Noninvasive graft monitoring using donor-derived cell-free DNA in Japanese liver transplantation.

AIM: To evaluate the use of donor-derived cell-free DNA (dd-cfDNA) in diagnosing graft injuries in Japanese liver transplantation (LTx), including family-related living donors. METHODS: A total of 321 samples from 10 newly operated LTx recipients were collected to monitor the early dynamics of dd-cfDNA levels after LTx. Fifty-five samples from 55 recipients were collected during protocol biopsies (PB), whereas 36 samples from 27 recipients were collected during event biopsies, consisting of 11 biopsy-proven acute rejection (AR), 20 acute dysfunctions without rejection (ADWR), and 5 chronic rejections. The levels of dd-cfDNA were quantified using a next-generation sequencer based on single nucleotide polymorphisms. RESULTS: The dd-cfDNA levels were elevated significantly after LTx, followed by a rapid decline to the baseline in patients without graft injury within 30 days post-LTx. The dd-cfDNA levels were significantly higher in the 11 samples obtained during AR than those obtained during PB (p < 0.0001), which decreased promptly after treatment. The receiver operator characteristic curve analysis of diagnostic ability yielded areas under the curve of 0.975 and 0.897 for AR (rejection activity index [RAI] ≥3) versus PB and versus non-AR (ADWR + PB). The dd-cfDNA levels during AR were elevated earlier and correlated more strongly with the RAI (r = 0.740) than aspartate aminotransferase/alanine aminotransferase. The dd-cfDNA levels were neither associated with graft fibrosis based on histology nor the status of donor-specific antibodies in PB samples. CONCLUSIONS: Donor-derived cell-free DNA serves as a sensitive biomarker for detecting graft injuries in LTx. Further large-scale cohort studies are warranted to optimize its use in differentiating various post-LTx etiologies.

Application of omics technologies in cariology research: A critical review with bibliometric analysis.

OBJECTIVES: To review the application of omics technologies in the field of cariology research and provide critical insights into the emerging opportunities and challenges. DATA & SOURCES: Publications on the application of omics technologies in cariology research up to December 2022 were sourced from online databases, including PubMed, Web of Science and Scopus. Two independent reviewers assessed the relevance of the publications to the objective of this review. STUDY SELECTION: Studies that employed omics technologies to investigate dental caries were selected from the initial pool of identified publications. A total of 922 publications with one or more omics technologies adopted were included for comprehensive bibliographic analysis. (Meta)genomics (676/922, 73 %) is the predominant omics technology applied for cariology research in the included studies. Other applied omics technologies are metabolomics (108/922, 12 %), proteomics (105/922, 11 %), and transcriptomics (76/922, 8 %). CONCLUSION: This study identified an emerging trend in the application of multiple omics technologies in cariology research. Omics technologies possess significant potential in developing strategies for the detection, staging evaluation, risk assessment, prevention, and management of dental caries. Despite the numerous challenges that lie ahead, the integration of multi-omics data obtained from individual biological samples, in conjunction with artificial intelligence technology, may offer potential avenues for further exploration in caries research. CLINICAL SIGNIFICANCE: This review presented a comprehensive overview of the application of omics technologies in cariology research and discussed the advantages and challenges of using these methods to detect, assess, predict, prevent, and treat dental caries. It contributes to steering research for improved understanding of dental caries and advancing clinical translation of cariology research outcomes.

Historical Cohort Study of Congenital Isolated Hypoganglionosis of the Intestine: Determining the Best Surgical Interventions.

No standard diagnostic method or surgical treatment for congenital isolated hypoganglionosis (CIHG) has been established. This study aimed to analyze the clinical outcomes of patients with CIHG and identify the best surgical interventions provided thus far. Data on surgical interventions in 19 patients were collected between 1992 and 2020, including the type of enterostomy, type of revision, and length of the intestines. Ganglion cells in the myenteric plexus were enumerated using Hu C/D staining. The ratio of the length of the small intestine to its height was defined as the intestinal ratio (IR). The outcomes were assessed using the stoma output, growth parameters including the body mass index (BMI), and parenteral nutrition (PN) dependency. All patients required a diverting enterostomy. The IR ranged from 0.51 to 1.75 after multiple non-transplant surgeries. The stoma types were tube-stoma, end-stoma, Santulli-type, and Bishop-Koop (BK)-type. Patients with Santulli- or BK-type stomas had better BMIs and less PN dependency in terms of volume than those with end-stomas or tube-stomas. Two patients with BK-type stomas were off PN, and three who underwent an intestinal transplantation (Itx) achieved enteral autonomy. The management of CIHG involves a precise diagnosis using Hu C/D staining, neonatal enterostomy, and stoma revision using the adjusted IR and Itx if other treatments do not enable enteral autonomy.

Green Tea-Derived Catechins Suppress the Acid Productions of Streptococcus mutans and Enhance the Efficiency of Fluoride.

Green tea-derived catechins, which can be divided into galloylated (epicatechin gallate: ECG, epigallocatechin gallate: EGCG) and non-galloylated (catechin: C, epicatechin: EC, epigallocatechin: EGC) catechins, are considered to be the main contributors to the caries control potential of green tea. In this study, we intended to compare the antimicrobial effects of these representative green tea-derived catechins and their combined effects with fluoride on the acid production and aggregation of Streptococcus mutans. The effects of different catechins on the growth, aggregation and acid production of S. mutans, and the combined effect of catechins and potassium fluoride (2 mm at pH 7.0, 0.3 mm at pH 5.5) on S. mutans acid production were measured by anaerobic culture, turbidity changes due to aggregation, and pH-stat methods. Molecular docking simulations were also performed to investigate the interactions between catechins and membrane-embedded enzyme II complex (EIIC), a component of the phosphoenolpyruvate-dependent phosphotransferase system (sugar uptake-related enzyme). ECG or EGCG at 1 mg/mL significantly inhibited the growth of S. mutans, induced bacterial aggregation, and decreased glucose-induced acid production (p < 0.05). All catechins were able to bind to EIIC in silico, in the following order of affinity: EGCG, ECG, EGC, EC, and C. Furthermore, they enhanced the inhibitory effects of fluoride at pH 5.5 and significantly inhibited S. mutans acid production by 47.5-86.6% (p < 0.05). These results suggest that both galloylated and non-galloylated catechins exhibit antimicrobial activity, although the former type demonstrates stronger activity, and that the caries control effects of green tea may be due to the combined effects of multiple components, such as catechins and fluoride. The detailed mechanisms underlying these phenomena and the in vivo effect need to be explored further.

Abnormal distribution of fat tissue and its association with intestinal failure-associated liver disease in children and adolescents with long-time parenteral nutrition support: A case-control study.

BACKGROUND: Patients with intestinal failure (IF) often present with abnormal body composition characterized by high fat mass. However, the distribution of fat and its association with the development of IF-associated liver disease (IFALD) remain unclear. This study aims to investigate the body composition and its relationship with IFALD in older children and adolescents with IF. METHODS: This retrospective case-control study enrolled patients with IF receiving parenteral nutrition (PN) at Keio University Hospital who initiated PN before the age of 20 years (cases). The control group included patients with abdominal pain, with available computed tomography (CT) scan and anthropometric data. CT scan images of the third lumbar vertebra (L3) were used for body composition analysis and compared between the groups. Liver histology was compared with CT scan findings in IF patients who underwent biopsy. RESULTS: Nineteen IF patients and 124 control patients were included. To account for age distribution, 51 control patients were selected. The median skeletal muscle index was 33.9 (29.1-37.3) in the IF group and 42.1 (39.1-45.7) in the control group (P < 0.01). The median visceral adipose tissue index (VATI) was 9.6 (4.9-21.0) in the IF group and 4.6 (3.0-8.3) in the control group (P = 0.018). Among the 13 patients with IF who underwent liver biopsies, 11 (84.6%) had steatosis, and there was a tendency for fibrosis to correlate with VATI. CONCLUSION: Patients with IF exhibit low skeletal muscle mass and high visceral fat, which may be related to liver fibrosis. Routine monitoring of body composition is recommended.

Chapter 11: Future Perspectives in the Study of Dental Caries.

Dental caries is a disease that affects people of all ages since demineralization and remineralization of tooth surfaces occur in everyone's mouths, and caries lesions develop when there is an imbalance between demineralization and remineralization. In this way, teeth are exposed to a risk of caries. Prevention strategies aiming at "zero caries" and treatments aiming at "tooth recovery and regeneration" are the two main areas of caries research, and both basic and clinical research are required in these fields. The following future perspectives of caries research were identified: The disease concept of caries is undergoing rapid structural changes, as it will increasingly become a disease of all generations: Changes in our understanding of caries etiology (from cariogenic pathogens in the specific plaque hypothesis to the oral microbiome in the ecological plaque hypothesis) will alter the concept of caries-associated bacteria (from mutans streptococci to a group of bacteria with high acid-producing capacity and acid-tolerance or acidogenic/aciduric bacteria). In the field of prevention, more individualized, site-specific, and high-precision examinations for risk assessment and diagnostic methods, including genetic tests, will be developed, and advanced preventive, curative, and regenerative treatments will become possible. To achieve this, interdisciplinary, multidisciplinary, and transdisciplinary research are essential, and collaboration and fusion with other sciences, such as material science, engineering, food science, and nutritional science, are required. Furthermore, in order to put the results of such research into practice in society, it will be necessary to promote industry-academia collaborations; promote behavioral change through sociological approaches; and correct economic, informational, and educational inequalities. The sociological approach requires the coupling of epidemiology and data science as well as the validation of clinical applications, and artificial intelligence will play a powerful role in such analyses.

Potential benefit of rapid genetic testing for Pallister-Hall syndrome.

Pallister-Hall syndrome (PHS) is defined as a group of characteristic manifestations caused by a monoallelic GLI3 pathogenic variant. A two-month-old infant was referred to our institution because of undetermined sex. The infant had atypical genitalia with postaxial polysyndactyly, a hypothalamic mass, and an imperforate anus. We identified a known pathogenic variant of the GLI3 gene within one week and diagnosed the infant with PHS. The parents assigned the infant as male, considering the 46,XY karyotype, normal testosterone secretion, possible male identity, and the natural history of PHS. In infants with atypical genitalia and other malformations, such as polydactyly, a hypothalamic mass, or an imperforate anus, rapid GLI3 testing may provide information for planning lifelong management, including sex assignment.

Questionnaire survey on the satisfaction of SimEx dental education system.

Background/purpose: The SimEx is dental training system that applies new technology in a computerized dental simulator. The purpose of this study was to understand the usability satisfaction of the SimEx dental education and evaluation system by dental students and dentists at Tohoku University. Materials and methods: In this study, the Tohoku University IRB execution number was 2020-3-33. The number of subjects accepted was 59 at Tohoku University and divided into 4 groups based on years of clinical experience (Group A: 0 years; Group B: 1-2 years; Group C: 2-5 years; Group D: at least 5 years), and a total of 58 usability questionnaires were collected. Subjects completed the SimEx Usability Satisfaction Questionnaire after operating the SimEx (EPED Inc., Kaohsiung, Taiwan) course, which contained 16 questions. Results: Among the 58 questionnaires collected by Tohoku University, there were 19 undergraduate students (4th∼6th grade), 12 post-graduate students, 14 residents, and 13 dentists. Significant differences between Group A and Group B, and between Group A and Group D were found (P < 0.05). The same results were obtained for the "experience satisfaction index". In the items where significant differences were found, longer clinical experience tended to result in lower scores. Conclusion: From these results, we can conclude that the SimEx education and evaluation system facilitates students' self-learning, and this system is very useful for continued study and clinical skill training for dentists, especially for students and junior dentists with high usability satisfaction.

Glycolysis-Related Gene Analyses Indicate That DEPDC1 Promotes the Malignant Progression of Oral Squamous Cell Carcinoma via the WNT/ß-Catenin Signaling Pathway.

Increasing evidence suggests that aerobic glycolysis is related to the progression of oral squamous cell carcinoma (OSCC). Hence, we focused on glycolysis-related gene sets to screen for potential therapeutic targets for OSCC. The expression profiles of OSCC samples and normal controls were obtained from The Cancer Genome Atlas (TCGA). Then, the differentially expressed gene sets were selected from the official GSEA website following extraction of the differentially expressed core genes (DECGs). Subsequently, we tried to build a risk model on the basis of DECGs to predict the prognosis of OSCC patients via Cox regression analysis. Furthermore, crucial glycolysis-related genes were selected to explore their biological roles in OSCC. Two active glycolysis-related pathways were acquired and 66 DECGs were identified. Univariate Cox regression analysis showed that six genes, including HMMR, STC2, DDIT4, DEPDC1, SLC16A3, and AURKA, might be potential prognostic factors. Subsequently, a risk formula consisting of DEPDC1, DDIT4, and SLC16A3 was established on basis of the six molecules. Furthermore, DEPDC1 was proven to be related to advanced stage cancer and lymph node metastasis. Moreover, functional experiments suggested that DEPDC1 promoted the aerobic glycolysis, migration, and invasion of OSCC via the WNT/ß-catenin pathway. The risk score according to glycolysis-related gene expression might be an independent prognostic factor in OSCC. In addition, DEPDC1 was identified as playing a carcinogenic role in OSCC progression, suggesting that DEPDC1 might be a novel biomarker and therapeutic target for OSCC.

In situ detection of endogenous proteolytic activity and the effect of inhibitors on tooth root surface.

OBJECTIVES: The aim of this study was to clarify the distribution and activity of proteolytic enzymes and examine the inhibitory effects of various substances on this proteolytic activity on tooth root surfaces in situ. METHODS: Disk-shaped bovine tooth root samples were partly pretreated in acid solution (50 mM lactic acid buffer, pH 4.0) for 48 h. The fluorescence intensity of samples was detected with fluorescent substrate solution for collagenase and gelatinase using a stereoscopic fluorescence microscope for 60 min. The acid-pretreated and non-acid-pretreated root samples were treated with chlorhexidine (CHX), sodium fluoride (NaF), epigallocatechin gallate (EGCG), and calcium hydroxide (Ca(OH)2) for 10 min, and silver diamine fluoride (SDF) for 10, 30, and 60 s. These samples were immersed in the fluorescence substrate solution at pH 7.0, and the fluorescence intensity of samples was detected. The fluorescence intensity was calculated using analysis software. RESULTS: Gelatinase activity was detected in root samples. Gelatinase activity of the acid-pretreated side was significantly higher than that of the non-acid-pretreated side (1.63 times) at 60 min. CHX, EGCG, Ca(OH)2, and SDF decreased the gelatinase activity of root samples, while NaF had no effect. CONCLUSIONS: Gelatinase activity was detected from the root in situ and it was increased by acid-pretreatment. CHX, EGCG, Ca(OH)2, and SDF inhibited gelatinase activity. CLINICAL SIGNIFICANCE: Substances that inhibit proteolytic activity found in this research method will be useful for root caries prevention.

Combined Treatment with Fluoride and Antimicrobial Peptide GH12 Efficiently Controls Caries in vitro and in vivo.

Combining fluoride and antimicrobial agents enhances regulation of acid and exopolysaccharide production by biofilms. The combination also weakens the acidogenic and aciduric bacteria that contribute to caries, achieving stronger caries-controlling effects with lower concentrations of fluoride. In previous studies, antimicrobial peptide GH12 has been shown to inhibit lactic acid and exopolysaccharide synthesis in various cariogenic biofilm models, and reduce the proportion of acidogenic bacteria and Keyes caries scores in a rat caries model. The current study aimed to elucidate the effect of a combination of low concentrations of sodium fluoride (NaF) and GH12 and to determine the mechanism by which GH12/NaF combination controls caries. The GH12/NaF combination contained 8 mg/L GH12 and 250 ppm NaF. A rat caries model was built, and rat dental plaque was sampled and cultivated on bovine enamel slabs in vitro and subjected to short-term treatment (5 min, 3 times/day). The caries-controlling effects were evaluated using Keyes scoring and transverse microradiography. The results showed that the GH12/NaF combination significantly decreased the onset and development of dental caries, as well as mineral content loss and lesion depth in vitro (p < 0.05). For the caries-controlling mechanisms, 16S rRNA sequencing of in vivo dental plaque revealed that populations of commensal bacteria Rothia spp. and Streptococcus parasanguinis increased in the GH12/NaF group. In contrast, Veillonella, Lactobacillus, and Streptococcus mutans decreased. Furthermore, the GH12/NaF combination significantly reduced biomass, lactic acid, and exopolysaccharides production of in vitro biofilm (p < 0.05). Overall, fluoride and GH12 efficiently arrested caries development and demineralization by regulating the microbiota and suppressing acid and exopolysaccharide production in biofilms.

Investigation of drug resistance of caries-related streptococci to antimicrobial peptide GH12.

Dental caries is associated with caries-related streptococci and antimicrobial agents have been widely used for caries control, but troubled by antibiotic resistance. This study aimed to investigate the intrinsic and acquired resistance of caries-related streptococci to antimicrobial peptide GH12, which was proven promising for caries control, and preliminarily explore the phenotypic changes and whole genome of stable acquired resistant strains. In this study, susceptibility assays and resistance assays were performed, followed by stability assays of resistance, to evaluate the intrinsic resistance and the potential resistance of caries-related streptococci. Then, the phenotypic changes of the stable acquired resistant strain were explored. The whole genome of the resistant strain was sequenced and analyzed by second-generation and third-generation high-throughput sequencing technologies. Streptococcus gordonii and Streptococcus sanguinis were intrinsically resistant to GH12 compared to cariogenic Streptococcus mutans. Acquired GH12 resistance in one S. sanguinis and four S. mutans clinical strains was transient but stable in one S. mutans strain (COCC33-14). However, acquired resistance to daptomycin (DAP) and chlorhexidine in all strains was stable. Furthermore, the COCC33-14 showed cross-resistance to DAP and delayed growth rates and a lower population. However, no drug-resistant gene mutation was detected in this strain, but 6 new and 5 missing genes were found. Among them, annotation of one new gene (gene 1782|COCC33-14R) is related to the integral component of the membrane, and one missing gene rpsN is associated with the metabolism and growth of bacteria. The results indicate that stable resistant mutants of caries-related streptococci could hardly be selected by exposure to consecutive sublethal GH12, but the risk still existed. Resistance in COCC33-14R is mainly related to changes in the cell envelope.

Profiling of the microbiota of breast milk before and after feeding with an artificial nipple.

OBJECTIVES: Breast milk is a valuable and useful source of nutrition; however, surplus milk is routinely discarded for hygiene reasons despite an unclear scientific basis. Here, we profiled the microbiota of expressed breast milk before and after feeding with an artificial nipple and examined the bacterial survival in breast milk stored at 4 °C. METHODS: Eleven mother-baby pairs were included in the study. Samples of expressed breast milk were collected before and after feeding with an artificial nipple and examined both immediately (0 h) and after storage for 3 and 12 h at 4 °C. Each sample was inoculated onto a blood agar plate and incubated anaerobically and aerobically at 37 °C. Genomic DNA was extracted from individual bacterial colonies, which were identified by 16S rRNA gene sequencing. RESULTS: Before feeding, the bacterial counts at 0 and 12 h were (1.4 ± 1.6) × 105 colony-forming units (CFU)/mL and (1.4 ± 0.6) × 105 CFU/mL, respectively. Staphylococcus (47.7% and 41.9%, respectively), Cutibacterium (20.7% and 36.0%, respectively), and Streptococcus (16.1% and 6.6%, respectively) were identified among the samples. In contrast, after feeding, the bacterial counts at 0 and 12 h were (2.7 ± 1.7) × 105 CFU/mL and (2.1 ± 2.5) × 105 CFU/mL, respectively. Staphylococcus (30.1% and 37.4%, respectively), Cutibacterium (11.7% and 31.7%, respectively), and Streptococcus (41.5% and 25.2%, respectively), were identified among the samples. CONCLUSIONS: Bacteria were present in the breast milk before feeding. Although the main component of the microbiota shifted from Staphylococcus to Streptococcus species after feeding, these results suggest that surplus expressed breast milk may be preserved safely in a refrigerator for at least 12 h after feeding with an artificial nipple.

Microbiota profiles on the surface of non-woven fabric masks after wearing.

This study aimed to characterize commensal microbiota on the skin before and after wearing masks, and to characterize the microbiota on the surface of used masks after 1 week of drying. From the 13 human subjects (age range, 19-26 years), mean bacterial concentrations of (6.1 ± 11.0) × 105 and (1.0 ± 1.4) × 106 colony-forming units (CFU)/mL were recovered from the skin of the buccal areas wiped with a sterile cotton swab before and after wearing non-woven fabric masks for 8 h, respectively. Furthermore (3.4 ± 4.9) × 104 CFU/mL of bacteria were recovered from the mask surfaces. The bacteria contained in the masks, which consisted mainly of Cutibacterium acnes and Staphylococcus epidermidis/aureus, virtually disappeared after drying the masks indoors for 1 week.

Profiling of the microbiota in the remaining sports drink and orange juice in plastic bottles after direct drinking.

OBJECTIVES: The survival of bacteria in the sports drink and orange juice remaining in and at the mouth of bottles after direct drinking was examined after immediately drinking and incubation at 37 °C for 24 h. METHODS: Nine healthy participants were asked to drink approximately 100 mL of a plastic bottled sports drink or orange juice. The samples were cultured anaerobically at 37 °C for 7 days. Genomic DNA was extracted from the resulting individual colonies, and bacterial species were identified using 16 S rRNA gene sequencing. RESULTS: The mean amount of bacteria in the remaining sports drink and orange juice, immediately after drinking, were (1.6 ± 2.3) × 103 colony-forming units (CFU)/mL and (2.9 ± 3.3) × 103 CFU/mL, respectively. Additionally, bacteria recovered from the mouths of the sports drink and orange juice bottles were (2.5 ± 5.5) × 104 CFU/mL and (5.8 ± 2.4) × 103 CFU/mL, respectively. Oral bacteria, such as Streptococcus, Actinomyces, Neisseria, and Rothia were found to be transferred in the sports drink and orange juice, and the bacteria were scarcely detected after incubation at 37 °C for 24 h. CONCLUSIONS: The bacterial levels differed significantly from the previously reported levels in bottled tea 24 h after drinking, suggesting that remaining drinks with low pH levels can be preserved for a longer period.

Development and evaluation of a chewing gum containing antimicrobial peptide GH12 for caries prevention.

The purpose of this study was to develop a chewing gum containing a novel antimicrobial peptide GH12 and evaluate its biocompatibility, antimicrobial activity, and caries-preventive effects in vivo and in vitro. GH12 chewing gum was developed using a conventional method and its extracts were prepared in artificial saliva. GH12 concentration in the extracts was determined by high-performance liquid chromatography; extracts were used for growth curve assay, time-kill assay, crystal violet staining assay, scanning electron microscopy, and Cell Counting Kit-8 assay. A rat caries model was established, and molars were treated topically with extracts for 5 weeks. Weight gain monitoring, hematoxylin-eosin staining, micro-computed tomography, and Keyes scoring were conducted. Significant inhibition of Streptococcus mutans growth and biofilm formation was observed. Extracts displayed low cytotoxicity against human gingival epithelial cells. No significant differences in weight gain or signs of harm to the mucosal tissues in any of the rats were observed. Keyes scores of caries lesions in the GH12 chewing gum group were lower than those of the negative control group. It was concluded that GH12 chewing gum showed good biocompatibility, antimicrobial activity, and caries-preventive effects, exhibiting great potential to prevent dental caries as an adjuvant to regular oral hygiene.

Oral Microbiome Profiles and Inflammation in Pregnant Women Who Used Orthodontic Appliances.

It is common for women to undergo orthodontic treatment during pregnancy, especially through the use of fixed orthodontic devices. In changing the oral microbiome profile, it is crucial to increase the immune responses of pregnant women using fixed orthodontics; however, changes in the microbiomes of pregnant women with orthodontic appliances can be adjusted. Therefore, we aimed to conduct research on the oral cavity microbiome profiles, specifically IL-6 and TNF-α, of pregnant women using fixed orthodontic appliances. We proposed an observational analysis of 30 third-trimester pregnant women. OHI-S was recorded, saliva collection was performed using the passive drool method for IL-6 and TNF-α, and analysis and mucosal swabs were used to determine the oral microbiome profile. Kruskal−Wallis and post hoc Bonferroni tests were used to identify any significant differences with values of p < 0.05. Of these pregnant women, those with orthodontic appliances developed 10 types of bacteria at similar levels (>80%) from the genera Streptococcus, Lactobacillus, and Veillonella. There was no difference between the oral microbiomes of the control group and the pregnant women with a history of orthodontic appliance use. While the level of TNF-α in the women with orthodontic appliances was higher compared with the control group who had never used orthodontic appliances (p < 0.05), there was no difference in the IL-6 levels. The IL-6 and microbiome profile produced normal results, so the use of orthodontic appliances during pregnancy should be allowed with conditions. Pregnant women with orthodontic appliances must keep the oral cavity clean and their appliances well-maintained to avoid oral problems.

Influence of alcohol sensitivity on bone metastases and skeletal-related events in primary operable breast cancer: A retrospective cohort study.

BACKGROUND: Bone metastases in breast cancer patients are a common concern for medical doctors and dentists. Bone-modifying agents, which are necessary to prevent skeletal-related events (SREs), are associated with osteonecrosis of the jaw as an adverse side effect. Hypersensitivity to alcohol is an unfavorable response caused by deficiency of aldehyde dehydrogenase-2 (ALDH2) activity. Inactive ALDH2 is associated with osteoporosis, but its influence on bone metastases is unclear. The aim of our study was to evaluate the effects of alcohol sensitivity on bone metastases and SREs in primary operable breast cancer patients. METHODS: We retrospectively analyzed patients who were administered docetaxel, an anti-tumor agent, for histologically diagnosed breast cancer between April 2004 and September 2015. Alcohol sensitivity was assessed based on medical records of hypersensitivity to alcohol. The primary endpoint was time to bone metastases and the secondary endpoint was time to first SRE from the initial docetaxel administration. Data were stratified by alcohol sensitivity and tumor stages, and differences were estimated by the Kaplan-Meier method. Prognostic risk factors were analyzed by the multivariate Cox proportional hazards model. RESULTS: The median follow-up period of patients with high sensitivity to alcohol (n = 45) was 54 months and that for those with low sensitivity (n = 287) was 64 months. Stratification by alcohol sensitivity revealed that tumor stage exhibited significant correlations with the cumulative incidence of bone metastases in low-sensitivity patients; however, no differences were found in high-sensitivity patients. In multivariate analysis, alcohol sensitivity was a significant prognostic risk factor for bone metastases (HR 2.721, 95% CI 1.268-5.841, P = 0.010). CONCLUSION: Alcohol sensitivity may be a prognostic risk factor for bone metastases. More detailed genetic investigations and metabolic analyses are needed.

Migration of terephthalate from scraps of poly(ethylene terephthalate) (PET) in water and artificial seawater.

We report the migration of terephthalate and some low molecular weight organic compounds from poly(ethylene terephthalate) (PET) scraps in Milli-Q water and artificial seawater (ASW). The photochemical processes and the subsequent dark reactions were investigated using PET scraps obtained from postconsumer bottles of commercial non­carbonated mineral water. Concentrations of terephthalate exponentially increased with irradiation time, reaching approximately 6-8 µmol L-1 in ASW after 80 h irradiation. The photochemical migrations of compounds related to terephthalate were also observed. Concentrations of terephthalate and related compounds reached higher concentrations in ASW than in Milli-Q water. After 80 h irradiation, two dark experiments were conducted: one on the solutions after irradiation without PET scraps, and the other on photochemically damaged PET scraps. In ASW in the dark without PET scraps, the terephthalate concentration increased, and concentrations of other compounds related to terephthalate also changed. The results suggested that terephthalate was generated by hydrolytic reaction in dark ASW from the scission products of PET which were generated during the irradiation of PET scraps. Photochemically damaged PET scraps released terephthalate and related compounds in the dark. The half-life of the photo-irradiated PET scraps in the dark is approximately 205 years. Our results show that PET bottles in marine environments can continuously release terephthalate and other low molecular weight organic compounds during the day at the sunny surface, at the dark ocean floor, and during the night.

TDP-43 regulates cholesterol biosynthesis by inhibiting sterol regulatory element-binding protein 2.

Dyslipidemia is considered an essential component of the pathological process of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disease. Although TAR DNA Binding Protein 43 kDa (TDP-43) links both familial and sporadic forms of ALS and cytoplasmic aggregates are a hallmark of most cases of ALS, the molecular mechanism and the in vivo relation of ALS dyslipidemia with TDP-43 have been unclear. To analyze the dyslipidemia-related gene expression by TDP-43, we performed expression microarray and RNA deep sequencing (RNA-Seq) using cell lines expressing high levels of TDP-43 and identified 434 significantly altered genes including sterol regulatory element-binding protein 2 (SREBP2), a master regulator of cholesterol homeostasis and its downstream genes. Elevated TDP-43 impaired SREBP2 transcriptional activity, leading to inhibition of cholesterol biosynthesis. The amount of cholesterol was significantly decreased in the spinal cords of TDP-43-overexpressed ALS model mice and in the cerebrospinal fluids of ALS patients. These results suggested that TDP-43 could play an essential role in cholesterol biosynthesis in relation to ALS dyslipidemia.