Search

BackgroundCannabis exposures reported to the California Poison Control System increased following the initiation of recreational cannabis sales on 1 January 2018 (i.e., "commercialization"). We evaluated whether local cannabis control policies adopted by 2021 were associated with shifts in harmful cannabis exposures.MethodsUsing cannabis control policies collected for all 539 California cities and counties in 2020-2021, we applied a differences-in-differences design with negative binomial regression to test the association of policies with harmful cannabis exposures reported to California Poison Control System (2011-2020), before and after commercialization. We considered three policy categories: bans on storefront recreational retail cannabis businesses, overall restrictiveness, and specific recommended provisions (restricting product types or potency, packaging and labeling restrictions, and server training requirements).ResultsLocalities that ultimately banned storefront recreational retail cannabis businesses had fewer harmful cannabis exposures for children aged 13 years (rate ratio = 0.97; 95% confidence interval = 0.85, 1.11). Of 167 localities ultimately permitting recreational cannabis sales, overall restrictiveness was not associated with harmful cannabis exposures among children aged 13 years, a 1-standard deviation increase in ultimate restrictiveness was associated with fewer harmful cannabis exposures (rate ratio = 0.93; 95% confidence interval = 0.86, 1.01). For recommended provisions, estimates were generally too imprecise to detect associations with harmful cannabis exposures.ConclusionBans on storefront retail and other restrictive approaches to regulating recreational cannabis may be associated with fewer harmful cannabis exposures for some age groups following statewide commercialization.

Tumor evolution is driven by the progressive acquisition of genetic and epigenetic alterations that enable uncontrolled growth and expansion to neighboring and distal tissues. The study of phylogenetic relationships between cancer cells provides key insights into these processes. Here, we introduced an evolving lineage-tracing system with a single-cell RNA-seq readout into a mouse model of Kras;Trp53(KP)-driven lung adenocarcinoma and tracked tumor evolution from single-transformed cells to metastatic tumors at unprecedented resolution. We found that the loss of the initial, stable alveolar-type2-like state was accompanied by a transient increase in plasticity. This was followed by the adoption of distinct transcriptional programs that enable rapid expansion and, ultimately, clonal sweep of stable subclones capable of metastasizing. Finally, tumors develop through stereotypical evolutionary trajectories, and perturbing additional tumor suppressors accelerates progression by creating novel trajectories. Our study elucidates the hierarchical nature of tumor evolution and, more broadly, enables in-depth studies of tumor progression.

IntroductionSince 2012, eighteen states and the District of Columbia have legalized recreational cannabis. Past research suggests this policy change is associated with increased cannabis exposures however this has not yet been studied in California, despite its status as the world's largest legal cannabis market.MethodsThis observational, retrospective study analyzed trends in cannabis exposures reported to the California Poison Control System (CPCS) from 2010 to 2020. We assessed shifts in exposures before and after the legalization of recreational cannabis in November 2016, the establishment of recreational retail sales in January 2018, and the institution of a statewide shelter-in-place order due to the COVID-19 pandemic in March 2020 using interrupted time-series analysis and reviewed all records to identify specific products associated with exposures.ResultsBetween 2010 and 2020 edible exposures increased from near zero to 79% of exposures in 2020. Cannabis exposures significantly increased following recreational legalization in 2016 (by an estimated 2.07 exposures per month [CI: 0.60, 3.55]; p

IntroductionIn response to the opioid epidemic, California state officials sought to fund a variety of projects aimed at reducing opioid-related deaths. We describe the California Poison Control System's (CPCS) successful effort in integrating itself into the state's public health response to the opioid epidemic and describe poison control center staff attitudes and perceptions regarding the role of poison control centers at treating opioid withdrawal and addiction.MethodsThe CPCS created a leadership team and a separate 24/7 hotline, called the CPCS-Bridge line, to field calls from frontline health care providers interested in initiating medications for opioid use disorder for their patients. The implementation process also included training of all CPCS staff. In addition, the leadership team conducted an anonymous survey study to analyze attitudes and perceptions of poison center staff on the role of the poison center in the management of opioid use disorder. Descriptive statistics were used to characterize the data.ResultsCalls to the new hotline increased over time, along with CPCS-initiated outreach and advertisement. A majority of questions received by the hotline were related to uncomplicated buprenorphine starts in special populations. A pre-training survey was completed by 27 (58%) of CPCS specialists, many of whom had no prior experience treating patients with opioid use disorder. Only one specialist (2%) did not believe that poison centers should play a role in opioid addiction.ConclusionsThe California Poison Control System successfully created a hotline to assist frontline health care providers in treating patients with opioid use disorder and highlight the critical role of poison centers in the public health domain. Increased federal funding to poison centers is likely to be mutually beneficial to all parties involved.

Parthenolide, a natural product from the feverfew plant and member of the large family of sesquiterpene lactones, exerts multiple biological and therapeutic activities including anti-inflammatory and anti-cancer effects. Here, we further study the parthenolide mechanism of action using activity-based protein profiling-based chemoproteomic platforms to map additional covalent targets engaged by parthenolide in human breast cancer cells. We find that parthenolide, as well as other related exocyclic methylene lactone-containing sesquiterpenes, covalently modify cysteine 427 of focal adhesion kinase 1 (FAK1), leading to impairment of FAK1-dependent signaling pathways and breast cancer cell proliferation, survival, and motility. These studies reveal a functional target exploited by members of a large family of anti-cancer natural products.

BackgroundTapentadol (TAP) and tramadol (TRA) provide pain relief through similar monoaminergic and opioid agonist properties.ObjectiveTo compare clinical effects and medical outcomes between TAP and TRA exposures reported to the National Poison Data System of the American Association of Poison Control Centers.MethodsA retrospective cohort study was conducted analyzing national data for single medication TAP or TRA cases reported from June 2009 through December 2011. Case outcomes, dichotomized as severe versus mild; clinical effects; and use of naloxone were compared.ResultsThere were 217 TAP and 8566 TRA cases. Significantly more severe outcomes were associated with TAP exposures for an all-age comparison (relative risk [RR] = 1.24; 95% CI = 1.04-1.48), and for the

ObjectivesThe Internet may be the first source of information used by parents during a suspected poisoning of their children. Our primary aim was to assess the reliability of the Internet as a resource for information for parents to initially manage a suspected poisoning involving their child without outside consultation.MethodsWe distributed a self-administered survey to English-speaking parents to evaluate their Internet access behaviors so we could emulate their search strategies for a poisoning. A panel of clinical toxicologists performed an evaluation of Websites to determine the proportion that provided accurate and adequate information on common substances involved in poisonings.ResultsOf 21 parents surveyed, 15 (71%) used the Internet daily, with Google and Yahoo being the most commonly used search engines. Seven parents (39%) were somewhat to very likely to utilize the Internet during a poisoning scenario with prescription medications involving their child. Overall, only 27 (38%) of the Websites reviewed advised the user to call the poison center with the proper 800 telephone number, whereas no Website provided adequate information to manage the poisoning without outside consultation. Few Websites provided information on the toxic dose (13%), how to determine whether to manage the poisoning at home or in a hospital (22%), or first aid (28%).ConclusionsThe information provided on the Internet for substances involved in poisonings is variable and often incomplete. Reliance on the Internet for poisonings could create needless delays and inappropriate assessments and actions to manage a pediatric poisoning incident.

Objectives: The COVID-19 pandemic led to widespread fear of infection, with many people expanding their use of cleaning products and trying unproven prevention and treatment strategies. We described shifts in reported exposures related to COVID-19 home interventions. Methods: This study considered suspected toxicity exposures involving household cleaning products (bleach, peroxide, disinfectants), antimalarials (hydroxychloroquine and chloroquine), and ivermectin reported to the California Poison Control System from 2015 through 2021 and assessed trends in exposures by using interrupted time-series analyses. Results: We found a significant increase in exposures reported to the California Poison Control System related to household cleaning products and ivermectin during the COVID-19 pandemic. As of January 1, 2015, the baseline level of reported exposures to household cleaning products was 707.33 per month and was declining at a rate of 1.71 (95% CI, –2.87 to –0.56) per month through February 29, 2020. In March 2020, an increase of 466.57 (95% CI, 328.08-605.07) reported exposures above baseline occurred, after which exposures to cleaning products decreased at a rate of 23.40 (95% CI, –32.48 to –14.32) per month. The number of reported exposures to antimalarials did not change significantly before or during the pandemic. The number of reported ivermectin exposures before December 2020 was initially stable at 14.50 per month and then increased by 2.05 per month through December 2021. Conclusions: Our observations suggest that while some dangerous home prevention and treatment efforts resolve over time, further interventions may be needed to reduce the public health effects related to attempts to self-treat COVID-19 with ivermectin. [ABSTRACT FROM AUTHOR]

Introduction: Trendelenburg position (TP) is used to transport gaseous emboli away from the cerebral region during cardiac surgery. However, TP effectiveness has not been fully considered when combined with varying the cardiopulmonary bypass (CPB) flow. This study simulated the supine and TP at different pump flows and assessed the trapped emboli and embolic load entering the aortic arch branch arteries (AABA). Methods: A computational fluid dynamics (CFD) approach used a centrally cannulated adult patient-specific aorta model replicating a CPB circuit. Air emboli of 0.1 mm, 0.5 mm, and 1.0 mm (n = 700 each) were injected into the aorta placed in the supine position (0°) and the TP (−20°) at 2 L/min and 5 L/min. The number of emboli entering the AABA were compared. An aortic phantom flow experiment was performed to validate air bubble behaviour. Results: TP at 5 L/min had the lowest 0.1 mm mean (±SD) embolic load compared to the supine 2 L/min (55.3 ± 30.8 vs 64.3 ± 35.4). For both the supine and TP, the lower flow of 2 L/min had the highest number of simulated trapped emboli in higher elevated regions than at 5 L/min (541 ± 185 and 548 ± 191 vs 520 ± 159 and 512 ± 174), respectively. The flow experiment demonstrated that 2 L/min promoted bubble coalescence and high amounts of trapped emboli and 5 L/min transported air emboli away from the AABA. Conclusions: TP effectiveness was improved by using CPB flow to manage air emboli. These results provide insights for predicting emboli behaviour and improving emboli de-airing procedures. [ABSTRACT FROM AUTHOR]

Introduction: Varying the insertion depth of the aortic cannula during cardiopulmonary bypass (CPB) has been investigated as a strategy to mitigate cerebral emboli, yet its effectiveness associated with CPB flow is not fully understood. We compared different arterial cannula insertion depths and pump flow influencing air microemboli entering the aortic arch branch arteries (AABA). Methods: A computational approach used a patient-specific aorta model to evaluate four cannula locations at (1) proximal arch, (2) mid arch, (3) distal arch, and (4) descending aorta. We injected 0.1 mm microemboli (N=720) at 2 and 5 L/min and assessed the embolic load and the particle averaged transit times (entering the AABA. Results: Location 4 had the lowest embolic load (2 L/min: N= 63) and (5 L/min: N= 54) compared to locations 1 to 3 in the range of (N= 118 to 116 at 2 L/min:) and (N= 92 to 146 at 5 L/min). There was no significant difference between 2 L/min and 5 L/min (p = 0.31), despite 5 L/min attaining a lower mean (±standard deviation) than 2 L/min (38.0±23.4 vs 44.5±21.1), respectively. Progressing from location 1 to 4, increased 3.11s -7.40 s at 2 L/min and 1.81s -4.18s at 5 L/min. Conclusion: It was demonstrated that the elongated cannula insertion length resulted in lower embolic loads, particularly at a higher flow rate. The numerical results suggest that CPB management could combine active flow variation with improving cannula performance and provide a foundation for a future experimental and clinical investigation to reduce surgical cerebral air microemboli. [ABSTRACT FROM AUTHOR]

This article compares Chinese students' responses to local Chinese versus American professors, and the effectiveness of the professors' respective teaching techniques. A case study made at a single university in China, which had a joint academic program with the United States, found that Chinese students preferred local Chinese professors to American professors in spite of the students' perception that the American professors' were more highly qualified, and despite the American professors' student-centered teaching styles. The Chinese students consider local Chinese professors to be more effective in teaching and they have higher expectation of the Chinese students than the U.S. professors. This article explores the differences between Chinese and Western teaching styles and proposes approaches needed to guide Chinese students from their familiar teacher-centered classrooms toward accepting a student-centered classroom approach. Recommendations are offered for improving Western ways of educating Chinese students in China. (Contains 5 tables.)