Menthol and related compounds in waterpipe products.

INTRODUCTION: The addition of cooling substances, such as menthol, might be attractive for youth to start smoking waterpipe by reducing the harshness of the smoke, thereby facilitating inhalation. These compounds simultaneously increase the addictiveness of tobacco and related products by stimulating nicotine uptake. Some menthol-like compounds also increase attractiveness by imparting a menthol/mint flavor. We provide an overview of the frequency and quantities of use of menthol-like substances in waterpipe tobacco, herbal molasses and steam stones. METHODS: The primary data source of this study was the European Common Entry Gate (EU-CEG). Product names and ingredients were obtained for 282 waterpipe tobacco products notified to The Netherlands in 2020. Subsequently, gas-chromatography-mass spectrometry (GC-MS) analysis was used to quantify seven menthol-like substances and nicotine in waterpipe tobacco (n=5), herbal molasses (n=1) and steam stones (n=12). RESULTS: Of the 282 EU-CEG-notified products, 39% have a menthol/mint declared flavor. GC-MS showed that 15 of the 18 investigated waterpipe products contained one or more menthol-like ingredients. GC-MS analysis showed that products termed 'freeze', 'ice' or 'mint' contained higher median menthol concentrations than products without these terms. CONCLUSIONS: Nearly all investigated waterpipe products contained menthol-like compounds, irrespective of their flavor. Such compounds are known to provide flavoring or cooling effects, and some are known to be carcinogenic. Our results can support the regulation of these substances in waterpipe products. Regulators should screen all waterpipe products, not only those with menthol or a similar indicator in product names.

Validation of resting full-cycle ratio and diastolic pressure ratio with [15O]H2O positron emission tomography myocardial perfusion.

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging and clinical trials. New invasive pressure ratios that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy. The aim of this study was to validate the resting full-cycle ratio (RFR) and the diastolic pressure ratio (dPR), against [15O]H2O positron emission tomography (PET) imaging. A total of 129 symptomatic patients with an intermediate risk of coronary artery disease (CAD) were included. All patients underwent cardiac [15O]H2O PET with quantitative assessment of resting and hyperemic myocardial perfusion. Within a 2 week period, coronary angiography was performed. Intracoronary pressure measurements were obtained in 320 vessels and RFR, dPR, and FFR were computed. PET derived regional hyperemic myocardial blood flow (hMBF) and myocardial perfusion reserve (MPR) served as reference standards. In coronary arteries with stenoses (43%, 136 of 320), the overall diagnostic accuracies of RFR, dPR, and FFR did not differ when PET hyperemic MBF < 2.3 ml min-1 (69.9%, 70.6%, and 77.1%, respectively) and PET MPR < 2.5 (70.6%, 71.3%, and 66.9%, respectively) were considered as the reference for myocardial ischemia. Non-significant differences between the areas under the receiver operating characteristic (ROC) curve were found between the different indices. Furthermore, the integration of FFR with RFR (or dPR) does not enhance the diagnostic information already achieved by FFR in the characterization of ischemia via PET perfusion. In conclusion, the novel non-hyperemic pressure ratios, RFR and dPR, have a diagnostic performance comparable to FFR in assessing regional myocardial ischemia. These findings suggest that RFR and dPR may be considered as an FFR alternative for invasively guiding revascularization treatment in symptomatic patients with CAD.

Flavours and flavourings in waterpipe products: a comparison between tobacco, herbal molasses and steam stones.

ObjectivesFlavoured products are especially appealing to youth and contribute to the onset of waterpipe smoking and continued use of waterpipe tobacco. The goal of database and chemical analysis was to provide a clear overview of commonly used flavours and flavourings in tobacco and related waterpipe products, that is, herbal molasses and steam stones. METHODS: In 2019, 249 waterpipe tobacco products were registered in the European Common Entry Gate by manufacturers to be marketed in The Netherlands. Flavour categories were assigned to the registered products based on their brand names and product descriptions. Nicotine and eleven 1111 flavourings were identified and quantified in waterpipe tobacco (n=8), herbal molasses (n=7) and steam stones (n=4) by extraction and gas chromatography-mass spectrometry (GC-MS) analysis. RESULTS: Flavour categories could be assigned to 237 of 249 registered waterpipe tobacco products. Eight flavour main categories and 48 unique subcategories were identified and presented in a flavour wheel. All registered waterpipe tobacco products were flavoured, and the majority (78%) was fruit flavoured. Herbal molasses contained similar median flavouring levels, and steam stones contained lower median levels compared with waterpipe tobacco. Flavourings in waterpipe products were almost exclusively fruity and sweet, often in combination with menthol/mint flavourings. CONCLUSIONS: This study is the first to present a waterpipe tobacco flavour wheel, providing a quick overview of waterpipe tobacco flavours and thereby aiding communication among experts around the globe. GC-MS analysis revealed that the most prevalent flavourings are present in similar levels in herbal and tobacco waterpipe products. Banning flavourings in all waterpipe products would be a good strategy to reduce waterpipe smoking among youth.

Evaluation of Adverse Effects of Resorbable Hyaluronic Acid Fillers: Determination of Macrophage Responses.

Resorbable tissue fillers for aesthetic purposes can induce severe complications including product migration, late swelling, and inflammatory reactions. The relation between product characteristics and adverse effects is not well understood. We hypothesized that the degree of cross-linking hyaluronic acid (HA) fillers was associated with the occurrence of adverse effects. Five experimental HA preparations similar to HA fillers were synthesized with an increasing degree of cross-linking. Furthermore, a series of commercial fillers (Perfectha®) was obtained that differ in degradation time based on the size of their particulate HA components. Cytotoxic responses and cytokine production by human THP-1-derived macrophages exposed to extracts of the evaluated resorbable HA fillers were absent to minimal. Gene expression analysis of the HA-exposed macrophages revealed the responses related to cell cycle control and immune reactivity. Our results could not confirm the hypothesis that the level of cross-linking in our experimental HA fillers or the particulate size of commercial HA fillers is related to the induced biological responses. However, the evaluation of cytokine induction and gene expression in macrophages after biomaterial exposure presents promising opportunities for the development of methods to identify cellular processes that may be predictive for biomaterial-induced responses in patients.

Calibration of laboratory derived indices for non-target arthropod risk assessment with field data for plant protection products.

The Hazard Quotient (HQ) compares field application rate to intrinsic toxicity assessed with sensitive indicator species. As a hazard indicator for risk assessment, the HQ must be calibrated against measured effects under field conditions. Because protection goals may be context specific, we analyse how choice of acceptance criteria affects setting of the HQ and calibrate HQ for various scenarios under the strict condition that no false negative conclusions may be reached. We use Non-Target Arthropod toxicity data from laboratory studies on inert (Tier 1) and on natural substrates (Tier 2) and calibrate the HQ using application rates and arthropod abundance counts from field studies in orchards, arable fields, and hay meadows in 34 locations in Western Europe. With 21 formulations (17 active substances) tested in mostly multi-rate field studies, our reference data base has 120/121 values at Tier 1/Tier 2, respectively. We use the Proportion of Affected Taxa and Duration of Effect to jointly define acceptance criteria, starting with No Observed Effects. Absence of field effects is correctly predicted with HQ < 1.3 at Tier 1 and HQ < 0.48 at Tier 2, but these settings result in a high proportion of false positive outcomes. Increasing accepted duration of effect from 0 to 4 to 8 weeks results in HQ-threshold changes from 1.3 to 6.4 to 250 for Tier 1 studies and from 0.48 to 1.1 to 5.7 for Tier 2 studies. This coincides with a clear decrease in false positive outcomes. Recovery within a year is correctly concluded for 73% of the products passing the corresponding Tier 1 HQ < 2600 and for 92% of products at Tier 2 (HQ <230). Our analysis shows that the calibration is appropriate for a broad geographical range, for in-field and off-field situations and for phytophagous and non-phytophagous species alike.

Rapid and robust on-scene detection of cocaine in street samples using a handheld near-infrared spectrometer and machine learning algorithms.

On-scene drug detection is an increasingly significant challenge due to the fast-changing drug market as well as the risk of exposure to potent drug substances. Conventional colorimetric cocaine tests involve handling of the unknown material and are prone to false-positive reactions on common pharmaceuticals used as cutting agents. This study demonstrates the novel application of 740-1070 nm small-wavelength-range near-infrared (NIR) spectroscopy to confidently detect cocaine in case samples. Multistage machine learning algorithms are used to exploit the limited spectral features and predict not only the presence of cocaine but also the concentration and sample composition. A model based on more than 10,000 spectra from case samples yielded 97% true-positive and 98% true-negative results. The practical applicability is shown in more than 100 case samples not included in the model design. One of the most exciting aspects of this on-scene approach is that the model can almost instantly adapt to changes in the illicit-drug market by updating metadata with results from subsequent confirmatory laboratory analyses. These results demonstrate that advanced machine learning strategies applied on limited-range NIR spectra from economic handheld sensors can be a valuable procedure for rapid on-site detection of illicit substances by investigating officers. In addition to forensics, this interesting approach could be beneficial for screening and classification applications in the pharmaceutical, food-safety, and environmental domains.

GC-MS analysis of e-cigarette refill solutions: A comparison of flavoring composition between flavor categories.

OBJECTIVES: Electronic cigarette refill solutions (e-liquids) are available in various flavor descriptions that can be categorized as fruit, tobacco, and more. Flavors increase sensory appeal, thereby stimulating e-cigarette use, and flavoring ingredients can contribute to e-cigarette toxicity. We aim to inform toxicologists, sensory scientists, and regulators by determining flavoring compounds in e-liquids with various flavors, and compare results between flavor categories. METHODS: Gas chromatography - mass spectrometry (GC-MS) was used to identify 79 flavorings in 320 e-liquids, classified in 15 flavor categories. Ten flavorings highly prevalent in e-liquids according to information from manufacturers were quantified. Flavoring prevalence was defined as the number of e-liquids with the flavoring as percentage of the total number of e-liquids. The method was validated in terms of specificity, linearity, repeatability, recovery, and sensitivity. RESULTS: The mean number of flavorings per e-liquid was 6 ± 4. Flavoring prevalence was highest for vanillin (creamy/vanilla flavor), ethyl butyrate (ethereal/fruity), and cis-3-hexenol (fresh/green). Based on similarities in flavoring prevalence, four clusters of categories were distinguished: (1) fruit, candy, alcohol, beverages; (2) dessert, coffee/tea, nuts, sweets; (3) menthol/mint; and (4) spices, tobacco, and unflavored. Categories from cluster 4 generally had less flavorings per e-liquid than fruit, candy, alcohol, beverages (cluster 1) and dessert (cluster 2) (p < 0.05). Flavoring concentrations varied between e-liquids within the categories. CONCLUSIONS: We evaluated flavoring compositions of 320 e-liquids using a simple GC-MS method. Flavoring prevalence was similar within four clusters of typically fresh/sweet, warm/sweet, fresh/cooling, and non-sweet flavor categories. To compare flavoring concentrations between individual flavor categories, additional research is needed.

Benchtop NMR spectroscopy in the analysis of substandard and falsified medicines as well as illegal drugs.

Substandard and falsified medical products may cause harm to patients and fail to treat the diseases or conditions for which they were intended. It is therefore required to have analytical methods available to assess medical product quality. Benchtop NMR spectroscopy provides a generic, inherently quantitative, analytical method capable of separating specific signals from those of a matrix. We have developed an analytical method for the analysis of active ingredients in pharmaceutical products and illegal drugs, based on benchtop NMR spectroscopy. Within its resolution limits, benchtop NMR spectroscopy is useful in determining the identity of the active ingredients in products containing acetaminophen, aspirin, caffeine, diclofenac, ibuprofen, naproxen, sildenafil, tadalafil and sibutramine, cocaine, and gamma hydroxybutyric acid, with a limit of detection of about 1 mg/mL. Furthermore, the content of the active ingredient can be determined with an error of 10%. Additionally, a chemometrics approach is shown to be useful to classify spectra in order to identify the active substances present in the sample, reducing the need for expert interpretation of the spectra acquired.

Thermal comfort in urban green spaces: a survey on a Dutch university campus.

To better understand the influence of urban green infrastructure (UGI) on outdoor human thermal comfort, a survey and physical measurements were performed at the campus of the University of Groningen, The Netherlands, in spring and summer 2015. Three hundred eighty-nine respondents were interviewed in five different green spaces. We aimed to analyze people's thermal comfort perception and preference in outdoor urban green spaces, and to specify the combined effects between the thermal environmental and personal factors. The results imply that non-physical environmental and subjective factors (e.g., natural view, quiet environment, and emotional background) were more important in perceiving comfort than the actual thermal conditions. By applying a linear regression and probit analysis, the comfort temperature was found to be 22.2 °C and the preferred temperature was at a surprisingly high 35.7 °C. This can be explained by the observation that most respondents, who live in temperate regions, have a natural tendency to describe their preferred state as "warmer" even when feeling "warm" already. Using the Kruskal-Wallis H test, the four significant factors influencing thermal comfort were people's exposure time in green spaces, previous thermal environment and activity, and their thermal history. However, the effect of thermal history needs further investigation due to the unequal sample sizes of respondents from different climate regions. By providing evidence for the role of the objective and subjective factors on human thermal comfort, the relationship between UGI, microclimate, and thermal comfort can assist urban planning to make better use of green spaces for microclimate regulation.

Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework.

Non-communicable diseases (NCDs) are a major cause of premature mortality. Recent studies show that predispositions for NCDs may arise from early-life exposure to low concentrations of environmental contaminants. This developmental origins of health and disease (DOHaD) paradigm suggests that programming of an embryo can be disrupted, changing the homeostatic set point of biological functions. Epigenetic alterations are a possible underlying mechanism. Here, we investigated the DOHaD paradigm by exposing zebrafish to subtoxic concentrations of the ubiquitous contaminant cadmium during embryogenesis, followed by growth under normal conditions. Prolonged behavioral responses to physical stress and altered antioxidative physiology were observed approximately ten weeks after termination of embryonal exposure, at concentrations that were 50-3200-fold below the direct embryotoxic concentration, and interpreted as altered developmental programming. Literature was explored for possible mechanistic pathways that link embryonic subtoxic cadmium to the observed apical phenotypes, more specifically, the probability of molecular mechanisms induced by cadmium exposure leading to altered DNA methylation and subsequently to the observed apical phenotypes. This was done using the adverse outcome pathway model framework, and assessing key event relationship plausibility by tailored Bradford-Hill analysis. Thus, cadmium interaction with thiols appeared to be the major contributor to late-life effects. Cadmium-thiol interactions may lead to depletion of the methyl donor S-adenosyl-methionine, resulting in methylome alterations, and may, additionally, result in oxidative stress, which may lead to DNA oxidation, and subsequently altered DNA methyltransferase activity. In this way, DNA methylation may be affected at a critical developmental stage, causing the observed apical phenotypes.

Design and analysis of field studies with bees: A critical review of the draft EFSA guidance.

The specific protection goal, primary assessment endpoints, acceptable effect thresholds, and experimental design proposed in the European Food Safety Authority (EFSA) update of the bee guidance document are subjected to critical review. It is concluded that the negligible effect criteria were established without sufficient regulatory definition and without convincing scientific argumentation. For the assessment endpoints, effects on hive strength lack temporal definition and the reduction to numbers of bees is inappropriate to evaluate effects. Restricting mortality assessments to homing failure is not theoretically justified and specific criteria were incorrectly derived. The combination of acute effect estimates with models for chronic stressors is biased risk assessment and a temporal basis for the acceptability of effects is missing. Effects on overwintering success cannot be experimentally assessed using the proposed criteria. The experimental methodology proposed is inappropriate and the logistical consequences, in particular those related to replication and land use are such that field studies are no longer a feasible option for the risk assessment. It may be necessary to explore new lines of thought for the set-up of field studies and to clearly separate experimentation from monitoring. Integr Environ Assess Manag 2016;12:422-428. © 2015 SETAC.

Effects of urban green infrastructure (UGI) on local outdoor microclimate during the growing season.

This study analyzed how the variations of plant area index (PAI) and weather conditions alter the influence of urban green infrastructure (UGI) on microclimate. To observe how diverse UGIs affect the ambient microclimate through the seasons, microclimatic data were measured during the growing season at five sites in a local urban area in The Netherlands. Site A was located in an open space; sites B, C, and D were covered by different types and configurations of green infrastructure (grove, a single deciduous tree, and street trees, respectively); and site E was adjacent to buildings to study the effects of their façades on microclimate. Hemispherical photography and globe thermometers were used to quantify PAI and thermal comfort at both shaded and unshaded locations. The results showed that groves with high tree density (site B) have the strongest effect on microclimate conditions. Monthly variations in the differences of mean radiant temperature (∆Tmrt) between shaded and unshaded areas followed the same pattern as the PAI. Linear regression showed a significant positive correlation between PAI and ∆Tmrt. The difference of daily average air temperature (∆T a ) between shaded and unshaded areas was also positively correlated to PAI, but with a slope coefficient below the measurement accuracy (±0.5 °C). This study showed that weather conditions can significantly impact the effectiveness of UGI in regulating microclimate. The results of this study can support the development of appropriate UGI measures to enhance thermal comfort in urban areas.

Chemical fingerprinting of silicone-based breast implants.

With millions of women worldwide carrying them, silicone-based breast implants represent a large market. Even though silicone breast implants already have a history of use of more than 50 years, the discussion on their safety has not yet come to an end. To improve safety assessment, regulatory authorities should have the availability of a set of tests to be able to determine parameters of implant identity and quality. Therefore, the gels and envelopes of various brands and types of silicone-based breast implants have been subjected to infrared, Raman and NMR spectroscopy. We show that by using a combination of complementary spectroscopic techniques breast implants of various origins can be distinguished on typical chemical hallmarks. It was found that typical silicone-based implants display a surplus of vinyl signals in the gel, cyclosiloxane impurities are tolerable at low levels only and a barrier layer is present in the implant envelope. The techniques presented here and the results obtained offer a good starting point for market surveillance studies.

Human cytomegalovirus inhibits erythropoietin production.

Anemia is a feature of CKD and a complication of renal transplantation, often caused by impaired production of erythropoietin. The kidney is a target organ for human cytomegalovirus (hCMV) in such patients, but it is not known whether hCMV effects erythropoietin production. We found that kidneys from patients with CKD were positive for hCMV protein and that blood levels of hCMV IgG inversely correlated with red blood cell count. In mice, systemic murine cytomegalovirus infection decreased serum erythropoietin levels. In human erythropoietin-producing cells, hCMV inhibited hypoxia-induced expression of erythropoietin mRNA and protein. hCMV early gene expression was responsible, as ultraviolet-inactivated virus had no effect and valganciclovir treatment showed that late gene expression was nonessential. Hypoxia-induced gene transcription is controlled by the transcription factors hypoxia-inducible transcription factor (HIF)-1α and HIF2α, which are constitutively produced but stable only under low oxygen conditions. We found that hCMV inhibited constitutive production of HIF2α mRNA. HIF2α is thought to be the master regulator of erythropoietin transcription. Single-cell analysis revealed that nuclear accumulation of HIF2α was inhibited in hCMV-infected cells, and the extent of inhibition correlated with hCMV protein expression. Our findings suggest that renal hCMV infection could induce or exacerbate anemia in patients.

Contextual body image and athletes' disordered eating: the contribution of athletic body image to disordered eating in high performance women athletes.

The present study investigated the contribution of a contextual body image perspective to understanding disordered eating in high performance women athletes. Because existing questionnaires were not suitable for measuring body image in the contexts of sport and daily life, we developed the 'Contextual Body Image Questionnaire for Athletes' (CBIQA) in which body image is divided into 'appearance', 'muscularity', 'thin-fat self-evaluations' and 'thin-fat perceived opinions of others', in both contexts. In Study 1, the internal validity and reliability of this questionnaire was established in a general, heterogeneous sample of female sport participants and exercisers. In Study 2, the external validity was determined in a sample of 52 high performance women athletes who mainly participated in aesthetic or endurance sports, 19 of which were classified with and 33 without disordered eating. The results of Study 2 showed that both 'thin-fat self' and 'thin-fat opinions of others' in sport made significant unique contributions to explaining eating disorder variance, indicating the important role of athletic body image. In conclusion, the contextual body image approach seems to be a promising framework for a better understanding of athletes' disordered eating.

Thoughts and attention of athletes under pressure: skill-focus or performance worries?

Choking under pressure in sport has been explained by either explicit attention to skill execution (self-focus theories), or attention to performance worries (distraction theories). The aim of the present study was to find out which focus of attention occurs most often when expert athletes perform under pressure. Two retrospective methods were employed, namely, verbal reports and concept mapping. In the verbal reports, 70 expert athletes indicated their main focus of attention when performing under high pressure in competition. For concept mapping seven expert athletes generated statements about their focus of attention in such high-pressure situations. These statements were clustered and rated on how often they occurred and how important they were for choking. Both methods revealed that under pressure attention of expert athletes was often focused on worries and hardly ever on movement execution. Furthermore, the athletes reported that they focused attention on external factors and that they reverted to positive monitoring in an attempt to maintain performance. These results are more in line with distraction theories than self-focus theories, suggesting that attention to performance worries rather than to skill execution generally explains choking.

Ironic effects and final target fixation in a penalty shooting task.

The aim of the present study was to find out whether ironic effects in a far aiming task were accompanied by shorter final fixations on the target. Generally, it is well known that a sufficiently long final fixation on the target is of crucial importance for accurate performance in far aiming. Recently, it has been shown that ironic effects in golf putts and penalty kicks (in which one does the opposite of what was intended, e.g., shoot close to the keeper while attempting to avoid this) were preceded by longer fixations on the to-be-avoided area, which may have resulted in shorter final fixations on the target area. Therefore, in the current study we examined football players taking penalties in a simulated penalty environment with and without instructions to avoid the goalkeeper. The findings revealed that ironic effects were indeed accompanied by significantly shorter final fixations on the target area, i.e., the open goal space. It is concluded that in far aiming tasks, ironic effects are accompanied by insufficiently long final fixations on the target.

The bisphosphonate zoledronic acid has antimyeloma activity in vivo by inhibition of protein prenylation.

Nitrogen-containing bisphosphonates (N-BPs) are effective antiosteolytic agents in patients with multiple myeloma. Preclinical studies have also demonstrated that these agents have direct antitumor effects in vitro and can reduce tumor burden in a variety of animal models, although it is not clear whether such effects are caused by direct actions on tumor cells or by inhibition of bone resorption. N-BPs prevent bone destruction in myeloma by inhibiting the enzyme farnesyl pyrophosphate synthase in osteoclasts, thereby preventing the prenylation of small GTPase signaling proteins. In this study, utilizing a plasmacytoma xenograft model without complicating skeletal lesions, treatment with zoledronic acid (ZOL) led to significant prolongation of survival in severe combined immunodeficiency mice inoculated with human INA-6 plasma cells. Following treatment with a clinically relevant dose of ZOL, histological analysis of INA-6 tumors from the peritoneal cavity revealed extensive areas of apoptosis associated with poly (ADP-ribose) polymerase cleavage. Furthermore, Western blot analysis of tumor homogenates demonstrated the accumulation of unprenylated Rap1A, indicative of the uptake of ZOL by nonskeletal tumors and inhibition of farnesyl pyrophosphate synthase. These studies provide, for the first time, clear evidence that N-BPs have direct antitumor effects in plasma cell tumors in vivo and this is executed by a molecular mechanism similar to that observed in osteoclasts.

Stabilizing single atom contacts by molecular bridge formation.

Gold-molecule-gold junctions can be formed by carefully breaking a gold wire in a solution containing dithiolated molecules. Surprisingly, there is little understanding on the mechanical details of the bridge formation process and specifically on the role that the dithiol molecules play themselves. We propose that alkanedithiol molecules have already formed bridges between the gold electrodes before the atomic gold-gold junction is broken. This leads to stabilization of the single atomic gold junction, as observed experimentally. Our data can be understood within a simple spring model.

The influence of anxiety on visual attention in climbing.

The object of the current study was to investigate anxiety-induced changes in movement and gaze behavior in novices on a climbing wall. Identical traverses were situated at high and low levels on a climbing wall to manipulate anxiety. In line with earlier studies, climbing times and movement times increased under anxiety. These changes were accompanied by similar changes in total and average fixation duration and the number of fixations, which were primarily aimed at the holds used for climbing. In combination with these findings, a decrease in search rate provided evidence for a decrease in processing efficiency as anxiety increased.