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Multidrug-resistant enterococci are considered crucial drivers for the dissemination of antimicrobial resistance determinants within and beyond a genus. These organisms may pass numerous resistance determinants to other harmful pathogens, whose multiple resistances would cause adverse consequences. Therefore, an understanding of the coexistence epidemiology of resistance genes is critical, but such information remains limited. In this study, our first objective was to determine the prevalence of principal resistance phenotypes and genes among Enterococcus faecalis isolated from retail chicken domestic products collected throughout Japan. Subsequent analysis of these data by using an additive Bayesian network (ABN) model revealed the co-appearance patterns of resistance genes and identified the associations between resistance genes and phenotypes. The common phenotypes observed among E. faecalis isolated from the domestic products were the resistances to oxytetracycline (58.4%), dihydrostreptomycin (50.4%), and erythromycin (37.2%), and the gene tet(L) was detected in 46.0% of the isolates. The ABN model identified statistically significant associations between tet(L) and erm(B), tet(L) and ant(6)-Ia, ant(6)-Ia and aph(3')-IIIa, and aph(3')-IIIa and erm(B), which indicated that a multiple-resistance profile of tetracycline, erythromycin, streptomycin, and kanamycin is systematic rather than random. Conversely, the presence of tet(O) was only negatively associated with that of erm(B) and tet(M), which suggested that in the presence of tet(O), the aforementioned multiple resistance is unlikely to be observed. Such heterogeneity in linkages among genes that confer the same phenotypic resistance highlights the importance of incorporating genetic information when investigating the risk factors for the spread of resistance. The epidemiological factors that underlie the persistence of systematic multiple-resistance patterns warrant further investigations with appropriate adjustments for ecological and bacteriological factors.

Because antimicrobial resistance in food-producing animals is a major public health concern, many countries have implemented antimicrobial monitoring systems at a national level. When designing a sampling scheme for antimicrobial resistance monitoring, it is necessary to consider both cost effectiveness and statistical plausibility. In this study, we examined how sampling scheme precision and sensitivity can vary with the number of animals sampled from each farm, while keeping the overall sample size constant to avoid additional sampling costs. Five sampling strategies were investigated. These employed 1, 2, 3, 4 or 6 animal samples per farm, with a total of 12 animals sampled in each strategy. A total of 1,500 Escherichia coli isolates from 300 fattening pigs on 30 farms were tested for resistance against 12 antimicrobials. The performance of each sampling strategy was evaluated by bootstrap resampling from the observational data. In the bootstrapping procedure, farms, animals, and isolates were selected randomly with replacement, and a total of 10,000 replications were conducted. For each antimicrobial, we observed that the standard deviation and 2.5-97.5 percentile interval of resistance prevalence were smallest in the sampling strategy that employed 1 animal per farm. The proportion of bootstrap samples that included at least 1 isolate with resistance was also evaluated as an indicator of the sensitivity of the sampling strategy to previously unidentified antimicrobial resistance. The proportion was greatest with 1 sample per farm and decreased with larger samples per farm. We concluded that when the total number of samples is pre-specified, the most precise and sensitive sampling strategy involves collecting 1 sample per farm.

The epidermal tissue is the outmost component of the skin that plays an important role as a first barrier system in preventing the invasion of various environmental agents, such as bacteria. Recent studies have identified the importance of microbial competition between harmful and beneficial bacteria and the diversity of the skin surface on our health. We develop mathematical models (M1 and M2 models) for the inflammation process using ordinary differential equations and delay differential equations. In this paper, we study microbial community dynamics via transcription factors, protease and extracellular cytokines. We investigate possible mechanisms to induce community composition shift and analyze the vigorous competition dynamics between harmful and beneficial bacteria through immune activities. We found that the activation of proteases from the transcription factor within a cell plays a significant role in the regulation of bacterial persistence in the M1 model. The competition model (M2) predicts that different cytokine clearance levels may lead to a harmful bacteria persisting system, a bad bacteria-free state and the co-existence of harmful and good bacterial populations in Type I dynamics, while a bi-stable system without co-existence is illustrated in the Type II dynamics. This illustrates a possible phenotypic switch among harmful and good bacterial populations in a microenvironment. We also found that large time delays in the activation of immune responses on the dynamics of those bacterial populations lead to the onset of oscillations in harmful bacteria and immune activities. The mathematical model suggests possible annihilation of time-delay-driven oscillations by therapeutic drugs.

Solid Organ Transplant (SOT) recipients are at significant higher risk for COVID-19 and due to immunosuppressive medication, the immunogenicity after vaccination is suboptimal. In the previous studies, booster method showed significant benefit in this population. In the current study, we compared using a mix-and-match method vs. same vaccine as a third dose in SOT recipients. This was a patient-blinded, single center, randomized controlled trial comparing BNT162b2 vs. JNJ-78436735 vaccine as the third dose after two doses of BNT162b2 vaccine. We included adult SOT recipients with functional graft who had received two doses of BNT162b2 vaccine. Participants were randomly assigned to receive either BNT162b2 or JNJ-78436735 in one-to-one ratio. Primary outcome was SARS-CoV-2 IgG positivity at 1 month after the third dose. Sixty SOT recipients, including 36 kidney, 12 liver, 2 lung, 3 heart, and 5 combined transplants, were enrolled, and 57 recipients were analyzed per protocol. There were no statistically significant differences between the two vaccine protocols for IgG positivity (83.3% vs. 85.2% for BNT162b2 and JNJ-78436735, respectively, p = 0.85, Odds Ratio 0.95, 95% Confidence Interval 0.23-4.00). Comparison of the geometric mean titer demonstrated a higher trend with BNT162b2 ( p = 0.09). In this pilot randomized controlled trial comparing mix and match method vs. uniform vaccination in SOT recipients, both vaccines were safely used. Since this was a small sample sized study, there was no statistically significant difference in immunogenicity; though, the mix and match method showed relatively lower geometric mean titer, as compared to uniform vaccine. Further studies need to be conducted to determine duration of this immunogenicity. Clinical Trial Registration : https://clinicaltrials.gov/ct2/show/NCT05047640?term=20210641&draw=2&rank=1, identifier 20210641., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Natori, Martin, Mattiazzi, Arosemena, Ortigosa-Goggins, Shobana, Roth, Kupin, Burke, Ciancio, Morsi, Phancao, Munagala, Butrous, Manickavel, Sinha, Sota, Pallikkuth, Bini, Simkins, Anjan, Vianna and Guerra.)

Objectives: This study compared the balance function in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with their balance function after subsequent training sessions with a Balance Exercise Assist Robot (BEAR)., Methods: In this prospective observational study, inpatients who underwent allo-HSCT from human leukocyte antigen-mismatched relatives were enrolled from December 2015 to October 2017. Patients were allowed to leave their clean room after allo-HSCT and underwent balance exercise training using the BEAR. Sessions (20-40 min) were performed 5 days per week and consisted of three games that were performed four times each. A total of 15 sessions were performed by each patient. Patient balance function was assessed before BEAR therapy according to the mini-balance evaluation systems test (mini-BESTest), and patients were divided into two groups (Low and High) based on a 70% cut-off value for the total mini-BESTest score. Patient balance was also assessed after BEAR therapy., Results: Fourteen patients providing written informed consent fulfilled the protocol: six patients in the Low group, and eight patients in the High group. In the Low group, there was a statistically significant difference between pre- and post-evaluations in postural response, which a sub-item of the mini-BESTest. In the High group, there was no significant difference between pre- and post-evaluations in the mini-BESTest., Conclusions: BEAR sessions improve balance function in patients undergoing allo-HSCT., Competing Interests: CONFLICTS OF INTEREST: The authors have no conflicts of interest to declare., (2023 The Japanese Association of Rehabilitation Medicine.)

Potassium-sensing oligonucleotide, PSO, a conjugate of a quadruplex structure-forming oligonucleotide with a peptide incorporating a Förster Resonance Energy Transfer (FRET) chromophore pair, has been developed for fluorescent detection of potassium ion (K + ) in aqueous medium. PSO 1 could be introduced into cells for real-time imaging of cytoplasmic K + concentrations. To perform fluorescent imaging of K + on the cell surface, we synthesized twelve PSO derivatives with different types of peptide types and lengths, and oligonucleotide sequences including thrombin-binding aptamer (TBA) sequences with FAM and TAMRA as a FRET chromophore pair, and evaluated their performance. 1 was shown to respond selectively to K + , not to most ions present in vivo , and to show reciprocal fluorescence changes in response to K + concentration. For the peptide chains and oligonucleotide sequences examined in this study, the PSO derivatives had K values for K d in the range of 5-30 mM. All PSO derivatives showed high K + in the range of 5-30 mM. All PSO derivatives showed high K + selectivity even in the presence of excess Na + streptavidin (StAv). Fluorescence imaging of extracellular K via streptavidin (StAv). Fluorescence imaging of extracellular K + upon addition of apoptosis inducers was successfully achieved by 1 localized to the cell surface., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sato, Ohzawa, Sota, Sakamoto, Udo, Sueda, Matsuda, Nagai and Takenaka.)

Polyallylamine (PAA) has been utilized as a salt tolerant anion exchange chromatography ligand in downstream processing of biopharmaceuticals. We have developed novel MMC resins based on PAA polymer ligand partially modified with hydrophobic butyl or phenyl group. The resulting hydrophobic modified PAA ligand reduced HCP level to 12% (21-23 ppm) under 6 mS/cm in a flow-through polishing step of mAb, while not modified PAA ligand showed only 79% (145 ppm). We also found that structure of hydrophobic groups in the ligand mainly influenced on mAb yield. That is 25% increase of phenyl group modification ratio reduces mAb yield from 95% to 90%. On the other hand, modification with butyl group kept mAb yield more than 95%. The optimized ligand structure displayed a wide operational conductivity range. Extended purification studies of mAb using the MMC resin in the flow-through polishing step were carried out under optimized pH and conductivity condition as determined in a DOE study. The study revealed that the MMC resin was effective for developing one-step flow-through polishing workflow for mAb purification. In addition, the MMC flow-through polishing step could be directly coupled with a specified CEX chromatography step to efficiently remove mAb aggregates from 2.3% to <1.0% to achieve a biopharmaceutical-grade quality and a high yield of mAb (>93%) with a high loading capacity around 1000 mg/mL-resin. This new MMC resin will be useful in future mAb manufacturing platforms comprising of a robust and cost-effective flow-through polishing step., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: The Balance Exercise Assist Robot (BEAR) is a boarding-type robot developed to improve users' balance performance. However, the exercise load experienced by users of the BEAR remains unclear. Therefore, this study aimed to identify the exercise load of BEAR users., Methods: Recruited healthy participants were fitted with an expiratory gas analyzer, and instructed to control the avatar displayed on the computer monitor by shifting their weight on the BEAR. Three types of activity (tennis, skiing, and rodeo) were prepared for the BEAR, and the difficulty of each activity had 40 levels. Each balance exercise for each level lasted for 90 s. The BEAR was administered at levels 1, 5, 10, and then up to 40 in steps of 5 for each activity. The major parameters that were evaluated were oxygen consumption (grossVO 2 , netVO 2 ), metabolic equivalents (METs), and heart rate (HR). Two-way analysis of variance with Tukey's post hoc test was applied to each level of each activity., Results: Fourteen healthy participants were recruited. For the rodeo activity, netVO 2 and MET values were significantly higher than those for tennis and skiing at level 20 (tennis vs. skiing vs. rodeo: netVO 2 114.0±59.7 vs. 160.6±71.1 vs. 205.6±82.9, METs 1.47±0.22 vs. 1.72±0.37 vs. 1.90±0.29) and higher. Furthermore, comparisons within activity types showed that at level 40, netVO 2 and MET were significantly higher than for level 1. The exercise intensity was found to increase along with the exercise level for all three activity types, with rodeo being the highest at 2.74 METs., Conclusions: The current findings show that the BEAR can be used for balance practice without generating excessive cardiopulmonary stress., Competing Interests: CONFLICTS OF INTEREST: The authors have declared that no conflict of interest exists., (2021 The Japanese Association of Rehabilitation Medicine.)

Objective: Lymphoid hyperplasia is endoscopically observed as multiple small whitish round nodules or spots. This retrospective study was performed to examine the prevalence of that finding in patients with Barrett's epithelium and its relationship with the status of H. pylori infection., Methods: The study subjects were 3353 patients (males 2186, females 1167; mean age 55.2 ± 9.4 years) in whom the status of H. pylori infection had been determined. The presence of Barrett's epithelium ≥ 5 mm in length was endoscopically determined, and then endoscopic observations with blue laser imaging were used to investigate the presence of lymphoid hyperplasia in those areas., Results: Barrett's epithelium was diagnosed in 1884 (56.2%) of the subjects, and endoscopic findings of lymphoid hyperplasia were observed in 402 (21.3%) of those with Barrett's epithelium. Lymphoid hyperplasia in Barrett's epithelium was not present in any without a current or prior H. pylori infection, while the prevalence of lymphoid hyperplasia in H. pylori -positive and post-eradicated subjects was 48.4% and 30.4%, respectively ( p < 0.001). Multiple logistic regression analysis revealed that female gender, younger age, and higher degree of gastric mucosal atrophy were significant factors related to lymphoid hyperplasia positivity. In addition, the duration after H. pylori eradication was negatively correlated with its prevalence., Conclusion: Endoscopic findings of cardiac lymphoid hyperplasia were well correlated with H. pylori infection, although prevalence decreased over time following bacterial eradication., Competing Interests: The authors have no conflict of interest to declare in regard to this study., (© 2021 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Objective This study was conducted to clarify the prevalence of short segment Barrett's esophagus (SSBE) using endoscopic observations with linked color imaging (LCI). In addition, the relationship between the presence of Barrett's epithelium (BE) and the status of H. pylori infection was investigated. Methods The study subjects were 3,353 individuals (2,186 men, 1,167 women; mean age 55.2±9.4 years old) whose status of H. pylori infection had been determined. An endoscopic observation using LCI was performed to examine the distal margin of palisade vessels and confirm the area of BE. The prevalence of BE ≥5 mm in length was investigated. Results BE was diagnosed in 1,884 (56.2%) subjects, with lengths of <10, 10-19, 20-29, and ≥30 mm found in 1,005, 851, 27, and 1, respectively. Its prevalence in H. pylori-negative, H. pylori-positive, and post-eradicated subjects was 41.7%, 64.4%, and 69.9%, respectively (p<0.001). The duration since successful eradication of H. pylori did not affect the prevalence of BE. The degree of gastric mucosal atrophy was higher in cases with BE (p<0.001), although negativity for H. pylori infection and mild gastric mucosal atrophy were significant factors for the development of longer BE. Conclusion A high prevalence of SSBE was noted when LCI was used to determine the area of BE, as the distal end of the palisade vessels was easily visualized. Negativity for H. pylori infection and mild gastric mucosal atrophy were not correlated with SSBE prevalence.

Objective This retrospective study was performed to investigate the anti-Helicobacter pylori IgG antibody serum titers in H. pylori-negative subjects with different degrees of gastric mucosal atrophy including C0 grade atrophy. Methods The absence of H. pylori infection was determined based on both negative serum anti-H. pylori IgG antibody test findings and no endoscopic evidence of that infection. Cases negative for the antibody and with positive endoscopic findings of H. pylori infection were defined as H. pylori-positive. The serum anti-H. pylori IgG antibody titers were analyzed in H. pylori-negative (n=1,087), -positive (n=69), and post-eradicated (n=278) subjects. Results The serum antibody titer in subjects with H. pylori-positive endoscopy findings was significantly higher than that in H. pylori-negative subjects, even when the serum titer indicated a negative result. In addition, the anti-H. pylori IgG antibody serum titer was higher in H. pylori-negative subjects with a greater degree of gastric mucosal atrophy. In a comparison between H. pylori-negative C0 and C1 gastric mucosal atrophy cases, the antibody serum titer in those classified as C0 was significantly lower. An analysis of H. pylori post-eradicated cases showed that the serum antibody titer decreased over time after successful eradication. Conclusion The disappearance of H. pylori infection in H. pylori-negative individuals may occur later in those with a greater degree of gastric mucosal atrophy. The serum antibody titer difference between the H. pylori-negative C0 and C1 groups might have been caused by the differences in distribution between H. pylori-uninfected subjects and those in whom the infection had disappeared, thus additional investigation is needed to clarify the significance of gastric mucosal classification including the C0 grade.

Background: Functional electrical stimulation (FES) for patients with stroke and foot drop is an alternative to ankle foot orthoses. Characteristics of FES responders and nonresponders have not been clarified., Objectives: (1) To investigate the effects of treatment with FES on patients with stroke and foot drop and (2) to determine which factors may relate to responders and nonresponders., Design: Multicenter, nonrandomized, prospective study., Setting: Multicenter clinical trial., Participants: Participants included those who experienced foot drop resulting from stroke, were older than 20 years, and could provide consent to participate; they were enrolled from hospitals between January 2013 and September 2015 and performed rehabilitation with FES., Methods: Stroke Impairment Assessment Set Foot-Pat Test (SIAS-FP), Fugl-Meyer Assessment for Lower Extremity (FMA-LE), Modified Ashworth scale (MAS) for ankle joint dorsiflexion and plantar flexion muscles, range of motion (ROM) for ankle joint, 10-m walking test (10mWT), Timed Up & Go test (TUG), and 6-minute walking test (6MWT) were evaluated pre- and postintervention. Age, gender, type of stroke, onset times of stroke, paretic side, Brunnstrom stage of the lower extremity (Br. stage-LE), Functional Independence Measure (FIM), Functional Ambulation Category (FAC), poststroke months, number of interventions, total hours of interventions, and whether a brace was used were extracted from patients' medical records and collected on the physiological examination day., Main Outcome Measurements: The authors examined 10mWT and age, gender, type of stroke, onset times of stroke, paretic side, Br. stage-LE, FIM, FAC, poststroke months, number of interventions, total hours of interventions, whether a brace was used, SIAS-FP, FMA-LE, MAS, ROM, TUG, and 6MWT before intervention. Participants were divided into nonresponders and responders with a change in 10mWT of <0.1 and ≥0.1 m/s, respectively. Single and multiple regression analyses were used for data analysis. Additionally, the changes between groups were compared., Results: Fifty-eight responders and 43 nonresponders were enrolled. The between-group differences, compared for changes between pre- and postintervention, were significant in terms of changes in SIAS-FP (P = .02), 10mWT (P < .001), 10-m gait steps (P < .001), TUG (P = .04), and 6MWT (P = .006). In the adjusted regression model, gender (odds ratio [OR], 3.92; 95% confidence interval [CI], 1.426-12.25; P = .007), number of interventions (OR, 1.028; 95% CI, 1.003-1.070; P = .03), and active ankle joint dorsiflexion ROM (OR, 1.047; 95% CI, 1.014-1.088; P = .005) remained significant., Conclusion: The factors related to 10mWT showing changes beyond the minimal clinically important difference were found to be patient gender, number of interventions, and active ankle joint dorsiflexion ROM before intervention. When patients with stroke who have greater active ankle joint ROM, and are female, use FES positively, they may benefit more from using FES., Level of Evidence: II., (Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to investigate the relationship between corticosteroid dose and degree of physical function decrease in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients during the early stage of recovery. We further investigated the confounding factors affecting loss of physical function., Methods: The study included 113 patients who underwent allo-HSCT between July 2007 and April 2012 at Hyogo College of Medicine Hospital in Japan. Physical function was assessed using tests for hand-grip strength, knee-extensor strength, and the 6-min walk test (6MWT). Fatigue was measured using the Piper Fatigue Scale. Total corticosteroid dose, frequency of physical therapy, body weight, and nutritional status were also collected from medical records., Results: Total corticosteroid dose was correlated with decrease of hand-grip and knee-extensors strength (P < 0.01) but was not correlated with 6MWT performance. Results of multivariate analysis confirmed that low physical function was associated not only with high corticosteroid dose but also with low frequency of physical therapy, increase in fatigue, and body weight loss (P < 0.05). Also, hemoglobin levels were associated with 6MWT (P < 0.05)., Conclusions: This study showed the relationship between corticosteroid dose and declines in physical function and also showed other clinical factors affecting loss of physical function among allo-HSCT patients. Our results indicate that the effectiveness of rehabilitation may be influenced by corticosteroid treatment.

When a biotinylated FRET probe based on a peptide-thrombin binding aptamer conjugate was introduced together with streptavidin and biotinylated nuclear export signal peptide into HeLa cells, the resulting ternary complex enabled visualization of K(+) concentration changes in the cell., (This journal is © The Royal Society of Chemistry 2012)

The synthesis, antibacterial activity and oral absorption of new 7 beta-[D-alpha-amino-alpha-(4-hydroxyphenyl)acetamido]cephalosporins (1) with various O-substituents at the C-3 position of a cephalosporin nucleus are described. Of these, the cephalosporins (1b-1e) having an alkoxycarbonylmethoxy group at the C-3 position showed good oral absorption in rats as well as potent activity against Gram-positive bacteria. The structure-activity relationships of 1 are also presented.

A series of 17-succinyl derivatives of four corticosteroids was prepared. They were tested for vasoconstrictive activity in humans, using 9 alpha-fluoro-11 beta, 21-dihydroxy-16 beta-methyl-17 alpha-valeryloxy-1,4-pregnadiene-3,20-dione (betamethasone 17-valerate, BV) as a standard. The activities of the 21-chloro 17-methylsuccinate compounds (6A, 6C and 6D) were greater than that of BV. A structure-activity relationship study showed that the activities of the 21-chloro 17-methylsuccinates were more potent than those of the corresponding 21-esters.

The synthesis, antibacterial activity and oral absorption in rats of 3-alkoxycarbonyl-methoxy-7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-(O-substituted oxyimino)acetamido]cephalosporins (1) are described. In this cephalosporin series, 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-(carboxy-methoxyimino)acetamid o] cephalosporins (1b, 1i and 1j) with a lower alkoxycarbonylmethoxy group at the C-3 position of a cephem nucleus exhibited not only potent activity against Gram-negative bacteria but also good oral absorption in rats. Structure-activity relationships of 1 are also presented.

4,6-Disubstituted 2-(morpholinocarbonyl)furo[3,2-b]indole derivatives showed analgesic and antiinflammatory activities when assayed by the acetic acid writhing test in mice and the carrageenin edema test in rats. To understand how the substituents affect the biological activities, the quantitative structure-activity relationships (QSAR) of 38 compounds were analyzed using the adaptive least-squares method (ALS method). The resulting QSAR suggested that some chemical modifications of 4,6-disubstituted furo[3,2-b]indole derivatives would improve their biological activities. Thus, 15 additional compounds were synthesized to reinforce and confirm the correlation. Among these compounds, particularly 4-(2-ethylhexanoyl)-2-(morpholinocarbonyl)-6-(trifluoromethy l) furo[3,2-b]indole showed pronounced biological activities. This compound gave a pharmacological activity spectrum similar to that of tiaramide but exhibited much higher potency.

2-Acetylthio-3-benzoylpropionic acid derivatives having two benzene rings or condensed-ring moieties were prepared, and tested for hypolipidemic activity in normal rats. Some of these compounds were active. 2-Acetylthio-3-[4-(phenylthio)benzoyl]propionic acid (10) and its derivatives seemed to have the most potent hypocholesterolemic activities. Compound 10 showed strong activity, especially in cholesterol-fed rats.

As part of the search for new topical antiinflammatory agents, various 21-substituted corticosteroids having sulfur-containing moieties were prepared and tested for vasoconstrictive activity in humans. A structure-activity relationship study revealed that substitution of the 21-hydroxy group with a lower alkyl-thio group enhanced the activity. The activities of the 21-methylthio (3Ad) and the 21-ethylthio (3Ae) compounds were more potent than that of 9 alpha-fluoro-11 beta,21-dihydroxy-16 beta-methyl-17 alpha-valeroyloxy-1,4- pregnadiene-3,20-dione (betamethasone 17-valerate, BV).