Synergistic interaction of co-exposure to humidifier disinfectant chemicals CMIT/MIT and PHMG in lung injury.

A number of biocidal disinfectant chemicals are used as household products to prevent spread of pathogens. People are commonly exposed to multiple chemicals through those disinfectants. However, effects of interactions (e.g., synergism) between disinfectants on human health outcomes have been rarely studied. In this study, we aimed to investigate associations of a mixture of chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) and polyhexamethylene guanidine (PHMG), which had been used as humidifier disinfectants (HDs) in South Korea, with HD-associated lung injury (HDLI) in a Korean population (n = 4058) with HD exposure through use of HD products. Exposure to HD was retrospectively assessed by an interview-based standardized survey, and HDLI was determined by clinical assessment. After adjusting for covariates, PHMG-specific exposure indices (e.g., amount of use, indoor air concentration, and weekly exposure level) were dose-dependently associated with HDLI (their odds ratios for the comparison of third tertile versus first tertile were 1.95, 1.77, and 2.16, respectively). CMIT/MIT exposure was not observed to have a significant association with HDLI in a single chemical exposure model; however, associations between PHMG exposure and HDLI were strengthened by co-exposure to CMIT/MIT in combined chemical exposure models, where synergistic interactions between CMIT/MIT use and PHMG indices (amount of use and weekly exposure level) were observed (p-interaction in additive scale: 0.02 and 0.03, respectively). Our findings imply that adverse effects of PHMG exposure on lung injury among HD users might be worsened by co-exposure to CMIT/MIT. Given that plenty of household products contain disinfectants on global markets, epidemiological and toxicological investigations are warranted on interaction effects of co-exposure to disinfectants.

Exposures to humidifier disinfectant and various health conditions in Korean based on personal exposure assessment data of claimants for compensation.

BACKGROUND: Humidifier disinfectants (HDs) were commonly used household chemicals to prevent microbial growth in a humidifier water tank in South Korea. A growing body of evidence has indicated that its airborne exposure can induce severe lung injury. However, there has been low awareness of other health outcomes in HD users. This study aimed to evaluate health conditions appealed by claimants for compensation in relation with an increased exposure to HD. METHODS: From survey data of personal HD exposure assessment of claimants for compensation in Korea, we included a total of 4,179 subjects [cases in each dataset were defined by nine reported health conditions, i.e., pneumonia, asthma, cardiovascular disease, respiratory disease, otorhinolaryngologic disease, brain disease (including cerebrovascular disease), dermatological disease, lung cancer, and all cancers]. HD exposures was considered as the following exposure criteria: exposure duration, exposure proximity, exposure direction, chemical type, cumulative exposure time, indoor air concentration, and cumulative exposure level. Logistic regression models were used to evaluate the associations between HD exposure and health conditions. RESULTS: After adjusting for sociodemographic and health behavioral factors and other chemical exposures (households, environmental, and occupational exposures), an increase in cumulative HD exposure time was significantly associated with risks of all nine diseases (all p-trends < 0.05). An increase in HD exposure duration was associated with asthma, respiratory disease, otorhinolaryngologic disease, dermatological disease, all cancers, and lung cancer (p-trends < 0.05). Indoor HD concentration was associated with only pneumonia (p-trend = 0.015). CONCLUSIONS: Our findings suggest that cumulative exposures to airborne HD might potentially increase the risk of various reported health outcomes.

Exploring User Perspectives of and Ethical Experiences With Teletherapy Apps: Qualitative Analysis of User Reviews.

BACKGROUND: Teletherapy apps have emerged as a promising alternative to traditional in-person therapy, especially after the COVID-19 pandemic, as they help overcome a range of geographical and emotional barriers to accessing care. However, the rapid proliferation of teletherapy apps has occurred in an environment in which development has outpaced the various regulatory and ethical considerations of this space. Thus, researchers have raised concerns about the ethical implications and potential risks of teletherapy apps given the lack of regulation and oversight. Teletherapy apps have distinct aims to more directly replicate practices of traditional care, as opposed to mental health apps, which primarily provide supplemental support, suggesting a need to examine the ethical considerations of teletherapy apps from the lens of existing ethical guidelines for providing therapy. OBJECTIVE: In this study, we examined user reviews of commercial teletherapy apps to understand user perceptions of whether and how ethical principles are followed and incorporated. METHODS: We identified 8 mobile apps that (1) provided teletherapy on 2 dominant mobile app stores (Google Play and Apple App Store) and (2) had received >5000 app reviews on both app stores. We wrote Python scripts (Python Software Foundation) to scrape user reviews from the 8 apps, collecting 3268 user reviews combined across 2 app stores. We used thematic analysis to qualitatively analyze user reviews, developing a codebook drawing from the ethical codes of conduct for psychologists, psychiatrists, and social workers. RESULTS: The qualitative analysis of user reviews revealed the ethical concerns and opportunities of teletherapy app users. Users frequently perceived unprofessionalism in their teletherapists, mentioning that their therapists did not listen to them, were distracted during therapy sessions, and did not keep their appointments. Users also noted technical glitches and therapist unavailability on teletherapy apps that might affect their ability to provide continuity of care. Users held varied opinions on the affordability of those apps, with some perceiving them as affordable and others not. Users further brought up that the subscription model resulted in unfair pricing and expressed concerns about the lack of cost transparency. Users perceived that these apps could help promote access to care by overcoming geographical and social constraints. CONCLUSIONS: Our study suggests that users perceive commercial teletherapy apps as adhering to many ethical principles pertaining to therapy but falling short in key areas regarding professionalism, continuity of care, cost fairness, and cost transparency. Our findings suggest that, to provide high-quality care, teletherapy apps should prioritize fair compensation for therapists, develop more flexible and transparent payment models, and invest in measures to ensure app stability and therapist availability. Future work is needed to develop standards for teletherapy and improve the quality and accessibility of those services.

Deterioration of Mental Health in Children and Adolescents During the COVID-19 Pandemic.

This paper reviews the global effect of the coronavirus disease 2019 (COVID-19) pandemic on the mental health of children and adolescents in South Korea, the U.S., Japan, and China. We reviewed research on deteriorated mental health, including increased suicide, suicidal thoughts, and self-harm. Various studies have shown that students' mental health issues, such as depression and anxiety, have worsened during the COVID-19 pandemic. Furthermore, the number of students who committed suicide has significantly increased in the U.S. and Japan. Factors such as prior mental health status, change in daily routine, reduced physical activity, excessive screen time, overuse of electronic devices, and reduced social support have been reported to have a significant effect. The chain of deteriorating mental health among the youth began at the onset of COVID-19, social distancing, and school closure. As youths began to stay at home instead of going to school, they lost opportunities to connect with their friends or teachers, who could provide support outside of their homes. Young people spent less time on physical activity and more time online, which damaged their sleeping schedule and daily routine. In preparing for the post-pandemic phase, we should thoroughly analyze the long-term effects of the pandemic on youth mental health, while simultaneously tackling current imminent issues.

New-Onset and Exacerbation of Lung Diseases after Short-Term Exposures to Humidifier Disinfectant during Hospitalization.

(1) Background: Humidifier disinfectant (HD) is a biocidal chemical to keep the water tank inside a humidifier clean. Thousands of Koreans have experienced HD-related lung injuries. Of them, 6.9% were exposed to HD in hospitals. (2) Methods: This study investigated changes of diseases in patients (or caregivers) who experienced HD exposures during hospitalization and also investigated characteristics of hospital exposure using data from all HD-related lung injury enrollment in Korea. (3) Results: Of a total of 162 subjects, 139 subjects were hospitalized for non-lung diseases, and 23 people were hospitalized for lung diseases at the time of hospitalization. During hospital exposure, 99 (71.2%) of those hospitalized with non-lung disease experienced a new-onset of lung disease, and 15 (65.2%) of those hospitalized with lung diseases experienced exacerbation of their existing lung diseases. When we compared their exposure characteristics, those exposed in hospitals (vs. non-hospital, mostly home) were exposed for shorter periods, at closer distances, at higher HD indoor concentrations, constantly all day, and directly in the facial direction. (4) Conclusion: In conclusion, HD exposures in hospital with a high intensity even for a short term were associated with new-onset or exacerbation of lung diseases. Our findings suggest that acute exposures to HD can cause lung diseases.

Designing Flexible Longitudinal Regimens: Supporting Clinician Planning for Discontinuation of Psychiatric Drugs.

Clinical decision support tools have typically focused on one-time support for diagnosis or prognosis, but have the ability to support providers in longitudinal planning of patient care regimens amidst infrastructural challenges. We explore an opportunity for technology support for discontinuing antidepressants, where clinical guidelines increasingly recommend gradual discontinuation over abruptly stopping to avoid withdrawal symptoms, but providers have varying levels of experience and diverse strategies for supporting patients through discontinuation. We conducted two studies with 12 providers, identifying providers' needs in developing discontinuation plans and deriving design guidelines. We then iteratively designed and implemented AT Planner, instantiating the guidelines by projecting taper schedules and providing flexibility for adjustment. Provider feedback on AT Planner highlighted that discontinuation plans required balancing interpersonal and infrastructural constraints and surfaced the need for different technological support based on clinical experience. We discuss the benefits and challenges of incorporating flexibility and advice into clinical planning tools.

The Effect of Using Countermeasures in Interpreter-Absent and Interpreter-Present Interviews

Background: In two experiments we examined whether lie tellers, after reading articles about the Model Statement interview tool and/or about the verbal cues complications, common knowledge details and self-handicapping strategies, can successfully use countermeasures by adjusting their statements so that they sound like truth tellers. We also examined whether the presence of an interpreter affect these results. Method: In both experiments, truth tellers discussed a trip they had made; lie tellers fabricated a story. Participants were of Lebanese, Mexican and South-Korean origin. Prior to the interview participants in Experiment 1 did or did not receive information about (i) the working of the Model Statement tool and (ii) three types of verbal detail: complications, common knowledge details and self-handicapping strategies. In Experiment 2 the Model Statement Pre-Information factor was replaced by the presence/absence of an interpreter. Results/Conclusions: We found no evidence that lie tellers adjusted their responses after being informed about the Model Statement and / or the types of detail we examined. (AU)

Antecedentes: Se analiza en dos experimentos si las personas que mienten, una vez han leído artículos sobre la entrevista estándar de obtención de la declaración y auto-depreciación sobre los problemas de los indicios verbales verbales, detalles de conocimiento común y las estrategias de autojustificación pueden utilizar eficazmente contramedidas para ajustar sus declaraciones de modo que parezca que dicen la verdad. También analizamos si influye en estos resultados la presencia de un intérprete. Método: En ambos experimentos, los sujetos que decían la verdad hablaban de un viaje que habían hecho, mientras que los que mentían se inventaban una historia. Los participantes eran de origen libanés, mexicano y surcoreano. Antes de la entrevista los participantes en el experimento 1 no recibían información sobre (i) el funcionamiento de la entrevista estándar de obtención de la declaración y (ii) sobre los tres tipos de detalles verbales: complicaciones, detalles del conocimiento común y estrategias de auto-depreciación. En el experimento 2 se sustituyó el factor información previa sobre la entrevista estándar de obtención de la declaración por la presencia/ausencia de un intérprete. Resultados/Conclusiones: Los resultados nos prestaron apoyo a que los que mienten ajusten sus respuestas tras ser informados sobre la entrevista estándar de obtención de la declaración o los tipos de detalles examinados. (AU)

Misclassification and characterization of exposure to humidifier disinfectants using a questionnaire.

BACKGROUND: Lung disease caused by exposure to chemical substances such as polyhexamethylene guanidine (PHMG) used in humidifier disinfectants (HDs) has been identified in Korea. Several researchers reported that exposure classification using a questionnaire might not correlate with the clinical severity classes determined through clinical diagnosis. It was asserted that the lack of correlation was due to misclassification in the exposure assessment due to recall bias. We identified the cause of uncertainty to recognize the limitations of differences between exposure assessment and clinical outcomes assumed to be true value. Therefore, it was intended to check the availability of survey using questionnaires and required to reduce misclassification error/bias in exposure assessment. METHODS: HDs exposure assessment was conducted as a face-to-face interview, using a questionnaire. A total of 5245 applicants participated in the exposure assessment survey. The questionnaire included information on sociodemographic and exposure characteristics such as the period, frequency, and daily usage amount of HDs. Based on clinical diagnosis, a 4 × 4 cross-tabulation of exposure and clinical classification was constructed. When the values of the exposure rating minus the clinical class were ≥ 2 and ≤ - 2, we assigned the cases to the overestimation and underestimation groups, respectively. RESULTS: The sex ratio was similar in the overestimation and underestimation groups. In terms of age, in the overestimation group, 90 subjects (24.7%) were under the age of 10, followed by 52 subjects (14.2%) in their 50s. In the underestimation group, 195 subjects (56.7%) were under the age of 10, followed by 80 subjects (23.3%) in their 30s. The overestimation group may have already recovered and responded excessively due to psychological anxiety or to receive compensation. However, relatively high mortality rates and surrogate responses observed among those under 10 years of age may have resulted in inaccurate exposure in the underestimation group. CONCLUSIONS: HDs exposure assessment using a questionnaire might not correlate with adverse health effects due to recall bias and various other causes such as recovery of injury and psychological anxiety. This study revealed exposure misclassification and characteristics affected by HDs and proposed a questionnaire-based exposure assessment methodology to overcome the limitations of past exposure assessment.

FGF12 (Fibroblast Growth Factor 12) Inhibits Vascular Smooth Muscle Cell Remodeling in Pulmonary Arterial Hypertension.

Loss of BMP (bone morphogenic protein) signaling induces a phenotype switch of pulmonary arterial smooth muscle cells (PASMCs), which is the pathological basis of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Here, we identified FGF12 (fibroblast growth factor 12) as a novel regulator of the BMP-induced phenotype change in PASMCs and elucidated its role in pulmonary vascular remodeling during PAH development. Using murine models of PAH and lung specimens of patients with PAH, we observed that FGF12 expression was significantly reduced in PASMCs. In human PASMCs, FGF12 expression was increased by canonical BMP signaling. FGF12 knockdown blocked the antiproliferative and prodifferentiation effect of BMP on human PASMCs, suggesting that FGF12 is required for the BMP-mediated acquisition of the quiescent and differentiated PASMC phenotype. Mechanistically, FGF12 regulated the BMP-induced phenotype change by inducing MEF2a (myocyte enhancer factor 2a) phosphorylation via p38MAPK signaling, thereby modulating the expression of MEF2a target genes involved in cell proliferation and differentiation. Furthermore, we observed that TG (transgenic) mice with smooth muscle cell-specific FGF12 overexpression were protected from chronic hypoxia-induced PAH development, pulmonary vascular remodeling, and right ventricular hypertrophy. Consistent with the in vitro data using human PASMCs, FGF12 TG mice showed increased MEF2a phosphorylation and a substantial change in MEF2a target gene expression, compared with the WT (wild type) controls. Overall, our findings demonstrate a novel BMP/FGF12/MEF2a pathway regulating the PASMC phenotype switch and suggest FGF12 as a potential target for the development of therapeutics for ameliorating pulmonary vascular remodeling in PAH.

The efficacy of using countermeasures in a model statement interview / La eficacia del uso de contramedidas en una entrevista de declaración modelo

In a countermeasures experiment, we examined to what extent liars who learn about the Model Statement tool and about the proportion of complications (complications/complications + common knowledge details + self-handicapping strategies) can successfully adjust their responses so that they sound like truth tellers. Truth tellers discussed a trip they had made; liars fabricated a story. Participants were of Lebanese, Mexican, and South-Korean origin. Prior to the interview they did or did not receive information about (I) the working of the Model statement and (II) three types of verbal detail: complications, common knowledge details and self-handicapping strategies. We found no evidence that liars sounded like truth tellers after being informed about the Model Statement and/or types of detail we examined. Actually, veracity differences were similar across experimental conditions, with truth tellers reporting more detail and more complications and obtaining a higher proportion of complications score than liars

En un experimento de contramedidas examinamos hasta qué punto los mentirosos que reciben información sobre la Declaración modelo y la proporción de complicaciones que presenta (complicaciones / complicaciones + detalles de conocimiento general + estrategias de autoobstaculización) pueden ajustar sus respuestas con éxito para que parezca que dicen la verdad. Los que dicen la verdad declararon sobre un viaje que habían hecho; los mentirosos inventaron una historia. Los participantes eran de origen libanés, mexicano y surcoreano. Antes de la entrevista habían recibido o no información sobre (I) el funcionamiento de la Declaración modelo y (II) tres tipos de detalles verbales: complicaciones, detalles de conocimiento general y estrategias de autoobstaculización. No encontramos evidencia de que los mentirosos se parecieran a los que dicen la verdad después de ser informados sobre la Declaración modelo y los tipos de detalle que examinamos. En realidad, las diferencias de veracidad fueron semejantes en todas las condiciones experimentales: los que decían la verdad informaron con mayor detalle y de más complicaciones y obtuvieron una mayor puntuación en la proporción de complicaciones que los mentirosos

Rater experience and the predictive validity of Psychopathy Checklist: Youth Version scores.

We compared the predictive validity of Psychopathy Checklist: Youth Version (PCL:YV) scores assigned by a licensed clinician to scores assigned by a graduate student across a sample of 82 juvenile offenders. Although both raters completed in-depth training and practice scoring cases, the graduate student had no prior clinical experience. The raters showed a high level of agreement in their scoring for 11 reliability check cases (intraclass correlation coefficient, ICCA,1 = .90 for PCL:YV Total score), but the scores assigned by the licensed clinician were better predictors of post-release recidivism (area under the curve, AUC = .77) than those assigned by the graduate student (AUC = .45). There was more variability in the scores assigned by the licensed clinician than those assigned by the graduate student, suggesting that more experienced clinicians' willingness to assign both high and low scores may help explain rater differences in predictive validity.

Using the model statement to elicit information and cues to deceit in interpreter-based interviews.

We examined how the presence of an interpreter during an interview affects eliciting information and cues to deceit, while using a method that encourages interviewees to provide more detail (model statement, MS). A total of 199 Hispanic, Korean and Russian participants were interviewed either in their own native language without an interpreter, or through an interpreter. Interviewees either lied or told the truth about a trip they made during the last twelve months. Half of the participants listened to a MS at the beginning of the interview. The dependent variables were 'detail', 'complications', 'common knowledge details', 'self-handicapping strategies' and 'ratio of complications'. In the MS-absent condition, the interviews resulted in less detail when an interpreter was present than when an interpreter was absent. In the MS-present condition, the interviews resulted in a similar amount of detail in the interpreter present and absent conditions. Truthful statements included more complications and fewer common knowledge details and self-handicapping strategies than deceptive statements, and the ratio of complications was higher for truth tellers than liars. The MS strengthened these results, whereas an interpreter had no effect on these results.

Fibroblast Growth Factor 12 Is a Novel Regulator of Vascular Smooth Muscle Cell Plasticity and Fate.

OBJECTIVE: Vascular smooth muscle cells (VSMCs) modulate their phenotype between synthetic and contractile states in response to environmental changes; this modulation plays a crucial role in the pathogenesis of restenosis and atherosclerosis. Here, we identified fibroblast growth factor 12 (FGF12) as a novel key regulator of the VSMC phenotype switch. APPROACH AND RESULTS: Using murine models and human specimens, we found that FGF12 was highly expressed in contractile VSMCs of normal vessel walls but was downregulated in synthetic VSMCs from injured and atherosclerotic vessels. In human VSMCs, FGF12 expression was inhibited at the transcriptional level by platelet-derived growth factor-BB. Gain- and loss-of-function experiments showed that FGF12 was both necessary and sufficient for inducing and maintaining the quiescent and contractile phenotypes of VSMCs. FGF12 inhibited cell proliferation through the p53 pathway and upregulated the key factors involved in VSMC lineage differentiation, such as myocardin and serum response factor. Such FGF12-induced phenotypic change was mediated by the p38 MAPK (mitogen-activated protein kinase) pathway. Moreover, FGF12 promoted the differentiation of mouse embryonic stem cells and the transdifferentiation of human dermal fibroblasts into SMC-like cells. Furthermore, adenoviral infection of FGF12 substantially decreased neointima hyperplasia in a rat carotid artery injury model. CONCLUSIONS: In general, FGF family members induce a synthetic VSMC phenotype. Interestingly, the present study showed the unanticipated finding that FGF12 belonging to FGF family, strongly induced the quiescent and contractile VSMC phenotypes and directly promoted VSMC lineage differentiation. These novel findings suggested that FGF12 could be a new therapeutic target for treating restenosis and atherosclerosis.

Multiresidue pesticide analysis in Korean ginseng by gas chromatography-triple quadrupole tandem mass spectrometry.

In this study, a new analytical method was developed based on gas chromatography-triple quadrupole tandem mass spectrometry (GC-MS/MS) and used to determine 32 multiclass pesticides in ginseng products. The analytical method was validated, yielding recovery rates in the range of 55.2-108.3%, with precision values expressed as relative standard deviation (RSD) lower or equal to 12% at the spiking levels of 30, 100, and 1000 µg/kg. Correlation coefficients and LOQs (limit of quantification) were in the range 0.9801-0.9989 and 0.15-70 g/kg, respectively. With these validation data and this method, multiresidue pesticides of ginseng samples (fresh ginseng (n=118), red ginseng (n=24), dried ginseng (n=10)) were analysed. Among them, the most frequently detected pesticide was tolclofos-methyl. Tolclofos-methyl was detected in 86.4% of fresh ginseng (18.25-404.5 µg/kg), 91.7% of red ginseng (13.14-119.4 µg/kg), and 87.5% of dried ginseng (23.15-3673 µg/kg).

Analysis of low molecular weight plasma proteins using ultrafiltration and large gel two-dimensional electrophoresis.

In this study, various solvent systems were applied to obtain a high and consistent recovery rate of low molecular weight plasma proteins (LMPP) from human plasma. A buffer system containing 7 M urea, 2 M thiourea, 25 mM NH(4)HCO(3) + 20% ACN (pH 8.2) produced the highest recovery rate of LMPP. To validate the recovery of cut off membrane (COM) obtained using the urea buffer system, 27 different 30 kDa COMs were used to prepare the LMPP sample which were then subjected to 1-D SDS-PAGE. Statistical analysis showed that the buffer system with COM produced a consistent the recovery of LMPP. In addition, 2-DE analysis was also conducted to determine the relative intensity of each protein spot. When molecular weight ranges over 30 kDa and under 30 kDa were evaluated, 953 and 587 protein spots were observed in the gels, respectively, resulting in a total of 1540 protein spots being resolved. Identification of the major proteins were then performed using a nano-LC/MS system comprised of an HPLC system and an ESI-quadrupole IT MS equipped with a nano-ESI source.