Predicting Adolescent Electronic Cigarette Use: Differences by Never, Ever, and Current Users.

OBJECTIVE: Rising rates of adolescent electronic cigarette (ECIG) use is concerning because it can lead to adverse health outcomes and increased risk behavior. There are known predictors of ever versus never ECIG use, but less are known about risk factors for ever versus current use of ECIGs. Problem behavior theory (PBT) was used to evaluate possible risk factors for different ECIG use status. METHODS: Participants were 573 high school students who completed questionnaires measuring ECIG use, as well as constructs within the Social Environment, Perceived Environment, Personality, and Behavior domains of PBT. Multinomial logistic regression was used to evaluate how predictor variables differentiated between participants who reported (a) never use, (b) ever ECIG use, or (c) current ECIG use. RESULTS: Adolescents were more likely to endorse ever ECIG use than never use if they reported peer ECIG use, perceived more benefits and fewer costs (e.g., health) of ECIG use, higher extraversion, alcohol and cigarette use (never vs. ever vs. past 30 days), or attended a school with a higher percentage of socioeconomically disadvantaged students. Adolescents were more likely to report current ECIG use than ever ECIG use if they perceived fewer costs of ECIG use or used cannabis in their lifetime (yes/no). CONCLUSIONS: PBT variables differentiated between ever ECIG use and never ECIG use. However, these variables did not differentiate between ever and current ECIG use. Identifying unique risk factors for current versus ever ECIG use is important to understanding persistent ECIG use and subsequent targeted prevention and intervention programs.

The [underutilized] power of independent pharmacies to promote public health in rural communities: A call to action.

Independent community pharmacies are in a unique and powerful position to promote public and individual health in their communities. Independent pharmacies are particularly important in rural communities where there are few chain pharmacies and accessible health clinics. West Virginia received national attention recently when they opted out of the Federal Pharmacy Program collaborating with CVS and Walgreens and developed their own plan for COVID-19 vaccine distribution and administration, heavily relying on independent pharmacies and the infrastructure they already have in local communities. However, in other areas of public health with urgent, unmet need, such as pregnancy prevention, there is considerable room for independent pharmacies to improve. The pandemic has allowed independent pharmacies to shine during the vaccination effort and has demonstrated what can be accomplished when policymakers, providers, and pharmacists work together for the benefit of community health. Expanding such collaboration to include contraceptive provision and counseling in a timely, nonjudgmental manner could play a pivotal role in preventing unintended and unwanted pregnancies.

Associations Between Peer Use, Costs and Benefits, Self-Efficacy, and Adolescent E-cigarette Use.

OBJECTIVE: Prior research identified peer use as a salient risk factor of adolescent electronic cigarette (e-cigarette) use, but has not expanded on the mechanisms of this association. METHODS: Participants were 562 adolescents recruited from rural and suburban public high schools and an adolescent medicine clinic in the mid-Atlantic United States. Participants completed a packet of questionnaires that assessed demographics, substance use, expectations about the consequences of e-cigarette use, and perceptions of their own self-efficacy to resist using e-cigarettes. We estimated a series of mediation models using the MODEL INDIRECT command in MPLUS statistical software. In all models, significance of indirect effects from peer e-cigarette use to self-reported e-cigarette use were tested via two variables: (a) expected costs, (b) benefits of e-cigarette use, and (c) the perceived self-efficacy of the individual to refrain from e-cigarette use. RESULTS: Adolescents with more peers using e-cigarettes were more likely to have ever used an e-cigarette and perceived greater benefits and fewer costs, which was associated with a reduced self-efficacy to refrain from e-cigarette smoking (Model 1). Those with more peers using e-cigarettes were more likely to be currently using e-cigarettes themselves because they perceived greater benefits and fewer costs, which was associated with a reduced self-efficacy to refrain from e-cigarette smoking (Model 2). CONCLUSION: Peer use, self-efficacy to resist use, and expectations of cost and benefits of e-cigarette use should be considered as possible targets when devising tailored interventions and policies to prevent or reduce negative health consequences of long-term e-cigarette use.

Pyruvate anaplerosis is a mechanism of resistance to pharmacological glutaminase inhibition in triple-receptor negative breast cancer.

BACKGROUND: Glutamine serves as an important nutrient with many cancer types displaying glutamine dependence. Following cellular uptake glutamine is converted to glutamate in a reaction catalysed by mitochondrial glutaminase. This glutamate has many uses, including acting as an anaplerotic substrate (via alpha-ketoglutarate) to replenish TCA cycle intermediates. CB-839 is a potent, selective, orally bioavailable inhibitor of glutaminase that has activity in Triple receptor-Negative Breast Cancer (TNBC) cell lines and evidence of efficacy in advanced TNBC patients. METHODS: A panel of eleven breast cancer cell lines was used to investigate the anti-proliferative effects of the glutaminase inhibitors CB-839 and BPTES in different types of culture medium, with or without additional pyruvate supplementation. The abundance of the TCA cycle intermediate fumarate was quantified as a measure if TCA cycle anaplerosis. Pyruvate secretion by TNBC cultures was then assessed with or without AZD3965, a monocarboxylate transporter 1 (MCT1) inhibitor. Finally, two dimensional (2D) monolayer and three dimensional (3D) spheroid assays were used to compare the effect of microenvironmental growth conditions on CB-839 activity. RESULTS: The anti-proliferative activity of CB-839 in a panel of breast cancer cell lines was similar to published reports, but with a major caveat; growth inhibition by CB-839 was strongly attenuated in culture medium containing pyruvate. This pyruvate-dependent attenuation was also observed with a related glutaminase inhibitor, BPTES. Studies demonstrated that exogenous pyruvate acted as an anaplerotic substrate preventing the decrease of fumarate in CB-839-treated conditions. Furthermore, endogenously produced pyruvate secreted by TNBC cell lines was able to act in a paracrine manner to significantly decrease the sensitivity of recipient cells to glutaminase inhibition. Suppression of pyruvate secretion using the MCT1 inhibitor AZD3965, antagonised this paracrine effect and increased CB-839 activity. Finally, CB-839 activity was significantly compromised in 3D compared with 2D TNBC culture models, suggesting that 3D microenvironmental features impair glutaminase inhibitor responsiveness. CONCLUSION: This study highlights the potential influence that both circulating and tumour-derived pyruvate can have on glutaminase inhibitor efficacy. Furthermore, it highlights the benefits of 3D spheroid cultures to model the features of the tumour microenvironment and improve the in vitro investigation of cancer metabolism-targeted therapeutics.

Anticancer Characteristics of Fomitopsis pinicola Extract in a Xenograft Mouse Model-a Preliminary Study.

Introduction: Medicinal mushrooms have been used for the treatment of diseases and general promotion of health for many centuries. Recent pharmacological research into medicinal mushrooms has identified various therapeutic properties, with applications in modern medicine.Aim: To evaluate the anti-cancer activities of Fomitopsis pinicola (F. pinicola) alcoholic extract in an in vivo setting.Methods: The anti-tumour effect of the F. pinicola extract was tested in a xenograft immune-compromised Rag-1 mouse model. This was followed by RT-PCR and metabolomics analyses.Results: There were no observable differences in tumor growth between treated and non-treated groups. The bioactive components were not detected in the mouse plasma or the tumor site.Conclusions: The extract was poorly absorbed; this is likely due to the timing of treatment, dosage levels and modifications made to the extract where the alcohol-based solvent was replaced with water. This, in combination with fractionation studies which identified most anti-cancer compounds to be hydrophobic, largely explained the lack of anti-cancer activities in vivo.

Harder to get than you think: Levonorgestrel emergency contraception access in West Virginia community pharmacies.

OBJECTIVES: Emergency contraception (EC) is the only noninvasive form of contraception available after risk exposure and is an important tool for preventing unintended pregnancy resulting from unprotected sex, sexual assault, or contraceptive failure. The U.S. Food and Drug Administration (FDA) removed age restrictions on levonorgestrel EC and made it available over-the-counter to everyone in 2013. Despite improved availability and accessibility since the change in FDA regulations, community pharmacies have not uniformly embraced the policy. West Virginia is a rural state with high rates of poverty and teen pregnancy. DESIGN: The investigators called community pharmacies in West Virginia to assess the availability and accessibility of levonorgestrel EC in addition to the pharmacy staff's knowledge of effectiveness for this cross-sectional study. SETTING AND PARTICIPANTS: The study sample consisted of 509 community pharmacies throughout the state. OUTCOME MEASURES: A structured script was employed to conduct phone calls to community pharmacies with items assessing availability, accessibility, and knowledge of effectiveness. RESULTS: At the time of the phone calls, levonorgestrel EC was reported to be available in 48.9% of the community pharmacies in West Virginia. Chain pharmacies were more likely to report EC as being in stock (0.76) than independent pharmacies (0.15.). Other measures of accessibility also favored chain pharmacies versus independent pharmacies. The overall accessibility of EC at West Virginia community pharmacies was derived from a binary composite variable of "completely accessible" or "not completely accessible" by combining 5 predetermined items. Overall, EC was completely accessible to callers in 0.27 of all pharmacies with significant differences by pharmacy type (0.47 of chain pharmacies as compared with 0.03 of independent pharmacies). CONCLUSION: Accessible EC could reduce unintended pregnancy and help break the state's generational cycle of poverty and poor educational, social, and health outcomes. Pharmacists will be instrumental in expanding access to EC.

Not all clots are created equal: a review of deficient thrombolysis with tissue plasminogen activator (tPA) in patients with metabolic syndrome.

Metabolic syndrome is a cluster of cardiovascular risk factors associated with a prothrombotic, proinflammatory and hypofibrinolysis state. Although resistance to tissue plasminogen activator (tPA) in metabolic syndrome patients has been associated with a defective fibrinolytic system, the factors and mechanisms underlining such resistance is unclear. While there is a great debate on proposed mechanisms, fundamental questions regarding resistance to tPA in metabolic syndrome patients with ischemic stroke remain unanswered. This article reviews articles and documents published between 2001 and 2017, and provides an overview of metabolic syndrome, factors associated with tPA resistance in metabolic syndrome, conflicting evidence of insufficient dosing of tPA in overweight/obese patients and future directions for research.

Illness Representations of Pertussis and Predictors of Child Vaccination Among Mothers in a Strict Vaccination Exemption State.

Background Vaccine preventable diseases are making a comeback in the US. However, research is lacking on illness representations of vaccine preventable diseases and their application in improving childhood immunization. Objective We utilized the common sense model of self-regulation to examine illness representations of pertussis and their associations with child's receipt of any vaccine, up-to-date vaccination status, and mothers' intentions to follow the recommended vaccination schedule in the future. Methods We developed vaccine worry and vaccine hassles scales to assess mothers' worries and hassles for child vaccination, and used an open ended question to assess mother's illness representations of pertussis. We surveyed mothers with children <3 years old (N = 160) in the Appalachian state of West Virginia, which only allows medical vaccine exemptions. Results Some children (5.0%) had received no vaccination, 15.0% were not up-to-date with the recommended vaccination schedule, and 13.8% mothers reported no intention to follow the recommended schedule in future (future intention). Illness representations included identity (17.8%), timeline (61.8%), consequences (58.6%), cause (35.0%), and cure/control (56.7%). Higher vaccine worry was associated with child receiving no vaccine. Not using daycare, higher vaccine worry, and difficulty breathing (identity) were associated with child not being up-to-date. Higher vaccine worry, cough (identity), and belief that vaccines are ineffective (cure/control) were associated with no future intention. Conclusions Vaccination interventions need to address mothers' worry regarding vaccine safety. 'Common Sense' beliefs regarding vaccines need to be reconciled with scientific data about vaccine safety and effectiveness, even among those with high socio-economic status in a strict vaccination state.

Car Seat Safety: Typologies of Protective Health and Safety Behaviors for Mothers in West Virginia.

Objective Parenting practices differ for a variety of reasons, and three parenting behaviors may be directly influenced by research, policy, and overall parenting trends: car safety seats, vaccination, and breastfeeding. Mothers were categorized in terms of their rear-facing car safety seat utilization and its relationship to other parental health and safety behaviors. Methods A cross-sectional, online survey of mothers of children under 3 years of age (n = 124) was conducted. Items assessed mother's perceived risk and worry about being in an automobile accident, as well as duration of rear-facing car seat utilization. A cluster analysis based on these variables was performed to differentiate the sample into four distinct groups. Outcomes were knowledge of car safety seats, breastfeeding duration, and adherence to vaccination schedules. Results The sample was predominantly White, had an average age of 32 years, had breastfed, and had at least some college education. Two groups of interest had (Group 1) long duration of rear-facing use with low perceived risk and worry and (Group 2) short use with high perceived risk and worry. Fisher's Exact test indicated Group 1 had higher knowledge of airbag use with car seats (p = 0.035), lower intentions to use the recommended vaccinations schedule (p = 0.005), and were more likely to breastfeed (p = 0.044) for longer duration (p = 0.012). Conclusion Propensity for mothers' risk aversion may be the crucial element in both an appropriate duration of rear-facing car safety seat use and refusal of recommended vaccination schedule.

Human Intervention Study to Assess the Effects of Supplementation with Olive Leaf Extract on Peripheral Blood Mononuclear Cell Gene Expression.

Olive leaf extract (OLE) has been used for many years for its putative health benefits, but, to date, scientific evidence for the basis of these effects has been weak. Although recent literature has described a link between ailments such as cardiovascular disease, diabetes and cancer and a protective effect of polyphenols in the OLE, the mode of action is still unclear. Here, we describe a double-blinded placebo (PBO)-controlled trial, in which gene expression profiles of peripheral blood mononuclear cells from healthy male volunteers (n = 29) were analysed to identify genes that responded to OLE, following an eight-week intervention with 20 mL daily consumption of either OLE or PBO. Differences between groups were determined using an adjusted linear model. Subsequent analyses indicated downregulation of genes important in inflammatory pathways, lipid metabolism and cancer as a result of OLE consumption. Gene expression was verified by real-time PCR for three genes (EGR1, COX-2 and ID3). The results presented here suggest that OLE consumption may result in health benefits through influencing the expression of genes in inflammatory and metabolic pathways. Future studies with a larger study group, including male and female participants, looking into direct effects of OLE on lipid metabolism and inflammation are warranted.

Obesity hypoventilation syndrome in a 12-year-old child requiring therapeutic phlebotomy: case report and review of the literature.

The childhood obesity epidemic involves unusual and underrecognized complications associated with this clinical and public health problem. Obesity hypoventilation syndrome (OHS) is defined as the triad of obesity, daytime hypoventilation, and sleep-disordered breathing in the absence of an alternative neuromuscular, mechanical or metabolic explanation for hypoventilation. We herewith report a 12-year-old boy who was diagnosed with OHS. The patient improved with phlebotomy and bi-level positive airway pressure. To the best of our knowledge, this is the first reported case of secondary polycythemia due to OHS requiring therapeutic phlebotomy.

Menstrual Products: Attitudes About Taxation and Safety.

Background: This study explored factors associated with the differences between women and men in attitudes, norms, and the support of taxation of menstrual products (MPs) and menstrual-adjacent products. It also investigated the use of these products in women. Methods: Young adults from 18 to 30 years of age were recruited via social media, listserve emails, and flyers placed throughout a university campus. Following cognitive interviewing, a survey investigated attitudes, beliefs, and behaviors associated with MPs. Results: Individuals self-identified as men or women. Women (n = 154) had more positive general attitudes, less positive safety attitudes, and less support for taxation of MPs than men (n = 43). Regression analyses indicated that factors, such as race, age, attitudes, norms, and taxation, were associated with product use. Conclusions: Attitudes about safety and taxation differ for men and women. Tax policies and attitude-shifting interventions need to be tailored to their audience, and our study can inform that effort.

Adolescents' attitudes toward expedited partner therapy for sexually transmitted infections.

Adolescents (N = 392) attending 2 urban adolescent health clinics in 2010 were surveyed regarding likelihood completing expedited partner therapy (EPT), by bringing a partner exposed to chlamydia a prescription. Eighty-five percent (330/387; 95% confidence interval, 81%-89%), reported acceptance of EPT. Adjusted analyses showed higher education, notification self-efficacy, and romantic partner were associated with EPT acceptance.

Levonorgestrel Emergency Contraception Information Accuracy From West Virginia Community Pharmacies: A Mystery Caller Approach.

BACKGROUND: To ensure access to effective levonorgestrel (LNG) emergency contraception (EC), pharmacies must keep medication in stock or available for quick delivery, and pharmacists must be knowledgeable about sales restrictions and the therapeutic window for EC. We conducted a mystery caller study to assess LNG EC availability and information accuracy provided by staff in West Virginia community pharmacies. METHODS: A female research team member posed as a 16-year-old caller to ask pharmacy staff questions about whether LNG EC was in stock, the requirements for purchase, and when it should be taken for effectiveness. Data were analyzed with SPSS using the Pearson's χ2 test to determine if there was a relationship between pharmacy type and response accuracy to our questions about point-of-sale requirements and timing for effectiveness for LNG EC. RESULTS: Of the 506 pharmacies in the sample, 275 (54.3%) were chain pharmacies and 231 (45.7%) were independent. Overall, chain pharmacies provided significantly more accurate answers than independent pharmacies on all point-of-sale requirements. Regarding timing for effectiveness, 49.2% of all pharmacies provided an accurate response (62.9% for chain pharmacies vs. 32.9% for independent pharmacies). CONCLUSIONS: Overall, availability and accuracy regarding LNG EC were poor in West Virginia pharmacies. Pharmacists, particularly those at independent pharmacies serving rural communities, are in a critical and powerful position to influence community health by providing accurate and timely information and access to all contraceptive options, including LNG EC.

Rural Appalachian Women Will Suffer Disproportionately if Attempts to Further Restrict Emergency Contraception are Successful.

The removal of federal abortion protection has incited fear that restrictions on contraception may be next. Many states now imposing abortion restrictions and bans are in the South and Appalachian Regions of the U.S., where rates of unplanned pregnancy and poor health outcomes are already disproportionately high. Numerous studies have documented variable access to levonorgestrel EC (LNG EC) in community pharmacies, with particularly low rates of access at independent pharmacies that are more likely to be located in rural communities than chain pharmacies. Since the overturn of Roe v. Wade, some large chain pharmacies and online retailers are restricting the purchase of LNG EC, limiting its availability. Some legislators and activists are calling for a ban on EC based on a misunderstanding about its mechanism of action, equating it with abortion. At a time when access to the full range of contraceptive options is more critical than ever, already limited access to LNG EC is worsening. Extensive data on LNG EC availability in 509 pharmacies and 400 health clinics across West Virginia, contextualized with socioeconomic demographics, illustrate existing disparities in LNG EC access.

The management of menstrual suppression and uterine bleeding: a survey of current practices in the Pediatric Blood and Marrow Transplant Consortium.

BACKGROUND: Current guidelines recommend the use of combined hormonal contraceptive pills for menstrual suppression in pediatric blood and marrow transplant (BMT) recipients but recent research reveals that provider practice varies. This study was designed to describe the current practice for managing menstrual issues, that is, menstrual suppression and uterine bleeding, in pediatric BMT patients and to better understand health care providers' practices in the use of gonadotropin-releasing hormone agonists (GnRHa). PROCEDURE: A cross sectional survey consisting of 53 questions was distributed via email to principal investigators in the Pediatric Blood and Marrow Transplant Consortium (PBMTC). Responses were collected using www.surveymonkey.com. RESULTS: Menstrual suppression and uterine bleeding in pediatric BMT patients are primarily managed by pediatric oncologists (97%). The most frequently reported hormonal method used for induction of therapeutic amenorrhea was GnRHa (41%). The top three reasons for choosing a method were greater likelihood of amenorrhea, concerns about side effects, and possible gonadal protection. Continuous combined hormonal contraceptive pills were the most commonly used method for the management of clinically significant uterine bleeding regardless of primary method used for menstrual suppression. CONCLUSION: Despite the 2002 PBMTC guidelines, wide variation in menstrual suppression management practices still exists. Our data show that use of GnRHa is more common than previously reported. Additional research is needed to develop evidence-based practice guidelines in pediatric BMT patients.

The impact of caller characteristics on levonorgestrel emergency contraception access in West Virginia community pharmacies.

OBJECTIVE: Access to levonorgestrel (LNG) emergency contraception (EC) has increased since the FDA removed age restrictions on over-the-counter (OTC) LNG EC in 2013, but availability is highly variable and numerous barriers to access remain. The purpose of this study was to assess availability and accessibility of LNG EC at community pharmacies in West Virginia (WV). METHODS: A mystery caller cross-sectional study was conducted to assess availability and accessibility of LNG EC. Inquiries were made by identified 'research' staff and by staff presenting as a 16 y/o. RESULTS: Nearly half of community pharmacies reported having LNG EC in stock. Pharmacy staff were significantly more likely to tell research callers LNG EC was in stock (53%) and more likely to report willingness to order it (50%) than 'teen' callers (45% and 34%, respectively). There was no significant difference between caller types on the five barriers assessed. CONCLUSION: Lack of availability may contribute to teen and unintended pregnancies.

Acceptability of Time-Limited Eating in Pediatric Weight Management.

Background: Adherence to dietary interventions is a significant barrier in the treatment of childhood obesity. Time-limited eating (TLE) is a simple dietary approach that limits food intake to a given number of consecutive hours per day, but parental and youth acceptability of TLE in youth with obesity is unknown. This study explored the feasibility of utilizing TLE among parents and youth attending pediatric weight management (PWM). Methods: Members of COMPASS (Childhood Obesity Multi-Program Analysis and Study System) developed a survey to assess the acceptability of TLE in families attending PWM, which included patient characteristics, current diet and sleep schedules, and interests in trying TLE. The survey was administered electronically via REDCap or manually to parents of patients between the ages of 8-17 years old and to patients 11-17 years old attending one of five PWM practices in the COMPASS network. Results: Patients (n=213) were 13.0 ± 2.5 years old, 58% female, 52% White, 22% Black, 17% Hispanic/Latino, and 47% reported a diagnosed psychological disorder. On average, parents reported their child's daily eating spanned 12.5 ± 1.9 hours (7:35am - 8:05pm) and included 5.6 ± 1.6 eating bouts (meals + snacks). Most parents reported being likely to try TLE ≤12 hours/d (TLE12: 66%), which was similar to the likelihood of following a nutrient-balanced diet (59%). Likelihood was lower for TLE ≤10 hours/d (TLE10: 39%) or ≤8 hours/d (TLE8: 26%) (p<0.001 for both). Interest in TLE was not consistently related to patient age, sex, or ethnicity, but was lower in patients with a psychiatric diagnosis vs. no diagnosis (TLE8: 19% vs. 32%; p=0.034). Patients of parents who reported being likely to try TLE, compared to those unlikely to try TLE, had shorter eating windows (p<0.001) and ate fewer snacks (p=0.006). Conclusions: Two-thirds of parents with children attending PWM programs report interest in TLE ≤12 hours/d regardless of demographic characteristics, but interest wanes when limiting eating to ≤10 or ≤8 hours per day. Time-limited eating appears to be a feasible option in PWM settings provided treatment options are individualized based on the interests and barriers of patients and their families.

Quinazolines as novel anti-inflammatory histone deacetylase inhibitors.

Histone deacetylase (HDAC) inhibitors regulate many biological responses, including anti-inflammatory and anti-cancer effects. We sought to identify novel classes of HDAC inhibitors from in-house compound libraries. Initially, compounds from 26 different structural classes that showed anti-inflammatory effects in a pre-screen in HEK293T cells were tested in vitro for HDAC inhibition, using a commercial fluorescence assay. The known HDAC inhibitors suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) were used as positive controls. Examples of three different structural classes (anilinoacridines, phenylpyrrolocarbazoles and benzofurylquinazolines) showed significant inhibition in the HDAC assay, and small subsets of these were also evaluated, seeking initial structure-activity relationships (SAR) for each class. Several of the most effective compounds from this HDAC screen were evaluated for their effects on the expression of the pro-inflammatory gene, IL1-alpha, and the cancer-related genes, p53, p21, E-cadherin and C-MYC. While the benzofurylquinazolines increased the expression level of the pro-inflammatory gene IL1-alpha as well as p21 and p53 in the PC3 cell line, a phenylpyrrolocarbazole had the converse effect on p53 expression. Several of the compounds showed in vitro HDAC inhibition ability in PC3, HCT116 and NIH-3T3 cell lines comparable to that of SAHA.