Refugees' Experiences Accessing and Receiving Health care in the Southwestern U.S.

Resettled refugees face physical and mental health challenges including the violence and trauma of their displacement. Once resettled in the U.S.

Experimentally measured assembly indices are required to determine the threshold for life.

Assembly theory (AT) aims to distinguish living from non-living systems by explaining and quantifying selection and evolution. The theory proposes that the degree of assembly depends on the number of complex objects, with complexity measured using a combination of the object's assembly index (AI) and its abundance. We previously provided experimental evidence supporting AT's predictive power, finding that abiotic systems do not randomly produce organic molecules with an AI greater than approximately 15 in detectable amounts.

Multipartite Fluorogenic Sensors for Monitoring Tyrosine Phosphatase Activity.

Fluorogenic substrates are essential tools for studying the activity of many enzymes including the protein tyrosine phosphatases (PTPs). Here, we have taken the first step toward the development of genetically encodable sensors for PTP activity using fluorescent and fluorogen-activating proteins. The Fluorescence-Activating and absorption Shifting Tag (FAST) is a small protein that becomes fluorescent upon binding to a small molecule dye.

Self-organization in computation and chemistry: Return to AlChemy.

How do complex adaptive systems, such as life, emerge from simple constituent parts? In the 1990s, Walter Fontana and Leo Buss proposed a novel modeling approach to this question, based on a formal model of computation known as the λ calculus. The model demonstrated how simple rules, embedded in a combinatorially large space of possibilities, could yield complex, dynamically stable organizations, reminiscent of biochemical reaction networks. Here, we revisit this classic model, called AlChemy, which has been understudied over the past 30 years.

A novel mouse model reproducing frontal alterations related to the prodromal stage of dementia with LEWY bodies.

Background: Dementia with Lewy bodies (DLB) is the second most common age-related neurocognitive pathology after Alzheimer's disease. Animal models characterizing this disease are lacking and their development would ameliorate both the understanding of neuropathological mechanisms underlying DLB as well as the efficacy of pre-clinical studies tackling this disease.

Methods: We performed extensive phenotypic characterization of a transgenic mouse model overexpressing, most prominently in the dorsal hippocampus (DH) and frontal cortex (FC), wild-type form of the human α-synuclein gene (mThy1-hSNCA, 12 to 14-month-old males).

Sexual and Reproductive Healthcare Needs of Refugee Women Exposed to Gender-Based Violence: The Case for Trauma-Informed Care in Resettlement Contexts.

This paper assesses literature regarding the sexual and reproductive healthcare (SRH) needs of resettled refugee women who experienced gender-based violence (GBV) and trauma-informed care (TIC) principles utilized among SRH service providers. A systematic search identified relevant studies published between 2000 and 2021; no articles found reflected both SRH and TIC principles among refugee women. The search was therefore separated into two aims: to review the literature about SRH needs for refugee women in resettlement countries who experienced GBV (Aim 1) and to examine the use of TIC principles in SRH care among women who experienced GBV (Aim 2).

Implementation and Assessment of Tau Thresholds in Non-Demented Individuals as Predictors of Cognitive Decline in Tau Imaging Studies.

Background: Tau accumulation in Alzheimer's disease is associated with short term clinical progression and faster rates of cognitive decline in individuals with high amyloid-β deposition. Defining an optimal threshold of tau accumulation predictive of cognitive decline remains a challenge.

Objective: We tested the ability of regional tau PET sensitivity and specificity thresholds to predict longitudinal cognitive decline.

Ligand-based design of [F]OXD-2314 for PET imaging in non-Alzheimer's disease tauopathies.

Positron emission tomography (PET) imaging of tau aggregation in Alzheimer's disease (AD) is helping to map and quantify the in vivo progression of AD pathology. To date, no high-affinity tau-PET radiopharmaceutical has been optimized for imaging non-AD tauopathies. Here we show the properties of analogues of a first-in-class 4R-tau lead, [F]OXD-2115, using ligand-based design.

Investigating and Quantifying Molecular Complexity Using Assembly Theory and Spectroscopy.

Current approaches to evaluate molecular complexity use algorithmic complexity, rooted in computer science, and thus are not experimentally measurable. Directly evaluating molecular complexity could be used to study directed vs undirected processes in the creation of molecules, with potential applications in drug discovery, the origin of life, and artificial life. Assembly theory has been developed to quantify the complexity of a molecule by finding the shortest path to construct the molecule from building blocks, revealing its molecular assembly index (MA).

Kinetic modeling of the monoamine oxidase-B radioligand [F]SMBT-1 in human brain with positron emission tomography.

This paper describes pharmacokinetic analyses of the monoamine-oxidase-B (MAO-B) radiotracer [F]()-(2-methylpyrid-5-yl)-6-[(3-fluoro-2-hydroxy)propoxy]quinoline ([F]SMBT-1) for positron emission tomography (PET) brain imaging. Brain MAO-B expression is widespread, predominantly within astrocytes. Reactive astrogliosis in response to neurodegenerative disease pathology is associated with MAO-B overexpression.

In vitro evaluation of [H]PI-2620 and structural derivatives in non-Alzheimer's tauopathies.

Alzheimer's disease (AD) and non-AD tauopathies such as chronic traumatic encephalopathy (CTE), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD) are characterized by the abnormal aggregation of three-repeat (3R) and/or four-repeat (4R) tau isoforms. Several tau-PET tracers have been applied for human imaging of AD and non-AD tauopathies including [F]PI-2620. Our objective is to evaluate [H]PI-2620 and two promising structural derivatives, [H]PI-2014 and [H]F-4, using in vitro saturation assays and competitive binding assays against new chemical entities based on this scaffold in human AD tissues for comparison with PSP, CBD and CTE tissues.

Development of Pyridothiophene Compounds for PET Imaging of α-Synuclein.

Aggregated α-synuclein (α-syn) protein is a pathological hallmark of Parkinson's disease (PD) and Lewy body dementia (LBD). Development of positron emission tomography (PET) radiotracers to image α-syn aggregates has been a longstanding goal. This work explores the suitability of a pyridothiophene scaffold for α-syn PET radiotracers, where 47 derivatives of a potent pyridothiophene (asyn-44; K=1.

Association Between β-Amyloid Accumulation and Incident Dementia in Individuals 80 Years or Older Without Dementia.

Background And Objectives: While the highest prevalence of dementia occurs in individuals older than 80 years, most imaging studies focused on younger populations. The rates of β-amyloid (Aβ) accumulation and the effect of Alzheimer disease (AD) pathology on progression to dementia in this age group remain unexplored. In this study, we examined the relationship between changes in Aβ deposition over time and incident dementia in nondemented individuals followed during a period of 11 years.

False Positives and the Challenge of Testing the Alien Hypothesis.

The origin of life and the detection of alien life have historically been treated as separate scientific research problems. However, they are not strictly independent. Here, we discuss the need for a better integration of the sciences of life detection and origins of life.

Life detection in a universe of false positives: Can the Fatal Flaws of Exoplanet Biosignatures be Overcome Absent a Theory of Life?

Astrobiology aims to determine the distribution and diversity of life in the universe. But as the word "biosignature" suggests, what will be detected is not life itself, but an observation implicating living systems. Our limited access to other worlds suggests this observation is more likely to reflect out-of-equilibrium gasses than a writhing octopus.

Low thalamic activity during a digit-symbol substitution task is associated with symptoms of subjective cognitive decline.

Introduction: Subjective cognitive decline (SCD) may represent the earliest preclinical stage of Alzheimer's Disease (AD) for some older adults. However, the underlying neurobiology of SCD is not completely understood. Since executive function may be affected earlier than memory function in the progression of AD, we aimed to characterize SCD symptoms in terms of fMRI brain activity during the computerized digit-symbol substitution task (DSST), an executive function task.

Nicotine-mediated effects in neuronal and mouse models of synucleinopathy.

Introduction: Alpha-synuclein (α-Syn) aggregation, transmission, and contribution to neurotoxicity represent central mechanisms underlying Parkinson's disease. The plant alkaloid "nicotine" was reported to attenuate α-Syn aggregation in different models, but its precise mode of action remains unclear.

Methods: In this study, we investigated the effect of 2-week chronic nicotine treatment on α-Syn aggregation, neuroinflammation, neurodegeneration, and motor deficits in D-line α-Syn transgenic mice.

Biostatistical Estimation of Tau Threshold Hallmarks (BETTH) Algorithm for Human Tau PET Imaging Studies.

A methodology for determining tau PET thresholds is needed to confidently detect early tau deposition. We compared multiple threshold-determining methods in participants who underwent either F-flortaucipir or F-MK-6240 PET scans. F-flortaucipir ( = 798) and F-MK-6240 ( = 216) scans were processed and sampled to obtain regional SUV ratios.

A Novel Brain PET Radiotracer for Imaging Alpha Synuclein Fibrils in Multiple System Atrophy.

Abnormal α-synuclein (α-syn) aggregation characterizes α-synucleinopathies, including Parkinson's disease (PD) and multiple system atrophy (MSA). However, no suitable positron emission tomography (PET) radiotracer for imaging α-syn in PD and MSA exists currently. Our structure-activity relationship studies identified 4-methoxy--(4-(3-(pyridin-2-yl)-3,8-diazabicyclo[3.

Systematic review of the human health hazards of propylene dichloride.

Propylene dichloride (PDC) is a chlorinated substance used primarily as an intermediate in basic organic chemical manufacturing. The United States Environmental Protection Agency (EPA) is currently evaluating PDC as a high-priority substance under the Toxic Substances Control Act (TSCA). We conducted a systematic review of the non-cancer and cancer hazards of PDC using the EPA TSCA and Integrated Risk Information System (IRIS) frameworks.

Discovery and Subsequent Characterization of Potent 4R-Tauopathy Positron Emission Tomography Radiotracers.

A chemical fingerprint search identified Z3777013540 (1-(5-(6-fluoro-1-indol-2-yl)pyrimidin-2-yl)piperidin-4-ol; ) as a potential 4R-tau binding ligand. Binding assays in post-mortem Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD) brain with [H] provided (nM) values in AD = 4.0, PSP = 5.

Use of Electronic Ecological Momentary Assessment Methodologies in Physical Activity, Sedentary Behavior, and Sleep Research in Young Adults: Systematic Review.

Background: Recent technological advances allow for the repeated sampling of real-time data in natural settings using electronic ecological momentary assessment (eEMA). These advances are particularly meaningful for investigating physical activity, sedentary behavior, and sleep in young adults who are in a critical life stage for the development of healthy lifestyle behaviors.

Objective: This study aims to describe the use of eEMA methodologies in physical activity, sedentary behavior, and sleep research in young adults.