Mycb and Mych stimulate Müller glial cell reprogramming and proliferation in the uninjured and injured zebrafish retina.

In the injured zebrafish retina, Müller glial cells (MG) reprogram to adopt retinal stem cell properties and regenerate damaged neurons. The strongest zebrafish reprogramming factors might be good candidates for stimulating a similar regenerative response by mammalian MG. Myc proteins are potent reprogramming factors that can stimulate cellular plasticity in differentiated cells; however, their role in MG reprogramming and retina regeneration remains poorly explored. Here we report that retinal injury stimulates mycb and mych expression and that although both Mycb and Mych stimulate MG reprogramming and proliferation, only Mych enhances retinal neuron apoptosis. RNAseq analysis of Wt, mychmut, and mycbmut fish revealed Mycb and Mych regulate ∼40% and ∼16%, respectively, of the genes contributing to MG's regeneration-associated transcriptome. Of these genes, those that are induced are biased towards regulating ribosome biogenesis, protein synthesis, DNA synthesis, and cell division which are the top cellular processes regulated by retinal injury and this suggests Mycb and Mych are potent MG reprogramming factors. Consistent with this, forced expression of either of these proteins is sufficient to stimulate MG proliferation in the uninjured retina.

Heterozygous variants in SIX3 and POU1F1 cause pituitary hormone deficiency in mouse and man.

Congenital hypopituitarism is a genetically heterogeneous condition that is part of a spectrum disorder that can include holoprosencephaly. Heterozygous mutations in SIX3 cause variable holoprosencephaly in humans and mice. We identified two children with neonatal hypopituitarism and thin pituitary stalk who were doubly heterozygous for rare, likely deleterious variants in the transcription factors SIX3 and POU1F1. We used genetically engineered mice to understand the disease pathophysiology. Pou1f1 loss-of-function heterozygotes are unaffected; Six3 heterozygotes have pituitary gland dysmorphology and incompletely ossified palate; and the Six3+/-; Pou1f1+/dw double heterozygote mice have a pronounced phenotype, including pituitary growth through the palate. The interaction of Pou1f1 and Six3 in mice supports the possibility of digenic pituitary disease in children. Disruption of Six3 expression in the oral ectoderm completely ablated anterior pituitary development, and deletion of Six3 in the neural ectoderm blocked the development of the pituitary stalk and both anterior and posterior pituitary lobes. Six3 is required in both oral and neural ectodermal tissues for the activation of signaling pathways and transcription factors necessary for pituitary cell fate. These studies clarify the mechanism of SIX3 action in pituitary development and provide support for a digenic basis for hypopituitarism.

Vegf signaling between Müller glia and vascular endothelial cells is regulated by immune cells and stimulates retina regeneration.

In the zebrafish retina, Müller glia (MG) can regenerate retinal neurons lost to injury or disease. Even though zebrafish MG share structure and function with those of mammals, only in zebrafish do MG function as retinal stem cells. Previous studies suggest dying neurons, microglia/macrophage, and T cells contribute to MG's regenerative response [White et al., Proc. Natl. Acad. Sci. U.S.A. 114, E3719 (2017); Hui et al., Dev. Cell 43, 659 (2017)]. Although MG end-feet abut vascular endothelial (VE) cells to form the blood-retina barrier, a role for VE cells in retina regeneration has not been explored. Here, we report that MG-derived Vegfaa and Pgfa engage Flt1 and Kdrl receptors on VE cells to regulate MG gene expression, Notch signaling, proliferation, and neuronal regeneration. Remarkably, vegfaa and pgfa expression is regulated by microglia/macrophages, while Notch signaling in MG is regulated by a Vegf-dll4 signaling system in VE cells. Thus, our studies link microglia/macrophage, MG, and VE cells in a multicomponent signaling pathway that controls MG reprogramming and proliferation.

The risk of obstructive sleep apnea is highly correlated with depressive symptoms among the Korean adults population: results from the 2020 Korea National Health and Nutrition Examination Survey.

OBJECTIVES: We aimed to examine the association between Obstructive Sleep Apnea (OSA) risk, health behaviors, and depressive symptoms in a representative Korean sample. METHODS: Cross-sectional data from the 2020 Korea National Health and Nutrition Examination Survey (KNHANES) were analyzed. The sample included 4,352 adults aged 40 years and older. Multiple linear regression analysis was performed to examine the association between OSA risk, health behaviors, and depressive symptoms. RESULTS: In total, 23.1% of the participants reported a high risk of OSA. Of the respondents, 39.8%, 19.0%, 27.2%, and 8.7% reported hypertension, snoring, tiredness, and observed apnea, respectively. The prevalence of moderate-severe depressive symptoms among adults with high-risk OSA was 7.5%. The significant associations between OSA risk and sex with PHQ-9 were shown in univariate linear regression. In the multiple linear regression analysis, the association between high risk of OSA and PHQ-9 showed in total (B = 1.58; P < 0.001), male (B = 1.21; P < 0.001), and female (B = 1.93; P < 0.001). CONCLUSIONS: A high risk of OSA was associated with an increased prevalence of depressive symptoms. Monitoring the risk factors of depressive symptoms, including OSA, or unhealthy behaviors may decrease the mental health issues of middle-aged and older adults.

Attention, Externalizing and Internalizing Problems Mediated Differently on Internet Gaming Disorder Among Children and Adolescents With a Family History of Addiction as an Adverse Childhood Experience.

BACKGROUND: This study aimed to examine the factors associated with internet gaming disorder (IGD) and the mediating role of pediatric symptoms (attention, externalizing problems and internalizing problems) in children and adolescents with a family history of addiction as an adverse childhood experience (ACE). METHODS: A total of 2,586 children and adolescents (mean age = 14.04 ± 2.34; age range = 11-19 years; 50.5% boys) completed the Internet Game Use-Elicited Symptom Screen and the Pediatric Symptom Checklist-17. IBM SPSS Statistics 21 was used to calculate descriptive statistics and Pearson correlation coefficients and to conduct multiple regression analyses. Mediation analysis was performed using the Sobel test and the SPSS PROCESS macro. Serial multiple mediation analysis was performed using bootstrapping with 5,000 replications. RESULTS: The higher levels of Attention problems (ß = -0.228, P < 0.001) and externalizing problems (ß = -0.213, P < 0.001) were associated with IGD. Furthermore, the indirect effect of the independent variable on the dependent variable through the mediators was significant (Sobel's T: Z = -5.006, P < 0.001). These findings suggest that attention and externalizing problems mediate the effect of family history of addiction on IGD. CONCLUSION: This study demonstrated the associations among the family history of addiction, IGD, and pediatric symptoms (attention, externalizing problems, and internalizing problems) among Korean children and adolescents. Therefore, we need to pay attention to pediatric symptoms and develop systematic alternatives to improve mental health among Korean children and adolescents with a family history of addiction as ACEs.

Can We Notice the Suicidal Warning Signs of Adolescents With Different Psychometric Profiles Before Their Death?: Analysis of Teachers' Reports.

BACKGROUND: This study aimed to analyze the suicidal warning signs of Korean students with different psychometric profiles based on teacher reports. METHODS: This was a retrospective cohort study based on Korean school teachers' responses to the Student Suicide Report Form. In total, 546 consecutive cases of student suicide were reported from 2017 to 2020. After missing data were excluded, 528 cases were included. The report consisted of demographic factors, the Korean version of the Strengths and Difficulties Questionnaire (SDQ) for teacher reporting, and warning signs of suicide. Frequency analysis, multiple response analysis, the χ² test, and Latent Class Analysis (LCA) were performed. RESULTS: Based on the scores of the Korean version of the teacher-reported SDQ, the group was divided into nonsymptomatic (n = 411) and symptomatic (n = 117) groups. Based on the LCA results, four latent hierarchical models were selected. The four classes of deceased students showed significant differences in school type (χ² = 20.410, P < 0.01), physical illness (χ² = 7.928, P < 0.05), mental illness (χ² = 94.332, P < 0.001), trigger events (χ² = 14.817, P < 0.01), self-harm experience (χ² = 30.618, P < 0.001), suicide attempts (χ² = 24.072, P < 0.001), depressive symptoms (χ² = 59.561, P < 0.001), anxiety (χ² = 58.165, P < 0.001), impulsivity (χ² = 62.241, P < 0.001), and social problems (χ² = 64.952, P < 0.001). CONCLUSION: Notably, many students who committed suicide did not have any psychiatric pathology. The proportion of the group with a prosocial appearance was also high. Therefore, the actual suicide warning signals were similar regardless of students' difficulties and prosocial behaviors, so it is necessary to include this information in gatekeeper education.

Household use of crop residues and fuelwood for cooking and newborn birth size in rural Bangladesh.

OBJECTIVES: We aimed to investigate the association between type of cooking biomass fuels (crop residues vs fuelwood) and newborn birth outcomes in Bangladeshi children. METHODS: In this birth cohort study, pregnant women who were 18 years or older with ultrasound confirmed singleton pregnancy of ≤16 weeks of gestation were enrolled from two Bangladesh clinics between January 2008 and June 2011. Exposure to cooking biomass fuels during pregnancy was assessed by an administered questionnaire. The newborn size metrics were measured at the time of delivery. We used multiple linear regression and logistic regression to assess the associations between the type of cooking biomass fuels and birth outcomes after adjusting for covariates. RESULTS: A total of 1137 participants were using biomass fuels, including crop residues (30.3%) and fuelwood (69.7%), respectively, for cooking. After adjusting for covariates, the use of crop residues for cooking was associated with a 0.13 SD decrease in birth length (95% CI 0.25 to -0.01), a 0.14 SD decrease in head circumference (95% CI -0.27 to -0.02), and increased risk of low birth weight (LBW, OR 1.52, 95% CI 1.07 to 2.15) compared with the use of fuelwood. CONCLUSION: The use of crop residues for cooking was associated with reduced birth size and increased risk for LBW in Bangladeshi children, implying that the use of crop residues during pregnancy may have a detrimental effect on fetal growth.

Comparative Analysis of the Psychosocial Symptoms and Experiences of Bereaved Parents and Parents of Children Who Survived the Sewol Ferry Accident After 5 Years: A Qualitative Interview Study.

BACKGROUND: This study aimed to investigate the psychosocial symptoms and experiences of bereaved parents of victims and parents of survivors of the Sewol Ferry accident five years after the accident. METHODS: In-depth interviews of 186 bereaved parents of victims or survivors of the Sewol Ferry accident were conducted. We elicited and categorized meaning units relevant to the psychological, cognitive, and physical traits of the participants from these interviews. Differences in responses between bereaved parents and survivors' parents and between genders were examined using frequency analyses and χ² tests. RESULTS: Data were organized under seven headings: observed attitude and impression of participants, difficulties due to mental health problems, difficulties due to physical pain, difficulties in relationships, negative changes following the incident, positive changes following the incident, and help needed. Within these headings, 27 themes, 60 sub-themes, and 80 meaning units were elicited. CONCLUSION: This study explored the psychiatric, physical, and relational problems reported by bereaved parents and those of survivors as well as major changes in their personal and social lives after the Sewol Ferry accident. Differences in responses according to gender were also identified. The results from this study could inform and facilitate the implementation of intervention measures, such as long-term psychological evaluation, to bereaved parents of victims or survivors of disasters.

Efficacy of the 'Children in Disaster: Evaluation and Recovery (CIDER)' Protocol for Traumatized Adolescents in Korea.

BACKGROUND: We aimed to evaluate the feasibility of trauma-focused group therapy in adolescents exposed to traumatic events in Korea. METHODS: We recruited 22 adolescents (mean age, 16 years; standard deviation, 1.43; range, 13-18 years). Children in Disaster: Evaluation and Recovery (CIDER) V1.0 is a trauma-focused group therapy comprising eight 50-minute-long sessions. The effectiveness of the intervention was evaluated using the Korean version of the Children's Response to Traumatic Events Scale-Revised (K-CRTES-R), the Beck Depression Inventory (BDI), the State Anxiety Inventory for Children (SAIC), and the Pediatric Quality of Life Inventory (PedsQL). The data were analyzed by the Wilcoxon signed-rank test. RESULTS: A significant improvement was revealed in trauma-related symptom scores (Z = -2.85, P < 0.01), depressive symptom scores (Z = -2.35, P < 0.05) and quality of life scores (Z = -3.08, P < 0.01). Additionally, a marginally significant improvement was found in anxiety symptom scores (Z = -1.90, P = 0.058). CONCLUSION: CIDER is a potentially effective intervention for adolescents exposed to traumatic events. Larger controlled trials are needed. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0004681.

Exposure to Adverse Childhood Experiences (ACEs) and Stress among the Community-based Urban Pediatric Population in Korea.

BACKGROUND: This study aimed to investigate the impact of exposure to adverse childhood experiences (ACEs) and stress among the community-based urban pediatric population in Korea. METHODS: In 2017, the analysis was conducted on 3,937 children and adolescents in an urban area in Korea based on the impact of actual traumatic experience, addiction, and mental health. The respondents were excluded if they were missing data on the survey, resulting in a final sample size of 3,556. The collected data were analyzed by applying cross-sectional and correlation analyses. RESULTS: Among the respondents in the study group (mean age = 13.77), 43.1% were boys (n = 1,532) and 56.9% were girls (n = 2,024). Overall, 23.5% (n = 835) reported at least one ACE and 1.8% (n = 63) reported experiencing four or more ACEs. Emotional abuse (13.2%) was the most commonly reported ACE, followed by abandonment (7.7%) and physical abuse (7.5%). Self-reported measures of stress were associated with the ACE scores. CONCLUSION: This is the first study of self-reported ACEs from a community-based pediatric population in Korea. We found that the number of the students revealed more than one ACEs was similar to the data in the US community study with self-reporting among the community samples and exposure to adverse experiences is highly correlated with various stress responses.

The Mediating Effect of Depressive Symptoms on the Relationship between Adverse Childhood Experiences and Problematic Internet Use in Children and Adolescents.

The purpose of this study was to evaluate the mediating effect of depressive symptoms on the relationship between adverse childhood experiences (ACEs) and problematic internet use. The study participants were 180 students between the ages of 9 and 18 years. Path analysis was performed to measure the relationships among ACEs, depressive symptoms and problematic internet use. ACEs significantly affected depressive symptoms (standardized regression weight, 0.36; P < 0.01), and depressive symptoms also affected problematic internet use (standardized regression weight, 0.40; P < 0.01). We found that depressive symptoms had a significant mediating effect on the relationship between problematic internet use and ACEs. The management of depressive symptoms would be important to prevent problematic internet use in children and adolescents with ACEs.

Psychiatric Symptoms and Clinical Diagnosis in High School Students Exposed to the Sewol Ferry Disaster.

BACKGROUND: Two hundred and fifty 11th grade students and teachers from Danwon High School drowned, during a school trip, in the Sewol Ferry Disaster. The goal of this study was to investigate the experiences of the psychiatrists who volunteered and provided psychiatric services to the students at Danwon High School. METHODS: From the second day to the 138th day after the disaster, pro bono psychiatrists provided post-disaster interventions to the 10th and 12th-grade Danwon High School students who did not attend the trip. Officially, 167 psychiatrists conducted outreach in approximately 550 encounters. The study questionnaires were distributed retrospectively to psychiatric volunteers who conducted outreach at Danwon High School. We surveyed the pro bono psychiatrists about their experiences, including the students' chief complaints, psychiatric problems, clinical diagnoses, and psychiatrists' treatment recommendations. RESULTS: We reached 72 (43.1%) of the 167 volunteers, and they reported on 212 (38.6%) of the 550 encounters. The common chief complaints were mental health problems, companion problems, and family problems. The most frequent psychiatric symptoms were anxiety (76.89%), depressive mood (51.42%), and concentration difficulty (50.94%). The most frequent clinical diagnoses of the students were normal reaction (41.04%), acute stress disorder (24.53%), adjustment disorder (17.92%), anxiety disorders (9.43%), and posttraumatic stress disorder (6.60%). More than half of the students needed "additional counseling/therapy" (41.04%) or "referral to psychiatric treatment" (14.15%). CONCLUSION: During the acute aftermath of the Sewol Ferry Disaster, volunteer psychiatrists were able to provide services. These services included psychiatric assessments, crisis counseling, psychological first aid, and referrals for ongoing care. More than half of the students were perceived to have a psychiatric diagnosis, and a substantial proportion of students needed further treatment. Future research should focus on the short- and long-term effects of psychiatric interventions and the characterization of post-disaster mental health needs and service provision patterns.

The predictive role of health-promoting behaviours and perceived stress in aneurysmal rupture.

AIMS AND OBJECTIVES: To examine the roles of two modifiable factors-health-promoting behaviours and perceived stress-in predicting aneurysmal rupture. BACKGROUND: Unruptured intracranial aneurysm detection produces significant stress and anxiety in patients because of the risk of rupture. Compared to nonmodifiable risk factors for rupture such as age, gender and aneurysm size/location, less attention has been given to modifiable risk factors. Two modifiable factors, health-promoting behaviours and perceived stress, have hardly been examined as potential predictors of rupture. DESIGN: This study used a cross-sectional design. METHODS: We assessed 155 patients with intracranial aneurysms-that is, subarachnoid haemorrhage (n = 77) or unruptured intracranial aneurysm (n = 78)-to examine (i) baseline characteristics (patient and aneurysmal factors), (ii) health-related factors (lifestyle habits and health-promoting behaviour) and (iii) perceived stress levels (psychological stress and physical stress). Patient records provided medical histories and aneurysmal factors; other data were collected using a structured questionnaire addressing lifestyle habits, the Health-Promoting Lifestyle Profile-II to measure health-promoting behaviour and the Perceived Stress Questionnaire to measure perceived-psychological stress and perceived-physical stress levels. RESULTS: Bivariate analysis indicated that aneurysm rupture risk was associated with female gender, aneurysm size/location, defecation frequency, hyperlipidaemia, sedentary time, low Health-Promoting Lifestyle Profile-II mean scores and high perceived-psychological stress scores. After adjusting for known risk factors, the mean Health-Promoting Lifestyle Profile-II and perceived-psychological stress scores remained robust predictors of rupture. Furthermore, known risk factors combined with these scores had greater predictive power than known risk factors alone. CONCLUSION: Health-promoting behaviour and psychological stress are promising modifiable factors for reducing risk of aneurysmal rupture. RELEVANCE TO CLINICAL PRACTICE: Our findings may stimulate greater understanding of mechanisms underlying aneurysmal rupture and suggest practical strategies for nurses to employ in optimising conservative management of rupture risk by teaching patients how to modify their risk. Both health-promoting behaviour and perceived stress should be addressed when designing preventive nursing interventions for patients with unruptured intracranial aneurysm.

Muscle-specific deletion of signal transducer and activator of transcription 5 augments lipid accumulation in skeletal muscle and liver of mice in response to high-fat diet.

PURPOSE: Growth hormone (GH) controls liver metabolism through the transcription factor signal transducer and activator of transcription 5 (STAT5). However, it remains to be fully understood to what extent other GH/STAT5 target tissues contribute to lipid and glucose metabolism. This question was now addressed in muscle-specific STAT5 knockout (STAT5 MKO) mice model. METHODS: Changes in lipid and glucose metabolism were investigated at physiological and molecular levels in muscle and liver tissues of STAT5 MKO mice under normal diet or high-fat diet (HFD) conditions. RESULTS: STAT5 MKO mice exhibited an increased intramyocellular lipid (IMCL) accumulation in the quadriceps in HFD group. Decreased lipolytic hormone-sensitive lipase transcript levels may contribute to the increased IMCL accumulation in STAT5 MKO mice. STAT5 MKO induced hepatic lipid accumulation without deregulated STAT5 signaling. The upregulation of lipoprotein lipase and Cd36 mRNA levels, an increased trend of very low-density lipoprotein receptor mRNA levels, and elevated circulating concentrations of free fatty acid, triglyceride, and total cholesterol support the increase in hepatic lipid accumulation. CONCLUSIONS: STAT5 MKO in conjunction with a HFD deregulated both lipid and glucose metabolism in skeletal muscle, and this deregulation induced hepatic fat accumulation via increased circulating glucose, FFA, and TG concentrations. Our study emphasizes that muscle-specific STAT5 signaling is important for balancing lipid and glucose metabolism in peripheral tissues, including muscle and liver and that the deregulation of local STAT5 signaling augments HFD-induced lipid accumulation in both muscle and liver.

Nicotine, aerosol particles, carbonyls and volatile organic compounds in tobacco- and menthol-flavored e-cigarettes.

BACKGROUND: We aimed to assess the content of electronic cigarette (EC) emissions for five groups of potentially toxic compounds that are known to be present in tobacco smoke: nicotine, particles, carbonyls, volatile organic compounds (VOCs), and trace elements by flavor and puffing time. METHODS: We used ECs containing a common nicotine strength (1.8%) and the most popular flavors, tobacco and menthol. An automatic multiple smoking machine was used to generate EC aerosols under controlled conditions. Using a dilution chamber, we targeted nicotine concentrations similar to that of exposure in a general indoor environment. The selected toxic compounds were extracted from EC aerosols into a solid or liquid phase and analyzed with chromatographic and spectroscopic methods. RESULTS: We found that EC aerosols contained toxic compounds including nicotine, fine and nanoparticles, carbonyls, and some toxic VOCs such as benzene and toluene. Higher mass and number concentrations of aerosol particles were generated from tobacco-flavored ECs than from menthol-flavored ECs. CONCLUSION: We found that diluted machine-generated EC aerosols contain some pollutants. These findings are limited by the small number of ECs tested and the conditions of testing. More comprehensive research on EC exposure extending to more brands and flavor compounds is warranted.

The effect of fluidotherapy on hand dexterity and activities of daily living in patients with edema on stroke.

[Purpose] The purpose of this study was to investigate the effect of fluidotherapy on hand's dexterity and activities of daily living for stroke patients with upper limb edema. [Subjects and Methods] The objective of the present study was to treat 30 stroke patients with a three-week course of fluidotherapy to investigate the efficacy of such therapy for reduction of edema. For accurate baseline and post-intervention assessment of edema volume, hand edema was measured in the morning using a forearm volumeter. [Results] Mean edematous volume in the affected side measured 600.53 ± 29.94 ml prior to intervention, significantly decreasing to 533.53 ± 27.85 ml after three weeks of fluidotherapy. To investigate how such reduction may have enhanced the ability to perform activities of daily living, Korean Version of Modified Barthel Index assessment was performed. The results showed 46.10 ± 4.27 points at baseline and significantly improved to a mean score of 49.96 ± 4.34 points at the time of reassessment. Furthermore, Box and Block Test was performed to investigate hand dexterity. Before fluidotherapy, affected patients transferred 21.13 ± 3.63 blocks in one minute, increasing to 23.20 ± 3.42 blocks transferred in one minute following three weeks of treatment. Although the number of blocks transferred did increase slightly, the difference was not statistically significant. [Conclusion] These findings suggest that using fluidotherapy can reduce edema, and such a reduction can have a positive effect on activities of daily living. Based on our current findings, we hypothesize that long-term fluidotherapy treatment may be more effective in reducing edema.

IFT46 plays an essential role in cilia development.

Cilia are microtubule-based structures that project into the extracellular space. Ciliary defects are associated with several human diseases, including polycystic kidney disease, primary ciliary dyskinesia, left-right axis patterning, hydrocephalus and retinal degeneration. However, the genetic and cellular biological control of ciliogenesis remains poorly understood. The IFT46 is one of the highly conserved intraflagellar transport complex B proteins. In zebrafish, ift46 is expressed in various ciliated tissues such as Kupffer׳s vesicle, pronephric ducts, ears and spinal cord. We show that ift46 is localized to the basal body. Knockdown of ift46 gene results in multiple phenotypes associated with various ciliopathies including kidney cysts, pericardial edema and ventral axis curvature. In ift46 morphants, cilia in kidney and spinal canal are shortened and abnormal. Similar ciliary defects are observed in otic vesicles, lateral line hair cells, olfactory pits, but not in Kupffer׳s vesicle. To explore the functions of Ift46 during mouse development, we have generated Ift46 knock-out mice. The Ift46 mutants have developmental defects in brain, neural tube and heart. In particular Ift46(-/-) homozygotes displays randomization of the embryo heart looping, which is a hallmark of defective left-right (L/R) axis patterning. Taken together, our results demonstrated that IFT46 has an essential role in vertebrate ciliary development.

Dosage-dependent role of Rac1 in podocyte injury.

Activation of small GTPase Rac1 in podocytes is associated with rodent models of kidney injury and familial nephrotic syndrome. Induced Rac1 activation in podocytes in transgenic mice results in rapid transient proteinuria and foot process effacement, but not glomerular sclerosis. Thus it remains an open question whether abnormal activation of Rac1 in podocytes is sufficient to cause permanent podocyte damage. Using a number of transgenic zebrafish models, we showed that moderate elevation of Rac1 activity in podocytes did not impair the glomerular filtration barrier but aggravated metronidazole-induced podocyte injury, while inhibition of Rac1 activity ameliorated metronidazole-induced podocyte injury. Furthermore, a further increase in Rac1 activity in podocytes was sufficient to cause proteinuria and foot process effacement, which resulted in edema and lethality in juvenile zebrafish. We also found that activation of Rac1 in podocytes significantly downregulated the expression of nephrin and podocin, suggesting an adverse effect of Rac1 on slit diaphragm protein expression. Taken together, our data have demonstrated a causal link between excessive Rac1 activity and podocyte injury in a dosage-dependent manner, and transgenic zebrafish of variable Rac1 activities in podocytes may serve as useful animal models for the study of Rac1-related podocytopathy.

Commuting mode and pulmonary function in Shanghai, China.

Exposure to air pollution can be particularly high during commuting and may depend on the mode of transportation. We investigated the impact of commuting mode on pulmonary function in Shanghai, China.The Shanghai Putuo Study is a cross-sectional, population-based study. Our primary outcomes were forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) % predicted, and the secondary outcome was spirometric airflow obstruction. We tested the association between mode of transportation and these outcomes after adjusting for confounders.The study population consisted of 20 102 subjects. After adjusting for confounders, the change (95% CI) in FEV1 was -2.15% pred (-2.88- -1.42% pred) among pedestrians, -1.32% pred (-2.05- -0.59% pred) among those taking buses without air conditioning, -1.33% pred (-2.05- -0.61% pred) among those taking buses with air conditioning and -2.83% pred (-5.56- -0.10% pred) among those using underground railways, as compared to cyclists (the reference group). The effects of mode on FVC % predicted were in the same direction. Private car use had a significant protective effect on FVC % predicted and the risk of airflow obstruction (defined by Global Initiative for Chronic Obstructive Lung Disease but not by lower limit of normal criteria).Mode of transportation is associated with differences in lung function, which may reflect pollution levels in different transportation microenvironments.