceived barriers to and facilitators of practice., Methods: A web-based cross-sectional survey was conducted with occupational, physical, and respiratory therapists and dietitians in Canada (in French and English) and the Netherlands (in Dutch and English) between November 2021 and March 2022. Recruitment was conducted through advertisements on social media platforms and email invitations facilitated by regulatory and professional bodies. The survey included demographic and practice setting information; whether respondents delivered TR, and if so, components of delivery; confidence and satisfaction ratings with delivery; and barriers to and facilitators of use. TR satisfaction and uptake were measured using the Telehealth Usability Questionnaire and modified Technology Acceptance Model. Data were first summarized descriptively, and then, comparisons were conducted between professions., Results: Overall, 723 survey responses were received, mostly from Canada (n=666, 92.1%) and occupational therapists (n=434, 60%). Only 28.1% (203/723) reported receiving specific training in TR, with 1.2% (9/723) indicating that it was part of their professional education. Approximately 19.5% (139/712) reported not using TR at all, whereas most participants (366/712, 51.4%) had been using this approach for 1 to 2 years. Services delivered were primarily teleconsultation and teletreatment with individuals. Respondents offering TR were moderately satisfied with their service delivery and found it to be effective; 90.1% (498/553) indicated that they were likely to continue offering TR after the pandemic. Technology access, confidence, and setup were rated the highest as facilitators, whereas technology issues and the clinical need for physical contact were the most common barriers., Conclusions: Professional practice and experience with TR were similar in both countries, suggesting the potential for common strategic approaches. The high prevalence of current practice and strong indicators of TR uptake suggest that therapists are likely to continue TR delivery after the pandemic; however, most therapists (461/712, 64.7%) felt ill prepared for practice, and the need to target TR competencies during professional and postprofessional education is critical. Future studies should explore best practice for preparatory and continuing education., (©Edward Giesbrecht, Mel E Major, Moni Fricke, Pamela Wener, Maarten van Egmond, Jesse J Aarden, Cara L Brown, Margriet Pol, Marike van der Schaaf. Originally published in JMIR Rehabilitation and Assistive Technology (https://rehab.jmir.org), 20.02.2023.)

C-reactive protein (CRP) is an early-stage acute phase protein and highly upregulated in response to inflammatory reactions. We recently identified a novel mechanism that leads to a conformational change from the native, functionally relatively inert, pentameric CRP (pCRP) structure to a pentameric CRP intermediate (pCRP*) and ultimately to the monomeric CRP (mCRP) form, both exhibiting highly pro-inflammatory effects. This transition in the inflammatory profile of CRP is mediated by binding of pCRP to activated/damaged cell membranes via exposed phosphocholine lipid head groups. We designed a tool compound as a low molecular weight CRP inhibitor using the structure of phosphocholine as a template. X-ray crystallography revealed specific binding to the phosphocholine binding pockets of pCRP. We provide in vitro and in vivo proof-of-concept data demonstrating that the low molecular weight tool compound inhibits CRP-driven exacerbation of local inflammatory responses, while potentially preserving pathogen-defense functions of CRP. The inhibition of the conformational change generating pro-inflammatory CRP isoforms via phosphocholine-mimicking compounds represents a promising, potentially broadly applicable anti-inflammatory therapy., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

Introduction: Spatial navigation is a complex cognitive function that declines in older age. Finding one's way around in familiar and new environments is crucial to live and function independently. However, the current literature illustrates the efficacy of spatial navigation interventions in rehabilitative contexts such as pathological aging and traumatic injury, but an overview of existing training studies for healthy older adults is missing. This scoping review aims to identify current evidence on existing spatial navigation interventions in healthy older adults and analyze their efficacy., Methods: To identify spatial navigation interventions and assessments and investigate their effectiveness, four electronic databases were searched (Pubmed, Web of Science, CINAHL and EMBASE). Two independent reviewers conducted a screening of title, abstract and full-texts and performed a quality assessment. Studies were eligible if (1) published in English, (2) the full text was accessible, (3) at least one group of healthy older adults was included with (4) mean age of 65 years or older, (5) three or more spatial navigation-related training sessions were conducted and (6) at least one spatial ability outcome was reported., Results: Ten studies were included ( N  = 1,003, age-range 20-95 years, 51.5% female), only healthy older adults ( n  = 368, mean age ≥ 65) were assessed further. Studies differed in sample size ( n  = 22-401), type of training, total intervention duration (100 min-50 h), and intervention period (1-16 weeks)., Conclusion: The spatial navigation abilities addressed and the measures applied to elicit intervention effects varied in quantity and methodology. Significant improvements were found for at least one spatial ability-related outcome in six of 10 interventions. Two interventions achieved a non-significant positive trend, another revealed no measurable post-training improvement, and one study did not report pre-post-differences. The results indicate that different types of spatial navigation interventions improve components of spatial abilities in healthy older adults. The existing body of research does not allow conclusions on transferability of the trained components on everyday life spatial navigation performance. Future research should focus on reproducing and extending the promising approaches of available evidence. From this, valuable insights on healthy aging could emerge., Trial Registration: This scoping review was preregistered at Open Science Framework (https://osf.io/m9ab6)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fricke, Morawietz, Wunderlich, Muehlbauer, Jansen, Gramann and Wollesen.)

Introduction: Team-based care has been integrated into primary care (PC) across Canada because it improves patient safety, effectiveness, efficiency, person-centredness, and equity. However, this integration in and of itself may not lead to improved patient care without effective interpersonal relationships amongst team members. Currently, teams have few tools to guide the development of collaborative relationships. The Interprofessional Collaborative Relationship-building Model (ICRB) was developed to be a tool for understanding the stages of development of the interprofessional team's relationship-building., Purpose: This qualitative secondary data analysis illuminates a PC team's experiences of their developing interprofessional relationships with occupational therapists and physical therapists who joined the PC team., Method: Eleven team member interviews of one primary care team from a family medicine teaching clinic affiliated with a training university and the health region in central Canada were analyzed using secondary data analysis. The team included family physicians ( n = 4), nurses ( n = 2), a social worker ( n = 1), a mental health counselor ( n = 1), occupational therapists ( n = 2), and a physical therapist ( n = 1). We used the ICRB for directed content analysis using the phased approach that includes the three main steps of data preparation, data organization and data presentation., Results: This team experienced the ICRB stages of Looking For Help, Fitting-In, and Growing Reciprocity thereby learning about one another to better understand what OT and PT may bring to the PC setting. However, contrary to the ICRB, co-location, was the context within which the collaborative relationship-building took place rather than a distinct developmental stage. Although team members did experience some level of Growing Reciprocity, this developing team had not yet established collaborative leadership processes. As the ICRB originally posited, communication and patient focus facilitated all stages of the relationship-building process and helped the team develop shared values and role clarity that establish how different team members contribute to improving quality care., Conclusions: The context of co-location with a patient focus and open communication facilitated the team's development with the occupational therapists and physical therapist. Collaborative leadership is a worthy goal for future research and clinical focus as it has implications for improving overall patient quality care and team member work satisfaction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wener, Leclair, Fricke and Brown.)

Purpose: Multiple Canadian jurisdictions have curtailed public funding for outpatient physiotherapy services, impacting access and potentially creating or worsening inequities in access. We sought to identify evaluated organizational strategies that aimed to improve access to physiotherapy services for community-dwelling persons. Method: We used Arksey and O'Malley's scoping review methods, including a systematic search of CINAHL, MEDLINE, and Embase for relevant peer-reviewed texts published in English, French, or German, and we performed a qualitative content analysis of included articles. Results: Fifty-one peer-reviewed articles met inclusion criteria. Most studies of interventions or system changes to improve access took place in the United Kingdom (17), the United States (12), Australia (9), and Canada (8). Twenty-nine studies aimed to improve access for patients with musculoskeletal conditions; only five studies examined interventions to improve equitable access for underserved populations. The most common interventions and system changes studied were expanded physiotherapy roles, direct access, rapid access systems, telerehabilitation, and new community settings. Conclusions: Studies evaluating interventions and health system changes to improve access to physiotherapy services have been limited in focus, and most have neglected to address inequities in access. To improve equitable access to physiotherapy services in Canada, physiotherapy providers in local settings can implement and evaluate transferable patient-centred access strategies, particularly telerehabilitation and primary care integration., (© Canadian Physiotherapy Association.)

Background: Since facial paralysis is a dynamic condition, the analysis of still photographs is not sufficient for measurement of facial reanimation outcomes. This study aimed at evaluating an artificial intelligence (AI)-driven software as a novel video assessment tool for smile reanimation surgery and at comparing it with the Terzis score. Methods: Patients with facial paralysis undergoing smile reanimation surgery between January 2008 and April 2020 were eligible for this retrospective study. Inclusion criteria were at least 6 months of follow-up and availability of both pre- and post-operative video documentation. The software output was given as intensity score (IS) values between 0 and 1, representing emotions/action units (AUs) that are absent or fully present, respectively. Results: During the study period, 240 patients underwent facial reanimation surgery, of whom 63 patients met the inclusion criteria. Postoperatively, the median IS of the happiness emotion and lip corner puller AU increased significantly ( p  < 0.001). There was a positive correlation of Terzis score with the IS of happiness emotion ( r  = 0.8) and lip corner puller AU ( r  = 0.74). Conclusions: The novel AI-driven video analysis is strongly correlated with the Terzis score and shows promise for objective functional outcome evaluation after smile reanimation surgery.

Previous research has shown that as the level of background noise increases, auditory word recognition performance drops off more rapidly for bilinguals than monolinguals. This disproportionate bilingual deficit has often been attributed to a presumed increase in cross-language activation in noise, although no studies have specifically tested for such an increase. We propose two distinct mechanisms by which background noise could cause an increase in cross-language activation: a phonetically based account and an executive function-based account. We explore the evidence for the phonetically based account by comparing cognate facilitation effects for three groups of native English listeners (monolinguals, late (L2) learners of Spanish, and heritage Spanish speakers) and four noise conditions (no noise, speech-shaped noise, English two-talker babble, and Spanish two-talker babble) during an auditory lexical decision task in English. By examining word recognition in the dominant language, the role of language control mechanisms is minimized, and by examining three different types of competing noise, the role of energetic vs. informational masking can be assessed. Contrary to predictions, we find no evidence that background noise modulates cross-language activation; cognate facilitation is constant across the four noise conditions. Instead, several indices of word recognition performance are found to correlate with aspects of linguistic experience: (1) The magnitude of the cognate facilitation effect is correlated with heritage listeners' self-ratings of Spanish proficiency; (2) Overall noise deficits are marginally larger for heritage listeners with lower English vocabulary scores; (3) Heritage listeners' Spanish self-ratings predict their magnitude of informational masking; (4) For all bilinguals, the degree of masking incurred in both English and Spanish two-talker babble is correlated with self-reported daily exposure to Spanish; and (5) The degree of masking incurred by Spanish babble is correlated with Spanish vocabulary knowledge. The results enrich our understanding of auditory word recognition in heritage speakers in particular and provide evidence that informational masking is most subject to modulation due to variation in linguistic experience. It remains to be seen whether cross-language activation is modulated by noise when the target language is the less dominant one., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fricke.)

A fundamental regulator of neuronal network development and plasticity is the extracellular matrix (ECM) of the brain. The ECM provides a scaffold stabilizing synaptic circuits, while the proteolytic cleavage of its components and cell surface proteins are thought to have permissive roles in the regulation of plasticity. The enzymatic proteolysis is thought to be crucial for homeostasis between stability and reorganizational plasticity and facilitated largely by a family of proteinases named matrix metalloproteinases (MMPs). Here, we investigated whether MMP2 and MMP9 play a role in mediating adult primary visual cortex (V1) plasticity as well as stroke-induced impairments of visual cortex plasticity in mice. In healthy adult mice, selective inhibition of MMP2/9 for 7 d suppressed ocular dominance plasticity. In contrast, brief inhibition of MMP2/9 after a cortical stroke rescued compromised plasticity. Our data indicate that the proteolytic activity of MMP2 and MMP9 is critical and required to be within a narrow range to allow adult visual plasticity. SIGNIFICANCE STATEMENT Learning and recovery from injuries depend on the plasticity of neuronal connections. The brain's extracellular matrix (ECM) provides a scaffold for stabilizing synaptic circuits, while its enzymatic proteolysis is hypothesized to regulate homeostasis between stability and reorganizational plasticity. ECM digestion is facilitated by a family of matrix metalloproteinases (MMPs). Here, we show that treatments that inhibit MMP2/9 can either inhibit or rescue cortical plasticity depending on cortical state: in the visual cortex of healthy adult mice, inhibition of MMP2/9 suppressed cortical plasticity. In contrast, brief inhibition of MMP2/9 after a stroke rescued compromised plasticity. Our data provide strong evidence that an optimal level of MMP2/9 proteolytic activity is crucial for adult visual plasticity., (Copyright © 2022 the authors.)

Background: Hearing impairments are associated with reduced walking performance under Dual-task (DT) conditions. Little is known about the neural representation of DT performance while walking in this target group compared to healthy controls or younger adults. Therefore, utilizing the Mobile Brain/Body Imaging approach (MoBI), we aim at gaining deeper insights into the brain dynamics underlying the interaction of cognitive and motor processes during different DT conditions (visual and auditory) controlling for age and the potential performance decrements of older adults with hearing impairments. Methods: The cross-sectional study integrates a multifactorial mixed-measure design. Between-subject factors grouping the sample will be age (younger vs. older adults) and hearing impairment (mild vs. not hearing impaired). The within-subject factors will be the task complexity (single- vs. DT) and cognitive task modality (visual vs. auditory). Stimuli of the cognitive task will vary according to the stimulus modality (visual vs. auditory), presentation side (left vs. right), and presentation-response compatibility (ipsilateral vs. contralateral). Analyses of DT costs and underlying neuronal correlates focus either on gait or cognitive performance. Based on an a priori sample size calculation 96 (48 healthy and 48 mildly hearing impaired) community-dwelling older adults (50-70 years) and 48 younger adults (20-30 years) will be recruited. Gait parameters of speed and rhythm will be captured. EEG activity will be recorded using 64 active electrodes. Discussion: The study evaluates cognitive-motor interference (CMI) in groups of young and older adults as well as older adults with hearing impairment. The underlying processes of the interaction between motor and cognitive tasks will be identified at a behavioral and neurophysiological level comparing an auditory or a visual secondary task. We assume that performance differences are linked to different cognitive-motor processes, i.e., stimulus input, resource allocation, and movement execution. Moreover, for the different DT conditions (auditory vs. visual) we assume performance decrements within the auditory condition, especially for older, hearing-impaired adults. Findings will provide evidence of general mechanisms of CMI (ST vs. DT walking) as well as task-specific effects in dual-task performance while over ground walking., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wunderlich, Vogel, Šömen, Peskar, Fricke, Gramann, Protzak, Marusic and Wollesen.)

Phagocytosis and the formation of reactive oxygen species (ROS) in phagocytic leukocytes are an effective killing mechanism of the innate host defense. These cellular processes of innate immunity function in a complex interplay with humoral factors. C-reactive protein (CRP) in its activated, monomeric isoform (mCRP) has been shown to activate immune cells via the classical complement pathway. We investigated the complement-dependent effects of monomeric CRP (mCRP) on neutrophils and monocyte subtypes using complement-specific inhibitors by both flow cytometry and confocal fluorescence microscopy. We demonstrate that CRP-induced ROS generation is a conformation-specific and complement-dependent process in leukocyte subsets with classical monocytes as the primary source of ROS amongst human monocyte subsets. Elucidation of this complex interplay of CRP and complement in inflammation pathophysiology might help to improve anti-inflammatory therapeutic strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zeller, Bogner, Kiefer, Braig, Winninger, Fricke, Karasu, Peter, Huber-Lang and Eisenhardt.)

The pseudocubic (PC) parameterization of O 4 tetrahedra [Reifenberg & Thomas (2018). Acta Cryst. B74, 165-181] is applied to quartz (SiO 2 ) and its structural analogue germanium dioxide (GeO 2 ). In α-quartz and GeO 2 , the pseudocubes are defined by three length parameters, a PC , b PC and c PC , together with an angle parameter α PC . In β-quartz, α PC has a fixed value of 90°. For quartz, the temperature evolution of parameters for the pseudocubes and the silicon ion network is established by reference to the structural refinements of Antao [Acta Cryst. (2016), B72, 249-262]. In α-quartz, the curve-fitting employed to express the non-linear temperature dependence of pseudocubic length and Si parameters exploits the model of a first-order Landau phase transition utilized by Grimm & Dorner [J. Phys. Chem. Solids (1975), 36, 407-413]. Since values of tetrahedral tilt angles about ⟨100⟩ axes also result from the pseudocubic transformation, a curve for the observed non-monotonic variation of α PC with temperature can also be fitted. Reverse transformation of curve-derived values of [Si+PC] parameters to crystallographic parameters a, c, x Si , x O , y O and z O at interpolated or extrapolated temperatures is demonstrated for α-quartz. A reverse transformation to crystallographic parameters a, c, x O is likewise carried out for β-quartz. This capability corresponds to a method of structure prediction. Support for the applicability of the approach to GeO 2 is provided by analysing the structural refinements of Haines et al. [J. Solid State Chem. (2002), 166, 434-441]. An analysis of trends in tetrahedral distortion and tilt angle in α-quartz and GeO 2 supports the view that GeO 2 is a good model for quartz at high pressure., (open access.)

The precise mechanisms underlying the detrimental effects of early life adversity (ELA) on adult mental health remain still elusive. To date, most studies have exclusively targeted neuronal populations and not considered neuron-glia crosstalk as a crucially important element for the integrity of stress-related brain function. Here, we have investigated the impact of ELA, in the form of a limited bedding and nesting material (LBN) paradigm, on a glial subpopulation with unique properties in brain homeostasis, the NG2+ cells. First, we have established a link between maternal behavior, activation of the offspring's stress response and heterogeneity in the outcome to LBN manipulation. We further showed that LBN targets the hippocampal NG2+ transcriptome with glucocorticoids being an important mediator of the LBN-induced molecular changes. LBN altered the NG2+ transcriptome and these transcriptional effects were correlated with glucocorticoids levels. The functional relevance of one LBN-induced candidate gene, Scn7a , could be confirmed by an increase in the density of voltage-gated sodium (Na v ) channel activated currents in hippocampal NG2+ cells. Scn7a remained upregulated until adulthood in LBN animals, which displayed impaired cognitive performance. Considering that Na v channels are important for NG2+ cell-to-neuron communication, our findings provide novel insights into the disruption of this process in LBN mice., Competing Interests: GW reported having received lecture/consultancy fees from H. Lundbeck A/S, Servier SA, Astra Zeneca AB, Eli Lilly A/S, Sun Pharma Pty Ltd, Pfizer Inc, Shire A/S, HB Pharma A/S, Arla Foods A.m. b.A., Alkermes Inc, and Mundipharma International Ltd., Janssen AB. All other authors report no biomedical financial interests or potential conflicts of interest. This manuscript has been posted on a preprint server., (© 2021 The Authors.)

The freshwater microalga Chlamydomonas reinhardtii, which lives in wet soil, has served for decades as a model for numerous biological processes, and many tools have been introduced for this organism. Here, we have established a stable nuclear transformation for its marine counterpart, Chlamydomonas sp. SAG25.89, by fusing specific cis-acting elements from its Actin gene with the gene providing hygromycin resistance and using an elaborated electroporation protocol. Like C. reinhardtii, Chlamydomonas sp. has a high GC content, allowing reporter genes and selection markers to be applicable in both organisms. Chlamydomonas sp. grows purely photoautotrophically and requires ammonia as a nitrogen source because its nuclear genome lacks some of the genes required for nitrogen metabolism. Interestingly, it can grow well under both low and very high salinities (up to 50 g · L -1 ) rendering it as a model for osmotolerance. We further show that Chlamydomonas sp. grows well from 15 to 28°C, but halts its growth at 32°C. The genome of Chlamydomonas sp. contains some gene homologs the expression of which is regulated according to the ambient temperatures and/or confer thermal acclimation in C. reinhardtii. Thus, knowledge of temperature acclimation can now be compared to the marine species. Furthermore, Chlamydomonas sp. can serve as a model for studying marine microbial interactions and for comparing mechanisms in freshwater and marine environments. Chlamydomonas sp. was previously shown to be immobilized rapidly by a cyclic lipopeptide secreted from the antagonistic bacterium Pseudomonas protegens PF-5, which deflagellates C. reinhardtii., (© 2020 The Authors. Journal of Phycology published by Wiley Periodicals LLC on behalf of Phycological Society of America.)

Previous studies argued that body turns are executed in an ordered sequence: the eyes turn first, followed by the head and then by the trunk. The purpose of this study was to find out whether this sequence holds even if body turns are not explicitly instructed, but nevertheless are necessary to reach an instructed distal goal. We asked participants to shop for grocery products in a simulated supermarket. To retrieve each product, they had to walk down and aisle, and then turn left or right into a corridor that led towards the target shelf. The need to make a turn was never mentioned by the experimenter, but it nevertheless was required in order to approach the target shelf. Main variables of interest were the delay between eye and head turns towards the target shelf, as well as the delay between head and trunk turns towards the target shelf. We found that both delays were consistently positive, and that their magnitude was near the top of the range reported in literature. We conclude that the ordered sequence of eye - then head - then trunk turns can be observed not only with a proximal, but also with a distal goal.

Background: In nursing home residents, the combination of decreasing mobility and declining cognitive abilities, including spatial orientation, often leads to reduced physical activity (PA) and life-space (LS) mobility. As a consequence of sedentary behavior, there is a lack of social interaction and cognitive stimulation, resulting in low quality of life. It has not yet been examined whether cognitive-motor training including spatial cognitive tasks is suitable to improve spatial orientation and, as a consequence, to enlarge LS mobility, and increase well-being and general cognitive-motor functioning. Therefore, the overall goal of this multicentric randomized controlled trial (RCT) is to compare the effect of three different intervention approaches including functional exercise and orientation tasks on PA, LS and spatial orientation in nursing home residents., Methods: A three-arm single-blinded multicenter RCT with a wait-list control group will be conducted in a sample of 513 individuals (needed according to power analysis) in three different regions in Germany. In each nursing home, one of three different intervention approaches will be delivered to participating residents for 12 weeks, twice a week for 45 min each: The PROfit basic group will perform functional strength, balance, flexibility, and walking exercises always at the same location, whereas the PROfit plus group changes the location three times while performing similar/the same exercises as the PROfit basic group. The PROfit orientation group receives navigation tasks in addition to the relocation during the intervention. Physical and cognitive functioning as well as psychological measures will be assessed in all study groups at baseline. Participants will then be randomized into either the intervention group or the wait-list control group. After 12 weeks, and after 24 weeks the measures will be repeated., Discussion: This study evaluates whether the three different interventions are feasible to reduce the decline of or even improve PA, LS, and spatial orientation in nursing home residents. By adding different training locations in PROfit plus, the program is expected to be superior to PROfit basic in increasing physical and cognitive parameters. Moreover, we expect the PROfit orientation intervention to be most effective in terms of PA, LS, and spatial orientation due to two mechanisms: (1) increased physical and cognitive activity will enhance cognitive-motor capacity and (2) the spatial training will help to build up cognitive strategies to compensate for age-related loss of spatial orientation abilities and related limitations., Trial Registration: The trial was prospectively registered at DRKS.de with registration number DRKS00021423 on April 16, 2020 and was granted permission by the Technical University Berlin local ethics committee (No. GR&#95;14&#95;20191217).

Hepatitis C virus (HCV) infects liver cells and often causes chronic infection, also leading to liver cirrhosis and cancer. In the cytoplasm, the viral structural and non-structural (NS) proteins are directly translated from the plus strand HCV RNA genome. The viral proteins NS3 to NS5B proteins constitute the replication complex that is required for RNA genome replication via a minus strand antigenome. The most C-terminal protein in the genome is the NS5B replicase, which needs to initiate antigenome RNA synthesis at the very 3'-end of the plus strand. Using ribosome profiling of cells replicating full-length infectious HCV genomes, we uncovered that ribosomes accumulate at the HCV stop codon and about 30 nucleotides upstream of it. This pausing is due to the presence of conserved rare, inefficient Wobble codons upstream of the termination site. Synonymous substitution of these inefficient codons to efficient codons has negative consequences for viral RNA replication but not for viral protein synthesis. This pausing may allow the enzymatically active replicase core to find its genuine RNA template in cis , while the protein is still held in place by being stuck with its C-terminus in the exit tunnel of the paused ribosome.

Zika virus (ZIKV) is an arthropod-borne emerging pathogen causing febrile illness. ZIKV is associated Guillain-Barré syndrome and other neurological complications. Infection during pregnancy is associated with pregnancy complications and developmental and neurological abnormalities collectively defined as congenital Zika syndrome. There is still no vaccine or specific treatment for ZIKV infection. To identify host factors that can rescue cells from ZIKV infection, we used a genome-scale CRISPR activation screen. Our highly ranking hits included a short list of interferon-stimulated genes (ISGs) previously reported to have antiviral activity. Validation of the screen results highlighted interferon lambda 2 (IFN-λ2) and interferon alpha-inducible protein 6 (IFI6) as genes providing high levels of protection from ZIKV. Activation of these genes had an effect on an early stage in viral infection. In addition, infected cells expressing single guide RNAs (sgRNAs) for both of these genes displayed lower levels of cell death than did the controls. Furthermore, the identified genes were significantly induced in ZIKV-infected placenta explants. Thus, these results highlight a set of ISGs directly relevant for rescuing cells from ZIKV infection or its associated cell death and substantiate CRISPR activation screens as a tool to identify host factors impeding pathogen infection. IMPORTANCE Zika virus (ZIKV) is an emerging vector-borne pathogen causing a febrile disease. ZIKV infection might also trigger Guillain-Barré syndrome, neuropathy, and myelitis. Vertical transmission of ZIKV can cause fetus demise, stillbirth, or severe congenital abnormalities and neurological complications. There is no vaccine or specific antiviral treatment against ZIKV. We used a genome-wide CRISPR activation screen, where genes are activated from their native promoters to identify host cell factors that protect cells from ZIKV infection or associated cell death. The results provide a better understanding of key host factors that protect cells from ZIKV infection and might assist in identifying novel antiviral targets., (Copyright © 2019 American Society for Microbiology.)

Background: Hepatitis C virus (HCV) infects human liver hepatocytes, often leading to liver cirrhosis and hepatocellular carcinoma (HCC). It is believed that chronic infection alters host gene expression and favors HCC development. In particular, HCV replication in Endoplasmic Reticulum (ER) derived membranes induces chronic ER stress. How HCV replication affects host mRNA translation and transcription at a genome wide level is not yet known., Methods: We used Riboseq (Ribosome Profiling) to analyze transcriptome and translatome changes in the Huh-7.5 hepatocarcinoma cell line replicating HCV for 6 days., Results: Established viral replication does not cause global changes in host gene expression-only around 30 genes are significantly differentially expressed. Upregulated genes are related to ER stress and HCV replication, and several regulated genes are known to be involved in HCC development. Some mRNAs ( PPP1R15A / GADD34 , DDIT3 / CHOP , and TRIB3 ) may be subject to upstream open reading frame (uORF) mediated translation control. Transcriptional downregulation mainly affects mitochondrial respiratory chain complex core subunit genes., Conclusion: After establishing HCV replication, the lack of global changes in cellular gene expression indicates an adaptation to chronic infection, while the downregulation of mitochondrial respiratory chain genes indicates how a virus may further contribute to cancer cell-like metabolic reprogramming ("Warburg effect") even in the hepatocellular carcinoma cells used here.