ATBS1-INTERACTING FACTOR 2 Positively Regulates Freezing Tolerance via INDUCER OF CBF EXPRESSION 1/C-REPEAT BINDING FACTOR-Induced Cold Acclimation Pathway.

The INDUCER OF CBF EXPRESSION 1/C-REPEAT BINDING FACTOR (ICE1/CBF) pathway plays a crucial role in plant responses to cold stress, impacting growth and development. Here, we demonstrated that ATBS1-INTERACTING FACTOR 2 (AIF2), a non-DNA-binding basic helix-loop-helix transcription factor, positively regulates freezing tolerance through the ICE1/CBF-induced cold tolerance pathway in Arabidopsis. Cold stress transcriptionally upregulated AIF2 expression and induced AIF2 phosphorylation, thereby stabilizing the AIF2 protein during early stages of cold acclimation. The AIF2 loss-of-function mutant, aif2-1, exhibited heightened sensitivity to freezing before and after cold acclimation. In contrast, ectopic expression of AIF2, but not the C-terminal-deleted AIF2 variant, restored freezing tolerance. AIF2 enhanced ICE1 stability during cold acclimation and promoted the transcriptional expression of CBFs and downstream cold-responsive genes, ultimately enhancing plant tolerance to freezing stress. MITOGEN-ACTIVATED PROTEIN KINASES 3 and 6 (MPK3/6), known negative regulators of freezing tolerance, interacted with and phosphorylated AIF2, subjecting it to protein degradation. Furthermore, transient co-expression of MPK3/6 with AIF2 and ICE1 downregulated AIF2/ICE1-induced transactivation of CBF2 expression. AIF2 interacted preferentially with BIN2 and MPK3/6 during the early and later stages of cold acclimation, respectively, thereby differentially regulating AIF2 activity in a cold acclimation time-dependent manner. Moreover, AIF2 acted additively in a gain-of-function mutant of BRASSINAZOLE-RESISTANT 1 (BZR1; bzr1-1D) and a triple knockout mutant of BRASSINOSTEROID-INSENSITIVE 2 (BIN2) and its homologs (bin2bil1bil2) to induce CBFs-mediated freezing tolerance. This suggests that cold-induced AIF2 coordinates freezing tolerance along with BZR1 and BIN2, key positive and negative components, respectively, of brassinosteroid signaling pathways.

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.

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.

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.

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.

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.

Brassinosteroid-Induced Transcriptional Repression and Dephosphorylation-Dependent Protein Degradation Negatively Regulate BIN2-Interacting AIF2 (a BR Signaling-Negative Regulator) bHLH Transcription Factor.

Brassinosteroids (BRs) are plant polyhydroxy-steroids that play important roles in plant growth and development via extensive signal integration through direct interactions between regulatory components of different signaling pathways. Recent studies have shown that diverse helix-loop-helix/basic helix-loop-helix (HLH/bHLH) family proteins are actively involved in control of BR signaling pathways and interact with other signaling pathways. In this study, we show that ATBS1-INTERACTING FACTOR 2 (AIF2), a nuclear-localized atypical bHLH transcription factor, specifically interacts with BRASSINOSTEROID-INSENSITIVE 2 (BIN2) among other BR signaling molecules. Overexpression of AIF2 down-regulated transcript expression of growth-promoting genes, thus resulting in retardation of growth. AIF2 renders plants hyposensitive to BR-induced root growth inhibition, but shows little effects on BR-promoted hypocotyl elongation. Notably, AIF2 was dephosphorylated by BR, and the dephosphorylated AIF2 was subject to proteasome-mediated degradation. AIF2 degradation was greatly induced by BR and ABA, but relatively slightly by other hormones such as auxin, gibberellin, cytokinin and ethylene. Moreover, AIF2 transcription was significantly suppressed by a BRI1/BZR1-mediated BR signaling pathway through a direct binding of BRASSINAZOLE RESISTANT 1 (BZR1) to the BR response element (BRRE) region of the AIF2 promoter. In conclusion, our study suggests that BIN2-driven AIF2 phosphorylation could augment the BIN2/AIF2-mediated negative circuit of BR signaling pathways, and the BR-induced transcriptional repression and protein degradation negatively regulate AIF2 transcription factor, reinforcing the BZR1/BES1-mediated positive BR signaling pathway.

Aberrant expression of plasma microRNA-33a in an atherosclerosis-risk group.

In order to investigate whether plasma microRNA-33a (miR-33a) can be a biomarker for the early detection of atherosclerosis and to reexamine the assumption that miR-33a represses the expression of ABCA1, we compared the expression levels of miR-33a and ATP-binding cassette A1 (ABCA1) using human plasma and supernatants of macrophage cultured media. We first separated ample number of plasma samples from left-over whole blood samples based on the criteria for normal or dyslipidemia, and stored them at -20 °C until use. Then we selected 18 plasma samples for each normal, athero-risk and treated group using a metabolic disease cohort in which candidate subjects have participated. For classifying into three groups, we primarily relied on the records of physicians' comments, prescriptions, treatment history, lipid profiles and test results from medical equipment aimed at the diagnosis for atherosclerosis or cardiovascular disease. After collecting the final 54 plasma samples, we analyzed and compared the expression levels of miR-33a and ABCA1 at the plasma levels. In the comparison of plasma levels of the three groups, the miR-33a expression level of athero-risk group was 5.01-fold higher than that of normal group. Meanwhile, in the culture of foam cells transfected with anti-miR-33a oligonucleotides, the miR-33a level significantly decreased, while ABCA1 level significantly increased. The results suggest that enhanced expression of miR-33a might induce cholesterol accumulation and aggravate inflammation in vessel walls by suppressing the expression of ABCA1 in macrophages. Thus, plasma miR-33a can be considered as a candidate biomarker of atherosclerosis.

Intralipid Restoration of Myocardial Contractions Following Bupivacaine-Induced Asystole: Concentration- and Time-Dependence In Vitro.

BACKGROUND: The concentration- and time-response relationships of lipid emulsion (LE; Intralipid) on the recovery of myocardial contractility following bupivacaine (BPV)-induced asystole are poorly defined. METHODS: After achieving asystole by 500-µM BPV, varied concentrations of LE were applied to determine the recovery of stimulated contractile responses and contractions in the cardiac tissues of guinea pigs at a 1.2-Hz stimulation rate. These experiments were performed with LE in either a recirculating (2%-16%) or washout (nonrecirculating) condition (0.05%-12%) for 60 minutes. The effect of LE itself (0.05%-12%) was examined. Oxfenicine was used to evaluate the metabolic action of LE to reverse asystole. BPV concentrations in solution and myocardial tissues were measured. RESULTS: In the recirculation condition, partial recovery of contractile forces was observed for 60 minutes at 4%, 8%, and 12% LE. A contracture followed after exposure to 16% LE in some asystolic muscles. In the washout experiments, following asystole, LE (0.05%-12%) had no effect on the recovery time of the first and regular contractile responses. LE (0.1%-8%) restored contractility to baseline levels after 45 minutes; partial recovery was shown with lower (0.05%) and higher (12%) concentrations. Oxfenicine did not alter the recovery of contractile forces. Contractile depression was observed with 12% LE alone. Concentration-related reduction of tissue BPV concentration by LE was observed in both circulating conditions. CONCLUSIONS: LE induced time- and concentration-dependent recovery of stimulated myocardial contractions from BPV-induced asystole. The lipid uptake effect, along with other undefined mechanisms of LE, seems to contribute to the recovery of contractile function; however, the LE effect on myocardial metabolism is less likely involved at this concentration (500 µM) of BPV.

Fluoroscopic-guided stent placement in failed tentative endoscopic approaches to malignant gastroduodenal obstructions.

Background Fluoroscopic or endoscopic placement of metallic stents is used as a safe, non-surgical, palliative treatment option for malignant gastroduodenal obstructions. However, endoscopic stent placement is not always feasible, due to the tight or tortuous stricture of the obstructed area and insufficient visualization of the stomach due to remnant food material. Purpose To assess the technical feasibility and clinical outcomes of fluoroscopic-guided stent placement in malignant gastroduodenal obstructions following the technical failure of endoscopic stent placement. Material and Methods In all, 19 patients (14 men, 5 women; age range, 36-85 years) were referred due to technical failures of tentative endoscopic stent placement. Indications were failure to pass the guide wire through the obstruction (n = 13), failure to reach the stricture lesion due to short endoscope (n = 5), and acute angulation of the stricture lesion (n = 1). Data were retrospectively collected regarding the technical and clinical success of the fluoroscopy, the dysphagia score before and after stent placement, and major complications and their management. Results Fluoroscopic stent placement was technically successful in 15/19 patients (79%). Failures were due to complete obstruction (n = 3) and acute angulation of the stricture lesion (n = 1). Clinical success was achieved in all 15 patients with successful stent placement. The dysphagia score significantly improved after stent placement ( P < 0.001). Complications occurred in 4/15 patients (27%), including tumor overgrowth (n = 2), stent collapse (n = 1), and jaundice (n = 1). Conclusion Fluoroscopic stent placement in malignant gastroduodenal obstructions following a technical failure of endoscopic stent placement is technically feasible and has an acceptable clinical outcome.

Genetic polymorphisms to predict gains in maximal O2 uptake and knee peak torque after a high intensity training program in humans.

PURPOSE: The study aimed to identify single nucleotide polymorphisms (SNPs) that significantly influenced the level of improvement of two kinds of training responses, including maximal O2 uptake (V'O2max) and knee peak torque of healthy adults participating in the high intensity training (HIT) program. The study also aimed to use these SNPs to develop prediction models for individual training responses. METHODS: 79 Healthy volunteers participated in the HIT program. A genome-wide association study, based on 2,391,739 SNPs, was performed to identify SNPs that were significantly associated with gains in V'O2max and knee peak torque, following 9 weeks of the HIT program. To predict two training responses, two independent SNPs sets were determined using linear regression and iterative binary logistic regression analysis. False discovery rate analysis and permutation tests were performed to avoid false-positive findings. RESULTS: To predict gains in V'O2max, 7 SNPs were identified. These SNPs accounted for 26.0 % of the variance in the increment of V'O2max, and discriminated the subjects into three subgroups, non-responders, medium responders, and high responders, with prediction accuracy of 86.1 %. For the knee peak torque, 6 SNPs were identified, and accounted for 27.5 % of the variance in the increment of knee peak torque. The prediction accuracy discriminating the subjects into the three subgroups was estimated as 77.2 %. CONCLUSIONS: Novel SNPs found in this study could explain, and predict inter-individual variability in gains of V'O2max, and knee peak torque. Furthermore, with these genetic markers, a methodology suggested in this study provides a sound approach for the personalized training program.

Brassinazole resistant 1 (BZR1)-dependent brassinosteroid signalling pathway leads to ectopic activation of quiescent cell division and suppresses columella stem cell differentiation.

Previous publications have shown that BRI1 EMS suppressor 1 (BES1), a positive regulator of the brassinosteroid (BR) signalling pathway, enhances cell divisions in the quiescent centre (QC) and stimulates columella stem cell differentiation. Here, it is demonstrated that BZR1, a BES1 homologue, also promotes cell divisions in the QC, but it suppresses columella stem cell differentiation, opposite to the action of BES1. In addition, BR and its BZR1-mediated signalling pathway are shown to alter the expression/subcellular distribution of pin-formed (PINs), which may result in changes in auxin movement. BR promotes intense nuclear accumulation of BZR1 in the root tip area, and the binding of BZR1 to the promoters of several root development-regulating genes, modulating their expression in the root stem cell niche area. These BZR1-mediated signalling cascades may account for both the ectopic activation of QC cell divisions as well as the suppression of the columella stem cell differentiation. They could also inhibit auxin-dependent distal stem cell differentiation by antagonizing the auxin/WOX5-dependent pathway. In conclusion, BZR1-/BES1-mediated BR signalling pathways show differential effects on the maintenance of root apical meristem activities: they stimulate ectopic QC division while they show opposite effects on the differentiation of distal columella stem cells in a BR concentration- and BZR1-/BES1-dependent manner.

Migration of retrievable expandable metallic stents inserted for malignant esophageal strictures: incidence, management, and prognostic factors in 332 patients.

OBJECTIVE: The purpose of this study was to evaluate the incidence, prognostic factors, and secondary management of stent migration in patients with malignant esophageal strictures. MATERIALS AND METHODS: A retrospective study was performed in a single tertiary referral university hospital to identify the incidence, management, and prognostic factors for stent migration in 332 consecutive patients with placement of a retrievable expandable metallic stent. Stent migration was classified into four patterns as locations of a migrated stent: pattern I, partially migrated in the proximal direction; pattern II, partially migrated in the distal direction; pattern III, completely migrated into the stomach; and pattern IV, completely migrated into the bowel. RESULTS: Stent migration occurred in 42 (12.6%) of 332 patients. Migration was partial (n = 21) or complete (n = 21), and nine (21%), 12 (29%), 11 (26%), and 10 (24%) patients had patterns I, II, III, and IV, respectively. Multivariate analysis identified the following prognostic factors: esophagogastric junction strictures caused by cancer of the gastric cardia (odds ratio 1.330; p = 0.004), patients who underwent anticancer treatment after stent placement (17.514; p < 0.001), and patients with a longer survival time (1.994; p < 0.001). Secondary management was needed for 33 of 42 patients. The strictures in the remaining nine patients improved throughout follow-up. CONCLUSION: Stent migration occurs most commonly in patients with cancer of the gastric cardia, patients with longer survival time, and those who underwent anticancer treatment after stent placement. Stent migration is successfully managed by further intervention. Accurate knowledge of the pattern of stent migration is important for successful management.

Full-thickness esophageal perforation after fluoroscopic balloon dilation: incidence and management in 820 adult patients.

OBJECTIVE: The purpose of this study is to investigate the incidence, management, and outcomes of esophageal perforation after fluoroscopic balloon dilation in 820 adult patients with esophageal diseases. MATERIALS AND METHODS: Between December 1990 and April 2014, a total of 820 adult patients (age range, 21-93 years) underwent 1869 fluoroscopic balloon dilation sessions (mean, 2.3 sessions/patient; range, 1-29 sessions/patient) for esophageal diseases. We retrospectively reviewed the prospectively collected medical records and images of these patients and collected the data of patients who developed esophageal perforations after fluoroscopic balloon dilation. RESULTS: During this period, 12 patients (six men and six women; mean age, 51 years; age range, 28-69 years) developed perforations. The perforation rate was 1.5% per patient and 0.6% per dilation. Among the first eight patients, four who were treated with surgery had perforations 2 cm or larger, and the other four who underwent fasting, parenteral alimentation, and treatment with antibiotics had perforations smaller than 2 cm. The last four patients underwent stent placement immediately after the diagnosis, regardless of the perforation's size. The median hospital stay was 11.5 days. CONCLUSION: Fluoroscopic balloon dilation of esophageal diseases is a safe procedure with a low perforation rate. A perforation size greater than 2 cm is considered large and requires aggressive treatment. Although the number of patients with esophageal perforation we treated is relatively small and further clinical trials are needed, temporary stent placement seems to be an initial choice in the management of esophageal perforations after fluoroscopic balloon dilation.

Preliminary Results of Percutaneous Radiologic Gastrostomy in a Pediatric Population: A Modified Chiba-Needle Puncture Technique With Single Gastropexy.

OBJECTIVE: The purpose of this study was to evaluate the technical feasibility, safety, and clinical effectiveness of percutaneous radiologic gastrostomy using a modified Chiba-needle puncture technique with single gastropexy in pediatric patients. MATERIALS AND METHODS: From July 2006 to December 2013, percutaneous radiologic gastrostomy was performed in 12 children (median age, 21 months; range, 6-46 months). Their stomachs were punctured using a 21-gauge Chiba needle. A single Cope gastrointestinal suture anchor was used for gastropexy, and a tube was inserted through the same tract as the anchor using a 12- or 14-French Dawson-Mueller pigtail drainage catheter. We then evaluated the technical success of the procedure, the number of puncture attempts using a 21-gauge Chiba needle, the procedure time, complications, and treatment of complications. RESULTS: Percutaneous radiologic gastrostomy was technically successful in all patients. Only a single puncture attempt was required in 10 patients (83%); two attempts were needed in two patients (17%). The average procedure time was 10 minutes 25 seconds (range, 5 minutes 5 seconds to 25 minutes 24 seconds). Pneumoperitoneum requiring tube exchange occurred in two of the 12 patients (17%). Two patients experienced pain immediately after the procedure. Three patients who had esophagogastric reflux after percutaneous radiologic gastrostomy underwent conversion percutaneous radiologic gastrojejunostomy. CONCLUSION: Percutaneous radiologic gastrostomy using a modified Chiba-needle technique with single gastropexy in pediatric patients is technically feasible and safe.

Metallic stent placement in patients with recurrent malignant obstruction in the surgically altered stomach.

PURPOSE: The purpose of this study was to assess the technical feasibility and clinical effectiveness of expandable metallic stent placement in 196 patients with recurrent malignant obstruction in their surgically altered stomach. METHODS: The 196 patients were treated using five different types of gastric surgery performed for gastric cancer: total gastrectomy (type 1) in 73 patients; distal gastrectomy with gastroduodenostomy (type 2) in 39 patients; distal gastrectomy with a Roux-en-Y gastrojejunostomy (type 3) in 21 patients; distal gastrectomy with a gastrojejunostomy (type 4) in 49 patients; and palliative gastrojejunostomy for unresectable gastric cancer (type 5) in 14 patients. The technical and clinical success rates, complications, dysphagia score, and influence of chemotherapy were evaluated and the complications compared between the two stent types. The overall survival and stent patency were calculated using the Kaplan-Meier method. RESULTS: Stent placement was technically successful in 192 of 196 patients (97.9 %), with 184 of the 192 patients (95.8 %) showing symptomatic improvement. The mean dysphagia score improved from 3.24 ± 0.64 to 1.48 ± 0.82 (p < 0.001). The complication rate was 25 %. The incidence of stent migration was significantly higher in fully covered stents and in patients who underwent chemotherapy (p < 0.001 and p = 0.005, respectively). Chemotherapy was significantly associated with an increase of survival (p < 0.001). The median survival and stent patency were 131 and 90 days, respectively. CONCLUSION: Placement of expandable metallic stents in patients with recurrent cancer after a surgically altered stomach is technically feasible and clinically effective. Chemotherapy was associated with increased stent migration and prolonged survival.

Polydioxanone biodegradable stent placement in a canine urethral model: analysis of inflammatory reaction and biodegradation.

PURPOSE: To investigate the inflammatory reaction and perform quantitative analysis of biodegradation after placement of a polydioxanone (PDO) biodegradable stent in a canine urethral model. MATERIALS AND METHODS: PDO biodegradable stents were placed in the proximal and distal urethra of nine male mongrel dogs. The dogs were euthanized 4 weeks (group A; n = 3), 8 weeks (group B; n = 3), or 12 weeks (group C; n = 3) after stent placement. The luminal diameter of the stent-implanted urethra was assessed by follow-up retrograde urethrography, and histologic findings were obtained after the dogs were killed. Stents were removed after euthanasia, and their surface morphology and molecular weight were evaluated. Hematologic examination was performed to evaluate inflammatory reaction. RESULTS: Stent placement was technically successful in all dogs. The average luminal diameter gradually decreased. The average number of epithelial layers (2.93 vs 4.42; P < .001), the average thickness of papillary projection (0.80 mm vs 1.28 mm; P < .001), and the average thickness of submucosal fibrosis (0.34 mm vs 0.49 mm ; P < .001) were significantly increased in group B versus group A. There were no significant differences between group B and group C. The average inflammatory cell infiltration did not differ significantly in the three groups. Molecular weight losses were 54% in group A and 84% in group B. In group C, PDO stents were completely decomposed. CONCLUSIONS: An experimental study in a canine urethral model has demonstrated acceptable inflammatory reaction with gradually increasing granulation tissue but no luminal obstruction within 12 weeks.

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.

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.