-Cyclooctene Isomerization Catalyzed by Thiamine Degradation Products in Cell Culture Media.

PET imaging of intrathecally dosed ASO neurology drugs is challenging due to the long time needed to achieve steady-state brain distribution, making the use of a simple F tag impossible with its short radioactive half-life. To overcome this challenge, a pretargeted imaging solution has been developed in which an ASO tagged with a tetrazine is dosed intrathecally, and after 24 h a reactive -cyclooctene (TCO) tagged with F is dosed intravenously. The two molecules form a click-chemistry adduct, allowing for PET imaging scans immediately following F-TCO administration.

Poor Sleep Health Early After Stroke is Associated with Lower Quality of Life Later After Stroke.

Background: Factors early after stroke that are predictive of outcomes can help guide rehabilitation interventions. There is a growing understanding of the importance of sleep for recovery after stroke.

Objectives: To explore factors at 10 days post stroke, including sleep health (SH), that may be associated with QOL at 60 days post stroke.

A Bayesian spatial measurement error approach to incorporate heterogeneous population-at-risk uncertainty in estimating small-area opioid mortality rates.

Monitoring small-area geographical population trends in opioid mortality has significant implications for informing preventative resource allocation. A common approach to estimating small-area opioid mortality uses a standard disease mapping method where population-at-risk estimates (denominators) are treated as fixed. This assumption ignores the uncertainty in small-area population estimates, potentially biasing risk estimates and underestimating their uncertainties.

Fusing GPS, Activity Monitors, and Self-Report to Improve Assessment of Walking Activity and Community Participation After Stroke.

Background And Purpose: Walking and participation in the community are important goals for people post-stroke (PPS). These constructs are challenging to measure given limitations in current data collection methodologies. The purpose of this study was to (1) develop a data fusion approach that combined data from global positioning system (GPS), activity monitor (AM), and daily trip log to identify walking activity and participation in the community, and (2) to examine the construct validity of the data fusion method.

PET imaging of antisense oligonucleotide distribution in rat and nonhuman primate brains using click chemistry.

Determination of a drug's biodistribution is critical to ensure that it reaches the target tissue of interest. This is particularly challenging in the brain, where invasive sampling methods may not be possible. Here, we present a pretargeted positron emission tomography (PET) imaging methodology that uses bioorthogonal click chemistry to determine the distribution of an antisense oligonucleotide (ASO) in the brains of rats and nonhuman primates after intrathecal dosing of ASO.

Sleep Health During Recovery After Stroke.

Study Objectives: People with stroke are susceptible to developing sleep disorders, which may negatively impact recovery. Little is known about sleep health (SH) broadly and its impact on recovery after stroke. The purpose of this study was to explore factors that are associated with SH during recovery after stroke.

Determining physiological responses of mussels () to hypoxia by combining multiple sensor techniques.

Intertidal bivalves survive longer without oxygen when aerially exposed during low tide than when submerged in hypoxic water. To understand this, we combined three biosensors to continuously monitor responses of individual blue mussels () to aerial exposure in simulated low-tide conditions and during aqueous hypoxia. A valve sensor, heart rate monitor, and an in-shell oxygen microsensor simultaneously recorded behavioural and physiological responses.

Patterns of non-fatal overdose and injection-related bacterial infections during pregnancy and the postpartum year among New York State residents.

Objectives: Overdoses are a leading cause of maternal mortality in the US, but limited evidence exists about patterns of nonfatal overdose, a key risk factor for subsequent fatal overdose, or of other drug-related harms. Here, we estimate prevalences of nonfatal overdose and injection-related endocarditis and abscesses/cellulitis across the 21 months spanning pregnancy and the postpartum year.

Methods: Among people who experienced an in-hospital birth in New York State between 9/1/2016 and 1/1/2018 (N=330,872), we estimated the prevalences of hospital-based diagnoses of nonfatal overdose and of injection-related bacterial infections (i.

Insufficient LGBTQ+ education across disciplines suggested by national survey of health professionals in training.

Health professionals often feel underprepared to treat patients who identify as lesbian, gay, bisexual, transgender, and/or queer (LGBTQ+). Additionally, lack of access to professionals who are knowledgeable about LGBTQ+ inclusive care contributes to the myriad of health disparities experienced by LGBTQ+ communities. This cross-sectional survey study explores the preparedness of healthcare profession trainees for caring for LGBTQ+ patients by quantifying the hours and quality of training health profession trainees receive in LGBTQ+ education across disciplines.

Rheumatoid Arthritis: Diagnosis and Management for the Family Physician.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes joint inflammation, erosion, and deformity. The prevalence of RA in North America is 0.5% to 1%.

Relation between Deese-Roediger-Mcdermott recall measures of false memory and the fading affect bias.

The fading affect bias (FAB) is the faster fading of unpleasant affect than pleasant affect for autobiographical event memories, and it is considered a healthy coping mechanism because it is positively related to healthy measures (e.g., self-esteem and positive PANAS), whereas it is negatively related to unhealthy measures (e.

In-Person and Online Studies Examining the Influence of Problem Solving on the Fading Affect Bias.

The fading affect bias (FAB) occurs in autobiographical memory when unpleasant emotions fade faster than pleasant emotions and the phenomenon appears to be a form of emotion regulation. As emotion regulation is positively related to problem solving, the current study examined FAB in the context of problem solving. In-person and online studies asked participants to provide basic demographics, describe their problem-solving abilities, and rate various healthy and unhealthy variables, including emotional intelligence and positive problem-solving attitudes.

Screening college athletes for sexual violence: athletes' experiences and opinions on best practices.

Objectives: College athletes are at elevated risk for sexual violence, yet few formally report it and screening for sexual violence is uncommon. This study aimed to evaluate the nature of screening occurring among college athletes and collect athletes' opinions on how best to screen for sexual violence.

Methods: This was a mixed-methods study combining a cross-sectional survey with small group interviews.

The Impact of Lunch Timing on Nap Quality.

Purpose: Previous research has established that food intake is a biological regulator of the human sleep-wake cycle. As such, the timing of eating relative to sleep may influence the quality of sleep, including daytime naps. Here, we examine whether the timing of lunch (1 h vs.

Why educators endorse a neuromyth: relationships among educational priorities, beliefs about learning styles, and instructional decisions.

Despite evidence to the contrary, many people believe in learning styles (LS)-the idea that students learn best in their preferred modality, such as visual, auditory, or kinesthetic. However, the impact of this belief on instructional decisions remains unclear. Therefore, this study investigated how belief in the neuromyth impacts instructional choices and why educators choose an LS lesson plan or an alternative.

A Tiny Pocket Packs a Punch: Leveraging Pyridones for the Discovery of CNS-Penetrant Aza-indazole IRAK4 Inhibitors.

We herein report the discovery, synthesis, and evolution of a series of indazoles and azaindazoles as CNS-penetrant IRAK4 inhibitors. Described is the use of structure-based and property-based drug design strategically leveraged to guide the property profile of a key series into a favorable property space while maintaining potency and selectivity. Our rationale that led toward functionalities with potency improvements, CNS-penetration, solubility, and favorable drug-like properties is portrayed.

Discovery of BIO-8169─A Highly Potent, Selective, and Brain-Penetrant IRAK4 Inhibitor for the Treatment of Neuroinflammation.

Interleukin receptor associated kinase 4 (IRAK4) plays an important role in innate immune signaling through Toll-like and interleukin-1 receptors and represents an attractive target for the treatment of inflammatory diseases and cancer. We previously reported the development of a potent, selective, and brain-penetrant imidazopyrimidine series of IRAK4 inhibitors. However, lead molecule BIO-7488 () suffered from low solubility which led to variable PK, compound accumulation, and poor in vivo tolerability.

The Discovery of 7-Isopropoxy-2-(1-methyl-2-oxabicyclo[2.1.1]hexan-4-yl)--(6-methylpyrazolo[1,5-]pyrimidin-3-yl)imidazo[1,2-]pyrimidine-6-carboxamide (BIO-7488), a Potent, Selective, and CNS-Penetrant IRAK4 Inhibitor for the Treatment of Ischemic Stroke.

Interleukin receptor-associated kinase 4 (IRAK4) is a key node of signaling within the innate immune system that regulates the production of inflammatory cytokines and chemokines. The presence of amage-ssociated olecular patterns (DAMPs) after tissue damage such as stroke or traumatic brain injury (TBI) initiates signaling through the IRAK4 pathway that can lead to a feed-forward inflammatory loop that can ultimately hinder patient recovery. Herein, we describe the first potent, selective, and CNS-penetrant IRAK4 inhibitors for the treatment of neuroinflammation.

Migraine headache: When to consider these newer agents.

These agents are as effective as traditional acute and preventive treatments, cause fewer adverse effects, and can simplify regimens.

Impacts of census differential privacy for small-area disease mapping to monitor health inequities.

The U.S. Census Bureau will implement a modernized privacy-preserving disclosure avoidance system (DAS), which includes application of differential privacy, on publicly released 2020 census data.

U.S. Adult Critical Care Beds Per Capita: A 2021 County-Level Cross-Sectional Study.

Unlabelled: Per capita geographic distribution of adult critical care beds can be utilized for healthcare resources assessments.

Objectives: Describe the per capita distribution of staffed adult critical care beds across the United States.

Design Setting And Participants: Cross-sectional epidemiologic assessment of November 2021 hospital data from the Department of Health and Human Services' Protect Public Data Hub.

Mapping Uncharted Terrain: A Systematic Review of Complementary and Integrative Health Communication Using Observational Data in Biomedical Settings.

Complementary and integrative health (CIH) use is diverse and highly prevalent worldwide. Prior research of CIH communication in biomedical encounters address safety, efficacy, symptom management, and overall wellness. Observational methods are rarely used to study CIH communication and avoid recall bias, preserve ecological validity, and contextualize situated clinical communication.

Discrimination, identity connectedness and tobacco use in a sample of sexual and gender minority young adults.

Introduction: Studies show that tobacco use among sexual and gender minority (SGM) populations is disproportionately higher than heterosexual or cisgender populations. However, few studies have examined tobacco use among SGM subgroups by race/ethnicity or associations between SGM-specific discrimination and connection to SGM identity and tobacco use.

Methods: This study analysed survey data from 11 313 SGM (gay, lesbian, bisexual, other sexual minority or gender minority) young adults in the USA and reported current cigarette, e-cigarette, other tobacco (cigar, smokeless tobacco, hookah) and polytobacco use.