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Abstract Microglia are critically involved in post‐stroke inflammation affecting neurological outcomes. Lipid droplet (LD) accumulation in microglia results in a dysfunctional and pro‐inflammatory state in the aged brain and worsens the outcome of neuroinflammatory and neurodegenerative diseases. However, the role of LD‐rich microglia (LDRM) under stroke conditions is unknown. Using in vitro and in vivo stroke models, herein accumulation patterns of microglial LD and their corresponding microglial inflammatory signaling cascades are studied. Interactions between temporal and spatial dynamics of lipid profiles and microglial phenotypes in different post‐stroke brain regions are found. Hence, microglia display enhanced levels of LD accumulation and elevated perilipin 2 (PLIN2) expression patterns when exposed to hypoxia or stroke. Such LDRM exhibit high levels of TNF‐α, IL‐6, and IL‐1β as well as a pro‐inflammatory phenotype and differentially expressed lipid metabolism‐related genes. These post‐ischemic alterations result in distinct lipid profiles with spatial and temporal dynamics, especially with regard to cholesteryl ester and triacylglycerol levels, further exacerbating post‐ischemic inflammation. The present study sheds new light on the dynamic changes of brain lipid profiles and aggregation patterns of LD in microglia exposed to ischemia, demonstrating a mutual mechanism between microglial phenotype and function, which contributes to progression of brain injury.

Abstract Electronic immunosensors are indispensable tools for diagnostics, particularly in scenarios demanding immediate results. Conventionally, these sensors rely on the chemical immobilization of antibodies onto electrodes. However, globular proteins tend to adsorb and unfold on these surfaces. Therefore, self‐assembled monolayers (SAMs) of thiolated alkyl molecules are commonly used for indirect gold–antibody coupling. Here, a limitation associated with SAMs is revealed, wherein they curtail the longevity of protein sensors, particularly when integrated into the state‐of‐the‐art transducer of organic bioelectronics—the organic electrochemical transistor. The SpyDirect method is introduced, generating an ultrahigh‐density array of oriented nanobody receptors stably linked to the gold electrode without any SAMs. It is accomplished by directly coupling cysteine‐terminated and orientation‐optimized spyTag peptides, onto which nanobody‐spyCatcher fusion proteins are autocatalytically attached, yielding a dense and uniform biorecognition layer. The structure‐guided design optimizes the conformation and packing of flexibly tethered nanobodies. This biolayer enhances shelf‐life and reduces background noise in various complex media. SpyDirect functionalization is faster and easier than SAM‐based methods and does not necessitate organic solvents, rendering the sensors eco‐friendly, accessible, and amenable to scalability. SpyDirect represents a broadly applicable biofunctionalization method for enhancing the cost‐effectiveness, sustainability, and longevity of electronic biosensors, all without compromising sensitivity.

Abstract Wiedemann‐Rautenstrauch Syndrome (WRS; MIM 264090) is an extremely rare and highly heterogeneous syndrome that is inherited in a recessive fashion. The patients have hallmark features such as prenatal and postnatal growth retardation, short stature, a progeroid appearance, hypotonia, facial dysmorphology, hypomyelination leukodystrophy, and mental impairment. Biallelic disease‐causing variants in the RNA polymerase III subunit A (POLR3A) have been associated with WRS. Here, we report the first identified cases of WRS syndrome with novel phenotypes in three consanguineous families (two Omani and one Saudi) characterized by biallelic variants in POLR3A. Using whole‐exome sequencing, we identified one novel homozygous missense variant (NM_007055: c.2456C>T; p. Pro819Leu) in two Omani families and one novel homozygous variant (c.1895G>T; p Cys632Phe) in Saudi family that segregates with the disease in the POLR3A gene. In silico homology modeling of wild‐type and mutated proteins revealed a substantial change in the structure and stability of both proteins, demonstrating a possible effect on function. By identifying the homozygous variants in the exon 14 and 18 of the POLR3A gene, our findings will contribute to a better understanding of the phenotype‐genotype relationship and molecular etiology of WRS syndrome.

Abstract Introduction There is growing evidence to support the use of co‐design in developing interventions across many disciplines. This scoping review aims to examine how co‐design methodology has been used in the development of cardiovascular disease (CVD) secondary prevention interventions within health and community settings. Methods We searched four academic databases for studies that used the co‐design approach to develop their intervention. Studies were included if consumers (adults with CVD) and key stakeholders (e.g. clinicians, service providers) were involved in the co‐design process. The review focused on methodology rather than traditional study outcomes; therefore, co‐design processes and activities were extracted and evaluated against a selected co‐design framework. Results Twenty‐two studies were included in this review. Studies were implemented across various settings with consumers and stakeholder groups most frequently consisting of patients and healthcare professionals, respectively. Most studies specifically stated that they used a ‘co‐design’ approach (n = 10); others used terms such as participatory action research (n = 3), user‐centred design (n = 3) and community‐based participatory research (n = 2). Although there was variability in terminology, co‐design processes, and participants, all studies adhered to the key principles of consumer engagement. Predominant co‐design activities included semistructured interviews, focus groups, co‐design/development workshops and advisory group meetings. Intervention effectiveness was assessed in eight studies showing mixed results. Conclusions This review provides an overview of how the co‐design approach has previously been used in the development of CVD secondary prevention interventions. These findings provide methodological considerations that can guide researchers and healthcare services when implementing co‐design to develop feasible and acceptable interventions that can improve outcomes for CVD populations. Patient or Public Contribution No patients, service users, caregivers, people with lived experience or members of the public were involved in this scoping review. This review article was written by academics who have undertaken a significant amount of co‐design work with consumers and stakeholders.

Abstract Central hypothyroidism might be another clinical sign of SSADH deficiency which prompts urinary organic acid screening for GHB in central hypothyroidism patients. Studies on GABA and thyroid hormone interaction might be a concept of a new therapy.

Abstract Objective Hematoma enlargement (HE) is associated with clinical outcomes after supratentorial intracerebral hemorrhage (ICH). This study evaluates whether HE characteristics and association with functional outcome differ in deep versus lobar ICH. Methods Pooled analysis of individual patient data between January 2006 and December 2015 from a German‐wide cohort study (RETRACE, I + II) investigating ICH related to oral anticoagulants (OAC) at 22 participating centers, and from one single‐center registry (UKER‐ICH) investigating non‐OAC‐ICH patients. Altogether, 1954 supratentorial ICH patients were eligible for outcome analyses, which were separately conducted or controlled for OAC, that is, vitamin‐K‐antagonists (VKA, n = 1186) and non‐vitamin‐K‐antagonist‐oral‐anticoagulants (NOAC, n = 107). Confounding was addressed using propensity score matching, cox regression modeling and multivariate modeling. Main outcomes were occurrence, extent, and timing of HE (>33%/>6 mL) and its association with 3‐month functional outcome. Results Occurrence of HE was not different after deep versus lobar ICH in patients with non‐OAC‐ICH (39/356 [11.0%] vs. 36/305 [11.8%], P = 0.73), VKA‐ICH (249/681 [36.6%] vs. 183/505 [36.2%], P = 0.91), and NOAC‐ICH (21/69 [30.4%] vs. 12/38 [31.6%], P = 0.90). HE extent did not differ after non‐OAC‐ICH (deep:+59% [40–122] vs. lobar:+74% [37–124], P = 0.65), but both patients with VKA‐ICH and NOAC‐ICH showed greater HE extent after deep ICH [VKA‐ICH, deep: +94% [54–199] vs. lobar: +56% [35–116], P

Background Data on the relative contribution of clinical and neuroimaging risk factors to acute ischemic stroke (AIS) versus intracerebral hemorrhage (ICH) occurring on oral anticoagulant treatment are scarce. Methods and Results Cross‐sectional study was done on consecutive oral anticoagulant–treated patients presenting with AIS, transient ischemic attack (TIA), or ICH from the prospective observational NOACISP (Novel‐Oral‐Anticoagulants‐In‐Stroke‐Patients)‐Acute registry. We compared clinical and neuroimaging characteristics (small vessel disease markers and atherosclerosis) in ICH versus AIS/TIA (reference) using logistic regression. Among 734 patients presenting with stroke on oral anticoagulant treatment (404 [55%] direct oral anticoagulants, 330 [45%] vitamin K antagonists), 605 patients (82%) had AIS/TIA and 129 (18%) had ICH. Prior AIS/TIA, coronary artery disease, dyslipidemia, and worse renal function were associated with AIS/TIA (adjusted odds ratio [aOR] [95% CI] 0.51 [0.32–0.82], 0.48 [0.26–0.86], 0.55 [0.34–0.89], and 0.82 [0.75–0.90] per 10 mL/min). Prior ICH, older age, higher admission blood pressure, and statin treatment were associated with ICH (aOR [95% CI] 6.33 [2.87–14.04], 1.37 [1.04–1.81] per 10 years, 1.19 [1.10–1.29] per 10 mm Hg, and 1.81 [1.09–3.03]). Cerebral microbleeds and moderate‐to‐severe white matter hyperintensities contributed more to ICH (aOR [95% CI] 2.77 [1.34–6.18], and 2.62 [1.28–5.63]). Aortic arch, common and internal carotid artery atherosclerosis, and internal carotid artery stenosis ≥50% contributed more to AIS/TIA (aOR [95% CI] 0.54 [0.31–0.90], 0.29 [0.05–0.97], 0.48 [0.30–0.76], and 0.32 [0.13–0.67]). Conclusions In patients presenting with stroke on oral anticoagulant, AIS/TIA was 5 times more common than ICH. A high atherosclerotic burden (indicated by cardiovascular comorbidities and extracranial atherosclerosis) and prior AIS/TIA contributed more to AIS/TIA, while small vessel disease markers and prior ICH were stronger determinants for ICH. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02353585.

Background Prehospital delay reduces the proportion of patients with stroke treated with recanalization therapies. We aimed to identify novel and modifiable risk factors for prehospital delay. Methods and Results We included patients with an ischemic stroke confirmed by diffusion‐weighted magnetic resonance imaging, symptom onset within 24 hours and hospitalized in the Stroke Center of the University Hospital Basel, Switzerland. Trained study nurses interviewed patients and proxies along a standardized questionnaire. Prehospital delay was defined as >4.5 hours between stroke onset—or time point of wake‐up—and admission. Overall, 336 patients were enrolled. Prehospital delay was observed in 140 patients (42%). The first healthcare professionals to be alarmed were family doctors for 29% of patients (97/336), and a quarter of these patients had a baseline National Institute of Health Stroke Scale score of 4 or higher. The main modifiable risk factor for prehospital delay was a face‐to‐face visit to the family doctor (adjusted odds ratio, 4.19; 95% CI, 1.85–9.46). Despite transport by emergency medical services being associated with less prehospital delay (adjusted odds ratio, 0.41; 95% CI, 0.24–0.71), a minority of patients (39%) who first called their family doctor were transported by emergency medical services to the hospital. The second risk factor was lack of awareness of stroke symptoms (adjusted odds ratio, 4.14; 95% CI, 2.36–7.24). Conclusions Almost 1 in 3 patients with a diffusion‐weighted magnetic resonance imaging–confirmed ischemic stroke first called the family doctor practice. Face‐to‐face visits to the family doctor quadrupled the odds of prehospital delay. Efforts to reduce prehospital delay should address family doctors and their staffs as important partners in the prehospital pathway. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02798770.

BackgroundExamination of linked data on patient outcomes and cost of care may help identify areas where stroke care can be improved. We report on the association between variations in stroke severity, patient outcomes, cost, and treatment patterns observed over the acute hospital stay and through the 12‐month follow‐up for subjects receiving endovascular therapy compared to intravenous tissue plasminogen activator alone in the IMS (Interventional Management of Stroke) III Trial. Methods and ResultsProspective data collected for a prespecified economic analysis of the trial were used. Data included hospital billing records for the initial stroke admission and subsequent detailed resource use after the acute hospitalization collected at 3, 6, 9, and 12 months. Cost of follow‐up care varied 6‐fold for patients in the lowest (0–1) and highest (20+) National Institutes of Health Stroke Scale category at 5 days, and by modified Rankin Scale at 3 months. The kind of resources used postdischarge also varied between treatment groups. Incremental short‐term cost‐effectiveness ratios varied greatly when treatments were compared for patient subgroups. Patient subgroups predefined by stroke severity had incremental cost‐effectiveness ratios of $97 303/quality‐adjusted life year (severe stroke) and $3 187 805/quality‐adjusted life year (moderately severe stroke). ConclusionsDetailed economic and resource utilization data from IMS III provide powerful evidence for the large effect that patient outcome has on the economic value of medical and endovascular reperfusion therapies. These data can be used to inform process improvements for stroke care and to estimate the cost‐effectiveness of endovascular therapy in the US health system for stroke intervention trials. Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Registration number: NCT00359424.

Beauveria bassiana (Fungi: Ascomycota) is an entomopathogenic fungus that serves as a biological control agent of Mormon crickets Anabrus simplex Haldeman (Orthoptera: Tettigoniidae) and other grasshopper pests. To measure the dose-dependent response of Mormon crickets to fungal attack, we applied B. bassiana strain GHA topically to adults using doses of 5.13 × 104 to 1.75 × 106 conidia in sunflower oil, with oil only as a control. After three weeks, we assessed the survivors' hemolymph for fungal cells, active phenoloxidase (PO), and lysozyme. Mortality increased and body mass of survivors decreased with conidial dose. survivors' PO activity was elevated to the same level independent of dose. Those with fungal cells visible in their hemolymph did not differ in PO activity from those with clear hemolymph. We conclude that circulating PO may be an important enzymatic defense against Beauveria infection and that it is associated with attempted clearing of Beauveria blastospores and hyphae from Mormon cricket hemolymph.

Abstract Background and Aims Regular physical activity holds numerous health benefits for older people, yet the majority of older people do not meet the World Health Organization's physical activity recommendations. Brief physical activity screening tools can support healthcare professionals in identifying patients who would benefit from physical activity promotion and counselling. The Rapid Assessment of Physical Activity (RAPA) questionnaire is a validated brief physical activity screening tool designed for clinical practice. Methods We conducted a psychometric validation of a new German translation of the RAPA by performing a secondary analysis of survey data from 234 former cardiac rehabilitation patients (mean [SD] age 69 ± 11 years, 23% female) in Austria. For psychometric validation, we used the following survey measures: the new German version of the RAPA, two customized questions about physical activity behavior, one customized question about perceived health self‐management, and the German version of the EuroQol health‐related quality of life questionnaire. We performed Spearman's correlations to assess the relationship between the German RAPA and the other measures (i.e., physical activity behavior, self‐management of health and health‐related quality of life). Results Aerobic physical activity level according to the RAPA correlated significantly with weekly frequency (Spearman's rho = 0.31, 95% CI [0.18, 0.43], p < .001) and volume of PA (rho = 0.34, 95% CI [0.21, 0.45], p < .001), as well as perceived health self‐management and five out of six dimensions of the EuroQol questionnaire. Conclusion Our data demonstrate convergent validity and contribute to the psychometric validation of the new German version of the RAPA. These initial findings lend themselves to future dedicated psychometric validation studies of the German RAPA (against gold‐standard physical activity questionnaires or direct physical activity measures) to further explore the potential of this tool for use in German‐speaking geriatrics healthcare.

Abstract Introduction This study evaluates the clinical value of a deep learning–based artificial intelligence (AI) system that performs rapid brain volumetry with automatic lobe segmentation and age‐ and sex‐adjusted percentile comparisons. Methods Fifty‐five patients—17 with Alzheimer's disease (AD), 18 with frontotemporal dementia (FTD), and 20 healthy controls—underwent cranial magnetic resonance imaging scans. Two board‐certified neuroradiologists (BCNR), two board‐certified radiologists (BCR), and three radiology residents (RR) assessed the scans twice: first without AI support and then with AI assistance. Results AI significantly improved diagnostic accuracy for AD (area under the curve −AI: 0.800, +AI: 0.926, p

Abstract Introduction We investigated the agreement between automated and gold‐standard manual transcriptions of telephone chatbot‐based semantic verbal fluency testing. Methods We examined 78 cases from the Screening over Speech in Unselected Populations for Clinical Trials in AD (PROSPECT‐AD) study, including cognitively normal individuals and individuals with subjective cognitive decline, mild cognitive impairment, and dementia. We used Bayesian Bland–Altman analysis of word count and the qualitative features of semantic cluster size, cluster switches, and word frequencies. Results We found high levels of agreement for word count, with a 93% probability of a newly observed difference being below the minimally important difference. The qualitative features had fair levels of agreement. Word count reached high levels of discrimination between cognitively impaired and unimpaired individuals, regardless of transcription mode. Discussion Our results support the use of automated speech recognition particularly for the assessment of quantitative speech features, even when using data from telephone calls with cognitively impaired individuals in their homes. Highlights High levels of agreement were found between automated and gold‐standard manual transcriptions of telephone chatbot‐based semantic verbal fluency testing, particularly for word count. The qualitative features had fair levels of agreement. Word count reached high levels of discrimination between cognitively impaired and unimpaired individuals, regardless of transcription mode. Automated speech recognition for the assessment of quantitative and qualitative speech features, even when using data from telephone calls with cognitively impaired individuals in their homes, seems feasible and reliable.