Aflatoxin B1 exposure triggers hepatic lipotoxicity via p53 and perilipin 2 interaction-mediated mitochondria-lipid droplet contacts: An in vitro and in vivo assessment.

Aflatoxin B1 (AFB1) is one of the most toxic mycotoxins widely found in food contaminants, and its target organ is the liver. It poses a major food security and public health threat worldwide. However, the lipotoxicity mechanism of AFB1 exposure-induced liver injury remains unclear and requires further elucidation. Herein, we investigated the potential hepatic lipotoxicity of AFB1 exposure using in vitro and in vivo models to assess the public health hazards of high dietary AFB1 exposure. We demonstrated that low-dose of AFB1 (1.25 µM for 48 h, about one-fifth of the IC50 in HepG2 and HepaRG cells, IC50 are 5.995 µM and 5.266 µM, respectively) exposure significantly induced hepatic lipotoxicity, including abnormal lipid droplets (LDs) growth, mitochondria-LDs contacts increase, lipophagy disruption, and lipid accumulation. Mechanistically, we showed that AFB1 exposure promoted the mitochondrial p53 (mito-p53) and LDs-associated protein perilipin 2 (PLIN2) interaction-mediated mitochondria-LDs contacts, resulting in lipid accumulation in hepatocytes. Mito-p53-targeted inhibition, knockdown of PLIN2, and rapamycin application efficiently promoted the lysosome-dependent lipophagy and alleviated the hepatic lipotoxicity and liver injury induced by AFB1 exposure. Overall, our study found that mito-p53 and PLIN2 interaction mediates three organelles-mitochondria, LDs, and lysosomal networks to regulate lipid homeostasis in AFB1 exposure-induced hepatotoxicity, revealing how this unique trio of organelles works together and provides a novel insight into the targeted intervention in inter-organelle lipid sensing and trafficking for alleviating hazardous materials-induced hepatic lipotoxicity.

Assessment of Occlusal Vertical Dimension Change in Mechanical and Virtual Articulation: A Pilot Study.

The aim of this clinical study was to investigate the change in occlusal vertical dimension (OVD) with dental casts mounted on a mechanical articulator using an average axis facebow and on a virtual articulator mounted using the Bonwill triangle and the Balkwill angle and compare these groups with OVD change observed clinically in patients. Casts were obtained from each patient (n = 14) and mounted on a semi-adjustable articulator in the facebow preservation group (FPG) and on a virtual articulator using average anatomic values in the average mounting group (AMG). Customized mandibular anterior splints were virtually designed at an OVD increased by 3, 6, and 9 mm. Digital buccal scans were performed with the anterior devices in the participants' mouths in the intraoral group (IOG), AMG, and FPG at the different OVD increases accordingly. While no statistically significant differences (p > 0.05) were observed in the posterior interocclusal measurements with the incisal guide pin raised by 3 mm and 6 mm among all groups, a 9 mm increase resulted in a significant difference between AMG and IOG. The interocclusal posterior-to-anterior opening ratio observed clinically was 1:1.575. Increases in OVD up to 6 mm on dental casts mounted using average anatomic values performed similarly to the actual intraoral changes.

The Power of Women: Does increasing women's parliamentary representation reduce intake of sugar-sweetened beverages among children and adolescents?

OBJECTIVE: Consumption of sugar-sweetened beverages (SSBs) is associated with overweight and obesity in children and adolescents. Although existing research confirms the significance of economic and social factors as determinants of SSB intake, comparative studies on political factors and cross-national analyses are lacking. Research indicates that including women in the process of political decision-making promotes healthcare and child protection. This study examined how women's parliamentary representation influences children's and adolescents' SSB intake compared to adults. DESIGN: The study used cross-national food and beverage intake data from the Global Dietary Database. The outcome measurement was SSB consumption (g/day) for different population groups. We modeled SSB intake as a function of age groups, women's parliamentary representation at the national level (the independent variable), regime types (the contextual factor), and import tariffs on SSBs (the mediator) using country and time fixed effects regression models. SETTING: 185 countries across three waves from 2005 to 2015. PARTICIPANTS: Different population groups. RESULTS: The impact of female representation on reducing SSB consumption is more prevalent in children and adolescents than in adults. Furthermore, the effect of women's parliamentary representation on SSB consumption among children and adolescents is conditional on a country's democratic status. Finally, the marginal effect decreases when import tariffs on SSBs are considered a link in a causal chain. No changes in adult SSB intake are statistically significant. CONCLUSIONS: The findings suggest that the presence of women in the legislature can have a substantial impact on child and adolescent health.

Is trade a blessing or a curse? A panel data analysis of the determinants of depressive disorders.

OBJECTIVES: Given the speculation of the market economy causing an epidemic of depression, this study aimed to examine the influence of international trade on the prevalence of depressive disorders. METHODS: We used panel data from 1993 to 2015 covering 170 countries (n = 3787) and applied fixed effects regression models. We modeled the prevalence of depressive disorders as a function of international trade, adjusting for economic development, economic growth, and population size. Regime types, media freedom, and capital-labor ratio were included as moderators. RESULTS: A 100% point increase in the value of international trade indicated a 0.09% point decrease in the prevalence of depressive disorders (- 0.09, confidence interval [CI] - 0.01 to - 0.18). However, this effect existed only for democratic countries (- 0.15, CI - 0.03 to - 0.28). The effect was more prevalent when the governments allowed the media more freedom (score of 100, - 0.31, CI - 0.17 to - 0.45) or when a country's capital-labor ratio of endowments was high (50,000, - 0.22, CI - 0.08 to - 0.35). CONCLUSIONS: Trade brings about positive mental health outcomes in democracies, countries having free media, or capital-abundant economies.

How time horizons of autocrats impact health expenditure: a mixed methods research.

BACKGROUND: A country's spending on healthcare significantly improves its population health status. No comparative study has examined how the threat perceived by leaders influences health expenditure and cross-national analyses of authoritarian regimes. The objectives of this study are to examine how time horizons of autocrats influence health expenditure. METHODS: We designed a mixed methods research approach. First, the study used panel data from 1995 to 2010 covering 95 countries (n = 1208) and applied fixed effects regression models. As a proxy for time horizons, the study generated the predicted survival time for each regime-year using parametric survival analysis and the predictors to model regime failure. Second, we chose Chad, Rwanda and Ivory Coast to apply synthetic control methods for comparative case studies. Armed conflict had significant effects on regime duration and was used for an intervention. We constructed a synthetic version of each country, combining counties that did not or did experience armed conflict to resemble the values of health expenditure predictors for the actual country prior to the intervention. RESULTS: We found that an increase in the natural log form of survival time by 1 resulted in a 1.14 percentage point increase in health expenditure (% of GDP) (1.14, 95% CI = 0.60-1.69). Furthermore, we found that the difference in health expenditure between the actual Chad and its synthetic version starts to grow following the civil war in 2004 (in 2004, actual: 5.72%, synthetic: 5.91%; in 2005, actual: 3.91%, synthetic: 6.74%). Similarly, a large health expenditure gap between the actual Rwanda and its synthetic control resulted after the peace deal was signed in 2002 (in 2002, actual: 4.18%, synthetic: 4.77%; in 2003, actual: 6.34%, synthetic: 5.03%). In Ivory Coast, the two series diverge substantially during the civil war from 1999 to 2005 (in 1998, actual: 7.30%, synthetic: 7.11%; in 2002, actual: 4.47%, synthetic: 7.43%; in 2007, actual: 6.35%, synthetic: 6.50%). CONCLUSIONS: The findings suggest that health expenditure decreases as regime time horizons shrink, and reducing armed conflict is a way to promote regime stability.

The Impact of Dengue on Economic Growth: The Case of Southern Taiwan.

Dengue has long been a public health problem in tropical and subtropical countries. In 2015, a dengue outbreak occurred in Taiwan, where 43,784 cases were reported. This study aims to assess the impact of dengue on Southern Taiwan's economic growth according to the economic growth model-based regression approach recommended by the World Health Organization (WHO). Herein, annual data from Southern Taiwan on the number of dengue cases, income growth, and demographics from 2010-2015 were analyzed. The percentage of reduction of the average income per capita in 2015 due to the dengue outbreak was estimated. Dengue was determined to have a negative linear economic impact on Southern Taiwan's economic growth. In particular, a reduction of 0.26% in the average income per capita was estimated in Southern Taiwan due to the 2015 outbreak. If the model is applied alongside other dengue outbreak forecast models, then the forecast for economic reduction due to a future dengue outbreak may also be estimated. Prevention and recovery policies may subsequently be decided upon based on not only the number of dengue cases but also the degree of economic burden resulting from an outbreak.

A Dictator's Gift: Dominant party regimes and health expenditures.

BACKGROUND: A country's health expenditure significantly improves its population health status. This study aims to examine the determinants of health expenditure in dictatorships. METHODS: We designed a mixed methods research approach. First, we used panel data from 1995 to 2014 covering 99 countries (n = 1488). Fixed effects regression models were fitted to determine how different types of authoritarianism relate to health expenditure. Second, we chose Ivory Coast to apply the synthetic control methods for a case study. We constructed a synthetic Ivory Coast, combining other dominant party regimes to resemble the values of health expenditure predictors for Ivory Coast prior to a regime change from a dominant party system to personalist dictatorships in 2000. RESULTS: We found that dominant party autocracies, compared with non-dominant party regimes, increased health expenditure (% of GDP) (1.36 percentage point increase, CI = 0.59-2.12). The marginal effect, however, decreased when an autocrat in this type of regime held elections (0.86 percentage point decrease, CI = 0.20-1.52). Furthermore, we found the difference in health expenditure between the actual Ivory Coast and its synthetic version starts to grow following the regime change in 2000 (in 2000, actual: 6.00%, synthetic: 6.04%; in 2001, actual: 4.85%, synthetic: 5.99%), suggesting a pronounced negative effect of the government transition on Ivory Coast health expenditure. CONCLUSION: The findings suggest that different forms of dictatorship are associated with varying levels of health expenditure. Where dictatorships rely on popular support, as is the case with dominant party dictatorships, health expenditure is generally greater.

Lack of mutagenicity, genotoxicity and developmental toxicity in safety assessment tests of Lactobacillus mali APS1.

Lactobacillus (L.) mali APS1 isolated from sugary kefir grains has been proven to affect energy and glucose homeostasis. However, without proper safety assessment it cannot be recommended as probiotics for human consumption. For genotoxicity, the Ames test showed no mutagenic effect of L. mali APS1 in the presence or absence of S9 mix metabolic activation. In-vitro mammalian chromosomal aberration test showed that the number of Chinese hamster ovary cells with abnormal chromosomes was <5% after L. mali APS1 treatment. Moreover, L. mali APS1 showed no risk of genotoxicity potential compared to the control. L. mali APS1 administration did not cause significant (p>0.05) changes in body weight, the number of reticulocytes, or in the occurrence percentage of micronucleus in Imprinting Control Region (ICR) mice. Based on the absence of maternal or fetal effects at any dosage level investigated, the teratogenicity could be defined as greater than 1,670 mg/kg b.w./day for maternal general toxicity and fetal development when L. mali APS1 was orally administered by gavage to pregnant SD rats during gestation days 6 to 15.

Histopathological assessment of inflammation and expression of inflammatory markers in patients with ketamine-induced cystitis.

The aim of the current study was to evaluate the histopathological features of inflammation and the expression levels of inflammatory markers in tissue samples from patients with ketamine­induced cystitis. Bladder biopsy samples for histological analysis were obtained from 23 patients (18 men and 5 women) with a self­reported history of ketamine use and who were treated for cystitis at the Tri­Service General Hospital of Taipei, Taiwan. Immunohistochemical staining for cyclooxygenase­2 (COX­2), inducible nitric oxide synthase (iNOS), matrix metallopeptidase­9 (MMP­9), mammalian target of rapamycin (mTOR), and phosphorylated 40S ribosomal protein S6 (Phos­S6) was performed. The results revealed urothelial atypia in all patients, and intravascular eosinophil accumulation in 22 patients. Histopathological features included denuded urothelial mucosa, ulceration, collagen deposition, smooth muscle degeneration and vessel proliferation. Tissue samples were immunopositive for all of the inflammation markers, including the urothelium, vessel walls, and smooth muscle. COX­2 staining revealed a significant difference between the inflammatory levels in the urothelium and smooth muscle, and iNOS staining differed significantly between inflammatory levels in smooth muscle (p=0.029). A positive correlation was observed between the percentage of Phos­S6­positive cells and the levels of inflammation in the urothelium. These results add to the descriptive literature on the histopathological aspects of ketamine­induced cystitis, emphasizing the inflammatory nature and a possible role for proteins such as COX­2, iNOS and Phos­S6 in the degree of inflammation.

(11)C-acetate as a new biomarker for PET/CT in patients with multiple myeloma: initial staging and postinduction response assessment.

PURPOSE: We investigated the potential value of (11)C-acetate (ACT) PET/CT in characterizing multiple myeloma (MM) compared with (18)F-FDG PET/CT. Bone marrow histological and whole-body (WB) MRI findings served as the reference standards. METHODS: In this prospective study, 15 untreated MM patients (10 men and 5 women, age range 48-69 years) underwent dual-tracer (11)C-ACT and (18)F-FDG PET/CT and WB MRI for pretreatment staging, and 13 of them had repeated examinations after induction therapy. Diffuse and focal bone marrow uptake was assessed by visual and quantitative analyses, including measurement of the maximum standardized uptake value (SUVmax). Between-group differences and correlations were assessed with the Mann-Whitney U test and the Pearson test. RESULTS: At staging, all 15 patients had diffuse myeloma involvement upon bone marrow examination with 30-90 % of plasma cell infiltrates. Diffuse infiltration was detected in all of them (100 %) using (11)C-ACT with a positive correlation between bone marrow uptake values and percentages of plasma cell infiltrates (r = +0.63, p=0.01). In contrast, a diagnosis of diffuse infiltration could be established using (18)F-FDG in only six patients (40 %). Focal lesions were shown in 13 patients on both (11)C-ACT PET/CT and WB MRI, and in 10 patients on (18)F-FDG PET/CT. Focal lesions demonstrated (11)C-ACT uptake with a mean SUVmax of 11.4 ± 3.3 (range 4.6-19.6, n=59), which was significantly higher than the (18)F-FDG uptake (mean SUVmax 6.6 ± 3.1, range 2.3-13.7, n=29; p<0.0001). After treatment, the diffuse bone marrow (11)C-ACT uptake showed a mean SUVmax reduction of 66 % in patients with at least a very good partial response versus 34 % in those with at most a partial response only (p=0.01). CONCLUSION: PET/CT using (11)C-ACT as a biomarker showed a higher detection rate for both diffuse and focal myeloma lesions at diagnosis than using (18)F-FDG, and may be valuable for response assessment.

Extracorporeal shock wave therapy reverses ischemia-related left ventricular dysfunction and remodeling: molecular-cellular and functional assessment.

An optimal treatment for patients with diffuse obstructive arterial disease unsuitable for catheter-based or surgical intervention is still pending. This study tested the hypothesis that extracorporeal shock wave (ECSW) therapy may be a therapeutic alternative under such clinical situation. Myocardial ischemia was induced in male mini-pigs through applying an ameroid constrictor over mid-left anterior descending artery (LAD). Twelve mini-pigs were equally randomized into group 1 (Constrictor over LAD only) and group 2 (Constrictor over LAD plus ECSW [800 impulses at 0.09 mJ/mm(2)] once 3 months after the procedure). Results showed that the parameters measured by echocardiography did not differ between two groups on days 0 and 90. However, echocardiography and left ventricular (LV) angiography showed higher LV ejection fraction and lower LV end-systolic dimension and volume in group 2 on day 180 (p<0.035). Besides, mRNA and protein expressions of CXCR4 and SDF-1α were increased in group 2 (p<0.04). Immunofluorescence staining also showed higher number of vWF-, CD31-, SDF-1α-, and CXCR4-positive cells in group 2 (all p<0.04). Moreover, immunohistochemical staining showed notably higher vessel density but lower mean fibrosis area, number of CD40-positive cells and apoptotic nuclei in group 2 (all p<0.045). Mitochondrial protein expression of oxidative stress was lower, whereas cytochrome-C was higher in group 2 (all p<0.03). Furthermore, mRNA expressions of MMP-9, Bax and caspase-3 were lower, whereas Bcl-2, eNOS, VEGF and PGC-1α were higher in group 2 (all p<0.01). In conclusion, ECSW therapy effectively reversed ischemia-elicited LV dysfunction and remodeling through enhancing angiogenesis and attenuating inflammation and oxidative stress.