Search Results (11)

Background/Objectives: Nisin A, an antimicrobial peptide produced by Lactococcus lactis, primarily shows antimicrobial activity against Gram-positive bacteria, with efficacy increased when used in combination with an antimicrobial drug. On the other hand, oral candidiasis, caused by Candida, occurs in immunocompromised patients and requires antifungal therapy. However, antifungal drug-resistant Candida strains are increasing worldwide, leading to serious problems. Methods: To examine the effects of nisin A against Candida species, we investigated the combined effects of nisin A and antifungal drugs on the growth and viability of Candida strains. Results: While nisin A alone had no antifungal effect, together with amphotericin (AMPH), it showed synergistic effects towards C. albicans, as well as the non-albican strains C. glabrata, C tropicalis, and C. parapsilosis in checkerboard assay results. Furthermore, nisin A with miconazole (MCZ) or micafungin (MCFG) demonstrated a synergistic or additive effect on those strains. Cell viability assay results showed that nisin A enhanced the fungicidal activity of AMPH against both C. albicans and C. glabrata. Biofilm reduction assays showed that nisin A with AMPH, MCZ, or MCFG inhibited biofilm activity against C. albicans as compared with each antifungal drug alone. Finally, nisin A with AMPH, MCZ, or MCFG resulted in a reduced minimum inhibitory concentration of those antifungal drugs against clinically isolated C. albicans and C. glabrata.Conclusions: When used in combination with nisin A, the antifungal drug dosage can be lowered, thus helping to prevent adverse side effects and the emergence of drug-resistant oral Candida species. Full article

Immune checkpoint inhibitor (ICI)-induced liver injury (LI) is a common adverse event, but the clinical characteristics based on the classification of hepatocellular injury and cholestatic types are not fully evaluated. This study aims to analyze risk factors and histological findings in relation to the classification of ICI-induced LI. In total, 254 ICI-induced LI patients among 1086 treated with ICIs between September 2014 and March 2022 were classified according to the diagnostic criteria for drug-induced LI (DILI), and their risk factors and outcomes were evaluated. Kaplan–Meier analyses showed that overall survival in patients with hepatocellular-injury-type LI was significantly longer than others (p < 0.05). Regarding pre-treatment factors, the lymphocyte count was significantly higher in patients with ICI-induced LI, especially in hepatocellular-injury-type LI. Gamma glutamyl transferase (γGTP) and alkaline phosphatase (ALP) were also significantly lower in patients with ICI-induced LI (p < 0.05). Multivariate analyses revealed that malignant melanoma, high lymphocyte count, and low ALP levels were extracted as factors contributing to hepatocellular-injury-type LI. The histological findings among 37 patients diagnosed as ICI-induced LI via liver biopsy also revealed that the spotty/focal necrosis was significantly frequent in hepatocellular-injury-type LI, whereas ductular reactions were frequently observed in cholestatic-type LI. It is suggested that the histological inflammation pattern in patients with LI is closely correlated with the type of DILI. Full article

The incidence of oral cancer has recently been increasing worldwide, particularly among young individuals and women. The primary risk factors for head and neck cancers, including oral and pharyngeal cancers, are smoking, alcohol consumption, poor oral hygiene, and repeated exposure to mechanical stimuli. However, approximately one-third of the patients with oral and pharyngeal cancers are neither smokers nor drinkers, which points to the existence of other mechanisms. Recently, human microbes have been linked to various diseases, including cancer. Oral pathogens, especially periodontal pathobionts, are reported to play a role in the development of colon and other types of cancer. In this study, we employed a series of bioinformatics analyses to pinpoint Fusobacterium nucleatum as the predominant oral bacterial species in oral and pharyngeal cancer tissue samples. We successfully isolated Fn. polymorphum from the saliva of patients with oral cancer and demonstrated that Fn. polymorphum indeed promoted oral squamous cell carcinoma development by activating YAP in a mouse tongue cancer model. Our research offers scientific evidence for the role of the oral microbiome in oral cancer progression and provides insights that would help in devising preventative strategies against oral cancer, potentially by altering oral bacterial profiles. Full article

A total of 137 HCC patients treated with atezolizumab plus bevacizumab from October 2020 to September 2022 were enrolled. The median overall survival (OS) and progression-free survival (PFS) from the beginning of atezolizumab plus bevacizumab were 21.1 months (range, 18.8 months–not reached) and 10.5 months (range, 8.2–12.1 months), respectively. Fifty patients were diagnosed with progressive disease after atezolizumab plus bevacizumab. Of this group, 24 patients were administered lenvatinib, and the median OS and PFS from the beginning of lenvatinib were 15.3 months (range, 10.5 months–not reached) and 4.0 months (range, 2.5–6.4 months), respectively. The objective response rates based on the response evaluation criteria in solid tumors (RECISTs) criteria version 1.1 and modified RECISTs were 33.3% and 54.2%, respectively. There was no significant difference in the median serum alpha-fetoprotein level between before and after lenvatinib. In the multivariate analysis, Child–Pugh class A (hazard ratio 0.02, 95% confidence interval (CI) 0.02–0.76, p = 0.02) and intrahepatic tumor occupancy rate < 50% (hazard ratio < 0.01, 95% CI 0.003–0.35, p < 0.01) were the significant factors for OS. There were some frequent adverse events (AEs) in patients treated with lenvatinib such as hypertension, fatigue, anorexia, proteinuria, and so on, but none directly caused death. In conclusion, lenvatinib after atezolizumab plus bevacizumab for unresectable HCC should be considered an effective treatment option. Full article

Atezolizumab plus bevacizumab combination therapy (Atezo + Beva) is currently positioned as the first-line therapy for unresectable hepatocellular carcinoma (u-HCC). It may be difficult to decide whether to continue this treatment if radiological response is assessed as stable disease (SD). Therefore, the relationship between radiological response and prognosis was analyzed. A total of 109 patients with u-HCC and Child–Pugh Score of 5–7 received this treatment. Radiological response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST at the first and second evaluations. Of SD patients (n = 71) at the first RECIST evaluation, partial response, SD, and progressive disease (PD) were seen in 10, 55, and 6 patients, respectively, at the second evaluation. On multivariate analysis, in patients with SD at the first RECIST evaluation, a 25% or greater increase in the alpha-fetoprotein (AFP) value from initiation of treatment (odds ratio, 7.38; p = 0.037) was the independent factor for PD at the second evaluation. In patients with SD (n = 59) at the second RECIST evaluation, decreased AFP from initiation of treatment (hazard ratio, 0.46; p = 0.022) was the independent factor related to progression-free survival on multivariate analysis. AFP trends could help decide the Atezo + Beva treatment strategy. Full article

The occurrence of sexual dysfunction in couples after childbirth is well recognized, yet sexual satisfaction in couples with young children (CYC) has received little research attention. This study sought to enable this construct to be measured by developing and validating a Japanese version of the Index of Sexual Satisfaction (ISS) in CYC. Data were collected using a self-administered questionnaire. Scale construction and validation were conducted using two independent samples drawn from 316 mothers and 272 fathers in Japan who had at least one child aged 6 or younger. Two underlying factors were identified using exploratory factor analysis: sexual satisfaction, measured by eight items, and sexual dissatisfaction, measured by three. Polychoric ordinal alpha coefficients indicated the reliability of the resulting scale (overall: 0.89, factor 1: 0.89, factor 2: 0.78), and confirmatory factor analysis and testing supported its validity, showing good model fit (goodness of fit index: 0.984, root mean square residual: 0.062) and satisfactory composite reliability (scale: 0.93, factor 1: 0.90, factor 2: 0.81) and average variance extracted (all ≥0.5). The Japanese version of the ISS for Couples with Young Children will be useful for investigating sexual satisfaction, which is essential to marital stability. Full article

Serum C-reactive protein (CRP) is known to be a biomarker for systemic inflammatory reactions. In the present study, we sought to measure the predictive value of serum CRP level for metastatic renal cell carcinoma (mRCC) treated with first-line ipilimumab and nivolumab using our real-world clinical dataset including non-clear cell RCC (nccRCC). The clinical record of patients who underwent the first-line ipilimumab plus nivolumab treatment for mRCC including ccRCC and nccRCC from 2018 to 2021 was retrospectively analyzed. All patients were diagnosed with either intermediate or poor-risk group defined by IMCD (international metastatic RCC database consortium). In total, 74 patients were involved. The median age was 68 years and 24 (32.4%) patients deceased during the follow-up. Forty-five (61%) and 29 (39%) patients were classified into intermediate and poor-risk groups. The one-year overall survival (OS) rate and objective response rate were 65% and 41% for all 74 mRCC patients, respectively. The receiver operating characteristic curve identified 1.0 mg/dL of serum CRP level as an ideal cut-off for predicting overall survival (OS). Serum CRP > 1.0 mg/dL and nccRCC were the independent predictors for OS in 74 mRCC patients. OS for patients with CRP > 1 mg/dL was significantly shorter than those with CRP < 1 mg/dL in both ccRCC (58 patient: p = 0.009) and nccRCC (16 patients: p = 0.008). The present study indicated that serum CRP level is a prognostic indicator for OS in both ccRCC and nccRCC patients treated with the first-line ipilimumab plus nivolumab treatment. Full article

Background: The coronavirus disease 2019 (COVID-19) pandemic has restricted people’s activities and necessitated the discontinuation of cardiac rehabilitation (CR) programs for outpatients. In our hospital, CR for outpatients had to be discontinued for 3 months. We investigated the influence of this discontinuation of CR on physical activity, body composition, and dietary intake in cardiovascular outpatients. Method: Seventy-eight outpatients who restarted CR were investigated. We measured body composition, balance test, stage of locomotive syndrome, and food frequency questionnaire (FFQ) results at restart and 3 months later. We also investigated the results of examination that were obtained before discontinuation. Results: With regard to baseline characteristics, the percentage of male was 62.7% (n = 49), and average age and body mass index were 74.1 ± 8.5 years and 24.9 ± 7.0 kg/m², respectively. Stage of locomotive syndrome and the results of FFQ did not change significantly. The one-leg standing time with eyes open test significantly worsened at restart (p < 0.001) and significantly improved 3 months later (p = 0.007). With regard to body composition, all limb muscle masses were decreased at restart and decreased even further 3 months later. Conclusions: Discontinuation of CR influenced standing balance and limb muscle mass. While the restart of CR may improve a patient’s balance, more time is required for additional daily physical activities. The recent pandemic-related interruption of CR should inspire the development of alternatives that could ensure the continuity of CR in a future crisis. Full article

Flow injection analysis–tandem mass spectrometry (FIA-TMS) has been applied in a first-tier test of newborn screening (NBS). Although isovalerylcarnitine (i-C5), which is a diagnostic indicator of isovaleric acidemia (IVA), is isobaric with pivaloylcarnitine (p-C5), 2-methylbutyrylcarnitine, and n-valerylcarnitine, these isomers cannot be distinguished by the FIA-TMS. There are many reports of false positives derived from p-C5 due to the use of pivalate-conjugated antibiotics. In this study, we developed a new FIA-TMS method to distinguish i-C5 and p-C5. We found that the intensity ratio of product ions for i-C5 and p-C5 was different in a certain range even under the same analytical conditions. The product ions with the most distinct differences in ionic intensity between the isomers and the collision energies that produce them were determined to be m/z 246.2 > 187.1 and −15 V, respectively. In addition to the quantification ion, a reference ion was defined, and the similarity of the i-C5 and p-C5 reference ion ratios (i-C5 score and p-C5 score, respectively) were used to estimate which isomer (i-C5 and p-C5) was responsible for elevated C5 acylcarnitine in dried blood spots (DBSs). As a result of analyses of 11 DBS samples derived from pivalate-conjugated antibiotics and four DBS samples from IVA patients using our method, it was found that our method was able to correctly determine the type of C5-acylcarnitine (i-C5 or p-C5) in the DBS samples. Implementation of this new FIA-TMS method into the current NBS protocol will allow for a reduction in false positives in IVA. Full article

L-carnitine (LC) supplementation improves cardiac function in hemodialysis (HD) patients. However, whether reducing LC supplementation affects carnitine kinetics and cardiac function in HD patients treated with LC remains unclear. Fifty-nine HD patients previously treated with intravenous LC 1000 mg per HD session (three times weekly) were allocated to three groups: LC injection three times weekly, once weekly, and placebo, and prospectively followed up for six months. Carnitine fractions were assessed by enzyme cycling methods. Plasma and red blood cell (RBC) acylcarnitines were profiled using tandem mass spectrometry. Cardiac function was evaluated using echocardiography and plasma B-type natriuretic peptide (BNP) levels. Reducing LC administration to once weekly significantly decreased plasma carnitine fractions and RBC-free carnitine levels during the study period, which were further decreased in the placebo group (p < 0.001). Plasma BNP levels were significantly elevated in the placebo group (p = 0.03). Furthermore, changes in RBC (C16 + C18:1)/C2 acylcarnitine ratio were positively correlated with changes in plasma BNP levels (β = 0.389, p = 0.005). Reducing LC administration for six months significantly decreased both plasma and RBC carnitine levels, while the full termination of LC increased plasma BNP levels; however, it did not influence cardiac function in HD patients. Full article

We conducted a double-blind randomized controlled study of elderly individuals in a nursing home to investigate the effect of the consumption of jelly containing sea cucumber on their oral Candida load. The jelly contained a hydrolysate of the sea cucumber Stichopus japonicus, which contained triterpene glycosides called holotoxins. The holotoxins worked as a fungicide, and their minimum inhibitory concentrations for Candida albicans were 7 µg/mL. Eight individuals in the nursing home took the sea cucumber jelly for a week and their oral Candida were counted before and after the intervention. Nine individuals took a control jelly without S. japonicus. The sea cucumber jelly showed inhibitory effects on the oral Candida. Thus, daily consumption of the S. japonicus jelly has the potential to reduce the oral Candida load in the elderly in nursing homes. Full article