Glucose-lowering efficacy of Xultophy with low doses by FreeStyle Libre as continuous glucose monitoring (CGM)

The daily profile of blood glucose can be detected by continuous glucose monitoring (CGM) using FreeStyle Libre. The case was a 51-year-old female with type 2 diabetes mellitus (T2DM) for uncontrolled glucose variability as HbA1c 10.3%. During CGM measurement, diabetic treatment was changed from multiple daily insulin injections (MDI) to Xultophy (insulin degludec and liraglutide). Xultophy starting from 10 to 18 doses has brought the improvement of glucose variability, such as decreased pre-prandial glucose from 268 mg/dL to 101 mg/dL. Consequently, detailed data of glucose variability on Xultophy using CGM would be beneficial and become some reference for further clinical diabetic research

Assessment of skin inflammation using near-infrared Raman spectroscopy combined with artificial intelligence analysis in an animal model

Raman spectroscopy is a powerful method for estimating the molecular structure of a target that can be adapted for biomedical analysis given its non-destructive nature. Inflammatory skin diseases impair the skin’s barrier function and interfere with the patient’s quality of life. There are limited methods for non-invasive and objective assessment of skin inflammation. We examined whether Raman spectroscopy can be used to predict skin inflammation with high sensitivity and specificity when combined with artificial intelligence (AI) analysis. Inflammation was chemically induced in mouse ears, and Raman spectra induced by a 785 nm laser were recorded. A principal component (PC) analysis of the Raman spectra was performed to extract PCs with the highest percentage of variance and to estimate the statistical score. The accuracy in predicting inflammation based on the Raman spectra with or without AI analysis was assessed using receiver operating characteristic (ROC) curves. We observed some typical changes in the Raman spectra upon skin inflammation, which may have resulted from vasodilation and interstitial oedema. The estimated statistical scores based on spectral changes correlated with the histopathological changes in the skin. The ROC curve based on PC2, which appeared to include some spectral features, revealed a maximum accuracy rate of 80.0% with an area under the curve (AUC) of 0.864. The AI analysis improved the accuracy rate to 93.1% with an AUC of 0.972. The current findings demonstrate that the combination of Raman spectroscopy with near-infrared excitation and AI analysis can provide highly accurate information on the pathology of skin inflammation

Pretreatment glasgow prognostic score predicts survival among patients administered first-line atezolizumab plus carboplatin and etoposide for small cell lung cancer

BackgroundThere are no established predictive biomarkers for the effectiveness of first-line atezolizumab plus carboplatin and etoposide therapy in patients with small-cell lung cancer (SCLC). Therefore, the current study aimed to investigate whether the Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), and body mass index (BMI) can predict the effectiveness of first-line atezolizumab plus carboplatin and etoposide therapy in patients with extensive-disease SCLC.MethodsWe reviewed data from 84 patients who received first-line atezolizumab plus carboplatin and etoposide therapy for SCLC at nine Japanese institutions between August 2019 and May 2021. Further, we evaluated the prognostic value of the GPS, NLR, and BMI. The Kaplan–Meier and Cox proportional hazard models were used to examine differences in progression-free survival (PFS) and overall survival (OS). Moreover, the GPS, NLR, and BMI consisted of C-reactive protein and albumin concentrations, neutrophil and lymphocyte counts, and body weight and height, respectively.ResultsThe response rate was 72.6% (95% confidence interval: 63.0–82.1%). The median PFS and OS from the initiation of treatment were 5.4 (95% CI: 4.9–5.9) months and 15.4 (95% CI: 11.4–16.8) months, respectively. The GPS independently predicted the effectiveness of first-line atezolizumab plus carboplatin and etoposide treatment, as a favorable GPS (GPS 0–1) was correlated with significantly better PFS and OS rates compared to a poor GPS (GPS 2) (PFS: 5.8 vs. 3.8 months, p = 0.0005; OS: 16.5 vs. 8.4 months, p<0.0001).ConclusionsThis is the first analysis to evaluate the association between the GPS, NLR, and BMI and the treatment effectiveness of survival among patients receiving first-line atezolizumab plus carboplatin and etoposide therapy for SCLC. Among patients receiving this treatment for SCLC, GPS was significantly associated with the PFS and OS rates, suggesting that GPS might be useful for evaluating therapeutic outcomes in these patients

The C. elegans Opa1 Homologue EAT-3 Is Essential for Resistance to Free Radicals

The C. elegans eat-3 gene encodes a mitochondrial dynamin family member homologous to Opa1 in humans and Mgm1 in yeast. We find that mutations in the C. elegans eat-3 locus cause mitochondria to fragment in agreement with the mutant phenotypes observed in yeast and mammalian cells. Electron microscopy shows that the matrices of fragmented mitochondria in eat-3 mutants are divided by inner membrane septae, suggestive of a specific defect in fusion of the mitochondrial inner membrane. In addition, we find that C. elegans eat-3 mutant animals are smaller, grow slower, and have smaller broodsizes than C. elegans mutants with defects in other mitochondrial fission and fusion proteins. Although mammalian Opa1 is antiapoptotic, mutations in the canonical C. elegans cell death genes ced-3 and ced-4 do not suppress the slow growth and small broodsize phenotypes of eat-3 mutants. Instead, the phenotypes of eat-3 mutants are consistent with defects in oxidative phosphorylation. Moreover, eat-3 mutants are hypersensitive to paraquat, which promotes damage by free radicals, and they are sensitive to loss of the mitochondrial superoxide dismutase sod-2. We conclude that free radicals contribute to the pathology of C. elegans eat-3 mutants

The relationship between atopic dermatitis and indoor environmental factors : a cross-sectional study among Japanese elementary school children

Objectives: This study aimed to determine that home environmental factors were associated with atopic dermatitis in Japanese elementary school children. Methods: In this cross-sectional study, a total of 4,254 children in 12 public elementary schools in Sapporo city in Hokkaido, Japan were examined. Atopic dermatitis was defined using the International Study of Asthma and Allergies in Childhood questionnaire. The questionnaires also contained 14 questions about the child’s home environment. To obtain multivariate-adjusted ORs for atopic dermatitis in relation to the home environment, we controlled for possible confounders including gender, school grade, parental history of allergies, number of siblings, and whether the child was firstborn. The study participants were then divided into two groups according to gender, and a stratified analysis was performed to obtain adjusted ORs for atopic dermatitis in relation to the home environment. Results: The prevalence of atopic dermatitis in our sample was 16.7 %. Using fully adjusted models, the risk factors for atopic dermatitis were found to be the household use of a non-electric heating system without a ventilation duct to the outside (compared to the use of an electric heating system), having visible mould in the house, having a mouldy odour in the house, and condensation on the windowpanes in the house odds ratios (OR 1.25–1.54). In our stratified analysis, having visible mould and having a mouldy odour in the house were relevantly found to be risk factors for boys (OR 1.28–1.64). However, these associations were not found among girls. Conclusions: To improve children’s health, further study is needed to corroborate the findings

Comparisons of urinary phthalate metabolites and daily phthalate intakes among Japanese families

We measured urinary phthalate metabolites, including di-n-butyl phthalate (DnBP), di-isobutyl phthalate, benzyl butyl phthalate (BBzP), and di(2-ethylhexyl) phthalate (DEHP), from 178 school-aged children and their 284 family members using gas chromatography-mass spectrometry, and we calculated daily phthalate intakes. The highest median levels of phthalate metabolites were for mono-isobutyl phthalate in all participants except schoolchildren, where the highest levels were for mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP). Comparing the schoolchildren with their parents, the schoolchildren had significantly higher urinary metabolites for MEOHP, mono-(2-ethyl-5-carboxypentyl) phthalate, and EDEHP. Regarding daily intakes, the schoolchildren had significantly higher daily intakes of DnBP, BBzP, and EDEHP. All phthalate metabolite and sums of metabolite levels in the schoolchildren were positively correlated with their mothers' levels, except for MEHP, whereas fathers were less correlated with their children. The DEHP intake in this study was higher than that of most other studies. Moreover, 10% of the children and 3% of the adults exceeded the Reference Dose (RfD) value (20 mu g/kg/day) of the U.S. Environmental Protection Agency, which indicates that it is important to focus on children's DEHP exposure because the children exceeded the RID more than adults among the same families who shared similar exposure sources. Our results will contribute to considerations of the regulations for some phthalates and the actual phthalate exposure levels in the Japanese population. (C) 2015 Elsevier GmbH. All rights reserved

Association of Mechanical Ventilation and Flue Use in Heaters With Asthma Symptoms in Japanese Schoolchildren : A Cross-Sectional Study in Sapporo, Japan

Background: Use of fuel heaters is associated with childhood asthma. However, no studies have evaluated the associations of flue use and mechanical ventilation (ventilation) with asthma symptoms in schoolchildren. Methods: This cross-sectional study investigated schoolchildren in grades 1 through 6 (age 6-12 years) in Sapporo, Japan. From November 2008 through January 2009, parents completed questionnaires regarding their home environment and their children's asthma symptoms. Results: In total, 4445 (69.5%) parents of 6393 children returned the questionnaire. After excluding incomplete responses, data on 3874 children (60.6%) were analyzed. The prevalence of current asthma symptoms and ever asthma symptoms were 12.8% and 30.9%, respectively. As compared with electric heaters, current asthma symptoms was associated with use of flued heaters without ventilation (OR = 1.62; 95% CI, 1.03-2.64) and unflued heaters with ventilation (OR = 1.77; 95% CI, 1.09-2.95) or without ventilation (OR = 2.23; 95% CI, 1.31-3.85). Regardless of dampness, unflued heaters were significantly associated with current asthma symptoms in the presence and absence of ventilation. Conclusions: Use of unflued heaters was associated with current asthma symptoms, regardless of dampness. In particular, the prevalence of current asthma symptoms was higher in the absence of ventilation than in the presence of ventilation. Ever asthma symptoms was only associated with use of unflued heaters without ventilation. Consequently, use of fuel heaters, especially those that have no flue or ventilation, deserves attention, as their use might be associated with childhood asthma symptoms

Detection and intake assessment of organophosphate flame retardants in house dust in Japanese dwellings

The demand for phosphorus flame retardants (PFRs) has recently increased as an alternative to polybrominated diphenyl ether (PBDE). PFRs have been detected in house dust, but little is known about the concentrations of PFRs in private homes and the effects on human health. We measured the levels of 10 PFRs in indoor floor dust and upper surface dust from 128 Japanese dwellings of families with children in elementary school. The median (min–max) concentrations (μg/g) of PFRs were as follows: tris(2-butoxyethyl) phosphate (TBOEP), 30.88 (< 0.61–936.65); tris(2-chloro-iso-propyl) phosphate (TCIPP), 0.74 (< 0.56–392.52); and triphenyl phosphate (TPHP), 0.87 (< 0.80–23.35). These values exceeded 50% detection rates, and the rates are median over the LOD in floor dust. The concentrations (μg/g) of TBOEP 26.55 (< 0.61–1933.24), TCIPP 2.23 (< 0.56–621.23), TPHP 3.13 (< 0.80–27.47), tris(2-chloroethyl) phosphate (TCEP) 1.17 (< 0.65–92.22), and tributyl phosphate (TNBP) 0.74 (< 0.36–60.64) exceeded 50% detection rates in the upper surface dust. A significant positive correlation (P < 0.05) between the concentrations of TCIPP and TBOEP was shown in floor dust and upper surface dust (n = 48). Estimated median and 95th percentile daily intake was calculated for toddlers and elementary school children and was compared with reference dose values (RfD) from the literature. For TBOEP, the estimated 95th percentile intake from floor dust was 14% of RfD for toddlers and 4% for school children. The estimated intake from upper surface dust was somewhat lower. Estimated median intake of TBOEP and median intake for the other PFRs were less than 1% of the RfD. TBOEP, TCIPP and TPHP were the main PFRs in the dust. The median levels of PFRs are well below the RfD values