Leached Compounds from Smoked Cigarettes and Their Potential for Bioaccumulation in Rainbow Trout (Oncorhynchus mykiss).

Cigarette butts are one of the most prevalent forms of litter worldwide and may leach toxic compounds when deposited in aquatic environments. Previous studies demonstrated that smoked cigarette leachate is toxic toward aquatic organisms. However, the specific bioavailable chemicals from the leachate and the potential for human and wildlife exposure through the food chain were unknown. Using a nontargeted analytical approach based on GC×GC/TOF-MS, 43 compounds were confirmed to leach from smoked cigarettes when exposed to a water source. Additionally, the bioaccumulation potential of organic contaminants in an edible fish, rainbow trout (Oncorhynchus mykiss), was assessed through direct exposure to the leachate of smoked cigarettes at 0.5 CB/L for 28 days. There was a significant reduction in fish mass among the exposed rainbow trout vs the control group (χ2 (1) = 5.3, p = 0.021). Both nontargeted and targeted chemical analysis of representative fish tissue identified four tobacco alkaloids, nicotine, nicotyrine, myosmine, and 2,2'-bipyridine. Their average tissue concentrations were 466, 55.4, 94.1, and 70.8 ng/g, respectively. This study identifies leached compounds from smoked cigarettes and demonstrates the uptake of specific chemicals in rainbow trout, thus suggesting a potential for accumulation in food webs, resulting in human and wildlife exposure.

Exacerbating factors in elderly patients with Mycobacterium avium complex pulmonary disease.

No previous studies have examined Mycobacterium avium complex pulmonary disease (MAC-PD) in only elderly patients ⩾75 years old. Here, we investigated the exacerbating factors of MAC-PD in elderly patients and clarified cases that can be followed up without MAC medication. From April 2011 to March 2019, 126 advanced aged patients at our institute were newly diagnosed with MAC-PD, and could be observed based on radiological findings for over a year. Their medical records were retrospectively examined for clinical and radiological findings at the time of diagnosis and 1 year later. To identify the predictors of exacerbation, clinical characteristics of 109 treatment-naïve patients were compared between exacerbated and unchanged groups. Additionally, the unchanged group was followed for one more year. In the current study, positive acid-fast bacilli smears from the sputum test, the presence of cavitary lesions and extensive radiological findings, particularly abnormal shadows in ⩾3 lobes, were predictive of exacerbation among treatment-naïve elderly MAC-PD patients. In the unchanged group, <10% showed exacerbation of radiological findings within the subsequent year. In conclusion, if the sputum smear is negative, no cavitary lesions are present, and abnormal shadows are restricted to ⩽2 lobes, elderly patients with MAC-PD may remain untreated for a few years.

Remediating Thirdhand Smoke Pollution in Multiunit Housing: Temporary Reductions and the Challenges of Persistent Reservoirs.

INTRODUCTION: Toxic tobacco smoke residue, also known as thirdhand smoke (THS), can persist in indoor environments long after tobacco has been smoked. This study examined the effects of different cleaning methods on nicotine in dust and on surfaces. AIMS AND METHODS: Participants had strict indoor home smoking bans and were randomly assigned to: dry/damp cleaning followed by wet cleaning 1 month later (N = 10), wet cleaning followed by dry/damp cleaning (N = 10) 1 month later, and dry/damp and wet cleaning applied the same day (N = 28). Nicotine on surfaces and in dust served as markers of THS and were measured before, immediately after, and 3 months after the cleaning, using liquid chromatography with triple quadrupole mass spectrometry (LC-MS/MS). RESULTS: Over a 4-month period prior to cleaning, surface nicotine levels remained unchanged (GeoMean change: -11% to +8%; repeated measures r = .94; p < .001). Used separately, dry/damp and wet cleaning methods showed limited benefits. When applied in combination, however, we observed significantly reduced nicotine on surfaces and in dust. Compared with baseline, GeoMean surface nicotine was 43% lower immediately after (z = -3.73, p < .001) and 53% lower 3 months later (z = -3.96, p < .001). GeoMean dust nicotine loading declined by 60% immediately after (z = -3.55, p < .001) and then increased 3 months later to precleaning levels (z = -1.18, p = .237). CONCLUSIONS: Cleaning interventions reduced but did not permanently remove nicotine in dust and on surfaces. Cleaning efforts for THS need to address persistent pollutant reservoirs and replenishment of reservoirs from new tobacco smoke intrusion. THS contamination in low-income homes may contribute to health disparities, particularly in children. IMPLICATIONS: Administered sequentially or simultaneously, the tested cleaning protocols reduced nicotine on surfaces by ~50% immediately after and 3 months after the cleaning. Nicotine dust loading was reduced by ~60% immediately after cleaning, but it then rebounded to precleaning levels 3 months later. Cleaning protocols were unable to completely remove THS, and pollutants in dust were replenished from remaining pollutant reservoirs or new secondhand smoke intrusion. To achieve better outcomes, cleaning protocols should be systematically repeated to remove newly accumulated pollutants. New secondhand smoke intrusions need to be prevented, and remaining THS reservoirs should be identified, cleaned, or removed to prevent pollutants from these reservoirs to accumulate in dust and on surfaces.

A Casino goes smoke free: a longitudinal study of secondhand and thirdhand smoke pollution and exposure.

BACKGROUND: Secondhand smoke (SHS) in US casinos is common, but little is known about the residue of tobacco smoke pollutants left behind in dust and on surfaces, commonly referred to as thirdhand smoke (THS). We examined SHS and THS pollution and exposure before and during a casino smoking ban and after smoking resumed. METHODS: A casino was visited nine times over a 15-month period to collect dust, surface and air samples in eight locations. Finger wipe and urine samples were collected from non-smoking confederates before and after a 4-hour casino visit. Samples were analysed for markers of SHS and THS pollution and exposure. RESULTS: Exceptionally high levels of THS were found in dust and on surfaces. Although the smoking ban led to immediate improvements in air quality, surface nicotine levels were unchanged and remained very high for the first month of the smoking ban. Surface nicotine decreased by 90% after 1 month (P<0.01), but nicotine and tobacco-specific nitrosamines in dust decreased more slowly, declining by 90% only after 3 months (P<0.01). Exposure was significantly reduced after the ban, but the benefits of the ban were reversed after smoking resumed. CONCLUSIONS: Long-term smoking in a casino creates deep THS reservoirs that persist for months after a smoking ban. A complete smoking ban immediately improves air quality and significantly reduces exposure to SHS and THS. However, THS reservoirs contribute to continued low-level exposure to toxicants. To accelerate the effect of smoking bans, remediation efforts should address specific THS reservoirs, which may require intensive cleaning as well as replacement of carpets, furniture and building materials.

Evaluation of Inhaled Procaterol for Potential Assist Use in Patients with Stable Chronic Obstructive Pulmonary Disease.

OBJECTIVES: International guidelines recommend the use of long-acting bronchodilators for the treatment of chronic obstructive pulmonary disease (COPD), but the usefulness of short-acting bronchodilator assist use for stable COPD remains uncertain. The purpose of the present study was to objectively demonstrate the effects of assist use of procaterol, a short-acting ß2-agonist, on the respiratory mechanics of stable COPD patients treated with a long-acting bronchodilator using forced oscillation technique (FOT) and conventional spirometry. We also confirmed the length of time for which procaterol assist could significantly improve the pulmonary function. METHODS: We enrolled 28 outpatients with mild to severe COPD (Global Initiative for Obstructive Lung Disease stages I-III), who had used the same long-acting bronchodilator for longer than 3 months and who were in stable condition. All measures were performed using both FOT and spirometry sequentially from 15 min to 2 h after inhalation. RESULTS: Compared to baseline, inhaled procaterol assist use modestly but significantly improved spirometric and FOT measurements within 2 h after inhalation. These significant effects continued for at least 2 h. -Significant correlations were found between parameters -measured by spirometry and those measured by FOT. CONCLUSIONS: Procaterol assist use modestly but significantly improved pulmonary function determined by spirometry and respiratory mechanics in patients with stable COPD treated with long-acting bronchodilators. Thus, inhaled procaterol has the potential for assist use for COPD.

When smokers quit: exposure to nicotine and carcinogens persists from thirdhand smoke pollution.

BACKGROUND: Over a 6-month period, we examined tobacco smoke pollutants (also known as thirdhand smoke, THS) that remained in the homes of former smokers and the exposure to these pollutants. METHODS: 90 smokers completed study measures at baseline (BL). Measures were repeated among verified quitters 1 week (W1), 1 month (M1), 3 months (M3) and 6 months (M6) following cessation. Measures were analysed for THS pollutants on household surfaces, fingers and in dust (ie, nicotine, tobacco-specific nitrosamines) and for urinary markers of exposure (ie, cotinine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)). RESULTS: We observed significant short-term reduction of nicotine on surfaces (BL: 22.2 µg/m2, W1: 10.8 µg/m2) and on fingers of non-smoking residents (BL: 29.1 ng/wipe, W1: 9.1 ng/wipe) without further significant changes. Concentrations of nicotine and nicotine-derived nitrosamine ketone (NNK) in dust did not change and remained near BL levels after cessation. Dust nicotine and NNK loadings significantly increased immediately following cessation (nicotine BL: 5.0 µg/m2, W1: 9.3 µg/m2; NNK BL: 11.6 ng/m2, W1: 36.3 ng/m2) before returning to and remaining at near BL levels. Cotinine and NNAL showed significant initial declines (cotinine BL: 4.6 ng/mL, W1: 1.3 ng/mL; NNAL BL: 10.0 pg/mL, W1: 4.2 pg/mL) without further significant changes. CONCLUSIONS: Homes of smokers remained polluted with THS for up to 6 months after cessation. Residents continued to be exposed to THS toxicants that accumulated in settled house dust and on surfaces before smoking cessation. Further research is needed to better understand the consequences of continued THS exposure after cessation and the efforts necessary to remove THS.

Monitoring Influenza C and D Viruses in Patients With Respiratory Diseases in Japan, January 2018 to March 2023.

BACKGROUND: Influenza viruses can cause zoonotic infections that pose public health risks. Surveillance of influenza A and B viruses is conducted globally; however, information on influenza C and D viruses is limited. Longitudinal monitoring of influenza C virus in humans has been conducted in several countries, but there has been no long-term monitoring of influenza D virus in humans. The public health risks associated with the influenza D virus therefore remain unknown. METHODS: We established a duplex real-time RT-PCR to detect influenza C and D viruses and analyzed respiratory specimens collected from 2144 patients in Japan with respiratory diseases between January 2018 and March 2023. We isolated viruses and conducted hemagglutination inhibition tests to examine antigenicity and focus reduction assays to determine susceptibility to the cap-dependent endonuclease inhibitor baloxavir marboxil. RESULTS: We detected three influenza C viruses belonging to the C/Kanagawa- or C/Sao Paulo-lineages, which recently circulated globally. None of the specimens was positive for the influenza D virus. The C/Yokohama/1/2022 strain, isolated from the specimen with the highest viral RNA load and belonging to the C/Kanagawa-lineage, showed similar antigenicity to the reference C/Kanagawa-lineage strain and was susceptible to baloxavir. CONCLUSIONS: Our duplex real-time RT-PCR is useful for the simultaneous detection of influenza C and D viruses from the same specimen. Adding the influenza D virus to the monitoring of the influenza C virus would help in assessing the public health risks posed by this virus.

Waterproofing Spray-Associated Lung Injury Review: Differences between Cases of Early and Delayed Improvement of Waterproofing Spray-Associated Lung Injury.

Waterproofing spray-associated lung injury (WALI) is an acute respiratory disorder characterized by bilateral diffuse lung injury on chest computed tomography (CT). In most cases, the symptoms and abnormal radiographic findings of WALI patients improve spontaneously over several days; however, some cases have persistent symptoms and abnormal shadows for >1 week. The distinctive features of each WALI are unknown. Herein, we present two new cases of WALI that we encountered in our hospital, and we previously reported two other cases of WALI. We examined the characteristics of WALI in our cases and 39 other cases of WALI definitively diagnosed and reported in PubMed and the Japan medical board with verifiable data during a 15-year period. We compared the clinical characteristics of the 22 cases in which the patients' symptoms were resolved within 1 week (early improvement) to those of the 21 cases in which the symptoms were resolved after >1 week (delayed improvement). The WALI cases with delayed improvement had significantly more shadowing that extended over the entire lung field and was not biased in intensity toward the upper or lower lung field. In addition, the serum white blood cell (WBC) counts and serum Krebs von den Lungen-6 (KL-6) levels differed significantly between the cases of early and delayed improvement of WALI.

Toxicity of cigarette butts, and their chemical components, to marine and freshwater fish.

BACKGROUND: Cigarette butts are the most common form of litter, as an estimated 4.5 trillion cigarette butts are thrown away every year worldwide. Many chemical products are used during the course of growing tobacco and manufacturing cigarettes, the residues of which may be found in cigarettes prepared for consumption. Additionally, over 4000 chemicals may also be introduced to the environment via cigarette particulate matter (tar) and mainstream smoke. METHODS: Using US Environmental Protection Agency standard acute fish bioassays, cigarette butt-derived leachate was analysed for aquatic toxicity. Survival was the single endpoint and data were analysed using Comprehensive Environmental Toxicity Information System to identify the LC50 of cigarette butt leachate to fish. RESULTS: The LC50 for leachate from smoked cigarette butts (smoked filter + tobacco) was approximately one cigarette butt/l for both the marine topsmelt (Atherinops affinis) and the freshwater fathead minnow (Pimephales promelas). Leachate from smoked cigarette filters (no tobacco), was less toxic, with LC50 values of 1.8 and 4.3 cigarette butts/l, respectively for both fish species. Unsmoked cigarette filters (no tobacco) were also found to be toxic, with LC50 values of 5.1 and 13.5 cigarette butts/l, respectively, for both fish species. CONCLUSION: Toxicity of cigarette butt leachate was found to increase from unsmoked cigarette filters (no tobacco) to smoked cigarette filters (no tobacco) to smoked cigarette butts (smoked filter + tobacco). This study represents the first in the literature to investigate and affirm the toxicity of cigarette butts to fish, and will assist in assessing the potential ecological risks of cigarette butts to the aquatic environment.

Association between serum anti-glycopeptidolipid-core IgA antibody titers and clinical characteristics of Mycobacterium avium complex pulmonary disease.

OBJECTIVES: Mycobacterium avium complex pulmonary disease (MAC-PD) can be serologically diagnosed according to the presence of anti-glycopeptidolipid (GPL)-core IgA antibodies. However, few studies have examined the association between serum anti-GPL-core IgA antibody titers and the clinical characteristics of patients with MAC-PD. METHODS: From April 2014 to June 2019, the levels of anti-GPL-core IgA antibodies in 489 MAC-PD patients were determined at the current institute. Of them, 89 patients fulfilled the criteria of the American Thoracic Society and the Infectious Diseases Society of America statement on the diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Patients were categorized into the antibody strong-positive (n = 27), weak-positive (n = 32), and negative (n = 30) groups according to their serum anti-GPL-core IgA antibody results. Their clinical characteristics were retrospectively compared. RESULTS: Disease progression requiring treatment and extensive radiological findings were significantly abundant in the strong-positive group compared with the weak-positive group. Clinical characteristics of the antibody weak-positive and negative groups did not significantly differ. CONCLUSIONS: The findings revealed that serum anti-GPL-core IgA antibody titers are useful for diagnosing MAC-PD and also for predicting the risk of exacerbation.

Tobacco smoke is a likely source of lead and cadmium in settled house dust.

INTRODUCTION: Environmental exposure to lead (Pb) and cadmium (Cd) are risk factors for adverse health outcomes in children and adults. This study examined whether thirdhand smoke residue contributes to Pb and Cd in settled house dust. METHODS: Participants were 60 multiunit housing residents in San Diego, California. All had indoor smoking bans during the study period, and 55 were nonsmokers. Wipe samples from different surfaces and vacuum floor dust samples were analyzed for nicotine, a marker of thirdhand smoke, and for Pb and Cd using liquid chromatography-triple quadrupole mass spectrometry and inductively coupled plasma-mass spectrometry, respectively. RESULTS: Examined in each sample type separately, Pb and Cd loadings were significantly correlated (r = 0.73, vacuum floor dust; 0.52, floor wipes; 0.72, window sill/trough wipes; all p < 0.0025). Pb and Cd loadings from different sample types were not correlated (all p > 0.30). Nicotine loading in dust was significantly correlated with Pb and Cd loading in dust (r = 0.49 for Pb; r = 0.39 for Cd, all p < 0.0025). Pb and Cd loadings on floor or window surfaces, showed no association with nicotine loading in dust, on floors, or on furniture (all p < 0.30). CONCLUSIONS: Tobacco smoke is a likely source of Pb and Cd that accumulates in settled house dust in multiunit housing, suggesting that Pb and Cd are constituents of thirdhand smoke that lingers long after smoking has ended.

Predictors of radiological aggravations of pulmonary MAC disease.

BACKGROUND AND OBJECTIVES: The number of patients with pulmonary Mycobacterium avium complex (MAC) disease is increasing worldwide, especially among middle-aged women and never-smokers. However, little is known about the factors causing exacerbations of pulmonary MAC disease in untreated patients. The aim of the present study was to identify the predictors of radiological aggravations of pulmonary MAC disease. METHODS: From April 2011 to December 2018, 238 MAC patients at our institute were newly diagnosed with pulmonary MAC disease according to the 2007 American Thoracic Society/Infectious Disease Society guideline. Their medical records were examined retrospectively for their clinical findings. The radiological findings at the time of the diagnosis and 1 year later were evaluated. To identify the predictors of radiological aggravation, multivariable analysis was performed with the data of 167 treatment-naïve patients. RESULTS: Female, never-smoker, and nodular/bronchiectatic (NB) type were predominant in patients with pulmonary MAC disease. Univariate analysis of data from treatment-naïve subjects showed that no lung diseases other than MAC, extensive radiological findings, and a positive acid-fast bacilli (AFB) smear were significantly associated with radiological aggravations. On multivariate analysis, the radiological factor (larger affected area) and absence of other lung disease were significantly associated with radiological aggravations. In particular, the presence of abnormal shadows in more than 3 lobes was significantly associated with radiological aggravations. CONCLUSIONS: In this study, the presence of extensive radiological findings and the absence of lung diseases other than MAC were predictors of radiological aggravations of treatment-naïve pulmonary MAC disease. In particular, the presence of abnormal shadows in more than 3 lobes was significantly associated with radiological aggravations.

A retrospective clinical research of relapsed organizing pneumonia.

BACKGROUND: Organizing pneumonia (OP) usually responds spectacularly well to initial treatment, but relapses can occur and some cases run a fatal course. Still, the issue of relapse has been addressed in relatively few studies, and predictors have not been clarified. The purpose of this study was to examine the pattern of relapses in OP, to determine whether relapse affects morbidity and mortality, and to identify possible predictors of relapse. METHODS: Blood sampling, pulmonary function testing, computed tomography (CT) of the chest, and bronchofiberscopy were performed for all patients and were retrospectively reviewed along with clinical information. Periodical chest CT was conducted and additional chest CT was performed when relapse of OP was clinically suspected. All patients were followed regarding treatment response, treatment duration, and presence of relapse. Results were compared between two groups based on serum concentrations of surfactant protein (SP)-D: normal SP-D and high SP-D. RESULTS: Twenty-two patients were analyzed in this study. SP-D showed a negative correlation with percutaneous oxygen saturation and positive correlations with serum lactate dehydrogenase, Krebs von den Lungen (KL)-6, and percentage of lymphocytes in bronchoalveolar lavage (BAL). Prognosis was good for all patients, but relapse was significantly more frequent in the high SP-D group (6 cases) than in the normal SP-D group (0 cases; P = 0.049). Serum KL-6 and percentage of monocytes in BAL were significantly higher, and pulmonary vital capacity and forced expiratory volume in 1 s were significantly lower in the high SP-D group than in the low SP-D group. CONCLUSIONS: When treating cases of OP with high serum concentrations of SP-D, attention should be paid to the possibility of relapse.

Organic contaminants in human breast milk identified by non-targeted analysis.

Understanding the health implications of human exposure to mixtures of chemical contaminants is aided by analytical methods that can screen for a broad range of both expected and unexpected compounds. We performed a proof-of-concept analysis combining human breast milk, a biomonitoring matrix for determining contaminant exposure to mothers and infants, with a non-targeted method based on comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC/TOF-MS). A total of 172 presumably anthropogenic halogenated compounds and non-halogenated cyclic and aromatic compounds were tentatively identified in breast milk from San Diego, California through mass spectral database searches. Forty of the compounds were prioritized for confirmation based on halogenation or 100% frequency of detection, and the identities of 30 were verified using authentic standards. Thirty-four (85%) of the prioritized contaminants are not typically monitored in breast milk surveys, and 31 (77%) are regulated in at least one market worldwide, indicating breast milk may be a useful biomonitoring matrix for non-targeted analysis and the assessment of human exposure to future emerging or undiscovered contaminants.

Persistent tobacco smoke residue in multiunit housing: Legacy of permissive indoor smoking policies and challenges in the implementation of smoking bans.

Secondhand smoke (SHS) is a common indoor pollutant in multiunit housing (MUH). It is also the precursor of thirdhand smoke (THS), the toxic mixture of tobacco smoke residue that accumulates in indoor environments where tobacco has been used. This study examined the levels, distribution, and factors associated with THS pollution in low-income MUH. Interviews were conducted 2016-2018 in a cross-sectional study of N = 220 MUH homes in San Diego, California. Two surface wipe samples were collected per home and analyzed for nicotine, a THS marker, using liquid chromatography-triple quadrupole mass spectrometry. Nicotine was detected in all homes of nonsmokers with indoor smoking bans (Geo Mean = 1.67 µg/m2; 95% CI = [1.23;2.30]) and smokers regardless of an indoor ban (Geo Mean = 4.80 µg/m2; 95% CI = [1.89;12.19]). Approximately 10% of nonsmokers' homes with smoking bans showed nicotine levels higher than the average level in homes of smokers without smoking bans from previous studies (≥30 µg/m2). Housing for seniors, smoking bans on balconies, indoor tobacco use, difficult to reach surfaces, and self-reported African-American race/ethnicity were independently associated with higher THS levels. Individual cases demonstrated that high levels of surface nicotine may persist in nonsmoker homes for years after tobacco use even in the presence of indoor smoking bans. To achieve MUH free of tobacco smoke pollutants, attention must be given to identifying and remediating highly polluted units and to implementing smoking policies that prevent new accumulation of THS. As THS is a form of toxic tobacco product waste, responsibility for preventing and mitigating harmful impacts should include manufacturers, suppliers, and retailers.

Temporal pattern in levels of the neonicotinoid insecticide, imidacloprid, in an urban stream.

Imidacloprid is a widely used insecticide with high runoff potential posing a significant threat to aquatic ecosystems. In order to determine the spatial and temporal concentrations of imidacloprid in Forester Creek, a tributary to the San Diego River, surface water samples were collected from two sites under wet-weather and dry-weather conditions. Solid phase extraction and liquid chromatography tandem mass spectrometry were utilized to quantify imidacloprid levels in all samples. Imidacloprid was detected with 100% frequency in surface water samples from Forester Creek with a median concentration of 16.9 ng/L (range: 3.8-96.8 ng/L). Over 60% of samples exceeded U.S. EPA's chronic exposure benchmark (10 ng/L). Temporal analysis displayed significantly higher levels in wet-weather than dry-weather (median 45.6 ng/L vs. 8.2 ng/L (p < 0.05)), demonstrating the influence of wet-weather runoff on stream quality. Imidacloprid generally followed a first flush pattern with the highest levels observed on the rising portion of the hydrograph as compared to the remainder of the storm, further indicating that the build-up and wash off from land surfaces during storms is a major source of imidacloprid into urban surface waters. To our knowledge, the present study is the first to document this first flush pattern for imidacloprid in an urban stream in southern California. Such data on the occurrence and levels of imidacloprid in this urban stream contribute to the limited knowledge on imidacloprid in urban environments and will promote a better understanding of sources and effects of the neonicotinoid pesticide within the southern California region.

Proof of concept testing of a positive reference material for in vivo and in vitro skin irritation testing.

In vivo and in vitro irritation testing is important for evaluating the biological safety of medical devices. Here, the performance of positive reference materials for skin irritation testing was evaluated. Four reference standards, referred to as Y-series materials, were analyzed: a polyvinyl chloride (PVC) sheet spiked with 0 (Y-1), 1.0 (Y-2), 1.5 (Y-3), or 10 (Y-4) parts of Genapol X-080 per 100 parts of PVC by weight. Y-1, Y-2, and Y-3 did not induce skin irritation responses in an in vitro reconstructed human epidermis (RhE) tissue model, as measured by tissue viability or interleukin-1α release, or in an in vivo intracutaneous response test using rabbits. In contrast, Y-4 extracts prepared with saline or sesame oil at 37°C and 50°C clearly elicited positive irritation responses, including reduced viability (< 50%) and significantly higher interleukin-1α release compared with the solvent alone group, in the RhE tissue model and an intracutaneous response test, where substantial necrosis was observed by histopathology. The positive skin irritation responses induced in vitro under various extraction conditions, as well as those elicited in vivo, indicate that Y-4 is an effective extractable positive control material for in vivo and in vitro skin irritation tests of medical devices. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2807-2814, 2018.

Alternative plasticizer, 4-cyclohexene-1,2-dicarboxylic acid dinonyl ester, for blood containers with protective effects on red blood cells and improved cold resistance.

Di (2-ethylhexyl) phthalate (DEHP), a typical plasticizer used for polyvinyl chloride (PVC), is eluted from PVC-made blood containers and protects against red blood cell (RBC) hemolysis. However, concerns have arisen regarding the reproductive and developmental risks of DEHP in humans, and the use of alternative plasticizers for medical devices has been recommended worldwide. In this study, we propose that the use of a novel plasticizer, 4-cyclohexene-1,2-dicarboxylic acid dinonyl ester (DL9TH), could help produce more useful and safe blood containers. PVC sheet containing DL9TH and di (2-ethylhexyl) 4-cyclohexene-1,2-dicarboxylate (DOTH) provides comparable or superior protective effects to RBCs relative to PVC sheet containing DEHP or di-isononyl-cyclohexane-1,2-dicarboxylate (DINCH® , an alternative plasticizer that has been used in PVC sheets for blood containers). The total amount of plasticizer eluted from DOTH/DL9TH-PVC sheets is nearly the same as that eluted from DEHP-PVC sheets. In addition, DOTH/DL9TH-PVC has better cold resistance than DEHP- and DINCH® -PVC sheets. In vitro and in vivo tests for biological safety based on International Organization for Standardization guidelines (10993 series) suggest that the DOTH/DL9TH-PVC sheet can be used safely. Subchronic toxicity testing of DL9TH in male rats in accordance with the principles of Organisation for Economic Co-operation and Development Test Guideline 408 showed that DL9TH did not induce adverse effects up to the highest dose level tested (717 mg/kg body weight/day). There were no effects on testicular histopathology and sperm counts, and no indications of endocrine effects: testosterone, thyroid-stimulating hormone, follicle-stimulating hormone, and 17ß-estradiol were unchanged by the treatment, compared with the control group. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1052-1063, 2018.

Conceptual model of health information ethics as a basis for computer-based instructions for electronic patient record systems.

A computer-based learning system called Electronic Patient Record (EPR) Laboratory has been developed for students to acquire knowledge and practical skills of EPR systems. The Laboratory is basically for self-learning. Among the subjects dealt with in the system is health information ethics. We consider this to be of the utmost importance for personnel involved in patient information handling. The variety of material on the subject has led to a problem in dealing with it in a methodical manner. In this paper, we present a conceptual model of health information ethics developed using UML to represent the semantics and the knowledge of the domain. Based on the model, we could represent the scope of health information ethics, give structure to the learning materials, and build a control mechanism for a test, fail and review cycle. We consider that the approach is applicable to other domains.