Development of a versatile laboratory experiment to teach the metabolic transformation of hydrolysis

In this paper we describe an easy, reliable, versatile and inexpensive laboratory experiment to teach the metabolic transformation of hydrolysis to Pharmacy students. The experiment does not require the sacrifice of any experimental animal, or any work with organs or tissues, and so can be implemented in a typical university chemistry laboratory. We used acetylsalicylic acid (ASA), hexyl salicylate (HS) and two enzymes, a lipase and an esterase. Since both ASS and HS liberate salicylic acid (SA) upon hydrolysis, students can evaluate the different enzymatic transformations by monitoring the amount of SA liberated. The learning outcomes are an enhanced student understanding of: (1) the process of hydrolysis; (2) the application of enzymatic transformations of molecules from food to xenobiotics; (3) the differences between the general specificity of substrate of both enzymes; (4) the concepts of the lipophilic pocket; (5) the catalytic triad and its regioselectivity in relation to the ester bond. A questionnaire was administered to participating students at three points in time: at the beginning of the module, after enzymatic hydrolysis was taught in class, and after the laboratory experiment. From an analysis of the questionnaire data we conclude that this practical helped Pharmacy students to understand these concepts

Effect of thermomechanical processing defects on fatigue and fracture behaviour of forged magnesium

The microstructural origins of premature fatigue failures were investigated on a variety of forged components manufactured from AZ80 and ZK60 magnesium, both at the test specimen level and the full-scale component level. Both stress and strain-controlled approaches were used to characterize the macroscopically defect-free forged material behaviour as well as with varying levels of defect intensities. The effect of thermomechanical processing defects due to forging of a industrially relevant full-scale component were characterized and quantified using a variety of techniques. The fracture initiation and early crack growth behaviour was deterministically traced back to a combination of various effects having both geometric and microstructural origins, including poor fusion during forging, entrainment of contaminants sub-surface, as well as other inhomogeneities in the thermomechanical processing history.             At the test specimen level, the fracture behaviour under both stress and strain controlled uniaxial loading was characterized for forged AZ80 Mg and a structure-property relationship was developed. The fracture surface morphology was quantitatively assessed revealing key features which characterize the presence and severity of intrinsic forging defects.  A significant degradation in fatigue performance was observed as a result of forging defects accelerating fracture initiation and early crack growth, up to 6 times reduction in life (relative to the defect free material) under constant amplitude fully reversed fatigue loading.             At the full-scale component level, the fatigue and fracture behaviour under combined structural loading was also characterized for a number of ZK60 forged components with varying levels of intrinsic thermomechanical processing defects. A novel in-situ non-contact approach (utilizing Digital-Image Correlation) was used as a screening test to establish the presence of these intrinsic defects and reliably predict their effect on the final fracture behaviour in an accelerated manner compared to conventional methods

Combination of fast-ion diagnostics in velocity-space tomographies:Paper

Fast-ion Dα (FIDA) and collective Thomson scattering (CTS) diagnostics provide indirect measurements of fastion velocity distribution functions in magnetically confined plasmas. Here we present the first prescription for velocity-space tomographic inversion of CTS and FIDA measurements that can use CTS and FIDA measurements together and that takes uncertainties in such measurements into account. Our prescription is general and could be applied to other diagnostics. We demonstrate tomographic reconstructions of an ASDEX Upgrade beam ion velocity distribution function. First, we compute synthetic measurements from two CTS views and two FIDA views using a TRANSP/NUBEAM simulation, and then we compute joint tomographic inversions in velocity-space from these. The overall shape of the 2D velocity distribution function and the location of the maxima at full and half beam injection energy are well reproduced in velocity-space tomographic inversions, if the noise level in the measurements is below 10%. Our results suggest that 2D fast-ion velocity distribution functions can be directly inferred from fast-ion measurements and their uncertainties, even if the measurements are taken with different diagnostic methods

Pharmacist insights into adolescent human papillomavirus vaccination provision in the United States

HPV vaccination coverage in the United States (US) falls short of the Healthy People 2020 goal of 80% coverage among 13–15 year-old adolescents. Pharmacies are a promising alternative vaccine delivery site that may increase access to HPV vaccination. Our objective was to assess pharmacists’ insights into HPV vaccination provision to adolescents. We recruited 40 licensed pharmacists in eight states with different pharmacy vaccination laws: Alabama, California, Indiana, Kentucky, Maine, Tennessee, Texas, and Washington. Eligible pharmacists either previously provided or were currently providing HPV, tetanus-diphtheria-pertussis, or meningococcal vaccines to adolescents aged 9–17 years. Pharmacists were administered a semi-structured survey to explore insights into HPV vaccination provision. Forty-five percent of surveyed pharmacies offered HPV vaccination to adolescents. Pharmacists’ reported challenges to providing HPV vaccination were parental consent (28%), tracking and patient recall (17%), perceived stigma of vaccination (17%), and education about or promotion of vaccination (17%). Pharmacists offering HPV vaccination sent patient reminders for vaccines with multiple doses (89%) and utilized telephone reminders (72%). Pharmacists informed patients’ primary care providers of HPV vaccination doses most commonly through fax (72%) and updating electronic medical records (22%). One-third of pharmacists reported vaccination provision using the state immunization information system (IIS). Seventy-five percent reported vaccination rates could be increased at their respective pharmacy. Pharmacies are underutilized, although highly accessible, for HPV vaccination in the US. National efforts should expand educational programs to improve public awareness of in-pharmacy HPV vaccination, and improve the utilization of state IIS for reporting immunization coverage of adolescents by pharmacists

Using rapid indicators for Enterococcus to assess the risk of illness after exposure to urban runoff contaminated marine water

Background: Traditional fecal indicator bacteria (FIB) measurement is too slow (>18 h) for timely swimmer warnings. Objectives: Assess relationship of rapid indicator methods (qPCR) to illness at a marine beach impacted by urban runoff. Methods: We measured baseline and two-week health in 9525 individuals visiting Doheny Beach 2007-08. Illness rates were compared (swimmers vs. non-swimmers). FIB measured by traditional (Enterococcus spp. by EPA Method 1600 or Enterolert™, fecal coliforms, total coliforms) and three rapid qPCR assays for Enterococcus spp. (Taqman, Scorpion-1, Scorpion-2) were compared to health. Primary bacterial source was a creek flowing untreated into ocean; the creek did not reach the ocean when a sand berm formed. This provided a natural experiment for examining FIB-health relationships under varying conditions. Results: We observed significant increases in diarrhea (OR 1.90, 95% CI 1.29-2.80 for swallowing water) and other outcomes in swimmers compared to non-swimmers. Exposure (body immersion, head immersion, swallowed water) was associated with increasing risk of gastrointestinal illness (GI). Daily GI incidence patterns were different: swimmers (2-day peak) and non-swimmers (no peak). With berm-open, we observed associations between GI and traditional and rapid methods for Enterococcus; fewer associations occurred when berm status was not considered. Conclusions: We found increased risk of GI at this urban runoff beach. When FIB source flowed freely (berm-open), several traditional and rapid indicators were related to illness. When FIB source was weak (berm-closed) fewer illness associations were seen. These different relationships under different conditions at a single beach demonstrate the difficulties using these indicators to predict health risk

Roadmap on dynamics of molecules and clusters in the gas phase

This roadmap article highlights recent advances, challenges and future prospects in studies of the dynamics of molecules and clusters in the gas phase. It comprises nineteen contributions by scientists with leading expertise in complementary experimental and theoretical techniques to probe the dynamics on timescales spanning twenty order of magnitudes, from attoseconds to minutes and beyond, and for systems ranging in complexity from the smallest (diatomic) molecules to clusters and nanoparticles. Combining some of these techniques opens up new avenues to unravel hitherto unexplored reaction pathways and mechanisms, and to establish their significance in, e.g. radiotherapy and radiation damage on the nanoscale, astrophysics, astrochemistry and atmospheric science

MC1R variants in childhood and adolescent melanoma: a retrospective pooled analysis of a multicentre cohort

BACKGROUND: Germline variants in the melanocortin 1 receptor gene (MC1R) might increase the risk of childhood and adolescent melanoma, but a clear conclusion is challenging because of the low number of studies and cases. We assessed the association of MC1R variants with childhood and adolescent melanoma in a large study comparing the prevalence of MC1R variants in child or adolescent patients with melanoma to that in adult patients with melanoma and in healthy adult controls. METHODS: In this retrospective pooled analysis, we used the M-SKIP Project, the Italian Melanoma Intergroup, and other European groups (with participants from Australia, Canada, France, Greece, Italy, the Netherlands, Serbia, Spain, Sweden, Turkey, and the USA) to assemble an international multicentre cohort. We gathered phenotypic and genetic data from children or adolescents diagnosed with sporadic single-primary cutaneous melanoma at age 20 years or younger, adult patients with sporadic single-primary cutaneous melanoma diagnosed at age 35 years or older, and healthy adult individuals as controls. We calculated odds ratios (ORs) for childhood and adolescent melanoma associated with MC1R variants by multivariable logistic regression. Subgroup analysis was done for children aged 18 or younger and 14 years or younger. FINDINGS: We analysed data from 233 young patients, 932 adult patients, and 932 healthy adult controls. Children and adolescents had higher odds of carrying MC1R r variants than did adult patients (OR 1·54, 95% CI 1·02-2·33), including when analysis was restricted to patients aged 18 years or younger (1·80, 1·06-3·07). All investigated variants, except Arg160Trp, tended, to varying degrees, to have higher frequencies in young patients than in adult patients, with significantly higher frequencies found for Val60Leu (OR 1·60, 95% CI 1·05-2·44; p=0·04) and Asp294His (2·15, 1·05-4·40; p=0·04). Compared with those of healthy controls, young patients with melanoma had significantly higher frequencies of any MC1R variants. INTERPRETATION: Our pooled analysis of MC1R genetic data of young patients with melanoma showed that MC1R r variants were more prevalent in childhood and adolescent melanoma than in adult melanoma, especially in patients aged 18 years or younger. Our findings support the role of MC1R in childhood and adolescent melanoma susceptibility, with a potential clinical relevance for developing early melanoma detection and preventive strategies. FUNDING: SPD-Pilot/Project-Award-2015; AIRC-MFAG-11831

Nongenetic Determinants of Risk for Early-Onset Colorectal Cancer

Background: Incidence of early-onset (younger than 50 years of age) colorectal cancer (CRC) is increasing in many countries. Thus, elucidating the role of traditional CRC risk factors in early-onset CRC is a high priority. We sought to determine whether risk factors associated with late-onset CRC were also linked to early-onset CRC and whether association patterns differed by anatomic subsite. Methods: Using data pooled from 13 population-based studies, we studied 3767 CRC cases and 4049 controls aged younger than 50 years and 23 437 CRC cases and 35 311 controls aged 50 years and older. Using multivariable and multinomial logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to assess the association between risk factors and early-onset CRC and by anatomic subsite. Results: Early-onset CRC was associated with not regularly using nonsteroidal anti-inflammatory drugs (OR = 1.43, 95% CI = 1.21 to 1.68), greater red meat intake (OR = 1.10, 95% CI = 1.04 to 1.16), lower educational attainment (OR = 1.10, 95% CI = 1.04 to 1.16), alcohol abstinence (OR = 1.23, 95% CI = 1.08 to 1.39), and heavier alcohol use (OR = 1.25, 95% CI = 1.04 to 1.50). No factors exhibited a greater excess in early-onset compared with late-onset CRC. Evaluating risks by anatomic subsite, we found that lower total fiber intake was linked more strongly to rectal (OR = 1.30, 95% CI = 1.14 to 1.48) than colon cancer (OR = 1.14, 95% CI = 1.02 to 1.27; P =. 04). Conclusion: In this large study, we identified several nongenetic risk factors associated with early-onset CRC, providing a basis for targeted identification of those most at risk, which is imperative in mitigating the rising burden of this disease