ESEM-EDX Mineralization and Morphological Analysis of Human Retrieved Maxillary Sinus Bone Graft Biopsies before Loading.

This study aimed to analyze the morphology of bone graft granules, the presence of granule demineralization, and bone morphology in retrieved human maxillary sinus bone graft biopsies. Healthy patients underwent sinus bone augmentation using lateral access. Two different dimensions of the antrostomy were performed, a 4 mm or 8 mm height. After 6 months, all sites received one implant using a flap technique, crestal positioning, and submerged healing. Implant biopsies were retrieved after 3 months and were histologically processed. The ESEM analysis was performed on the entire portion of the peri-implant bone (up to 750 µm from the implant thread). Three different regions of interest (ROIs) were selected: the coronal, middle, and apical portions of the implant. In these areas, EDX was performed, and calcium (Ca), phosphate (P), nitrogen (N), and their atomic ratios (Ca/P, Ca/N, and P/N) were calculated. Different bone tissue electron-dense areas were detected through grayscale intensity quantification of ESEM images with different organic (N) or inorganic (Ca,P) compositions. A total of 16 biopsies from 16 healthy patients were analyzed. Bone graft granules were mostly detected in the apical ROI. New bone tissue bridges were detected in the apical and middle ROI. These structures, with lower Ca/N and P/N ratios, were connected and enveloped the bone graft granules. Cortical ROI revealed the most mineralized bone tissue. Conclusions: After 9 months, bone graft resorption was only partially completed and new bone tissue appeared less mineralized in the middle and apical ROI than in the coronal ROI.

[New Methods of Evaluating Health Effects of Combined Exposures to Chemicals and Their Problems to Be Solved].

There are several basic prerequisites for the risk assessment of combined exposures to pesticides and dioxins using human health effects as the endpoint. First, all the target chemical substances exert the same toxicity to humans through the same mechanisms. Second, there is a linear dose-response relationship between the toxicity and effects of individual chemicals. With these two prerequisites, the effects of combined exposures are estimated as the sum of the toxicities of individual chemicals. For example, the toxicities of dioxins are calculated using their toxic equivalent quantities (TEQ) by considering the assigned toxic equivalent factor (TEF) of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) set individually from their isomers and homologs. In conventional epidemiological studies, when the impact of each of multiple chemical substances is examined, methods such as multiple regression analysis or using a generalized linear model (GLM) have been used on the basis of the same prerequisites. However, in practice, some of the chemicals exhibit collinearity in their effects or do not show a linear dose-response relationship. In recent years, there have been several methods developed in the field of machine learning being applied to epidemiological research. Typical examples were methods using Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS), and the shrinkage method, i.e., using the least absolute shrinkage and selection operator (Lasso) and elastic network model (ENM). In the future, while taking into account the findings of experimental studies in biology, epidemiology, and other fields, it is expected that various methods will be applied and selected.

Telomere length and urinary 8-hydroxy-2'-deoxyguanosine and essential trace element concentrations in female Japanese university students.

Telomere length is thought to be a biomarker of biological aging. This study examined whether telomere length was associated with urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative stress, and antioxidative trace elements in 73 female Japanese university students (age: 19.2 ± 0.7 years). We quantified 8-OHdG and selenium in urine by liquid chromatography-mass spectrometry and inductively coupled plasma-mass spectrometry, respectively. Telomere length and urinary concentrations of other essential trace elements (molybdenum, cobalt, and chromium) that were previously measured in the same study participants, were used in this study. We used multiple linear regression analysis to examine the associations of telomere length with urinary 8-OHdG and essential trace element concentrations (covariates: urinary cotinine concentration, age, BMI, and drinking status). The geometric means (geometric standard deviation) of 8-OHdG and selenium were 3.4 (1.5) and 31 (1.3) µg/g creatinine, respectively. Telomere length was not associated with urinary 8-OHdG concentration, but was negatively associated with urinary selenium concentration. In conclusion, telomere length was not associated with urinary 8-OHdG concentration in the young women in this study. Longitudinal studies should be conducted to clarify the association between telomere shortening rate and oxidative stress level.

Transmembrane G protein-coupled receptor 5 signaling stimulates fibroblast growth factor 21 expression concomitant with up-regulation of the transcription factor nuclear receptor Nr4a1.

Fibroblast growth factor 21 (FGF21) acts as an endocrine factor, playing important roles in the regulation of energy homeostasis, glucose and lipid metabolism. It is induced by diverse metabolic and cellular stresses, such as starvation and cold challenge, which in turn facilitate adaptation to the stress environment. The pharmacological action of FGF21 has received much attention, because the administration of FGF21 or its analogs has been shown to have an anti-obesity effect in rodent models. In the present study, we found that 3-O-acetyloleanolic acid, an active constituent isolated from the fruits of Forsythia suspensa, stimulated FGF21 production concomitant with the up-regulation of a transcription factor, nuclear receptor Nr4a1, in C2C12 myotubes. Additionally, significant increases in mFgf21 promoter activity were observed in C2C12 cells overexpressing TGR5 receptor in response to 3-O-acetyloleanolic acid treatment. Treatment with the p38 MAPK inhibitor SB203580 was effective at suppressing these stimulatory effects of 3-O-acetyloleanolic acid. Pretreatment with SB203580 also significantly repressed FGF21 mRNA abundance and FGF21 secretion in C2C12 myotubes after 3-O-acetyloleanolic acid stimulation, suggesting that p38 activation is required for the induction of FGF21 by ligand-activated TGR5 in C2C12 myotubes. These findings collectively indicated that TGR5 receptor signaling drives FGF21 expression via p38 activation, at least partly, by mediating Nr4a1 expression. Thus, the novel biological function of 3-O-acetyloleanolic acid as an agent having anti-obesity effects is likely to be mediated through the activation of TGR5 receptors.

Influence of Anatomical Parameters on the Dimensions of the Subantral Space and Sinus Mucosa Thickening after Sinus Floor Elevation. A Retrospective Cone Beam Computed Tomography Study.

BACKGROUND: Various anatomical parameters might influence the surgical approach for maxillary sinus floor elevation. The objective of the present study was to retrospectively evaluate the influence of anatomical parameters on the dimensions of the subantral space and of the sinus mucosa thickening after sinus floor elevation. MATERIAL AND METHODS: Seventy-eight maxillary sinuses in sixty-five patients were evaluated on cone beam computed tomographies taken before surgery and after one week (t1w) and nine months (t9m). Several parameters such as the distance XF between an axis parallel to the base of the nose (X-axes) and the sinus floor (F) were correlated with the height gain (IF) at t1w and t9m and the post-surgical edema. RESULTS: A weak significant positive correlation was observed between height gain vs. sinus height of interest (XF), the balcony, and the sinus floor angle. The post-surgical edema was influenced by the initial mucosa thickness and the xenograft used. CONCLUSIONS: Various parameters might affect height gain and sinus mucosa thickening after sinus floor elevation. The height of interest, the balcony, and the sinus floor angle showed significant correlations with height gain. The initial thickness of the mucosa and the biomaterial used influenced the post-surgical edema.

Association between nutrient intake and telomere length in Japanese female university students.

OBJECTIVE: Telomere length can be a biomarker of cumulative oxidative stress and inflammation indicating biological aging. Previous studies examined association of nutrient intake with telomere length targeting middle-aged and elderly individuals. This study examined whether dietary macro- and micronutrient intake was associated with telomere length in young females. METHODS: Seventy-four Japanese young females (median (interquartile range) age was 19 (19 - 20) years) participated. We estimated their intake of nutrients (energy, protein, fat, carbohydrate, essential elements, vitamins, fatty acids, and dietary fibre) using a semi-quantitative food frequency questionnaire and measured telomere length (T/S ratio, the ratio of telomere repeat copy number (T) to single-copy gene number (S)) of DNA extracted from blood by qPCR. The association between telomere length and tertiles of nutrient intake were analysed. RESULTS: The median (interquartile range) of telomere length was 0.70 (0.52 - 0.98). Vitamin A intake was positively associated with telomere length (tertile 1 vs. 2, coefficient [95% confidence interval] = 0.42 [0.12, 0.71]; tertile 1 vs. 3, coefficient [95% confidence interval] = 0.33 [0.04, 0.62]) after adjusting for covariates (age, BMI, passive smoking, and drinking). CONCLUSIONS: Our findings suggest that variation in vitamin A intake might influence telomere attrition in healthy individuals.

Involvement of the maxillary sinus ostium (MSO) in the edematous processes after sinus floor augmentation: a cone-beam computed tomographic study.

BACKGROUND: After sinus floor augmentation, a thickening of the sinus mucosa has been described. The aim of the present study was to evaluate the involvement of the maxillary sinus ostium in the edematous processes after a sinus floor augmentation procedure. METHODS: Seventy-two cone-beam computerized tomographies (CBSTs) were taken before sinus floor augmentation and after 1 week and 9 months from surgery and analyses. Sinus mucosa thickness and area, ostium diameter and patency, and extension of the post-surgical transient mucosal thickening in relation to the ostium were evaluated on the CBCTs for all three periods. The term "virtual" when referring to sinus mucosa thickness and area was introduced because of the edema and bleeding that both contributed to a transient thickening and additional elevation of the sinus mucosa. RESULTS: The mean virtual thickness of the sinus mucosa was 2.7 ± 4.0 mm, 7.7 ± 7.1 mm, 1.7 ± 2.0 mm before surgery, and after 1 week and 9 months. The virtual mucosa area was 37.2 ± 52.5 mm2, 184.5 ± 153.8 mm2, and 34.0 ± 50.7 mm2. The ostium diameter at the three periods evaluated was 1.8 ± 0.5 mm, 1.1 ± 0.6 mm, 1.5 ± 0.8 mm, respectively. Three infundibula (4.2%) were found out of patency before surgery while this number increased to 14 (19.4%) after 1 week. Nine months after surgery, only one infundibulum (1.4%) was out of patency, however, without presenting signs of sinus pathologies. The extension of the mucosal edema on the palatal sinus was reduced after 9 months of healing. CONCLUSIONS: One week after sinus floor augmentation, the maxillary sinus mucosa increased in dimensions and in several cases involved the ostium, reducing its diameter and producing a transient loss of patency. After 9 months of healing, the initial conditions were recovered.

Influence of the Dimensions of the Antrostomy on Osseointegration of Mini-implants Placed in the Grafted Region After Sinus Floor Elevation: A Randomized Clinical Trial.

PURPOSE: To evaluate the osseointegration of mini-implants placed in grafted sinuses with lateral windows of two different dimensions. MATERIALS AND METHODS: Sinus floor augmentation was performed in volunteers using a lateral window. The antrostomy was systematically prepared with a height of either 8 mm (large group) or 4 mm (small group). After 6 months of healing, mini-implants were placed in the grafted region. Biopsy specimens including the mini-implants were harvested 3 months after placement. RESULTS: Twenty biopsy specimens, 10 from each group, were suitable for the histologic analysis. Similar amounts of new bone-to-implant contact were obtained in both the large (41.1% ± 19.5%) and the small (42.8% ± 13.2%) groups (P = .940). Small percentages of residues of xenograft were found in contact with the implant surface, with 0.6% ± 1.1% in the large group and 5.9% ± 9.5% in the small group (P = .098). The new bone density around the implants was 31.7% ± 8.2% and 34.0% ± 7.9% in the large and small groups, respectively (P = .623). CONCLUSION: The dimensions of the antrostomy did not influence the histologic healing of implants placed 6 months after sinus floor augmentation.

Tomographic Assessment on the Influence of the Use of a Collagen Membrane on Dimensional Variations to Protect the Antrostomy After Maxillary Sinus Floor Augmentation: A Randomized Clinical Trial.

PURPOSE: To evaluate the dimensional variations after elevation of the maxillary sinus floor and the healing of the antrostomy left unprotected or protected by a collagen membrane. MATERIALS AND METHODS: Twenty patients were included in the study. After the elevation of the sinus mucosa, natural bovine bone was grafted into the elevated space. In 10 randomly selected patients, a native collagen membrane made of porcine corium was placed on the antrostomy (membrane group). In the other 10 patients, the antrostomy was left uncovered (no-membrane group). Cone beam computed tomography (CBCT) images were taken for all patients before surgery (T0), 1 week after sinus floor augmentation (T1), and after 9 months of healing (T2), and evaluations of dimensional variations over time of soft and hard tissues were performed. RESULTS: At T1, the elevation of the sinus floor in the middle aspect was 12.5 ± 3.8 mm and 11.9 ± 3.6 mm in the membrane and no-membrane groups, respectively. At T2, the reduction in height of the elevated space was 0.6 ± 0.9 mm and 0.8 ± 0.8 mm in the membrane and no-membrane groups, respectively. The elevated area decreased between ~10% and 11% in the membrane group and between ~15% to 20% in the no-membrane group. However, no statistically significant differences were found. CONCLUSION: The use of a collagen membrane to cover the antrostomy after sinus floor elevation did not produce significant clinical effects on dimensional variations over time.

Cadmium Exposure and Blood Telomere Length in Female University Students in Japan.

Cadmium is a toxic metal found ubiquitously throughout the world. Our study evaluated whether cadmium exposure was associated with telomere length in 73 female university students. Determination of telomere length was performed by quantitative polymerase chain reaction using DNA in blood. Urinary cadmium concentration was measured by inductively coupled plasma mass spectrometry. The students' physiological attributes and lifestyle were surveyed by means of a self-administered questionnaire. The geometric mean of urinary cadmium concentration was 0.312 µg/g creatinine, which was lower than the levels previously reported for Japan. Urinary cadmium concentration was not significantly associated with telomere length, though the exposure level of the present subjects was similar to that of previous study subjects which found significantly negative associations. It is possible that other factors affected telomere length in this study population.

Urinary 8-Hydroxy-2'-deoxyguanosine (8-OHdG) Concentrations and Menstrual Cycle Characteristics in Female University Students.

Higher concentrations of oxidative stress biomarkers are found in women with polycystic ovary syndrome (PCOS) and endometriosis, conditions linked to irregular menstrual cycles and menstrual pain. The aim of the present study was to test whether women with higher oxidative stress are more likely to show irregular menstrual cycles and severe menstrual pain compared with women with lower oxidative stress. A cross-sectional study was conducted targeting female university students with a mean (SD) age of 20.5 (1.8) years (n = 188). Participants completed a questionnaire on reproductive characteristics and anthropometry and kept a menstrual cycle diary for 5 consecutive months. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), cotinine, and creatinine concentrations were measured once during the study period. The mean (SD) value of the urinary 8-OHdG concentration was 4.7 (2.0) µg/g of creatinine. A total of 1021 menstrual cycles were recorded. The participants were categorized as either having regular (68%) or irregular (18%) cycles or oligomenorrhea (13%) or polymenorrhea (1%). The urinary 8-OHdG concentration did not significantly differ across menstrual cycle regularity or pain categories. Even after adjusting for age, body mass index (BMI), and urinary cotinine concentrations, having irregular cycles or more severe menstrual pain was not associated with urinary 8-OHdG concentration.

Enzyme-Treated Asparagus Extract (ETAS) Facilitates the Turnover of UV-B-Irradiated Keratinocytes.

Enzyme-treated asparagus extract (ETAS) is prepared from the lower, residual parts of asparagus, and some functionalities, such as anti-oxidative and neuroprotective activities, have been suggested. The purpose of the present study was to investigate the effects of ETAS on photoaging in the epidermal layer of the skin using cultured keratinocytes. Normal human epidermal keratinocytes were irradiated or left unirradiated with UV-B (10 mJ/cm2) and incubated with ETAS (0.5 or 2 mg/mL) or vehicle. After 3 or 13 h, molecular examinations were performed, and after 24 or 48 h, cell viabilities were determined by a CCK-8 assay. ETAS addition may induce keratinocyte migration and proliferation as well as apoptosis under molecular examination. These results suggest that ETAS might accelerate turnover of keratinocytes.

Inter- and intra-individual variation in urinary concentrations of parabens in male and female Japanese subjects.

We evaluated the representativeness of concentrations of parabens in a spot urine sample for the assessment of long-term exposure levels. Urine sample was taken monthly from 10 male Japanese subjects (35.9 ± 6.8 years) and 12 female Japanese university students (21.1 ± 0.4 years) for 5 months and measured for methyl (MP), ethyl (EP), propyl (PP) and butyl (BP) parabens by liquid chromatography-tandem mass spectrometry. Median (min-max) specific-gravity-adjusted urinary concentrations of the male group (n = 10) were 39.7 (2.99-268), 1.69 (< 0.045-75.2), 0.569 (< 0.11-123) and 0.0264 (< 0.020-24.4) ng mL-1 for MP, EP, PP and BP, respectively. Those of the female group (n = 12) were 283 (5.49-1687), 9.30 (0.290-487), 22.9 (< 0.11-307) and 3.76 (< 0.020-135) ng mL-1, respectively, which were significantly higher than those of the male group. Intra-class correlation coefficients (ICCs) were calculated for the four parabens to find 0.56, 0.58, 0.39 and 0.28 for MP, EP, PP and BP, respectively, in the male group, and 0.40, 0.43, 0.41 and 0.37 for MP, EP, PP and BP, respectively, in the female group. The results suggested that four paraben concentrations in a spot urine sample moderately reflected long-term paraben exposure of Japanese subjects. Source of exposure to parabens is also discussed.

Association between paraben exposure and menstrual cycle in female university students in Japan.

Parabens have been known to have estrogenic activity in many in vivo and in vitro studies and biomonitoring data indicated ubiquitous exposure in general populations. However, there are few human studies on reproductive effects of parabens. In this study, menstrual cycle length and its intra-individual variation were investigated by bleeding record over the period of 5 months and urinary concentrations of parabens were measured for 128 female Japanese university students. We found significantly negative relationships between menstrual cycle length and urinary estrogen-equivalent total paraben (odds=0.73, 95% CI 0.56-0.96) and butyl paraben concentrations (odds=0.83, 0.70-0.99), which indicated shortened cycle length in women with high urinary paraben concentrations. This study indicated that paraben exposure at not excessive levels is associated with menstrual cycle length or its variability among general female subjects. These results suggest a possibility that parabens exposure is one of the environmental causes of human reproductive problem.

[Menstrual cycle length and source of its variation in female university students majoring in nursing sciences].

OBJECTIVES: To acquire fundamental knowledge on menstrual cycle and its intraindividual variation in healthy Japanese female students and their association with biological attributes, lifestyle and food habit. METHODS: We asked female students of a nursing school to keep a diary of their menstruation over 5 consecutive months and to fill a questionnaire on their biological attributes, lifestyle and consumption frequency of some food items during the period from November 2012 to January 2014. RESULTS: The mean±standard deviation (SD) of cycle lengths of 180 women (20.4±0.9 yrs) was 34.2±10.5 days. Of these 180 women, 141 had a cycle length within the normal range (25-38 days) while 10 had a shorter cycle and 20 had a longer cycle. The intraindividual variations of the cycle, defined as "range" (difference between the longest and shortest cycles of an individual) and "SD" (SD of mean of multiple lengths within an individual), were 11.4±10.3 and 7.9±11.8 days, respectively. Of 177 women, 73 and 109 had normal range and SD (≤6 days), respectively. The mean age of women with long cycles was older than that of women with short cycle (Kruscal-Wallis test, p<0.05), and women with greater intraindividual variations were older than those with small variations (U-test, p<0.05). Subjects with menstrual pain had greater "SD" than did those without pain (Chi-square test, p<0.05). Neither lifestyle nor food habit was associated with the length and intraindividual variations of the menstrual cycle. CONCLUSIONS: The present results provided fundamental knowledge on the length and intraindividual variations of the menstrual cycle and the sources of these variations in female Japanese university students.

Neurotropin promotes NGF signaling through interaction of GM1 ganglioside with Trk neurotrophin receptor in PC12 cells.

Activation of the high-affinity nerve growth factor (NGF) receptor Trk occurs through multiple processes consisted of translocation and clustering within the plasma membrane lipid rafts, dimerization and autophosphorylation. Here we found that a nonprotein extract of inflamed rabbit skin inoculated with vaccinia virus (Neurotropin(®)) enhanced efficiency of NGF signaling. In rat pheochromocytoma PC12 cells overexpressing Trk (PCtrk cells), Neurotropin augmented insufficient neurite outgrowth observed at suboptimal concentration of NGF (2ng/mL) in a manner depending on Trk kinase activity. Cellular exposure to Neurotropin resulted in an accumulation of Trk-GM1 complexes without affecting dimerization or phosphorylation states of Trk. Following NGF stimulation, Neurotropin significantly facilitated the time course of NGF-induced Trk autophosphorylation. These observations provide a unique mechanism controlling efficiency of NGF signaling, and raise the therapeutic potential of Neurotropin for various neurological conditions associated with neurotrophin dysfunction.

Association of antimüllerian hormone levels with menstrual-cycle type and dysmenorrhea in young asymptomatic women.

OBJECTIVE: To examine the association between antimüllerian hormone (AMH) levels and menstrual-cycle and lifestyle characteristics among young Japanese women. DESIGN: Cross-sectional study. SETTING: University. PATIENT(S): Female students aged 20-22 years (n=65) who had never used oral contraceptives. INTERVENTION(S): Participants completed a questionnaire on reproductive and lifestyle characteristics, and kept a menstrual-cycle diary for 5 consecutive months. Serum AMH was measured once during the study period. MAIN OUTCOME MEASURE(S): Serum AMH concentration. RESULT(S): Compared with women with very mild menstrual pain, serum AMH concentration was 49.6% (95% CI 6.5%-72.8%) lower among women with severe menstrual pain. Higher AMH concentration was associated with irregular menstrual cycles. Even after adjusting for menstrual-cycle regularity and its interaction, more-severe menstrual pain was associated with significantly lower AMH concentration. CONCLUSION(S): Circulating AMH concentration was significantly lower among young Japanese women who had more-severe menstrual pain. Underlying physiological mechanisms need to be addressed in future studies.

Temporomandibular joint intermittent closed lock: clinic and magnetic resonance imaging findings.

OBJECTIVE: This study was carried out to describe the clinical and magnetic resonance imaging (MRI) findings of patients with intermittent closed lock (ICL) of the temporomandibular joint (TMJ). STUDY DESIGN: This retrospective study included 58 joints with ICL and 526 joints without ICL as controls. We compared the MRI findings between the patients with and without ICL and investigated clinical and MRI finding of ICL patients. We divided ICL patients into 2 groups based on the treatment efficacy: effective and ineffective. RESULTS: There were significant differences in the prevalence of disk deformity between the joints with and without ICL. Masticatory muscle pain was observed in 41.7% of the effective group and in 80% of the ineffective group, respectively. CONCLUSIONS: These results suggest that there is a relationship among the onset of ICL and disk deformation. Masticatory musclepain was significantly observed in the ineffective group.

Sufficient and necessary condition for zero quantum entropy rates under any coupling to the environment.

We find the necessary and sufficient conditions for the entropy rate of the system to be zero under any system-environment Hamiltonian interaction. We call the class of system-environment states that satisfy this condition lazy states. They are a generalization of classically correlated states defined by quantum discord, but based on projective measurements of any rank. The concept of lazy states permits the construction of a protocol for detecting global quantum correlations using only local dynamical information. We show how quantum correlations to the environment provide bounds to the entropy rate, and how to estimate dissipation rates for general non-Markovian open quantum systems.

Maternal exposure to isobutyl-paraben impairs social recognition in adult female rats.

Isobutyl-paraben (IBP), a widely used preservative, exhibits estrogenic activity. We analyzed the effects of exposure to IBP during gestation and lactation via dam on social recognition behavior in ovariectomized offspring of Sprague-Dawley rats. Offspring were ovariectomized at 7 weeks of age, and were used in a social recognition test at 16 weeks of age. Each offspring was exposed to a novel ovariectomized rat four times and to a second novel rat in a fifth exposure. We counted the investigations by offspring of intruder rats. The IBP-exposed rats showed impaired social behavior compared with controls. These data imply that early exposure to IBP may have an effect on adult social behavior, which is reported to be an autism spectrum disorders in humans.