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Cannabis Use and Metabolic Syndrome Among Clients with First Episode Psychosis

Cannabis Use and Metabolic Syndrome Among Clients with First Episode Psychosis

Primary author: Erik Stiles
Co-author(s): Karl Alcover; Oladunni Oluwoye
Faculty sponsor: Michael McDonell, PhD

Primary college/unit: Elson S. Floyd College of Medicine
Campus: Spokane

Abstract:

Aim: We sought to explore the relationship between cannabis use and metabolic syndrome (MetS) among those with a first episode psychosis (FEP).

Background: Individuals diagnosed with a psychotic disorder are three times more likely to suffer from cardiovascular disease (CVD) than the general population. CVD accounts for approximately 16% of deaths among individuals diagnosed with schizophrenia-spectrum disorders.

Methods: We conducted a retrospective analysis of 404 participants enrolled in the Recovery After Initial Schizophrenia Episode – Early Treatment Program. Metabolic syndrome was defined according to the Adult Treatment Panel III guidelines. Using multiple logistic regression, we investigated the correlation between cannabis use and rate of metabolic syndrome. Demographics, time, baseline MetS and potential confounders were separated and analyzed. Finally, we explored the derangement of MetS components among cannabis users and abstainers.

Results: Cannabis users versus abstainers had similar rates of MetS at baseline (10% versus 13.7%, p=0.520). Those who used cannabis at any time during the study period tended to have lower triglycerides (OR=0.3, p=0.001) and higher high-density lipoprotein (OR=0.4, p=0.017). Cannabis users were less likely to develop MetS, relative to non-users (OR = 0.42, 95% CI [0.22-0.80], p=0.008). This effect remained after controlling for type of psychiatric medication (e.g., first- or second-generation antipsychotics, long-acting injectables).

Conclusions: Cannabis use may be associated with lower incidence of MetS in patients experiencing psychosis. Our findings may contribute to mitigating the elevated CVD risk in this population. Further research is indicated to explore and develop these observations.

Examining pilot safety performance indicators at critical phases of flight across multiple flight legs during commercial airline trips

Examining pilot safety performance indicators at critical phases of flight across multiple flight legs during commercial airline trips

Primary author: Rhiannon Soriano Smith
Co-author(s): Amanda Lamp; Ian Rasmussen; Ewa Basiarz; Chandler Keller; Gregory Belenky

Primary college/unit: Elson S. Floyd College of Medicine
Campus: Spokane

Abstract:

Prior simulation and operational studies began to address whether the number of consecutive flight segments negatively affects cognitive performance, fatigue, and sleepiness, without reaching a clear consensus. This study expands this literature by determining whether there are significant changes in cognitive performance, fatigue, and sleepiness at critical phases of flight across multiple flight segments, while accounting for the number of segments, flight direction, trip day, and time-of-day.
Fifty commercial airline pilots were studied, each flying two separate short-haul trips ranging from 1-4 days and 1-10 flight segments. Cognitive performance, fatigue, and sleepiness were assessed at top-of-climb (TOC) and top-of-descent (TOD) of each flight segment and trip day. Cognitive performance, fatigue, and sleepiness were assessed using Psychomotor Vigilance Task (PVT) speed, Samn-Perelli (SP) ratings, and Karolinska Sleepiness Scale (KSS) ratings, respectively. Data were analyzed using Wilcoxon t-tests and verified using ANOVAs.
Mean PVT speed (d =0.57), SP (d = 0.73), and KSS (d = 0.63) were significantly worse at TOD than TOC (p < 0.001); and varied across flight segments (p<0.001). Cognitive performance, fatigue, and sleepiness were consistently degraded around the fifth flight segment, improved around the sixth to eighth flights segments, and were subsequently degraded around the eighth to tenth flight segments.
The results indicate that cognitive performance, fatigue, and sleepiness vary across flight segments, trip day, and phase of flight. Results suggest that these safety performance indices degrade after five segments, and further degrade after eight flight segments. The results presented could inform future airline scheduling and regulation.

Predicted Dermacentor andersoni iron metabolism genes and their response to iron reduction in cultured tick cells

Predicted Dermacentor andersoni iron metabolism genes and their response to iron reduction in cultured tick cellsPredicted Dermacentor andersoni iron metabolism genes and their response to iron reduction in cultured tick cells

Primary author: Muna Solyman
Faculty sponsor: Susan M. Noh

Primary college/unit: College of Veterinary Medicine
Campus: Pullman

Abstract:

For most organisms, iron is an essential nutrient due to its role in many cellular processes. Consequently, insufficient iron levels cause cell damage and death while high concentrations of iron are toxic due to the formation of oxidative radicals, which damage cellular components. As obligate hematophagous parasites, ticks have access to large amounts of iron. Unlike all other hematophagous invertebrates, blood meal digestion within ticks occurs intracellularly rather than in the gut lumen. Due to their unique physiology, little is known about iron uptake and regulation in ticks. Some genes have been identified that are hypothesized to be involved in iron metabolism based on the presence of conserved domains and some limited experimental evidence. In this project, thirteen likely iron metabolism genes were chosen based on the literature and bioinformatics. Using, Dermacentor andersoni ticks, which do not have a published genome, we identified and sequenced these genes. Next, we developed a method to reduce iron in cultured tick cells using an iron chelator 2,2′-bipyridyl and measured the transcriptional response of the D. andersoni iron metabolism genes to iron reduction. Overall, the response of tick cells to iron reduction was less marked than in mammalian cells. The iron transport gene, ferritin 2, and the mitochondrial iron transporters ferrochelatase and mitoferrin were down regulated, while iron regulator protein 1 was up-regulated in response to reduced iron levels. This work lays a foundation for an improved understanding of iron metabolism in ticks and the potential identification of anti-tick targets.

Thin Filament Length Regulation Function of Leiomodin is Affected by its Affinity for Tropomyosin

Thin Filament Length Regulation Function of Leiomodin is Affected by its Affinity for Tropomyosin

Primary author: Garry Smith
Faculty sponsor: Alla Kostyukova

Primary college/unit: Voiland College of Engineering and Architecture
Campus: Pullman

Abstract:

Striated muscle is composed of organized arrays of basic contractile units, sarcomeres, which must be assembled and maintained for proper muscle function. In sarcomeres, thin and thick filaments, composed primarily of actin and myosin respectively, slide against each other to create muscle contraction. For this system to perform, thin filament length must be strictly regulated. It is not fully understood how this is achieved. Leiomodin (Lmod) and tropomodulin (Tmod), homologous muscle proteins binding to actin and tropomyosin (Tpm), participate in regulating thin filament length. In cells, both are found at the slow-growing pointed end of the thin filament, and, according to an earlier proposed competition mechanism, the two have opposite effects; Tmod halts thin filament growth while Lmod allows it. The 3-dimensional structure of the Lmod/Tpm interaction site shows that Lmod binds to Tpm such that it can only occur at the pointed end. We hypothesize binding to Tpm is crucial for Lmod and Tmod competition for the pointed end. Based on the aforementioned 3-dimensional structure, we designed Lmod mutants to have decreased affinity for Tpm. We used circular dichroism (CD) spectroscopy to confirm the affinity and tested mutants in cardiomyocytes. CD experiments showed L24G mutant did not bind while S23L had decreased affinity. Cardiomyocyte experiments showed the L24G mutation resulted in shortened thin filaments and increased Tmod assembly at the pointed end, while the S23L mutation had no effect. This demonstrates that binding to Tpm is important for Lmod function and proper pointed end formation.

Transcriptional R-loops in Archaea

Transcriptional R-loops in Archaea

Primary author: Marguerite Smith
Co-author(s): Michael Rolfsmeier; Cynthia Haseltine
Faculty sponsor: Cynthia Haseltine

Primary college/unit: College of Veterinary Medicine
Campus: Pullman

Abstract:

To maintain genome integrity, cells must contend with multiple DNA structures that arise during replication, transcription, and repair. Transcriptionally active regions of the genome are particularly susceptible to DNA damage through the production of R-loop regions, consisting of an RNA:DNA hybrid along with a displaced ssDNA non-template strand, which is particularly susceptible to damage. Failure to dissociate RNA:DNA hybrids can lead to extensive ssDNA regions, stalled transcription machinery, or persistent protein:DNA complexes, all of which are potentially deleterious to the cell. Thus, all organisms must have robust mechanisms to contend with RNA:DNA hybrids within actively transcribed regions of the genome. While transcriptionally associated R-loops have been detected in bacteria and eukaryotes, there have been no reports of their occurrence in archaea. We used the hyperthermophilic crenarchaeon Sulfolobus solfataricus as a model archaeal species to investigate the formation of RNA:DNA hybrids. We established methodology for immunoprecipitation of RNA:DNA hybrids from S. solfataricus and evaluated abundance and persistence of these hybrids for both transcriptionally active and inactive regions of the genome using multiple cell backgrounds. In parallel, we examined topological alterations in the supercoiling state of a plasmid carrying an inducible gene using an in vitro transcription approach. Our molecular characterization of RNA:DNA hybrids in S. solfataricus indicates they are strongly associated with transcriptionally active regions and likely represent R-loop structures. Additionally, variation of production and persistence of these R-loops in strain backgrounds with differential DNA damage responses implicates DSB repair processes in maintaining genome stability during transcriptional activities in S. solfataricus.

Fecal microbiome profiles of neonatal dairy calves with gastrointestinal disease

Fecal microbiome profiles of neonatal dairy calves with gastrointestinal disease

Primary author: Giovana Slanzon
Co-author(s): Lindsay Parrish; Sophie Trombetta; William Sischo; Craig McConnel
Faculty sponsor: Dr. Craig Stephen McConnel

Primary college/unit: College of Veterinary Medicine
Campus: Pullman

Abstract:

Gastrointestinal disease is the most common illness in preweaned dairy calves. Studies have associated fecal microbiome composition with health status, but changes in the microbiome across varying levels of GI disease remain unclear. Our objective was to show a correlation between clinical symptoms and shifts in the microbiome composition. Calves (n=360) were enrolled in a sampling scheme of repeat fecal collections throughout 5-15 d of age. Daily evaluations assessed health status based on clinical signs and treatments. Calves with fecal scores of 3 (loose) or 4 (watery) were diagnosed with diarrhea and classified as bright-sick (BS) or depressed-sick (DS) according to their behavior and appetite. Calves with fecal scores <3 and no clinical illness were classified as healthy. Sixty-one fecal samples from healthy calves and 30 samples from diarrheic calves were selected to represent different breeds and ages. The V3-V4 region of the 16S rRNA gene was sequenced and analyzed using DADA2 pipeline. The ASV table was used to compare the taxonomic profiles, differences were identified by LEfSe (p2). Healthy calves had greater enrichment of the families Bifidobacteriaceae, Bacteroidaceae, Prevotellaceae, Eubacteriaceae, Ruminococcaceae, Erysipelotrichaceae. In BS calves Listeriaceae, Clostridiaceae and Lachnospiraceae were more enriched. DS calves had enriched Lactobacillaceae, Streptococcaceae and Enterobacteriaceae in their microbiome. Breed differences included the association of Bacteroidaceae, Eubacteriaceae, Erysipelotrichaceae and Fusobacteriaceae with healthy Jersey calves. Bifidobacteriaceae was more enriched in healthy Holstein calves. On the other hand, Enterobacteriaceae was associated with DS Holstein calves. For DS Jersey calves, the order Lactobacillales was enriched.

Relationship between Sleepiness Symptoms Questionnaire Ratings and Psychomotor Vigilance Test Performance in a Laboratory-Based Sleep Deprivation Study

Relationship between Sleepiness Symptoms Questionnaire Ratings and Psychomotor Vigilance Test Performance in a Laboratory-Based Sleep Deprivation Study

Primary author: Alicja Skwara
Co-author(s): Lillian Skeiky; Hans Van Dongen; Devon Hansen

Primary college/unit: Elson S. Floyd College of Medicine
Campus: Spokane

Abstract:

Sleep deprivation has been demonstrated to adversely impact on cognitive performance and safety. Measuring the impairment caused by sleep deprivation is best done with objective performance assessments such as the psychomotor vigilance test (PVT), but subjective self-report assessments may provide a more practical alternative in real-world settings. The Sleepiness Symptoms Questionnaire (SSQ) is a self-report instrument based on ratings of observable symptoms of sleepiness and motor vehicle driving performance impairment. In a laboratory-based sleep deprivation study, we compared SSQ ratings to performance impairment on a 10min PVT.
Twelve healthy normal sleepers (ages 21-39y, 6 females) participated in a 4-day in-laboratory study. Between a baseline day and a recovery day, participants underwent 38 hours of total sleep deprivation. Participants completed the SSQ and PVT following 6.5, 14.5, 22.5, and 30.5 hours of sleep deprivation, and 6.5 hours after recovery sleep.
As sleep deprivation progressed, the SSQ sleepiness ratings and the number of lapses (reaction times > 500 ms) on the PVT were elevated, peaking after 22.5 hours awake. Both measures returned to baseline levels after recovery sleep. There was a moderate correlation between SSQ ratings and PVT lapses (r=0.44, F1,43=24.1, p<0.001). Subjective sleepiness on the SSQ and objective performance impairment on the PVT reflected expected changes by time awake and time of day during sleep deprivation and following recovery sleep. The moderate correlation we observed suggests that the SSQ may be reasonably reliable for measuring impairment under conditions of acute sleep deprivation.

Rest-Activity Patterns in Adults Receiving Methadone for Medication-Assisted Treatment of Opioid Use Disorder

Rest-Activity Patterns in Adults Receiving Methadone for Medication-Assisted Treatment of Opioid Use Disorder

Primary author: Lillian Skeiky
Co-author(s): Marian Wilson; Matthew Layton; Raymond Quock; Hans Van Dongen; Devon Hansen
Faculty sponsor: Devon A. Hansen, PhD, LMHC

Primary college/unit: Arts and Sciences
Campus: Spokane

Abstract:
Individuals with opioid use disorder (OUD) report significant sleep/wake disturbances, which continue even when they stabilize with medication-assisted treatment. However, the nature of reported sleep/wake disturbances has not been well documented. We compared rest/activity patterns observed with a wrist-worn activity monitor, which provides objective estimates of sleep/wake disturbances, to control groups comprised of nurses working day or night shifts.

Seven adults undergoing methadone treatment for OUD wore a wrist activity monitor continuously for 7 days. Hospital nurses – 7 on a day shift schedule and 7 on a night shift schedule (six 12-hour shifts within a two-week period) – also wore a wrist activity monitor continuously for 14 days. The observed rest/activity patterns were analyzed through cosinor analysis to evaluate circadian rhythmicity, and through analysis of the distribution of inactive periods to estimate sleep continuity.

As expected, nurses working day shifts displayed strong circadian rhythmicity and high sleep continuity. Nurses working night shifts showed dampened circadian rhythmicity, but exhibited high sleep continuity. For the OUD methadone treatment group, the strength of circadian rhythmicity was between that of nurses on day versus night shifts, and this group experienced reduced sleep continuity.

These findings suggest disturbed sleep in individuals receiving methadone for medication-assisted treatment of OUD. This may interfere with their ability to achieve OUD recovery goals, and is worthy of investigation in a laboratory setting. This research was partially supported by the State of Washington via the Alcohol and Drug Abuse Research Program.

Community Organizing: A Novel Approach to Identifying Healthcare Needs

Community Organizing: A Novel Approach to Identifying Healthcare Needs

Primary author: Katie Schmidt
Co-author(s): Carly Celebrezze; Kelly Anne Hennessey; Andrew Liechty; Courtney Roberts
Faculty sponsor: Dr. Luis Manriquez

Primary college/unit: Elson S. Floyd College of Medicine
Campus: Spokane

Abstract:
The Spokane Alliance is a non-partisan organization of religious institutions, educators, unions and other civic non-profits organizing for the common good in Spokane, Washington. The Healthcare Research Action Team (HRAT) was formed in response to Alliance members attesting that healthcare is a significant stressor in their lives.

The HRAT, led by medical students from WSU and UW, conducted a health needs assessment of its 31 member organizations. Listening sessions were held with 13 Spokane Alliance organizations in 2018 to qualitatively ascertain healthcare needs among community members.

111 Spokane community members participated. Three themes emerged as common issues: healthcare system complexity, affordability, and mental health needs.

Forty-six stories were shared regarding healthcare system complexity. Members stated they had difficulty navigating both the healthcare and insurance systems. They also expressed frustration with the lack of communication between providers and confusion related to healthcare paperwork.

Twenty-six Spokane Alliance members shared about issues with healthcare affordability, regardless of their health insurance status. Eight members stated they experienced challenges accessing mental health services and stigma surrounding mental health needs.

Community organizing methods can yield rich qualitative data on healthcare needs. The issues identified by Spokane Alliance members indicate a need for improvements in healthcare system navigability, affordability, and access to mental health services in Spokane. Since this needs assessment was conducted, the WSU mobile medicine program has launched its first mobile medical unit, which is equipped to provide primary care and reproductive health services, informed, in part, by the results of this needs assessment.

Impact of glucose consumption on hibernation phenotype of adipose tissue in brown bears

Impact of glucose consumption on hibernation phenotype of adipose tissue in brown bears

Primary author: Michael Saxton
Faculty sponsor: Joanna Kelley

Primary college/unit: Arts and Sciences
Campus: Pullman

Abstract:

To survive the cold environments and winter food shortage for which they are adapted, brown bears undergo seasonal shifts from maximizing energy gain and storage in summer and fall, to conserving energy in winter hibernation. During hibernation, bears experience a mild decrease in body temperature but up to a 75% reduction in basal metabolic rate, as well as reduced heart rate, respiration rate, and insulin sensitivity. On arousal from hibernation, the bears return to active season physiology, which includes a reversal of the insulin resistance. Fluctuations in weight and high overall adiposity, like those seen in bears, are contributing factors to cardiovascular disease and diabetes in humans. In this study bears were fed dextrose during hibernation to determine the effect of glucose consumption on hibernation and insulin sensitivity. We collected serum from the bears and evaluated the effect of that serum on gene transcription in bear adipose cells grown in vitro. We found a strong cell by serum interaction, with cells collected in hibernation and grown with pre-dextrose hibernation serum showing a starkly different gene expression profile than those grown with either active season or post-dextrose hibernation serum. Though cells treated with post-dextrose hibernation serum closely matched the expression profile of cells grown with active serum, proteomic analysis of serum showed that post-dextrose serum more closely matched hibernation serum. Therefore one of these limited changes in serum proteins after consumption of dextrose leads to near complete reversal of the hibernation phenotype in brown bear adipose tissue.