Hong Kong consensus recommendations on the management of pancreatic ductal adenocarcinoma.

This project was undertaken to develop the first set of consensus statements regarding the management of pancreatic ductal adenocarcinoma (PDAC) in Hong Kong, with the goal of providing guidance to local clinicians. A multidisciplinary panel of experts discussed issues surrounding current PDAC management and reviewed evidence gathered in the local context to propose treatment recommendations. The experts used the Delphi approach to finalise management recommendations. Consensus was defined as ≥80% acceptance among all expert panel members. Thirty-nine consensus statements were established. These statements cover all aspects of PDAC management, including diagnosis, resectability criteria, treatment modalities according to resectability, personalised management based on molecular profiling, palliative care, and supportive care. This project fulfils the need for guidance regarding PDAC management in Hong Kong. To assist clinicians with treatment decisions based on varying levels of evidence and clinical experience, treatment options are listed in several consensus statements.

Medical school dermatology education: a scoping review.

Dermatological diseases are widespread and have a significant impact on the quality of life of patients; however, access to appropriate care is often limited. Improved early training during medical school represents a potential upstream solution. This scoping review explores dermatology education during medical school, with a focus on identifying the factors associated with optimizing the preparation of future physicians to provide care for patients with skin disease. A literature search was conducted using online databases (Embase, MEDLINE, CINAHL and Scopus) to identify relevant studies. The Joanna Briggs Institute methodological framework for scoping reviews was used, including quantitative and qualitative data analysis following a grounded theory approach. From 1490 articles identified, 376 articles were included. Most studies were from the USA (46.3%), UK (16.2%), Germany (6.4%) and Canada (5.6%). Only 46.8% were published as original articles, with a relatively large proportion either as letters (29.2%) or abstracts (12.2%). Literature was grouped into three themes: teaching content, delivery and assessment. Core learning objectives were country dependent; however, a common thread was the importance of skin cancer teaching and recognition that diversity and cultural competence need greater fostering. Various methods of delivery and assessment were identified, including computer-aided and online, audiovisual, clinical immersion, didactic, simulation and peer-led approaches. The advantages and disadvantages of each need to be weighed when deciding which is most appropriate for a given learning outcome. The broader teaching-learning ecosystem is influenced by (i) community health needs and medical school resources, and (ii) the student and their ability to learn and perform. Efforts to optimize dermatology education may use this review to further investigate and adapt teaching according to local needs and context.

Antimicrobial effects of Melaleuca alternifolia (tea tree) essential oil against biofilm-forming multidrug-resistant cystic fibrosis-associated Pseudomonas aeruginosa as a single agent and in combination with commonly nebulized antibiotics.

Broth microdilution assays were used to determine minimum inhibitory concentrations (MICs) and fractional inhibitory concentration indices (FICIs) of tea tree oil (TTO), tobramycin, colistin and aztreonam (ATM) against clinical cystic fibrosis-associated Pseudomonas aeruginosa (CFPA) isolates (n = 20). The minimum biofilm eradication concentration (MBEC) and fractional biofilm eradication concentration index (FBECI) were also determined using a similar microbroth dilution checkerboard assay, with biofilms formed using the MBEC device® . TTO was effective at lower concentrations against multidrug-resistant (MDR) CFPA isolates (n = 3) in a biofilm compared to in a planktonic state (MBEC 18·7-fold lower than MIC). CFPA within biofilm was less susceptible to ATM, colistin and tobramycin compared to planktonic cells (MBEC 6·3-fold, 9·3-fold, and 2·1-fold higher than MIC respectively). All combinations of essential oil and antibiotic showed indifferent relationships (FICI 0·52-1·72) when tested against planktonic MDR CFPA isolates (n = 5). Against CFPA isolates (n = 3) in biofilm, combinations of TTO/aztreonam and TTO/colistin showed indifferent relationships (mean FBECI 0·85 and 0·60 respectively), whereas TTO/tobramycin showed a synergistic relationship (mean FBECI 0·42). The antibiofilm properties of TTO and the synergistic relationship seen between TTO and tobramycin against CFPA in vitro make inhaled TTO a promising candidate as a potential therapeutic agent.

High-level semi-synthetic production of the potent antimalarial artemisinin.

In 2010 there were more than 200 million cases of malaria, and at least 655,000 deaths. The World Health Organization has recommended artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria caused by the parasite Plasmodium falciparum. Artemisinin is a sesquiterpene endoperoxide with potent antimalarial properties, produced by the plant Artemisia annua. However, the supply of plant-derived artemisinin is unstable, resulting in shortages and price fluctuations, complicating production planning by ACT manufacturers. A stable source of affordable artemisinin is required. Here we use synthetic biology to develop strains of Saccharomyces cerevisiae (baker's yeast) for high-yielding biological production of artemisinic acid, a precursor of artemisinin. Previous attempts to produce commercially relevant concentrations of artemisinic acid were unsuccessful, allowing production of only 1.6 grams per litre of artemisinic acid. Here we demonstrate the complete biosynthetic pathway, including the discovery of a plant dehydrogenase and a second cytochrome that provide an efficient biosynthetic route to artemisinic acid, with fermentation titres of 25 grams per litre of artemisinic acid. Furthermore, we have developed a practical, efficient and scalable chemical process for the conversion of artemisinic acid to artemisinin using a chemical source of singlet oxygen, thus avoiding the need for specialized photochemical equipment. The strains and processes described here form the basis of a viable industrial process for the production of semi-synthetic artemisinin to stabilize the supply of artemisinin for derivatization into active pharmaceutical ingredients (for example, artesunate) for incorporation into ACTs. Because all intellectual property rights have been provided free of charge, this technology has the potential to increase provision of first-line antimalarial treatments to the developing world at a reduced average annual price.

Clinical and microbiological characteristics of Eggerthella lenta bacteremia.

Eggerthella lenta is an emerging pathogen that has been underrecognized due to historical difficulties with phenotypic identification. Until now, its pathogenicity, antimicrobial susceptibility profile, and optimal treatment have been poorly characterized. In this article, we report the largest cohort of patients with E. lenta bacteremia to date and describe in detail their clinical features, microbiologic characteristics, treatment, and outcomes. We identified 33 patients; the median age was 68 years, and there was no gender predominance. Twenty-seven patients (82%) had serious intra-abdominal pathology, often requiring a medical procedure. Of those who received antibiotics (28/33, 85%), the median duration of treatment was 21.5 days. Mortality from all causes was 6% at 7 days, 12% at 30 days, and 33% at 1 year. Of 26 isolates available for further testing, all were identified as E. lenta by both commercially available matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) systems, and none were found to harbor a vanA or vanB gene. Of 23 isolates which underwent susceptibility testing, all were susceptible to amoxicillin-clavulanate, cefoxitin, metronidazole, piperacillin-tazobactam, ertapenem, and meropenem, 91% were susceptible to clindamycin, 74% were susceptible to moxifloxacin, and 39% were susceptible to penicillin.

Texture analysis of cosmetic/pharmaceutical raw materials and formulations.

OBJECTIVES: The purpose of this work was to quantify textural properties of cosmetic and pharmaceutical raw materials. METHODS: Textural parameters such as hardness, consistency, cohesiveness, index of viscosity, stickiness and resilience were evaluated. The measurements were performed using texture analyser - a tensile metre equipped with special probes (in the form of acrylic cylinder and stainless steel sphere), which can penetrate the measured sample of a product recording the force, distance and time. The instrument simulates the action of a human finger touching the surface and probing the properties of an object. The set-up has been previously shown to quantify the rheological/textural properties of cosmetic and pharmaceutical products such as creams, lotion and gels as well as rheological behaviour of human skin. RESULTS AND CONCLUSIONS: The results include the analysis of water, glycerine and mineral oil as well as aqueous solutions of thickeners such as Acrylates/C10-30 Alkyl Acrylate Crosspolymer (Ultrez-20 obtained from Noveon) and carbomer. Solutions of common surfactants and complex surfactant formulations such as shampoos have also been investigated. The results, in the form plots of force as a function of time or distance, resulting from slow bidirectional probe movement (submergence and desubmergence) in the analysed fluid, were interpreted by considering buoyancy, drag and viscous drag force given by Stokes equation. The data can be used to correlate with tactile evaluations of products by trained panel evaluations.

The Clot Thickens: Differential Coagulotoxic and Cardiotoxic Activities of Anguimorpha Lizard Venoms.

Despite their evolutionary novelty, lizard venoms are much less studied in comparison to the intense research on snake venoms. While the venoms of helodermatid lizards have long been assumed to be for defensive purposes, there is increasing evidence of toxic activities more useful for predation than defence (such as paralytic neurotoxicity). This study aimed to ascertain the effects of Heloderma, Lanthanotus, and Varanus lizard venoms on the coagulation and cardiovascular systems. Anticoagulant toxicity was demonstrated for the Varanus species studied, with the venoms prolonging clotting times in human and bird plasma due to the destructive cleavage of fibrinogen. In contrast, thromboelastographic analyses on human and bird plasmas in this study demonstrated a procoagulant bioactivity for Heloderma venoms. A previous study on Heloderma venom using factor-depleted plasmas as a proxy model suggested a procoagulant factor was present that activated either Factor XI or Factor XII, but could not ascertain the precise target. Our activation studies using purified zymogens confirmed FXII activation. Comparisons of neonate and adult H. exasperatum, revealed the neonates to be more potent in the ability to activate FXII, being more similar to the venom of the smaller species H. suspectum than the adult H. exasperatum. This suggests potent FXII activation a basal trait in the genus, present in the small bodied last common ancestor. This also indicates an ontogenetic difference in prey preferences in the larger Heloderma species paralleing the change in venom biochemistry. In addition, as birds lack Factor XII, the ability to clot avian plasma suggested an additional procoagulant site of action, which was revealed to be the activation of Factor VII, with H. horridum being the most potent. This study also examined the effects upon the cardiovascular system, including the liberation of kinins from kininogen, which contributes to hypotension induction. This form of toxicity was previously described for Heloderma venoms, and was revealed in this study was to also be a pathophysiological effect of Lanthanotus and Varanus venoms. This suggests that this toxic activity was present in the venom of the last common ancestor of the anguimorph lizards, which is consistent with kallikrein enzymes being a shared toxin trait. This study therefore uncovered novel actions of anguimorph lizard venoms, not only contributing to the evolutionary biology body of knowledge but also revealing novel activities to mine for drug design lead compounds.

The value of pre-exposure prophylaxis: A case series of US Marines infected with leptospirosis.

BACKGROUND: Leptospirosis is an ever-present threat found in the freshwater areas in many tropical and sub-tropical regions throughout the world and travelers to these areas are at increased risk of infection. This study describes a case series of 47 US Marines who experienced a single point leptospirosis exposure in 2014 and were admitted to a military treatment facility. METHODS: Descriptive statistics were conducted for patient demographics, symptoms, laboratory results, and outcomes. Hypothesis tests were conducted to identify significant outcomes (length of hospitalization, severity of infection, intensive care unit (ICU) admission, and cholecystectomy). Patient data was applied to five leptospirosis scoring models to assess their accuracy in the context of this population. RESULTS: The patients were all male (n = 47, 100%), had a median age of 22 (range 19-37), a mean body mass index of 24.3 (SD 2.5), and most were taking antibiotic prophylaxis (n = 40, 85.1%). Most patients experienced thrombocytopenia (n = 37, 78.7%), proteinuria (n = 35, 74.5%), and transaminitis (n = 37, 78.7%). Correct classification of infection varied among the models from 42.6% (n = 20) to 10.6% (n = 5). Not taking pre-exposure prophylaxis was significantly correlated with severe infection (p = 0.02), undergoing a cholecystectomy (p = 0.01), and being admitted to the ICU (p < 0.01). No other results were found to be both clinically and statistically significant. CONCLUSIONS: Leptospirosis diagnostic models currently in use may be less effective in predicting disease severity in young and healthy populations who are taking antibiotic prophylaxis. The use of pre-exposure prophylaxis significantly correlates with less severe health outcomes.

CpG-induced tyrosine phosphorylation occurs via a TLR9-independent mechanism and is required for cytokine secretion.

Toll-like receptors (TLRs) recognize molecular patterns preferentially expressed by pathogens. In endosomes, TLR9 is activated by unmethylated bacterial DNA, resulting in proinflammatory cytokine secretion via the adaptor protein MyD88. We demonstrate that CpG oligonucleotides activate a TLR9-independent pathway initiated by two Src family kinases, Hck and Lyn, which trigger a tyrosine phosphorylation-mediated signaling cascade. This cascade induces actin cytoskeleton reorganization, resulting in cell spreading, adhesion, and motility. CpG-induced actin polymerization originates at the plasma membrane, rather than in endosomes. Chloroquine, an inhibitor of CpG-triggered cytokine secretion, blocked TLR9/MyD88-dependent cytokine secretion as expected but failed to inhibit CpG-induced Src family kinase activation and its dependent cellular responses. Knock down of Src family kinase expression or the use of specific kinase inhibitors blocked MyD88-dependent signaling and cytokine secretion, providing evidence that tyrosine phosphorylation is both CpG induced and an upstream requirement for the engagement of TLR9. The Src family pathway intersects the TLR9-MyD88 pathway by promoting the tyrosine phosphorylation of TLR9 and the recruitment of Syk to this receptor.

Clostridioides difficile colonization and infection in a cohort of Australian adults with cystic fibrosis.

BACKGROUND: Little is known about Clostridioides difficile infection (CDI) in patients with cystic fibrosis (CF). The aim of this study was to investigate the prevalence, molecular epidemiology and risk factors for CDI in asymptomatic and symptomatic adults with CF in Western Australia. METHODS: Faecal samples from symptomatic and asymptomatic patients were prospectively collected and tested for the presence of C. difficile by toxigenic culture. Ribotyping was performed by established protocols. Logistic regression analysis was performed to analyse the risk factors for C. difficile colonization and infection. Extensive environmental sampling was performed within the CF clinic in Perth. RESULTS: The prevalence rates of asymptomatic toxigenic and non-toxigenic C. difficile colonization were 30% (14/46 patients) and 24% (11/46 patients), respectively. Fifteen ribotypes (RTs) of C. difficile were identified, of which non-toxigenic RT 039 was the most common. Among the symptomatic patients, the prevalence of toxigenic CDI was 33% (11/33 patients). Impaired glucose tolerance/diabetes mellitus and duration of intravenous antibiotic use in the past 12 months were significantly associated with increased risk of asymptomatic toxigenic C. difficile carriage and CDI. A trend towards higher CF transmembrane conductance regulator modulator treatment was observed in the CDI group. Extensive environmental sampling showed no evidence of toxigenic C. difficile contamination within the CF clinic. CONCLUSIONS: A high prevalence of asymptomatic carriage of toxigenic C. difficile was observed in adults with CF, comparable with that observed in the symptomatic CF population. There was no evidence of direct person-to-person transmission.

COVID-19 Case and Contact Investigation in an Office Workspace.

This investigation report describes a case of COVID-19 in a combined military and civilian office workspace and the contact investigation and mitigation efforts that followed. This office space included an embedded public health officer who was able to conduct the contact investigation and advise on the outbreak response. Over a 3-day period, the index case unintentionally exposed 150 coworkers to SARS-CoV-2 through participation in carpools, conferences, and small meetings. Of these exposures 37 were considered medium risk at the time and 113 were considered low risk. A total of 5 contacts reported COVID-like-symptoms at the time of the investigation and another 5 developed symptoms during the 14-day quarantine period and all were directed to self-isolate. None of the contacts required hospitalization and all the symptomatic contacts tested negative for SARS-CoV-2. With the advice and aid of the embedded public health officer, the office authorized telework, conducted thorough cleaning of spaces, distributed informative messaging, conducted virtual question-and-answer forums, and evaluated outbreak policies. This report demonstrates that the close integration of public health and office management can lead to rapid identification of those at risk of infection and implementation of mitigation and control efforts to stop the spread of disease.

Say something nice: A meta-analytic review of peer reporting interventions.

Peer reporting interventions (i.e., Positive Peer Reporting and tootling) are commonly used peer-mediated interventions in schools. These interventions involve training students to make reports about peers' prosocial behaviors, whether in oral or written form. Although peer reporting interventions have been included in meta-analyses of group contingencies, this study is the first meta-analytic review of single-case research focusing exclusively on peer reporting interventions. The literature search and application of inclusion criteria yielded 21 studies examining the impact of a peer reporting intervention on student behavior compared to baseline conditions. All studies used single-case experimental designs including at least three demonstrations of an effect and at least three data points per phase. Several aspects of studies, participants, and interventions were coded. Log response ratios and Tau were calculated as effect size estimates. Effect size estimates were synthesized in a multi-level meta-analysis with random effects for (a) studies and (b) cases within studies. Overall results indicated peer reporting interventions had a non-zero and positive impact on student outcomes. This was also true when data were subset by outcome (i.e., disruptive behavior, academically engaged behavior, and social behavior). Results were suggestive of more between- than within-study variability. Moderator analyses were conducted to identify aspects of studies, participants, or peer reporting interventions associated with differential effectiveness. Moderator analyses suggested published studies were associated with higher effect sizes than unpublished studies (i.e., theses/dissertations). This meta-analysis suggests peer reporting interventions are effective in improving student behavior compared to baseline conditions. Implications and directions for future investigation are discussed.

Cytoplasmic dynein regulation by subunit heterogeneity and its role in apical transport.

Despite the existence of multiple subunit isoforms for the microtubule motor cytoplasmic dynein, it has not yet been directly shown that dynein complexes with different compositions exhibit different properties. The 14-kD dynein light chain Tctex-1, but not its homologue RP3, binds directly to rhodopsin's cytoplasmic COOH-terminal tail, which encodes an apical targeting determinant in polarized epithelial Madin-Darby canine kidney (MDCK) cells. We demonstrate that Tctex-1 and RP3 compete for binding to dynein intermediate chain and that overexpressed RP3 displaces endogenous Tctex-1 from dynein complexes in MDCK cells. Furthermore, replacement of Tctex-1 by RP3 selectively disrupts the translocation of rhodopsin to the MDCK apical surface. These results directly show that cytoplasmic dynein function can be regulated by its subunit composition and that cytoplasmic dynein is essential for at least one mode of apical transport in polarized epithelia.

Decreasing Inappropriate Use of Mobile Devices in Urban High School Classrooms: Comparing an Antecedent Intervention With and Without the Good Behavior Game.

As the capabilities of portable technology continue to advance and become more accessible, educators express concern about the impact of the inappropriate use of mobile devices on academic engagement and learning. An alternating treatments design was used to compare the effectiveness of an antecedent (Clear Box) intervention and an interdependent group contingency (Clear Box + Good Behavior Game [GBG]) intervention to typical classroom management techniques (Control) in increasing the academic engagement and decreasing mobile device use of high school students during instruction. The results indicate an increase in academic engagement and a decrease in the inappropriate presence of mobile devices in both classrooms with the implementation of the Clear Box + GBG, as compared with the Clear Box and Control conditions. In addition, teacher and student social validity data suggested that teachers and students viewed the Clear Box + GBG intervention favorably. Discussion focuses on contributions to the current literature, implications for practice, and suggestions for future areas of research.

Vape and Aviate: Electronic-Cigarette Use and Misuse in Naval Aviation.

Introduction: Electronic cigarettes (EC) are an emerging form of nicotine replacement that has had a discernible increase in prevalence in the general population. Little is known regarding EC use among different military demographic groups or the extent of influence that social determinants of health may have on the behavior. The purpose of this study was to assess the prevalence and correlates of EC use in a select population of active duty U.S. Naval personnel. This study is unique in that it allows for EC behavior comparison between a traditionally healthy demographic (aviators, a subset of aircrew) and a representative general military population sample. Materials and methods: Cross-sectional survey data were collected anonymously and analyzed in 2015-2016. Active duty Naval personnel (n = 977) were asked about ever trying ECs, frequency of use, and when was the last time an EC was used. Participants were assessed similarly regarding cigarette use. Descriptive and inferential statistics as well as multinomial logistic regression analyses were conducted using categorical and ordinal variables assigned to usage and demographic factors. This protocol was approved by the Institutional Review Board at Naval Hospital Portsmouth located in Portsmouth, Virginia. Results: Within the study population, 31.4% have tried ECs, 9.3% were current users, and only 3.8% were dual (EC and cigarettes) users. EC use was significantly associated with paygrade (enlisted), primary job duty (non-aircrew), and education (less than a bachelor degree, p < 0.001, p < 0.01, and p < 0.001, respectively). ECs were used at some point as a smoking cessation tool for 43.6% of current EC users (p < 0.001), 21.6% of current smokers, and only 5.6% of former smokers. Continued EC use after ever trying ECs (30.0%) was only slightly more prevalent as continued cigarette use after ever trying cigarettes (27.3%). Smokers were nearly five times more likely to currently use ECs compared with non-smokers. Trying cigarettes was associated with nearly 12 times the risk for trying ECs compared with those who never tried cigarettes. No significant misuse of ECs was noted; however, several cases of drinking, tasting, and touching EC fluid were reported. Conclusion: This study is unique in that it examines the use of electronic cigarettes among selected healthy and baseline groups within the active duty U.S. Navy population. The current prevalence of EC use among active duty personnel is much higher than previously thought. Continued use of ECs after ever trying them appears to exceed that of cigarettes even among healthy populations such as aircrew. The findings of increased risk of EC use among those with lower income and less than a bachelor's degree suggest social determinants of health implications. This study sheds new light on EC use, characteristics of use, addiction implications, and highlights concerns for a growing health risk behavior.

Interferon-Gamma Release Assay is Not Appropriate for the Diagnosis of Active Tuberculosis in High-Burden Tuberculosis Settings: A Retrospective Multicenter Investigation.

BACKGROUND: Interferon-gamma release assay (IGRA) has been used in latent tuberculosis (TB) infection and TB diagnosis, but the results from different high TB-endemic countries are different. The aim of this study was to investigate the value of IGRA in the diagnosis of active pulmonary TB (PTB) in China. METHODS: We conducted a large-scale retrospective multicenter investigation to further evaluate the role of IGRA in the diagnosis of active PTB in high TB-epidemic populations and the factors affecting the performance of the assay. All patients who underwent valid T-SPOT.TB assays from December 2012 to November 2015 in six large-scale specialized TB hospitals in China and met the study criteria were retrospectively evaluated. Patients were divided into three groups: Group 1, sputum culture-positive PTB patients, confirmed by positive Mycobacterium tuberculosis sputum culture; Group 2, sputum culture-negative PTB patients; and Group 3, non-TB respiratory diseases. The medical records of all patients were collected. Chi-square tests and Fisher's exact test were used to compare categorical data. Multivariable logistic analyses were performed to evaluate the relationship between the results of T-SPOT in TB patients and other factors. RESULTS: A total of 3082 patients for whom complete information was available were included in the investigation, including 905 sputum culture-positive PTB cases, 914 sputum culture-negative PTB cases, and 1263 non-TB respiratory disease cases. The positive rate of T-SPOT.TB was 93.3% in the culture-positive PTB group and 86.1% in the culture-negative PTB group. In the non-PTB group, the positive rate of T-SPOT.TB was 43.6%. The positive rate of T-SPOT.TB in the culture-positive PTB group was significantly higher than that in the culture-negative PTB group (χ2 = 25.118, P < 0.01), which in turn was significantly higher than that in the non-TB group (χ2 = 566.116, P < 0.01). The overall results were as follows: sensitivity, 89.7%; specificity, 56.37%; positive predictive value, 74.75%; negative predictive value, 79.11%; and accuracy, 76.02%. CONCLUSIONS: High false-positive rates of T-SPOT.TB assays in the non-TB group limit the usefulness as a single test to diagnose active TB in China. We highly recommend that IGRAs not be used for the diagnosis of active TB in high-burden TB settings.

Induction of neurite outgrowth in PC12 cells by the medium-chain fatty acid octanoic acid.

It has been shown that polyunsaturated fatty acids such as arachinonic and docosahexanoic acids but not monounsaturated and saturated long-chain fatty acids promote basal and nerve growth factor (NGF)-induced neurite extension of PC12 cells, a line derived from a rat pheochromocytoma. On the other hand, short-chain fatty acids and valproic acid (2-propylpentanoic acid) enhance the growth of neurite processes of the cells only in the presence of inducers. In this study, we demonstrated that straight medium-chain fatty acids (MCFAs) at millimolar concentrations alone potently induced neuronal differentiation of PC12 cells. Hexanoic, heptanoic and octanoic acids dose-dependently induced neurite outgrowth of the cells: their maximal effects determined 2 days after addition to the culture medium were more marked than the effect of NGF. PC12 cells exposed to octanoic acid expressed increased levels of the neuronal marker beta-tubulin isotype III. Nonanoic, decanoic, and dodecanoic acids also induced growth of neurite processes, but their maximal effects were less marked than that of octanoic acid. In contrast, the polyunsaturated fatty acid linoleic acid and short-chain fatty acids had only slight or almost no effects on neurite formation in the absence of NGF. The effect of octanoic acid was synergistic with or additive to the effects of NGF and dibutyryl cyclic AMP. Octanoic acid upregulated phosphorylation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK), critical signaling molecules in neuronal differentiation, but not phosphorylation of Akt, a signaling molecule downstream of phosphatidylinositol 3-kinase (PI3K). Moreover, growth of neurites induced by octanoic acid was potently inhibited by treatment of cells with the p38 MAPK inhibitor SB203580 and the ERK kinase inhibitor PD98059 but not inhibited and only slightly inhibited by the JNK inhibitor SP600125 and the PI3K inhibitor wortmannin, respectively. Taken together, our results indicate that MCFAs, including octanoic acid, induced neurite outgrowth of PC12 cells in the absence of NGF and suggest that the activation of p38 MAPK and ERK pathways is involved in this process.

Perceptions of harm from electronic-cigarette use among a sample of US Navy personnel.

INTRODUCTION: Scant information exists on the perceptions and behaviors surrounding electronic cigarette (EC) use in the U.S. military. The Health Belief Model (HBM) enables factors influencing behavior adoption to be assessed. Utilizing this model, this study explored five EC-related perceptions among a sample of active-duty Navy personnel. METHODS: Participants were invited to complete a questionnaire involving EC use and perceptions. Demographics were reported and perceptions assessed using multiple choice and answer questions. Analyses included benefit and harm ratios and non-parametric tests. RESULTS: Among the 977 participants, 29.7% tried ECs, 9.5% were current users and 3.8% were dual users. A large proportion of the population believed that ECs were less harmful than cigarettes, the safest alternative to cigarettes, accepted by non-users, and allowed in areas where cigarettes are prohibited. On the other hand, the majority believed that ECs did not make the user look cool or fit in and were not safe to use around children. EC users, cigarette smokers, men, those under 30 years of age, and those with less than a bachelor degree were more likely to have positive beliefs and perceptions about EC use. CONCLUSIONS: The majority of the population studied has negative perceptions and beliefs about EC use. Several groups have beliefs that highlight vulnerabilities to EC experimentation and use. The findings illustrated concepts related to cessation and behavior adoption, harm-to-self and second-hand vapor, and smoke-free zones. These findings may help to identify motivations for experimentation and use, as well as to direct future EC intervention and prevention efforts.