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To facilitate Safe and Sustainable by Design (SSbD) strategies during the development of nanomaterials (NMs), quick and easy in vitro assays to test for hazard potential at an early stage of NM development are essential. The formation of reactive oxygen species (ROS) and the induction of oxidative stress are considered important mechanisms that can lead to NM toxicity. In vitro assays measuring oxidative stress are therefore commonly included in NM hazard assessment strategies. The fluorescence-based dichloro-dihydro-fluorescein (DCFH) assay for cellular oxidative stress is a simple and cost-effective assay, making it a good candidate assay for SSbD hazard testing strategies. It is however subject to several pitfalls and caveats. Here, we provide further optimizations to the assay using 5-(6)-Chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate acetyl ester (CM-H2DCFDA-AE, referred to as DCFH probe), known for its improved cell retention. We measured the release of metabolic products of the DCFH probe from cells to supernatant, direct reactions of CM-H2DCFDA-AE with positive controls, and compared the commonly used plate reader-based DCFH assay protocol with fluorescence microscopy and flow cytometry-based protocols. After loading cells with DCFH probe, translocation of several metabolic products of the DCFH probe to the supernatant was observed in multiple cell types. Translocated DCFH products are then able to react with test substances including positive controls. Our results also indicate that intracellularly oxidized fluorescent DCF is able to translocate from cells to the supernatant. In either way, this will lead to a fluorescent supernatant, making it difficult to discriminate between intra- and extra-cellular ROS production, risking misinterpretation of possible oxidative stress when measuring fluorescence on a plate reader. The use of flow cytometry instead of plate reader-based measurements resolved these issues, and also impro

The world is warming up, causing the rising water levels. The Netherlands has a rich history in the field of water protection: throughout the centuries, the country's increasingly improved its defences with the help of new techniques, technological advancements, and better regulated management. However, since the end of the previous century, there has been a shift in the way water is dealt with. No longer is the motto 'keeping the water out', but rather 'learning to live with water'. This thesis investigates the reasons behind this change in Dutch policy by answering the following question: "What are the historical architectural adaptations of the Netherlands before 1953 to effectively handle water within the face of rising water levels and why did this strategy change after 1953 from 'keeping the water out' to 'learning to live with water'?"

The world is warming up, causing a rise in water levels. The Netherlands has a rich history in the field of water protection: throughout the centuries, the country has increasingly improved its defenses with the help of new techniques, technological advancements, and better regulated management. However, since the end of the previous century, there has been a shift in the way water is dealt with. No langer is the motto "keeping the water out," but rather "learning to live with water." This thesis investigates the reasons behind this change in Dutch policy by answering the following question: 'What are the historica/ architectura/ adaptations of the Netherlands before 1953 to effectively hand/e water within the face of rising water levels and why did this strategy change after 1953 from 'keeping the water out' to 'learning to live with water?' To answer this question correctly, two periods, each with sub-periods, have been examined: before the flood disaster of 1953, and from 1953 to the present. When examinIng the sub-periods, the relationship between catastrophic events, water management, and technological advancements was looked at. By addressing architectural cases, this relationship could be clearly defined. The results indicate a correlation between when these events occur and how they are responded to with technology and water management. Another correlation was observed in how technological progress also led to better organization: improved technology enabled larger projects, which in turn required larger farms of water management. However, the flood disaster of 1953 revealed that there is a limit to protection against water. The floods of 1953, 1993, and 1995 made the Dutch realize that merely protecting against water is not sufficient; a new strategy of water management was needed, one in which we also learn to live with water. This strategy must ensure that the Netherlands remains safe from water in the future, even with the e, AR2A011, Architectural History Thesis, Architecture, Urbanism and Building Sciences

Over the recent years, EU chemicals legislation, guidance and test guidelines have been developed or adapted for nanomaterials to facilitate safe use of nanomaterials. This paper provides an overview of the information requirements across different EU regulatory areas. For each information requirement, a group of 22 experts identified potential needs for further action to accommodate guidance and test guidelines to nanomaterials. Eleven different needs for action were identified, capturing twenty-two information requirements that are specific to nanomaterials and relevant to multiple regulatory areas. These were further reduced to three overarching issues: 1) resolve issues around nanomaterial dispersion stability and dosing in toxicity testing, in particular for human health endpoints, 2) further develop tests or guidance on degradation and transformation of organic nanomaterials or nanomaterials with organic components, and 3) further develop tests and guidance to measure (a)cellular reactivity of nanomaterials. Efforts towards addressing these issues will result in better fit-for-purpose test methods for (EU) regulatory compliance. Moreover, it secures validity of hazard and risk assessments of nanomaterials. The results of the study accentuate the need for a structural process of identification of information needs and knowledge generation, preferably as part of risk governance and closely connected to technological innovation policy.

The Safe-by-Design (SbD) concept aims to facilitate the development of safer materials/products, safer production, and safer use and end-of-life by performing timely SbD interventions to reduce hazard, exposure, or both. Early hazard screening is a crucial first step in this process. In this review, for the first time, commonly used in vitro assays are evaluated for their suitability for SbD hazard testing of nanomaterials (NMs). The goal of SbD hazard testing is identifying hazard warnings in the early stages of innovation. For this purpose, assays should be simple, cost-effective, predictive, robust, and compatible. For several toxicological endpoints, there are indications that commonly used in vitro assays are able to predict hazard warnings. In addition to the evaluation of assays, this review provides insights into the effects of the choice of cell type, exposure and dispersion protocol, and the (in)accurate determination of dose delivered to cells on predictivity. Furthermore, compatibility of assays with challenging advanced materials and NMs released from nano-enabled products (NEPs) during the lifecycle is assessed, as these aspects are crucial for SbD hazard testing. To conclude, hazard screening of NMs is complex and joint efforts between innovators, scientists, and regulators are needed to further improve SbD hazard testing.

RIVM rapport:Patients suffering from pelvic organ prolapse (POP) can be treated by placing mesh implants in the body. The Health and Youth Care Inspectorate (IGJ) asked RIVM to conduct a laboratory analysis on mesh implants used to treat POP in the Netherlands in 2018. The request was to analyse various properties of these products. The results of this laboratory analysis do not indicate that the tested products are unsafe for patients. The laboratory study consisted of various types of tests. From six mesh implants from different manufacturers we analysed the chemical composition, as well as the structure and dimensions of various components of the products. The results of these tests were in line with the descriptions in the technical documentation for these products. Furthermore, we tested whether the mesh implants are harmful to laboratory-grown biological cells. The results of this test were also in line with the test results described by the manufacturers in the technical documentation. Five of the six products triggered no response in the cells used in the test. One product triggered a mild cellular response. This particular product is designed to be partially absorbed in the body. In comparison, the other tested mesh products are non-absorbable. This difference might play a role in the observed mild cellular response with this product. The test with biological cells is part of the standard set of tests prescribed for the biological evaluation of implants. Based on this broader set of tests, the manufacturer tested this product more extensively before it was authorised to be placed on the market. The combined results from these laboratory tests gave no indication of harmful effects. RIVM puts up for debate whether the test using lab-grown cells is suitable to assess the safety of partially absorbable mesh implants. It therefore recommends taking this consideration into account in the periodic review of the international document that describes this test method., Bekkenbodemmatjes zijn implantaten die in het lichaam kunnen worden geplaatst om verzakkingen van organen in het gebied van de bekkenbodem te behandelen. De Inspectie Gezondheidszorg en Jeugd (IGJ(Inspectie Gezondheidszorg en Jeugd)) heeft het RIVM gevraagd om laboratoriumonderzoek te doen naar bekkenbodemmatjes die artsen in 2018 in Nederland hebben geplaatst. De vraag was om verschillende eigenschappen van de producten te onderzoeken. In dit laboratoriumonderzoek zijn geen resultaten gevonden die aangeven dat de producten onveilig zijn voor patienten. Het laboratoriumonderzoek bestond uit verschillende typen analyses. Zo is van zes bekkenbodemmatjes van verschillende fabrikanten onderzocht van welke materialen ze gemaakt zijn. Ook is gekeken naar de opbouw en afmetingen van verschillende onderdelen van de matjes. De resultaten hiervan kloppen met wat de fabrikanten beschrijven in de technische documentatie over hun producten. Met een ander soort analyse is gekeken of bekkenbodemmatjes een schadelijke reactie veroorzaken in cellen die in het laboratorium zijn gekweekt. Ook deze resultaten komen overeen met wat de fabrikanten in de technische documentatie vermelden. Bij vijf van de zes producten was er geen reactie te zien in de cellen waarmee ze werden getest. Bij een product was een milde reactie in de cellen te zien. Dit product is zo gemaakt dat het voor een deel in het lichaam wordt afgebroken, terwijl dit bij de andere producten niet het geval is. Dat kan een verklaring zijn voor de milde reactie in de cellen bij dit ene product. De test die is gedaan, is onderdeel van een standaardpakket van testen die worden voorgeschreven om te testen of implantaten mogelijk nadelige effecten op het lichaam hebben. Voor de toelating op de markt heeft de fabrikant dit product veel uitgebreider getest. De gecombineerde resultaten van het hele pakket aan laboratoriumtesten gaven geen aanwijzingen voor schadelijke effecten. Het RIVM vraagt zich wel af of de test met cellen in h

Air-liquid interface (ALI) lung cell models cultured on permeable transwell inserts are increasingly used for respiratory hazard assessment requiring controlled aerosolization and deposition of any material on ALI cells. The approach presented herein aimed to assess the transwell insert-delivered dose of aerosolized materials using the VITROCELL® Cloud12 system, a commercially available aerosol-cell exposure system. An inter-laboratory comparison study was conducted with seven European partners having different levels of experience with the VITROCELL® Cloud12. A standard operating procedure (SOP) was developed and applied by all partners for aerosolized delivery of materials, i.e., a water-soluble molecular substance (fluorescence-spiked salt) and two poorly soluble particles, crystalline silica quartz (DQ 12) and titanium dioxide nanoparticles (TiO 2 NM-105). The material dose delivered to transwell inserts was quantified with spectrofluorometry (fluorescein) and with the quartz crystal microbalance (QCM) integrated in the VITROCELL® Cloud12 system. The shape and agglomeration state of the deposited particles were confirmed with transmission electron microscopy (TEM). Inter-laboratory comparison of the device-specific performance was conducted in two steps, first for molecular substances (fluorescein-spiked salt), and then for particles. Device- and/or handling-specific differences in aerosol deposition of VITROCELL® Cloud12 systems were characterized in terms of the so-called deposition factor (DF), which allows for prediction of the transwell insert-deposited particle dose from the particle concentration in the aerosolized suspension. Albeit DF varied between the different labs from 0.39 to 0.87 (mean (coefficient of variation (CV)): 0.64 (28%)), the QCM of each VITROCELL® Cloud 12 system accurately measured the respective transwell insert-deposited dose. Aerosolized delivery of DQ 12 and TiO 2 NM-105 particles showed good linearity (R 2 > 0.95) between par

Item does not contain fulltext, PURPOSE: Elucidating the complex interactions between physical activity (PA), a multidimensional concept, and physical capacity (PC) may reveal ways to improve rehabilitation interventions. This cross-sectional study aimed to explore which PA dimensions are related to PC in people after minor stroke. MATERIALS AND METHODS: Community dwelling individuals >6 months after minor stroke were evaluated with a 10-Meter-Walking-Test (10MWT), Timed-Up & Go, and the Mini Balance Evaluation System Test. The following PA outcomes were measured with an Activ8 accelerometer: counts per minute during walking (CPM(walking); a measure of intensity), number of active bouts (frequency), mean length of active bouts (distribution), and percentage of waking hours in upright positions (duration). Multivariable linear regression models, adjusted for age, sex and BMI, were used to assess the relationships between PC and PA outcomes. RESULTS: Sixty-nine participants [62.2 ± 9.8 years, 61% male, 20 months post onset (IQR 13.0-53.5)] were included in the analysis. CPM(walking) was significantly associated to PC in the 10MWT (std. ß = 0.409, p = 0.002), whereas other associations between PA and PC were not significant. CONCLUSIONS: The PA dimension intensity of walking is significantly associated with PC, and appears to be an important tool for future interventions in rehabilitation after minor stroke.Implications for rehabilitationIt is recommended to express physical activity after minor stroke in multiple dimensions such as intensity, frequency, duration and distribution.In particular, intensity of physical activity measured with accelerometer counts is most closely related to physical capacity.The findings of this study underline the importance of being physically active beyond a certain intensity.In future development of interventions and guidelines that aim to promote daily physical activity, intensity should be taken into account.

Contains fulltext : 287121.pdf (Publisher’s version ) (Open Access), PURPOSE: Elucidating the complex interactions between physical activity (PA), a multidimensional concept, and physical capacity (PC) may reveal ways to improve rehabilitation interventions. This cross-sectional study aimed to explore which PA dimensions are related to PC in people after minor stroke. MATERIALS AND METHODS: Community dwelling individuals >6 months after minor stroke were evaluated with a 10-Meter-Walking-Test (10MWT), Timed-Up & Go, and the Mini Balance Evaluation System Test. The following PA outcomes were measured with an Activ8 accelerometer: counts per minute during walking (CPM(walking); a measure of intensity), number of active bouts (frequency), mean length of active bouts (distribution), and percentage of waking hours in upright positions (duration). Multivariable linear regression models, adjusted for age, sex and BMI, were used to assess the relationships between PC and PA outcomes. RESULTS: Sixty-nine participants [62.2 ± 9.8 years, 61% male, 20 months post onset (IQR 13.0-53.5)] were included in the analysis. CPM(walking) was significantly associated to PC in the 10MWT (std. ß = 0.409, p = 0.002), whereas other associations between PA and PC were not significant. CONCLUSIONS: The PA dimension intensity of walking is significantly associated with PC, and appears to be an important tool for future interventions in rehabilitation after minor stroke.Implications for rehabilitationIt is recommended to express physical activity after minor stroke in multiple dimensions such as intensity, frequency, duration and distribution.In particular, intensity of physical activity measured with accelerometer counts is most closely related to physical capacity.The findings of this study underline the importance of being physically active beyond a certain intensity.In future development of interventions and guidelines that aim to promote daily physical activity, intensity should be taken into account.

Purpose: Elucidating the complex interactions between physical activity (PA), a multidimensional concept, and physical capacity (PC) may reveal ways to improve rehabilitation interventions. This cross-sectional study aimed to explore which PA dimensions are related to PC in people after minor stroke. Materials and methods: Community dwelling individuals >6 months after minor stroke were evaluated with a 10-Meter-Walking-Test (10MWT), Timed-Up & Go, and the Mini Balance Evaluation System Test. The following PA outcomes were measured with an Activ8 accelerometer: counts per minute during walking (CPM walking; a measure of intensity), number of active bouts (frequency), mean length of active bouts (distribution), and percentage of waking hours in upright positions (duration). Multivariable linear regression models, adjusted for age, sex and BMI, were used to assess the relationships between PC and PA outcomes. Results: Sixty-nine participants [62.2 ± 9.8 years, 61% male, 20 months post onset (IQR 13.0–53.5)] were included in the analysis. CPM walking was significantly associated to PC in the 10MWT (std. ß = 0.409, p = 0.002), whereas other associations between PA and PC were not significant. Conclusions: The PA dimension intensity of walking is significantly associated with PC, and appears to be an important tool for future interventions in rehabilitation after minor stroke.Implications for rehabilitation It is recommended to express physical activity after minor stroke in multiple dimensions such as intensity, frequency, duration and distribution. In particular, intensity of physical activity measured with accelerometer counts is most closely related to physical capacity. The findings of this study underline the importance of being physically active beyond a certain intensity. In future development of interventions and guidelines that aim to promote daily physical activity, intensity should be taken into account.

Inhalation exposure to environmental and occupational aerosol contaminants is associated with many respiratory health problems. To realistically mimic long-term inhalation exposure for toxicity testing, lung epithelial cells need to maintained and exposed under air-liquid interface (ALI) conditions for a prolonged period of time. In addition, to study cellular responses to aerosol particles, lung epithelial cells have to be co-cultured with macrophages. To that aim, we evaluated human bronchial epithelial Calu-3, 16HBE14o- (16HBE), H292, and BEAS-2B cell lines with respect to epithelial morphology, barrier function and cell viability under prolonged ALI culture conditions. Only the Calu-3 cells can retain the monolayer structure and maintain a strong tight junction under long-term ALI culture at least up to 2 weeks. As such, Calu-3 cells were applied as the structural barrier to create co-culture models with human monocyte-derived macrophages (MDMs) and THP-1 derived macrophages (TDMs). Adhesion of macrophages onto the epithelial monolayer was allowed for 4 h with a density of 5 × 104 macrophages/cm2. In comparison to the Calu-3 mono-culture model, Calu-3 + TDM and Calu-3 + MDM co-culture models showed an increased sensitivity in inflammatory responses to lipopolysaccharide (LPS) aerosol at Day 1 of co-culture, with the Calu-3 + MDM model giving a stronger response than Calu-3 + TDM. Therefore, the epithelial monolayer integrity and increased sensitivity make the Calu-3 + MDM co-culture model a preferred option for ALI exposure to inhaled aerosols for toxicity testing.

Physical activity monitoring with wearable technology has the potential to support stroke rehabilitation. Little is known about how physical therapists use and value the use of wearable activity monitors. This cross-sectional study explores the use, perspectives, and barriers to wearable activity monitoring in day-to-day stroke care routines amongst physical therapists. Over 300 physical therapists in primary and geriatric care and rehabilitation centers in the Netherlands were invited to fill in an online survey that was developed based on previous studies and interviews with experts. In total, 103 complete surveys were analyzed. Out of the 103 surveys, 27% of the respondents were already using activity monitoring. Of the suggested treatment purposes of activity monitoring, 86% were perceived as useful by more than 55% of the therapists. The most recognized barriers to clinical implementation were lack of skills and knowledge of patients (65%) and not knowing what brand and t

Human papilloma virus (HPV) is a well-established causative factor in a subset of squamous cell carcinomas of the head and neck (HNSCC). Although HPV can be detected in various anatomical subsites, HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) is the most common HPV-related malignancy of the head and neck, and its worldwide incidence is constantly rising. Patients with OPSCC are generally younger, have less co-morbidities and generally have better prognosis due to different biological mechanisms of carcinogenesis. These facts have generated hypotheses on potential treatment modifications, aiming to minimize treatment-related toxicities without compromising therapy efficacy. Numerous randomized clinical trials have been designed to verify this strategy and increasingly real-world evidence data from retrospective, observational studies is becoming available. Until now, the data do not support any modification in contemporary treatment protocols. In this narrative review, we outline recent data provided by both randomized controlled trials and real-world evidence of HPV-positive OPSCC in terms of clinical value. We critically analyze the potential value and drawbacks of the available data and highlight future research directions. This article was written by members and invitees of the International Head and Neck Scientific Group.(www.IHNSG.com).

Background: Stroke survivors show deteriorated physical functioning and physical activity levels. Physical activity levels of stroke survivors are generally low. It is increasingly recognized that physical activity is a multidimensional construct that cannot be captured in a single outcome. In-depth insight into multidimensional physical activity patterns may guide the development and timing of targeted rehabilitation interventions. This longitudinal cohort study explored how multidimensional physical activity outcomes develop during recovery in the subacute phase after stroke and if changes in physical activity were correlated to recovery of lower limb motor function. Methods: Patients were recruited during inpatient rehabilitation. At 3, 12, and 26 weeks post-onset, motor function was measured by the Fugl-Meyer Lower Extremity Assessment (FMA-LE). Physical activity was measured with the Activ8 accelerometer in multiple outcomes: counts per minute during walking (CPMwalking; a measure of Intensity), number of active bouts (Frequency), mean length of active bouts (Distribution) and % of waking time in upright positions (Duration). Generalized estimating equations (GEE) were used to study changes in physical activity over time and the relation with the change in lower limb motor recovery. Results: Thirty-nine patients (age 56 ± 9, 77% male, 89% ischemic stroke) were included. GEE models showed a significant main effect of time for PA Intensity (+ 13%, p = 0.007) and Duration (+ 64%, p = 0.012) between 3 and 12 weeks. Motor function did not show a significant effect in all PA models across the 3 timepoints (p > 0.020). A significant interaction effect of time × motor function was observed (p < 0.001). Conclusions: Patterns of PA recovery depend on the PA dimensions: PA Intensity and Duration increased mostly between 3 and 12 weeks post-stroke, whereas Frequency and Distribution did not show substantial changes. Further, no strong associations with

Objective: The purpose of this study was to investigate the relationship between body mass index (BMI) class and physical activity and sedentary behavior in patients with acute coronary syndrome (ACS) during cardiac rehabilitation (CR). Methods: This study was a secondary analysis of the OPTICARE trial. Physical activity and sedentary behavior were measured in participants with ACS (n = 359) using actigraphy at baseline, directly after completion of a multidisciplinary 12-week exercise-based CR program and 9 months thereafter. Outcome measures were step count and duration of time (percentage of wear time) spent in light physical activity, moderate-to-vigorous physical activity, and sedentary behavior. Participants were classified as normal weight (BMI = 18.5-24.99 kg/m2; n = 82), overweight (BMI = 25.0-29.99 kg/m2; n = 182), or obese (BMI ≥ 30.0 kg/m2; n = 95). Linear mixed-effects models were applied to study the relationship between BMI class and physical activity and sedentary behavior. Results: At the start of CR, compared with participants with normal weight, participants with obesity made on average 1.11 steps fewer per minute (952 steps/d), spent 2.9% (25 min/d) less time in light physical activity, and spent 3.31% (28 min/d) more time in sedentary behavior. Participants of all BMI classes improved their physical activity and sedentary behavior levels similarly during CR, and these improvements were maintained after completion of CR. Conclusion: Participants with ACS who had obesity started CR with a less favorable physical activity and sedentary behavior profile than that of participants with normal weight. Because all BMI classes showed similar improvement during CR, this deficit was preserved. Impact: This study indicates that reconsideration of the CR program in the Netherlands for patients with ACS and obesity is warranted, and development of more inclusive interventions for specific populations is needed. A new program for people with obesity should

Physical activity monitoring with wearable technology has the potential to support stroke rehabilitation. Little is known about how physical therapists use and value the use of wearable activity monitors. This cross-sectional study explores the use, perspectives, and barriers to wearable activity monitoring in day-to-day stroke care routines amongst physical therapists. Over 300 physical therapists in primary and geriatric care and rehabilitation centers in the Netherlands were invited to fill in an online survey that was developed based on previous studies and interviews with experts. In total, 103 complete surveys were analyzed. Out of the 103 surveys, 27% of the respondents were already using activity monitoring. Of the suggested treatment purposes of activity monitoring, 86% were perceived as useful by more than 55% of the therapists. The most recognized barriers to clinical implementation were lack of skills and knowledge of patients (65%) and not knowing what brand and type of monitor to choose (54%). Of the non-users, 79% were willing to use it in the future. In conclusion, although the concept of remote activity monitoring was perceived as useful, it was not widely adopted by physical therapists involved in stroke care. To date, skills, beliefs, and attitudes of individual therapists determine the current use of wearable technology.

For toxicity testing of airborne particles, air-liquid interface (ALI) exposure systems have been developed for in vitro tests in order to mimic realistic exposure conditions. This puts specific demands on the cell culture models. Many cell types are negatively affected by exposure to air (e.g., drying out) and only remain viable for a few days. This limits the exposure conditions that can be used in these models: usually relatively high concentrations are applied as a cloud (i.e., droplets containing particles, which settle down rapidly) within a short period of time. Such experimental conditions do not reflect realistic long-term exposure to low concentrations of particles. To overcome these limitations the use of a human bronchial epithelial cell line, Calu-3 was investigated. These cells can be cultured at ALI conditions for several weeks while retaining a healthy morphology and a stable monolayer with tight junctions. In addition, this bronchial model is suitable for testing the effects of repeated exposures to low, realistic concentrations of airborne particles using an ALI exposure system. This system uses a continuous airflow in contrast to other ALI exposure systems that use a single nebulization producing a cloud. Therefore, the continuous flow system is suitable for repeated and prolonged exposure to airborne particles while continuously monitoring the particle characteristics, exposure concentration, and delivered dose. Taken together, this bronchial model, in combination with the continuous flow exposure system, is able to mimic realistic, repeated inhalation exposure conditions that can be used for toxicity testing.

According to some legislation grouping can streamline data gap filling for the hazard assessment of substances. The GRACIOUS Framework aims to facilitate the application of grouping of nanomaterials or nanoforms (NFs), in a regulatory context and to support innovation. This includes using grouping to enable read-across from (a) source(s), for which data and information exist, to a similar target NF where information is lacking. The Framework provides an initial set of hypotheses for the grouping of NFs which take into account the identity and use(s) of the NFs, as well as the purpose of grouping. Initial collection of basic information allows selection of an appropriate pre-defined grouping hypothesis and a tailored Integrated Approach to Testing and Assessment (IATA), designed to generate new evidence to support acceptance or rejection of the hypothesis. Users needing to develop their own user-defined hypothesis (and IATA) are also supported by the Framework. In addition, the IATA guides acquisition of the information needed to support read-across. This approach gathers information to render risk assessment more efficient, affordable, as well as reducing the use of test animals.

Contains fulltext : 229866.pdf (publisher's version ) (Open Access), E-cigarettes have become increasingly popular in the last decade and are considered less harmful than traditional tobacco products due to the lower content of toxic and carcinogenic compounds. However, this is still a controversial issue. This paper contains a review of previous reports on the composition of e-cigarettes and their impact on the pathogenesis and risk of head and neck cancer (HNC). The objective of the review was to compare the molecular and health effects of e-cigarette use in relation to the effects of traditional cigarette smoking in the upper respiratory tract, and to assess the safety and effect of e-cigarettes on HNC risk. A review for English language articles published until 31 August 2020 was made, using a PubMed (including MEDLINE), CINAHL Plus, Embase, Cochrane Library and Web of Science data. The authors reviewed articles on both toxic and carcinogenic compounds contained in e-cigarettes and their molecular and health effects on the upper respiratory tract in comparison to tobacco cigarettes. The risk of developing head and neck squamous cell carcinoma (HNSCC) remains lower in users of e-cigarettes compared with tobacco smokers. However, more long-term studies are needed to better address the safety of e-cigarettes.

Contains fulltext : 229866.pdf (publisher's version ) (Open Access), E-cigarettes have become increasingly popular in the last decade and are considered less harmful than traditional tobacco products due to the lower content of toxic and carcinogenic compounds. However, this is still a controversial issue. This paper contains a review of previous reports on the composition of e-cigarettes and their impact on the pathogenesis and risk of head and neck cancer (HNC). The objective of the review was to compare the molecular and health effects of e-cigarette use in relation to the effects of traditional cigarette smoking in the upper respiratory tract, and to assess the safety and effect of e-cigarettes on HNC risk. A review for English language articles published until 31 August 2020 was made, using a PubMed (including MEDLINE), CINAHL Plus, Embase, Cochrane Library and Web of Science data. The authors reviewed articles on both toxic and carcinogenic compounds contained in e-cigarettes and their molecular and health effects on the upper respiratory tract in comparison to tobacco cigarettes. The risk of developing head and neck squamous cell carcinoma (HNSCC) remains lower in users of e-cigarettes compared with tobacco smokers. However, more long-term studies are needed to better address the safety of e-cigarettes.

Contains fulltext : 229866.pdf (publisher's version ) (Open Access), E-cigarettes have become increasingly popular in the last decade and are considered less harmful than traditional tobacco products due to the lower content of toxic and carcinogenic compounds. However, this is still a controversial issue. This paper contains a review of previous reports on the composition of e-cigarettes and their impact on the pathogenesis and risk of head and neck cancer (HNC). The objective of the review was to compare the molecular and health effects of e-cigarette use in relation to the effects of traditional cigarette smoking in the upper respiratory tract, and to assess the safety and effect of e-cigarettes on HNC risk. A review for English language articles published until 31 August 2020 was made, using a PubMed (including MEDLINE), CINAHL Plus, Embase, Cochrane Library and Web of Science data. The authors reviewed articles on both toxic and carcinogenic compounds contained in e-cigarettes and their molecular and health effects on the upper respiratory tract in comparison to tobacco cigarettes. The risk of developing head and neck squamous cell carcinoma (HNSCC) remains lower in users of e-cigarettes compared with tobacco smokers. However, more long-term studies are needed to better address the safety of e-cigarettes.

According to some legislation grouping can streamline data gap filling for the hazard assessment of substances. The GRACIOUS Framework aims to facilitate the application of grouping of nanomaterials or nanoforms (NFs), in a regulatory context and to support innovation. This includes using grouping to enable read-across from (a) source(s), for which data and information exist, to a similar target NF where information is lacking. The Framework provides an initial set of hypotheses for the grouping of NFs which take into account the identity and use(s) of the NFs, as well as the purpose of grouping. Initial collection of basic information allows selection of an appropriate pre-defined grouping hypothesis and a tailored Integrated Approach to Testing and Assessment (IATA), designed to generate new evidence to support acceptance or rejection of the hypothesis. Users needing to develop their own user-defined hypothesis (and IATA) are also supported by the Framework. In addition, the IATA guides acquisition of the information needed to support read-across. This approach gathers information to render risk assessment more efficient, affordable, as well as reducing the use of test animals.

Recent studies reported adverse liver effects and intestinal tumor formation after oral exposure to titanium dioxide (TiO2). Other oral toxicological studies, however, observed no effects on liver and intestine, despite prolonged exposure and/or high doses. In the present assessment, we aimed to better understand whether TiO2 can induce such effects at conditions relevant for humans. Therefore, we focused not only on the clinical and histopathological observations, but also used Adverse Outcome Pathways (AOPs) to consider earlier steps (Key Events). In addition, aiming for a more accurate risk assessment, the available information on organ concentrations of Ti (resulting from exposure to TiO2) from oral animal studies was compared to recently reported concentrations found in human postmortem organs. The overview obtained with the AOP approach indicates that TiO2 can trigger a number of key events in liver and intestine: Reactive Oxygen Species (ROS) generation, induction of oxidative stress and inflammation. TiO2 seems to be able to exert these early effects in animal studies at Ti liver concentrations that are only a factor of 30 and 6 times higher than the median and highest liver concentration found in humans, respectively. This confirms earlier conclusions that adverse effects on the liver in humans as a result of (oral) TiO2 exposure cannot be excluded. Data for comparison with Ti levels in human intestinal tissue, spleen and kidney with effect concentrations were too limited to draw firm conclusions. The Ti levels, though, are similar or higher than those found in liver, suggesting these tissues may be relevant too.

We evaluated electrochemical degradation (ECD) and photocatalytic degradation (PCD) technologies for saline water purification, with a focus on rate comparison and formation and degradation of chlorinated aromatic intermediates using the same non-chlorinated parent compound, 4-ethylphenol (4EP). At 15 mA·cm-2, and in the absence of chloride (0.6 mol·L-1 NaNO3 was used as supporting electrolyte), ECD resulted in an apparent zero-order rate of 30 μmol L-1·h-1, whereas rates of ?300 μmol L-1·h-1 and ?3750 μmol L-1·h-1 were computed for low (0.03 mol·L-1) and high (0.6 mol·L-1) NaCl concentration, respectively. For PCD, initial rates of ?330 μmol L-1·h-1 and 205 μmol L-1·h-1 were found for low and high NaCl concentrations, at a photocatalyst (TiO2) concentration of 0.5 g·L-1, and illumination at λmax ≈ 375 nm, with an intensity ?0.32 mW·cm-2. In the chlorine mediated ECD approach, significant quantities of free chlorine (hypochlorite, Cl2) and chlorinated hydrocarbons were formed in solution, while photocatalytic degradation did not show the formation of free chlorine, nor chlorine-containing intermediates, and resulted in better removal of non-purgeable hydrocarbons than ECD. The origin of the minimal formation of free chlorine and chlorinated compounds in photocatalytic degradation is discussed based on photoelectrochemical results and existing literature, and explained by a chloride-mediated surface-charge recombination mechanism.

Item does not contain fulltext, The objective of the review was to compare molecular and health effects of tobacco smoking using cigars, cigarillos, pipe and water pipe in relation to the effects of cigarette smoking. In this review we will focus on the upper respiratory tract. Mechanisms of interaction of tobacco smoke constituents after products other than cigarettes are similar to these associated with cigarette smoking. Carcinogenic activity was demonstrated for any type of tobacco smoking, although the risk of developing head and neck squamous cell carcinoma (HNSCC) remains lower in users of cigars, traditional pipe and water pipe as compared to cigarette smoking. Nevertheless, there is no way of safe tobacco smoking.

Contains fulltext : 203203.pdf (publisher's version ) (Closed access), OBJECTIVE: To provide a perspective on the significance of recent reports for optimizing cancer free surgical margins that have challenged standard practices. METHODS: We conducted a review of the recent literature (2012-2018) using the keywords surgical margin analysis, frozen and paraffin section techniques, head and neck cancer, spectroscopy and molecular markers. RESULTS: Of significance are the reports indicating superiority of tumor specimen directed sampling of margins compared to patient directed (tumor bed) sampling for frozen section control of oral cancers. With reference to optimal distance between tumor and the surgical margin, recent reports recommended cutoffs less than 5mm. Employment of new technologies such as light spectroscopy and molecular analysis of tissues, provide opportunities for a "real time" assessment of surgical margins. CONCLUSIONS: The commonly practiced method of patient directed margin sampling involving previous studies raises concern over conclusions made regarding the efficacy of frozen section margin control. The recent studies that challenge the optimal distance for clear surgical margins are retrospective and address patient cohorts with inherently confounding factors. The use of novel ancillary techniques require further refinements, clinical trial validation, and justification based on the additional resources.

Item does not contain fulltext, The objective of the review was to compare molecular and health effects of tobacco smoking using cigars, cigarillos, pipe and water pipe in relation to the effects of cigarette smoking. In this review we will focus on the upper respiratory tract. Mechanisms of interaction of tobacco smoke constituents after products other than cigarettes are similar to these associated with cigarette smoking. Carcinogenic activity was demonstrated for any type of tobacco smoking, although the risk of developing head and neck squamous cell carcinoma (HNSCC) remains lower in users of cigars, traditional pipe and water pipe as compared to cigarette smoking. Nevertheless, there is no way of safe tobacco smoking.

Contains fulltext : 203203.pdf (publisher's version ) (Closed access), OBJECTIVE: To provide a perspective on the significance of recent reports for optimizing cancer free surgical margins that have challenged standard practices. METHODS: We conducted a review of the recent literature (2012-2018) using the keywords surgical margin analysis, frozen and paraffin section techniques, head and neck cancer, spectroscopy and molecular markers. RESULTS: Of significance are the reports indicating superiority of tumor specimen directed sampling of margins compared to patient directed (tumor bed) sampling for frozen section control of oral cancers. With reference to optimal distance between tumor and the surgical margin, recent reports recommended cutoffs less than 5mm. Employment of new technologies such as light spectroscopy and molecular analysis of tissues, provide opportunities for a "real time" assessment of surgical margins. CONCLUSIONS: The commonly practiced method of patient directed margin sampling involving previous studies raises concern over conclusions made regarding the efficacy of frozen section margin control. The recent studies that challenge the optimal distance for clear surgical margins are retrospective and address patient cohorts with inherently confounding factors. The use of novel ancillary techniques require further refinements, clinical trial validation, and justification based on the additional resources.

Contains fulltext : 203203.pdf (publisher's version ) (Closed access), OBJECTIVE: To provide a perspective on the significance of recent reports for optimizing cancer free surgical margins that have challenged standard practices. METHODS: We conducted a review of the recent literature (2012-2018) using the keywords surgical margin analysis, frozen and paraffin section techniques, head and neck cancer, spectroscopy and molecular markers. RESULTS: Of significance are the reports indicating superiority of tumor specimen directed sampling of margins compared to patient directed (tumor bed) sampling for frozen section control of oral cancers. With reference to optimal distance between tumor and the surgical margin, recent reports recommended cutoffs less than 5mm. Employment of new technologies such as light spectroscopy and molecular analysis of tissues, provide opportunities for a "real time" assessment of surgical margins. CONCLUSIONS: The commonly practiced method of patient directed margin sampling involving previous studies raises concern over conclusions made regarding the efficacy of frozen section margin control. The recent studies that challenge the optimal distance for clear surgical margins are retrospective and address patient cohorts with inherently confounding factors. The use of novel ancillary techniques require further refinements, clinical trial validation, and justification based on the additional resources.

Item does not contain fulltext, The objective of the review was to compare molecular and health effects of tobacco smoking using cigars, cigarillos, pipe and water pipe in relation to the effects of cigarette smoking. In this review we will focus on the upper respiratory tract. Mechanisms of interaction of tobacco smoke constituents after products other than cigarettes are similar to these associated with cigarette smoking. Carcinogenic activity was demonstrated for any type of tobacco smoking, although the risk of developing head and neck squamous cell carcinoma (HNSCC) remains lower in users of cigars, traditional pipe and water pipe as compared to cigarette smoking. Nevertheless, there is no way of safe tobacco smoking.