Prognostic factors for tracheostomy early decannulation in acquired brain injury patients.

After severe brain injuries, a tracheostomy tube is usually inserted for respiratory support. This study aimed to clarify the prognostic factors for tracheostomy early decannulation in patients with acquired brain injuries. We retrospectively reviewed the medical records of inpatients with acquired brain injuries who underwent successful tracheostomy decannulation between March 2021 and June 2022. Fifty-six patients were included; median age was 68 (59-72) years; 28 (50%) were men; 28 (50%) underwent tracheostomy due to stroke. The median time to decannulation was 47 days. The patients were divided into the early and the late decannulation groups based on the median time, and compared. In univariate analysis, the early decannulation group had a higher BMI, peak cough flow, and acquired brain injuries due to trauma, and a lower penetration-aspiration scale score, duration of antibiotic use, and duration of oxygen use. Multivariate Cox regression analysis revealed that a higher initial peak cough flow [hazard ratio (HR) 1.142; 95% confidence interval (CI) 0.912-0.954; P  < 0.001] and lower duration of oxygen use (HR 0.930; 95% CI 0.502-0.864; P  = 0.016) were independent factors for early tracheostomy decannulation, with each unit increase in peak cough flow corresponding to a 14.2% increase and each additional day of duration of oxygen use corresponding to a 7.0% decrease in the likelihood of early decannulation. In conclusion, key prognostic factors for early tracheostomy decannulation were identified as the initial cough strength and duration of oxygen use. These results could play important role in decannulation plans for patients with tracheostomy tube.

Serping1 associated with α-synuclein increase in colonic smooth muscles of MPTP-induced Parkinson's disease mice.

Patients with Parkinson's disease (PD) have gastrointestinal motility disorders, which are common non-motor symptoms. However, the reasons for these motility disorders remain unclear. Increased alpha-synuclein (α-syn) is considered an important factor in peristalsis dysfunction in colonic smooth muscles in patients with PD. In this study, the morphological changes and association between serping1 and α-syn were investigated in the colon of the 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-induced chronic PD model. Increased serping1 and α-syn were noted in the colon of the PD model, and decreased serping1 also induced a decrease in α-syn in C2C12 cells. Serping1 is a major regulator of physiological processes in the kallikrein-kinin system, controlling processes including inflammation and vasodilation. The kinin system also comprises bradykinin and bradykinin receptor 1. The factors related to the kallikrein-kinin system, bradykinin, and bradykinin receptor 1 were regulated by serping1 in C2C12 cells. The expression levels of bradykinin and bradykinin receptor 1, modulated by serping1 also increased in the colon of the PD model. These results suggest that the regulation of increased serping1 could alleviate Lewy-type α-synucleinopathy, a characteristic of PD. Furthermore, this study could have a positive effect on the early stages of PD progression because of the perception that α-syn in colonic tissues is present prior to the development of PD motor symptoms.

Association between Decreased SGK1 and Increased Intestinal α-Synuclein in an MPTP Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is a globally common progressive neurodegenerative disease resulting from the loss of dopaminergic neurons in the brain. Increased α-synuclein (α-syn) is associated with the degeneration of dopaminergic neurons and non-motor symptoms like gastrointestinal disorders. In this study, we investigated the association between serum/glucocorticoid-related kinase 1 (SGK1) and α-syn in the colon of a PD mouse model. SGK1 and α-syn expression patterns were opposite in the surrounding colon tissue, with decreased SGK1 expression and increased α-syn expression in the PD group. Immunofluorescence analyses revealed the colocation of SGK1 and α-syn; the PD group demonstrated weaker SGK1 expression and stronger α-syn expression than the control group. Immunoblotting analysis showed that Na+/K+ pump ATPase α1 expression levels were significantly increased in the PD group. In SW480 cells with SGK1 knockdown using SGK1 siRNA, decreasing SGK1 levels corresponded with significant increases in the expression levels of α-syn and ATPase α1. These results suggest that SGK1 significantly regulates Na+/K+ pump ATPase, influencing the relationship between electrolyte balance and fecal formation in the PD mouse model. Gastrointestinal disorders are some of the major prodromal symptoms of PD. Therefore, modulating SGK1 expression could be an important strategy for controlling PD.

Comparison of the efficacy of physical and chemical strategies for the inactivation of biofilm cells of foodborne pathogens.

Biofilm formation is a strategy in which microorganisms generate a matrix of extracellular polymeric substances to increase survival under harsh conditions. The efficacy of sanitization processes is lowered when biofilms form, in particular on industrial devices. While various traditional and emerging technologies have been explored for the eradication of biofilms, cell resistance under a range of environmental conditions renders evaluation of the efficacy of control challenging. This review aimed to: (1) classify biofilm control measures into chemical, physical, and combination methods, (2) discuss mechanisms underlying inactivation by each method, and (3) summarize the reduction of biofilm cells after each treatment. The review is expected to be useful for future experimental studies and help to guide the establishment of biofilm control strategies in the food industry.

Transcriptional control of hydrogen peroxide homeostasis regulates ground tissue patterning in the Arabidopsis root.

In multicellular organisms, including higher plants, asymmetric cell divisions (ACDs) play a crucial role in generating distinct cell types. The Arabidopsis root ground tissue initially has two layers: endodermis (inside) and cortex (outside). In the mature root, the endodermis undergoes additional ACDs to produce the endodermis itself and the middle cortex (MC), located between the endodermis and the pre-existing cortex. In the Arabidopsis root, gibberellic acid (GA) deficiency and hydrogen peroxide (H2O2) precociously induced more frequent ACDs in the endodermis for MC formation. Thus, these findings suggest that GA and H2O2 play roles in regulating the timing and extent of MC formation. However, details of the molecular interaction between GA signaling and H2O2 homeostasis remain elusive. In this study, we identified the PEROXIDASE 34 (PRX34) gene, which encodes a class III peroxidase, as a molecular link to elucidate the interconnected regulatory network involved in H2O2- and GA-mediated MC formation. Under normal conditions, prx34 showed a reduced frequency of MC formation, whereas the occurrence of MC in prx34 was restored to nearly WT levels in the presence of H2O2. Our results suggest that PRX34 plays a role in H2O2-mediated MC production. Furthermore, we provide evidence that SCARECROW-LIKE 3 (SCL3) regulates H2O2 homeostasis by controlling transcription of PRX34 during root ground tissue maturation. Taken together, our findings provide new insights into how H2O2 homeostasis is achieved by SCL3 to ensure correct radial tissue patterning in the Arabidopsis root.

Effect of high hydrostatic pressure treatment on the inactivation and sublethal injury of foodborne pathogens and quality of apple puree at different pH.

The objectives of this study were to evaluate the survival of high hydrostatic pressure (HHP)-treated Salmonella Typhimurium, Escherichia coli O157:H7, and Listeria monocytogenes in apple puree, as well as to determine the levels of HHP-induced cell injury according to the pressure level, holding time, and pH of apple puree. Apple puree was inoculated with three foodborne pathogens and treated at pressures of 300-600 MPa for up to 7 min at 22 °C using HHP equipment. Increasing the pressure level and lowering the pH of apple puree led to larger microbial reductions, and E. coli O157:H7 showed higher resistance compared to S. Typhimurium and L. monocytogenes. Besides, approximately 5-log injured cells of E. coli O157:H7 were induced in apple puree at pH 3.5 and 3.8. HHP treatment at 500 MPa for 2 min effectively achieved complete inactivation of the three pathogens in apple puree at pH 3.5. For apple puree at pH 3.8, more than 2 min treatment of HHP at 600 MPa is seemingly needed to achieve complete inactivation of the three pathogens. Transmission electron microscopy analysis was conducted to identify ultrastructural changes in the injured or dead cells after HHP treatment. Plasmolysis and uneven cavities in the cytoplasm were observed in injured cells, and additional deformations, such as distorted and rough cell envelopes, and cell disruption occurred in dead cells. No changes in solid soluble content (SSC) and color of apple puree were observed after HHP treatment, and no differences were detected between control and HHP-treated samples during 10 d of storage at 5 °C. The results of this study could be useful in determining the acidity of apple purees or the treatment time at specific acidity levels when applying the HHP processing.

Inactivation of Foodborne Pathogen Biofilm Cells Using a Combination Treatment with Gaseous Chlorine Dioxide and Aerosolized Sanitizers.

A biofilm is a three-dimensional microbial community, which is difficult to completely control with a typical sanitizer owing to its complex structure. The aim of this study was to establish a system for the combined treatment of biofilms with 10 ppmv gaseous chlorine dioxide (ClO2) and antimicrobial agents (2% citric acid, 2% hydrogen peroxide [H2O2], and 100 ppm peracetic acid [PAA]), and to investigate the synergistic microbicidal efficacy of the combination treatments to inactivate Listeria monocytogenes, Salmonella Typhimurium, and Escherichia coli O157:H7 in biofilms. The antimicrobial agents were aerosolized using a humidifier on top of a chamber to achieve a relative humidity of 90% (within a range of ±2%). While biofilm treatment with the aerosolized antimicrobial agents for 20 min inactivated approximately 1 log CFU/cm2 (0.72-1.26 log CFU/cm2) of the pathogens and the gaseous ClO2 gas treatment for 20 min inactivated <3 log CFU/cm2 (2.19-2.77 log CFU/cm2), combination treatment with citric acid, H2O2, and PAA for 20 min achieved microbial reductions of 2.71-3.79, 4.56-5.12, and 4.45-4.67 log CFU/cm2, respectively. Our study demonstrates that foodborne pathogens in biofilms can be inactivated by combining gaseous ClO2 treatment with aerosolized antimicrobial agents. The results of this study provide baseline data for the food industry to help control foodborne pathogens in biofilms on inaccessible surfaces.

Inactivation of Bacillus cereus endospores on black pepper by pulsed superheated steam system.

In this study, a superheated steam (SHS) system was constructed to inactivate Bacillus cereus endospores on the surface of black pepper, and continuous and pulsed treatment was applied to compare sporicidal effects. Additionally, inactivation mechanisms were analyzed to investigate the differences between pulsed and continuous SHS treatments. SHS at 250 °C and 300 °C for 1 min achieved more than a 3 log reduction, whereas SHS at 200 °C for 1 min achieved less than 2 log reduction in the number of endospores. In addition, higher microbicidal effects were confirmed with pulsed SHS treatment with a shorter duty ratio. To elucidate the inactivation mechanisms, inner membrane damage (dipicolinic acid release), intracellular enzyme activities, and DNA integrity were measured after 300 °C SHS pulsed or continuous treatments. After pulsed SHS treatment for up to 20 s, intracellular enzymes were inactivated more rapidly than after continuous treatment, and more DPA was released after 40 s of treatment, indicating that enzyme inactivation occurred prior to inner membrane damage, and pulsed treatment accelerated this mode of action. DNA integrity was significantly lower after 60 s of pulsed or continuous treatment; however, there was no difference in between pulsed and continuous treatments. Our results provide fundamental insights for the sterilization of black pepper by SHS treatment in food industries.

Quercetin mediated antimicrobial photodynamic treatment using blue light on Escherichia coli O157:H7 and Listeria monocytogenes.

Interest in using an antimicrobial photodynamic treatment (aPDT) for the microbial decontamination of food has been growing. In this study, quercetin, a substance found ubiquitously in plants, was used as a novel exogenous photosensitizer with 405 nm blue light (BL) for the aPDT on foodborne pathogens, and the inactivation mechanism was elucidated. The inactivation of Escherichia coli O157:H7 and Listeria monocytogenes in PBS solution by the quercetin and BL combination treatment reached a log reduction of 6.2 and more than 7.55 at 80 J/cm2 (68 min 21 s), respectively. When EDTA was added to investigate the reason for different resistance between two bacteria, the effect of aPDT was enhanced against E. coli O157:H7 but not L. monocytogenes. This result indicated that the lipopolysaccharide of Gram-negative bacteria operated as a protective barrier. It was experimentally demonstrated that quercetin generated the superoxide anion and hydrogen peroxide as the reactive oxygen species that oxidize and inactivate cell components. The damage to the bacterial cell membrane by aPDT was evaluated by propidium iodide, where the membrane integrity significantly (P < 0.05) decreased from 40 J/cm2 compared to control. In addition, DNA integrity of bacteria was significantly (P < 0.05) more decreased after aPDT than BL treatment. The inactivation results could be applied in liquid food industries for decontamination of foodborne pathogens, and the mechanisms data was potentially utilized for further studies about aPDT using quercetin.

Ran-GTP/-GDP-dependent nuclear accumulation of NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 and TGACG-BINDING FACTOR2 controls salicylic acid-induced leaf senescence.

Leaf senescence is the final stage of leaf development and can be triggered by various external factors, such as hormones and light deprivation. In this study, we demonstrate that the overexpression of the GTP-bound form of Arabidopsis (Arabidopsis thaliana) Ran1 (a Ras-related nuclear small G-protein, AtRan1) efficiently promotes age-dependent and dark-triggered leaf senescence, while Ran-GDP has the opposite effect. Transcriptome analysis comparing AtRan1-GDP- and AtRan1-GTP-overexpressing transgenic plants (Ran1T27Nox and Ran1G22Vox, respectively) revealed that differentially expressed genes (DEGs) related to the senescence-promoting hormones salicylic acid (SA), jasmonic acid, abscisic acid, and ethylene (ET) were significantly upregulated in dark-triggered senescing leaves of Ran1G22Vox, indicating that these hormones are actively involved in Ran-GTP/-GDP-dependent, dark-triggered leaf senescence. Bioinformatic analysis of the promoter regions of DEGs identified diverse consensus motifs, including the bZIP motif, a common binding site for TGACG-BINDING FACTOR (TGA) transcription factors. Interestingly, TGA2 and its interactor, NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 (NPR1), which are two positive transcriptional regulators of SA signaling, differed in their extent of accumulation in the nucleus versus cytoplasm of Ran1T27Nox and Ran1G22Vox plants. Moreover, SA-induced, Ran-GTP-/-GDP-dependent functions of NPR1 included genome-wide global transcriptional reprogramming of genes involved in cell death, aging, and chloroplast organization. Furthermore, the expression of AtRan1-GTP in SA signaling-defective npr1 and SA biosynthesis-deficient SA-induction deficient2 genetic backgrounds abolished the effects of AtRan1-GTP, thus retarding age-promoted leaf senescence. However, ET-induced leaf senescence was not mediated by Ran machinery-dependent nuclear shuttling of ETHYLENE-INSENSITIVE3 and ETHYLENE-INSENSITIVE3-LIKE1 proteins. We conclude that Ran-GTP/-GDP-dependent nuclear accumulation of NPR1 and TGA2 represents another regulatory node for SA-induced leaf senescence.

ATBS1-INTERACTING FACTOR 2 Negatively Modulates Pollen Production and Seed Formation in Arabidopsis.

ATBS1-INTERACTING FACTOR 2 (AIF2) is a non-DNA-binding basic-helix-loop-helix (bHLH) transcription factor. Here, we demonstrate that AIF2 negatively modulates brassinosteroid (BR)-induced, BRASSINAZOLE RESISTANT 1 (BZR1)-mediated pollen and seed formation. AIF2-overexpressing Arabidopsis plants (AIF2ox) showed defective pollen grains and seed production while two AIF2 knockout mutants, aif2-1 and aif2-1/aif4-1, displayed opposite phenotypes. Genes encoding BZR1-regulated positive factors of seed size determination (SHB1, IKU1, MINI3) were suppressed in AIF2ox and genes for negative factors (AP2 and ARF2) were enhanced. Surprisingly, BZR1-regulated pollen genes such as SPL, MS1, and TDF1 were aberrantly up-regulated in AIF2ox plants. This stage-independent abnormal expression may lead to a retarded and defective progression of microsporogenesis, producing abnormal tetrad microspores and pollen grains with less-effective pollen tube germination. Auxin plays important roles in proper development of flower and seeds: genes for auxin biosynthesis such as TCPs and YUCCAs as well as for positive auxin signalling such as ARFs were suppressed in AIF2ox flowers. Moreover, lipid biosynthesis- and sucrose transport-related genes were repressed, resulting in impaired starch accumulation. Contrarily, sucrose and BR repressed ectopic accumulation of AIF2, thereby increasing silique length and the number of seeds. Taken together, we propose that AIF2 is negatively involved in pollen development and seed formation, and that sucrose- and BR-induced repression of AIF2 positively promotes pollen production and seed formation in Arabidopsis.

Thermal and non-thermal treatment effects on Staphylococcus aureus biofilms formed at different temperatures and maturation periods.

The objective of this study was to investigate the effect of temperature and maturation period on the resistance of Staphylococcus aureus biofilms to thermal and non-thermal treatments. First, biofilm development was compared at three different temperatures (15, 25, and 37°C) for 5 days. The cell population at 15 and 25°C remained relatively consistent approximately at 6.3 log CFU/cm2, whereas 37°C resulted in the highest cell population on day 1 (7.6 log CFU/cm2) followed by a continual decline. Then, biofilm resistance to steam and sodium hypochlorite (NaOCl) treatments was evaluated. Obtained results highlighted that biofilms had different resistance to both treatments depending on development conditions. Specifically, steam treatment of 10 s eliminated 4.1 log CFU/cm2 of the biofilm formed at 25°C for 5 days. The same treatment inactivated over 5 log population of biofilms developed in other temperature and maturation period conditions. Treatment with NaOCl reduced approximately 1 log CFU/cm2 of biofilm cells developed at 25°C for 5 days. However, inactivation was found to be over 2 log CFU/cm2 under other development conditions. An extracellular polymeric substances (EPS) quantification using 96-well plates and stainless steel coupons was conducted. In the 96-well plate experiment, it was found that the highest amount of polysaccharide was secreted at 25°C (p < 0.05), while total biomass and protein contents were greatest at 37°C (p < 0.05). No significant difference in EPS content was observed for stainless steel, but the results displayed a similar trend to the 96-well plate. In particular, biofilms developed at 25°C tended to secret the highest amount of polysaccharide, which aligned with the current literature. This finding indicated that polysaccharide was the main contribution to the enhanced resistance of S. aureus biofilms. Overall, it was shown that biofilms formed at 25°C for 5 days exhibited the greatest resistance to thermal and nonthermal treatments due to the elevated exopolysaccharide secretion. This study demonstrates that temperature and maturation period significantly affect the resistance of S. aureus biofilms to thermal and non-thermal treatments.

Evaluation and live monitoring of pH-responsive HSA-ZnO nanoparticles using a lung-on-a-chip model.

One of the key problems that have hindered the development and approval of anticancer nanoparticle drug delivery systems is the limited predictability of 2D cell culture and animal models. Here, we describe a biomimetic alveolus-epithelium-on-a-chip (AEOC) model with in-built sensors for monitoring and evaluating pH-responsive zinc oxide quantum dots (QDs)-loaded human serum albumin nanoparticles. This AEOC model closely represents the cancerous alveolus epithelium, which comprises lung cancer cells, as well as stromal cells, such as fibroblasts along with extracellular matrix (ECM) in the form of collagen. ZnO QDs were encapsulated in the HSA nanoparticles with a diameter of 60 nm. The physicochemical properties, quantum dots release, in vitro cytotoxicity, and cellular uptake of HSA-ZnO were evaluated. HSA-ZnO showed higher ZnO loading and encapsulation efficacy. TEER and pH sensors were used to monitor the cells over three days, and real-time data with and without nanoparticle treatment were obtained. Cell viability after treatment with 10 and 50 µg/mL of HSA-ZnO nanoparticles and confocal imaging data confirmed the significant internalization of the nanoparticles under co-culture cellular conditions in the AEOC model. Our designed organ-on-a-chip model has potentially expanded the capabilities of cell culture in biomimetic conditions, and therefore, can provide a low-cost alternative to expensive and tedious animal models for the evaluation of nanomedicines.

ATBS1-INTERACTING FACTOR 2 negatively regulates dark- and brassinosteroid-induced leaf senescence through interactions with INDUCER OF CBF EXPRESSION 1.

ATBS1-INTERACTING FACTOR 2 (AIF2) is a non-DNA-binding basic helix-loop-helix (bHLH) transcription factor. We demonstrated that AIF2 retards dark-triggered and brassinosteroid (BR)-induced leaf senescence in Arabidopsis thaliana. Dark-triggered BR synthesis and the subsequent activation of BRASSINAZOLE RESISTANT 1 (BZR1), a BR signaling positive regulator, result in BZR1 binding to the AIF2 promoter in a dark-dependent manner, reducing AIF2 transcript levels and accelerating senescence. BR-induced down-regulation of AIF2 protein stability partly contributes to the progression of dark-induced leaf senescence. Furthermore, AIF2 interacts with INDUCER OF CBF EXPRESSION 1 (ICE1) via their C-termini. Formation of the AIF2-ICE1 complex and subsequent up-regulation of C-REPEAT BINDING FACTORs (CBFs) negatively regulates dark-triggered, BR-induced leaf senescence. This involves antagonistic down-regulation of PHYTOCHROME INTERACTING FACTOR 4 (PIF4), modulated through AIF2-dependent inhibition of ICE1's binding to the promoter. PIF4-dependent activities respond to dark-induced early senescence and may promote BR synthesis and BZR1 activation to suppress AIF2 and accelerate dark-induced senescence. Taken together, these findings suggest a coordination of AIF2 and ICE1 functions in maintaining stay-green traits.

Inactivation of Bacillus cereus Spores on Stainless Steel by Combined Superheated Steam and UV-C Irradiation Treatment.

Bacillus cereus spore contamination on food contact surfaces is of great concern in the food industry. Thus, in the present study, superheated steam (SHS) was used alone or combined with UV-C irradiation for inactivation of B. cereus spores inoculated on stainless steel coupons. Temperatures higher than 250°C were needed to effectively inactivate B. cereus spores by SHS treatment alone, while a synergistic bactericidal effect resulted from the sequential treatment of SHS before or after UV-C irradiation. The increased dipicolinic acid ratio obtained by the combined treatment had a significant role in the synergistic bactericidal effect. Therefore, the combined treatment of SHS and UV-C could be used effectively to inactivate B. cereus on stainless steel. It is recommended to use hurdle technology with reduced energy consumption to ensure microbiological safety on food contact surfaces.

Inactivation of Staphylococcus aureus Biofilms on Food Contact Surfaces by Superheated Steam Treatment.

The objective of this study was to compare the inactivation efficacy of saturated steam (SS) and superheated steam (SHS) on Staphylococcus aureus biofilms on food contact surfaces, including type 304 stainless steel coupons with No. 4 finish (STS No. 4), type 304 stainless steel coupons with 2B finish (STS 2B), high-density polyethylene (HDPE), and polypropylene (PP). In addition, the effects of the surface characteristics on the inactivation efficacy were evaluated. Biofilms were formed on each food contact coupon surface using a three-strain cocktail of S. aureus. Five-day-old biofilms on STS No. 4, STS 2B, HDPE, and PP coupons were treated with SS at 100°C and SHS at 125 and 150°C for 2, 4, 7, 10, 15, and 20 s. Among all coupon types, SHS was more effective than SS in inactivating the S. aureus biofilms. S. aureus biofilms on steel coupons were more susceptible to most SS and SHS treatments than the biofilms on plastic coupons. S. aureus biofilms on HDPE and PP coupons were reduced by 4.00 and 5.22 log CFU per coupon, respectively, after SS treatment (100°C) for 20 s. SS treatment for 20 s reduced the amount of S. aureus biofilm on STS No. 4 and STS 2B coupons to below the detection limit. With SHS treatment (150°C), S. aureus biofilms on HDPE and PP needed 15 s to be inactivated to below the detection limit, while steel coupons only needed 10 s. The results of this study suggest that SHS treatment has potential as a biofilm control intervention for the food industry.

Small-molecule drug screening identifies drug Ro 31-8220 that reduces toxic phosphorylated tau in Drosophila melanogaster.

The intraneuronal aggregates of hyperphosphorylated and misfolded tau (neurofibrillary tangles, NFTs) cause a stereotypical spatiotemporal Alzheimer's disease (AD) progression that correlates with the severity of the associated cognitive decline. Kinase activity contributes to the balance between neuron survival and cell death. Hyperactivation of kinases including the conventional protein kinase C (PKC) is a defective molecular event accompanying associative memory loss, tau phosphorylation, and progression of AD or related neurodegenerative diseases. Here, we investigated the ability of small therapeutic compounds (a custom library) to improve tau-induced rough-eye phenotype in a Drosophila melanogaster model of frontotemporal dementia. We also assessed the tau phosphorylation in vivo and selected hit compounds. Among the potential hits, we investigated Ro 31-8220, described earlier as a potent PKCα inhibitor. Ro 31-8220 robustly improved the rough-eye phenotype, reduced phosphorylated tau species in vitro and in vivo, reversed tau-induced memory impairment, and improved the fly motor functions. In a human neuroblastoma cell line, Ro 31-8220 reduced the PKC activity and the tau phosphorylation pattern, but we also have to acknowledge the compound's wide range of biological activity. Nevertheless, Ro 31-8220 is a novel therapeutic mitigator of tau-induced neurotoxocity.

Predicting risk of type 2 diabetes mellitus in Korean adults aged 40-69 by integrating clinical and genetic factors.

AIMS: The purpose of our investigation was to identify the genetic and clinical risk factors of type 2 diabetes mellitus (T2DM) and to predict the incidence of T2DM in Korean adults aged 40-69 at follow-up intervals of 5, 7, and 10years. METHODS: Korean Genome and Epidemiology Study (KoGES) cohort data (n=10,030) were used to develop T2DM prediction models. Both clinical-only and integrated (clinical factors+genetic factors) models were derived using the Cox proportional hazards model. Internal validation was performed to evaluate the prediction capabilities of the clinical and integrated models. RESULTS: The clinical model included 10 selected clinical risk factors. The selected SNPs for the integrated model were rs9311835 in PTPRG, rs10975266 in RIC1, rs11057302 in TMED2, rs17154562 in ADAM12, and rs8038172 in CGNL1. For the clinical model, validated c-indices with time points of 5, 7, and 10 years were 0.744, 0.732, and 0.732, respectively. Slightly higher validated c-indices were observed for the integrated model at 0.747, 0.736, and 0.738, respectively. The p-values of the survival net reclassification improvement (NRI) for the SNP point-based score were statistically significant. CONCLUSIONS: Clinical and integrated models can be effectively used to predict the incidence of T2DM in Koreans.

Association between hepatic steatosis and the development of hepatocellular carcinoma in patients with chronic hepatitis B.

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is becoming a worldwide epidemic, and is frequently found in patients with chronic hepatitis B (CHB). We investigated the impact of histologically proven hepatic steatosis on the risk for hepatocellular carcinoma (HCC) in CHB patients without excessive alcohol intake. METHODS: Consecutive CHB patients who underwent liver biopsy from January 2007 to December 2015 were included. The association between hepatic steatosis (≥ 5%) and subsequent HCC risk was analyzed. Inverse probability weighting (IPW) using the propensity score was applied to adjust for differences in patient characteristics, including metabolic factors. RESULTS: Fatty liver was histologically proven in 70 patients (21.8%) among a total of 321 patients. During the median (interquartile range) follow-up of 5.3 (2.9-8.3) years, 17 of 321 patients (5.3%) developed HCC: 8 of 70 patients (11.4%) with fatty liver and 9 of 251 patients (3.6%) without fatty liver. The five-year cumulative incidences of HCC among patients without and with fatty liver were 1.9% and 8.2%, respectively (P=0.004). Coexisting fatty liver was associated with a higher risk for HCC (adjusted hazards ratio [HR], 3.005; 95% confidence interval [CI], 1.122-8.051; P=0.03). After balancing with IPW, HCC incidences were not significantly different between the groups (P=0.19), and the association between fatty liver and HCC was not significant (adjusted HR, 1.709; 95% CI, 0.404-7.228; P=0.47). CONCLUSION: Superimposed NAFLD was associated with a higher HCC risk in CHB patients. However, the association between steatosis per se and HCC risk was not evident after adjustment for metabolic factors.