Estrogens influence female itch sensitivity via the spinal gastrin-releasing peptide receptor neurons.

There are sex differences in somatosensory sensitivity. Circulating estrogens appear to have a pronociceptive effect that explains why females are reported to be more sensitive to pain than males. Although itch symptoms develop during pregnancy in many women, the underlying mechanism of female-specific pruritus is unknown. Here, we demonstrate that estradiol, but not progesterone, enhances histamine-evoked scratching behavior indicative of itch in female rats. Estradiol increased the expression of the spinal itch mediator, gastrin-releasing peptide (GRP), and increased the histamine-evoked activity of itch-processing neurons that express the GRP receptor (GRPR) in the spinal dorsal horn. The enhancement of itch behavior by estradiol was suppressed by intrathecal administration of a GRPR blocker. In vivo electrophysiological analysis showed that estradiol increased the histamine-evoked firing frequency and prolonged the response of spinal GRP-sensitive neurons in female rats. On the other hand, estradiol did not affect the threshold of noxious thermal pain and decreased touch sensitivity, indicating that estradiol separately affects itch, pain, and touch modalities. Thus, estrogens selectively enhance histamine-evoked itch in females via the spinal GRP/GRPR system. This may explain why itch sensation varies with estrogen levels and provides a basis for treating itch in females by targeting GRPR.

Association between prior-night sleep and next-day fatigue in older adults: a daily diary study.

BACKGROUND: Fatigue is known as an element of frailty. Sleep problems (e.g., short sleep duration and low sleep quality) can increase fatigue, but the day-to-day relationship between sleep and fatigue has not been studied well in older adults. Using a daily diary method, this study examined the within- and between-person associations between sleep and fatigue in older adults. METHODS: The study recruited 56 Japanese community dwellers (age: 82-86 years; female: 37.5%). Participants responded to a daily diary questionnaire at the end of each day. Over seven days, time in bed and satisfaction were measured after waking up, whereas fatigue was assessed before going to bed. We included person-level covariates (demographic factors, and physical and mental health) and day-level covariates (time in study, and positive and negative emotions). Multilevel models were estimated to examine within- and between-person associations. RESULTS: At the within-person level, on days following short and long time in bed and days following low levels of sleep satisfaction, individuals felt higher levels of fatigue compared with usual days. At the between-person level, no statistically significant differences in fatigue were observed between individuals with long and short time in bed. CONCLUSIONS: The findings suggest that prior-day sleep is associated with next-day fatigue in older adults. Long and short sleep duration and low sleep quality can lead to fatigue. Considering that sleep is a modifiable health behavior, appropriate management of sleep behavior may reduce fatigue.

Sweep imaging with Fourier transform as a tool with MRI for evaluating the effect of teriparatide on cortical bone formation in an ovariectomized rat model.

BACKGROUND: Teriparatide (TPTD) is a drug for osteoporosis that promotes bone formation and improves bone quality. However, the effects of TPTD on cortical bone are not well understood. Sweep imaging with Fourier transform (SWIFT) has been reported as a useful tool for evaluating bound water of cortical bone, but it has yet to be used to investigate the effects of TPTD on cortical bone. This study aimed to evaluate the consequences of the effect of TPTD on cortical bone formation using SWIFT. METHODS: Twelve-week-old female Sprague-Dawley rats (n = 36) were reared after ovariectomy to create a postmenopausal osteoporosis model. They were divided into two groups: the TPTD and non-TPTD groups. Rats were euthanized at 4, 12, and 24 weeks after initiating TPTD treatment. Tibial bones were evaluated using magnetic resonance imaging (MRI) and bone histomorphometry. In MRI, proton density-weighted imaging (PDWI) and SWIFT imaging were performed. The signal-to-noise ratio (SNR) was calculated for each method. The same area evaluated by MRI was then used to calculate the bone formation rate by bone histomorphometry. Measurements were compared using the Mann-Whitney U-test, and a P-value of < 0.05 was considered significant. RESULTS: PDWI-SNR was not significantly different between the two groups at any time point (P = 0.589, 0.394, and 0.394 at 4, 12, and 24 weeks, respectively). Contrarily, SWIFT-SNR was significantly higher in the TPTD group than in the non-TPTD group at 4 weeks after initiating treatment, but it was not significantly different at 12 and 24 weeks (P = 0.009, 0.937, and 0.818 at 4, 12, and 24 weeks, respectively). The bone formation rate assessed by histomorphometry was significantly higher in the TPTD group than in the non-TPTD group at all timepoints (P < 0.05, all weeks). In particular, at 4 weeks, the bone formation rate was markedly higher in the TPTD group than in the non-TPTD group (P = 0.028, 1.98 ± 0.33 vs. 0.09 ± 0.05 µm3/µm2/day). CONCLUSIONS: SWIFT could detect increased signals of bound water, reflecting the effect of TPTD on the cortical bone. The signal detected by SWIFT reflects a marked increase in the cortical bone formation rate.

Subcellular dynamics of estrogen-related receptors involved in transrepression through interactions with scaffold attachment factor B1.

Estrogen-related receptor (ERR), a member of the nuclear receptor superfamily, consists of three subtypes (α, ß, γ) and has strong homology with estrogen receptor. No endogenous ligands have been identified for ERRs, but they play key roles in metabolic, hormonal, and developmental processes as transcription factors without ligand binding. Although subnuclear dynamics are essential for nuclear events including nuclear receptor-mediated transcriptional regulation, the dynamics of ERRs are poorly understood. Here, we report that ERRs show subcellular kinetic changes in response to diethylstilbestrol (DES), a synthetic estrogen that represses the transactivity of all three ERR subtypes, using live-cell imaging with fluorescent protein labeling. Upon DES treatment, all ERR subtypes formed discrete clusters in the nucleus, with ERRγ also displaying nuclear export. Fluorescence recovery after photobleaching analyses revealed significant reductions in the intranuclear mobility of DES-bound ERRα and ERRß, and a slight reduction in the intranuclear mobility of DES-bound ERRγ. After DES treatment, colocalization of all ERR subtypes with scaffold attachment factor B1 (SAFB1), a nuclear matrix-associated protein, was observed in dot-like subnuclear clusters, suggesting interactions of the ERRs with the nuclear matrix. Consistently, co-immunoprecipitation analyses confirmed enhanced interactions between ERRs and SAFB1 in the presence of DES. SAFB1 was clarified to repress the transactivity of all ERR subtypes through the ERR-response element. These results demonstrate ligand-dependent cluster formation of ERRs in the nucleus that is closely associated with SAFB1-mediated transrepression. Taken together, the present findings provide a new understanding of the pathophysiology regulated by ERR/SAFB1 signaling pathways and their subcellular dynamics.

Novel metabolic system for lactic acid via LRPGC1/ERRγ signaling pathway.

Lactic acid (LA) is a byproduct of glycolysis resulting from intense exercise or a metabolic defect in aerobic processes. LA metabolism is essential to prevent lactic acidosis, but the mechanism through which LA regulates its own metabolism is largely unknown. Here, we identified a LA-responsive protein, named LRPGC1, which has a distinct role from PGC1α, a key metabolic regulator, and report that LRPGC1 particularly mediates LA response to activate liver LA metabolism. Following LA stimulation, LRPGC1, but not PGC1α, translocates from the cytoplasm to the nucleus through deactivation of nuclear export signals, interacts with the nuclear receptor ERRγ, and upregulates TFAM, which ensures mitochondrial biogenesis. Knockout of PGC1 gene in HepG2 hepatocarcinoma cells decreased the LA consumption and TFAM expression, which were rescued by LRPGC1 expression, but not by PGC1α. These LRPGC1-induced effects were mediated by ERRγ, concomitantly with mitochondrial activation. The response element for LRPGC1/ERRγ signaling pathway was identified in TFAM promoter. Notably, the survival rate of a mouse model of lactic acidosis was reduced by the liver-targeted silencing of Lrpgc1, while it was significantly ameliorated by the pharmacological activation of ERRγ. These findings demonstrate LA-responsive transactivation via LRPGC1 that highlight an intrinsic molecular mechanism for LA homeostasis.

Scaffold attachment factor B: distribution and interaction with ERα in the rat brain.

Scaffold attachment factor (SAFB) 1 and its homologue SAFB2 are multifunctional proteins that are involved in various cellular mechanisms, including chromatin organization and transcriptional regulation, and are also corepressors of estrogen receptor alpha (ERα). Both SAFBs are expressed at high levels in the brain. However, the distributions of SAFB1 and SAFB2 have yet to be characterized in detail and it is unclear whether both proteins interact with ERα in the brain. In this study, we investigated the expression and distribution of both SAFBs and their interaction with ERα in adult male rat brain. Immunohistochemical staining showed that SAFB1 and SAFB2 have a similar distribution pattern and are widely expressed throughout the brain. Double-fluorescence immunohistochemical and immunocytochemical analyses in primary cultures showed that the two SAFB proteins are localized in nuclei of neurons, astrocytes, and oligodendrocytes. Of note, SAFB2 was also found in cytoplasmic regions in these cell lineages. Both SAFB proteins were also expressed in ERα-positive cells in the medial preoptic area (MPOA) and arcuate and ventromedial hypothalamic nuclei. Co-immunoprecipitation experiments revealed that both SAFB proteins from the MPOA reciprocally interact with endogenous ERα. These results indicate that, in addition to a role in basal cellular function in the brain, the SAFB proteins may serve as ERα corepressors in hormone-sensitive regions.

Status of growth plates can be monitored by MRI.

BACKGROUND: Growth plate injuries and disorders cause premature closure, resulting in shortened or deformed limbs. Quantitative assessment by MRI might monitor the status of the growth plate and may assist in the prediction of these deformations. PURPOSE: To investigate whether the status of the growth plate can be monitored by quantitative evaluation using MRI of the noninjured region of the growth plate in a physeal injury model. STUDY TYPE: Prospective, longitudinal. ANIMAL MODEL: A 3.0-mm drill was used to create an injury to the central region of the right proximal tibial growth plate in 5-week-old male Japanese white rabbits (N = 18). The left tibia served as the control. FIELD STRENGTH/SEQUENCE: 7.04T, T2 -weighted imaging, diffusion-weighted imaging. ASSESSMENT: Eight of 18 rabbits underwent MRI, proton density-weighted imaging, and T2 -weighted and diffusion-weighted imaging. T2 and apparent diffusion coefficient (ADC) maps were generated for each image. The growth plate height and the T2 and ADC values of the noninjured region were measured. Two rabbits were sacrificed at 2, 4, 6, 8, and 10 weeks postinjury. Proximal tibial bones were evaluated using microcomputed tomography, histological, and immunohistological methods. STATISTICAL TESTS: Data were compared using repeated-measures analysis of variance followed by Tukey post-hoc multiple comparison. RESULTS: Growth plate height decreased at 10 weeks postinjury (P = 0.018) on the injured side. T2 values were greater at 2 weeks postinjury (P = 0.0478) and decreased at 8 and 10 weeks (P = 0.0226, P = 0.0470, respectively) on the injured side. ADC values increased at 6 weeks on the lateral side (P = 0.0304) and decreased at 8 weeks and 10 weeks postinjury (P < 0.01) on the medial and injured sides, respectively. DATA CONCLUSION: Quantitative MRI can help monitor the status of the growth plate and capture its changes early. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:133-143.

Determination of the lingual border of lower complete dentures: How to use a silicone impression material?

OBJECTIVES: This study aimed to clarify the efficacy of a border-moulding procedure with low-flow silicone impression material compared with a conventional compound to complete denture fabrication. It also aimed to evaluate the influence of various functional tasks during the lingual-side moulding procedure regarding the depth and width of the border. METHODS: Ten dentate subjects (three men, seven women; average age 30 years) were enrolled in this study after giving informed consent. A specially designed custom impression tray for the mandibular lingual side was fabricated for each subject. With the tray and heavy-body-type silicone material, lingual border moulding was performed that included four functional tasks: tongue protrusion (TP), licking the upper lip with the tongue (UL), swallowing (SW), and placing the tongue tip to the palate (PP). RESULTS: Within the limitations of this study, the results suggested that heavy-body silicone impression material is satisfactory for use in the border-moulding procedure, giving reproducible results. CONCLUSION: There were no significant differences among the functional tasks regarding the depth and width of the lingual flange except for swallowing, which exhibited the largest values.

Lack of posterior occlusal support predicts the reduction in walking speed in 80-year-old Japanese adults: A 3-year prospective cohort study with propensity score analysis by the SONIC Study Group.

OBJECTIVE: To investigate the association between posterior occlusal support by residual teeth and the reduction in walking speed in 80-year-old Japanese adults using propensity score matching. BACKGROUND DATA DISCUSSING THE PRESENT STATUS OF THE FIELD: Previous studies have demonstrated an association between oral status and motor function; however, most of these studies had a cross-sectional design. MATERIAL AND METHOD: This study included 353 community-dwelling Japanese people aged 79-81 years. Low walking speed was defined as ≤0.8 m/s, and participants with a low walking speed at baseline were excluded. The participants were divided into two groups: with or without posterior occlusal support by residual teeth at baseline. Propensity score matching was used to reduce the effects of bias by matching participants with and without posterior occlusal support according to similar background factors at baseline. Conditional logistic regression was conducted to determine low walking speed at the 3-year follow-up, which included posterior occlusal support as an independent variable with matching data. RESULTS: Before matching for posterior occlusal support, significant differences existed between the groups in terms of sex, years of education, height, weight and grip strength. However, after matching, there was no significant difference between the groups in any characteristic. Logistic regression analysis showed that posterior occlusal support is a significant variable (odds ratio = 1.88; P = 0.04) associated with reduced walking speed. CONCLUSION: Lack of posterior occlusal support at baseline independently predicted the incidence of reduced walking speed over 3 years.

Depressive-Like Behaviors Are Regulated by NOX1/NADPH Oxidase by Redox Modification of NMDA Receptor 1.

Involvement of reactive oxygen species (ROS) has been suggested in the development of psychiatric disorders. NOX1 is a nonphagocytic form of NADPH oxidase whose expression in the nervous system is negligible compared with other NOX isoforms. However, NOX1-derived ROS increase inflammatory pain and tolerance to opioid analgesia. To clarify the role of NOX1 in the brain, we examined depressive-like behaviors in mice deficient in Nox1 (Nox1-/Y). Depressive-like behaviors induced by chronic social defeat stress or administration of corticosterone (CORT) were significantly ameliorated in Nox1-/Y Generation of ROS was significantly elevated in the prefrontal cortex (PFC) of mice administrated with CORT, while NOX1 mRNA was upregulated only in the ventral tegmental area (VTA) among brain areas responsible for emotional behaviors. Delivery of miRNA against NOX1 to VTA restored CORT-induced depressive-like behaviors in wild-type (WT) littermates. Administration of CORT to WT, but not to Nox1-/Y, significantly reduced transcript levels of brain-derived neurotrophic factor (bdnf), with a concomitant increase in DNA methylation of the promoter regions in bdnf Delivery of miRNA against NOX1 to VTA restored the level of BDNF mRNA in WT PFC. Redox proteome analyses demonstrated that NMDA receptor 1 (NR1) was among the molecules redox regulated by NOX1. In cultured cortical neurons, hydrogen peroxide significantly suppressed NMDA-induced upregulation of BDNF transcripts in NR1-expressing cells but not in cells harboring mutant NR1 (C744A). Together, these findings suggest a key role of NOX1 in depressive-like behaviors through NR1-mediated epigenetic modification of bdnf in the mesoprefrontal projection.SIGNIFICANCE STATEMENT NADPH oxidase is a source of reactive oxygen species (ROS) that have been implicated in the pathogenesis of various neurological disorders. We presently showed the involvement of a nonphagocytic type of NADPH oxidase, NOX1, in major depressive disorders, including behavioral, biochemical, and anatomical changes in mice. The oxidation of NR1 by NOX1-derived ROS was demonstrated in prefrontal cortex (PFC), which may be causally linked to the downregulation of BDNF, promoting depressive-like behaviors. Given that NOX1 is upregulated only in VTA but not in PFC, mesocortical projections appear to play a crucial role in NOX1-dependent depressive-like behaviors. Our study is the first to present the potential molecular mechanism underlying the development of major depression through the NOX1-induced oxidation of NR1 and epigenetic modification of bdnf.

Early detection of osteoarthritis in rabbits using MRI with a double-contrast agent.

BACKGROUND: Articular cartilage degeneration has been evaluated by magnetic resonance imaging (MRI). However, this method has several problems, including its time-consuming nature and the requirement of a high magnetic field or specialized hardware. The purpose of this study was to sequentially assess early degenerative changes in rabbit knee articular cartilage using MRI with a new double-contrast agent. METHODS: We induced osteoarthritis (OA) in the right knee of rabbits by anterior cruciate ligament transection and partial medial meniscectomy. Proton density-weighted images and T2-calculated images were obtained before and after contrast agent injection into the knee. The signal intensity ratio (SIR) values on the proton density-weighted images were calculated by dividing the signal intensity of the articular cartilage by that of joint fluid. Six rabbits were examined using MRI at 2 (designated 2-w OA) and 4 weeks (4-w OA) after the operation. Histological examination was performed 4 weeks after the operation. One rabbit was histologically examined 2 weeks after the operation. The control consisted of six rabbits that were not subjected to the operation. The SIR values, T2 values and the thicknesses of the cartilage of the 2-w OA, 4-w OA and the control before and after contrast agent injection were analyzed. The Mankin score and OARSI (Osteoarthritis Research Society International) score were used for the histological evaluation. RESULTS: Significant differences in the SIR and T2 values of the medial and lateral condyles of the femur were found between the control and the 4-w OA only after contrast agent injection. No significant differences were found in the SIR and T2 values before contrast agent injection between the control, the 2-w OA and 4-w OA. The thickness of the articular cartilage revealed no significant differences. In the histological assessment, the Mankin score and OARSI score sequentially increased from the control to the 4-w OA. CONCLUSION: We evaluated the SIR and T2 values of the knees in a rabbit OA model and a control model using a new double-contrast agent. MRI with this agent enabled OA detection earlier than using conventional MRI.

Relationship between gerotranscendence and oral health-related quality of life.

OBJECTIVES: The purpose of our cross-sectional study was to investigate the relationship between gerotranscendence and oral health-related quality of life (OHR-QOL). To our knowledge, this is the first study to investigate the relationship between gerotranscendence and OHR-QOL. METHODS: Participants (total n = 1969; 70-year-old group, n = 999; 80-year-old group, n = 970) were drawn from resident lists in four areas of Japan: one urban area and one rural area in each of two geographical regions. OHR-QOL was measured using the Geriatric Oral Health Assessment Index (GOHAI). Measurement of occlusal force was performed using pressure-sensitive sheets. Gerotranscendence was assessed with the Japanese Gerotranscendence Scale Revised (JGS-R). We used multiple linear regression analysis to examine the relationships among OHR-QOL and other variables. RESULTS: Geriatric Oral Health Assessment Index score was significantly correlated with occlusal force, number of teeth, financial status and JGS-R score on linear regression analysis. CONCLUSION: Degree of gerotranscendence was significantly and independently correlated with degree of OHR-QOL in our sample.

Association of handgrip strength with various oral functions in 82- to 84-year-old community-dwelling Japanese.

OBJECTIVE: The purpose of this study was to elucidate the associations between muscle strength and several oral functions in a large cohort of community-dwelling, 82- to 84-year-old community-dwelling Japanese people. BACKGROUND DATA DISCUSSING THE PRESENT STATUS OF THE FIELD: Several studies have examined the relationships between physical performance and oral functions. However, no studies have investigated the associations of muscle strength with various objectively evaluated oral functional parameters in a large cohort of very old adults. MATERIALS AND METHODS: This study included 809 community-dwelling Japanese people (407 men and 402 women) aged 82-84 years. The oral functions examined were the maximal occlusal force, masticatory performance, stimulated salivary flow rate, repetitive saliva-swallowing test (RSST) score, tongue pressure and mouth-opening distance. Handgrip strength was measured, and its correlations with oral functions were assessed. Multiple linear and logistic regression analyses were performed to investigate the relationships between oral functions and handgrip strength. RESULTS: Multivariate analysis revealed that handgrip strength was correlated with not only the maximal occlusal force, masticatory performance and tongue pressure but also the RSST score and mouth-opening distance after adjustment for sex, number of teeth, use of removable denture, periodontal condition, instrumental activities of daily living, body mass index. When we examine the elderly people whose handgrip strength is declining, we should predict that their various oral functions may be declining. CONCLUSION: Handgrip strength was related to various oral functions after adjustment for the number of teeth in this population of community-dwelling 82- to 84-year-old Japanese.

Effect of Footprint Preparation on Tendon-to-Bone Healing: A Histologic and Biomechanical Study in a Rat Rotator Cuff Repair Model.

PURPOSE: To compare the histologic and biomechanical effects of 3 different footprint preparations for repair of tendon-to-bone insertions and to assess the behavior of bone marrow-derived cells in each method of insertion repair. METHODS: We randomized 81 male Sprague-Dawley rats and green fluorescent protein-bone marrow chimeric rats into 3 groups. In group A, we performed rotator cuff repair after separating the supraspinatus tendon from the greater tuberosity and removing the residual tendon tissue. In group B, we also drilled 3 holes into the footprint. The native fibrocartilage was preserved in groups A and B. In group C, we excavated the footprint until the cancellous bone was exposed. Histologic repair of the tendon-to-bone insertion, behavior of the bone marrow-derived cells, and ultimate force to failure were examined postoperatively. RESULTS: The areas of metachromasia in groups A, B, and C were 0.033 ± 0.019, 0.089 ± 0.022, and 0.002 ± 0.001 mm2/mm2, respectively, at 4 weeks and 0.029 ± 0.022, 0.090 ± 0.039, and 0.003 ± 0.001 mm2/mm2, respectively, at 8 weeks. At 4 and 8 weeks postoperatively, significantly higher cartilage matrix production was observed in group B than in group C (4 weeks, P = .002; 8 weeks, P < .001). In green fluorescent protein-bone marrow chimeric rats in group B, bone marrow-derived chondrogenic cells infiltrated the fibrocartilage layer. Ultimate force to failure was significantly higher in group B (19.7 ± 3.4 N) than in group C (16.7 ± 2.0 N) at 8 weeks (P = .031). CONCLUSIONS: Drilling into the footprint and preserving the fibrocartilage improved the quality of repair tissue and biomechanical strength at the tendon-to-bone insertion after rotator cuff repair in an animal model. CLINICAL RELEVANCE: Drilling into the footprint and preserving the fibrocartilage can enhance repair of tendon-to-bone insertions. This method may be clinically useful in rotator cuff repair.

Estrogen-related Receptor ß Reduces the Subnuclear Mobility of Estrogen Receptor α and Suppresses Estrogen-dependent Cellular Function.

Estrogen-related receptor (ERR) is a member of the nuclear receptor superfamily that has strong homology with estrogen receptor (ER) α. ERR has three subtypes (α, ß, and γ) expressed in estrogen-sensitive organs, including ovary, breast, and brain. No endogenous ligands of ERRs have been identified, but these receptors share a common DNA element with ERα and control estrogen-mediated gene transcription. Recent evidence suggests a role of ERRs in estrogen-related pathophysiology, but the detailed mechanisms of ERR functions in estrogen-related tissues are unclear. Using live-cell imaging with fluorescent protein labeling, we found that only ERRß among the ERRs exhibits a punctate intranuclear pattern overlapping with ERα following 17ß-estradiol (E2)-stimulation. Fluorescence recovery after photobleaching showed significant reduction of the mobility of ligand-activated ERα with co-expression of ERRß. Fluorescence resonance energy transfer revealed that ERRß directly interacts with ERα. The N-terminal domain of ERRß was identified as the region that interacts with ERα. We also found a correlation between punctate cluster formation of ERα and interaction between the receptors. Expression of ERRß significantly repressed ERα-mediated transactivity, whereas that of other ERR subtypes had no effect on the transactivity of ERα. Consistent with this finding, E2-stimulated proliferation of MCF-7 breast carcinoma cells and bcl-2 expression was significantly inhibited by expression of ERRß. These results provide strong evidence for a suppressive effect of ERRß on estrogen signaling through reduction of the intranuclear mobility of ERα. The findings further suggest a unique inhibitory role for ERRß in estrogen-dependent cellular function such as cancer cell proliferation.

Cortical bone water changes in ovariectomized rats during the early postoperative period: Objective evaluation using sweep imaging with Fourier transform.

PURPOSE: To evaluate the cortical bone signal-to-noise ratio (SNR) in ovariectomized (OVX) rats during the early postoperative period as a method to measure bone quality using the sweep imaging with Fourier transform (SWIFT) technique. MATERIALS AND METHODS: Twelve-week-old female Sprague-Dawley rats (n = 64) were divided into sham and OVX groups. Preoperative tetracycline was immediately administered subcutaneously to distinguish new cortical bone area, and tibial samples were collected at 2, 4, 8, and 12 weeks postoperatively. Magnetic resonance imaging (MRI) was performed using proton density-weighted imaging (PDWI) and SWIFT to obtain cross-sectional images of the tibial diaphysis. The cortical bone SNR was calculated. Bone histomorphometry was performed. RESULTS: Histomorphometry findings showed that the new bone area was significantly greater at 8 and 12 weeks postoperatively in the OVX group (P < 0.05) while the porosity area decreased gradually in both groups (P < 0.001). The difference of SNR receiving PDWI did not reach statistical significance (P = 0.057). The SWIFT technique showed that the SNR was significantly higher at 8 and 12 weeks postoperatively in the OVX group (P < 0.05) and was correlated with the new bone area (R(2) = 0.430). CONCLUSION: The SWIFT findings suggest that the SWIFT technique may depict early changes in cortical bone quality.

Impact of periodontal maintenance on tooth survival in patients with removable partial dentures.

AIM: Removable partial dentures (RPDs) may have a negative impact on oral health and have the potential to cause further tooth loss, especially of abutment teeth. However, no evidence indicates the effective interval of regular periodontal maintenance after RPD provision. This practice-based cohort study aimed to examine the impact of regular periodontal maintenance visits on survival of RPD abutment teeth. MATERIALS AND METHODS: One hundred and ninety-two patients had been previously provided with 304 new clasp-retained RPDs at Osaka University Dental Hospital, Japan. Using the Kaplan-Meier method and log-rank test, 1094 abutments were analysed to illustrate survival curves and to compare each curve. According to the frequency of periodontal maintenance, study samples were divided into three groups; every 3-6 months (3-6M) group, 1-year (1Y) group and no-maintenance (NM) group. RESULTS: Seven-year cumulative survival rates were 83.7% (3-6M), 75.5% (1Y) and 71.9% (NM) respectively. Survival of abutment teeth in the 3-6M group was significantly better than both 1Y (p = 0.005) and NM (p < 0.001) groups. CONCLUSION: These longitudinal clinical data indicates that periodontal maintenance at least once in 6 months had the most favourable outcome. Frequent periodontal maintenance after RPD provision could be effective in preventing further tooth loss.

Bisphenol A regulates the estrogen receptor alpha signaling in developing hippocampus of male rats through estrogen receptor.

Bisphenol A (BPA), one of the most common environmental endocrine disruptors, has been recognized to have wide adverse effects on the brain development and behavior. These adversities are related to its ability to bind estrogen receptor (ER) with subsequent alteration of its expression in the target areas. However, very little is known about whether BPA exposure also affects ER phosphorylation and its translocation to nucleus during postnatal development, two critical steps for its function. Here, we found that during development from postnatal day 7 (P7) to P21, the alpha subtype of ER (ERα) in the hippocampus of male rats experienced remarkable alterations in terms of its expression, phosphorylation and translocation to nucleus. Exposure to low level of BPA had bidirectional, development-dependent effects on the expression of ERα mRNA and protein, but decreased ERα phosphorylation and impaired its translocation to nucleus throughout the period investigated. Treatment with low dose of ICI 182,780 (ICI), an ER antagonist to block the binding of ER with BPA, reversed the altered ERα following BPA exposure, highlighting critical involvement of ER. Moreover, ICI treatment rescued the hippocampus-dependent behavioral deficits in the adult rats experiencing early-life BPA exposure. Overall, our results indicate that BPA interferes with the ERα signaling in the developing hippocampus in an ER-dependent manner, which may underlie its adverse behavioral and cognitive outcomes in adult animals.

Selective visualization of rabbit knee cartilage using MR imaging with a double-contrast agent.

PURPOSE: To establish a reliable method and efficient contrast agent for selective MR imaging of articular cartilage to improve the diagnosis of cartilage disorders. MATERIALS AND METHODS: A standard trace element replenisher (Mineric), which includes manganese chloride, cupric sulfate (both positive MR contrast agents), and colloidal ferric chloride (a negative contrast agent), was evaluated in comparison with gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) as a potential contrast agent. Normal saline was used as a control. The agents were injected into bilateral knee joints, and the entire joint block was dissected. Coronal images of femorotibial joints were obtained at 7.05 Tesla. Signal intensity ratios (SIRs) of cartilage to joint fluid were calculated for T1 and T2 values. The side effects of the agents were also investigated. Finally, histological evaluations were performed. RESULTS: SIRs were significantly increased in the Mineric treatment group compared with the Gd-DTPA and saline treatment groups. The T1 values of cartilage and fluid were significantly decreased in the Gd-DTPA and Mineric treatment groups. The T2 values of fluid were significantly decreased in the Mineric treatment group. No apparent side effects or degenerative changes in the joints were observed. CONCLUSION: A clinical trace element mixture was used as a novel double-contrast agent, and it exhibits selective MR contrast in articular cartilage.

Histological analysis of neuronal changes in the olfactory cortex during pregnancy.

Fluctuations in olfactory sensitivity are widely known to occur during pregnancy and may be responsible for hyperemesis gravidarum. These changes are thought to be caused by structural and functional alterations in neurons in response to marked changes of the hormonal milieu. In this study, we examined changes in neurons in the olfactory cortex during pregnancy and after delivery in rats. Dendritic spine densities were measured in the piriform cortex (PIR) and posterolateral cortical amygdala (COApl), which are involved in olfaction. The results showed increased numbers of dendritic spines in the PIR in mid-pregnancy and in the COApl during early and late pregnancy, but not in the motor area of the cerebral cortex, indicating a correlation with changes in olfactory sensitivity during pregnancy. Immunohistochemical analysis of expression of ovarian hormone receptors in these brain regions revealed a decrease in the number of estrogen receptor α-positive cells during pregnancy in the PIR and during pregnancy and the postpartum period in the COApl. Regarding pregnancy-related peptide hormones, oxytocin receptors were expressed in the PIR and COApl, while prolactin receptors were not found in these regions. Accordingly, oxytocin-containing neurites were distributed in both regions. These results suggest that the balance of these hormonal signals has an effect on olfactory sensitivity in pregnant females.