[Socio-technical innovations and participation]. / Soziotechnische Innovationen und Partizipation.

BACKGROUND: The dual nature of socio-technical systems requires new design paradigms that go beyond conventional informatic instrumental approaches. With the realization that digital applications change social practice but also that social influences affect design principles of digital technologies, design principles must be oriented towards real-world practices and thus towards situated forms of appropriation of the intended user groups. This is achieved with newer approaches of practice-based design, which are based on ethnography-based and participatory design principles and share a number of basic assumptions of participatory approaches in gerontology. OBJECTIVE: The aim of the article is to explain basic approaches of practice-based design from the field of socio-informatics and to relate them to participatory approaches in gerontology. MATERIAL AND METHODS: The article develops an interdisciplinary perspective on the design of socio-technical systems. RESULTS AND DISCUSSION: Interdisciplinary connecting lines are listed that can inspire current development projects, thus opening a corridor for efforts in the further development of analytical, conceptual and methodological perspectives. The discussion provides interdisciplinary approaches for the conception, design and appropriation of IT applications and infrastructures for and with older people on the basis of participatory and qualitative empirical approaches. The aim is to align IT design more closely with situated practices, sociocultural contexts and sense-making processes of older people.

Structural basis for ArfA-RF2-mediated translation termination on mRNAs lacking stop codons.

In bacteria, ribosomes stalled on truncated mRNAs that lack a stop codon are rescued by the transfer-messenger RNA (tmRNA), alternative rescue factor A (ArfA) or ArfB systems. Although tmRNA-ribosome and ArfB-ribosome structures have been determined, how ArfA recognizes the presence of truncated mRNAs and recruits the canonical termination release factor RF2 to rescue the stalled ribosomes is unclear. Here we present a cryo-electron microscopy reconstruction of the Escherichia coli 70S ribosome stalled on a truncated mRNA in the presence of ArfA and RF2. The structure shows that the C terminus of ArfA binds within the mRNA entry channel on the small ribosomal subunit, and explains how ArfA distinguishes between ribosomes that bear truncated or full-length mRNAs. The N terminus of ArfA establishes several interactions with the decoding domain of RF2, and this finding illustrates how ArfA recruits RF2 to the stalled ribosome. Furthermore, ArfA is shown to stabilize a unique conformation of the switch loop of RF2, which mimics the canonical translation termination state by directing the catalytically important GGQ motif within domain 3 of RF2 towards the peptidyl-transferase centre of the ribosome. Thus, our structure reveals not only how ArfA recruits RF2 to the ribosome but also how it promotes an active conformation of RF2 to enable translation termination in the absence of a stop codon.

Practices of Care in Participatory Design With Older Adults During the COVID-19 Pandemic: Digitally Mediated Study.

BACKGROUND: Participatory Design (PD), albeit an established approach in User-Centered Design, comes with specific challenges when working with older adults as research participants. Addressing these challenges relates to the reflection and negotiation of the positionalities of the researchers and research participants and includes various acts of giving and receiving help. During the COVID-19 pandemic, facets of positionalities and (mutual) care became particularly evident in qualitative and participatory research settings. OBJECTIVE: The aim of this paper was to systematically analyze care practices of participatory (design) research, which are to different extents practices of the latter. Using a multiyear PD project with older people that had to take place remotely over many months, we specify different practices of care; how they relate to collaborative work in the design project; and represent foundational practices for sustainable, long-term co-design. Our research questions were "How can digitally-mediated PD work during COVID-19 and can we understand such digital PD as 'care'?" METHODS: Our data comes from the Joint Programming Initiative "More Years, Better Lives" (JPI MYBL), a European Union project that aims to promote digital literacy and technology appropriation among older adults in domestic settings. It targeted the cocreation, by older adults and university researchers, of a mobile demo kit website with cocreated resources, aimed at improving the understanding of use options of digital tools. Through a series of workshops, a range of current IT products was explored by a group of 21 older adults, which served as the basis for joint cocreative work on generating design ideas and prototypes. We reflect on the PD process and examine how the actors enact and manifest care. RESULTS: The use of digital technology allowed the participatory project to continue during the COVID-19 pandemic and accentuated the digital skills of older adults and the improvement of digital literacy as part of "care." We provide empirically based evidence of PD with older adults developing digital literacy and sensitizing concepts, based on the notion of care by Tronto for differentiating aspects and processes of care. The data suggest that it is not enough to focus solely on the technologies and how they are used; it is also necessary to focus on the social structures in which help is available and in which technologies offer opportunities to do care work. CONCLUSIONS: We document that the cocreation of different digital media tools can be used to provide a community with mutual care. Our study demonstrates how research participants effectively enact different forms of care and how such "care" is a necessary basis for a genuinely participatory approach, which became especially meaningful as a form of support during COVID-19. We reflect on how notions of "care" and "caring" that were central to the pandemic response are also central to PD.

Patterns of cardio-respiratory motor outputs during acute and subacute exposure to chlorpyrifos in an ex-vivo in situ preparation in rats.

While a considerable body of literature has characterized the clinical features induced by organophosphate pesticides, the field lacks scrutiny into cardio-respiratory changes in different phases of poisoning. Herein, we evaluated the impact of chlorpyrifos (CPF) and its active metabolite chlorpyrifos-oxon (CPO) on the cardiorespiratory system during acute and subacute phases of poisoning using an in situ experimental rodent model. CPF (30 mg/kg) was injected intraperitoneally to rats beforehand (24 h) whereas CPO (15 mg/kg) was added into the perfusate reservoir to evaluate the effects on the motor outputs throughout the three phases of the respiratory cycle: inspiration, post-inspiration and late expiration. Phrenic, recurrent laryngeal (RLN) and thoracic sympathetic nerve activity (tSNA) were recorded. Heart rate was derived from the electrocardiogram (ECG) and the baro- and chemo-reflexes tested. CPF and CPO led to a time-dependent change in cardiorespiratory motor outputs. In the acute phase, the CPO induced bradypnea, transiently reduced the inspiratory time (TI), and increased the amplitude of phrenic. Post-inspiratory (PI) discharge recorded from the RLN was progressively reduced while tSNA was increased. CPO significantly depressed the chemoreflex but had no effect on baroreflex. During subacute phase, CPF prolongated TI with no effect on respiratory rate. Both the RLN PI discharge, the chemoreflex and the baroreflex sympathetic gain were reduced. In addition, both CPF and CPO shifted the cardiac sympatho-vagal balance towards sympathetic dominance. Our data show that different phases of poisoning are associated with specific changes in the cardio-respiratory system and might therefore demand distinct approaches by health care providers.

Results of the Cologne Corona surveillance (CoCoS) study - a prospective population-based cohort study: incidence data and potential underestimation of new SARS-CoV-2 adult infections by health authorities.

BACKGROUND: Current incidence estimates of SARS-CoV-2 in Germany rely to a large extent on case notifications. However, the large number of mild or asymptomatic infections is likely to result in underestimation. Population-based studies can provide valid estimates of the SARS-CoV-2 incidence and thus support health authorities to monitor the epidemiological situation and to initiate, maintain, strengthen or relax effective countermeasures. METHODS: This study was conducted in Cologne, Germany. Six-thousand randomly drawn Cologne residents, 18 years of age or older, were contacted by mail in March 2021. Study envelopes contained a kit for self-administered saliva sample and access details to a questionnaire on sociodemographic characteristics, previous positive SARS-CoV-2 RT-qPCR and completed COVID-19 vaccinations. Participants were again invited for a second round in June 2021, while those who declined participation were replaced by additional randomly drawn Cologne residents in order to reach a total of 6000 potential participants again. The saliva samples were sent to the laboratory by mail and tested for SARS-CoV-2 using RT-qPCR. The incidence estimates were adjusted for sensitivity and specificity of the test procedure and compared with the official numbers of new SARS-CoV-2 cases in the adult Cologne population. RESULTS: The first surveillance round in March 2021 (response rate: 34.08%, N = 2045) showed a SARS-CoV-2 seven-day incidence of 85 cases per 100,000 adult Cologne residents (95% CI: 9 to 319). In the same period, the officially registered cases were 125 per 100,000. The second surveillance round in June 2021 (response rate: 36.53%, N = 2192) showed a seven-day incidence of 27 per 100,000 adult Cologne residents (95% CI: 1 to 142), while the official figures for newly registered SARS-CoV-2 cases in the same period were 15 per 100,000. CONCLUSIONS: The incidence estimates do not indicate relevant underestimation of new SARS-CoV-2 infections based on case notification. Regular use of the surveillance method developed here may nevertheless complement the efforts of the health authorities to assess the epidemiological situation. TRIAL REGISTRATION: DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046 , Registered on 25 February 2021.

Structural Basis for Ribosome Rescue in Bacteria.

Ribosomes that translate mRNAs lacking stop codons become stalled at the 3' end of the mRNA. Recycling of these stalled ribosomes is essential for cell viability. In bacteria three ribosome rescue systems have been identified so far, with the most ubiquitous and best characterized being the trans-translation system mediated by transfer-messenger RNA (tmRNA) and small protein B (SmpB). The two additional rescue systems present in some bacteria employ alternative rescue factor (Arf) A and release factor (RF) 2 or ArfB. Recent structures have revealed how ArfA mediates ribosome rescue by recruiting the canonical termination factor RF2 to ribosomes stalled on truncated mRNAs. This now provides us with the opportunity to compare and contrast the available structures of all three bacterial ribosome rescue systems.

Impact of binding mode of low-sulfated hyaluronan to 3D collagen matrices on its osteoinductive effect for human bone marrow stromal cells.

Synthetically sulfated hyaluronan derivatives were shown to facilitate osteogenic differentiation of human bone marrow stromal cells (hBMSC) by application in solution or incorporated in thin collagen-based coatings. In the presented study, using a biomimetic three-dimensional (3D) cell culture model based on fibrillary collagen I (3D Col matrix), we asked on the impact of binding mode of low sulfated hyaluronan (sHA) in terms of adsorptive and covalent binding on osteogenic differentiation of hBMSC. Both binding modes of sHA induced osteogenic differentiation. Although for adsorptive binding of sHA a strong intracellular uptake of sHA was observed, implicating an intracellular mode of action, covalent binding of sHA to the 3D matrix induced also intense osteoinductive effects pointing towards an extracellular mode of action of sHA in osteogenic differentiation. In summary, the results emphasize the relevance of fibrillary 3D Col matrices as a model to study hBMSC differentiation in vitro in a physiological-like environment and that sHA can display dose-dependent osteoinductive effects in dependence on presentation mode in cell culture scaffolds.

Identification of intracellular glycosaminoglycan-interacting proteins by affinity purification mass spectrometry.

Glycosaminoglycans (GAGs) are essential functional components of the extracellular matrix (ECM). Artificial GAGs like sulfated hyaluronan (sHA) exhibit pro-osteogenic properties and boost healing processes. Hence, they are of high interest for supporting bone regeneration and wound healing. Although sulfated GAGs (sGAGs) appear intracellularly, the knowledge about intracellular effects and putative interaction partners is scarce. Here we used an affinity-purification mass spectrometry-based (AP-MS) approach to identify novel and particularly intracellular sGAG-interacting proteins in human bone marrow stromal cells (hBMSC). Overall, 477 proteins were found interacting with at least one of four distinct sGAGs. Enrichment analysis for protein localization showed that mainly intracellular and cell-associated interacting proteins were identified. The interaction of sGAG with α2-macroglobulin receptor-associated protein (LRPAP1), exportin-1 (XPO1), and serine protease HTRA1 (HTRA1) was confirmed in reverse assays. Consecutive pathway and cluster analysis led to the identification of biological processes, namely processes involving binding and processing of nucleic acids, LRP1-dependent endocytosis, and exosome formation. Respecting the preferentially intracellular localization of sGAG in vesicle-like structures, also the interaction data indicate sGAG-specific modulation of vesicle-based transport processes. By identifying many sGAG-specific interacting proteins, our data provide a resource for upcoming studies aimed at molecular mechanisms and understanding of sGAG cellular effects.

Protocol of the Cologne Corona Surveillance (CoCoS) Study- a prospective population-based cohort study.

BACKGROUND: Surveillance strategies are critical to cope with the current SARS-CoV-2 pandemic and to evaluate, as well as adjust government-imposed countermeasures. Incidence estimates are widely based on laboratory confirmed cases reported by health authorities. Prevalence and incidence data of SARS-CoV-2 is still scarce, along with demographic and behavioural factors associated with infection risk. METHODS: The Cologne Corona Surveillance Study will be conducted in the City of Cologne, which is the fourth-largest city in Germany with a population of approximately 1.1 million. Researchers will apply self-sampling surveillance to a rolling cohort of Cologne residents. Random samples of 6000 Cologne residents 18 years of age and older will be drawn from the registration office. Upon receiving the information and saliva sample kit, participants will be asked to fill out a questionnaire online or via phone, sign written informed consent, and send back written consent, as well as saliva sample. The saliva samples will be tested for SARS-CoV-2 by reverse PCR. The questionnaire will be administered to gather information about personal characteristics such as health status and risks. A second round of testing will take place 6 weeks after the first. DISCUSSION: Self-administered saliva sampling proved to be a legitimate and feasible alternative to nasopharyngeal swabs taken by health professionals. However, it is unclear whether the targeted response rate of 40% can be achieved and whether the results are representative of the population. TRIAL REGISTRATION: DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046 , Registered on 25 February 2021.

The antidotes atropine and pralidoxime distinctively recover cardiorespiratory components impaired by acute poisoning with chlorpyrifos in rats.

In a previous work we showed that the organophosphate pesticide (OP) chlorpyrifos (CPF) reduces the protective chemoreflex and baroreflex responses in rats. However, whether the antidotes atropine (ATR) and pralidoxime (2-PAM) are capable of restoring these reflex functions remains unexplored. Rats were poisoned with CPF (30 mg.kg-1, i.p.) and one hour after the intoxication, ATR (10 mg.kg-1, i.p.) and 2-PAM (40 mg.kg-1, i.p.) were administrated separately or in combination. Cardiorespiratory parameters were recorded in awake rats 24 h after CPF. Systolic blood pressure (SBP) and heart rate (HR) variability and spontaneous baroreflex sensitivity (sBRS) were derived from undisturbed recordings (30 min), while chemoreflex was assessed through potassium cyanide (KCN) i.v. injections (10, 20, 40, 80 µg/rat). CPF poisoning increased SBP variability and low frequency/high frequency (LF/HF) ratio of the HR variability spectrum, indicating autonomic imbalance with increased cardiac sympathetic tone. sBRS was not changed. Treatment with 2-PAM restored SBP variability, whilst both antidotes increased LF/HF ratio. CPF poisoning reduced the hypertensive, bradycardic and tachypneic chemoreflex responses. Chemoreflex-induced hypertensive response was restored by 2-PAM treatment, while ATR recovered the bradycardic response. Both antidotes restored the chemoreflex tachypneic response. Our data show distinct effects of ATR and 2-PAM on cardiorespiratory parameters affected by OP poisoning. While 2-PAM rescued the chemoreflex hypertensive response, ATR reversed chemoreflex bradycardic dysfunction. Although 2-PAM clinical use is questioned in some countries, our data indicate that summation of effects of both antidotes appears beneficial on the cardiorespiratory system and peripheral chemoreflex function.

Preparation and characterization of Nephila clavipes tubuliform silk gut.

Tubuliform silk glands were dissected from Nephila clavipes spiders, and silk gut fibers were produced by immersing the glands in a mild acid solution and subsequent stretching. The tensile properties of the as produced fibers were obtained through tensile tests, and the stress-strain curves were compared with those of naturally spun tubuliform silk fibers. The influence on the mechanical properties of the fibers after immersion in water and drying was also discerned. The microstructure of the silk guts was obtained by X-ray diffraction (XRD) and infrared spectroscopy (FTIR). It was found that the stress-strain curves of the stretched tubuliform silk guts concur with those of their natural counterparts (tubuliform silk fibers).

Crude extracts of recombinant baculovirus expressing rabbit hemorrhagic disease virus 2 VLPs from both insect and rabbit cells protect rabbits from rabbit hemorrhagic disease caused by RHDV2.

Vaccines against viral pathogens are often composed of recombinant proteins expressed in different systems. Such proteins expressed by recombinant baculoviruses have been proven to be effective for vaccination. Especially, after codon usage optimization high amounts of recombinant viral proteins can be obtained which can assemble to virus like particles (VLPs) spontaneously. In this study we compared two different codon usages of RHDV2-VP1 to improve the expression of recombinant VP1 of RHDV2 by recombinant baculoviruses after infection of insect SF9 cells or transduction of mammalian RK13 cells in order to gain high protein yields. Also the influence on the auto-assembly of RHDV2-VP1 to VLPs was investigated. Finally, the immunogenic potential of such recombinant vaccines against RHDV2 to induce a protective immune response in rabbits against RHDV2 should be characterized. There was no influence of different codon usages on RHDV2-VP1 gene expression in the respective cell lines detected. However, in insect cell line SF9 higher rates of recombinant VP1 were measured in comparison to the transduction of mammalian cells RK13. Auto-assembly of RHDV2-VP1 to VLPs was observed in both cell systems by electron microscopy. Finally, both RHDV-VP1 VLPs derived from mammalian and insect cells were able to induce a protective humoral immune response in rabbits against RHDV2.

Cytokine profiling in anti neutrophil cytoplasmic antibody-associated vasculitis: a cross-sectional cohort study.

ANCA-associated vasculitides (AAV) are severe diseases, potentially affecting lungs, kidney, and other organs. Nevertheless, risk profiling remains difficult. Aim of the current study was to analyze serological characteristics in AAV. The principal goal was to identify diagnostic markers that potentially allow a more sophisticated risk profiling in AAV. AAV subjects were recruited and evaluated for disease activity, disease stage, medication, and laboratory findings. Serum concentrations of the following parameters were measured: IL-1ß, IL-6, IL-17 A, IL-17 F, IL-21, IL-22, IL-23, TNF-α, sCD40L, IL-4, IL-10, IL-25, IL-31, IL-33, and INF-γ. A total number of 62 AAV subjects was included in the study (39 females; 23 males). Forty-five subjects were PR3+, 17 subjects showed ANCA specificity for MPO. The majority of all cytokines fell under the lower detection limit of the assay. Serum IL-10 was higher in both, AAV and SSc as compared to controls; it was also higher in early systemic AAV. Serum IL-33 was elevated in AAV and SSc; in AAV, higher levels were found in non-necrotizing GN and RTX untreated subjects. Serum CD40L was raised in AAV as well; higher concentrations were also found in PR3+ and MPO+ patients and early systemic, generalized, and refractory AAV. IL-10 may potentially serve as a marker of early systemic AAV. IL-33 may help to identify subjects with a higher risk for necrotizing GN in AAV.

Fragments of the Nonlytic Proline-Rich Antimicrobial Peptide Bac5 Kill Escherichia coli Cells by Inhibiting Protein Synthesis.

Unlike most antimicrobial peptides (AMPs), the main mode of action of the subclass of proline-rich antimicrobial peptides (PrAMPs) is not based on disruption of the bacterial membrane. Instead, PrAMPs exploit the inner membrane transporters SbmA and YjiL/MdtM to pass through the bacterial membrane and enter the cytosol of specific Gram-negative bacteria, where they exert an inhibitory effect on protein synthesis. Despite sharing a high proline and arginine content with other characterized PrAMPs, the PrAMP Bac5 has a low sequence identity with them. Here we investigated the mode of action of three N-terminal Bac5 fragments, Bac5(1-15), Bac5(1-25), and Bac5(1-31). We show that Bac5(1-25) and Bac5(1-31) retained excellent antimicrobial activity toward Escherichia coli and low toxicity toward eukaryotic cells, whereas Bac5(1-15) was inactive. Bac5(1-25) and Bac5(1-31) inhibited bacterial protein synthesis in vitro and in vivo Competition assays suggested that the binding site of Bac5 is within the ribosomal tunnel, where it prevents the transition from the initiation to the elongation phase of translation, as reported for other PrAMPs, such as the bovine PrAMP Bac7. Surprisingly, unlike Bac7, Bac5(1-25) exhibited species-specific inhibition, being an excellent inhibitor of protein synthesis on E. coli ribosomes but a poor inhibitor on Thermus thermophilus ribosomes. This indicates that while Bac5 most likely has an overlapping binding site with Bac7, the mode of interaction is distinct, suggesting that Bac5 fragments may be interesting alternative lead compounds for the development of new antimicrobial agents.

Concise Review: MSC Adhesion Cascade-Insights into Homing and Transendothelial Migration.

Mesenchymal stem cells (MSCs) are promising candidates for adult cell therapies in regenerative medicine. To fully exert their potential, efficient homing and migration toward lesion sites play an important role. Local transplantation deposits MSC in spatial proximity to the lesion, but often requires invasive procedures. Systemic administration routes are favored, but require the targeted extravasation of the circulating MSC at the site of injury. Transplanted MSC can indeed leave the blood flow and transmigrate through the endothelial barrier, and reach the lesion site. However, the underlying processes are not completely dissolved yet. Recent in vitro and in vivo research identified some key molecules scattered light on the extravasation mechanism. This review provides a detailed overview over the current knowledge of MSC transendothelial migration. We use the leukocyte extravasation process as a role model to build a comprehensive concept of MSC egress mechanisms from the blood stream and identified relevant similarities as well as important differences between the extravasation mechanisms. Stem Cells 2017;35:1446-1460.

Validation of the Telephone Interview of Cognitive Status and Telephone Montreal Cognitive Assessment Against Detailed Cognitive Testing and Clinical Diagnosis of Mild Cognitive Impairment After Stroke.

BACKGROUND AND PURPOSE: Assessment of cognitive status poststroke is recommended by guidelines but follow-up can often not be done in person. The Telephone Interview of Cognitive Status (TICS) and the Telephone Montreal Cognitive Assessment (T-MoCA) are considered useful screening instruments. Yet, evidence to define optimal cut-offs for mild cognitive impairment (MCI) after stroke is limited. METHODS: We studied 105 patients enrolled in the prospective DEDEMAS study (Determinants of Dementia After Stroke; NCT01334749). Follow-up visits at 6, 12, 36, and 60 months included comprehensive neuropsychological testing and the Clinical Dementia Rating scale, both of which served as reference standards. The original TICS and T-MoCA were obtained in 2 separate telephone interviews each separated from the personal visits by 1 week (1 before and 1 after the visit) with the order of interviews (TICS versus T-MoCA) alternating between subjects. Area under the receiver-operating characteristic curves was determined. RESULTS: Ninety-six patients completed both the face-to-face visits and the 2 interviews. Area under the receiver-operating characteristic curves ranged between 0.76 and 0.83 for TICS and between 0.73 and 0.94 for T-MoCA depending on MCI definition. For multidomain MCI defined by multiple-tests definition derived from comprehensive neuropsychological testing optimal sensitivities and specificities were achieved at cut-offs <36 (TICS) and <18 (T-MoCA). Validity was lower using single-test definition, and cut-offs were higher compared with multiple-test definitions. Using Clinical Dementia Rating as the reference, optimal cut-offs for MCI were <36 (TICS) and approximately 19 (T-MoCA). CONCLUSIONS: Both the TICS and T-MoCA are valid screening tools poststroke, particularly for multidomain MCI using multiple-test definition.

Prevalence of Amyloid Positron Emission Tomographic Positivity in Poststroke Mild Cognitive Impairment.

BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) is common after stroke and associated with poor outcome. However, the mechanisms underlying poststroke MCI (PS-MCI) are insufficiently understood. We performed amyloid-ß positron emission tomography (PET) in a prospective cohort of stroke survivors to determine the role of amyloid pathology in PS-MCI. METHODS: We studied 178 consecutive patients enrolled into the prospective DEDEMAS study (Determinants of Dementia After Stroke). Follow-up visits 6 months post stroke included detailed cognitive testing, standardized magnetic resonance imaging, and amyloid-ß imaging using flutemetamol ((18)F) PET. MCI was defined by the modified Petersen criteria. Amyloid-positivity was assessed visually and quantitatively. Fifty-six (31%) patients agreed to undergo PET imaging. RESULTS: Thirty-eight (68%) patients who consented to PET imaging had PS-MCI. Visual assessment revealed amyloid PET positivity in 2 (5%) of the 38 PS-MCI patients and in 2 (11%) of the 18 cognitively healthy stroke survivors. There was no correlation between flutemetamol ((18)F) standardized uptake value ratios and cognitive scores in the 56 patients. PS-MCI patients had significant cognitive impairments on executive function (P<0.01) and memory tests (P<0.01) when compared with cognitively healthy stroke survivors (P<0.01). CONCLUSIONS: The prevalence of amyloid-pathology in patients with PS-MCI is not increased when compared with cognitively healthy stroke survivors and to recent estimates for cognitively healthy elderly subjects. Factors other than amyloid-pathology likely contribute to the development of PS-MCI. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01334749.