Human gingival fibroblast feeder cells promote maturation of induced pluripotent stem cells into cardiomyocytes.

The use of human induced pluripotent stem (iPS) cells has been investigated in multiple regenerative medicine studies. However, although methods for efficient differentiation of iPS cells into heart tissues have been devised, it remains difficult to obtain cardiac tissue with high contractility. Herein, we established a method for differentiating iPS cells into highly contractile cardiomyocytes (CMs), and demonstrate that the use of human gingival fibroblasts (HGFs) as a feeder cells promotes maturation of iPS-derived CMs (iPS-CMs) in vitro. After CM differentiation of iPS cells, iPS-CMs showed increased mRNA expression of the CM specific maker cardiac troponin T (cTnT) in the absence and presence (on-feeder condition) of cocultured HGFs, and decreased expression of pluripotent markers was observed under both conditions. Protein expression of cTnT was also observed in immunocytochemical analyses, although on-feeder CMs showed comparatively robust sarcomere structure and significantly stronger contractility than feederless cardiomyocytes, suggesting that HGF feeder cells facilitate CM differentiation of iPS cells.

Preventive Effects of Sustainable and Developmental Perioperative Oral Management Using the "Oral Triage" System on Postoperative Pneumonia after Cancer Surgery.

Perioperative oral management is widely recognized in the healthcare system of Japan. Conventionally, the surgeon refers patients with oral problems to a dental or oral surgery clinic in the hospital. However, frequent in-house referrals were found to increase the number of incoming patients resulting in unsustainable situations due to an insufficient workforce. In 2011, the Center for Perioperative Medicine was established at our hospital to function as a management gateway for patients scheduled to undergo surgery under general anesthesia. The "oral triage" system, wherein a dental hygienist conducts an oral screening to select patients who need preoperative oral hygiene and functional management, was established in 2012. A total of 37,557 patients who underwent surgery at our hospital from April 2010 to March 2019 (two years before and seven years after introducing the system) were evaluated in this study. The sustainability and effectiveness of introducing the system were examined in 7715 cancer surgery patients. An oral management intervention rate of 20% and a significant decrease in the incidence of postoperative pneumonia (aOR = 0.50, p = 0.03) indicated that this system could be useful as a sustainable and developmental oral management strategy to manage surgical patients with minimal human resources.

Effect of new bone substitute materials consisting of collagen and tricalcium phosphate.

The purpose of this study was to investigate the effect of new bone substitute materials consisting of collagen and tricalcium phosphate (TCP). Prior to the experiment, mandibular dog teeth were extracted. After 3 months, specific cavities were prepared on the alveolar ridge. In one group, cavities were filled with collagen sponge (CS group), in the other, cavities were filled with TCP sponge (TCP group). Cavities with no fillings (Cont group) were created as controls. Mandibular bone was evaluated histopathologically at experimental time periods of 1, 2, 4, and 8 weeks. Due to the non critical inflammatory symptoms that each group showed throughout all the time periods investigated, a low irritation level was observed. Absorption of material was almost complete at after 4 weeks in the CS group, and at after 8 weeks in the TCP group. At the top of the cavity, the TCP group exceeded the Cont group in amount of neogenesis at after 8 weeks. The materials examined in this study showed good osteoconduction and biodegradable character. The TCP Group, in particular, showed highly acceptable results, demonstrating that the materials used were excellent candidates as bone substitute materials.

Transplantation of human tooth with proliferating periodontal tissue--long-term clinical follow-up study--.

A case report is presented on transplantation of a left third molar to replace a right second molar lost due to large furcation perforation. Two weeks after surgery, a reentry surgical procedure was performed on the furcation defect of the second molar to remove membrane and retrieve proliferating periodontal tissue. The left third molar and proliferating periodontal tissue were then transplanted into the bone defect of the right second molar. Radiographically, the transplanted tooth showed no root resorption over a 3-year period. The results indicate that teeth replanted with proliferating periodontal tissue have a favorable long-term prognosis.

Clinical, radiographic, and histologic evaluation of localized ridge augmentation using a mandibular bone block.

This clinical case report presents a new technique for reconstructing the vertical and horizontal dimensions of the alveolar ridge using a mandibular bone block at sites planned for single implants. Augmentation was eased with the use of a mandibular bone block, which was shaped after placement with a round bur to passively fit the dimensions of the defect, at the recipient site. After treatment, approximately 7 mm of horizontal and 3 mm of vertical augmentation were gained. Histologic observation showed that the grafted bone was well integrated with the original bone. The volume of tissue gained was sufficient for placing an implant in an optimal position. The gain in the vertical and horizontal dimensions allowed an esthetic result with a single-tooth crown.

Tracing whale myoglobin evolution by resurrecting ancient proteins.

Extant cetaceans, such as sperm whale, acquired the great ability to dive into the ocean depths during the evolution from their terrestrial ancestor that lived about 50 million years ago. Myoglobin (Mb) is highly concentrated in the myocytes of diving animals, in comparison with those of land animals, and is thought to play a crucial role in their adaptation as the molecular aqualung. Here, we resurrected ancestral whale Mbs, which are from the common ancestor between toothed and baleen whales (Basilosaurus), and from a further common quadrupedal ancestor between whale and hippopotamus (Pakicetus). The experimental and theoretical analyses demonstrated that whale Mb adopted two distinguished strategies to increase the protein concentration in vivo along the evolutionary history of deep sea adaptation; gaining precipitant tolerance in the early phase of the evolution, and increase of folding stability in the late phase.

A new drug delivery system targeting ileal epithelial cells induced electrogenic sodium absorption: possible promotion of intestinal adaptation.

We previously demonstrated the induction of the epithelial sodium channel, prostasin, and 11beta-hydroxysteroid dehydrogenase type 2 and activation of sodium transport mediated by those molecules in the remnant ileum after total proctocolectomy. The aims of the present study were to develop a new drug delivery system that targets ileal epithelial cells and to enhance local mineralocorticoid action without systemic effects. Orally administered D-aldosterone-containing D,L-lactide/glycolide acid copolymer microspheres are absorbed in the rat terminal ileum and released aldosterone. Blood and terminal ileal tissues were collected 2 weeks after the administration of the microspheres, and the aldosterone concentrations, mRNA, and protein expressions of the above molecules and sodium transport were evaluated. Significantly high levels of tissue aldosterone in the absence of elevated plasma levels were detected in the microspheres-treated rats. Epithelial mRNA and protein expression of the above molecules increased significantly in the microspheres-treated animals. Electrogenic sodium transport in the ileum was enhanced in the microspheres-treated rats. Aldosterone-containing microspheres successfully induced the expression of the above molecules and activated sodium transport in the ileal mucosa, both of which are essential for intestinal adaptation. Pre- and/or postoperative treatment with this drug may compensate for the excessive loss of sodium and water following proctocolectomy.

The effect of periodontal disease on medical and dental costs in a middle-aged Japanese population: a longitudinal worksite study.

BACKGROUND: Although periodontal disease is one of the most common chronic diseases, it is not clear whether periodontal disease is associated with increased health care costs. The authors examined the effect of periodontal disease on medical and dental costs and use for 3.5 years prospectively. METHODS: The data were derived from health and dental examinations and health insurance claims of 4,285 Japanese civil officers aged 40 to 59 years. The subjects were divided into three categories: no pathological pocket, moderate periodontitis, and severe periodontitis. Age, gender, smoking, body mass index, and hypertension were adjusted in a multivariate analysis after excluding subjects with any history of liver disease, heart disease, or diabetes mellitus. RESULTS: The cumulative cost for subjects with severe periodontitis was approximately 21% higher than for subjects with no pathological pocket, and the hospital admission rates of subjects with severe periodontitis were highest (male: odds ratio [OR]=.34; 95% confidence interval [CI]: 1.00 to 1.80; female: OR=1.29; 95% CI: 0.75 to 2.20). In males, the annual hospital costs of subjects with severe periodontitis were 75% higher than for subjects with no pathological pocket. There was no clear trend identified for outpatient care. The annual dental visit rates and costs for subjects with severe periodontitis were highest in both genders. Periodontal disease might increase the medical care costs for diabetes mellitus, digestive disease, and liver disease. CONCLUSION: Periodontal disease may have played an important role in the cumulative health care cost increases in middle-aged adults over a period of only a few years.

Decreased serum free testosterone in workers exposed to high levels of di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP): a cross-sectional study in China.

BACKGROUND: Observations of adverse developmental and reproductive effects in laboratory animals and wildlife have fueled increasing public concern regarding the potential for various chemicals to impair human fertility. OBJECTIVE: Our objective in this study was to assess the effect of occupational exposure to high levels of phthalate esters on the balance of gonadotropin and gonadal hormones including luteinizing hormone, follicle-stimulating hormone, free testosterone (fT), and estradiol. METHODS: We examined urine and blood samples of 74 male workers at a factory producing unfoamed polyvinyl chloride flooring exposed to di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) and compared them with samples from 63 male workers from a construction company, group matched for age and smoking status. RESULTS: Compared to the unexposed workers, the exposed workers had substantially and significantly elevated concentrations of mono-n-butyl phthalate (MBP; 644.3 vs. 129.6 microg/g creatinine, p < 0.001) and mono-2-ethylhexyl phthalate (MEHP; 565.7 vs. 5.7 microg/g creatinine, p < 0.001). fT was significantly lower (8.4 vs. 9.7 microg/g creatinine, p = 0.019) in exposed workers than in unexposed workers. fT was negatively correlated to MBP (r = -0.25, p = 0.03) and MEHP (r = -0.19, p = 0.095) in the exposed worker group. Regression analyses revealed that fT decreases significantly with increasing total phthalate ester score (the sum of quartiles of MBP and MEHP; r = -0.26, p = 0.002). CONCLUSION: We observed a modest and significant reduction of serum fT in workers with higher levels of urinary MBP and MEHP compared with unexposed workers.

Association of psychological well-being with oral conditions in Japanese workers.

Although the effect of disorders on psychological well-being is well-known, there are few studies focusing on oral conditions at the worksite. The present study examined the association between psychological well-being and oral conditions of Japanese workers. A cross-sectional study was performed using data from 1381 Japanese civil service officers aged 20-59 yr old. Psychological well-being was measured with the 12-item version of the General Health Questionnaire (GHQ-12) in a comprehensive health questionnaire, while measures for oral condition included self-rated oral health, oral symptoms and clinical indicators: dental caries, periodontal status and number of missing teeth. The mean GHQ scores according to the levels of each oral condition were estimated by analysis of variance, separately for males and females. Higher scores corresponded to poorer psychological well-being. Age, gender, smoking and type of occupation were adjusted in a multivariate analysis. Psychological well-being was not associated significantly with dental caries, periodontal status or number of missing teeth. The adjusted means of the GHQ scores for ;conscious of appearance of mouth' were significantly different among the categories for both genders (male: p<0.001, female: p=0.018). For five of six oral symptoms, the adjusted means of GHQ scores were lowest for those respondents who rated their oral symptoms as ;never or hardly ever.' Our results did not show that psychological well-being was associated with oral conditions measured by clinical indicators. However, an association was found between some oral symptoms and psychological well-being. Absence of oral symptoms seems to be related to better psychological well-being.

Mortality of iron-steel workers in Anshan, China: a retrospective cohort study.

Foundry workers have increased mortality and morbidity risks from numerous causes, including various cancers. A retrospective Chinese iron-steel cohort study was conducted to examine the mortality effects of exposure to foundry work. Standardized mortality ratios (SMRs) and standardized rate ratios (SRRs) were calculated to evaluate mortality risks among male workers with exposure to 15 hazardous factors, adjusting for confounders. During 14 years of follow-up, 13,363 of 121,846 male workers died. SMR analysis showed a healthy-worker effect in comparison with the general population. SRR analysis showed increased risks for all causes, all neoplasms, and others among the exposed workers compared with non-exposed blue-collar workers. Combined exposure to polycyclic aromatic hydrocarbons and two or more dusts increased the risks of lung cancer (SRR = 654; 95% CI: 113-3,780) and other malignancies. Foundry work has adverse health effects, including carcinogenic risks.

A retrospective cohort study among iron-steel workers in Anshan, China: exposure assessment.

Although adequate assessment of exposure is needed in epidemiological studies among foundry workers, previous studies are often lacking in this aspect. We conducted a retrospective cohort study of a Chinese iron and steel company with a 14-yr follow up during 1980-1993. Exposure assessment was performed for a single job, i.e., the current job for the active worker and the longest job for the retired or deceased worker as of the end of the follow-up, which was allocated as the surrogate of lifetime job and was applied to a job-exposure matrix. Of the 147,062 cohort members, 52,394 males (43%) and 5,291 females (21%) were exposed to any of 15 hazardous factors such as dust, silica, PAHs (polycyclic aromatic hydrocarbons), CO (carbon monoxide) and heat. In 2,104 randomly selected samples, the exposure assessment of exposed workers based on a single job was found to be 12-14% lower than the real situation. This study suggests that the exposure assessment is valuable in evaluating the health effects among the foundry workers, despite some limitations such as underestimation of exposure assessment and the lack of data regarding smoking and drinking habits.

Transcervical excision of thymoma and video-assisted thoracoscopic extended thymectomy (VATET) for ectopic cervical thymoma with myasthenia gravis: report of a case.

Myasthenia gravis is the most common disease associated with thymoma, but it is rarely accompanied by ectopic thymoma. We describe a 47-year-old woman who presented with an ectopic cervical thymoma with myasthenia gravis. She was admitted to our neurology department with ptosis, diplopia, and mandibular muscle fatigue, and was diagnosed with myasthenia gravis. The mass was located posterior to the right lobe of thyroid gland on computed tomography and was diagnosed as ectopic thymoma on fine-needle aspiration biopsy examination. Transcervical excision of thymoma and VATET were performed. The patient has been free of neurological symptoms and has displayed no evidence of recurrent thymoma for 2 years.

Curly vibrissae, a new mutation in the Wistar-derived rat.

A new mutation was identified in the PD (Preaxial Duplication) strain of rats, the main manifestations of which were curly and sparse vibrissae with retarded outer hair growth. As the main characteristic of this mutant rat is abnormally curled appearance of the vibrissae, "curly vibrissae" is proposed as the name of this mutant gene, and "cv" as its symbol. Genetic analyses reveal that the mutant characteristics are inherited as autosomal recessive traits and the cv gene is independent from the pd gene that carried by the original PD colony. The cv/cv homozygous rats have a small number of short and/or curly vibrissae around the nose. The vibrissae on the cheek and/or above the eyes are also short and curled; however, no vibrissa appears on the lower mandible. Although hair growth seems to be retarded, the outer hairs showed nearly normal length by 10 weeks of age. The outer hairs of matured cv/cv rats appear silky and translucent. The adult mutant rats often exhibit loss of hair on the head and/or back. Lactating females usually lose their abdominal hair. Both sexes of cv/cv homozygotes have normal reproductive ability. No internal malformations accompany vibrissa and hair abnormalities.

Regression of Hodgkin lymphoma in response to antiviral therapy for hepatitis C virus infection.

Links between hepatitis C virus (HCV) infection and several non-Hodgkin lymphomas have been suggested by epidemiological studies. We herein report the first documented case of a patient with HCV-associated Hodgkin lymphoma who showed a marked regression following interferon-based antiviral therapy. This unique case extends the spectrum of HCV-associated malignant lymphomas, confirms the efficacy of antiviral therapy for this rare extrahepatic manifestation and provides valuable clues for achieving a better understanding of lymphomagenesis in HCV.

Genetic heterogeneity of hepatitis C virus in association with antiviral therapy determined by ultra-deep sequencing.

BACKGROUND AND AIMS: The hepatitis C virus (HCV) invariably shows wide heterogeneity in infected patients, referred to as a quasispecies population. Massive amounts of genetic information due to the abundance of HCV variants could be an obstacle to evaluate the viral genetic heterogeneity in detail. METHODS: Using a newly developed massive-parallel ultra-deep sequencing technique, we investigated the viral genetic heterogeneity in 27 chronic hepatitis C patients receiving peg-interferon (IFN) α2b plus ribavirin therapy. RESULTS: Ultra-deep sequencing determined a total of more than 10 million nucleotides of the HCV genome, corresponding to a mean of more than 1000 clones in each specimen, and unveiled extremely high genetic heterogeneity in the genotype 1b HCV population. There was no significant difference in the level of viral complexity between immediate virologic responders and non-responders at baseline (p = 0.39). Immediate virologic responders (n = 8) showed a significant reduction in the genetic complexity spanning all the viral genetic regions at the early phase of IFN administration (p = 0.037). In contrast, non-virologic responders (n = 8) showed no significant changes in the level of viral quasispecies (p = 0.12), indicating that very few viral clones are sensitive to IFN treatment. We also demonstrated that clones resistant to direct-acting antivirals for HCV, such as viral protease and polymerase inhibitors, preexist with various abundances in all 27 treatment-naïve patients, suggesting the risk of the development of drug resistance against these agents. CONCLUSION: Use of the ultra-deep sequencing technology revealed massive genetic heterogeneity of HCV, which has important implications regarding the treatment response and outcome of antiviral therapy.

Relationships between diabetes and medical and dental care costs: findings from a worksite cohort study in Japan.

The purpose of this study was to evaluate the relationships between diabetes and medical and dental care costs from a 5-yr prospective observation of Japanese workers. The data were derived from health and dental examinations and health insurance claims of 4,086 workers aged 40-54 yr. At baseline, the subjects were assigned to four categories: known diabetes; undiagnosed diabetes; impaired fasting glucose (IFG); and non-diabetic. The differences in health care costs among the non-diabetics, IFG and undiagnosed diabetes groups were not seen at baseline, but the costs incurred by the subjects with undiagnosed diabetes substantially increased thereafter. Over 5 yr of the study period, compared with the non-diabetic group, subjects with known diabetes incurred 3.9- and 2.9-fold higher annual inpatient and outpatient costs, respectively, while subjects in the undiagnosed diabetes group incurred 3.0- and 1.6-fold higher costs, respectively. There were no significant associations between annual dental care costs and diabetic status. The excess costs of medical care among subjects with diabetes were attributable to diabetes itself, heart disease and cerebrovascular disease, but not cancer. Among middle-aged workers, diabetics incurred significantly greater medical care costs than non-diabetics, whereas IFG was not associated with higher costs.

Effect of calcium polycarbophil on bowel function after restorative proctocolectomy for ulcerative colitis: a randomized controlled trial.

The aim of the present study was to determine if calcium polycarbophil ameliorates diarrhea after ileal J-pouch anal anastomosis for ulcerative colitis. Twenty-one randomized patients were given either bifidobacterium (3 g/day) plus calcium polycarbophil (3 g/day), in the polycarbophil group (11 patients), or bifidobacterium (3 g/day), in the control group (10 patients), p.o. for 6 months. Anal manometry was performed and bowel function (stool frequency, stool consistency, and nighttime soiling) was assessed via a questionnaire before and 1, 3, and 6 months after drug administration. Eight patients were deemed eligible in each group; five patients were excluded from the study, including two patients whose stool consistency was too firm and who experienced difficulty in defecating attributed to polycarbophil. Anal manometry and stool consistency did not change with time and did not differ between the polycarbophil and the control groups. Stool frequency decreased with time in both groups and did not differ between the groups. Nighttime soiling improved with time in the polycarbophil group but did not change in the control subjects. These results suggest that polycarbophil might be able to improve nighttime soiling without obviously affecting stool frequency and consistency after ileal J-pouch anal anastomosis for ulcerative colitis.