Multiclass Steroid Profiling in Short-Finned Pilot Whale Blubber Using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).

Rationale: Wildlife scientists are quantifying steroid hormones in a growing number of tissues and employing novel methods that must undergo validation before application. This study tested the accuracy and precision of liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for use on blubber samples from short-finned pilot whales (Globicephala macrorhynchus). We expanded upon a method for corticosteroid quantification by adding analytes and optimizing internal standard (IS) application.

Commutability assessment of new standard reference materials (SRMs) for determining serum total 25-hydroxyvitamin D using ligand binding and liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays.

Commutability is where the measurement response for a reference material (RM) is the same as for an individual patient sample with the same concentration of analyte measured using two or more measurement systems. Assessment of commutability is essential when the RM is used in a calibration hierarchy or to ensure that clinical measurements are comparable across different measurement procedures and at different times. The commutability of three new Standard Reference Materials (SRMs) for determining serum total 25-hydroxyvitamin D [25(OH)D], defined as the sum of 25-hydroxyvitamin D [25(OH)D] and 25-hydroxyvitamin D [25(OH)D], was assessed through an interlaboratory study.

Real life retrospective study of cannabidiol therapy in alternating hemiplegia of childhood.

Background: Many alternating hemiplegia of childhood (AHC) patients have received Cannabidiol (CBD) but, to our knowledge, there are no published data available.

Goals: Test the hypothesis that CBD has favorable effects on AHC spells.

Methods: Retrospective review of available data of AHC patients who received CBD.

Characteristics of non-sleep related apneas in children with alternating hemiplegia of childhood.

Background: Non-sleep related apnea (NSA) has been observed in alternating hemiplegia of childhood (AHC) but has yet to be characterized.

Goals: Investigate the following hypotheses: 1) AHC patients manifest NSA that is often severe. 2) NSA is usually triggered by precipitating events.

Development and testing of methods to record and follow up spells in patients with alternating hemiplegia of childhood.

Background: Developing methods to record Alternating Hemiplegia of Childhood (AHC) spells is essential for clinical trials and patient care.

Objectives: Test the following hypotheses: 1) Video-library training improves participants' ability to correctly identify AHC spells. 2) A custom-designed event-calendar with weekly reviews results in consistent documentation of such events over time.

A sensitive and reproducible qRT-PCR assay detects physiological relevant trace levels of FMR1 mRNA in individuals with Fragile X syndrome.

Fragile X syndrome (FXS) is the most common inherited intellectual disability. FXS is caused by a trinucleotide repeat expansion in the 5' untranslated region of the FMR1 gene, which leads to gene methylation, transcriptional silencing, and lack of expression of Fragile X Messenger Riboprotein (FMRP). Currently available FXS therapies are inefficient, and the disease severity is highly variable, making it difficult to predict disease trajectory and treatment response.

A sound-driven cortical phase-locking change in the Fmr1 KO mouse requires Fmr1 deletion in a subpopulation of brainstem neurons.

Background: Sensory impairments commonly occur in patients with autism or intellectual disability. Fragile X syndrome (FXS) is one form of intellectual disability that is often comorbid with autism. In electroencephalographic (EEG) recordings obtained from humans with FXS, the ability of cortical regions to consistently synchronize, or "phase-lock", to modulated auditory stimuli is reduced compared to that of typically developing individuals.

Characterization of sedation and anesthesia complications in patients with alternating hemiplegia of childhood.

Background: Alternating hemiplegia of childhood (AHC) pathophysiology suggests predisposition to sedation and anesthesia complications.

Goals: Hypotheses: 1) AHC patients experience high rates of sedation-anesthesia complications. 2) ATP1A3 mutation genotype positivity, age, and AHC severity correlate with more severe complications.

Optimization, validation and initial clinical implications of a Luminex-based immunoassay for the quantification of Fragile X Protein from dried blood spots.

Fragile X Syndrome (FXS) is caused by a trinucleotide expansion leading to silencing of the FMR1 gene and lack of expression of Fragile X Protein (FXP, formerly known as Fragile X Mental Retardation Protein, FMRP). Phenotypic presentation of FXS is highly variable, and the lack of reproducible, sensitive assays to detect FXP makes evaluation of peripheral FXP as a source of clinical variability challenging. We optimized a Luminex-based assay to detect FXP in dried blot spots for increased reproducibility and sensitivity by improving reagent concentrations and buffer conditions.

A Facility-Wide Plan to Increase Access to Medication for Opioid Use Disorder in Primary Care and General Mental Health Settings.

Background: The opioid epidemic in the United States has generated a pressing need to enhance access to medications for opioid use disorder (MOUD). This program description illustrates a quality-improvement effort to extend MOUD to primary care and general mental health clinics within the US Department of Veterans Affairs (VA) Connecticut Healthcare system (VACHS), and to examine barriers and facilitators to implementation of MOUD in target clinics.

Observations: As part of the national VA Stepped Care for Opioid Use Disorder Train the Trainer (SCOUTT) initiative to improve MOUD access, a VACHS team identified and resolved barriers to MOUD in target clinics.

Steroid hormone profiles and body conditions of migrating male humpback whales (Megaptera novaeangliae).

Simultaneous analysis of multiple steroid hormones from remotely obtained blubber biopsies has the potential to concurrently provide information regarding stress and reproductive status from free-swimming cetaceans, while also investigating correlations between hormone concentrations and other health biomarkers. In this study we measured blubber concentration profiles of eight reproductive and adrenal steroid hormones (17α-hydroxy-progesterone, testosterone, androstenedione, progesterone, cortisol, 11-deoxy-corticosterone, oestrone, and oestradiol) together with body condition, as determined by the inverse Adipocyte Index, of 101 male humpback whales. Whales were sampled randomly at two time points, while migrating to and from their northeast Australian breeding grounds, allowing for intra- and inter-seasonal profile analysis.

Using a population health management approach to enroll participants in a diabetes prevention trial: reach outcomes from the PREDICTS randomized clinical trial.

Population health management (PHM) strategies to address diabetes prevention have the potential to engage large numbers of at-risk individuals in a short duration. We examined a PHM approach to recruit participants to a diabetes prevention clinical trial in a metropolitan health system. We examined reach and representativeness and assessed differences from active and passive respondents to recruitment outreach, and participants enrolled through two clinical screening protocols.

Development of a pregnancy-specific reference material for thyroid biomarkers, vitamin D, and nutritional trace elements in serum.

Objectives: Matrix differences among serum samples from non-pregnant and pregnant patients could bias measurements. Standard Reference Material 1949, Frozen Human Prenatal Serum, was developed to provide a quality assurance material for the measurement of hormones and nutritional elements throughout pregnancy.

Methods: Serum from non-pregnant women and women in each trimester were bottled into four levels based on pregnancy status and trimester.

Liquid chromatography tandem mass spectrometry for the quantification of steroid hormone profiles in blubber from stranded humpback whales ().

Marine mammal blubber is known to have quantifiable concentrations of steroid hormones and is increasingly chosen as a matrix for the detection of these reproductive and stress biomarkers. Steroid hormones act through complex cascades, often in concert, yet studies conducted on cetaceans have rarely measured more than two steroids simultaneously. Due to the role of steroid hormones in multiple physiological processes, and variability in concentration among individuals, data on single compounds are often difficult to interpret.

TNFAIP8 controls murine intestinal stem cell homeostasis and regeneration by regulating microbiome-induced Akt signaling.

The intestine is a highly dynamic environment that requires tight control of the various inputs to maintain homeostasis and allow for proper responses to injury. It was recently found that the stem cell niche and epithelium is regenerated after injury by de-differentiated adult cells, through a process that gives rise to Sca1+ fetal-like cells and is driven by a transient population of Clu revival stem cells (revSCs). However, the molecular mechanisms that regulate this dynamic process have not been fully defined.

The TIPE Molecular Pilot That Directs Lymphocyte Migration in Health and Inflammation.

Lymphocytes are some of the most motile cells of vertebrates, constantly navigating through various organ systems. Their specific positioning in the body is delicately controlled by site-specific directional cues such as chemokines. While it has long been suspected that an intrinsic molecular pilot, akin to a ship's pilot, guides lymphocyte navigation, the nature of this pilot is unknown.

Androstenedione and testosterone but not progesterone are potential biomarkers of pregnancy in Humpback Whales (Megaptera novaeangliae) approaching parturition.

The blubber steroid hormone profiles of 52 female humpback whales migrating along the east coast of Australia were investigated for seasonal endocrine changes associated with reproduction. Individuals were randomly sampled during two stages of the annual migration: before reaching the breeding grounds (northward migration; June/July), and after departing from the breeding grounds (southward migration; September/October). Assignment of reproductive status of the sampled individuals was based on season, single-hormone ranks and multi-variate analysis of the hormonal profiles.

Associations between prenatal diet quality and gestational weight gain.

Background: Improving prenatal diet quality may promote appropriate gestational weight gain (GWG).

Aim: To examine relationships between dietary quality in the second and third trimesters of pregnancy and GWG.

Methods: Participants' ( = 41) dietary intake was assessed at 14-20 and 35 weeks gestation via the Automated Self-Administered 24-h recall (ASA-24).

Social impairments in alternating hemiplegia of childhood.

Aim: To evaluate presence and severity of social impairments in alternating hemiplegia of childhood (AHC) and determine factors that are associated with social impairments.

Method: This was a retrospective analysis of 34 consecutive patients with AHC (19 females, 15 males; mean age: 9y 7mo, SD 8y 2mo, range 2y 7mo-40y), evaluated with the Social Responsiveness Scale, Second Edition (SRS-2).

Results: SRS-2 scores, indicating level of social impairment, were higher than population means (75, SD 14 vs 50, SD 10, p<0.

Assessing a method and reference material for quantification of vitamin D binding protein during pregnancy.

Vitamin D plays a vital role in successful pregnancy outcomes for both the mother and fetus. Vitamin D is bound to vitamin D binding protein (VDBP) in blood and is carried to the liver, kidneys and other target tissues. Accurate measurements of the clinically measured metabolite of vitamin D, 25-hydroxyvitamin D [25(OH)D], depend on complete removal from the binding protein.

Exploring the who, what, when, where, and why of automated vehicle disengagements.

Automated vehicles are emerging on the transportation networks as manufacturers test their automated driving system (ADS) capabilities in complex real-world environments in testing operations like California's Autonomous Vehicle Tester Program. A more comprehensive understanding of the ADS safety performances can be established through the California Department of Motor Vehicle disengagement and crash reports. This study comprehensively examines the safety performances (159,840 disengagements, 124 crashes, and 3,669,472 automated vehicle miles traveled by the manufacturers) documented since the inauguration of the testing program.

Exploratory analysis of automated vehicle crashes in California: A text analytics & hierarchical Bayesian heterogeneity-based approach.

Automated vehicles (AVs) represent an opportunity to reduce crash frequency by eliminating driver error, as safety studies reveal human error contributes to the majority of crashes. To provide insights into the contributing factors of AV crashes, this study created a unique database from the California Department of Motor Vehicles 124 manufacturer-reported Traffic Collision Reports and was linked with detailed data on roadway and built-environment attributes. A novel text analysis was first conducted to extract useful information from crash report narratives.

Preventing diabetes with digital health and coaching for translation and scalability (PREDICTS): A type 1 hybrid effectiveness-implementation trial protocol.

Background: Diabetes prevention remains a top public health priority; digital approaches are potential solutions to existing scalability and accessibility challenges. There remains a gap in our understanding of the relationship between effectiveness, costs, and potential for sustained implementation of digital diabetes prevention strategies within typical healthcare settings.

Purpose: To describe the methods and design of a type 1 hybrid effectiveness-implementation trial of a digital diabetes prevention program (DPP) using the iPARIHS and RE-AIM frameworks.

Blubber steroid hormone profiles as indicators of physiological state in free-ranging common bottlenose dolphins (Tursiops truncatus).

Blubber has been proposed as a possible alternative to blood in the assessment of endocrine physiology in marine mammals because it can be collected via remote biopsy, which removes some of the confounding variables and logistical constraints associated with blood collection. To date, few studies have directly assessed the relationships between circulating versus blubber steroid hormone profiles in marine mammals, and these studies have been limited to a small subset of steroid hormones, which collectively limit the current utility of blubber steroid hormone measurements. In this study, we used liquid-chromatography tandem-mass spectrometry (LC-MS/MS) to screen for 16 steroid hormones in matched blood and blubber samples from free-ranging common bottlenose dolphins (Tursiops truncatus).

The Feasibility and Efficacy of a Behavioral Intervention to Promote Appropriate Gestational Weight Gain.

Introduction: Nearly half of all women gain above gestational weight gain (GWG) recommendations. This study assessed the feasibility and efficacy of a pilot behavioral intervention on GWG and physical activity behaviors.

Methods: Women (n = 45) 14-20 weeks gestation enrolled in a behavioral intervention.