Synthesis of triazole- and tetrazole-xyloside analogues as potent hyaluronidase inhibitors

Hyaluronidase is one of the most important enzymes in the development of many diseases. In this study, a series of xyloside analogues bearing a triazole and tetrazole at the anomeric position were prepared from xylosylthioureas and evaluated their inhibitory effects on the hyaluronidase. Triazole and tetrazole skeletons were formed via the Hg(OAc)₂-mediated desulfurizative cyclization through carbodiimide intermediates. According to in vitro anti-hyaluronidase assay, tetrazole-xylosides having p-chloro- or p-nitro-substitution exhibited the high inhibition rates, whereas the compound having p-trifluoromethyl group on the structure did not show the potency. Our results demonstrated the importance of tetrazole-xylosides as hyaluronidase inhibitors.     

Long-term in vivo gene expression in mouse kidney using ϕC31 integrase and electroporation

Background: Achieving long-term gene expression in kidney will be beneficial for gene therapy of renal and congenital diseases, genetic studies constructing animal disease models, and the functional analysis of disease-related genes.

Purpose: The purpose of this study was to develop an in vivo long-term gene expression system in murine kidney using ?C31 integrase.

Methods: Gene expression in cultured RENCA, TCMK-1, and HEK293 cells was assessed. The long-term in vivo gene expression system in the kidney was achieved by co-transfecting 5?µg of pORF-luc/attB as a donor plasmid and 20?µg of pCMV-luc as a helper plasmid into the right kidney of mice by electroporation. Luciferase expression levels were measured to determine longevity of the expression.

Results: Significantly high luciferase expression levels were observed in cultured RENCA, TCMK-1, and HEK293 cells over 1 month compared with controls (non-integrase system). The luciferase cDNA sequence was integrated at a pseudo attP site termed mpsL1. In vivo luciferase expression levels in the integrase group were sustained and significantly higher than those in the control group over 2 months. Furthermore, ?C31 integrase-transfected cells had less genomic DNA damage caused by integrase expression.

Discussion and conclusion: These results demonstrated that the ?C31 integrase system could produce long-term (2 months) in vivo gene expression in mouse kidney.     

Clinical significance of left atrial geometry in dilated cardiomyopathy patients: A cardiovascular magnetic resonance study

BackgroundClinical significance of left atrial (LA) function and geometry in patients with dilated cardiomyopathy (DCM) remains uncertain.HypothesisLA geometric parameters assessed by cardiac magnetic resonance (CMR) predict the prognosis in patients with DCM.MethodsThe present study included patients with DCM and sinus rhythm who underwent CMR between December 2007 and April 2018. LA volume was measured using CMR. LA sphericity index was computed as the ratio of the measured maximum LA volume by the volume of a sphere with maximum LA length diameter.ResultsWe included 255 patients in this study. During the mean follow‐up of 3.92 years, hospitalization for HF occurred in 37 patients. The LA sphericity index was significantly higher in patients with hospitalization for HF than in those without (0.78 ± 0.35 vs. 0.58 ± 0.18, p < .001). Multivariable Cox regression analysis identified a higher LA sphericity index as an independent predictor of hospitalization for HF. Patients were categorized based on the median of LA sphericity index. The Kaplan–Meier curve showed that patients with a high LA sphericity index (≥0.57) had a significantly higher risk of hospitalization for HF than those with a low LA sphericity index (<0.57).ConclusionLA sphericity index was an independent predictor of hospitalization for HF. Assessment of LA geometric parameters might be useful for risk stratification in patients with DCM.     

Effects of functional movement screen training in high-school baseball players: A randomized controlled clinical trial

Background:In recent years, the functional movement screen (FMS) and FMS training have attracted attention as a means of preventing injury, but no studies have examined the effect of such training in high-school baseball players. The aim of this study was to clarify the effect of FMS training on FMS score, physical function and baseball performance in high-school baseball players.Methods:Subjects in this randomized controlled clinical trial were high-school male baseball players assigned to either an FMS training group (intervention group) or a control group. The intervention group performed FMS training 4 times per week for 12 weeks. FMS ability, physical function, and baseball performance were measured prior to the intervention, 8, 12, and 24 weeks after the intervention in the subjects’ school environment.Results:A total of 71 baseball players aged 15 to 17 years were recruited and assigned to either an intervention group (n = 37) or control group (n = 34). There was no significant difference in the characteristics of participants between the 2 groups. Most FMS scores improved to 12 weeks after continued training. In the intervention group compared with the control group, deep squat, hurdle step, inline lunge, active straight leg raise, trunk stability push-up and rotary stability FMS score, total FMS score and eyes closed single leg stance time significantly increased after 8 weeks of training. While hurdle step, inline lunge, active straight leg raise, trunk stability push-up, total FMS score, and eyes closed single leg stance time significantly increased, pitching ball speed significantly decreased at the end of the 12 week training period. Eyes closed single leg stance time and feeling of fatigue significantly improved 12 weeks after training. The number of subjects who scored less than 14 for the total FMS score in the intervention group compared with control group were significantly less after 8 and 12 weeks of FMS training.Conclusion:FMS training for 8 weeks contributes to improving FMS scores for high-school baseball players, but FMS scores go down if FMS training is not continued.Trial registration:University Hospital Medical Information Network Center, Tokyo, Japan: UMIN000027553. Registered on May 30, 2017.     

Neglect‐induced pseudo‐thrombotic thrombocytopenic purpura due to vitamin B12 deficiency

Although thrombotic thrombocytopenic purpura (TTP) is rare, early diagnosis and treatment are important for decreasing the mortality rate. Acquired vitamin B12 deficiency is frequently overlooked because of its rarity in developed countries, particularly in children and adolescents. The hematological changes in vitamin B12 deficiency present as megaloblastic anemia, increased lactate dehydrogenase, vasoconstriction, increased platelet aggregation, and abnormal activation of the coagulation followed by microangiopathy as well as neutropenia and thrombocytopenia. We report herein the case of a 15‐year‐old girl who had been neglected, which might have caused pseudo‐TTP through malnutrition, particularly vitamin B12 deficiency. When we encounter cases of TTP in children, clinicians must be aware of the possibility of malnutrition, particularly with vitamin B12 deficiency, even in developed countries, and investigate the cause of malnutrition including neglect.     

Microscopic observation of chemical modification in sections using scanning acoustic microscopy

A scanning acoustic microscope (SAM) calculates the speed of sound (SOS) through tissues and plots the data on the screen to form images. Hard tissues result in greater SOS; based on these differences in tissue properties regarding SOS, SAM can provide data on tissue elasticity. The present study evaluated whether tissue modifications, such as formalin fixation, periodic acid‐Schiff (PAS) reactions and protein degradation, changed the acoustic properties of the tissues and whether SAM could be a useful tool for following chemical changes in sections. The fixation process was observable by the increased SOS. During the PAS reaction, the glycosylation of tissues was characterized by an increased SOS. Mucous or glycogen distribution was visualized and was found to be statistically comparable among lesions and states. Protease digestion by pepsin led to a decreased SOS. Tissue sensitivity to proteases varied due to the stage, cause and duration of inflammation or ageing. Changes in acoustic properties were more sensitive than those in optical histology. SAM facilitates the visualisation of the time course or distribution of chemical modifications in tissue sections, thus aiding their comparison among tissues. SAM may be an effective tool for studying changes such as protein cross‐linkage, tissue repair and ageing.     

Electrochemical oxidation of As(iii) on Pd immobilized Pt surface: kinetics and sensing performance

Pd nanoparticles were electrochemically immobilized on a Pt surface in the presence of sodium dodecyl sulfate (SDS) molecules to study the electrokinetics of arsenite oxidation reactions and the corresponding sensing activities. The X-ray photoelectron spectroscopy (XPS) analysis showed that on the Pt surface, Pd atoms exist as adatoms and the contents of Pd(0) and Pd(ii) were 75.72 and 24.28 at%, respectively, and the particle sizes were in the range of 61–145 nm. The experimental results revealed that the catalytic efficiency as well as the charge transfer resistance (at the redox potential of the Fe(ii)/Fe(iii) couple) increased in the order of Pt < Pt–Pd < Pt–Pd_sds. A Pt–Pd_sds electrode exhibited an open circuit potential (OCP) of 0.65 V in acidic conditions; however, when 50.0 mM NaAsO₂ was present, the OCP value shifted to 0.42 V. It has been projected that the As(iii) oxidation proceeds using a sequential pathway: As(iii) → As(iv) → As(v). After optimization of the square wave voltammetric data, the limits of detection of As(iii) were obtained as 1.3 μg L⁻¹ and 0.2 μg L⁻¹ when the surface modification of the Pt surface was executed with Pd particles in the absence and presence of the SDS surfactant, respectively. Finally, real samples were analyzed with excellent recovery performance.

Amplification of true surface area can be improved when Pd particles are deposited on a substrate in the presence of sodium dodecyl sulfate (SDS) surfactant. In acidic medium, As(iii) undergoes a two-step oxidation process.     

Oral vancomycin versus metronidazole for the treatment of Clostridioides difficile infection: Meta-analysis of randomized controlled trials

At present, vancomycin (VCM) and metronidazole (MNZ) are used for the first-line standard treatment of Clostridioides difficile infection (CDI). However, their differential use has not been sufficiently investigated. In this study, a meta-analysis on differences in the efficacy for CDI between VCM and MNZ was performed. Reports of randomized controlled studies using VCM or MNZ to treat CDI were surveyed. Meta-analysis was performed using the Mantel-Haenszel method and random-effects model, and the risk ratio and 95% confidence interval were calculated. Excluding overlapping reports, 1043 reports were extracted and 5 randomized controlled studies were extracted. There was no difference in therapeutic effects for CDI between VCM and MNZ (RR = 1.08, 95% CI (0.99–1.17), p = 0.09, I² = 37%). On subgroup analysis by the severity, there was no difference in the clinical effects for CDI between VCM and MNZ in non-severe cases (risk ratio: 1.09, 95% confidence interval: 1.00–1.19, p = 0.06), but the clinical effects of VCM were significantly higher than those of MNZ in severe cases (risk ratio: 1.19, 95% confidence interval: 1.02–1.39, p = 0.03). No significant difference was noted in the recurrence rate, incidence of adverse event, time to exhibit therapeutic effects, or judgment of the bacteriological effects. As the therapeutic effects of VCM were superior in severe CDI cases, VCM should be considered first in severe cases.     

Successful transcatheter arterial antimicrobial and steroid therapy for refractory liver abscess in chronic granulomatous disease: A case report and review of literature

Hepatic abscess in chronic granulomatous disease (CGD) is very refractory and frequently requires multiple surgeries with frequent morbidities. Although surgical interventions are often required, patients are often not able to have surgery for various reasons. We present the case of a 21-year-old man with recurrent hepatic abscess in CGD. We could not provide surgical interventions due to the lack of a fluid cavity and the patient's refusal, and therefore we administered transcatheter arterial antimicrobial and steroid therapy. He did not have any exacerbation for more than 18 months after the final transcatheter treatment. This is the first reported case of successful transcatheter arterial antimicrobial and steroid therapy for refractory hepatic abscess in CGD. Although the patient's burden and medical cost were not inconsequential, this case shows that the transcatheter arterial antimicrobial and steroid therapy may be a treatment option for patients who are not candidates for surgical interventions.