Impact of CancelRx on discontinuation of controlled substance prescriptions: an interrupted time series analysis.

BACKGROUND: Prescription opioid misuse is a serious national crisis; in 2018 the top drugs involved in prescription overdose deaths included pain medications (opioids), benzodiazepines, and stimulants. Health information technology (health IT) provides a means to address this crisis through technologies that streamline the prescribing and discontinuation process. CancelRx is a health IT function that communicates when medications, such as controlled substances, are discontinued at the clinic and therefore should not be filled at the pharmacy. Prior to CancelRx, the communication of discontinued medications was a manual process, requiring the patient or a clinic staff member to personally contact the pharmacy to inform them of the change. The objective of this study was to assess how controlled substance medication discontinuations were communicated over time, before and after the implementation of CancelRx. METHODS: Secondary data from a midwestern academic health system electronic health record and pharmacy platform were collected 12-months prior to CancelRx implementation and for 12-months post implementation. The study utilized an interrupted time series analysis (ITSA) to capture the percentage of controlled substance medications that were discontinued in the clinic's electronic health record and discontinued in the pharmacy's dispensing software. The ITSA plotted the percentage of successful discontinuation messages over time, particularly after the health system's implementation of CancelRx, a novel technology. RESULTS: After CancelRx implementation there was an immediate (change = 77.7 percentage point) and significant (p < 0.001) increase in the number of controlled substance medications that were successfully discontinued at the pharmacy after being discontinued in the clinic. This change was sustained in the year following CancelRx (slope = 0.03 pp, 95% CI - 0.050 to 0.110) and did not revert to pre-CancelRx levels. The health IT functionality was able to effectively complete discontinuation tasks and potentially reduce workload for clinic staff. CONCLUSIONS: Overall, this study demonstrates the role that technology can play in promoting communication between clinics and pharmacies, especially when medications such as controlled substances are discontinued.

Gut microbiota from high-risk men who have sex with men drive immune activation in gnotobiotic mice and in vitro HIV infection.

Men who have sex with men (MSM) have differences in immune activation and gut microbiome composition compared with men who have sex with women (MSW), even in the absence of HIV infection. Gut microbiome differences associated with HIV itself when controlling for MSM, as assessed by 16S rRNA sequencing, are relatively subtle. Understanding whether gut microbiome composition impacts immune activation in HIV-negative and HIV-positive MSM has important implications since immune activation has been associated with HIV acquisition risk and disease progression. To investigate the effects of MSM and HIV-associated gut microbiota on immune activation, we transplanted feces from HIV-negative MSW, HIV-negative MSM, and HIV-positive untreated MSM to gnotobiotic mice. Following transplant, 16S rRNA gene sequencing determined that the microbiomes of MSM and MSW maintained distinct compositions in mice and that specific microbial differences between MSM and MSW were replicated. Immunologically, HIV-negative MSM donors had higher frequencies of blood CD38+ HLADR+ and CD103+ T cells and their fecal recipients had higher frequencies of gut CD69+ and CD103+ T cells, compared with HIV-negative MSW donors and recipients, respectively. Significant microbiome differences were not detected between HIV-negative and HIV-positive MSM in this small donor cohort, and immune differences between their recipients were trending but not statistically significant. A larger donor cohort may therefore be needed to detect immune-modulating microbes associated with HIV. To investigate whether our findings in mice could have implications for HIV replication, we infected primary human lamina propria cells stimulated with isolated fecal microbiota, and found that microbiota from MSM stimulated higher frequencies of HIV-infected cells than microbiota from MSW. Finally, we identified several microbes that correlated with immune readouts in both fecal recipients and donors, and with in vitro HIV infection, which suggests a role for gut microbiota in immune activation and potentially HIV acquisition in MSM.

Impact of a pilot community pharmacy system redesign on reducing over-the-counter medication misuse in older adults.

BACKGROUND: No interventions have attempted to decrease misuse of over-the-counter (OTC) medications for adults aged 65 years or older (older adults) by addressing system barriers. An innovative structural pharmacy redesign (the Senior Section) was conceptualized to increase awareness of higher-risk OTC medications. The Senior Section contains a curated selection of OTC medications and is close to the prescription department to facilitate pharmacy staff-patient engagement to reduce misuse. OBJECTIVE: This pilot study examined the Senior Section's effectiveness at influencing OTC medication misuse in older adults. METHODS: A pretest-post-test nonequivalent groups design was used to recruit 87 older adults from 3 pharmacies. Using a hypothetical scenario, the participants selected an OTC medication that was compared with their medication list and health conditions, and their reported use was compared with the product labeling. Misuse outcomes comprised drug-drug, drug-disease, drug-age, and drug-label, with 5 subtypes. Patient characteristics were compiled into a propensity score matching logistic regression model to estimate their effects on the Senior Section's association with misuse at pre- or postimplementation. RESULTS: Patient characteristics were uniform between pre- and postimplementation, and, once entered into a propensity score matching model, drug-label misuse (exceeds daily dosage) statistically significantly lessened over time (z = -2.42, P = 0.015). In addition, the Senior Section reduced drug-label misuse (exceeds single dosage) for both the raw score model (z = -6.38, P = 0.011) and the model in which the patient characteristics propensity score was added (z = -5.82, P = 0.011). Despite these limited statistical effects, misuse was found to decrease after implementation for 7 of 11 comparisons. CONCLUSION: These nascent outcomes begin providing an evidence base to support a well-conceived, pharmacy-based OTC medication-aisle redesign for reducing older adult OTC medication misuse. The Senior Section, when broadly implemented, creates permanent structures and processes to assist older adults to access risk information when selecting safer OTC medications.

Environmentally prevalent polycyclic aromatic hydrocarbons can elicit co-carcinogenic properties in an in vitro murine lung epithelial cell model.

Low molecular weight (LMW) polycyclic aromatic hydrocarbons (PAH) are the most abundant PAHs environmentally, occupationally, and are in cigarette smoke; however, little is known about their carcinogenic potential. We hypothesized that LMW PAHs act as co-carcinogens in the presence of a known carcinogen (benzo[a]pyrene (B[a]P)) in a mouse non-tumorigenic type II cell line (C10 cells). Gap junctions are commonly suppressed and inflammation induced during tumor promotion, while DNA-adduct formation is observed during the initiation stage of cancer. We used these endpoints together as markers of carcinogenicity in these lung adenocarcinoma progenitor cells. LMW PAHs (1-methylanthracene and fluoranthene, 1-10 µM total in a 1:1 ratio) were used based on previous studies as well as B[a]P (0-3 µM) as the classic carcinogen; non-cytotoxic doses were used. B[a]P-induced inhibition of gap junctional intercellular communication (GJIC) was observed at low doses and further reduced in the presence of the LMW PAH mixture (P < 0.05), supporting a role for GJIC suppression in cancer development. Benzo[a]pyrene diol-epoxide (BPDE)-DNA adduct levels were significantly induced in B[a]P-treated C10 cells and additionally increased with the LMW PAH mixture (P < 0.05). Significant increases in cyclooxygenase (Cox-2) were observed in response to the B[a]P/LMW PAH mixture combinations. DNA adduct formation coincided with the inhibition of GJIC and increase in Cox-2 mRNA expression. Significant cytochrome p4501b1 increases and connexin 43 decreases in gene expression were also observed. These studies suggest that LMW PAHs in combination with B[a]P can elicit increased carcinogenic potential. Future studies will further address the mechanisms of co-carcinogenesis driving these responses.

Epiregulin is required for lung tumor promotion in a murine two-stage carcinogenesis model.

Adenocarcinoma accounts for ∼40% of lung cancer, equating to ∼88 500 new patients in 2015, most of who will succumb to this disease, thus, the public health burden is evident. Unfortunately, few early biomarkers as well as effective therapies exist, hence the need for novel targets in lung cancer treatment. We previously identified epiregulin (Ereg), an EGF-like ligand, as a biomarker in several mouse lung cancer models. In the present investigation we used a primary two-stage initiation/promotion model to test our hypothesis that Ereg deficiency would reduce lung tumor promotion in mice. We used 3-methylcholanthrene (initiator) or oil vehicle followed by multiple weekly exposures to butylated hydroxytoluene (BHT; promoter) in mice lacking Ereg (Ereg-/- ) and wildtype controls (BALB/ByJ; Ereg+/+ ) and examined multiple time points and endpoints (bronchoalveolar lavage analysis, tumor analysis, mRNA expression, ELISA, wound assay) during tumor promotion. At the early time points (4 and 12 wk), we observed significantly reduced amounts of inflammation (macrophages, PMNs) in the Ereg-/- mice compared to controls (Ereg+/+ ). At 20 wk, tumor multiplicity was also significantly decreased in the Ereg-/- mice versus controls (Ereg+/+ ). IL10 expression, an anti-inflammatory mediator, and downstream signaling events (Stat3) were significantly increased in the Ereg-/- mice in response to BHT, supporting both reduced inflammation and tumorigenesis. Lastly, wound healing was significantly increased with recombinant Ereg in both human and mouse lung epithelial cell lines. These results indicate that Ereg has proliferative potential and may be utilized as an early cancer biomarker as well as a novel potential therapeutic target. © 2016 Wiley Periodicals, Inc.

Differential innate immune cell signatures and effects regulated by toll-like receptor 4 during murine lung tumor promotion.

Tumor promotion is an early and critical stage during lung adenocarcinoma (ADC). We previously demonstrated that Tlr4 mutant mice were more susceptible to butylated hydroxytoluene (BHT)-induced pulmonary inflammation and tumor promotion in comparison to Tlr4-sufficient mice. Our study objective was to elucidate the underlying differences in Tlr4 mutant mice in innate immune cell populations, their functional responses, and the influence of these cellular differences on ADC progenitor (type II) cells following BHT-treatment. BALB (Tlr4-sufficient) and C.C3-Tlr4(Lps-d)/J (BALB(Lpsd); Tlr4 mutant) mice were treated with BHT (promoter) followed by bronchoalveolar lavage (BAL) and flow cytometry processing on the lungs. ELISAs, Club cell enrichment, macrophage function, and RNA isolation were also performed. Bone marrow-derived macrophages (BMDM) co-cultured with a type II cell line were used for wound healing assays. Innate immune cells significantly increased in whole lung in BHT-treated BALB(Lpsd) mice compared to BALB mice. BHT-treated BALB(Lpsd) mice demonstrated enhanced macrophage functionality, increased epithelial wound closure via BMDMs, and increased Club cell number in BALB(Lpsd) mice, all compared to BALB BHT-treated mice. Cytokine/chemokine (Kc, Mcp1) and growth factor (Igf1) levels also significantly differed among the strains and within macrophages, gene expression, and cell surface markers collectively demonstrated a more plastic phenotype in BALB(Lpsd) mice. Therefore, these correlative studies suggest that distinct innate immune cell populations are associated with the differences observed in the Tlr4-mutant model. Future studies will investigate the macrophage origins and the utility of the pathways identified herein as indicators of immune system deficiencies and lung tumorigenesis.

Community Health Workers to Increase Cancer Screening: 3 Community Guide Systematic Reviews.

INTRODUCTION: Many in the U.S. are not up to date with cancer screening. This systematic review examined the effectiveness of interventions engaging community health workers to increase breast, cervical, and colorectal cancer screening. METHODS: Authors identified relevant publications from previous Community Guide systematic reviews of interventions to increase cancer screening (1966 through 2013) and from an update search (January 2014-November 2021). Studies written in English and published in peer-reviewed journals were included if they assessed interventions implemented in high-income countries; reported screening for breast, cervical, or colorectal cancer; and engaged community health workers to implement part or all of the interventions. Community health workers needed to come from or have close knowledge of the intervention community. RESULTS: The review included 76 studies. Interventions engaging community health workers increased screening use for breast (median increase=11.5 percentage points, interquartile interval=5.5‒23.5), cervical (median increase=12.8 percentage points, interquartile interval=6.4‒21.0), and colorectal cancers (median increase=10.5 percentage points, interquartile interval=4.5‒17.5). Interventions were effective whether community health workers worked alone or as part of a team. Interventions increased cancer screening independent of race or ethnicity, income, or insurance status. DISCUSSION: Interventions engaging community health workers are recommended by the Community Preventive Services Task Force to increase cancer screening. These interventions are typically implemented in communities where people are underserved to improve health and can enhance health equity. Further training and financial support for community health workers should be considered to increase cancer screening uptake.

Utilizing a cognitive engineering approach to conduct a hierarchical task analysis to understand complex older adult decision-making during over-the-counter medication selection.

BACKGROUND: Adults aged 65+ (older adults) disproportionately consume 30% of over-the-counter (OTC) medications and are largely responsible for making OTC treatment decisions because providers lack awareness of their consumption. These treatment decisions are complex: older adults must navigate age-related body/cognitive changes, developed comorbidities, and complex medication regimens when selecting the right OTC. Yet little is known about how older adults make such decisions. OBJECTIVES: This study characterizes older adults' cognitive decision-making process when seeking to self-medicate with OTCs from their community pharmacy, and demonstrates how hierarchical task analysis (HTA) can be used to evaluate a pharmacy intervention's impact on their decision-making. METHODS: A pre-/post-implementation approach, using a think-aloud interview process, was conducted with older adults within a community pharmacy setting as they completed a hypothetical scenario to treat either pain, sleep, or cough/cold/allergy symptoms. HTA developed a conceptualization of older adult decision-making regarding OTC selection and use before/after Senior Section implementation. RESULTS: An HTA constructed from 12 purposefully-selected interviews (pre-n = 9/post-n = 3), consisting of 8 goals/15 sub-goals. While selecting an OTC, older adults considered quantity, cost, form, regimen, safety, strength, appropriateness of OTC safety, generic/name-brand, past experiences, and ingredients. The intervention reduced by half the number of factors considered. IMPLICATIONS: Older adult decision-making is more complex than just selecting OTC medication from a pharmacy shelf. HTA-informed decision profiles can provide pharmacists critical insights into safety issues that older adults may not be considering (e.g., factors related to safety, strength, or appropriateness of OTC for symptoms) so that pharmacists can support their decision-making.

A pharmacy-based intervention to improve safe over-the-counter medication use in older adults.

BACKGROUND: For older adults, health risks from inappropriate use of over-the-counter (OTC) medications represent a prevalent clinical and public health challenge. Focus groups with pharmacists led to the identification of a number of systems barriers to pharmacists supporting the safe selection and use of OTC medications by this population. Such feedback informed the development of the Senior Section™, a physical redesign that located a curated inventory of lower-risk OTC medications proximal to the prescription department. OBJECTIVES: To determine whether implementation of the Senior Section resulted in improvements to the ability of pharmacy staff to engage with older adult patients to support OTC medication safety issues. METHODS: A qualitative approach, in which pharmacy staff from 4 pharmacies within a single chain participated in a semi-structured interview, was used to evaluate the implementation of the Senior Section in their pharmacies. Interview transcripts underwent a deductive and iterative content analysis. RESULTS: Eight pharmacists and 5 technicians were interviewed. They viewed the Senior Section as contributing to notable improvements in proximity, medication safety, convenience, and patient selection behaviors. The Senior Section's safer OTC inventory and its sectional layout, its relationship to the prescription department, and its signage served to enhance its usefulness as an OTC safety improvement intervention. Moreover, it functioned beneficially while streamlining the coordination of services with between pharmacists and technicians, and did not interfere with existing pharmacy workflows. CONCLUSIONS: Pharmacy staff believed that the Senior Section facilitated their ability to engage with older adults to support safe OTC selection and use and thus to reduce OTC-related harms.

Using a scenario-based hybrid approach to understand participant health behavior.

BACKGROUND: Qualitative and mixed methods approaches are commonly used to understand participants' interactions with real-world settings and can help health services researchers to obtain realistic details about patients' health behaviors. However, interviews do not easily capture data about how patients perform health-related behaviors that are not part of their daily routine. A scenario-based approach is one method that can be used prospectively to explore how patients make decisions about their health-related behaviors. This approach is comprised of a set of small tailored probable circumstances with equally plausible situations, and are presented as narrative descriptions. To understand how older adults, a group at high-risk for OTC misuse, select over-the-counter (OTC) medication qualitative methods can be used. OBJECTIVES: This study describes a scenario-based hybrid approach that included a simulation exercise and a situational interview to understand how older adults first select and then take OTC medication. METHODS: The scenario-based hybrid approach consisted of 1) a simulation exercise to emulate participants' real-world experiences as they selected a medication in a store, followed by 2) a situational interview to capture how participants intended to take the medication they selected. Video recordings captured interview data as well as participants' body language, navigation patterns, and other nuanced data that would not have been captured in audio recordings. RESULTS/CONCLUSION: The scenario-based hybrid approach not only yielded detailed information about behavior, but also allowed investigators to discern participants' decision-making, influences, and the rationales they use when selecting and taking OTC medications. Studies aiming to capture participants' behavior in naturalistic situations can use these techniques to draw inferences from direct and indirect visual references that may not be captured otherwise. In this study, the goal was to understand how older adult participants select and take OTC medications. This approach allowed the research team to expediently recreate situations in which participants would purchase an OTC medication, a task that may not occur frequently and thus may not be amenable to participant observation or accurately recalled using retrospective interviewing.

FAM171B is a novel polyglutamine protein widely expressed in the mammalian brain.

Mutation in proteins containing polyglutamine (polyQ) tracts has been shown to underlie a number of severe human neurodegenerative disorders such as Huntington's Disease and Spinocerebellar Ataxia. In this study, we identify and describe FAM171B as a novel polyQ protein containing fourteen consecutive glutamine residues in its National Center for Biotechnology Information (NCBI) referenced sequence. Utilizing western blotting, in situ hybridization, and immunohistochemistry, we demonstrate that FAM171B is widely expressed in mouse brain with pronounced localization in the hippocampus, cerebellum, and cerebral cortex. Furthermore, immunofluorescence experiments reveal that FAM171B predominantly localizes to vesicle-like structures in the cytoplasm of neurons. Finally, bioinformatic analysis suggests that FAM171B is robustly expressed in human brain, and (similar to other polyQ disease genes) its polyQ tract is polymorphic within the general human population. Thus, as a polyQ protein that is expressed in brain, FAM171B should be considered a candidate gene for an as yet molecularly uncharacterized neurodegenerative disease.

CancelRx: a health IT tool to reduce medication discrepancies in the outpatient setting.

OBJECTIVE: Medication list discrepancies between outpatient clinics and pharmacies can lead to medication errors. Within the last decade, a new health information technology (IT), CancelRx, emerged to send a medication cancellation message from the clinic's electronic health record (EHR) to the outpatient pharmacy's software. The objective of this study was to measure the impact of CancelRx on reducing medication discrepancies between the EHR and pharmacy dispensing software. MATERIALS AND METHODS: CancelRx was implemented in October 2017 at an academic health system. For 12 months prior, and 12 months after CancelRx implementation, data were collected on discontinued medications in the health system's EHR and whether those prescriptions were successfully discontinued in the pharmacy's dispensing software. An interrupted time series analysis was conducted to model the occurrence of prescriptions successfully discontinued over time. RESULTS: There was an immediate (lag = 0), significant (P < 0.001), and sustained (post-implementation slope 0.02) increase in the proportion of successful medication discontinuations after CancelRx implementation (from 34% to 93%). CancelRx had variable impact based on whether the clinic was primary care (71.4% change prepost) or specialty care (53.9% change prepost). CancelRx reduced the time between when a medication was discontinued in the clinic EHR and pharmacy dispensing software. CONCLUSION: CancelRx automated a manual process and illustrated the role for health IT in communicating medication discontinuations between clinics and pharmacies. Overall, CancelRx had a marked benefit on medication list discrepancies and illustrated how health IT can be used across different settings to improve patient care.

Improving Patient-Pharmacist Encounters with Over-The-Counter Medications: A Mixed-Methods Pilot Study.

BACKGROUND AND OBJECTIVES: Over-the-counter (OTC) medication use has increased safety risks for adults older than 65. Most older adults purchase OTC medications from community pharmacies, where the considerable distance or visual obstructions between the prescription area and OTC aisles undermine pharmacists' ability to assist patients with OTC medication decisions. An innovative redesign of an abbreviated medication section specifically for older adults (called the Senior SectionTM ) can facilitate pharmacy staff/patient interaction, potentially improving safe medication selection and use. This study evaluated the impact of the Senior Section on the frequency and content of OTC encounters between pharmacy staff and patients. RESEARCH DESIGN AND METHODS: An intervention mixed-methods design generated data from patient OTC encounters, and interviews with two pharmacists and two technicians, throughout the study. NVivo was used to code interview transcripts, and frequencies and chi-square analyses demonstrated pre/post-intervention comparisons for the OTC encounter variables. RESULTS: After Senior Section implementation, pharmacy staff were more likely to initiate (and be involved in) patient encounters, address more topics or problem/symptoms, provide details about OTC products, discuss appropriateness of OTC use, and discuss medication classes highlighted in the Senior Section. Pharmacy staff were less likely to need to leave the prescription department for extended periods; they also had fewer prolonged encounters or encounters about product location. Importantly, the Senior Section did not impede pharmacy workflow. DISCUSSION AND IMPLICATIONS: The Senior Section prompted more frequent, effective, and efficient engagements between pharmacy staff and patients, which may substantially reduce OTC-related harms among older adults.

Team-Based Care to Improve Diabetes Management: A Community Guide Meta-analysis.

CONTEXT: Team-based care has been increasingly used to deliver care for patients with chronic conditions, but its effectiveness for managing diabetes has not been systematically assessed. EVIDENCE ACQUISITION: RCTs were identified from two sources: a high-quality, broader review comparing 11 quality improvement strategies for diabetes management (database inception to July 2010), and an updated search using the same search strategy (July 2010-October 2015). EVIDENCE SYNTHESIS: Thirty-five studies were included in the current review; a majority focused on patients with Type 2 diabetes. Teams included patients, their primary care providers, and one or two additional healthcare professionals (most often nurses or pharmacists). Random effect meta-analysis showed that, compared with controls, team-based care was associated with greater reductions in blood glucose levels (-0.5% in HbA1c, 95% CI= -0.7, -0.3) and greater improvements in blood pressure and lipid levels. Interventions also increased the proportion of patients who reached target blood glucose, blood pressure, and lipid levels, based on American Diabetes Association guidelines available at the time. Data analysis was completed in 2016. CONCLUSIONS: For patients with Type 2 diabetes, team-based care improves blood glucose, blood pressure, and lipid levels.

Economics of Community Health Workers for Chronic Disease: Findings From Community Guide Systematic Reviews.

CONTEXT: Cardiovascular disease in the U.S. accounted for healthcare cost and productivity losses of $330 billion in 2013-2014 and diabetes accounted for $327 billion in 2017. The impact is disproportionate on minority and low-SES populations. This paper examines the available evidence on cost, economic benefit, and cost effectiveness of interventions that engage community health workers to prevent cardiovascular disease, prevent type 2 diabetes, and manage type 2 diabetes. EVIDENCE ACQUISITION: Literature from the inception of databases through July 2016 was searched for studies with economic information, yielding nine studies in cardiovascular disease prevention, seven studies in type 2 diabetes prevention, and 13 studies in type 2 diabetes management. Analyses were done in 2017. Monetary values are reported in 2016 U.S. dollars. EVIDENCE SYNTHESIS: The median intervention cost per patient per year was $329 for cardiovascular disease prevention, $600 for type 2 diabetes prevention, and $571 for type 2 diabetes management. The median change in healthcare cost per patient per year was -$82 for cardiovascular disease prevention and -$72 for type 2 diabetes management. For type 2 diabetes prevention, one study saw no change and another reported -$1,242 for healthcare cost. One study reported a favorable 1.8 return on investment from engaging community health workers for cardiovascular disease prevention. Median cost per quality-adjusted life year gained was $17,670 for cardiovascular disease prevention, $17,138 (mean) for type 2 diabetes prevention, and $35,837 for type 2 diabetes management. CONCLUSIONS: Interventions engaging community health workers are cost effective for cardiovascular disease prevention and type 2 diabetes management, based on a conservative $50,000 benchmark for cost per quality-adjusted life year gained. Two cost per quality-adjusted life year estimates for type 2 diabetes prevention were far below the $50,000 benchmark.

Secondhand Smoke-Prevalent Polycyclic Aromatic Hydrocarbon Binary Mixture-Induced Specific Mitogenic and Pro-inflammatory Cell Signaling Events in Lung Epithelial Cells.

Low molecular weight polycyclic aromatic hydrocarbons (LMW PAHs; < 206.3 g/mol) are prevalent and ubiquitous environmental contaminants, presenting a human health concern, and have not been as thoroughly studied as the high MW PAHs. LMW PAHs exert their pulmonary effects, in part, through P38-dependent and -independent mechanisms involving cell-cell communication and the production of pro-inflammatory mediators known to contribute to lung disease. Specifically, we determined the effects of two representative LMW PAHs, 1-methylanthracene (1-MeA) and fluoranthene (Flthn), individually and as a binary PAH mixture on the dysregulation of gap junctional intercellular communication (GJIC) and connexin 43 (Cx43), activation of mitogen activated protein kinases (MAPK), and induction of inflammatory mediators in a mouse non-tumorigenic alveolar type II cell line (C10). Both 1-MeA, Flthn, and the binary PAH mixture of 1-MeA and Flthn dysregulated GJIC in a dose and time-dependent manner, reduced Cx43 protein, and activated the following MAPKs: P38, ERK1/2, and JNK. Inhibition of P38 MAPK prevented PAH-induced dysregulation of GJIC, whereas inhibiting ERK and JNK did not prevent these PAHs from dysregulating GJIC indicating a P38-dependent mechanism. A toxicogenomic approach revealed significant P38-dependent and -independent pathways involved in inflammation, steroid synthesis, metabolism, and oxidative responses. Genes in these pathways were significantly altered by the binary PAH mixture when compared with 1-MeA and Flthn alone suggesting interactive effects. Exposure to the binary PAH mixture induced the production and release of cytokines and metalloproteinases from the C10 cells. Our findings with a binary mixture of PAHs suggest that combinations of LMW PAHs may elicit synergistic or additive inflammatory responses which warrant further investigation and confirmation.

The Affordable Care Act and Cancer Stage at Diagnosis Among Young Adults.

The Affordable Care Act-dependent coverage expansion provision implemented in 2010 allows young adults to be covered under their parents' health insurance until age 26 years, and millions of young adults have gained insurance as a result. The impact of this policy on cancer patients has yet to be determined. Using 2007 to 2012 data from 18 registries of the Surveillance, Epidemiology, and End Results Program, comparing cancer patients age 19 to 25 years to a control group of patients age 26 to 34 years who were not affected by the provision, we observed a 2.0 (95% confidence interval [CI] = 0.7 to 3.4) percentage point decrease in uninsured rate and a 2.7 (95% CI = 0.6 to 4.8) percentage point increase in diagnosis at stage I disease for patients age 19-25 years. Further analyses by specific cancer site revealed that the statistically significant shifts were confined to carcinoma of cervix (21.2, 95% CI = 9.6 to 32.7 percentage points) and osseous and chondromatous neoplasms (14.4, 95% CI = 0.3 to 28.5 percentage points), which are detectable by either screening or clinical manifestation. These early observations suggest the policy has had positive benefits in cancer outcomes.

α7-Nicotinic acetylcholine receptor: role in early odor learning preference in mice.

Recently, we have shown that mice with decreased expression of α7-nicotinic acetylcholine receptors (α7) in the olfactory bulb were associated with a deficit in odor discrimination compared to wild-type mice. However, it is unknown if mice with decreased α7-receptor expression also show a deficit in early odor learning preference (ELP), an enhanced behavioral response to odors with attractive value observed in rats. In this study, we modified ELP methods performed in rats and implemented similar conditions in mice. From post-natal days 5-18, wild-type mice were stroked simultaneously with an odor presentation (conditioned odor) for 90 s daily. Control mice were only stroked, exposed to odor, or neither. On the day of testing (P21), mice that were stroked in concert with a conditioned odor significantly investigated the conditioned odor compared to a novel odor, as observed similarly in rats. However, mice with a decrease in α7-receptor expression that were stroked during a conditioned odor did not show a behavioral response to that odorant. These results suggest that decreased α7-receptor expression has a role in associative learning, olfactory preference, and/or sensory processing deficits.