NLRP3 activation and mitosis are mutually exclusive events coordinated by NEK7, a new inflammasome component.

The NLRP3 inflammasome responds to microbes and danger signals by processing and activating proinflammatory cytokines, including interleukin 1ß (IL-1ß) and IL-18. We found here that activation of the NLRP3 inflammasome was restricted to interphase of the cell cycle by NEK7, a serine-threonine kinase previously linked to mitosis. Activation of the NLRP3 inflammasome required NEK7, which bound to the leucine-rich repeat domain of NLRP3 in a kinase-independent manner downstream of the induction of mitochondrial reactive oxygen species (ROS). This interaction was necessary for the formation of a complex containing NLRP3 and the adaptor ASC, oligomerization of ASC and activation of caspase-1. NEK7 promoted the NLRP3-dependent cellular inflammatory response to intraperitoneal challenge with monosodium urate and the development of experimental autoimmune encephalitis in mice. Our findings suggest that NEK7 serves as a cellular switch that enforces mutual exclusivity of the inflammasome response and cell division.

Understanding the role of community pharmacies in current medication for opioid use disorder care practices.

BACKGROUND: Many barriers for patient access to medications for opioid use disorder (MOUD) exist in current care practices. Previous literature has evaluated subsets of pharmacists, patients, and prescribers; however, few have collectively evaluated the perspectives of all 3 groups. OBJECTIVE: The objective of the study was to identify barriers, facilitators, and opportunities for improvement in Indiana community pharmacy MOUD care practices from the perspectives of peer recovery coaches, community pharmacists, and prescribers to optimize patient care. METHODS: Individual semistructured interviews were conducted with each participant. Interviews explored stakeholders' perspectives on their current role in MOUD care practices and how current pharmacy practices could be improved. Data were analyzed using preconceived deductive and iterative inductive codes. The first author analyzed all transcripts, of which 3 were also analyzed separately by the last author to confirm consistent utilization of codes. All transcripts were coded once, followed by a second coding to ensure inductive codes were thoroughly applied. RESULTS: Ten peer recovery coaches, 10 pharmacists, and 6 prescribers were included. Interviews identified barriers, facilitators, and opportunities for improvement in current MOUD care practices. Stigma was a major barrier identified by all groups. Other barriers identified included limited patient engagement at pharmacies and lack of access to patient-specific health information in community pharmacy settings. Pharmacists also identified additional barriers including Drug Enforcement Administration regulations and difficulties balancing patient care with external factors like insurance and legal policies. Positive prescriber/pharmacist relationships were identified as a facilitator of care. Opportunities for improvement included having community MOUD resource information available at pharmacies, further education on MOUD for pharmacists, and increased collaboration between pharmacists and prescribers. CONCLUSION: Many barriers exist in current MOUD care practices. Additional pharmacist MOUD education and intentional collaboration between pharmacists, peer recovery coaches, and prescribers would facilitate better care and leverage the accessibility of pharmacists within their communities.

National survey identifying community pharmacist preceptors' experience, knowledge, attitudes, and behaviors influencing intent to recommend cannabidiol products.

OBJECTIVES: The primary study objective was to characterize community pharmacist preceptors' experience, clinical and legislative knowledge, attitudes, and behaviors regarding cannabidiol (CBD). The secondary study objective was to identify which of these factors influenced intent to recommend CBD products. METHODS: A 36-item survey was used to collect respondent demographics, experience, knowledge, attitudes, and behaviors regarding CBD. Items assessing attitudes, behaviors, and intent were developed using the Theory of Planned Behavior (TPB). Community pharmacist preceptors for schools of pharmacy across the United States were eligible to complete an electronic survey open for 12 weeks from January to April 2020. Descriptive statistics were used to summarize respondent demographics, experience, knowledge, and TPB constructs. Ordinal logistic regression was used to evaluate which factors influenced intent. RESULTS: The survey was disseminated to an estimated 2242 community pharmacist preceptors and received 295 responses (13.2% response rate). Of the 272 respondents who met eligibility criteria to progress through the survey, the survey was completed in its entirety by 236 respondents (86.8% completion rate). For experience items, most respondents (70.7%) reported receiving previous education on CBD. Almost half (48.4%) reported CBD sales in their pharmacies, whereas 89.1% reported answering clinical questions about CBD. For knowledge items, respondents performed poorly on CBD adverse effect and drug interaction items. Many respondents were not comfortable counseling on (49.0%) or recommending (56.1%) CBD products for patient use. Most (74.5%) believed more research was needed before they would feel comfortable recommending CBD products. Most (57.8%) reported not having reliable CBD resources available in their pharmacies. Subjective norms and previous CBD education or personal research were the only factors found to have direct influences on respondents' intent to recommend CBD products. CONCLUSION: Opportunities exist to fill knowledge gaps, enhance confidence, and provide desired educational resources for community pharmacist preceptors on CBD products.

Indiana community pharmacist preceptors' knowledge and perceptions of medication-assisted treatment.

OBJECTIVES: The study aim was to characterize the Indiana community-based pharmacist preceptors' knowledge and perceptions of medication-assisted treatment (MAT) for opioid use disorder (OUD). The secondary objectives were to explore the desired resources, dispensing concerns, and preceptors' involvement in precepting students. DESIGN: A 38-item survey was used to collect respondent demographics, knowledge, and perceptions of MAT for OUD. Perception questions were developed using the social cognitive theory and were adapted from previously published surveys with investigators' permission. SETTING: Community-based Indiana pharmacist preceptors were eligible to complete an electronic survey in February and March 2019. OUTCOME MEASURES: Descriptive statistics were used to characterize preceptor knowledge and perceptions of MAT for OUD. Desired MAT resources, dispensing concerns, and level of involvement in precepting students were collected. Respondent demographics were collected to characterize the study sample. RESULTS: Of the 116 survey responses, 104 were eligible, and 79 community-based pharmacist preceptors completed the survey, yielding a response rate of 76.0%. For knowledge questions, the overall correct score was 56.2%. Respondents had high correct scores on questions related to medication access. However, respondents either self-identified or performed poorly on the following knowledge items: Food and Drug Administration-approved MAT products for OUD, the need to provide an opioid-free interval before initiating treatment with buprenorphine and naltrexone, pregnancy recommendations, and treatment of severe OUD. Respondents reported positive perceptions on MAT for OUD, but identified concerns regarding diversion and misuse of MAT. Most respondents reported a desire for additional education on different aspects of MAT for OUD. Dispensing concerns and preceptors' involvement with students in MAT ranged from no concern and lack of involvement to many different concerns and full student involvement. CONCLUSION: Opportunities exist to fill identified gaps in knowledge, enhance perceptions, and provide desired continuing education for community-based pharmacist preceptors on MAT for OUD.

Perception of immunizations and vaccine recommendation sources for persons living with HIV compared with persons without HIV.

OBJECTIVES: To measure and compare the perception of immunizations, immunization status, and recommendation sources in persons living with HIV (PLWHs) and persons without HIV and determine a strategy for improving immunization rates by increasing awareness of pharmacy services. DESIGN: A 19-item survey based on the Health Belief Model assessed patients' perceptions and recommendation sources regarding immunization acceptance for specific vaccines: Tdap, pneumococcal, and hepatitis B (HepB). Survey items used a 5-point Likert-type scale assessing participants' perceptions, with questions identifying participants' most trusted sources of immunization information and patient demographics. Survey questions were designed to identify perceived susceptibility and severity of vaccine-preventable illness, barriers, benefits, and self-efficacy regarding immunization acceptance, and sources of patient-trusted immunization information. SETTING AND PARTICIPANTS: Survey recruitment occurred in Indiana and included any patient 18 years of age or older picking up medications at a specialty pharmacy predominantly serving PLWHs or a traditional community chain pharmacy. MAIN OUTCOME MEASURES: Primary outcomes included perceived barriers to immunization acceptance obtained from Likert-type scale questions, patient-reported immunization rates of selected vaccines (Tdap, pneumococcal pneumonia, and HepB), and trusted immunization recommendation sources. Logistic regression was performed to model association between perceived barriers, HIV status, and immunization recommendation sources. RESULTS: A total of 142 participants (68 PLWHs, 74 persons without HIV) completed the survey. PLWHs were more likely to have immunization barriers, but this was not statistically significant (odds ratio 2.537, 95% confidence interval 0.585-10.996). Both participant groups reported "family doctor" as the most trusted source, with only 5% selecting "pharmacist." Significantly fewer PLWHs reported completing the HepB series (18% vs. 52%; P = 0.0224). CONCLUSION: PLWHs possess barriers to immunization acceptance similar to persons without HIV yet report lower rates of HepB vaccine completion. Although pharmacists were less frequently selected as the most trusted source, additional studies on percptions of pharmacists' role in immunizing PLWHs should be considered.

Real-time resolution of point mutations that cause phenovariance in mice.

With the wide availability of massively parallel sequencing technologies, genetic mapping has become the rate limiting step in mammalian forward genetics. Here we introduce a method for real-time identification of N-ethyl-N-nitrosourea-induced mutations that cause phenotypes in mice. All mutations are identified by whole exome G1 progenitor sequencing and their zygosity is established in G2/G3 mice before phenotypic assessment. Quantitative and qualitative traits, including lethal effects, in single or multiple combined pedigrees are then analyzed with Linkage Analyzer, a software program that detects significant linkage between individual mutations and aberrant phenotypic scores and presents processed data as Manhattan plots. As multiple alleles of genes are acquired through mutagenesis, pooled "superpedigrees" are created to analyze the effects. Our method is distinguished from conventional forward genetic methods because it permits (1) unbiased declaration of mappable phenotypes, including those that are incompletely penetrant (2), automated identification of causative mutations concurrent with phenotypic screening, without the need to outcross mutant mice to another strain and backcross them, and (3) exclusion of genes not involved in phenotypes of interest. We validated our approach and Linkage Analyzer for the identification of 47 mutations in 45 previously known genes causative for adaptive immune phenotypes; our analysis also implicated 474 genes not previously associated with immune function. The method described here permits forward genetic analysis in mice, limited only by the rates of mutant production and screening.

Perceived utility of pharmacy licensure examination preparation tools.

OBJECTIVES: To identify board examination preparation tools most commonly used by recent pharmacy graduates and determine which tools are perceived as most valuable and representative of the actual content of licensure examinations. METHODS: An electronic survey was sent to all 2004 graduates of colleges of pharmacy in Indiana. Participants identified which specific preparation tools were used and rated tools based on usefulness, representativeness of licensure examination, and monetary value, and provided overall recommendations to future graduates. RESULTS: The most commonly used preparation tools were the Pharmacy Law Review Session offered by Dr. Thomas Wilson at Purdue University, the Complete Review for Pharmacy, Pre-NAPLEX, PharmPrep, and the Kaplan NAPLEX Review. Tools receiving high ratings in all categories included Dr. Wilson's Pharmacy Law Review Session, Pre-NAPLEX, Comprehensive Pharmacy Review, Kaplan NAPLEX Review, and Review of Pharmacy. CONCLUSIONS: Although no preparation tool was associated with a higher examination pass rate, certain tools were clearly rated higher than others by test takers.