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Matthew Bonomo,1,* Michael G Hermsen,1,* Samuel Kaskovich,1 Maximilian J Hemmrich,1 Juan C Rojas,2 Kyle A Carey,3 Laura Ruth Venable,4 Matthew M Churpek,5 Valerie G Press3,6 1Pritzker School of Medicine, University of Chicago, Chicago, IL, USA; 2Department of Medicine, Section of Pulmonary/Critical Care, University of Chicago, Chicago, IL, USA; 3Department of Medicine, Section of General Internal Medicine, University of Chicago, Chicago, IL, USA; 4Department of Medicine, Section of Hospitalist Medicine, University of Chicago, Chicago, IL, USA; 5Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin-Madison, Madison, WI, USA; 6Department of Pediatrics, Section of Academic Pediatrics, University of Chicago, Chicago, IL, USA*These authors contributed equally to this workCorrespondence: Valerie G Press, University of Chicago, 5841 S Maryland, MC 2007, Chicago, IL, 60637, USA, Tel +773-702-5170, Email vpress@medicine.bsd.uchicago.eduBackground: Chronic obstructive pulmonary disease (COPD) is a leading cause of hospital readmissions. Few existing tools use electronic health record (EHR) data to forecast patients’ readmission risk during index hospitalizations.Objective: We used machine learning and in-hospital data to model 90-day risk for and cause of readmission among inpatients with acute exacerbations of COPD (AE-COPD).Design: Retrospective cohort study.Participants: Adult patients admitted for AE-COPD at the University of Chicago Medicine between November 7, 2008 and December 31, 2018 meeting International Classification of Diseases (ICD)-9 or − 10 criteria consistent with AE-COPD were included.Methods: Random forest models were fit to predict readmission risk and respiratory-related readmission cause. Predictor variables included demographics, comorbidities, and EHR data from patients’ index hospital stays. Models were derived on 70% of observations and validated on a 30% holdout set. Performance of the readmission risk model was compared to that of the HOSPITAL score.Results: Among 3238 patients admitted for AE-COPD, 1103 patients were readmitted within 90 days. Of the readmission causes, 61% (n = 672) were respiratory-related and COPD (n = 452) was the most common. Our readmission risk model had a significantly higher area under the receiver operating characteristic curve (AUROC) (0.69 [0.66, 0.73]) compared to the HOSPITAL score (0.63 [0.59, 0.67]; p = 0.002). The respiratory-related readmission cause model had an AUROC of 0.73 [0.68, 0.79].Conclusion: Our models improve on current tools by predicting 90-day readmission risk and cause at the time of discharge from index admissions for AE-COPD. These models could be used to identify patients at higher risk of readmission and direct tailored post-discharge transition of care interventions that lower readmission risk.Keywords: chronic obstructive lung disease, COPD, readmissions, machine learning

BackgroundQuantification of biofluid cytokines is a rapidly growing area of translational research. However, comparability across the expanding number of available assay platforms for detection of the same proteins remains to be determined. We aimed to directly compare a panel of commonly measured cytokines in plasma of typically aging adults across two high sensitivity quantification platforms, Meso Scale Discovery high performance electrochemiluminiscence (HPE) and single-molecule immunosorbent assays (Simoa) by Quanterix.Methods57 community-dwelling older adults completed a blood draw, neuropsychological assessment, and brain MRI as part of a healthy brain aging study. Plasma samples from the same draw dates were analyzed for IL-10, IP-10, IL-6, TNFα, and IL-1β on HPE and Simoa, separately. Reliable detectability (coefficient of variance (CV)  0.32), with the exception of IL-1β which was only reliably measured using Simoa (68.4%). On average, CVs were acceptable at

Julio C Rojas1,2, F Gonzalez-Lima1 1Departments of Psychology, Pharmacology and Toxicology, University of Texas at Austin, Austin, TX; 2Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA Abstract: Low-level light therapy (LLLT) using red to near-infrared light energy has gained attention in recent years as a new scientific approach with therapeutic applications in ophthalmology, neurology, and psychiatry. The ongoing therapeutic revolution spearheaded by LLLT is largely propelled by progress in the basic science fields of photobiology and bioenergetics. This paper describes the mechanisms of action of LLLT at the molecular, cellular, and nervous tissue levels. Photoneuromodulation of cytochrome oxidase activity is the most important primary mechanism of action of LLLT. Cytochrome oxidase is the primary photoacceptor of light in the red to near-infrared region of the electromagnetic spectrum. It is also a key mitochondrial enzyme for cellular bioenergetics, especially for nerve cells in the retina and the brain. Evidence shows that LLLT can secondarily enhance neural metabolism by regulating mitochondrial function, intraneuronal signaling systems, and redox states. Current knowledge about LLLT dosimetry relevant for its hormetic effects on nervous tissue, including noninvasive in vivo retinal and transcranial effects, is also presented. Recent research is reviewed that supports LLLT potential benefits in retinal disease, stroke, neurotrauma, neurodegeneration, and memory and mood disorders. Since mitochondrial dysfunction plays a key role in neurodegeneration, LLLT has potential significant applications against retinal and brain damage by counteracting the consequences of mitochondrial failure. Upon transcranial delivery in vivo, LLLT induces brain metabolic and antioxidant beneficial effects, as measured by increases in cytochrome oxidase and superoxide dismutase activities. Increases in cerebral blood flow and cognitive functions induced by LLLT have also been observed in humans. Importantly, LLLT given at energy densities that exert beneficial effects does not induce adverse effects. This highlights the value of LLLT as a novel paradigm to treat visual, neurological, and psychological conditions, and supports that neuronal energy metabolism could constitute a major target for neurotherapeutics of the eye and brain. Keywords: photobiomodulation, cytochrome oxidase, neurotherapeutics, retinal disease, neurological disease, cognitive and mood disorders

The reelin pathway regulates interactions between migrating neurons and radial glia. The activation of this pathway is fundamental during the process of normal corticogenesis. The reelin pathway influences the cytoskeleton dynamics as well as the neural mechanisms of learning and memory and it may also playa critical role during neurodegenerative events. The reelin pathway may be disrupted by oxidative stress, excitotoxicity and other cellular anomalies caused by endogenous and exogenous factors. When disrupted, cytoskeleton components are inefficiently processed giving placetothe protein aggregates that characterize Alzheimer's disease. Such aggregates have been associated with the activation ofthe apoptotic cascade. Neuritic plaques and neurofibrillary tangles are not innocuous byproducts of neurodegeneration, since their presence induces neuroinflammation, cell death and cognitive impairment. However, it is possible that the clinical picture of Alzheimer's disease is perpetuated, but not initially caused by these protein aggregates. Elements ofthe Reelin pathway could represent targets of neuronal vulnerability mediating degenerative changes in the cortical pathways associated to Alzheimer's disease. Characterization of the reelin pathway could improve the understanding of the interactions between the risk factors associated with Alzheimer's disease and could facilitate the development of novel and effective neuroprotective interventions. [ABSTRACT FROM AUTHOR]

Scarab beetles use pheromones and volatiles to search for their partners and host plants. The perception of these compounds occurs in the beetle antennae, particularly in the sensilla. Relatively few studies have morphologically and physiologically characterized the sensilla of scarab beetles. Cyclocephala barrerai Martínez is a beetle distributed in Mexico. Male beetles have larger antennal lamellae than females, and in both cases, the size of this structure is related to their weight. Previous studies have reported that both sexes are attracted to bacterial volatiles isolated from the female genital chambers. Female cuticular hydrocarbons may act as a sexual contact pheromone. However, antennal sensilla and their electrophysiological responses to behaviorally relevant compounds remain to be investigated. Here, we describe and report the types, allometric relationships, and functions of sensilla found in the lamellae of both C. barrerai sexes. Sensilla were identified, classified, measured, and counted to identify intra and intersexual relationships. The single sensillum recordings showed that plant volatiles, hydrocarbons, and heat stimulated receptor neurons. We identified 2 new types of sensilla basiconica in the scape. Males have more and larger antennal sensilla placodea IV, which specializes in detecting pheromones, plant volatiles, and heat. Females have a greater diversity of sensilla., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Western countries have provided reference values (RV) for Alzheimer's disease (AD) plasma biomarkers, but there are not available in Sub-Saharan African populations., Objective: We provide preliminary RV for AD and other plasma biomarkers including amyloid- β (Aβ42/40), phosphorylated tau-181 and 217 (p-tau181, p-tau217), neurofilament light (Nfl), glial fibrillary acidic protein (GFAP), interleukin 1b and 10 (IL-1b and IL-10) and tumor necrosis factor α (TNFα) in Congolese adults with and without dementia., Methods: 85 adults (40 healthy and 45 dementia) over 50 years old were included. Blood samples were provided for plasma AD biomarkers Aβ42/40 and p-tau181, p-tau217; Nfl and GFAP; IL-1b and IL-10 and TNFα analyzed using SIMOA. Linear and logistic regressions were conducted to evaluate differences in biomarkers by age and gender and neurological status, and for the prediction of dementia status by each individual biomarker. RV were those that optimized sensitivity and specificity based on Youden's index., Results: In this sample of 85 adults, 45 (53%) had dementia, 38 (45%) were male, overall mean age was 73.2 (SD 7.6) years with 8.3 (5.4) years of education. There were no significant differences in age, gender, and education based on neurological status. Biomarker concentrations did not significantly differ by age except for p-tau181 and GFAP and did not differ by sex. Preliminary normal value cutoffs of various plasma in pg./mL were 0.061 for Aβ42/40, 4.50 for p-tau 181, 0.008 for p-tau 217, 36.5 for Nfl, 176 for GFAP, 1.16 for TNFa, 0.011 for IL-1b, and 0.38 for IL-10. All AUCs ranged between 0.64-0.74. P-tau 217 [0.72 (95% CI: 0.59, 0.84)] followed by GFAP [0.72 (95% CI: 0.61, 0.83)], and Nfl [0.73 (95% CI: 0.62, 0.84)] had the highest AUC compared to other plasma biomarkers., Conclusion: This study provides RV which could be of preliminary utility to facilitate the screening, clinical diagnostic adjudication, and classification, of dementia in Congolese adults., Competing Interests: AJ was employed by ALZpath, 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ikanga, Jean, Medina, Patel, Schwinne, Epenge, Gikelekele, Tshengele, Kavugho, Mampunza, Mananga, Teunissen, Stringer, Rojas, Chan, Lario Lago, Kramer, Boxer, Jeromin, Gross and Alonso.)

We present the case of a patient with Andersen-Tawil syndrome (ATS), a rare genetic disorder characterized by the presence of ventricular arrhythmias, skeletal dysmorphic features, and periodic muscle paralysis. The diagnosis was delayed due to the non-simultaneity of symptom presentation. The report highlights the importance of investigating neurological symptoms in the presence of ventricular arrhythmias of unclear origin or cardiac symptoms in patients with periodic paralysis. The diagnosis was confirmed by the identification of a mutation in the KCNJ2 gene (c.224C>T(p.Thr75Met)); this specific mutation has not been reported in the gnomAD database, suggesting a minor allele frequency (MAF) of less than 1%. The patient is currently managed pharmacologically with a beta-blocker and remains free of arrhythmias., Competing Interests: Conflicto de intereses: Los autores declaran no tener conflictos de intereses

Objectives: Cognitive and behavioral phenomena define behavioral variant frontotemporal dementia (bvFTD), but neuropsychiatric symptoms (NPS) outside the core criteria are common throughout the illness. Identifying how NPS cluster in bvFTD may clarify the underlying neurobiology of bvFTD-related NPS and guide development of therapies., Methodology: Participants (N=354) with sporadic and genetic bvFTD were enrolled in the ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration Consortium. Dementia stage was defined as early (CDR ® plus NACC FTLD ≤ 1) or advanced (CDR ® plus NACC FTLD ≥ 1). Baseline and annual follow-up visit data were analyzed to compare NPS across stages of bvFTD. Psychiatric states were captured using the Neuropsychiatric Inventory-Questionnaire and Clinician Judgement of Symptoms. Polychoric cluster analysis was used to describe NPS clusters., Results: NPS were highly prevalent (≥ 90%) in early and late bvFTD. Four NPS clusters were identified based on magnitude of factor loadings: affective, disinhibited, compulsive, and psychosis. Neuropsychiatric symptoms fluctuated across visits. In the affective cluster, depression and anxiety showed the least visit-to-visit stability. In the disinhibited cluster, elation showed the least stability. Symptoms in the psychosis and compulsive clusters (hallucinations, delusions, obsessions/compulsions, and hyperorality) were largely stable, persisting from visit-to-visit in more than 50% of cases., Conclusion: NPS in bvFTD are frequent and cluster into four discrete groups in bvFTD. These clusters may result from specific neural network disruptions that could serve as targets for future interventions. The fluctuating nature of NPS in bvFTD suggests that they are not reliable markers of disease progression or stage.

Objectives: Sentinel surveillance for bacterial pneumonia (SSBP) allows the monitoring of immunopreventable diseases. The results of the SSBP carried out at HOMI, Fundación Hospital pediátrico de la Misericordia, are presented., Methods: The daily active search for cases was carried out in accordance with the protocol of the Pan American Health Organization from January 2016 to December 2022., Results: There were 6970 suspected cases of bacterial pneumonia (BP). Among the 3048 (43.7%) patients with probable BP, cultures were obtained from 2777 (91.1%), and BP was confirmed in 190 (6.2%). The causes were Streptococcus pneumoniae in 98 (51.6%) cases, Spn19A in 47 (48%), Spn3 in 16 (16%), and Spn6C in 4 (4%). Haemophilus influenzae was found in 32 (16.8%) cases: non-typeable H. influenzae in 20 (62.5%), H. influenzae type b in five (15.6%), and H. influenzae type a in two (6.2%). Other bacteria were found in 60 (31.6%) cases. A total of 51.6% and 42.9% of patients with S. pneumoniae had decreased sensitivity to penicillin and ceftriaxone, respectively., Conclusions: The serotypes included in the conjugate vaccines for pneumococcus and H. influenzae b decreased significantly, and serotype turnover was observed. Among the S. pneumoniae cases, Spn19A, Spn3, and Spn6C were the most frequent serotypes and associated with multiresistance. The SSBP allows us to determine the clinical behavior of the disease and to detect the serotypes emergence., Competing Interests: Germán Camacho-Moreno has received support for participation in congresses and conference payments from Pfizer, Adium, Biomerieux, Sanofi and Merck Sharp and Dohme (MSD); has participated in the MSD advisory council; and has received support from Pfizer and MSD for other research. The other authors declare that they do not have conflicts of interest., (© 2024 The Authors.)

Background: Critical illness, or acute organ failure requiring life support, threatens over five million American lives annually. Electronic health record (EHR) data are a source of granular information that could generate crucial insights into the nature and optimal treatment of critical illness. However, data management, security, and standardization are barriers to large-scale critical illness EHR studies., Methods: A consortium of critical care physicians and data scientists from eight US healthcare systems developed the Common Longitudinal Intensive Care Unit (ICU) data Format (CLIF), an open-source database format that harmonizes a minimum set of ICU Data Elements for use in critical illness research. We created a pipeline to process adult ICU EHR data at each site. After development and iteration, we conducted two proof-of-concept studies with a federated research architecture: 1) an external validation of an in-hospital mortality prediction model for critically ill patients and 2) an assessment of 72-hour temperature trajectories and their association with mechanical ventilation and in-hospital mortality using group-based trajectory models., Results: We converted longitudinal data from 94,356 critically ill patients treated in 2020-2021 (mean age 60.6 years [standard deviation 17.2], 30% Black, 7% Hispanic, 45% female) across 8 health systems and 33 hospitals into the CLIF format, The in-hospital mortality prediction model performed well in the health system where it was derived (0.81 AUC, 0.06 Brier score). Performance across CLIF consortium sites varied (AUCs: 0.74-0.83, Brier scores: 0.06-0.01), and demonstrated some degradation in predictive capability. Temperature trajectories were similar across health systems. Hypothermic and hyperthermic-slow-resolver patients consistently had the highest mortality., Conclusions: CLIF facilitates efficient, rigorous, and reproducible critical care research. Our federated case studies showcase CLIF's potential for disease sub-phenotyping and clinical decision-support evaluation. Future applications include pragmatic EHR-based trials, target trial emulations, foundational multi-modal AI models of critical illness, and real-time critical care quality dashboards.

Objective: The hippocampus is one of the first brain structures affected by Alzheimer's disease (AD), and its atrophy is a strong indicator of the disease. This study investigates the ability of plasma biomarkers of AD and AD-related dementias-amyloid-β (Aβ42/40), phosphorylated tau-181 (p-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP)-to predict hippocampal atrophy in adult individuals in Kinshasa, Democratic Republic of Congo (DRC)., Methods: Eighty-five adult individuals (40 healthy and 45 suspected AD) over 65 years old were evaluated using the Community Screening Instrument for Dementia and Alzheimer's Questionnaire (AQ). Core AD biomarkers (Aβ42/40 and p-tau181) and non-specific neurodegeneration biomarkers (NfL, GFAP) were measured in blood samples collected at the study visit. Hippocampal volumes were measured using magnetic resonance imaging (MRI). General linear regression was used to evaluate differences in biomarker concentrations by neurological status. Logistic regression models were used to create receiver operating characteristic curves and calculate areas under the curve (AUCs) with and without clinical covariates to determine the ability of biomarker concentrations to predict hippocampal atrophy. Plasma biomarkers were used either individually or in combination in the models., Results: Elevated p-tau181 was associated with left hippocampal (LH) atrophy p= 0.020). Only higher p-tau181 concentrations were significantly associated with 4.2-fold increased odds [OR=4.2 (1.5-18.4)] of hippocampal atrophy per standard deviation. The AUC of plasma biomarkers without clinical covariates to discriminate LH, RH, and total hippocampal (TH) or both hippocampi atrophy ranged between 90% to 94%, 76% to 82%, and 85% to 87%, respectively. The AUC of models including clinical covariates and AD biomarkers used in combination to discriminate LH, RH, and TH ranged between 94%-96%, 81%-84%, and 88%-90%, respectively., Conclusion: These results indicate that, consistent with studies in other settings, core AD plasma biomarkers can predict hippocampal atrophy in a population in Sub-Saharan Africa., Competing Interests: CONFLICTS OF INTEREST AJ was employed by ALZpath, 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. JCR is a site PI for clinical trials sponsored by Eli-Lilly, Eisai and Amylyx.

Predator-prey interactions are the interspecific relationships of greatest interest in ecology. Spiders are among the most diverse and ubiquitous terrestrial predators on the planet. Their large dietary breadth is often linked with the development of specific predatory behaviors and morphological adaptations. However, studies on the predatory behavior of spiders have mostly focused on specialist species, leaving behind the ethological variability occurring in generalist species that allow them to respond to the different prey types. For three species of generalist wandering spiders, we searched images of predation events on the Internet to determine the most common prey. Subsequently, the focal predator species were then used in behavioral experiments. Using high-speed videos, handling patterns for different prey types (spider and cricket) were analyzed. Our results show a notable difference in handling patterns between prey types. We found that the spider prey was often rotated around the axis allowing the predator to bite in the ventral region of the prey and thus avoid a counterattack. Contrary, crickets were arbitrarily rotated. Our work may be an indication that these three species of generalist spiders have a preference for manipulating prey differently with a preference to rotate spiders, allowing them to exploit prey with various defensive mechanisms., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: We compared the accuracy of amyloid and [ 18 F]Flortaucipir (FTP) tau positron emission tomography (PET) visual reads for distinguishing patients with mild cognitive impairment (MCI) or dementia with fluid biomarker support of Alzheimer's disease (AD)., Methods: Participants with FTP-PET, amyloid-PET, and diagnosis of dementia-AD (n = 102), MCI-AD (n = 41), non-AD diseases (n = 76), and controls (n = 20) were included. AD status was determined independent of PET by cerebrospinal fluid or plasma biomarkers. The mean age was 66.9 years, and 44.8% were women. Three readers interpreted scans blindly and independently. Amyloid-PET was classified as positive/negative using tracer-specific criteria. FTP-PET was classified as positive with medial temporal lobe (MTL) binding as the minimum uptake indicating AD tau (tau-MTL+), positive with posterolateral temporal or extratemporal cortical binding in an AD-like pattern (tau-CTX+), or negative. The majority of scan interpretations were used to calculate diagnostic accuracy of visual reads in detecting MCI/dementia with fluid biomarker support for AD (MCI/dementia-AD)., Results: Sensitivity of amyloid-PET for MCI/dementia-AD was 95.8% (95% confidence interval 91.1-98.4%), which was comparable to tau-CTX+ 92.3% (86.7-96.1%, p = 0.67) and tau-MTL+ 97.2% (93.0-99.2%, p = 0.27). Specificity of amyloid-PET for biomarker-negative healthy and disease controls was 84.4% (75.5-91.0%), which was like tau-CTX+ 88.5% (80.4-94.1%, p = 0.34), and trended toward being higher than tau-MTL+ 75.0% (65.1-83.3%, p = 0.08). Tau-CTX+ had higher specificity than tau-MTL+ (p = 0.0002), but sensitivity was lower (p = 0.02), driven by decreased sensitivity for MCI-AD (80.5% [65.1-91.2] vs. 95.1% [83.5-99.4], p = 0.03)., Interpretation: Amyloid- and tau-PET visual reads have similar sensitivity/specificity for detecting AD in cognitively impaired patients. Visual tau-PET interpretations requiring cortical binding outside MTL increase specificity, but lower sensitivity for MCI-AD. ANN NEUROL 2024;96:476-487., (© 2024 American Neurological Association.)

Background and Objectives: Identification of fluid biomarkers for progressive supranuclear palsy (PSP) is critical to enhance therapeutic development. We implemented unbiased DNA aptamer (SOMAmer) proteomics to identify novel CSF PSP biomarkers., Methods: This is a cross-sectional study in original (18 clinically diagnosed PSP-Richardson syndrome [PSP-RS], 28 cognitively healthy controls]), validation (23 PSP-RS, 26 healthy controls), and neuropathology-confirmed (21 PSP, 52 non-PSP frontotemporal lobar degeneration) cohorts. Participants were recruited through the University of California, San Francisco, and the 4-Repeat Neuroimaging Initiative. The original and neuropathology cohorts were analyzed with the SomaScan platform version 3.0 (5026-plex) and the validation cohort with version 4.1 (7595-plex). Clinical severity was measured with the PSP Rating Scale (PSPRS). CSF proteomic data were analyzed to identify differentially expressed targets, implicated biological pathways using enrichment and weighted consensus gene coexpression analyses, diagnostic value of top targets with receiver-operating characteristic curves, and associations with disease severity with linear regressions., Results: A total of 136 participants were included (median age 70.6 ± 8 years, 68 [50%] women). One hundred fifty-five of 5,026 (3.1%), 959 of 7,595 (12.6%), and 321 of 5,026 (6.3%) SOMAmers were differentially expressed in PSP compared with controls in original, validation, and neuropathology-confirmed cohorts, with most of the SOMAmers showing reduced signal (83.1%, 95.1%, and 73.2%, respectively). Three coexpression modules were associated with PSP across cohorts: (1) synaptic function/JAK-STAT (β = -0.044, corrected p = 0.002), (2) vesicle cytoskeletal trafficking (β = 0.039, p = 0.007), and (3) cytokine-cytokine receptor interaction (β = -0.032, p = 0.035) pathways. Axon guidance was the top dysregulated pathway in PSP in original (strength = 1.71, p < 0.001), validation (strength = 0.84, p < 0.001), and neuropathology-confirmed (strength = 0.78, p < 0.001) cohorts. A panel of axon guidance pathway proteins discriminated between PSP and controls in original (area under the curve [AUC] = 0.924), validation (AUC = 0.815), and neuropathology-confirmed (AUC = 0.932) cohorts. Two inflammatory proteins, galectin-10 and cytotoxic T lymphocyte-associated protein-4, correlated with PSPRS scores across cohorts., Discussion: Axon guidance pathway proteins and several other molecular pathways are downregulated in PSP, compared with controls. Proteins in these pathways may be useful targets for biomarker or therapeutic development.

Background: Western countries have provided reference values (RV) for Alzheimer's disease (AD) plasma biomarkers, but there are not available in Sub-Saharan African populations., Objective: We provide preliminary RV for AD and other plasma biomarkers including amyloid- β (Aβ42/40), phosphorylated tau-181 and 217 (p-tau181, p-tau217), neurofilament light (Nfl), glial fibrillary acidic protein (GFAP), interleukin 1b and 10 (IL-1b and IL-10) and tumor necrosis factor α (TNFα) in Congolese adults with and without dementia., Methods: 85 adults (40 healthy and 45 dementia) over 50 years old were included. Blood samples were provided for plasma AD biomarkers Aβ42/40 and p-tau181, p-tau217; Nfl and GFAP; IL-1b and IL-10 and TNFα analyzed using SIMOA. Linear and logistic regressions were conducted to evaluate differences in biomarkers by age and gender and neurological status, and for the prediction of dementia status by each individual biomarker. RV were those that optimized sensitivity and specificity based on Youden's index., Results: In this sample of 85 adults, 40 (47%) had dementia, 38 (45.0%) were male, overall mean age was 73.2 (SD 7.6) years with 8.3 (5.4) years of education. There were no significant differences in age, gender, and education based on neurological status. Biomarker concentrations did not significantly differ by age except for p-tau181 and GFAP and did not differ by sex. Preliminary cutoffs of various plasma in pg/ml were 0.061 for Aβ42/40, 4.50 for p-tau 181, 0.008 for p-tau 217, 36.5 for Nfl, 176 for GFAP, 1.16 for TNFa, 0.011 for IL-1b, and 0.38 for IL-10. All AUCs ranged between 0.64-0.74. P-tau 217 [0.74 (0.61, 0.86)] followed by GFAP [0.72 (0.61, 0.83), and Nfl [0.71 (0.60, 0.82)] had the highest AUC compared to other plasma biomarkers., Conclusions: This study provides RV which could be of preliminary utility to facilitate the screening, clinical diagnostic adjudication, classification, and prognosis of AD in Congolese adults.

Rationale: Asthma poses a significant burden for U.S. patients and health systems, yet inpatient care quality is understudied. National chronic obstructive lung disease (COPD) readmission policies may affect inpatient asthma care through hospital responses to these policies because of imprecise diagnosis and identification of patients with COPD and asthma. Objectives: Evaluate inpatient care quality for patients hospitalized with asthma and potential collateral effects of the Medicare COPD Hospital Readmissions Reduction Program (HRRP). Methods: This was a retrospective cohort study of patients aged 18-54 years hospitalized for asthma across 924 U.S. hospitals (Premier Healthcare Database). Results: Care quality for patients with asthma was evaluated before HRRP implementation ( n  = 20,820; January 2010-September 2014) and after HRRP implementation ( n  = 26,885; October 2014-December 2018) using adherence to inpatient care guidelines (recommended, nonrecommended, and "ideal care" [all recommended with no nonrecommended care]). Between 2010 and 2018, at least 80% of patients received recommended care annually. Recommended care decreased similarly (rate of 0.02%/mo) after versus before HRRP ( P  = 0.8). Nonrecommended care decreased more rapidly after HRRP (rate of 0.29%/mo) versus before HRRP (rate of 0.17%/mo; P  < 0.001), with changes driven largely by decreased antibiotic prescribing. Ideal care increased more rapidly after HRRP (rate of 0.25%/mo) versus before HRRP (rate of 0.17%/mo; P  = 0.02), with changes driven largely by nonrecommended care improvements. Conclusions: Post-HRRP trends suggest asthma care improved with increased rates of guideline concordance in nonrecommended and ideal care. Although federal policies (e.g., HRRP) may have had positive collateral effects, such as with asthma care, parallel care efforts, including antibiotic stewardship, likely contributed to these improvements.

Objectives: To evaluate the effect of Alzheimer's disease (AD) -related biomarker change on clinical features, brain atrophy and functional connectivity of patients with corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP)., Methods: Data from patients with a clinical diagnosis of CBS, PSP, and AD and healthy controls were obtained from the 4-R-Tauopathy Neuroimaging Initiative 1 and 2, the Alzheimer's Disease Neuroimaging Initiative, and a local cohort from the Toronto Western Hospital. Patients with CBS and PSP were divided into AD-positive (CBS/PSP-AD) and AD-negative (CBS/PSP-noAD) groups based on fluid biomarkers and amyloid PET scans. Cognitive, motor, and depression scores; AD fluid biomarkers (cerebrospinal p-tau, t-tau, and amyloid-beta, and plasma ptau-217); and neuroimaging data (amyloid PET, MRI and fMRI) were collected. Clinical features, whole-brain gray matter volume and functional networks connectivity were compared across groups., Results: Data were analyzed from 87 CBS/PSP-noAD and 23 CBS/PSP-AD, 18 AD, and 30 healthy controls. CBS/PSP-noAD showed worse performance in comparison to CBS/PSP-AD in the PSPRS [mean(SD): 34.8(15.8) vs 23.3(11.6)] and the UPDRS scores [mean(SD): 34.2(17.0) vs 21.8(13.3)]. CBS/PSP-AD demonstrated atrophy in AD signature areas and brainstem, while CBS/PSP-noAD patients displayed atrophy in frontal and temporal areas, globus pallidus, and brainstem compared to healthy controls. The default mode network showed greatest disconnection in CBS/PSP-AD compared with CBS/PSP-no AD and controls. The thalamic network connectivity was most affected in CBS/PSP-noAD., Interpretation: AD biomarker positivity may modulate the clinical presentation of CBS/PSP, with evidence of distinctive structural and functional brain changes associated with the AD pathology/co-pathology. ANN NEUROL 2024;96:99-109., (© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Frontotemporal lobar degeneration (FTLD) is a leading cause of dementia in individuals aged <65 years. Several challenges to conducting in-person evaluations in FTLD illustrate an urgent need to develop remote, accessible, and low-burden assessment techniques. Studies of unobtrusive monitoring of at-home computer use in older adults with mild cognitive impairment show that declining function is reflected in reduced computer use; however, associations with smartphone use are unknown., Objective: This study aims to characterize daily trajectories in smartphone battery use, a proxy for smartphone use, and examine relationships with clinical indicators of severity in FTLD., Methods: Participants were 231 adults (mean age 52.5, SD 14.9 years; n=94, 40.7% men; n=223, 96.5% non-Hispanic White) enrolled in the Advancing Research and Treatment of Frontotemporal Lobar Degeneration (ARTFL study) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS study) Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) Mobile App study, including 49 (21.2%) with mild neurobehavioral changes and no functional impairment (ie, prodromal FTLD), 43 (18.6%) with neurobehavioral changes and functional impairment (ie, symptomatic FTLD), and 139 (60.2%) clinically normal adults, of whom 55 (39.6%) harbored heterozygous pathogenic or likely pathogenic variants in an autosomal dominant FTLD gene. Participants completed the Clinical Dementia Rating plus National Alzheimer's Coordinating Center Frontotemporal Lobar Degeneration Behavior and Language Domains (CDR+NACC FTLD) scale, a neuropsychological battery; the Neuropsychiatric Inventory; and brain magnetic resonance imaging. The ALLFTD Mobile App was installed on participants' smartphones for remote, passive, and continuous monitoring of smartphone use. Battery percentage was collected every 15 minutes over an average of 28 (SD 4.2; range 14-30) days. To determine whether temporal patterns of battery percentage varied as a function of disease severity, linear mixed effects models examined linear, quadratic, and cubic effects of the time of day and their interactions with each measure of disease severity on battery percentage. Models covaried for age, sex, smartphone type, and estimated smartphone age., Results: The CDR+NACC FTLD global score interacted with time on battery percentage such that participants with prodromal or symptomatic FTLD demonstrated less change in battery percentage throughout the day (a proxy for less smartphone use) than clinically normal participants (P<.001 in both cases). Additional models showed that worse performance in all cognitive domains assessed (ie, executive functioning, memory, language, and visuospatial skills), more neuropsychiatric symptoms, and smaller brain volumes also associated with less battery use throughout the day (P<.001 in all cases)., Conclusions: These findings support a proof of concept that passively collected data about smartphone use behaviors associate with clinical impairment in FTLD. This work underscores the need for future studies to develop and validate passive digital markers sensitive to longitudinal clinical decline across neurodegenerative diseases, with potential to enhance real-world monitoring of neurobehavioral change., (©Emily W Paolillo, Kaitlin B Casaletto, Annie L Clark, Jack C Taylor, Hilary W Heuer, Amy B Wise, Sreya Dhanam, Mark Sanderson-Cimino, Rowan Saloner, Joel H Kramer, John Kornak, Walter Kremers, Leah Forsberg, Brian Appleby, Ece Bayram, Andrea Bozoki, Danielle Brushaber, R Ryan Darby, Gregory S Day, Bradford C Dickerson, Kimiko Domoto-Reilly, Fanny Elahi, Julie A Fields, Nupur Ghoshal, Neill Graff-Radford, Matthew G H Hall, Lawrence S Honig, Edward D Huey, Maria I Lapid, Irene Litvan, Ian R Mackenzie, Joseph C Masdeu, Mario F Mendez, Carly Mester, Toji Miyagawa, Georges Naasan, Belen Pascual, Peter Pressman, Eliana Marisa Ramos, Katherine P Rankin, Jessica Rexach, Julio C Rojas, Lawren VandeVrede, Bonnie Wong, Zbigniew K Wszolek, Bradley F Boeve, Howard J Rosen, Adam L Boxer, Adam M Staffaroni, ALLFTD Consortium. Originally published in JMIR Aging (https://aging.jmir.org), 26.06.2024.)

Packaging design is pivotal in motivating consumer decisions, as a key communication tool from creation to purchase. Currently, the interpretation and evaluation of packaging's impact are shifting toward non-traditional methods. This pilot study evaluated the packaging perception of York Ham and Turkey Breast products. The event-related potential (ERP) technique, the methodology priming words (positive and negative), and target images (original and modified packaging) were applied. A total of 23 participants were sampled using a 32-channels scalp elastic electrode cap and viewed 200 trials of word-image matching. Participants responded whether the images and adjectives matched or not, using the two groups of images. The results demonstrate an N400 effect in the parietal area. This region was observed to show evidence of cognitive processing related to congruency or incongruency, by contrasting the priming and target of this study. The evaluation positioned the York Ham packaging as the best rated. The findings show a relevant contribution to ERPs and research related to the food packaging perception.

(1) Background/Objectives : Dexmedetomidine is a sedative for patients receiving invasive mechanical ventilation (IMV) that previous single-site studies have found to be associated with improved survival in patients with COVID-19. The reported clinical benefits include dampened inflammatory response, reduced respiratory depression, reduced agitation and delirium, improved preservation of responsiveness and arousability, and improved hypoxic pulmonary vasoconstriction and ventilation-perfusion ratio. Whether improved mortality is evident in large, multi-site COVID-19 data is understudied. (2) Methods : The association between dexmedetomidine use and mortality in patients with COVID-19 receiving IMV was assessed. This retrospective multi-center cohort study utilized patient data in the United States from health systems participating in the National COVID Cohort Collaborative (N3C) from 1 January 2020 to 3 November 2022. The primary outcome was 28-day mortality rate from the initiation of IMV. Propensity score matching adjusted for differences between the group with and without dexmedetomidine use. Adjusted hazard ratios (aHRs) for 28-day mortality were calculated using multivariable Cox proportional hazards models with dexmedetomidine use as a time-varying covariate. (3) Results : Among the 16,357,749 patients screened, 3806 patients across 17 health systems met the study criteria. Mortality was lower with dexmedetomidine use (aHR, 0.81; 95% CI, 0.73-0.90; p < 0.001). On subgroup analysis, mortality was lower with earlier dexmedetomidine use-initiated within the median of 3.5 days from the start of IMV-(aHR, 0.67; 95% CI, 0.60-0.76; p < 0.001) as well as use prior to standard, widespread use of dexamethasone for patients on respiratory support (prior to 30 July 2020) (aHR, 0.54; 95% CI, 0.42-0.69; p < 0.001). In a secondary model that was restricted to 576 patients across six health system sites with available PaO 2 /FiO 2 data, mortality was not lower with dexmedetomidine use (aHR 0.95, 95% CI, 0.72-1.25; p = 0.73); however, on subgroup analysis, mortality was lower with dexmedetomidine use initiated earlier than the median dexmedetomidine start time after IMV (aHR, 0.72; 95% CI, 0.53-0.98; p = 0.04) and use prior to 30 July 2020 (aHR, 0.22; 95% CI, 0.06-0.78; p = 0.02). (4) Conclusions : Dexmedetomidine use was associated with reduced mortality in patients with COVID-19 receiving IMV, particularly when initiated earlier, rather than later, during the course of IMV as well as use prior to the standard, widespread usage of dexamethasone during respiratory support. These particular findings might suggest that the associated mortality benefit with dexmedetomidine use is tied to immunomodulation. However, further research including a large randomized controlled trial is warranted to evaluate the potential mortality benefit of DEX use in COVID-19 and evaluate the physiologic changes influenced by DEX that may enhance survival.

Study Objectives: To determine the prevalence of preadmission insomnia symptoms among hospitalized patients and assess the association of insomnia symptoms with objective in-hospital sleep and clinical outcomes., Methods: We conducted a prospective cohort study of medicine inpatients (age ≥ 50, no previously diagnosed sleep disorders). Participants answered the Insomnia Severity Index (ISI) questionnaire to assess for preadmission insomnia symptoms (scored 0-28; higher scores suggest more insomnia symptoms). Sleep duration and efficiency were measured with actigraphy. Participants self-reported 30-day postdischarge readmissions and emergency department and/or urgent care visits., Results: Of 568 participants, 49% had ISI scores suggestive of possible undiagnosed insomnia (ISI ≥ 8). Higher ISI scores were associated with shorter sleep duration [β = -2.6, 95% confidence interval (CI) -4.1 to -1.1, P = .001] and lower sleep efficiency (β = -0.39, 95% CI -0.63 to -0.15, P = .001). When adjusted for age, sex, body mass index, and comorbidities, higher ISI scores were associated with longer length of stay (incidence rate ratio 1.01, 95% CI 1.00-1.02, P = .011), increased risk of 30-day readmission (odds ratio 1.04, 95% CI 1.01-1.07, P = .018), and increased risk of 30-day emergency department or urgent care visit (odds ratio 1.04, 95% CI 1.00-1.07, P = .043)., Conclusions: Among medicine inpatients, there was a high prevalence of preadmission insomnia symptoms suggestive of possible undiagnosed insomnia. Participants with higher ISI scores slept less with lower sleep efficiency during hospitalization. Higher ISI scores were associated with longer length of stay, increased risk of a 30-day postdischarge readmission, and increased risk of a 30-day postdischarge emergency department or urgent care visit., Citation: Neborak JM, Press VG, Parker WF, et al. Association of preadmission insomnia symptoms with objective in-hospital sleep and clinical outcomes among hospitalized patients. J Clin Sleep Med . 2024;20(5):681-687., (© 2024 American Academy of Sleep Medicine.)

Introduction: Lewy body disease (LBD) is a common primary or co-pathology in neurodegenerative syndromes. An alpha-synuclein seed amplification assay (αSyn-SAA) is clinically available, but clinical performance, especially lower sensitivity in amygdala-predominant cases, is not well understood., Methods: Antemortem CSF from neuropathology-confirmed LBD cases was tested with αSyn-SAA (N = 56). Diagnostic performance and clinicopathological correlations were examined., Results: Similar to prior reports, sensitivity was 100% for diffuse and transitional LBD (9/9), and overall specificity was 96.3% (26/27). Sensitivity was lower in amygdala-predominant (6/14, 42.8%) and brainstem-predominant LBD (1/6, 16.7%), but early spread outside these regions (without meeting criteria for higher stage) was more common in αSyn-SAA-positive cases (6/7, 85.7%) than negative (2/13, 15.4%)., Discussion: In this behavioral neurology cohort, αSyn-SAA had excellent diagnostic performance for cortical LBD. In amygdala- and brainstem-predominant cases, sensitivity was lower, but positivity was associated with anatomical spread, suggesting αSyn-SAA detects early LBD progression in these cohorts., Highlights: A cerebrospinal fluid alpha-synuclein assay detects cortical LBD with high sensitivity/specificity. Positivity in prodromal stages of LBD was associated with early cortical spread. The assay provides precision diagnosis of LBD that could support clinical trials. The assay can also identify LBD co-pathology, which may impact treatment responses., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Drosophila suzukii (Matsumura) is an exotic pest of economic importance that affects several soft-skinned fruits in Mexico. Previously, we found that yellow or yellow-green rectangular cards inside a transparent trap baited with attractants improved D . suzukii capture. In this study, we evaluated the influence of rectangular cards with different yellow shades inside a transparent multi-hole trap baited with apple cider vinegar (ACV) on D . suzukii capture in the field. Second, we tested whether ACV-baited traps with cards of other geometric shapes affected D . suzukii catches compared to traps with rectangular cards. Third, we evaluated the effects of commercial lures combined with a more efficient visual stimulus from previous experiments on trapping D . suzukii flies. We found that ACV-baited traps plus a yellow-shaded rectangle card with 67% reflectance at a 549.74 nm dominant wavelength captured more flies than ACV-baited traps with yellow rectangle cards with a higher reflectance. Overall, ACV-baited traps with rectangles and squares caught more flies than did ACV-baited traps without visual stimuli. The traps baited with SuzukiiLURE-Max, ACV and Z-Kinol plus yellow rectangles caught 57, 70 and 101% more flies, respectively, than the traps baited with the lure but without a visual stimulus.

Calling males of Anastrepha obliqua release volatile compounds to attract conspecific males to form leks and females to mate. Male volatiles from Mexican and Brazilian populations of A . obliqua have been previously identified. However, there are differences in the number and identity of volatile compounds between the populations. These differences in volatile profiles may be due to male origin (e.g. wild or mass-reared flies) or methodological issues (e.g. sampling techniques). In this study, we evaluated the attractiveness of wild, laboratory non-irradiated, and laboratory-irradiated flies under semi-field conditions. Male volatiles were collected using dynamic headspace sampling (DHS) and solid-phase microextraction (SPME) techniques, and identified using gas chromatography-coupled mass spectrometry. The results showed no difference in the attractiveness of wild, laboratory non-irradiated, and irradiated males to females. However, the number of captured females differed according to the origin; wild and non-irradiated females were captured more frequently than the irradiated flies. A total of 21 compounds were found using SPME, whereas only 12 were collected using DHS, although the relative amounts of these compounds were higher than those obtained using the former sampling technique. In addition, only laboratory non-irradiated males released α-pinene and menthol, which have not been previously reported in this fruit fly species. Additionally, we identified novel compounds in A . obliqua ; however, certain compounds previously reported were not detected. This study suggests that despite the qualitative and quantitative variations in the volatile profiles of A . obliqua males, their attractiveness was unaffected.

Background: The current study examined the sensitivity of two memory subtests and their corresponding learning slope metrics derived from the African Neuropsychology Battery (ANB) to detect amyloid pathology and APOEε4 status in adults from Kinshasa, the Democratic Republic of the Congo., Methods: 85 participants were classified for the presence of β-amyloid pathology and based on allelic presence of APOEε4 using Simoa. All participants were screened using CSID and AQ, underwent verbal and visuospatial memory testing from ANB, and provided blood samples for plasma Aβ 42 , Aβ 40 , and APOE proteotype. Pearson correlation, linear and logistic regression were conducted to compare amyloid pathology and APOEε4 status with derived learning scores, including initial learning, raw learning score, learning over trials, and learning ratio., Results: Our sample included 35 amyloid positive and 44 amyloid negative individuals as well as 42 without and 39 with APOEε4. All ROC AUC ranges for the prediction of amyloid pathology based on learning scores were low, ranging between 0.56-0.70 (95% CI ranging from 0.44-0.82). The sensitivity of all the scores ranged between 54.3-88.6, with some learning metrics demonstrating good sensitivity. Regarding APOEε4 prediction, all AUC values ranged between 0.60-0.69, with all sensitivity measures ranging between 53.8-89.7. There were minimal differences in the AUC values across learning slope metrics, largely due to the lack of ceiling effects in this sample., Discussion: This study demonstrates that some ANB memory subtests and learning slope metrics can discriminate those that are normal from those with amyloid pathology and those with and without APOEε4, consistent with findings reported in Western populations., Competing Interests: AJ was employed by ALZpath, Inc. KY was employed by company C2N Diagnostics. 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., (Copyright © 2024 Ikanga, Patrick, Schwinne, Patel, Epenge, Gikelekele, Tshengele, Kavugho, Mampunza, Yarasheski, Teunissen, Stringer, Levey, Rojas, Chan, Lario Lago, Kramer, Boxer, Jeromin, Alonso and Spencer.)

Voltage-gated sodium channels (Na V ) are pivotal proteins responsible for initiating and transmitting action potentials. Emerging evidence suggests that proteolytic cleavage of sodium channels by calpains is pivotal in diverse physiological scenarios, including ischemia, brain injury, and neuropathic pain associated with diabetes. Despite this significance, the precise mechanism by which calpains recognize sodium channels, especially given the multiple calpain isoforms expressed in neurons, remains elusive. In this work, we show the interaction of Calpain-10 with Na V 's C-terminus through a yeast 2-hybrid assay screening of a mouse brain cDNA library and in vitro by GST-pulldown. Later, we also obtained a structural and dynamic hypothesis of this interaction by modeling, docking, and molecular dynamics simulation. These results indicate that Calpain-10 interacts differentially with the C-terminus of Na V 1.2 and Na V 1.6. Calpain-10 interacts with Na V 1.2 through domains III and T in a stable manner. In contrast, its interaction with Na V 1.6 involves domains II and III, which could promote proteolysis through the Cys-catalytic site and C2 motifs., (© 2024. The Author(s).)

Introduction: With emergence of disease-modifying therapies, efficient diagnostic pathways are critically needed to identify treatment candidates, evaluate disease severity, and support prognosis. A combination of plasma biomarkers and brief digital cognitive assessments could provide a scalable alternative to current diagnostic work-up., Methods: We examined the accuracy of plasma biomarkers and a 10-minute supervised tablet-based cognitive assessment (Tablet-based Cognitive Assessment Tool Brain Health Assessment [TabCAT-BHA]) in predicting amyloid β positive (Aβ+) status on positron emission tomography (PET), concurrent disease severity, and functional decline in 309 older adults with subjective cognitive impairment (n = 49), mild cognitive impairment (n = 159), and dementia (n = 101)., Results: Combination of plasma pTau181, Aβ42/40, neurofilament light (NfL), and TabCAT-BHA was optimal for predicting Aβ-PET positivity (AUC = 0.962). Whereas NfL and TabCAT-BHA optimally predicted concurrent disease severity, combining these with pTau181 and glial fibrillary acidic protein was most accurate in predicting functional decline., Discussion: Combinations of plasma and digital cognitive markers show promise for scalable diagnosis and prognosis of ADRD., Highlights: The need for cost-efficient diagnostic and prognostic markers of AD is urgent. Plasma and digital cognitive markers provide complementary diagnostic contributions. Combination of these markers holds promise for scalable diagnosis and prognosis. Future validation in community cohorts is needed to inform clinical implementation., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Physician communication failures during transfers of patients from the intensive care unit (ICU) to the general ward are common and can lead to adverse events. Efforts to improve written handoffs during these transfers are increasingly prominent, but no instruments have been developed to assess the quality of physician ICU-ward transfer notes., Objective: To collect validity evidence for the modified nine-item Physician Documentation Quality Instrument (mPDQI-9) for assessing ICU-ward transfer note usefulness across several hospitals., Methods: Twenty-four physician raters independently used the mPDQI-9 to grade 12 notes collected from three academic hospitals. A priori , we excluded the "up-to-date" and "accurate" domains, because these could not be assessed without giving the rater access to the complete patient chart. Assessments therefore used the domains "thorough," "useful," "organized," "comprehensible," "succinct," "synthesized," and "consistent." Raters scored each domain on a Likert scale ranging from 1 ( low ) to 5 ( high ). The total mPDQI-9 was the sum of these domain scores. The primary outcome was the raters' perceived clinical utility of the notes, and the primary measures of interest were criterion validity (Spearman's ρ) and interrater reliability (intraclass correlation [ICC])., Results: Mean mPDQI-9 scores by note ranged from 19 (SD = 5.5) to 30 (SD = 4.2). Mean note ratings did not systematically differ by rater expertise (for interaction, P  = 0.15). The proportion of raters perceiving each note as independently sufficient for patient care (the primary outcome) ranged from 33% to 100% across the set of notes. We found a moderately positive correlation between mPDQI-9 ratings and raters' overall assessments of each note's clinical utility (ρ = 0.48, P  < 0.001). Interrater reliability was strong; the overall ICC was 0.89 (95% confidence interval [CI], 0.80-0.85), and ICCs were similar among reviewer groups. Finally, Cronbach's α was 0.87 (95% CI, 0.84-0.89), indicating good internal consistency., Conclusions: We report moderate validity evidence for the mPDQI-9 to assess the usefulness of ICU-ward transfer notes written by internal medicine residents., (Copyright © 2024 by the American Thoracic Society.)

Mining environmental liabilities generate environmental pollution. The objective of the present study was to determine the yield of white clover (Trifolium repens) and orchard grass (Dactylis glomerata) cultivated in mining environmental passives adding black earth and compost as a substrate in the Buenaventura Julcani Huancavelica Company. The treatments were the combinations: 4: 3.1: 3.1: 3:1.1 kg of RP: RP, TN: RP, C: RP, TN, C respectively. They were distributed in four treatments with twelve experimental units for each species of leguminous and gramineous grass, we worked according to the completely randomized design (DCA) with a 2 x 4 factorial arrangement, the experimental unit being a treatment with twelve repetitions. The variables evaluated were: germination percentage (TG) and stem survival percentage (TST). For the statistical analysis, the SPSS software was used.

Burn injuries, a major global health concern, result in an estimated 180,000 fatalities annually. Despite tremendous progress in treatment methods over the years, the morbidity and mortality associated with burns remain significant. Autologous skin grafting, particularly split-thickness skin grafting (STSG), has been a cornerstone in burn reconstruction, and it has facilitated survival and functional recovery for total body surface area (TBSA) significantly. However, the requirement for primary closure at the donor site due to the constraints of full-thickness donor harvesting continues to pose challenges. The introduction of dermal regenerative templates (DRT) in the late 1970s marked a substantial step forward in tissue engineering, addressing the inadequacy of dermal replacement with STSGs. This systematic review aimed to compare the outcomes of different graft types - bioengineered, autografts, allografts, and xenografts - in burn reconstruction over the last 24 years. The review focused on the pros and cons of each graft type, offering clinical insights grounded in experience and evidence. The approach involved a systematic review of studies published in English from January 2000 to January 2024, covering randomized controlled trials (RCTs), cohort studies, case-control studies, and case series. The participants comprised individuals of all ages who underwent burn reconstruction with skin grafts, specifically split-thickness grafts, full-thickness grafts, composite grafts, and epidermal grafts (autografts, allografts, and xenografts) and bioengineered grafts. The primary outcomes were functional and cosmetic results, patient satisfaction, graft survival, and complications. The risk of bias was evaluated using the Cochrane risk-of-bias tool for randomized trials version 2 (RoB 2), the Newcastle-Ottawa Scale (NOS) for non-randomized studies, and the Canada Institute for Health Economics (IHE) quality appraisal tool for case series. Our initial search yielded a total of 1,995 articles, out of which 10 studies were selected for final analysis. Among the four clinical trials assessed, 75% showed a high risk of bias. The studies reviewed involved various graft types, with six studies (60%) concentrating on allografts, three (30%) on autografts, and one (10%) on bioengineered skin grafts. The outcomes were varied, underlining the intricate nature of burn wound management. Our evaluation revealed promising results for autologous-engineered skin substitutes and allografts but also highlighted methodological disparities among the studies included. The dominance of observational studies and the diversity of outcome measures present obstacles to direct comparisons. Future research should address these limitations, employing well-structured RCTs, standardized outcome measures, and exploring long-term outcomes and patient-specific factors. The rapidly evolving field of regenerative medicine offers great potential for novel grafting methods. This systematic review provides valuable insights into the diverse outcomes of burn reconstruction using different graft types. Autologous-engineered skin substitutes and allografts seem to hold significant promise, suggesting a possible shift in grafting techniques. However, methodological inconsistencies and the lack of high-quality evidence underscore the necessity for further research to fine-tune burn care approaches., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Aleman Paredes et al.)

Background: Postoperative delirium is prevalent in older adults and has been shown to increase the risk of long-term cognitive decline. Plasma biomarkers to identify the risk for postoperative delirium and the risk of Alzheimer's disease and related dementias are needed., Methods: This biomarker discovery case-control study aimed to identify plasma biomarkers associated with postoperative delirium. Patients aged ≥65 years undergoing major elective noncardiac surgery were recruited. The preoperative plasma proteome was interrogated with SOMAmer-based technology targeting 1433 biomarkers., Results: In 40 patients (20 with vs. 20 without postoperative delirium), a preoperative panel of 12 biomarkers discriminated patients with postoperative delirium with an accuracy of 97.5%. The final model of five biomarkers delivered a leave-one-out cross-validation accuracy of 80%. Represented biological pathways included lysosomal and immune response functions., Conclusion: In older patients who have undergone major surgery, plasma SOMAmer proteomics may provide a relatively non-invasive benchmark to identify biomarkers associated with postoperative delirium., (© 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Tau PET has enabled the visualization of paired helical filaments of 3 or 4 C-terminal repeat tau in Alzheimer disease (AD), but its ability to detect aggregated tau in frontotemporal lobar degeneration (FTLD) spectrum disorders is uncertain. We investigated 2-(2-([ 18 F]fluoro)pyridin-4-yl)-9 H -pyrrolo[2,3-b:4,5c']dipyridine ([ 18 F]PI-2620), a newer tracer with ex vivo evidence for binding to FTLD tau, in a convenience sample of patients with suspected FTLD and AD using a static acquisition protocol and parametric SUV ratio (SUVr) images. Methods: We analyzed [ 18 F]PI-2620 PET data from 65 patients with clinical diagnoses associated with AD or FTLD neuropathology; most (60/65) also had amyloid-β (Aβ) PET. Scans were acquired 30-60 min after injection; SUVr maps (reference, inferior cerebellar cortex) were created for the full acquisition and for 10-min truncated sliding windows (30-40, 35-45,…50-60 min). Age- and sex-adjusted z score maps were computed for each patient, relative to 23 Aβ-negative cognitively healthy controls (HC). Mean SUVr in the globus pallidus, substantia nigra, subthalamic nuclei, dentate nuclei, white matter, and temporal gray matter was extracted for the full and truncated windows. Results: Patients with suspected AD neuropathology (Aβ-positive patients with mild cognitive impairment or AD dementia) showed high-intensity temporoparietal cortex-predominant [ 18 F]PI-2620 binding. At the group level, patients with clinical diagnoses associated with FTLD (progressive supranuclear palsy with Richardson syndrome [PSP Richardson syndrome], corticobasal syndrome, and nonfluent-variant primary progressive aphasia) exhibited higher globus pallidus SUVr than did HCs; pallidal retention was highest in the PSP Richardson syndrome group, in whom SUVr was correlated with symptom severity (ρ = 0.53, P = 0.05). At the individual level, only half of PSP Richardson syndrome, corticobasal syndrome, and nonfluent-variant primary progressive aphasia patients had a pallidal SUVr above that of HCs. Temporal SUVr discriminated AD patients from HCs with high accuracy (area under the receiver operating characteristic curve, 0.94 [95% CI, 0.83-1.00]) for all time windows, whereas discrimination between patients with PSP Richardson syndrome and HCs using pallidal SUVr was fair regardless of time window (area under the receiver operating characteristic curve, 0.77 [95% CI, 0.61-0.92] at 30-40 min vs. 0.81 [95% CI, 0.66-0.96] at 50-60 min; P = 0.67). Conclusion: [ 18 F]PI-2620 SUVr shows an intense and consistent signal in AD but lower-intensity, heterogeneous, and rapidly decreasing binding in patients with suspected FTLD. Further work is needed to delineate the substrate of [ 18 F]PI-2620 binding and the usefulness of [ 18 F]PI2620 SUVr quantification outside the AD continuum., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: The pathophysiology of delirium is incompletely understood, including what molecular pathways are involved in brain vulnerability to delirium. This study examined whether preoperative plasma neurodegeneration markers were elevated in patients who subsequently developed postoperative delirium through a retrospective case-control study., Methods: Inclusion criteria were patients of 65 yr of age or older, undergoing elective noncardiac surgery with a hospital stay of 2 days or more. Concentrations of preoperative plasma P-Tau181, neurofilament light chain, amyloid β1-42 (Aβ42), and glial fibrillary acidic protein were measured with a digital immunoassay platform. The primary outcome was postoperative delirium measured by the Confusion Assessment Method. The study included propensity score matching by age and sex with nearest neighbor, such that each patient in the delirium group was matched by age and sex with a patient in the no-delirium group., Results: The initial cohort consists of 189 patients with no delirium and 102 patients who developed postoperative delirium. Of 291 patients aged 72.5 ± 5.8 yr, 50.5% were women, and 102 (35%) developed postoperative delirium. The final cohort in the analysis consisted of a no-delirium group (n = 102) and a delirium group (n = 102) matched by age and sex using the propensity score method. Of the four biomarkers assayed, the median value for neurofilament light chain was 32.05 pg/ml for the delirium group versus 23.7 pg/ml in the no-delirium group. The distribution of biomarker values significantly differed between the delirium and no-delirium groups (P = 0.02 by the Kolmogorov-Smirnov test) with the largest cumulative probability difference appearing at the biomarker value of 32.05 pg/ml., Conclusions: These results suggest that patients who subsequently developed delirium are more likely to be experiencing clinically silent neurodegenerative changes before surgery, reflected by changes in plasma neurofilament light chain biomarker concentrations, which may identify individuals with a preoperative vulnerability to subsequent cognitive decline., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

Triatomines are vectors of Chagas disease. Due to failures in their control, there is an urgent need for more efficient and environmentally friendly monitoring and control tools. These hematophagous insects rely heavily on chemical information from the environment to detect hosts and cues/signals from conspecifics. Chemical ecology includes the elucidation of the functional role of chemicals mediating interactions between organisms. Studies on the chemical ecology of triatomines are leading to novel methods for their monitor and control. Thus, laboratory tests to develop chemical attractants and repellents are promissory and have led to the design of, for example, efficient baited traps. However, the monitoring and control tools proposed until now have not been as effective in the field., Competing Interests: Declaration of Competing Interest PGG was part of a provisional patent application in the United States (20UDA-04-P, filed on 09/10/2020), in relation to a volatile repellent for triatomines mentioned in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Predictive analytics based on artificial intelligence (AI) offer clinicians the opportunity to leverage big data available in electronic health records (EHR) to improve clinical decision-making, and thus patient outcomes. Despite this, many barriers exist to facilitating trust between clinicians and AI-based tools, limiting its current impact. Potential solutions are available at both the local and national level. It will take a broad and diverse coalition of stakeholders, from health-care systems, EHR vendors, and clinical educators to regulators, researchers and the patient community, to help facilitate this trust so that the promise of AI in health care can be realized., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Plasma phosphorylated tau (p-tau) has emerged as a promising biomarker for Alzheimer's disease (AD). Studies have reported strong associations between p-tau and tau-PET that are mainly driven by differences between amyloid-positive and amyloid-negative patients. However, the relationship between p-tau and tau-PET is less characterized within cognitively impaired patients with a biomarker-supported diagnosis of AD. We conducted a head-to-head comparison between plasma p-tau217 and tau-PET in patients at the clinical stage of AD and further assessed their relationships with demographic, clinical, and biomarker variables., Methods: We retrospectively included 87 amyloid-positive patients diagnosed with MCI or dementia due to AD who underwent structural MRI, amyloid-PET ( 11 C-PIB), tau-PET ( 18 F-flortaucipir, FTP), and blood draw assessments within 1 year (age = 66 ± 10, 48% female). Amyloid-PET was quantified in Centiloids (CL) while cortical tau-PET binding was measured using standardized uptake value ratios (SUVRs) referenced against inferior cerebellar cortex. Plasma p-tau217 concentrations were measured using an electrochemiluminescence-based assay on the Meso Scale Discovery platform. MRI-derived cortical volume was quantified with FreeSurfer. Mini-Mental State Examination (MMSE) scores were available at baseline (n = 85) and follow-up visits (n = 28; 1.5 ± 0.7 years)., Results: Plasma p-tau217 and cortical FTP-SUVR were correlated (r = 0.61, p < .001), especially in temporo-parietal and dorsolateral frontal cortices. Both higher p-tau217 and FTP-SUVR values were associated with younger age, female sex, and lower cortical volume, but not with APOE-ε4 carriership. PIB-PET Centiloids were weakly correlated with FTP-SUVR (r = 0.26, p = 0.02), but not with p-tau217 (r = 0.10, p = 0.36). Regional PET-plasma associations varied with amyloid burden, with p-tau217 being more strongly associated with tau-PET in temporal cortex among patients with moderate amyloid-PET burden, and with tau-PET in primary cortices among patients with high amyloid-PET burden. Higher p-tau217 and FTP-SUVR values were independently associated with lower MMSE scores cross-sectionally, while only baseline FTP-SUVR predicted longitudinal MMSE decline when both biomarkers were included in the same model., Conclusion: Plasma p-tau217 and tau-PET are strongly correlated in amyloid-PET-positive patients with MCI or dementia due to AD, and they exhibited comparable patterns of associations with demographic variables and with markers of downstream neurodegeneration., (© 2023. BioMed Central Ltd., part of Springer Nature.)

In recent years, the avocado has been one of the most dynamic fruits in the world market. In particular, cv. Hass stands out due to its productivity, nutritional quality, and acceptance. Under tropical conditions, weather elements, especially air temperature, and precipitation, affect the productivity and quality of cv. Hass. However, in tropical environments, many relationships between weather and phenological aspects of this cultivar are still unknown. Given this situation, our aim was to identify the variation and degree of association between the phenology of avocado cv. Hass and thermal time (TT) under low-latitude conditions. Eight commercial fields planted with cv. Hass grafted onto Antillean genotypes, located in an altitudinal transect between 1,700 and 2,500 m, were evaluated. The evaluation was carried out for three years and was focused on determining the differences in avocado phenological patterns associated with different environmental variables monitored by weather stations at each location. Air temperature data were used to calculate the base temperature (BT) using different methods for all phenological stages. Later the TT was determined for each stage and all locations. The results show that the duration of each phenological stage varies as a function of elevation (air temperature) and that the phenological stages overlap at the regional, crop field, and plant levels at different periods of the year, generating a high phenological variability but with specific patterns associated with temperature and precipitation. The BT for each phenological stage varied between 0.3 and 7.5 °C, and TT was found to vary depending on the method of calculation. Our work suggests that the generalization of a BT of 10 °C is not applicable for avocado cv. Hass crops under tropical conditions, specifically in the case of Colombia. Detailed studies of phenological relationships with respect to climatic variables will allow a better approximation of the productive behavior of avocado cv. Hass., Competing Interests: The authors declare no conflict of interest.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Amnestic mild cognitive impairment (aMCI) is a predementia stage of Alzheimer's disease associated with dysfunctional episodic memory and limited treatment options. We aimed to characterize feasibility, clinical, and biomarker effects of noninvasive neurostimulation for aMCI. 13 individuals with aMCI received eight 60-minute sessions of 40-Hz (gamma) transcranial alternating current stimulation (tACS) targeting regions related to episodic memory processing. Feasibility, episodic memory, and plasma Alzheimer's disease biomarkers were assessed. Neuroplastic changes were characterized by resting-state functional connectivity (RSFC) and neuronal excitatory/inhibitory balance. Gamma tACS was feasible and aMCI participants demonstrated improvement in multiple metrics of episodic memory, but no changes in biomarkers. Improvements in episodic memory were most pronounced in participants who had the highest modeled tACS-induced electric fields and exhibited the greatest changes in RSFC. Increased RSFC was also associated with greater hippocampal excitability and higher baseline white matter integrity. This study highlights initial feasibility and the potential of gamma tACS to rescue episodic memory in an aMCI population by modulating connectivity and excitability within an episodic memory network., Competing Interests: Disclosure statement A.G. is a scientific advisor for Neuroelectrics, which is the company that makes the neurostimulation device used in the current study., (Published by Elsevier Inc.)

Objectives: The transition from the intensive care unit (ICU) to the medical ward is a high-risk period due to medical complexity, reduced patient monitoring, and diagnostic uncertainty. Standardized handoff practices reduce errors associated with transitions of care, but little work has been done to standardize the ICU to ward handoff. Further, tools that exist do not focus on preventing diagnostic error. Using Human-Centered Design methods we previously created a novel EHR-based ICU-ward handoff tool (ICU-PAUSE) that embeds a diagnostic pause at the time of transfer. This study aims to explore barriers and facilitators to implementing a diagnostic pause at the ICU-to-ward transition., Methods: This is a multi-center qualitative study of semi-structured interviews with intensivists from ten academic medical centers. Interviews were analyzed iteratively through a grounded theory approach. The Sittig-Singh sociotechnical model was used as a unifying conceptual framework., Results: Across the eight domains of the model, we identified major benefits and barriers to implementation. The embedded pause to address diagnostic uncertainty was recognized as a key benefit. Participants agreed that standardization of verbal and written handoff would decrease variation in communication. The main barriers fell within the domains of workflow, institutional culture, people, and assessment., Conclusions: This study represents a novel application of the Sittig-Singh model in the assessment of a handoff tool. A unique feature of ICU-PAUSE is the explicit acknowledgement of diagnostic uncertainty, a practice that has been shown to reduce medical error and prevent premature closure. Results will be used to inform future multi-site implementation efforts., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Blood-based biomarkers offer a major advance in the clinical evaluation of neurodegenerative diseases. Currently, research studies have reported robust assays of blood markers for the detection of amyloid and tau pathologies specific to Alzheimer disease (amyloid-β peptides, and p-tau) and nonspecific blood markers of neuronal (neurofilament light, β-synuclein, and ubiquitin-C-terminal-hydrolase-L1) and glial degeneration (glial fibrillary acidic protein) that can measure key pathophysiologic processes in several neurodegenerative diseases. In the near future, these markers may be used for screening, diagnosis, or disease and treatment response monitoring. Blood-based biomarkers for neurodegenerative diseases have been rapidly implemented in research, and they have the potential to enter clinical use soon in different clinical settings. In this review, we will describe the main developments and their potential implications for the general neurologist., (© 2023 American Academy of Neurology.)