Supportive Resources for Unhoused Individuals & Families

Introduction Since 2016 King County’s unsheltered homeless individuals have increased by 24% and families experiencing homelessness have increased by 26% (National Alliance to End Homelessness, 2021). In the past 5 years, homelessness has risen by 10% in King County alone (NAEH, 2021). Our agency was an emergency family shelter located in King County that “ensures that no child sleeps outside by centering equity and opportunity for women and families” (Mary’s Place Seattle, n.d.-a). This facility has 5 other family center facilities that provide shelter and resources. Since 1999, our agency with its 6 facilities have aided thousands of women and families transition from homelessness into stable situations (Mary’s Place Seattle, n.d.-a). As students pursuing a Bachelor of Science in Nursing at Seattle Pacific University, we worked alongside this agency in their vision of making its shelter a community where families have safety, stability, and housing. We have a background in health sciences and have assessed that there was a knowledge deficit in the community regarding access to crisis hotlines. We based our work with this shelter to incorporate their vision of safety and value of collaboration to provide crisis hotline resources to the community (Mary’s Place Seattle, n.d.-b). As professionals with an understanding in health promotion, we provided the community with a breathing exercise to relieve stress and anxiety individuals may encounter when dealing with situations where crisis hotlines are needed. Our goal with this project was to ensure families have knowledge on existing resources in the community for crisis events such as domestic violence, suicidal thoughts, unplanned pregnancies, substance abuse, and more. We anticipate the families are able to utilize these hotlines and spread the resources to others through the use of our flyers and word of mouth. Background According to an article published by Harvard Public Health Review, suicide rates amongst the homeless population are nine times that of the general United States population (Holleran & Poon, 2018). This shocking statistic proves a need for better mental health crisis resources amongst the homeless population. To add to that, on one single night in King County, it was found that over 11,750 individuals experienced homelessness (Constantine, 2020). The community served by this organization is comprised of a variety of vulnerable populations with homelessness just being one factor of stress they may be experiencing. Residents of the community center may also be battling other issues such as substance use disorders, domestic violence, or managing medically fragile children. Providing them with a resource of national crisis hotlines and a stress reduction technique will give community members something easy and convenient to refer to in times of need. Project Activity & Rationale Our nursing diagnosis for the community was that there is a knowledge deficit related to mental health resources. Our goal was to increase the knowledge of crisis resources available to the community by the end of the quarter. This included providing the agency and their sites with crisis hotline resources in the form of flyers. The crisis hotlines offer individuals a platform to verbalize the situations that they are experiencing. Studies have shown that users feel a sense of relief in being able to talk through their experiences with staff (Rethink, n.d.). It reduces their sense of isolation and helps them to cope with “depression, anxiety, self-harm and suicide” (Rethink, n.d.). However, to benefit from these services, users must first be able to access them (Rethink, n.d.). Health-educational flyers are beneficial in situations where a wide audience of people needs to be reached for an extended period of time (Hasanica et al., 2020). They provide the necessary facts that individuals may need in a concise way. Abid et al. (2022) shows that a simple intervention, such as providing individuals with an information card, can greatly increase client-staff communication. Another part of the resource we provided to the agency was on the back of the flyer which displayed a box-breathing method. Studies have demonstrated that rhythmic breathing methods are a “practical and effective tool to alleviate stress, improve health, and increase wellness” (Sharma et al., 2015). Evidence shows that youth experiencing homelessness are at an increased risk for violence victimization and perpetration (Petering et al., 2015, as cited in Barr et al., 2021). Mindfulness-based interventions can be used to reduce these violent and aggressive behaviors and cause improved emotional regulation (Gillions et al., 2019, as cited in Barr et al., 2021). Box-breathing is a method that can help control an individual’s breathing pattern to bring it back to baseline. This can help to calm the individual and keep them focused on the moment at hand. Outcomes We were given the opportunity to work at the agency’s health fair where we measured our outcomes based on our outreach to the community. 50 flyers were printed to be distributed at the health fair with the goal of distributing 25 flyers. This would result in a desired outreach of 50 percent. By the end of the fair, we distributed 7 flyers not meeting our goal and resulting in a desired outreach of 14 percent. However, clients and staff that received flyers reacted positively, and the remaining flyers were left at the facility for further distribution on intake. The primary limitation of measuring our outcomes was not having enough people visit our booth when we were there. We also found that measuring calls to the hotlines was not applicable to our project as we are not able to track calls to these mental health resources due to their nature of anonymity. Conclusion Our project goal was to increase awareness and access to mental health resources and crisis lines. After conducting a windshield survey and touring the site, we recognized a need for a quick and accessible information sheet to be handed out at the agency. We designed flyers containing crisis line resources and boxed-breathing exercises in hopes of addressing a knowledge deficit in the community. Our group went to the site and handed out flyers at the health fair. Although we did not meet our goal of distributing 25 flyers, we were given positive feedback about the flyers. One limitation was the sample size of guests attending the health fair. Next time, we would consider coming in more than once to pass out our flyers, to allow for potentially more outreach. The second limitation was that for the majority of the people at the fair, English was not their primary language, so we hope that in the future, the agency can continue to utilize our flyers for years to come and expand it to be more inclusive by offering translations to different languages. References Abid, M. H., Lucier, D. J., Hidrue, M. K., & Geisler, B. P. (2022). The effect of standardized hospitalist information cards on the patient experience: A quasi-experimental prospective cohort study. Journal of General Internal Medicine, 37, 3931-3936. https://doi.org/10.1007/s11606-022-07674-3 Barr, N., Petering, R., Onasch-Vera, L., Thompson, N., & Polsky, R. (2021). MYPATH: A novel mindfulness and yoga-based leader intervention to prevent violence among youth experiencing homelessness. Journal of Community Psychology, 50(4), 1952-1965. https://doi.org/10.1002/jcop.22661 Constantine, D. (2020, July 1). Point-in-Time count estimates a 5 percent increase in people experiencing homelessness, newly updated data dashboards reveal more people receiving shelter and services. King County. https://kingcounty.gov/elected/executive/constantine/news/release/2020/July/01-homeless-count.aspx Hasanica, N., Ramic-Catak, A., Mujezinovic, A., Begagic, S., Galijasevic, K., & Oruc, M. (2020). The effectiveness of leaflets and posters as a health education method. Mater Sociomed, 32(2), 135-139. https://doi.org/10.5455/msm.2020.32.135-139 Holleran, L., & Poon, G. (2018). Dying in the shadows: suicide among the homeless. Harvard Public Health Review, 20, 1–5. https://www.jstor.org/stable/48515221 Mary’s Place Seattle. (n.d.-a). About Us. Mary’s Place. https://www.marysplaceseattle.org/about-us Mary’s Place Seattle. (n.d.-b). Our Mission. Mary’s Place. https://www.marysplaceseattle.org/missio

Population Pharmacokinetics and Exposure–Response Analysis for the Phase 3 COSMIC-311 Trial of Cabozantinib for Radioiodine-Refractory Differentiated Thyroid Cancer

Background and Objective In the USA, cabozantinib was approved for the treatment of patients aged ≥ 12 years with radioiodine-refractory differentiated thyroid cancer (DTC) who progressed on prior vascular endothelial growth factor (VEGFR)-targeted therapy based on the Phase 3 COSMIC-311 trial, which evaluated cabozantinib 60 mg/day versus placebo. Approved dosing is 60 mg/day for adults and for pediatric patients aged ≥ 12 years with body surface area (BSA) ≥ 1.2 m2, and 40 mg/day for pediatric patients aged ≥ 12 years with BSA \u3c 1.2 m2. This report describes a population pharmacokinetic (PopPK) and exposure–response analysis of COSMIC-311. Methods A PopPK model was developed using concentration-time data from COSMIC-311 and 6 other cabozantinib studies. The final (full) PopPK model was used to simulate the effect of sex, body weight, race, and patient population. For exposure–response analysis, derived datasets from COSMIC-311 were constructed for time-to-event analyses of progression-free survival (PFS) and safety endpoints. Results The PopPK analysis included 4746 cabozantinib PK samples from 1745 patients and healthy volunteers. Body weight had minimal impact on cabozantinib exposure but increasing body weight was associated with increased apparent volume of distribution. Based on model-based simulation, adolescents \u3c 40 kg had higher maximum plasma concentration at steady state of cabozantinib 60 mg/day compared to adults. Allometric scaling simulation in adolescents \u3c 40 kg demonstrated higher exposure with 60 mg/day relative to adults receiving the same dose, while exposure with 40 mg/day in adolescents \u3c 40 kg was similar to 60 mg/day in adults. The exposure–response analysis included 115 patients. There was no clear relationship between PFS or dose modification and cabozantinib exposure. A statistically significant relationship was demonstrated for cabozantinib exposure and hypertension (Grade ≥ 3) and fatigue/asthenia (Grade ≥ 3). Conclusions These results support the dosing strategy implemented in COSMIC-311 and the BSA-based label recommendations for adolescents. The cabozantinib dose should be reduced to manage adverse events as indicated

Combinatorial pharmacodynamics of polymyxin B and tigecycline against heteroresistant Acinetobacter baumannii

The prevalence of heteroresistant Acinetobacter baumannii is increasing. Infections due to these resistant pathogens pose a global treatment challenge. Here, the pharmacodynamic activities of polymyxin B (PMB) (2–20 mg/L) and tigecycline (0.15–4 mg/L) were evaluated as monotherapy and in combination using a 4 × 4 concentration array against two carbapenem-resistant and polymyxin-heteroresistant A. baumannii isolates. Time Kill Experiments was employed at starting inocula of 106 and 108 CFU/mL over 48 h. Clinically relevant combinations of PMB (2 mg/L) and tigecycline (0.90 mg/L) resulted in greater reductions in the bacterial population compared with polymyxin alone by 8 h (ATCC 19606, −6.38 vs. −3.43 log10 CFU/mL; FADDI AB115, −1.38 vs. 2.08 log10 CFU/mL). At 10× the clinically achievable concentration (PMB 20 mg/L in combination with tigecycline 0.90 mg/L), there was bactericidal activity against FADDI AB115 by 4 h that was sustained until 32 h, and against ATCC 19606 that was sustained for 48 h. These studies show that aggressive polymyxin-based dosing in combination with clinically achievable tigecycline concentrations results in early synergistic activity that is not sustained beyond 8 h, whereas combinations with higher tigecycline concentrations result in sustained bactericidal activity against both isolates at both inocula. These results indicate a need for optimised front-loaded polymyxin-based combination regimens that utilise high polymyxin doses at the onset of treatment to achieve good pharmacodynamic activity whilst minimising adverse events

Polymyxin B in combination with doripenem against heteroresistant Acinetobacter baumannii : pharmacodynamics of new dosing strategies

Polymyxin B is being increasingly utilized as a last resort against resistant Gram-negative bacteria. We examined the pharmacodynamics of novel dosing strategies for polymyxin B combinations to maximize efficacy and minimize the emergence of resistance and drug exposure against Acinetobacter baumannii

A taxonomic re-assessment of Oligodon cinereus (Günther, 1864) (Squamata, Serpentes, Colubridae) populations from southern Indochina

The ashy kukri snake Oligodon cinereus (Günther, 1864) is a widely distributed and morphologically variable species found throughout mainland Southeast Asia. In this paper, we re-assessed the taxonomic status of O. cinereus populations found in southern Indochina (southern Vietnam, Cambodia, and southern Laos), including the recently described Cat Tien kukri snake Oligodon cattienensis Vassilieva et al., 2013, which was previously confused with this species. Phylogenetic analyses using mitochondrial DNA from the 12S–16S ribosomal subunit and cytochrome b gene revealed that O. cattienensis is embedded in a mixed clade containing samples of the subspecies O. cinereus pallidocinctus, which bears a dorsal color pattern with white crossbars and black edges. This clade forms a strongly supported sister group with a topotypic sample of O. cinereus cinereus, representing populations bearing a uniform dorsal color pattern and slight reticulate markings, however the genetic divergence between the two clades is very low. The morphological characters used to distinguish O. cattienensis from O. cinereus sensu lato broadly overlap and supposed differences in hemipenial morphology between the two taxa are due to outdated terminologies used to describe the organ. We relegate both O. cattienensis and O. cinereus pallidocinctus to the junior synonymy of O. cinereus and consider all color patterns of this species found near the type locality in Cambodia, southern Laos, and southern Vietnam to represent O. cinereus sensu stricto. Future integrative investigations across the range of O. cinereus sensu lato are needed to resolve the status of the remaining subspecies and synonyms associated with this taxon. Problems associated with hemipenial morphology and Oligodon systematics are also discussed

Is Chytridiomycosis an Emerging Infectious Disease in Asia?

The disease chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), has caused dramatic amphibian population declines and extinctions in Australia, Central and North America, and Europe. Bd is associated with >200 species extinctions of amphibians, but not all species that become infected are susceptible to the disease. Specifically, Bd has rapidly emerged in some areas of the world, such as in Australia, USA, and throughout Central and South America, causing population and species collapse. The mechanism behind the rapid global emergence of the disease is poorly understood, in part due to an incomplete picture of the global distribution of Bd. At present, there is a considerable amount of geographic bias in survey effort for Bd, with Asia being the most neglected continent. To date, Bd surveys have been published for few Asian countries, and infected amphibians have been reported only from Indonesia, South Korea, China and Japan. Thus far, there have been no substantiated reports of enigmatic or suspected disease-caused population declines of the kind that has been attributed to Bd in other areas. In order to gain a more detailed picture of the distribution of Bd in Asia, we undertook a widespread, opportunistic survey of over 3,000 amphibians for Bd throughout Asia and adjoining Papua New Guinea. Survey sites spanned 15 countries, approximately 36° latitude, 111° longitude, and over 2000 m in elevation. Bd prevalence was very low throughout our survey area (2.35% overall) and infected animals were not clumped as would be expected in epizootic events. This suggests that Bd is either newly emerging in Asia, endemic at low prevalence, or that some other ecological factor is preventing Bd from fully invading Asian amphibians. The current observed pattern in Asia differs from that in many other parts of the world

Identification and functional caracterization of novel lipases/acyltransferases of yeasts

Les lipases/acyltransférases présentent des propriétés intermédiaires entre les lipases et les acyltransférases. Capables de se comporter comme des hydrolases, elles catalysent cependant la réaction de transfert d'acyle préférentiellement à l'hydrolyse même en milieu aqueux à forte activité thermodynamique de l'eau en présence de divers nucléophiles. La recherche de nouvelles lipases/acyltransférases, soit sécrétées par des levures sauvages, soit identifiées parmi les séquences protéiques disponibles dans des bases de données, nous a permis d'identifier deux nouvelles enzymes de ce type : CvisL2 de Candida viswanathii et CtroL4a de C. tropicalis. Cette dernière, produite par expression hétérologue, a été plus particulièrement étudiée en comparaison avec les deux lipases/acyltransférases déjà connues, CpLIP2 de C. parapsilosis et CaLIP4 de C. albicans, ainsi qu'avec des enzymes plus éloignées (AflaL0a d'Aspergilus flavus, isolée dans ce travail, et CaLA de C. antarctica, qui présentent respectivement 35 % et 31 % d'identité avec CpLIP2). Le caractère spécifique des acyltransférases semble relié à leur degré d'homologie et à leurs relations phylogénétiques. En effet, les trois lipases/acyltransférases étudiées appartiennent à un sous-groupe phylogénétique distinct composé de diverses autres protéines actuellement non-caractérisées présentant plus de 57 % d'identité avec CpLIP2. En plus de leur activité acyltransférase plus ou moins prononcée, ces nouveaux biocatalyseurs diffèrent par leur spécificité de substrat, leur stabilité en présence de fortes concentrations en alcool ou leur activité à basse température, élargissant ainsi le spectre des applications potentielles des lipases et lipases/acyltransférases.Lipases/acyltransferases have intermediate properties between lipases and acyltransferases. Although being active hydrolases, they catalyze acyltransfer reactions preferentially to hydrolysis even in an aqueous medium with a high thermodynamic activity of water in the presence of various nucleophiles. Searching for new lipases/acyltransferases, either secreted by wild yeast strains or identified in protein sequences databases, allowed us to identify two new enzymes of this type: CvisL2 from Candida viswanathii and CtroL4a from C. tropicalis. The latter, produced by heterologous expression, has been more particularly studied and compared with the two already known, closely related, lipases/acyltransferases, CpLIP2 from C. parapsilosis and CaLIP4 from C. albicans, and with two more distantly related lipases (a new lipase AflaL0a from Aspergillus flavus and CaLA from C. antarctica, with 35 % and 31 % identity with CpLIP2, respectively). The specific catalytic behavior of the acyltransferases seems to be associated with sequence homology and phylogenetic relationships. Indeed, the three lipases/acyltransferases studied are part of a phylogenetic subgroup composed of various proteins (identity with CpLIP2 higher than 57 %), currently not characterized. Besides their acyltransfer activity, these new biocatalysts differ in properties such as their substrate selectivity, their stability in the presence of high alcohol concentration or their activity at low temperature, opening the way to new applications