Cannabis Use Among Young Adults in Washington State After Legalization of Nonmedical Cannabis.

Objectives. To examine changes in prevalence of cannabis use and of cannabis use disorder symptomatology among young adults from 2014 to 2019 in Washington State, where nonmedical (or "recreational") cannabis was legalized in 2012 and retail stores opened in July 2014. Methods. We used 6 years of cross-sectional data collected annually from 2014 (premarket opening) to 2019 from 12 963 (∼2000 per year) young adults aged 18 to 25 years residing in Washington. Logistic regression models estimated yearly change in prevalence of cannabis use at different margins and related outcomes. Results. Prevalence of past-year, at least monthly, at least weekly, and daily use of cannabis increased for young adults, although increases were driven by changes among those aged 21 to 25 years. There was also a statistically significant increase in prevalence of endorsing at least 2 of 5 possible symptoms associated with cannabis use disorder. Conclusions. Among young adults in Washington, particularly those of legal age, prevalences of cannabis use and cannabis use disorder symptomatology have increased since legalization. This trend may require continued monitoring as the nonmedical cannabis market continues to evolve. (Am J Public Health. 2022;112(4):638-645. https://doi.org/10.2105/AJPH.2021.306641).

The adherens junctions control susceptibility to Staphylococcus aureus α-toxin.

Staphylococcus aureus is both a transient skin colonizer and a formidable human pathogen, ranking among the leading causes of skin and soft tissue infections as well as severe pneumonia. The secreted bacterial α-toxin is essential for S. aureus virulence in these epithelial diseases. To discover host cellular factors required for α-toxin cytotoxicity, we conducted a genetic screen using mutagenized haploid human cells. Our screen identified a cytoplasmic member of the adherens junctions, plekstrin-homology domain containing protein 7 (PLEKHA7), as the second most significantly enriched gene after the known α-toxin receptor, a disintegrin and metalloprotease 10 (ADAM10). Here we report a new, unexpected role for PLEKHA7 and several components of cellular adherens junctions in controlling susceptibility to S. aureus α-toxin. We find that despite being injured by α-toxin pore formation, PLEKHA7 knockout cells recover after intoxication. By infecting PLEKHA7(-/-) mice with methicillin-resistant S. aureus USA300 LAC strain, we demonstrate that this junctional protein controls disease severity in both skin infection and lethal S. aureus pneumonia. Our results suggest that adherens junctions actively control cellular responses to a potent pore-forming bacterial toxin and identify PLEKHA7 as a potential nonessential host target to reduce S. aureus virulence during epithelial infections.

Helicobacter pylori Activates and Expands Lgr5(+) Stem Cells Through Direct Colonization of the Gastric Glands.

BACKGROUND & AIMS: Helicobacter pylori infection is the main risk factor for gastric cancer. We characterized the interactions of H pylori with gastric epithelial progenitor and stem cells in humans and mice and investigated how these interactions contribute to H pylori-induced pathology. METHODS: We used quantitative confocal microscopy and 3-dimensional reconstruction of entire gastric glands to determine the localizations of H pylori in stomach tissues from humans and infected mice. Using lineage tracing to mark cells derived from leucine-rich repeat-containing G-protein coupled receptor 5-positive (Lgr5(+)) stem cells (Lgr5-eGFP-IRES-CreERT2/Rosa26-TdTomato mice) and in situ hybridization, we analyzed gastric stem cell responses to infection. Isogenic H pylori mutants were used to determine the role of specific virulence factors in stem cell activation and pathology. RESULTS: H pylori grow as distinct bacterial microcolonies deep in the stomach glands and interact directly with gastric progenitor and stem cells in tissues from mice and humans. These gland-associated bacteria activate stem cells, increasing the number of stem cells, accelerating Lgr5(+) stem cell proliferation, and up-regulating expression of stem cell-related genes. Mutant bacteria with defects in chemotaxis that are able to colonize the stomach surface but not the antral glands in mice do not activate stem cells. In addition, bacteria that are unable to inject the contact-dependent virulence factor CagA into the epithelium colonized stomach glands in mice, but did not activate stem cells or produce hyperplasia to the same extent as wild-type H pylori. CONCLUSIONS: H pylori colonize and manipulate the progenitor and stem cell compartments, which alters turnover kinetics and glandular hyperplasia. Bacterial ability to alter the stem cells has important implications for gastrointestinal stem cell biology and H pylori-induced gastric pathology.

Nicotine Vaping Expectancies: Organization and Activation in Memory Based on Vaping Use Patterns.

OBJECTIVE: Prevalence of smoking combustible cigarettes has decreased, but rates of nicotine vaping among adolescents and young adults have increased dramatically. Vaping is associated with acute health problems and exposes users to toxic metals with unknown long-term consequences. Research on factors influencing vaping is needed to inform development of effective prevention and intervention methods. Nicotine vaping expectancies, or expected effects related to vaping, may be an important target as they can predict vaping behaviors. The purpose of this study was to examine nicotine expectancy activation patterns with corresponding nicotine vaping behaviors. METHOD: Using methods from alcohol expectancy research, we applied a memory model approach to identifying nicotine vaping expectancies and modeling organization and activation patterns in relation to frequency of nicotine vaping. We created a memory model-based nicotine expectancy measure based on information from 200 adolescents in 8th and 12th grades, and 429 college students. Our expectancy measure was completed by a second sample of 862 college students. RESULTS: We mapped expectancies into network format using Individual Differences Scaling (INDSCAL) and we modeled likely paths of expectancy activation using Preference Mapping (PREFMAP). Non-users primarily emphasized a positive-negative expectancy dimension and were more likely to activate expectancies of negative internal experiences in relation to vaping. Students who vaped nicotine daily or almost daily primarily emphasized an external appearance-internal experience expectancy dimension and were more likely to activate expectancies of negative affect reduction and withdrawal relief. CONCLUSIONS: Our results identify specific targets for expectancy-based prevention and intervention methods that have the potential to be as effective as similar approaches to preventing and reducing alcohol use.

Daily level predictors of impaired driving behaviors in young adults: Protocol design for utilizing daily assessments.

BACKGROUND: Motor vehicle crashes remain a leading cause of death among young adults (ages 18-25) in the United States. Many drivers implicated in these crashes are under the influence of alcohol, cannabis, or the simultaneous use of alcohol and cannabis. Extremely limited research has assessed impaired driving behaviors and their predictors at the daily level. Perceived norms and motives to use substances have empirical support suggesting they may impact impaired driving-related behavior. Novel approaches to assess these associations at the daily level are needed and may inform future intervention and prevention programs. OBJECTIVE: The goal of the current study is to utilize electronic daily assessments to assess driving under the influence of alcohol, cannabis, or simultaneous use and riding with a driver impaired by these substances to assess variability and predictors of these impaired driving-related behaviors at the daily level. This present manuscript details a protocol, measures, and a plan of analyses to assess how within-person differences in perceived norms and motives to use are associated with the likelihood of engaging in impaired driving-related behaviors. METHODS: Participants include young adults in Washington State who report simultaneous use in the past month and either driving under the influence of alcohol, cannabis, or simultaneous use, or riding with a driver under the influence of both substances in the past 6 months. Individuals who verify their identity and meet eligibility requirements will complete a baseline assessment after which they will be scheduled for training on the daily assessment procedure via Zoom. Next, they will be invited to complete daily surveys on Thursday, Friday, Saturday, and Sunday every other week for 6 months and a 6-month follow up assessment. Analyses will utilize multilevel models with days nested within individuals. RESULTS: The study is currently recruiting participants. A total of 192 participants have been recruited and 100 have completed the study protocol. Data collection is expected to be completed in Fall 2022. CONCLUSIONS: This study utilizes a novel design to assess impaired driving and predictors at the daily level among young adults at high risk of impaired driving-related behaviors. Findings will provide unique data that will shape the knowledge base in the field of social science and public health substance use research and that may be helpful for future prevention and intervention efforts on impaired driving.

Retrospective evaluation of risk factors and outcome predictors in cats with diabetic ketoacidosis (1997-2007): 93 cases.

OBJECTIVES: To determine risk factors and outcome predictors in cats with diabetic ketoacidosis (DKA). DESIGN: Retrospective study. Inclusion in the DKA group required blood glucose concentration > 13.9 mmol/L (250 mg/dL), venous pH < 7.35, and urine or serum acetoacetate concentration greater than 1.5 mmol/L (15 mg/dL). Signalment and weight were recorded in all cats with uncomplicated diabetes mellitus (DM) without DKA and in all other nondiabetic cats examined during the study period. Clinicopathologic variables, concurrent disorders, and initial insulin intravenous (IV) continuous-rate infusion (CRI) concentration of 1.1 or 2.2 U/kg/240 mL bag of 0.9% NaCl, were examined for a possible association with outcome. SETTING: University teaching hospital. ANIMALS: Ninety-three cats with DKA, 682 cats with uncomplicated DM, and 16,926 cats without DM or DKA. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cats with DKA were younger (median age 9.4 years; range, 1-17.9 years) than cats with uncomplicated DM (median 11.6 years; range 0.7-19.5 years, P < 0.0003). Siamese cats were overrepresented in the DKA group compared to the uncomplicated DM or nondiabetic group (P = 0.038 and P = 0.01, respectively). Poor outcome (defined as death due to disease or by euthanasia) in 36 cats with DKA (39%) was associated with increased initial creatinine, BUN, total serum magnesium, and total bilirubin concentrations (P = 0.007, P = 0.005, P = 0.03, P = 0.03, respectively). Cats treated with a higher concentration of insulin were less likely to have a poor outcome compared to cats treated with a lower concentration of insulin (odds ratio 0.14, 95% confidence interval 0.02-1.16, P = 0.02). CONCLUSIONS: Cats with DKA are more likely to be Siamese than cats with uncomplicated DM. Poor outcome of cats with DKA is associated with increased initial creatinine, BUN, total magnesium, and total bilirubin concentrations. Good outcome was associated with a higher concentration of IV insulin CRI.

Peritoneal dialysis in veterinary medicine.

Peritoneal dialysis is a modality of renal replacement therapy that is commonly used in human medicine for treatment of chronic kidney disease and end-stage kidney failure. Peritoneal dialysis uses the peritoneum as a membrane across which fluids and uremic solutes are exchanged. In this process, dialysate is instilled into the peritoneal cavity and, through the process of diffusion and osmosis, water, toxins, electrolytes, and other small molecules, are allowed to equilibrate.

Regression of juvenile idiopathic scoliosis.

For a young scoliotic boy the customary "wait and watch" management program for rapidly progressive juvenile idiopathic scoliosis was considered unsatisfactory in view of the poor prognosis. The management program devised was based on the congenital postural induction concept of scoliosis with progression accruing from mechanically induced bioengineering fatigue, cumulative molecular scissions, laxity of ligaments, and secondary bone deformation. A coexisting pelvic tilt with restricted movement of the hip and shoulder joints was overlooked initially. Possibly induced simultaneously with the scoliosis, it is considered a contributory factor in scoliosis progression and requires early diagnosis and correction. The rapid improvement in this child's spinal status achieved by physiological traction and specifically designed exercises was such that as a preventive measure the technique warrants further clinical assessment on young scoliotics.