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ObjectivePsilocybin-assisted therapy has shown promising efficacy on clinical depressive symptoms. However, diverse psychological support or psychotherapy was performed with psilocybin treatment. This study aimed to explore the association of psychological protocols with the efficacy of psilocybin-assisted therapy for depressive symptoms.MethodFive major databases were systemic searched for clinical trials addressing psilocybin-assisted therapy for patients with clinical depressive symptoms. A Bayesian random-effects meta-analysis and meta-regression were performed. The effect size was mean difference (with 95% credible interval) measured by 17-Item Hamilton Depression Rating Scale.ResultsThere were 10 eligible studies including 515 adult patients with clinically diagnosed depression. The psychological protocols could be categorized into four types: (i) manualized directive psychotherapy(k=1); (ii) manualized nondirective psychological support(k=3), (iii) non-manualized nondirective psychological support(k=5); and (iv) non-manualized supportive psychotherapy(k=1). The pooled standard mean difference of psilocybin-assisted therapy was 10.08 (5.03-14.70).ConclusionCompared with manualized nondirective psychological support, the other three psychological approaches did not differ significantly. The improvement of depressive symptoms was not associated with the psychological protocols in adult patients receiving psilocybin-assisted therapy.Systemic review registrationOpen Science Framework: identifier (osf.io/3YUDV).

Abstract One recent study showed that atomoxetine-oxybutynin combination (AOC) use is effective in reducing obstructive sleep apnea (OSA) severity. We used a nationwide database to examine the association between AOC use and the risk of OSA incidence. This retrospective cohort study used Taiwan’s National Health Insurance Research Database between the years 2000 and 2015. The patients who used atomoxetine or oxybutynin were included as an exposed cohort. The exposed and unexposed groups were selected in a ratio of 1:3 with sex, age, and index year matching. We used the multivariate Cox proportional regression model to evaluate the association between AOC use and the risk of an incident diagnosis of OSA. The incidence rates of OSA in the exposed cohort (N = 8940) and the unexposed cohort (N = 26,820), were 21.92 and 22.93 per 100,000 person-years, respectively. The adjusted hazard ratio of oxybutynin use only and AOC with a treatment duration of ≥ 366 days were 0.307 (95% CI 0.204–0.995, P = 0.045) and 0.299 (95% CI 0.102–0.933, P = 0.002), respectively. Long-term atomoxetine-oxybutynin combination therapy may be beneficial to reduce the risk of obstructive sleep apnea. Further studies to examine these mechanisms are warranted.

Abstract Objective We have conducted a study to clarify the association between amphetamine‐related disorders (ARD) and the risk of developing dementia. Methods This study used a retrospective cohort design by using Taiwan’s National Health Research Institute Database. A random sample of 68,300 subjects between January 1, 2000, and December 31, 2015, was obtained, comprising of 17,075 patients with ARD, and 51,225 controls without ARD (1:3), matched for gender and age group. After adjusting for covariates, a Fine and Gray’s survival analysis (competing with mortality) was used to compare the risk of dementia during a 15‐year follow‐up period. Results In the present study, 1,751 of 17,075 patients with ARD and 2,147 of 51,225 in the control group without ARD (883.10 vs 342.83 per 100,000 person‐years) developed dementia. ARD cohort was more likely to develop dementia (hazard ratio = 4.936 [95% CI: 4.609–5.285, P

Abstract Background The risk of injury directly related to hospitalization for motor vehicle accidents (MVAs) in the obstructive sleep apnea (OSA) patients has not been thoroughly understood. Our study aimed to examine the association between the OSA and the hospitalization for an MVA injury. Methods This retrospective cohort study used Taiwan’s National Health Insurance Research Database (NHIRD) between 2000 and 2015. The OSA patients aged ≥20 years by age, sex, and index-year matched by non-OSA controls were enrolled (1:3). We used the Cox proportional regression model to evaluate the association between the OSA and the hospitalization for an MVA injury. Results The incidence rate of hospitalization for an MVA injury was higher in the OSA cohort (N = 3025) when compared with the non-OSA controls (N = 9075), as 575.3 and 372.0 per 100,000 person-years, respectively (p

Background:Chlamydia pneumoniae (CPn) is a common community-acquired pneumonia. In the literature, CPn infection is demonstrated to exhibit an association with Alzheimer dementia (AD). We executed the present nationwide, population-based research with the goal of probing the association of CPn infection and antibiotic therapy with AD risk.Methods: We conducted a cohort study using a database extracted from Taiwan's National Health Insurance Research Database (NHIRD). All medical conditions for each enrolled individuals were categorized using the International Classification of Diseases, ninth Revision classifications. Hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between CPn pneumonia-associated hospitalizations and AD were estimated using Fine and Gray's survival analysis and adjusted for comorbidities. The effects of the antibiotics on the HRs for AD in the patients with CPn pneumonia-associated hospitalization were also analyzed.Results: Our analyses included 6,628 individuals, including 1,657 CPn-infected patients, as well as 4,971 controls matched by age, index date, and sex (1:3). In this study, patients hospitalized for CPn pneumonia exhibited a significantly higher AD risk (adjusted HR = 1.599, 95% CI = 1.284–1.971, p < 0.001). We also noted an association of macrolide use (≥15 days) and fluoroquinolone use (≥15 days) with decreased AD risk.Conclusions: We determined CPn pneumonia to be associated with a relatively high AD risk. The result in this study confirmed the findings from previous literatures, by using a large, nationwide, population-based database. Appropriate macrolide and fluoroquinolone treatment may attenuate this risk.

Aim: This study aimed to investigate the association between males with pinworm infections and the risk of developing psychiatric disorders. Method: A total of 2044 enrolled patients, with 511 pinworm subjects and 1533 unexposed subjects (1:3) matched for sex, age and index year, from Taiwan's Longitudinal Health Insurance Database (LHID) from 2000 to 2015, selected from the National Health Insurance Research Database (NHIRD). After adjusting for confounding factors, the Cox regression model was used to compare the risk of developing psychiatric disorders during the 15 years of follow-up. Results: Of all the enrollees, 24 in the pinworm cohort and 18 in the unexposed cohort (343.10 vs 84.96 per 100,000 person-year) developed psychiatric disorders. The Cox regression model revealed that, after adjusting for sex, age, monthly income, urbanization level, geographic region, and comorbidities, the adjusted HR was 4.581 (95% CI: 2.214–9.480, p

Background: The aim of this study is to investigate the validity of the coin-in-the-hand (CIH) test with other neuropsychological tests for the detection of malingering in the memory. Materials and Methods: A simulated scenario design was developed to investigate the validity of the CIH test, entitled the Test of Memory Malingering (TOMM), associated with the Clinical Dementia Rating, the cognitive abilities screening instrument, the Mini-Mental Status Examination, and the WHO Quality of Life-BREF. The performances of the patients with dementia (n = 25) were compared with one group of normal controls (n = 9), and another group instructed to simulate malingering dementia (n = 19). Results: The CIH test demonstrated good validity and displayed a better sensitivity and a positive likelihood ratio than the TOMM, while patients with dementia could provide, on average, more than nine correct answers, in comparison to only more than six correct answers in the simulated malingering group. The optimal cutoff score of the CIH test is ≤8. Conclusions: This pilot study showed that the CIH test is a quick and practical test for detecting malingering in the memory.

Pinus taiwanensis Hayata (Pinaceae) is an endemic plant in Taiwan. According to the Chinese Materia Medica Grand Dictionary, the Pinus species is mainly used to relieve pain, and eliminate pus and toxicity. In this study, nineteen compounds were isolated from the ethyl acetate layer of the ethanolic extract of P. taiwanensis Hayata twigs using bioassay-guided fractionation, and their anti-melanoma effects were investigated through a B16-F10 mouse melanoma cell model. The structures of the purified compounds were identified by 2D-NMR, MS, and IR, including 1 triterpenoid, 9 diterpenoids, 2 lignans, 4 phenolics, 1 phenylpropanoid, 1 flavonoid, and 1 steroid. Among them, compound 3 was found to be a new diterpene. Some of the compounds (2, 5, 6, 17, 18) showed moderate cytotoxicity effects. On the other hand, the anti-melanoma effect was no better than that from the original ethyl acetate layer. We presumed it resulted from the synergistic effect, although further experimentation needs to be performed.

Background/ObjectiveIn previous reports, the usage of anticholinergic medications has been associated with an increased risk of dementia with prolonged usage or with a high Anticholinergic Cognitive Burden (ACB). This study aimed to investigate the association between anticholinergic medications and the risk of dementia using data from Taiwan's National Health Research Database (NHIRD).MethodsA total of 790,240 patients, with 197,560 patients receiving anticholinergic medications and 592,680 control patients (1:3) matched for sex, age, and index-year, were enrolled from the two million Longitudinal Health Insurance Dataset, a subdataset of the NHIRD, between 2000 and 2015. The time-dependent Cox regression analysis was used to explore the hazard ratio (HR) with a 95% confidence interval for the association between anticholinergics and the risk of dementia during the 15-year follow-up. The behavioral and psychological symptoms of dementia (BPSD) were recognized by the usage of psychotropics. The ACB ranged from zero to three, divided as score

Pentabromopseudilin (PBrP) is a marine antibiotic isolated from the marine bacteria Pseudomonas bromoutilis and Alteromonas luteoviolaceus. PBrP exhibits antimicrobial, anti-tumour, and phytotoxic activities. In mammalian cells, PBrP is known to act as a reversible and allosteric inhibitor of myosin Va (MyoVa). In this study, we report that PBrP is a potent inhibitor of transforming growth factor-β (TGF-β) activity. PBrP inhibits TGF-β-stimulated Smad2/3 phosphorylation, plasminogen activator inhibitor-1 (PAI-1) protein production and blocks TGF-β-induced epithelial–mesenchymal transition in epithelial cells. PBrP inhibits TGF-β signalling by reducing the cell-surface expression of type II TGF-β receptor (TβRII) and promotes receptor degradation. Gene silencing approaches suggest that MyoVa plays a crucial role in PBrP-induced TβRII turnover and the subsequent reduction of TGF-β signalling. Because, TGF-β signalling is crucial in the regulation of diverse pathophysiological processes such as tissue fibrosis and cancer development, PBrP should be further explored for its therapeutic role in treating fibrotic diseases and cancer.

Background: Morbid obesity is associated with various diseases, and the weight control surgery (WCS) is one of the treatments for morbid obesity. However, the association between the WCS and psychiatric disorders has yet to be elucidated. This study aimed to investigate the association between the WCS and the risk of developing psychiatric disorders. Materials and Methods: A total of 53,052 enrolled participants with 13,263 patients who received WCS and 39,789 controls with matched for sex and age, between January 1 and December 31, 2000, were selected from the National Health Insurance Research Database of Taiwan. After adjusting for confounding factors, Cox proportional hazards analysis was used to compare the risk of developing psychiatric disorders during 10 years of follow-up. Results: Of the study patients, 1170 (8.82%) developed psychiatric disorders when compared to 3490 (8.77%) in the control group. Cox proportional hazards regression analysis revealed that the study patients were more likely to develop psychiatric disorders (hazard ratio [HR]: 2.952, 95% confidence interval [CI] = 2.756–3.163, P < 0.001). After adjusting for gender, age, monthly income, urbanization level, geographic region, and comorbidities, the adjusted HR was 2.901 (95% CI = 2.701–3.115, P < 0.001). Among these psychiatric disorders, depressive disorders, bipolar disorders, and sleep disorders are with significantly increased risk. Conclusions: Patients who received the WCS have a higher risk of developing psychiatric disorders, and the risk was increased in the durations of

This study aimed to investigate the association between males with psychosexual disorders (PSDs) and the risk of developing psychiatric disorders. A total of 34,972 enrolled patients, with 8,743 subjects who had suffered from PSD and 26,229 controls (1:3) matched for age and index year, from Taiwan’s Longitudinal Health Insurance Database (LHID) from 2000 to 2015, selected from the National Health Insurance Research Database (NHIRD). After adjusting all the confounding factors, the multivariate Cox regression model was used to compare the risk of developing psychiatric disorders, between the PSD and non-PSD groups, during the 15 years of follow-up. Of the all enrollees, 1,113 in the PSD cohort and 2,611 in the non-PSD cohort (1,180.96 vs. 954.68 per 100,000 person-year) developed psychiatric disorders. Multivariate Cox regression model survival analysis revealed that, after adjusting for gender, age, monthly income, urbanization level, geographic region, and comorbidities, the adjusted hazard ratio (HR) was 2.448 (95% CI [2.227, 2.633], p < .001). PSD has been associated with the increased risk in anxiety disorders, depressive disorders, bipolar disorders, sleep disorders, and psychotic disorders, respectively. Sexual dysfunctions, paraphilia, and gender identity disorders were associated with the overall psychiatric disorders with adjusted HRs as 1.990 ( p < .001), 11.622 ( p < .001), and 5.472 ( p < .001), respectively. Male patients who suffered from PSD have a higher risk of developing psychiatric disorders, and this finding should be considered as a timely reminder for the clinicians to provide much more attention for these patients because of their mental health issues.

Mangroves play an important role in carbon sequestration. However, mangroves can be sources of greenhouse gas (GHG) emissions. In this study, methane (CH4) emissions and related soil properties were determined in multiple mangroves in Taiwan, including Kandelia obovata and Avicennia marina mangroves. K. obovata possess prop roots, whereas pneumatophores are found in A. marina. Our results showed that mangrove soils were significant sources of CH4 emissions, which should be accounted for in mangrove carbon budgets. In particular, CH4 emissions in the A. marina mangroves were approximately 50- to 100-fold those of the K. obovata mangroves and the adjoining mudflats. Multiple regression analyses indicated that the soil salinity and pH in K. obovata mangroves and the soil redox potential and organic content in the mudflats were the key factors affecting CH4 emissions. However, the pneumatophore density alone explained approximately 48% of the variation in CH4 emissions in the A. marina mangroves. More pneumatophores resulted in higher CH4 emissions in the A. marina mangroves. Thus, compared with the assessed soil properties, the contribution of pneumatophores to the transportation of CH4 from soil was more significant. In addition to soil properties, our results demonstrated that the root structure may also affect GHG emissions from mangroves.

Mangroves are one of the blue carbon ecosystems. However, greenhouse gas emissions from mangrove soils may reduce the capacity of carbon storage in these systems. In this study, methane (CH4) fluxes and soil properties of the top 10 cm layer were determined in subtropical (Kandelia obovata) and tropical (Avicennia marina) mangrove ecosystems of Taiwan for a complete seasonal cycle. Our results demonstrate that CH4 emissions in mangroves cannot be neglected when constructing the carbon budgets and estimating the carbon storage capacity. CH4 fluxes were significantly higher in summer than in winter in the Avicennia mangroves. However, no seasonal variation in CH4 flux was observed in the Kandelia mangroves. CH4 fluxes were significantly higher in the mangrove soils of Avicennia than in the adjoining mudflats; this trend, however, was not necessarily recapitulated at Kandelia. The results of multiple regression analyses show that soil water and organic matter content were the main factors regulating the CH4 fluxes in the Kandelia mangroves. However, none of the soil parameters assessed show a significant influence on the CH4 fluxes in the Avicennia mangroves. Since pneumatophores can transport CH4 from anaerobic deep soils, this study suggests that the pneumatophores of Avicennia marina played a more important role than soil properties in affecting soil CH4 fluxes. Our results show that different mangrove tree species and related root structures may affect greenhouse gas emissions from the soils.

Cosmeceutical peptides have become an important topic in recent decades in both academic and industrial fields. Many natural or synthetic peptides with different biological functions including anti-ageing, anti-oxidation, anti-infection and anti-pigmentation have been developed and commercialized. Current cosmeceutical peptides have already satisfied most market demand, remaining: “cargos carrying skin penetrating peptide with high safety” still an un-met need. To this aim, a cell-penetrating peptide, CPPAIF, which efficiently transported cargos into epithelial cells was exanimated. CPPAIF was evaluated with cell model and 3D skin model following OECD guidelines without using animal models. As a highly stable peptide, CPPAIF neither irritated nor sensitized skin, also did not disrupt skin barrier. In addition, such high safety peptide had anti-inflammation activity without allergic effect. Moreover, cargo carrying activity of CPPAIF was assayed using HaCaT cell model and rapid CPPAIF penetration was observed within 30 min. Finally, CPPAIF possessed transepidermal activity in water in oil formulation without disruption of skin barrier. All evidences indicated that CPPAIF was an ideal choice for skin penetrating and its anti-inflammatory activity could improve skin condition, which made CPPAIF suitable and attractive for novel cosmeceutical product development.

Background: Electroconvulsive therapy (ECT) is an effective treatment for schizophrenia, bipolar disorder, and major depressive disorder, and a temporary memory loss may occur after ECT. However, the association between ECT in patients with schizophrenia, bipolar disorder, and major depressive disorder, and the risk of dementia is yet to be examined.Objective: This study aimed to clarify as to whether ECT is associated with the risk of dementia after ECT in patients with schizophrenia, bipolar disorder, and major depressive disorder, using Taiwan's National Health Insurance Research Database (NHIRD).Methods: A total of 3,796 enrolled participants (schizophrenia, 46.68%; bipolar disorder, 11.77%; and major depressive disorder, 41.55%) with 994 patients who had received ECT and 2,982 controls matched for sex and age, between January 1, and December 31, 2000, were selected from the NHIRD. After adjusting for confounding factors, Fine and Gray's survival analysis was used to compare the risk of developing dementia during the 10 years of follow-up.Results: Of the study patients, 45 (4.53%) of them developed dementia when compared to 149 (5.0%) in the control group. Fine and Gray's survival analysis revealed that the study patients were not associated with an increased risk of dementia [hazard ratio (HR) = 0.612, 95% confidence interval (CI) = 0.438–1.854, P = 0.325]. After adjusting for sex, age, monthly income, urbanization level, geographic region, and comorbidities, the adjusted HR was 0.633 (95% CI = 0.448 – 1.895, P = 0.304).Conclusion: This study supports that ECT was not associated with the increased risk of dementia in patients with schizophrenia, bipolar disorder, and major depressive disorder, using the NHIRD.

Introduction: In our study, we aimed to investigate the association between a traumatic brain injury (TBI) and subsequent erectile dysfunction (ED). This is a population-based study using the claims dataset from The National Health Insurance Research Database. Methods: We included 72,642 patients with TBI aged over 20 years, retrospectively, selected from the longitudinal health insurance database during 2000–2010, according to the ICD-9-CM. The control group consisted of 217,872 patients without TBI that were randomly chosen from the database at a ratio of 1:3, with age- and index year matched. Cox proportional hazards analysis was used to estimate the association between the TBI and subsequent ED. Results: After a 10-year follow-up, the incidence rate of ED was higher in the TBI patients when compared with the non-TBI control group (24.66 and 19.07 per 100,000, respectively). Patients with TBI had a higher risk of developing ED than the non-TBI cohort after the adjustment of the confounding factors, such as age, comorbidity, residence of urbanization and locations, seasons, level of care, and insured premiums (adjusted hazard ratio (HR) = 2.569, 95% CI [1.890, 3.492], p < .001). Conclusion: This is the first study using a comprehensive nationwide database to analyze the association of ED and TBI in the Asian population. After adjusted the confounding factors, patients with TBI have a significantly higher risk of developing ED, especially organic ED, than the general population. This finding might remind clinicians that it’s crucial in early identification and treatment of ED in post-TBI patients.

Background/objectiveAllergic diseases, such as bronchial asthma, allergic rhinitis, atopic dermatitis, and psychiatric disorders, are major health issues. There have been reports that allergic diseases were associated with depression or anxiety disorders. This study aimed to investigate the association between these allergic diseases and the risk of developing overall psychiatric disorders in patients from Taiwan.MethodsThis cohort study used the database of the Taiwan National Health Insurance Program. A total of 186,588 enrolled patients, with 46,647 study subjects who had suffered from allergic diseases, and 139,941 controls matched for sex and age, from the Longitudinal Health Insurance Dataset of 2000–2015, were selected from a sub-dataset of the National Health Insurance Research Database. Fine and Gray’s competing risk model analysis was used to explore the hazard ratio (HR), and 95% confidence interval, for the risk of allergic diseases being associated with the risk of developing psychiatric disorders during the 15 years of follow-up.ResultsOf the study subjects, 5,038 (10.8%) developed psychiatric disorders when compared to 9,376 (6.7%) in the control group, with significant difference (p

Background: The aim of the present study was to determine the prevalence, profile, and severity of dementia and the relative impact of these factors on caregiver burden in a selected population of persons with dementia and their caregivers. Methods: A convenience sample of 100 outpatients and their family caregivers dyads who presented to a memory clinic in one medical center during one consecutive year were recruited. The diagnosis and severity of dementia were determined according to the Diagnostic and Statistical Manual of Mental Disorders, Version IV, Text Revision. The clinical dementia rating scale, mini-mental status examination, and Clinical Global Impression of severity were also administered. The caregiver strain index was used to assess caregiver burden. Results: Caregiver burden is related to the severity of dementia, impairment of cognitive function, and severity of neuropsychiatric symptoms. The caregivers who were younger, nonspousal family members, had a poor relationship with the dementia patient, and psychosomatic symptoms after caring for the patient, or provided longer hours of care-giving, experienced greater strains. Hiring foreign helpers was not associated with a lower caregiver burden. Conclusions: Greater caregiver burden is associated with several factors related to persons with dementia and their caregivers. A possible over-burden on caregivers should be of concern in Taiwan. Hiring foreign helpers was not associated with a lower caregiver burden.

Objective: Decreased heart rate variability (HRV) has been reported in persons with major depressive disorder (MDD), but the results obtained are inconsistent. Little is known about the impact of comorbid anxiety disorders on HRV in MDD patients. Both issues necessitate further investigation. Materials and Methods: Forty-nine unmedicated, physically healthy, MDD patients without comorbidity, 21 MDD patients with comorbid generalized anxiety disorder (GAD), 24 MDD patients with comorbid panic disorder (PD), and 81 matched controls were recruited. The Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale are employed to assess the severity of depression and anxiety, respectively. The cardiac autonomic function was evaluated by measuring the HRV parameters. The frequency-domain indices of HRV were obtained. Results: MDD patients without comorbidity had lower high-frequency (HF)-HRV (which reflected vagal control of HRV) than controls. Any comorbid anxiety disorder (GAD or PD) was associated with significantly faster heart rates, relative to the controls, and caused greater reductions in HF-HRV among MDD patients. MDD participants with comorbid GAD displayed the greatest reductions in HF-HRV, relative to controls. Correlation analyses revealed that the severity of both depression and anxiety were significantly associated with the mean R wave to R wave (R-R) intervals, variance, low-frequency (LF)-HRV, and HF-HRV. Conclusion: The present results show decreased HRV in MDD patients, suggesting that reduction in HRV is a psychophysiological marker of MDD. MDD patients with comorbid GAD had the greatest reductions in HRV. Further investigation of the links between MDD and comorbid GAD, HRV, and cardiovascular disease is warranted.

Transforming growth factor-β (TGF-β) responsiveness in cultured cells can be modulated by TGF-β partitioning between lipid raft/caveolae- and clathrin-mediated endocytosis pathways. Lipid rafts are plasma membrane microdomains with an important role in cell survival signaling, and cholesterol is necessary for the lipid rafts' structure and function. Euphol is a euphane-type triterpene alcohol that is structurally similar to cholesterol and has a wide range of pharmacological properties, including anti-inflammatory and anti-cancer effects. In the present study, euphol suppressed TGF-β signaling by inducing TGF-β receptor movement into lipid-raft microdomains and degrading TGF-β receptors.

Heart rate variability (HRV) modulates both the sympathetic nervous system and the parasympathetic nervous system (PNS) of the autonomic nervous system. Mood disorder is one of the contributing factors to influence HRV. The warm-water footbath as a relaxing way is used to enhance the PNS. In this study, we intended to explore the association between HRV and a footbath in the mood disorder group. Methods: We recruited 14 young male study participants to receive a 30-minute warm-water footbath three times a week. Furthermore, we monitored the heart rates electrocardiographically before, during, and after the intervention. Results: This study showed that the footbath not only significantly enhanced standard deviation of NN (SDNN) intervals, high-frequency (HF) power, and low-frequency (LF) power during the first five minutes footbath (p < 0.01) but also increased all the parameters in five minutes after finishing the footbath. SDNN intervals, HF power, and LF power remained significantly upward in the next five minutes (p < 0.05). Conclusion: In line with previous studies, this study showed that a footbath elevated the PNS-related HRV parameters. We suggest that a warm-water footbath improves the PNS modulation possibly through baroreflex. In addition, those with cardiac conditions and depression should be particularly attentive to their condition during and following a footbath. [ABSTRACT FROM AUTHOR]