Standardization of preoperative stoma site marking and its utility for preventing stoma leakage: a retrospective study of 519 patients who underwent laparoscopic/robotic rectal cancer surgery.

PURPOSE: Stoma site marking is an important preoperative intervention for preventing various stoma-associated complications. In our institution, standardized stoma site marking is routinely performed before rectal cancer surgery with stoma creation, and various stoma-associated factors are recorded in the ostomy-record template. The present study investigated risk factors for stoma leakage. METHODS: Our stoma site marking is standardized so that it can be performed by non-stoma specialists. To identify risk factors of stoma leakage at 3 months after surgery, various preoperative factors associated with stoma site marking in our ostomy-record template were retrospectively analyzed in 519 patients who underwent rectal cancer surgery with stoma creation from 2015 to 2020. RESULTS: Stoma leakage was seen in 35 of the 519 patients (6.7%). The distance between the stoma site marking and the umbilicus was less than 60 mm in 27 of the 35 patients (77%) who experienced stoma leakage, so a distance of less than 60 mm was identified as an independent risk factor for stoma leakage. Aside from preoperative factors, stoma leakage was also caused by postoperative skin wrinkles or surgical scars near the stoma site in 8 of 35 patients (23%). CONCLUSION: Preoperative standardized stoma site marking is necessary to achieve reliable marking that is easy to perform. To reduce the risk of stoma leakage, a distance of 60 mm or more between the stoma site marking and the umbilicus is ideal, and surgeons need to contrive ways to keep surgical scars away from the stoma site.

Long-term outcomes and recurrence-free interval after the treatment of keloids with a standardized protocol.

BACKGROUND: Recurrence rates of keloids have generally been reported at one time point. However, the longer the duration after treatment, the greater the likelihood that such lesions will recur. In this study, we analysed the time to recurrence during long-term follow-up. MATERIAL AND METHODS: We retrospectively reviewed recurrence-free interval in 52 patients with keloid (age 8-79 years) who had been treated between June 2006 and January 2011 using a standardised protocol developed by our group. RESULTS: Mean duration of follow-up was 37.5 (range, 7-120) months in patients with keloid. Kaplan-Meier survival curves revealed a statistically significant difference in recurrence-free interval between ear keloids and keloids excluding ear keloids. Recurrence rate for keloids was high in the first 2 years after treatment. CONCLUSIONS: Kaplan-Meier analysis was useful for understanding the tendency of recurrence of keloids after treatment using a standardised protocol.

Serum immunoglobulin G antibody titer to Fusobacterium nucleatum is associated with unfavorable outcome after stroke.

Stroke can be a cause of death, while in non-fatal cases it is a common cause of various disabilities resulting from associated brain damage. However, whether a specific periodontal pathogen is associated with increased risk of unfavorable outcome after stroke remains unknown. We examined risk factors for unfavorable outcome following stroke occurrence, including serum antibody titers to periodontal pathogens. The enrolled cohort included 534 patients who had experienced an acute stroke, who were divided into favorable (n = 337) and unfavorable (n = 197) outcome groups according to modified ranking scale (mRS) score determined at 3 months after onset (favorable = score 0 or 1; unfavorable = score 2-6). The associations of risk factors with unfavorable outcome, including serum titers of IgG antibodies to 16 periodontal pathogens, were examined. Logistic regression analysis showed that the initial National Institutes of Health stroke scale score [odds ratio (OR) = 1·24, 95% confidence interval (CI) = 1·18-1·31, P < 0·001] and C-reactive protein (OR = 1·29, 95% CI = 1·10-1·51, P = 0·002) were independently associated with unfavorable outcome after stroke. Following adjustment with those, detection of the antibody for Fusobacterium nucleatum ATCC 10953 in serum remained an independent predictor of unfavorable outcome (OR = 3·12, 95% CI = 1·55-6·29, P = 0·002). Determination of the antibody titer to F. nucleatum ATCC 10953 in serum may be useful as a predictor of unfavorable outcome after stroke.

Adjunctive perampanel in partial-onset seizures: Asia-Pacific, randomized phase III study.

OBJECTIVES: To evaluate the efficacy, safety, and tolerability of perampanel, a selective, non-competitive, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, as an adjunctive treatment for patients with refractory partial-onset seizures (POS) from Asia-Pacific. MATERIALS & METHODS: This multicenter, randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov identifier: NCT01618695) involved patients aged ≥12 years with refractory POS (receiving 1-3 antiepileptic drugs). Patients were randomized (1:1:1:1) to receive once-daily placebo or perampanel 4, 8, or 12 mg over a 6-week titration and 13-week maintenance double-blind period. Enzyme-inducing antiepileptic drugs were equally stratified between groups. The primary efficacy endpoint was percent change in POS frequency per 28 days (double-blind phase vs baseline). Other efficacy endpoints included ≥50% responder rate and seizure freedom. Treatment-emergent adverse events (TEAEs) were also monitored. RESULTS: Of 710 randomized patients, seizure frequency data were available for 704 patients. Median percent changes in POS frequency per 28 days indicated dose-proportional reductions in seizure frequency: -10.8% with placebo and -17.3% (P = .2330), -29.0% (P = .0003), and -38.0% (P < .0001) with perampanel 4, 8, and 12 mg, respectively. In total, 108 (15.3%) patients discontinued treatment; 44 (6.2%) due to TEAEs. TEAEs occurring in ≥5% of patients, and reported at least twice as frequently with perampanel vs placebo, included dizziness and irritability. CONCLUSIONS: Adjunctive perampanel (8 and 12 mg/d) significantly improved seizure control in patients with refractory POS. Safety and tolerability were acceptable at daily doses of perampanel 4-12 mg.

Observation and Control of Laser-Enabled Auger Decay.

Single-photon laser-enabled Auger decay (spLEAD) is predicted theoretically [B. Cooper and V. Averbukh, Phys. Rev. Lett. 111, 083004 (2013)PRLTAO0031-900710.1103/PhysRevLett.111.083004] and here we report its first experimental observation in neon. Using coherent, bichromatic free-electron laser pulses, we detect the process and coherently control the angular distribution of the emitted electrons by varying the phase difference between the two laser fields. Since spLEAD is highly sensitive to electron correlation, this is a promising method for probing both correlation and ultrafast hole migration in more complex systems.

Cheese supplemented with probiotics reduced the Candida levels in denture wearers-RCT.

OBJECTIVES: The access to probiotics should be facilitated in order to encourage their usage. We evaluated the effect of consumption of two experimental probiotic-containing cheeses on the oral colonization of Candida in denture wearers. METHODS: Sixty denture wearers harboring oral Candida were randomly allocated in groups who received cheese supplemented with Lactobacillus acidophilus NCFM (T1) or Lactobacillus rhamnosus Lr-32 (T2), daily for 8 weeks, and a control group (C) who received a control cheese. Oral samples were obtained through a mouthwash, and Candida levels were determined (CFU/mL) at baseline and after the 8-week experimental period. RESULTS: At baseline, the mean levels of Candida spp. (log CFU/mL) were similar among the groups. However, the mean levels of Candida were significantly reduced in groups T1 and T2 but not in C (Tukey, p<.05). The reduction in Candida oral levels occurred independently on the colonizing Candida species, participant age, and use of bi- or unimaxillary dentures. CONCLUSIONS: Daily consumption of cheese supplemented with probiotics, with either L. acidophilus NCFM or L. rhamnosus Lr-32, was able to reduce the colonization of oral Candida in complete denture wearers, suggesting its potential in reducing the risk of oral candidiasis in this highly susceptible population.

Inhibition of choroidal fibrovascular membrane formation by new class of RNA interference therapeutic agent targeting periostin.

Age-related macular degeneration (AMD) is a vision-threatening disease characterized by choroidal fibrovascular membrane (FVM) formation, choroidal neovascularization (CNV) and choroidal fibrosis. No safe and effective therapeutic method has been developed for the choroidal fibrosis, although anti-vascular endothelial growth factor therapy can partially shrink the CNV. We recently reported that periostin (POSTN), which is produced by retinal pigment epithelial cells, has an important role in the formation of preretinal FVMs, but its role in choroidal FVMs has not been determined. In this study, we used Postn knockout mice to investigate the role played by POSTN in choroidal FVM formation. In addition, we used a new class of RNA interference (RNAi) agent (NK0144) that targets POSTN and determined its effect on choroidal FVM development. Genetic ablation of Postn had an inhibitory effect not only on CNV formation but also on choroidal fibrosis in a mouse CNV model. NK0144 also had a greater inhibitory effect on both the CNV and choroidal fibrosis than control RNAi with no apparent adverse effects. These findings suggest a causal relationship between POSTN and choroidal FVM formation, and also a potential therapeutic role of intravitreal NK0144 for AMD.

Mutation in insulin receptor attenuates oxidative stress and apoptosis in pancreatic beta-cells induced by nutrition excess: reduced insulin signaling and ROS.

Type 2 diabetes results from the failure of beta-cells to adequately compensate for insulin resistance. Although the reduction of beta-cell mass is because of increased cell death and/or inadequate replication or neogenesis, the mechanism underlying beta-cell mass reduction is not fully understood. Here, we clarify the role of insulin signaling pathway in the beta-cell apoptosis using insulin resistant model mice. Wild-type mice and those carrying a mutation in the insulin receptor (mIR) were fed either regular chow or a high-fat diet for 6 weeks and subsequently investigated for beta-cell apoptosis, endoplasmic reticulum stress, and oxidative stress. Insulin tolerance tests revealed that mIR mice fed a high-fat diet (mIRHF) had higher insulin resistance. Beta-cell apoptosis was increased 2-fold in the wild-type mice fed a high-fat diet (wHF) compared with control mice, whereas beta-cell apoptosis in mIRHF mice did not increase compared with that in mIR mice. The expression of endoplasmic reticulum stress markers in isolated islets did not differ between the groups. Staining of 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal in islets of wHF mice significantly increased, but the staining in mIRHF mice was not different from that in control group. Gene expression of the antioxidant enzyme MnSOD was significantly higher in mIRHF mice than those in the other 3 groups. A mutation in the insulin receptor attenuated the oxidative stress and apoptosis in beta-cells even though high caloric nutrient was loaded. Our results suggest that reduced insulin signaling protects beta-cells thorough decline of oxidative stress.

[OPTIMIZATION OF THE METHOD OF SUPRAPANCREATIC LYMPH NODE DISSECTION IN LAPAROSCOPY-ASSISTED GASTRECTOMY (IN THE FINAL ANALYSIS OF INTERNATIONAL CONFERENCES <>)].

The article analyzed the methods of suprapancretic lymph node dissection in laparoscopic gastrectomy which were devel- oped and applied in Japan. The authors described the details of operation technique. There were noted the advantages of medial approach for suprapancreatic lymph node dissection.

Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin compared with α-glucosidase inhibitor in Japanese patients with type 2 diabetes inadequately controlled on sulfonylurea alone (SUCCESS-2): a multicenter, randomized, open-label, non-inferiority trial.

We assessed the efficacy and safety of sitagliptin compared with α-glucosidase inhibitor (αGI) in 120 of Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on stable ≤2 mg/day glimepiride alone [mean hemoglobin A1c (HbA1c) 7.7%] by the randomized, active-controlled, non-inferiority trial. Patients were randomly assigned to receive additional sitagliptin or αGI for 24 weeks. The primary endpoint was change in HbA1c from baseline to week 12. After 12 weeks, sitagliptin reduced HbA1c by -0.44% (p < 0.001) relative to αGI. At 24 weeks, the reduction was almost identical between the groups (-0.091%, p = 0.47). Gastrointestinal disorders were more common with αGI than with sitagliptin, but only minor hypoglycaemia occurred in both groups at similar frequency. These data suggested that sitagliptin was not inferior to αGI for reduction of HbA1c in Japanese T2DM patients receiving glimepiride alone, and well tolerated with minimum risk of gastrointestinal symptoms and hypoglycaemia.

Relationship between blood culture time to positivity, mortality rate, and severity of bacteremia.

OBJECTIVES: We investigated the association between patient severity or mortality and time to positivity in bacteremia caused by various pathogens. PATIENTS AND METHODS: This single-center retrospective study included patients with positive blood culture results. RESULTS: Longer time to positivity was associated with 30-day mortality for Staphylococcus aureus (221 cases, time to positivity: 17.4 h in the 30-day mortality group vs. 14.1 h in the survival group). Age, chronic kidney disease, cerebrovascular disease, hypertensive drug use, consciousness disorder, and minimal systolic blood pressure were significant predictors of 30-day mortality. For S. aureus, mortality within 30 days was significantly higher when time to positivity was > 24 h (p = 0.04). The time to positivity of Streptococcus pneumoniae, α, ß-hemolytic Streptococcus, Enterococcus sp., Enterobacteriaceae, glucose-nonfermenting Gram-negative rods, Candida sp., and anaerobe was not significantly associated with 30-day mortality. CONCLUSIONS: Among various pathogens, time to positivity > 24 h was associated with 30-day mortality for S. aureus.

Transformation of polar nematic phases in the presence of an electric field.

Only a few years have passed since the discovery of polar nematics, and now they are becoming the most actively studied liquid-crystal materials. Despite numerous breakthrough findings made recently, a theoretical systematization is still lacking. In the present paper, we take a step toward systematization. The powerful technique of molecular-statistical physics has been applied to an assembly of polar molecules influenced by electric field. Three polar nematic phases were found to be stable at various conditions: the double-splay ferroelectric nematic N_{F}^{2D} (observed in the lower-temperature range in the absence of or at low electric field), the double-splay antiferroelectric nematic N_{AF} (observed at intermediate temperature in the absence of or at low electric field), and the single-splay ferroelectric nematic N_{F}^{1D} (observed at moderate electric field at any temperature below transition into paraelectric nematic N and in the higher-temperature range (also below N) at low electric field or without it. A paradoxical transition from N_{F}^{1D} to N induced by application of higher electric field has been found and explained. A transformation of the structure of polar nematic phases at the application of electric field has also been investigated by Monte Carlo simulations and experimentally by observation of polarizing optical microscope images. In particular, it has been realized that, at planar anchoring, N_{AF} in the presence of a moderate out-of-plane electric field exhibits twofold splay modulation: antiferroelectric in the plane of the substrate and ferroelectric in the plane normal to the substrate. Several additional subtransitions related to fitting the confined geometry of the cell by the structure of polar phases were detected.

Percutaneous methods of vector delivery in preclinical models.

Cardiovascular disease remains a leading cause of hospitalization and mortality worldwide. Conventional heart failure treatment is making steady and substantial progress to reduce the burden of disease. Nevertheless novel therapies and especially cardiac gene therapy have been emerging in the past and successfully made their way into first clinical trials. Gene therapy was initially a visionary treatment strategy for inherited, monogenetic diseases but has now developed to have potential for polygenic diseases as atherosclerosis, arrhythmias and heart failure. These novel therapeutic strategies require testing in clinically relevant animal models to transition from 'bench to bedside'. One of the major hurdles for effective cardiovascular gene therapy is the delivery of the viral vectors to the heart. In this review we present the currently available vector-mediated cardiac gene delivery methods in vivo considering the specific merits and deficiencies.

Cardiac gene therapy in large animals: bridge from bench to bedside.

Several clinical trials are evaluating gene transfer as a therapeutic approach to treat cardiac diseases. Although it has just started on the path to clinical application, recent advances in gene delivery technologies with increasing knowledge of underlying mechanisms raise great expectations for the cardiac gene therapy. Although in vivo experiments using small animals provide the therapeutic potential of gene transfer, there exist many fundamental differences between the small animal and the human hearts. Before applying the therapy to clinical patients, large animal studies are a prerequisite to validate the efficacy in an animal model more relevant to the human heart. Several key factors including vector type, injected dose, delivery method and targeted cardiac disease are all important factors that determine the therapeutic efficacy. Selecting the most optimal combination of these factors is essential for successful gene therapy. In addition to the efficacy, safety profiles need to be addressed as well. In this regard, large animal studies are best suited for comprehensive evaluation at the preclinical stages of therapeutic development to ensure safe and effective gene transfer. As the cardiac gene therapy expands its potential, large animal studies will become more important to bridge the bench side knowledge to the clinical arena.

Prevalence and antimicrobial susceptibility of Salmonella in Japanese broiler flocks.

This study determined the prevalence and antimicrobial susceptibility of Salmonella isolated from broiler flocks in Japan. Caecal dropping samples were collected from 288 broiler flocks between November 2007 and February 2010. Salmonella was prevalent in 248 (86·1%) broiler flocks. The top three serovars were S. Infantis, S. Manhattan and S. Schwarzengrund. S. Infantis was found in all regions tested in this study. However, S. Manhattan and S. Schwarzengrund were frequently found only in the western part of Japan. High antimicrobial resistance rates were observed against oxytetracycline (90·2%), dihydrostreptomycin (86·7%) and ampicillin (36·5%), and 258 (90·5%) of 285 isolates were resistant to two or more antimicrobial agents. Interestingly, 26·3% of isolates were resistant to ceftiofur, especially 38·1% of S. Infantis isolates, although its use in broilers has not been approved in Japan. This study showed that Salmonella is highly prevalent (86·1%) in Japanese broiler flocks, that 90·5% of Salmonella isolates were multidrug-resistant, and that S. Infantis frequently exhibited resistance to cephalosporin antimicrobial agents.

Improvement in organic solvent tolerance by double disruptions of proV and marR genes in Escherichia coli.

AIMS: To investigate the involvement of osmoprotectant transporters in organic solvent tolerance in Escherichia coli and to construct an E. coli strain with high organic solvent tolerance. METHODS AND RESULTS: The organic solvent tolerance of ΔbetT, ΔproV, ΔproP or ΔputP single-gene knockout mutants of E. coli K-12 strain was examined. Among these mutants, the organic solvent tolerance of the ΔproV mutant remarkably increased compared with that of the parent strain. It has been known that a marR mutation confers tolerance on E. coli to organic solvents. A ΔproV and ΔmarR double-gene mutant was more tolerant to organic solvents than the ΔproV or ΔmarR single-gene mutant. The n-hexane amount accumulated in E. coli cells was examined after incubation in an n-hexane-aqueous medium two-phase system. The intracellular n-hexane level in the ΔproV and ΔmarR double-gene mutant was kept lower than those of the parent strain, ΔproV mutant and ΔmarR mutant. CONCLUSIONS: The organic solvent tolerance level in E. coli highly increased by dual disruption of proV and marR. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests a new strategy for increasing the organic solvent tolerance level in E. coli to improve the usability of the whole-cell biocatalysts in two-phase systems employing organic solvents.

Treatment with probiotics in experimental oral colonization by Candida albicans in murine model (DBA/2).

The aim of this study is to evaluate the oral colonization by Candida albicans in experimental murine immunosuppressed DBA/2 and treatment with probiotic bacteria. To achieve these objectives, 152 DBA/2-immunosuppressed mice were orally inoculated with a suspension of C. albicans containing 10(8) viable yeast cells, the animals were treated with nystatin or with the probiotics (Lactobacillus acidophilus and Lactobacillus rhamnosus). Evaluations were performed by Candida count from oral mucosa swabbing. The oral mucosa colonization by C. albicans started at day 1 after inoculation, remained maximal from day 3 until day 7, and then decreased significantly. Probiotics reduced the C. albicans colonization significantly on the oral mucosa in comparison with the untreated animal group. In the group treated with L. rhamnosus, the reduction in yeast colonization was significantly higher compared with that of the group receiving nystatin. Immunosuppressed animal model DBA/2 is a relevant model for experimental Candida oral colonization, and the treatment with probiotics in this model may be an effective alternative to prevent it.

Emergence of paraelectric, improper antiferroelectric, and proper ferroelectric nematic phases in a liquid crystal composed of polar molecules.

We have elaborated a theoretical approach for the description of polar nematic phases observed by Nishikawa et al. [Adv. Mater. 29, 1702354 (2017)0935-964810.1002/adma.201702354], their structures, and transitions between them. Specific symmetry contributions to the pair molecular potentials provide the molecular mechanisms responsible for the formation of proper and improper polarity on the macroscopic level. An improper antiferroelectric nematic M2 phase can arise between paraelectric nematic M1 and proper ferroelectric nematic MP in the temperature scale. The local polarization in M2 arises mostly due to the local splay deformation. The director distribution in M2 represents the conjugation of cylindrical waves with opposite splay and polarization signs. The director and polarization are parallel to the cylindrical domain axes in the middle of each cylinder but exhibit considerable (mostly radial) deformation on the periphery of each cylinder. Polarization vectors are mostly stacked antiparallel on the borders between the domains without the director disruption. The domain size decreases with the decreasing temperature, the percentage of the antiferroelectric decouplings increases, and M2 exhibits the first-order phase transition into proper ferroelectric MP. With the increasing temperature the domain size in the M2 phase increases, the domination of particular polar orientation of molecules reduces, and finally, the domain size diverges at particular temperature corresponding to the second-order phase transition from M2 to paraelectric M1. Variations of the polar and nonpolar orientational order parameters are estimated within each phase and between the phases. Our experimental and computer simulation results (also presented in the paper) fully support our theoretical findings.

Delivery of gelfoam-enabled cells and vectors into the pericardial space using a percutaneous approach in a porcine model.

Intrapericardial drug delivery is a promising procedure, with the ability to localize therapeutics with the heart. Gelfoam particles are nontoxic, inexpensive, nonimmunogenic and biodegradable compounds that can be used to deliver therapeutic agents. We developed a new percutaneous approach method for intrapericardial injection, puncturing the pericardial sac safely under fluoroscopy and intravascular ultrasound (IVUS) guidance. In a porcine model of myocardial infarction (MI), we deployed gelfoam particles carrying either (a) autologous mesenchymal stem cells (MSCs) or (b) an adenovirus encoding enhanced green fluorescent protein (eGFP) 48 h post-MI. The presence of MSCs and viral infection at the infarct zone was confirmed by immunoflourescence and PCR. Puncture was performed successfully in 16 animals. Using IVUS, we successfully determined the size of the pericardial space before the puncture, and safely accessed that space in setting of pericardial effusion and also adhesions induced by the MI. Intrapericardial injection of gelfoam was safe and reliable. Presence of the MSCs and eGFP expression from adenovirus in the myocardium were confirmed after delivery. Our novel percutaneous approach to deliver (stem-) cells or adenovirus was safe and efficient in this pre-clinical model. IVUS-guided delivery is a minimally invasive procedure that seems to be a promising new strategy to deliver therapeutic agents locally to the heart.

Second-order autocorrelation of XUV FEL pulses via time resolved two-photon single ionization of He.

Second-order autocorrelation spectra of XUV free-electron laser pulses from the Spring-8 Compact SASE Source (SCSS) have been recorded by time and momentum resolved detection of two-photon single ionization of He at 20.45 eV using a split-mirror delay-stage in combination with high-resolution recoil-ion momentum spectroscopy (COLTRIMS). From the autocorrelation trace we extract a coherence time of 8 ± 2 fs and a mean pulse duration of 28 ± 5 fs, much shorter than estimations based on electron bunch-length measurements. Simulations within the partial coherence model [Opt. Lett. 35, 3441 (2010)] are in agreement with experiment if a pulse-front tilt across the FEL beam diameter is taken into account that leads to a temporal shift of about 6 fs between both pulse replicas.