(a) To characterize the frequency of objective cognitive deficits and self-perceived cognitive difficulties and (b) to explore demographic and clinical predictors of cognitive dysfunction and cognitive complaints. One hundred and ten adults diagnosed with COVID-19 between March and November 2020, aged ≤ 74 years underwent a brief neuropsychological evaluation 12 months after infection, which included: Brief Visuospatial Memory Test-Revised, California Verbal Learning Test, and Symbol Digit Modalities Test. T scores < 38 were considered abnormal performance; cognitive dysfunction was defined as ≥ 2 abnormal tests. Participants also completed Broadbent's Cognitive Failure Questionnaires (CFQ), Hospital Anxiety and Depression Scale, Modified Fatigue Impact Scale, and Short-Form Health Survey. CFQ ≥ 43 was considered indicative of cognitive complaints. Twenty participants (18.2%) had cognitive dysfunction and 36 (33.3%) had cognitive complaints. Cognitive dysfunction was related to lower education, preinfection history of headache/migraine, and acute COVID-19 symptoms of headache and sleep disturbance. Cognitive complaints were more likely to occur in women, those with fewer years of education, and acute COVID-19 symptoms of headache and sleep disturbance. Cognitive complaints were also significantly related to symptoms of anxiety, depression, and fatigue. Sex and psychopathology were not significant predictors of cognitive dysfunction. Modest associations were found between CFQ total score and cognitive test performance. A subset of individuals develops cognitive difficulties in the context of post-COVID syndrome. Results may support the protective effect of education, a known proxy of cognitive reserve. COVID-19 infection symptoms of headache and sleep disturbance appear to be risk factors for long-term cognitive difficulties. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Intestinal stem cells (ISCs) fuel the lifelong self‐renewal of the intestinal tract and are paramount for epithelial repair. In this context, the Wnt pathway component LGR5 is the most consensual ISC marker to date. Still, the effort to better understand ISC identity and regulation remains a challenge. We have generated a Mex3a knockout mouse model and show that this RNA‐binding protein is crucial for the maintenance of the Lgr5 ⁺ ISC pool, as its absence disrupts epithelial turnover during postnatal development and stereotypical organoid maturation ex vivo . Transcriptomic profiling of intestinal crypts reveals that Mex3a deletion induces the peroxisome proliferator‐activated receptor (PPAR) pathway, along with a decrease in Wnt signalling and loss of the Lgr5 ⁺ stem cell signature. Furthermore, we identify PPARγ activity as a molecular intermediate of MEX3A‐mediated regulation. We also show that high PPARγ signalling impairs Lgr5 ⁺ ISC function, thus uncovering a new layer of post‐transcriptional regulation that critically contributes to intestinal homeostasis.

BACKGROUND: Large vessel occlusion acute ischemic stroke prognosis improved following the 2015 endovascular therapy (EVT) trials. Blood-based biomarkers may improve outcome prediction. We aimed to assess plasma brain-derived tau (BD-Tau) performance in predicting post-EVT large vessel occlusion acute ischemic stroke outcomes. METHODS: We included 2 temporally independent prospective cohorts of anterior circulation in patients with large vessel occlusion acute ischemic stroke who successfully recanalized post-EVT. We measured plasma BD-Tau, GFAP (glial-fibrillary-acidic-protein), NfL (neurofilament-light-chain), and total-Tau upon admission, immediately, 24 hours, and 72 hours post-EVT. Twenty-four-hour neuroimaging and 90-day functional outcomes were independently assessed using the Alberta Stroke Program Early Computed Tomography Score (good outcome: >7 or unchanged) and the modified Rankin Scale (favorable outcome <3 or unchanged), respectively. Based on the first cohort (derivation), we built a multivariable logistic regression model to predict a 90-day functional outcome. Model results were evaluated using the second cohort (evaluation). RESULTS: In the derivation cohort (n=78, mean age=72.9 years, 50% women), 62% of patients had a good 24-hour neuroimaging outcome, and 45% had a favorable 90-day functional outcome. GFAP admission-to-EVT rate-of-change was the best predictor for early neuroimaging outcome but not for 90-day functional outcome. At admission, BD-Tau levels presented the highest discriminative performance for 90-day functional outcomes (area under the curve, 0.76 [95% CI, 0.65–0.87]; P <0.001). The model incorporating age, admission BD-Tau, and 24-hour Alberta Stroke Program Early Computed Tomography Score achieved excellent discrimination of 90-day functional outcome (area under the curve, 0.89 [95% CI, 0.82–0.97]; P <0.001). The score’s predictive performance was maintained in the evaluation cohort (n=66; area under the curve, 0.82 [95% CI, 0.71–0.92]; P <0.001). CONCLUSIONS: Admission plasma BD-Tau accurately predicted 90-day functional outcomes in patients with large vessel occlusion acute ischemic stroke after successful EVT. The proposed model may predict functional outcomes using objective measures, minimizing human-related biases and serving as a simplified prognostic tool for AIS.

Stroke is a leading cause of death and disability in the world. To address such a problem, early diagnosis and tailored acute treatment represent one of the major priorities in acute stroke care. Since the efficacy of reperfusion treatments is highly time-dependent, there is a critical need to optimize procedures for faster and more precise diagnosis. We provide a concise review of the most relevant and well-documented blood–protein biomarkers that exhibit greater potential for translational to clinical practice in stroke differential diagnosis and to differentiate ischemic stroke from hemorrhagic stroke, followed by an overview of the most recent point-of-care technological approaches to address this problem. The integration of fluid-based biomarker profiling, using point-of-care biosensors with demographic, clinical, and neuroimaging parameters in multi-dimensional clinical decision-making algorithms, will be the next step in personalized stroke care.

Cerebral ischemia triggers a cascade of molecular events over minutes to days, which activate immune cells, inflammation, and coagulation, promoting cell death. These processes critically influence both short- and long-term outcomes in patients with stroke. In this review, we address the role of immune molecular and cellular factors, and the therapeutic approaches predicted to be targetable by specific agents under a timely application. We will focus on translational efforts targeting (thrombo)-inflammatory mechanisms, highlighting past missteps and current opportunities. Finally, we outline key mechanistic and methodological questions that may define a path forward.