Quantification of odorous and potentially harmful substances in acrylic paint.

Within this study sixteen odour active substances (1-butanol, butyl acetate, 3-methyl-4-heptanone, butyl acrylate, styrene, ethylbenzene, propylbenzene, cumene, sec-butylbenzene, benzaldehyde, 2-ethylhexyl acrylate, naphthalene, 1-methylnaphthalene, 2-methylnaphthalene, 1,2-dimethylnaphthalene, 1,7-dimethylnaphthalene), that have previously been identified in acryl paints were quantified in ten black acrylic paint samples using GC-GC-MS (heart-cut two-dimensional gas chromatography-mass spectrometry) after prior extraction and purification via solvent assisted flavour evaporation. In this case, the preceding analysis of the most abundant odour active volatiles via GC-O (gas chromatography-olfactometry) provided indications on which smell properties might be linked with elevated and concerning levels of possibly harmful substances. Based on that work, four samples raised attention due to their mainly repelling or unpleasant odour with mainly aromatic, solvent-like, mothball-like or geranium-like smell impressions. The remaining samples either showed fruity/fermented, fruity/apple juice-like, mushroom-like or cocoa-like/earthy odour qualities. The repelling and unpleasant odour was generally linked to naphthalene or benzene derivatives that are of concern with regard to being potential carcinogens. With concentrations ranging as high as from 3.75 mg/kg to 143.41 mg/kg, n-butanol was found to be the odour active substance with the highest concentrations in all but one paint sample. The results showed that all paints contain different and specific patterns of the analysed odour active substances and volatiles. Whereas only two samples revealed no elevated concentration of any of the quantified substances, two samples (A9 and A10) showed elevated levels for all or nearly all substances. The concentrations for single substances were generally lower than the recommended exposure limit and therefore unlikely to cause any adverse effects with regards to toxicity and irritation as single constituents. However, as a group of substances these might exert adverse health effects due to combined or synergistic effects. Based on these observations, the occurrence of combinations of potentially carcinogenic substances in products which are occupationally used on a daily basis or are in direct skin contact should thus be regarded with care in the future.

Influence of elongation and desaturation on chemosensory properties in acrylates and their corresponding 1-alken-3-ones.

Acrylates as well as 1-alken-3-ones are both known to be odour active substances but are generally identified in different materials. Nonetheless, butyl acrylate and 1-octen-3-one were both found to elicit a similar mushroom-like odour in previous studies. This led to the question of whether acrylates and enones with the same overall chain length generally elicited similar odours and whether they had similar odour thresholds. Overall, most of the investigated substances showed a mushroom-like, geranium-like or fruity odour. In contrast, short chained substances elicited garlic-like, lighter gas-like or glue-like, odour qualities, suggesting a correlation between the odour quality and the overall chain length. The results showed that only between the analogue structures butyl acrylate and 1-octen-3-one as well as hexyl acrylate and 1-decen-3-one could similar odour qualities be observed. All investigated substances showed low odour threshold values in air between 0.0032 ng/lair (1-hexen-3-one) and 55 ng/lair (1-dodecen-3-one). Overall, 1-alken-3-ones revealed a higher dependency on the chain length when compared to their respective acrylates. The introduction of a second terminal double bond led to a decrease of OT values in case of the acrylates and to an increase in case of the ketones that neither contained a second terminal double bond nor a double bond located close to the carbonyl group. Despite their structural similarities, the results suggest that both substance classes are perceived in a different manner and are therefore likely to be recognized by different types of receptors or are related to different activation patterns in multi-receptor stimulation processes.

Correlations between odour activity and the structural modifications of acrylates.

Acrylates (acrylic esters) are versatile monomers that are widely used in polymer formulations because of their highly reactive α,ß-unsaturated carboxyl structure. Commonly used acrylates such as butyl acrylate are known to emit a strong unpleasant odour, and the monomers are therefore potential off-odorants in acrylic polymers. However, up to now, the odour properties of structurally related acrylic esters have not been characterised in detail. To obtain deeper insights into the smell properties of different acrylates, we investigated the relationship between the molecular structure and odour thresholds as well as the odour qualities of 20 acrylic esters, nine of these synthesised here for the first time. The OT values of 16 acrylates fell within the range from 0.73 to 20 ng/Lair, corresponding to a high-odour activity. Moreover, sec-butyl acrylate and 2-methoxyphenyl acrylate showed even lower OT values of 0.073 and 0.068, respectively. On the other hand, the OT values of the hydroxylated acrylates 2-hydroxyethyl acrylate and 2-hydroxypropyl acrylate were 5-244 times higher than those of the other compounds, demonstrating that the presence of a hydroxyl group obviously favours odour inactivity.

Assigning clinical meaning to somatic and germ-line whole-exome sequencing data in a prospective cancer precision medicine study.

PURPOSE: Implementing cancer precision medicine in the clinic requires assessing the therapeutic relevance of genomic alterations. A main challenge is the systematic interpretation of whole-exome sequencing (WES) data for clinical care. METHODS: One hundred sixty-five adults with metastatic colorectal and lung adenocarcinomas were prospectively enrolled in the CanSeq study. WES was performed on DNA extracted from formalin-fixed paraffin-embedded tumor biopsy samples and matched blood samples. Somatic and germ-line alterations were ranked according to therapeutic or clinical relevance. Results were interpreted using an integrated somatic and germ-line framework and returned in accordance with patient preferences. RESULTS: At the time of this analysis, WES had been performed and results returned to the clinical team for 165 participants. Of 768 curated somatic alterations, only 31% were associated with clinical evidence and 69% with preclinical or inferential evidence. Of 806 curated germ-line variants, 5% were clinically relevant and 56% were classified as variants of unknown significance. The variant review and decision-making processes were effective when the process was changed from that of a Molecular Tumor Board to a protocol-based approach. CONCLUSION: The development of novel interpretive and decision-support tools that draw from scientific and clinical evidence will be crucial for the success of cancer precision medicine in WES studies.Genet Med advance online publication 26 January 2017.

A systematic review of methodologies, endpoints, and outcome measures in randomized trials of radiation therapy-induced nausea and vomiting.

PURPOSE: Clinical trials in radiation therapy-induced nausea and vomiting (RINV) appear to have varied methodologies, endpoints, and outcome measures. This complicates trial comparisons, weakens practice guideline recommendations, and contributes to variability in supportive care patterns of practice. We systematically reviewed RINV trials to describe and compare their pertinent design features. MATERIALS AND METHODS: Ovid versions of the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, EMBASE, and MEDLINE to January/February 2017 were searched for adult phase III trials of RINV management strategies. Key abstracted data included trial interventions and eligibility criteria, standard radiation therapy (RT) metrics, symptom assessment procedures, symptom definitions and grading systems, pre-specified and reported endpoints, and other outcome measures. RESULTS: From 1166 references identified in the initial database search, we selected 34 trials for analysis that collectively randomized 4529 patients (median 61, range 11-1492). Twenty-eight trials (82%) were published prior to the year 2000. Twenty-seven trials (79%) involved multiple fraction RT and 7 (21%) single fraction RT. Twenty-four trials (71%) evaluated prophylactic interventions, 9 (26%) rescue interventions, and 1 trial did not specify. Thirty-three trials (97%) evaluated pharmacologic interventions. Twenty trials (59%) had patient report symptoms, 5 (15%) healthcare professionals or researchers, and 10 (29%) did not specify. Nausea was not defined in any trial but was reported as a stand-alone symptom in 26 trials (76%) and was graded in 20 (59%), with categorical qualitative scales being the most common method. Vomiting was defined in 3 trials (9%), was reported as a stand-alone symptom in 17 (47%), and was graded in 7 (21%), with continuous numerical scales being the most common method. Retching was defined in 3 trials, was not reported as a stand-alone symptom in any trial, and was graded in 1 (3%). Twenty-one trials (62%) created compound symptom measures that combined individual symptoms. Fifteen trials (44%) reported "emetic episode/event" measures but only 9 defined them. Seventeen trials (50%) reported complicated endpoints (e.g., "response," "control," "success") that combined multiple symptom or compound symptom measures, but 7 did not define them comprehensively. Ten trials (29%) defined a primary endpoint a priori. CONCLUSIONS: Methodologies, endpoints, and outcome measures varied considerably among 34 randomized trials in RINV.

Anti-seizure medication treatment trials prior to pre-surgical evaluation.

Purpose: Our study evaluates patterns of anti-seizure medication (ASM) usage prior to pre-surgical evaluation in drug resistant epilepsy (DRE). Methods: We conducted a retrospective study of patients with DRE presenting for pre-surgical evaluation from 1/1/2017 to 12/31/2018. We abstracted demographic data, ASM usage, MRI and EEG findings, and distance from home to our center. Results: In total, 54 patients (23 female) were included. The mean number of ASM trials at the time of pre-surgical evaluation was 5.62 (±3.3; range 1-15). A mean of 0.4 ASMs (±1.1; range 0-6) were initiated at our center prior to pre-surgical evaluation. MRI localization to regions other than the hippocampal or temporal region (p = 0.002) was associated with higher numbers of ASM trials. A trend for a larger number of ASM trials was seen for increased distance of patient primary residence from our center, right-sided ictal EEG laterality, and posterior quadrant or non-localized ictal EEG patterns. Conclusions: Only 17% of patients were referred for pre-surgical evaluation after a trial of 1-2 ASMs. On average, patients tried 5.6 different ASMs with most of those trials predating referral to our center. Temporal lobe lesions were associated with fewer ASM trials prior to referral. Female sex was associated with an average of two more ASM trials than males. Our data do not allow us to determine how access to care, patient choice, and physician opinions impact the variability of ASM trials prior to referral for surgical evaluation. Our data indicate that delays to pre-surgical evaluation continue to occur.

Early longitudinal experiences increase medical student self-efficacy.

This article was migrated. The article was marked as recommended. Background: The purpose of this study was to investigate the impact of early longitudinal preceptorship experiences on the evolution of general self-efficacy and patient-centeredness self-efficacy through medical school. Methods:Validated surveys for general self-efficacy and patient-centeredness self-efficacy were administered in an allopathic medical school at three timepoints. These data were stratified by traditional and longitudinal preceptorship groups and analyzed using Generalized Estimating Equations. Qualitative analysis of narrative medicine essays by the same cohort during their preceptorship experiences was also performed. Results: While general self-efficacy remained largely unchanged over time, patient-centeredness self-efficacy measures increased throughout medical school in the whole cohort (N=157). The longitudinal preceptorship group had higher gains in patient-centeredness self-efficacy, especially in the domain of exploring patient perspectives (p<0.05). The qualitative analysis of narrative medicine essays showed those in longitudinal preceptorships were more likely to discuss health care systems issues, consider psychosocial factors, and perceive themselves as active members of the care team. Discussion:Our study indicates greater patient-centeredness attitudes over time among students who have early longitudinal experiences, perhaps due to the self-efficacy building nature of these experiences. Our research suggest that medical school programs should consider incorporating opportunities for early longitudinal clinical experiences for their students.

Quantification of Allyl Methyl Sulfide, Allyl Methyl Sulfoxide, and Allyl Methyl Sulfone in Human Milk and Urine After Ingestion of Cooked and Roasted Garlic.

Due to its characteristic flavor and positive effects on human health, garlic is a highly valued food ingredient. Consumption of garlic alters the quality of body odors, which may in some instances hinder social interaction but be beneficial in other contexts, as it is assumed to contribute to early flavor learning in the breastfeeding context, for example. In previous work, allyl methyl sulfide (AMS) has been identified as the major odor-active metabolite in urine and milk, being excreted together with the odorless metabolites allyl methyl sulfoxide (AMSO) and allyl methyl sulfone (AMSO2) after ingestion of raw garlic. The present work aimed to elucidate whether commonly used culinary thermal processing steps influence the excretion profiles of garlic-derived compounds. To this aim, urine (n = 6) and milk (n = 4) samples were donated before and after ingestion of roasted and cooked garlic and investigated by gas chromatography-olfactometry/mass spectrometry, and, in the case of milk, by aroma profile analysis. The concentrations of AMS, AMSO, and AMSO2 were determined by stable isotope dilution assays. Sensory evaluations revealed that a garlic-like odor was perceivable in milk samples donated after ingestion of roasted and cooked garlic. Besides AMS, AMSO, and AMSO2, no other odor-active or odorless compounds related to the ingestion of roasted or cooked garlic were detected in the urine and milk samples. Maximum concentrations of the metabolites were detected around 1-2 h after garlic intake. In some cases, a second maximum occurred around 6 h after ingestion of garlic. The cooking procedure led to a more important reduction of metabolite concentrations than the roasting procedure. These findings suggest that intake of processed garlic leads to a transfer of odor-active and odorless metabolites into milk, which contributes to early flavor learning during breastfeeding and may also have a physiological effect on the infant.

Characterization of Odorous and Potentially Harmful Substances in Artists' Acrylic Paint.

Acrylic paints are fast drying water based paints that are easy to handle and have a high covering capacity and therefore possess many characteristics that make them applicable in a wide range of applications, such as varnishes or artists paints. Due to their emitted volatile organic compounds, these paints are associated with different work-related diseases and are known to emit an unpleasant odor. In this study six acrylic paints for artists were analyzed regarding their odor-active constituents. Therefore, the samples were extracted with dichloromethane and purified via solvent assisted flavor evaporation prior to analysis of the distillates by gas chromatography-mass spectrometry (GC-MS), gas chromatography-olfactometry (GC-O), and GC-GC-MS/O. Additionally all samples were sensorially characterized by a trained sensory panel. The identified odorous substances were primarily benzene derivatives (styrene, ethylbenzene, allylbenzene, propylbenzene) with a plastic-like, aromatic and solvent-like odor. Thereby, polycyclic aromatic hydrocarbons (naphthalene, indane, and tetralin derivatives) contributed to the plastic- and mothball-like odor whereas acrylic monomers (butyl acrylate) were found to be responsible for a mushroom-like and geranium leaf-like odor. As most of these substances are also known to be harmful, a reduction or replacement of these substances by less toxic and non-odor active ingredients is likely to turn out to be advisable in order to reduce the odor and potential negative physiological effects of paints.

Resolving the smell of wood - identification of odour-active compounds in Scots pine (Pinus sylvestris L.).

Being one of the most common trees in forests, Pinus sylvestris L. is a frequently used raw material for wood products. Its specific odour is, however, mostly unresolved to date. Accordingly, we investigated Scots pine wood samples grown in Germany for their main odorant composition. We employed dedicated odorant analysis techniques such as gas chromatography-olfactometry (GC-O) and aroma extract dilution analysis (AEDA) and successfully detected 44 odour-active compounds; of these, 39 substances were successfully identified by gas chromatography-mass spectrometry/olfactometry (GC-MS/O) and two-dimensional gas chromatography-mass spectrometry/olfactometry (2D-GC-MS/O). Among the main odorants found were (E,E)-nona-2,4-dienal, vanillin, phenylacetic acid, 3-phenylpropanoic acid, δ-octalactone and α-pinene, all of them having been detected with high flavour dilution factors during GC-O analyses. The majority of the identified odorants were fatty acid degradation products, plus some terpenoic substances and odorous substances resulting from the degradation of lignin. Although some of the detected substances have previously been reported as constituents of wood, 11 substances are reported here for the first time as odour-active compounds in wood, amongst them heptanoic acid, γ-octalactone, δ-nonalactone and (E,Z,Z)-trideca-2,4,7-trienal.

Malignant Gastric Outlet Obstruction from Pancreatic Cancer.

Patients with advanced-stage pancreatic cancer are typically burdened by many symptoms that impair functioning and worsen quality of life. We report an exceptional case of a 73-year-old woman with T4N1M0 adenocarcinoma of the uncinate process of the pancreas who developed significant gastric outlet obstruction - an uncommon yet potentially life-threatening complication of disease progression. She developed progressive abdominal pain and emesis, and profound dilatation of her stomach was detected on a radiation therapy simulation CT scan that required urgent decompression. Malignant gastric outlet obstruction must be included in the differential diagnosis when patients with known advanced disease of the pancreas present with obstructive upper gastrointestinal symptoms.

Cerebellar volume and cognitive functioning in children who experienced early deprivation.

BACKGROUND: The cerebellum is a brain region recognized primarily in the coordination of movement and related accessory motor functions. In addition, emerging evidence implicates the cerebellum in cognitive processes and suggests that this brain region might be subject to experience-dependent changes in structure. Therefore, the aim of this study was to evaluate the role of early environmental deprivation in the maturation of the cerebellum and aspects of cognitive development. METHODS: Structural magnetic resonance imaging volumes of 12 cerebellar sub-regions from 31 previously neglected and 30 typically developing children were compared with subjects' corresponding neuropsychological test scores. RESULTS: Neglected children had smaller volume of the superior-posterior cerebellar lobes. Moreover, superior-posterior lobe volume was found to mediate neuropsychological test performance differences between groups, with larger volumes yielding better outcomes on tests of memory and planning. CONCLUSIONS: These data support the importance of experience-dependent changes in cerebellar structure and highlight the role of the cerebellum in higher cognitive functions.