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The basal forebrain (BF) plays crucial roles in arousal, attention, and memory, and its impairment is associated with a variety of cognitive deficits. The BF consists of cholinergic, GABAergic, and glutamatergic neurons. Electrical or optogenetic stimulation of BF cholinergic neurons enhances cortical processing and behavioral performance, but the natural activity of these cells during behavior is only beginning to be characterized. Even less is known about GABAergic and glutamatergic neurons. Here, we performed microendoscopic calcium imaging of BF neurons as mice engaged in spontaneous behaviors in their home cages (innate) or performed a go/no-go auditory discrimination task (learned). Cholinergic neurons were consistently excited during movement, including running and licking, but GABAergic and glutamatergic neurons exhibited diverse responses. All cell types were activated by overt punishment, either inside or outside of the discrimination task. These findings reveal functional similarities and distinctions between BF cell types during both spontaneous and task-related behaviors.

Introduction Although atopic dermatitis (AD) primarily affects the skin, it is increasingly recognized as a systemic inflammatory disease associated with immense patient burden and heterogenous impact on quality of life with significant implications for management and treatment. The AD treatment landscape is rapidly evolving with developments in biologic and non-biologic treatments, and it is therefore important to understand how patients make decisions between treatment benefits, administration, and risks. Objectives To quantify the impact of AD treatment attributes on patient preferences. Methods 400 adults with AD in the United States completed an online discrete choice experiment (DCE) survey between November 2023 and January 2024. DCE attributes and levels were selected based on a targeted literature review of evidence of approved AD treatments. In each task, patients chose between two hypothetical treatment profiles or opted to continue with their current treatment. The treatments were described by the chance of achieving clearer skin, achieving itch reduction, time to onset of action, risk of experiencing a side effect leading to treatment discontinuation, risk of injection site reaction, presence of FDA boxed warning, and type and frequency of administration. Patients also completed sociodemographic, quality of life, and clinical questionnaires and the Atopic Dermatitis Control Tool (ADCT). Preference data were analyzed using an effects-coded mixed-multinomial-logit model (MXL) and latent class logit model to identify if different preference patterns coexisted in the sample. Relative attribute importance (RAI) scores were calculated and patient willingness to trade-off between attributes was assessed. Results Mean age was 44.9 years (range: 18–83), 72% were female, 78% white, and 10% were Hispanic/Latino. Topical treatments were currently used by 78%, whilst 42% used oral, and 13% injectable. One-third (34%) had experience (currently or previously) using a medication with an FDA boxed warning. Patients had a mean ADCT score of 6.95, where ≥7 indicates poorly controlled AD. Three groups of patients with distinct preference patterns were identified: Boxed Warning Avoiders (BWA; 11.5%), Injectable Avoiders (IA; 23.1%) and Efficacy Focused (EF; 65.4%). Across all groups, increasing AD treatment benefits (achieving clearer skin RAI: 28%; reducing itch: 22%) had the greatest influence on treatment preference vs. avoiding risks (discontinuation: 9%; FDA warning: 9%; injection site reaction: 9%). However, the relative importance of attributes varied. Boxed Warning Avoiders were strongly averse to the FDA boxed warning and placed a higher importance on itch reduction and avoiding treatment discontinuation. Injectable Avoiders placed the highest importance on mode and frequency of administration, preferring oral or topical treatment vs. injection regardless of frequency; they also prioritized avoiding the risk of injection site reaction. Efficacy Focused prioritized itch reduction and clearer skin nearly twice as much as other groups, and placed less value on differentiating aspects of treatments including type and frequency of administration. Conclusions Overall, patients with AD valued clinical benefits and lower risks. Heterogeneity observed within the preferences demonstrated that while all groups valued efficacy, the extent to which they were willing to accept different modes of administration and levels of risk varied. This study offers insight into the value patients place on AD treatment attributes, and reflects the need for education to understand the factors that could contribute to selecting the appropriate treatment and to support shared decision-making between patients and their healthcare professionals. [ABSTRACT FROM AUTHOR]

N‐linked protein glycosylation in the brain is an understudied facet of glucose utilization that impacts a myriad of cellular processes including resting membrane potential, axon firing, and synaptic vesicle trafficking. Currently, a spatial map of N‐linked glycans within the normal and Alzheimer's disease (AD) human brain does not exist. A comprehensive analysis of the spatial N‐linked glycome would improve our understanding of brain energy metabolism, linking metabolism to signaling events perturbed during AD progression, and could illuminate new therapeutic strategies. Herein we report an optimized in situ workflow for enzyme‐assisted, matrix‐assisted laser desorption and ionization (MALDI) mass spectrometry imaging (MSI) of brain N‐linked glycans. Using this workflow, we spatially interrogated N‐linked glycan heterogeneity in both mouse and human AD brains and their respective age‐matched controls. We identified robust regional‐specific N‐linked glycan changes associated with AD in mice and humans. These data suggest that N‐linked glycan dysregulation could be an underpinning of AD pathologies. [ABSTRACT FROM AUTHOR]

A negative correlation between ambient temperature and COVID-19 mortality has been observed. However, the World Meteorological Organization (WMO) has reinforced the importance of government interventions and warned countries against relaxing control measures due to warmer temperatures. Further understanding of this relationship is needed to help plan vaccination campaigns opportunely. Using a two-stage regression model, we conducted cross-sectional and longitudinal analyses to evaluate the association between monthly ambient temperature lagged by one month with the COVID-19 number of deaths and the probability of high-level of COVID-19 mortality in 150 countries during time t = 60, 90, and 120 days since the onset. First, we computed a log-linear regression to predict the pre-COVID-19 respiratory disease mortality to homogenize the baseline disease burden within countries. Second, we employed negative binomial and logistic regressions to analyze the linkage between the ambient temperature and our outcomes, adjusting by pre-COVID-19 respiratory disease mortality rate, among other factors. The increase of one Celsius degree in ambient temperature decreases the incidence of COVID-19 deaths (IRR = 0.93; SE: 0.026, p-value<0.001) and the probability of high-level COVID-19 mortality (OR = 0.96; SE: 0.019; p-value<0.001) over time. High-income countries from the northern hemisphere had lower temperatures and were most affected by pre-COVID respiratory disease mortality and COVID-19 mortality. This study provides a global perspective corroborating the negative association between COVID-19 mortality and ambient temperature. Our longitudinal findings support the statement made by the WMO. Effective, opportune, and sustained reaction from countries can help capitalize on higher temperatures' protective role including the timely rollout of vaccination campaigns. [ABSTRACT FROM AUTHOR]