Miracle-dz/UniFAR-FTUs huggingface dataset:
Vitamin D–Independent Therapeutic Effects of Extracellular Calcium in a Mouse Model of Adult‐Onset Secondary Hyperparathyroidism

Cell proliferation and PTH secretion in the parathyroid gland are known to be regulated by vitamin D and extracellular calcium. Here, we examined the vitamin D–independent effects of correction of extracellular calcium in an adult‐onset secondary hyperparathyroidism (sHPT) model, using mice with a nonfunctioning vitamin D receptor (VDR). Wildtype and homozygous VDR mutant mice were kept on a rescue diet (RD) containing 2% calcium (Ca), 1.25% phosphorus (P), and 20% lactose until they were 4 mo or 1 yr of age. Subsequently, 4‐mo‐old mice were switched to a challenge diet (CD) containing the following: 0.5% Ca, 0.4% P, and 0% lactose. After 2 mo on the CD, groups of VDR mutant mice were either fed CD, a normal mouse chow with 0.9% Ca, 0.7% P, and 0% lactose, or the RD for another 3 mo. Feeding the RD protected VDR mutants against sHPT over 1 yr, showing that vitamin D is not essential for long‐term control of the function and proliferation of parathyroid cells. When 4‐mo‐old VDR mutants were switched from the RD to the CD for 2 mo, they developed severe sHPT associated with hypertrophy and hyperplasia of parathyroid glands and profound bone loss. Subsequent feeding of the RD during a 3‐mo therapy phase fully corrected sHPT, reduced chief cell proliferation, and reduced maximum parathyroid gland area by 25% by cell atrophy. There was no evidence of RD‐induced chief cell apoptosis. We conclude that signaling by the calcium‐sensing receptor regulates chief cell function and size in the absence of signaling through the VDR.
Differences in client and therapist views of the working alliance in drug treatment

Background: There is growing evidence that the therapeutic alliance is one of the most consistent predictors of retention and outcomes in drug treatment. Recent psychotherapy research has indicated that there is a lack of agreement between client, therapist and observer ratings of the therapeutic alliance; however, the clinical implications of this lack of consensus have not been explored. Aims: The aims of the study are to (1) explore the extent to which, in drug treatment, clients and counsellors agree in their perceptions of their alliance, and (2) investigate whether the degree of disagreement between clients and counsellors is related to retention in treatment. Methods: The study recruited 187 clients starting residential rehabilitation treatment for drug misuse in three UK services. Client and counsellor ratings of the therapeutic alliance (using the WAI‐S) were obtained during weeks 1–12. Retention was in this study defined as remaining in treatment for at least 12 weeks. Results: Client and counsellor ratings of the alliance were only weakly related (correlations ranging from r = 0.07 to 0.42) and tended to become more dissimilar over the first 12 weeks in treatment. However, whether or not clients and counsellors agreed on the quality of their relationship did not influence whether clients were retained in treatment. Conclusions: The low consensus between client and counsellor views of the alliance found in this and other studies highlights the need for drug counsellors to attend closely to their clients' perceptions of the alliance and to seek regular feedback from clients regarding their feelings about their therapeutic relationship.
Sex differences in gingivitis relate to interaction of oral health behaviors in young people.

BACKGROUND Although many epidemiologic surveys have shown that gingivitis is more prevalent in males than in females, few studies have clearly explained what causes this difference. The objective of the present study is to explain the sex difference in gingivitis based on the interaction between oral health behaviors and related factors, such as knowledge, attitude, and lifestyle, in young people. METHODS The study was comprised of 838 subjects (440 males and 398 females), aged 18 and 19 years. Gingivitis was assessed by the percentage of bleeding on probing (%BOP). Additional information was collected regarding oral hygiene status, oral health behaviors, and related factors. Structural equation modeling was used to test pathways from these factors to %BOP. Multiple-group modeling was also conducted to test for sex differences. RESULTS Females had greater knowledge, a more positive attitude, a healthier lifestyle, and higher level of oral health behaviors than males. There were significant differences in the paths (i.e., from lifestyle, knowledge, and attitude to %BOP) through oral health behaviors and oral health status. CONCLUSIONS Sex-based differences in gingivitis in young people can be explained by oral health behaviors and hygiene status, which are influenced by lifestyle, knowledge, and attitude. To prevent gingivitis, different approaches to males and females may be useful.
Osteoblast‐Derived TGF‐β1 Stimulates IL‐8 Release Through AP‐1 and NF‐κB in Human Cancer Cells

Introduction: The bone marrow microenvironment is further enriched by growth factors released during osteoclastic bone resorption. It has been reported that the chemokine interleukin (IL)‐8 is a potent and direct activator of osteoclastic differentiation and bone resorption. However, the effect of bone‐derived growth factors on the IL‐8 production in human cancer cells and the promotion of osteoclastogenesis are largely unknown. The aim of this study was to investigate whether osteoblast‐derived TGF‐β1 is associated with osteolytic bone diseases.
Biologic interaction of three-dimensional periodontal fibroblast spheroids with collagen-based and synthetic membranes.

BACKGROUND Cell-based therapy using autologous cells has been suggested as a potential approach for periodontal tissue regeneration. Spheroid systems are a form of three-dimensional cell culture that promotes cell matrix interaction, which could recapitulate the aspect of cell homeostasis in vivo. The aim of this study is to assess the interaction of periodontal fibroblast spheroids with synthetic and collagen-based membranes that have been used in guided tissue regeneration. METHODS Commercially available normal human periodontal ligament fibroblasts were grown in spheroid forms using a liquid overlay technique and then transplanted onto a collagen-based and a polyglycolic acid-based membrane. The biologic interaction of the spheroids with the membranes was assessed using basic histology, Alamar blue tissue viability assay, scanning electron microscopy, and immunohistochemical analysis. RESULTS Periodontal fibroblast spheroids adhered to both membranes, and the cells were able to proliferate and migrate from the spheroids both horizontally and vertically into the membrane scaffolds. Immunohistochemical analysis showed expression of collagen type I, periostin, and Runx2 by the periodontal fibroblasts. CONCLUSION Periodontal fibroblast spheroids were able to grow three-dimensionally on the biologic membranes and may have the potential to be used together with guided tissue regeneration approaches as an adjunct for periodontal regeneration.
Effect of phase I periodontal therapy on anti-cardiolipin antibodies in patients with acute myocardial infarction associated with chronic periodontitis.

BACKGROUND Serum anti-cardiolipin (aCL) antibodies are prevalent in patients with periodontal diseases. These increased aCL concentrations were identified to play a modulating role in cardiovascular diseases. The present study aims to explore the effect of phase I periodontal therapy on immunoglobulin (Ig)M and IgG aCL antibodies in patients with acute myocardial infarction (AMI) associated with chronic periodontitis. METHODS A cross-sectional randomized clinical study was conducted within two groups comprising a sample size of 72 patients (n = 36 each). Group 1 had clinical features of AMI, and group 2 had clinical features of AMI associated with chronic periodontitis. After a thorough clinical and oral examination, the plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment loss (AL) were recorded. Serum sample collection by venipuncture was done for estimation of serum IgM and IgG aCL concentration by using an enzyme-linked immunosorbent assay method. In group 2, phase I periodontal therapy was performed, and clinical and biochemical parameters were reanalyzed after 1 month. RESULTS In group 2, the mean PI, GI, PD, clinical AL, and serum IgM and IgG aCL antibody levels were significantly higher than in group 1 patients. In addition, study results showed significant alterations in concentrations of serum IgM (P = 0.008) and IgG (P <0.001) aCL along with periodontal parameters after phase I periodontal therapy. CONCLUSION The phase I periodontal therapy altered levels of serum IgG and IgM aCL antibodies in patients with AMI associated with chronic periodontitis.
Hormone Therapy Improves Femur Geometry Among Ethnically Diverse Postmenopausal Participants in the Women's Health Initiative Hormone Intervention Trials

Loss of bone strength underlies osteoporotic fragility fractures. We hypothesized that hormone interventions significantly improve the structural geometry of proximal femur cross‐sections. Study participants were from the Women's Health Initiative hormone intervention trials: either the conjugated equine estrogen (CEE) only (Nplacebo = 447, NCEE = 422) trial or the estrogen (E) plus progestin (P) (Nplacebo = 441, NE+P = 503) trial, who were 50–79 yr old at baseline and were followed up to 6 yr. BMD scans by DXA were conducted at baseline, year 1, year 3, and year 6. Femur geometry was derived from hip DXA scans using the hip structural analysis (HSA) method. Mixed effects models with the intent‐to‐treat analysis approach were used. There were no significant differences in treatment effects between the E‐alone and the E + P trial, so the analyses were conducted with participants combined from both trials. Treatment benefits (p < 0.05) on femur geometry were observed as early as 1 yr after the intervention. From baseline to year 6, section modulus (a measure of maximum bending stress) was preserved, and buckling ratio (an index of cortical instability under compression) was reduced by hormone interventions (p < 0.05); the differences in the percent changes from baseline to year 6 between women on hormone intervention versus women on placebo were 2.3–3.6% for section modulus and –5.3% to – 4.3% for buckling ratio. Hormone interventions led to favorable changes in femur geometry, which may help explain the reduced fracture risk observed in hormone interventions.
Effect of Temporal Changes in Bone Turnover on the Bone Mineralization Density Distribution: A Computer Simulation Study

The heterogeneous distribution of mineral content in trabecular bone reflects the continuous renewal of bone material in bone remodeling and the subsequent increase in mineral content in the newly formed bone packets. The bone mineralization density distribution (BMDD) is typically used to describe this nonuniform mineral content of the bone matrix. Our mathematical model describes changes of the BMDD of trabecular bone as a function of bone resorption and deposition rates and the mineralization kinetics in a newly formed bone packet. Input parameters used in the simulations were taken from experimental studies. The simulations of the time evolution of the BMDD after increase in bone turnover (perimenopausal period) resulted in a shift of the BMDD toward lower values of the mineral content. Transiently, there was a broadening of the BMDD configuration partly showing two peaks, which points to a strongly heterogeneous distribution of the mineral. Conversely, when the remodeling rate was reduced (antiresorptive therapy), the BMDD shifted toward higher values of the mineral content. There was a transient narrowing of the distribution before broadening again to reach the new steady state. Results from this latter simulation are in good agreement with measurements of the BMDD of patients after 3 and 5 yr of treatment with risedronate. Based on available experimental data on bone remodeling, this model gives reliable predictions of changes in BMDD, an important factor of bone material quality. With the availability of medications with a known effect on bone turnover, this knowledge opens the possibility for therapeutic manipulation of the BMDD.
Cytokine profile in the gingival crevicular fluid of periodontitis patients with and without type 2 diabetes: a literature review.

BACKGROUND Periodontitis may occur in patients with and without type 2 diabetes (T2D). It may be hypothesized that the gingival crevicular fluid (GCF) cytokine profile in patients with periodontitis with poorly controlled T2D may differ from the GCF cytokine profile in medically healthy individuals with periodontitis. The aim was to review the cytokine profiles in the GCF of patients with periodontitis with and without T2D. METHODS Databases were searched from 1988 to August 2011 using different combinations of various keywords. Titles and abstracts of articles that satisfied the eligibility criteria were screened by the authors and checked for agreement. Only articles published in English were included. RESULTS Ten studies were included. Two studies reported GCF concentrations of interleukin (IL)-6 to be higher in patients with periodontitis with T2D compared to medically healthy patients with periodontitis. Two studies showed GCF IL-6 levels to be higher in periodontitis with T2D compared to medically healthy subjects without periodontitis. In one study GCF levels of IL-17, IL-23, and interferon-γ were higher in patients with periodontitis with T2D compared to medically healthy patients with periodontitis. In one study, GCF concentrations of IL-8 were significantly higher in patients with periodontitis with T2D compared to medically healthy individuals with periodontitis. Three studies reported GCF levels of IL-1α to be significantly higher in patients with periodontitis with T2D compared to medically healthy individuals with periodontitis. CONCLUSION The GCF cytokine profile in patients with and without T2D seems to be governed by the intensity of periodontal inflammation and the role of T2D in this regard is rather secondary.
Histologic comparison of healing after tooth extraction with ridge preservation using mineralized versus demineralized freeze-dried bone allograft.

BACKGROUND Allografts, such as demineralized freeze-dried bone allograft (DFDBA) and mineralized freeze-dried bone allograft (FDBA) are commonly used by clinicians for ridge preservation procedures. The primary objective of this study is to histologically evaluate and compare the healing of non-molar extraction sockets grafted with DFDBA versus FDBA for ridge preservation. The secondary aim of this study is to compare dimensional changes in ridge height and width after grafting with these two materials. MATERIALS Forty patients were randomly divided into two groups of 20. Extraction sockets were filled with either FDBA or DFDBA. To minimize variables associated with the organ donor and with tissue processing, all of the graft material was procured from a single donor; the only difference in the two materials was the percentage mineralization of the final bone graft. A 2-mm-diameter core biopsy was taken from each grafted site ≈19 weeks after grafting. Histomorphometric analysis was performed to determine percentage of vital bone, residual graft particles, and connective tissue (CT)/other non-bone components. RESULTS There were no significant differences when comparing changes in alveolar ridge dimensions of the two groups. There was no significant difference in percentage CT/other between groups. DFDBA had a significantly greater percentage of vital bone at 38.42% versus FDBA at 24.63%. The DFDBA group also had a significantly lower mean percentage of residual graft particles at 8.88% compared to FDBA at 25.42%. CONCLUSION This study provides the first histologic and clinical evidence directly comparing ridge preservation with DFDBA versus FDBA in humans and demonstrates significantly greater new bone formation with DFDBA.
EFFECT OF LEUCINE SUPPLEMENTATION ON LOSS OF LEAN BODY MASS DURING PROLONGED HYPOXIC EXPOSURE: A DOUBLE-BLIND RANDOMIZED STUDY

Trekkers exposed to prolonged hypobaric hypoxia commonly experience weight loss, especially loss of lean body mass (LBM). Evidence indicates that protein supplementation, specifically leucine, potentially attenuates loss of LBM in a catabolic state. This study investigated if leucine supplementation would prevent the loss of LBM during prolonged hypoxia. 18 trekkers (M=10 and F=8; age: 47.2 ± 11.5; range: 28-70y), completed a 13-day trek in Nepal from Lukla (2180m) to Everest Base Camp (5364m) with a mean altitude of 4140m. Participants consumed a 7.0g leucine supplement or an isocaloric, isonitrogenous placebo twice daily prior to meals. Body composition, body weight, and circumferences of bicep, thigh, and calf were taken preand post-trek. The participants from both treatments experienced significant loss of LBM and weight loss after 13 days at altitudes above 2810m (P< 0.05). However, there was no difference in loss of LBM (leucine -1.2 ± 1.6%; placebo -2.1 ± 1.5%), body weight (leucine -2.2 ± 1.5%; placebo -2.3 ± 2.0%), or circumferences between the groups. Overall, our results indicate that under the conditions of this study, leucine did not significantly reduce LBM loss during 13 days of altitude-induced hypoxia. This study was funded by Glanbia Nutritionals. ABSTRACT.Ill LIST OF TABLES.v LIST OF FIGURES. vl.Ill LIST OF TABLES.v LIST OF FIGURES. vl INTRODUCTION.1 M ETHODS.4 Partlclpants.4 Study Design.4 Supplement.5 Anthropometrics, Body Composition, and Circumferences. 6 Diet and Physical A ctivity.7 Statistical Analysis.8 RESULTS. 9 DISCUSSION. 15 Strengths and Limitations.19 Conclusion.20 APPENDIX.21 REFERENCES. 29 TABLE OF CONTENTS
Deficiency of annexins A5 and A6 induces complex changes in the transcriptome of growth plate cartilage but does not inhibit the induction of mineralization

Initiation of mineralization during endochondral ossification is a multistep process and has been assumed to correlate with specific interactions of annexins A5 and A6 and collagens. However, skeletal development appears to be normal in mice deficient for either A5 or A6, and the highly conserved structures led to the assumption that A5 and A6 may fulfill redundant functions. We have now generated mice deficient of both proteins. These mice were viable and fertile and showed no obvious abnormalities. Assessment of skeletal elements using histologic, ultrastructural, and peripheral quantitative computed tomographic methods revealed that mineralization and development of the skeleton were not significantly affected in mutant mice. Otherwise, global gene expression analysis showed subtle changes at the transcriptome level of genes involved in cell growth and intermediate metabolism. These results indicate that annexins A5 and A6 may not represent the essential annexins that promote mineralization in vivo. © 2010 American Society for Bone and Mineral Research
Bone material quality in transiliac bone biopsies of postmenopausal osteoporotic women after 3 years of strontium ranelate treatment

Strontium ranelate (SrR) is a relatively new treatment for osteoporosis. In this study we investigated its potential impact on human bone material quality in transiliac bone biopsies from postmenopausal osteoporotic women treated 3 years with calcium and vitamin D plus either 2 g SrR per day or placebo. Bone mineralization density distribution (BMDD), strontium (Sr) concentration, collagen cross‐link ratio, and indentation modulus were analyzed by quantitative backscattered electron imaging, electron‐induced X‐ray fluorescence analysis, synchrotron radiation induced micro X‐ray fluorescence elemental mapping, Fourier transform infrared imaging, and nanoindentation, respectively. The BMDD of SrR‐treated patients was shifted to higher atomic numbers (Zmean +1.5%, p < .05 versus placebo). We observed Sr being preferentially incorporated in bone packets formed during SrR treatment up to 6% atom fraction [Sr/(Sr + Ca)] depending on the SrR serum levels of the individuals (correlation r = 0.84, p = .018). Collagen cross‐link ratio was preserved in SR‐treated bone. The indentation modulus was significantly decreased in younger versus older bone packets for both placebo‐ (−20.5%, p < .0001) and SrR‐treated individuals (−24.3%, p < .001), whereas no differences were found between the treatment groups. In conclusion, our findings indicate that after SrR treatment, Sr is heterogeneously distributed in bone and preferentially present in bone packets formed during treatment. The effect of SrR on BMDD seems to be due mainly to the uptake of Sr and not to changes in bone calcium content. Taken together, these data provide evidence that the investigated bone quality determinants at tissue level were preserved in postmenopausal osteoporotic women after 3‐year treatment with 2 g SrR per day plus calcium and vitamin D. © 2010 American Society for Bone and Mineral Research
Cbp recruitment of Csk into lipid rafts is critical to c‐Src kinase activity and bone resorption in osteoclasts

A tyrosine kinase, c‐Src, that plays an indispensable role in ruffled border formation and bone resorption is constitutively active in osteoclasts. However, to date, the molecular mechanism underlying increased c‐Src activity in osteoclasts is unknown. To address this, we first examined the expression levels and subcellular localization of Csk, a negative regulatory kinase for c‐Src. We found that the expression level of Csk in osteoclasts was comparable with that of other tissues. However, in osteoclasts, Csk was hardly localized in lipid rafts, where c‐Src is highly expressed. Interestingly, expression of Cbp, which recruits Csk into lipid rafts through physical interaction with Csk, was very low in osteoclasts compared with other tissues. To understand the importance of Cbp in osteoclasts, we introduced Cbp into osteoclasts using an adenovirus gene delivery system. Introduction of Cbp stimulated recruitment of Csk into lipid rafts and suppressed c‐Src activity in a dose‐dependent manner. Furthermore, introduction of Cbp markedly inhibited formation of actin rings and bone‐resorbing activity in osteoclasts. In addition, treatment with RANKL and overexpression of TRAF6 or NFAT2 inhibited Cbp expression in the osteoclastogenic cell line RAW264.7 along with osteoclastic differentiation. NFAT2 overexpression also inhibited Cbp expression in spleen macrophages. Collectively, our results indicate that reduction in Cbp expression is responsible for maintaining high c‐Src activity in osteoclasts. These findings contribute to an understanding of the unique regulatory system for c‐Src in osteoclasts. © 2010 American Society for Bone and Mineral Research