Effects of the DL76 Antagonist/Inverse Agonist of Histamine H3 Receptors on Experimental Periodontitis in Rats: Morphological Studies.

BACKGROUND: Periodontitis preceded by gingivitis is the most common form of periodontal disease and occurs due to the interaction of microorganisms present in the complex bacterial aggregates of dental plaque biofilm and their metabolism products with periodontal tissues. Histamine is a heterocyclic biogenic amine acting via four types of receptors. Histamine H3 receptors act as presynaptic auto/heteroreceptors to regulate the release of histamine and other neurotransmitters. AIM: Since the nervous system is able to regulate the progression of the inflammatory process and bone metabolism, the aim of this study was to investigate the effects of DL76, which acts as an antagonist/inverse agonist of H3 receptors, on the course of experimental periodontitis. MATERIALS AND METHODS: This study was conducted in 24 mature male Wistar rats weighing 245-360 g, aged 6-8 weeks. A silk ligature was placed on the second maxillary molar of the right maxilla under general anesthesia. From the day of ligating, DL76 and 0.9% NaCl solutions were administered subcutaneously for 28 days in the experimental and control groups, respectively. After the experiment, histopathological, immunohistochemical and radiological examinations were performed. RESULTS: Ligation led to the development of the inflammatory process with lymphocytic infiltration, increased epithelial RANKL and OPG expression as well as bone resorption. DL76 evoked a reduction in (1) lymphocytic infiltration, (2) RANKL and OPG expression as well as (3) bone resorption since the medians of the mesial and distal interdental spaces in the molars with induced periodontitis were 3.56-fold and 10-fold lower compared to the corresponding values in saline-treated animals with periodontitis. CONCLUSION: DL76 is able to inhibit the progression of experimental periodontitis in rats, as demonstrated by a reduction in the inflammatory cell infiltration, a decrease in the RANKL/RANK OPG pathway expression and a reduction in the alveolar bone resorption.

Association between PD-L1 Expression and the Prognosis and Clinicopathologic Features of Non-Clear Cell Renal Cell Carcinoma.

PD-L1 is one of the two programmed cell death 1 (PD-1) ligands and a part of an immune checkpoint system (PD-1/PD-L1) with widespread clinical application. The aim of this study was to investigate PD-L1 expression and its association with clinicopathological and prognostic significance in non-clear cell renal cell carcinoma (non-ccRCC) patients. A total of 41 papillary (pRCC) and 20 chromophobe (chRCC) RCC tumors were examined for PD-L1 expression by immunohistochemistry in the cancer cells and tumor-infiltrating mononuclear cells (TIMCs). PD-L1 positivity was detected in 36.6% pRCC and 85.0% chRCC cancer cells, while PD-L1 positivity was observed in 73.2% pRCC and 50.0% chRCC TIMCs. PD-L1 positivity in both pRCC and chRCC tumor cells was not correlated with any of the examined clinicopathological features, while PD-L1 positivity in TIMCs was associated with the age of patients with pRCC. During follow-up, the death was documented among 6 patients with pRCC. Papillary RCC patients with PD-L1-positive tumor cells were significantly associated with an increased risk of death compared with patients with PD-L1-negative cancer cells. A similar trend was observed when comparing PD-L1 expression in TIMCs. However, no differences in overall survival for PD-L1-positive pRCC patients with compared to PD-L1-negative patients were observed in tumor cells or TIMCs.

Height loss in postmenopausal women predicts multiple fractures in 10-year follow-up: results from the RAC-OST-POL study.

INTRODUCTION: In daily practice the diagnostic process for osteoporosis in elderly patients should also include physical assessment. The aim of the study was to verify the hypothesis that height loss (HL) predicts fracture incidence. MATERIAL AND METHODS: The study was performed in an epidemiological sample of postmenopausal women recruited in the RAC-OST-POL study. At baseline, data were collected in 978 postmenopausal women at a mean age of 66.48±7.6 years, and at 10-year follow-up 640 patients remained, with a mean age of 75.04 ± 6.95 years. Current height and HL were established in regard to maximal life height. Data on fracture incidence were gathered throughout the period of observation. RESULTS: During the follow-up period 190 osteoporotic fractures were noted. Ninety-one women had one fracture, and in 38 women, multiple fractures occurred. In the fractured and unfractured subgroups, HL was 5.45 ± 3.28 and 4.8 ± 3.56 cm, respectively, and differed significantly (p < 0.05). HL in subjects without fracture did not differ from those with one fracture (HL 4.8 ± 3.56 vs. 4.8 ± 2.66 cm, respectively). For patients with more than one fracture HL was 7.03 ± 4.06 cm and was significantly higher than in subjects with one or without any fracture (p < 0.01). Based on receiver operating characteristic (ROC) analysis, HL of 6 cm was identified as the cut-off point for high risk of multiple fractures. CONCLUSION: HL of at least 6 cm is the predictor of multiple fractures in a prospective observation of a representative epidemiological female sample. Therefore, the measurement of HL should always be included in patients' assessments.

Does the VHL polymorphisms rs779805 and rs1642742 affect renal cell carcinoma susceptibility, prognosis and survival in Central European population?

Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system. The von Hippel-Lindau (VHL) tumor suppressor gene play an essential role in the tumorigenic pathway of clear cell RCC (ccRCC). This study was aimed to clarify the influence of VHL polymorphisms on ccRCC susceptibility and survival in Central European population. We genotyped 2 single-nucleotide polymorphisms (SNPs) rs779805 and rs1642742 in VHL gene and assessed their associations with ccRCC risk, clinicopathologic parameters, and prognosis in 171 cases. The selected SNPs were genotyped by ROCHE LifeCycler 96 using tumor tissue-derived DNA. Both SNPs do not directly influence ccRCC susceptibility and overall survival. A significant associations were found between allele G and genotypes AG and GG of rs779805 in the VHL tumor suppressor gene and increased tumor size, as well as high nuclear grade. Furthermore, a statistically significant association was observed between rs1642742 of VHL gene and low pathological tumor stage and between rs779805 of VHL gene and high pathological tumor stage. Both investigated SNPs can be important prognostic indicators of RCC in the Central European population, because statistically significant associations were observed between evaluated VHL polymorphisms and the best known factors with proven prognostic significance in kidney cancer.

Height Loss Is an Independent Predictor of Fracture Incidence in Postmenopausal Women: The Results from the Gliwice Osteoporosis Study (GO Study).

BACKGROUND: The aim of a longitudinal, retrospective study was to establish variables predicting fracture incidence over a decade. METHODS: The study sample comprises a group of 457 postmenopausal women aged over 55 years, recruited from the database of an outpatient osteoporotic clinic. Several variables with potential influence on bone status, including the measurement of body height and hip bone densitometry, were collected. BMD at the femoral neck (FN BMD) was established using a Prodigy device (Lunar, GE, USA). Current body height was compared with the maximal historical body height in early adulthood, as reported by the patient. RESULTS: Three hundred and ninety-four women did not have fractures during the follow up, and 63 subjects presented fractures. Subjects with fracture had lower FN BMD with a T-score of -1.86 ± 1.04 compared to -1.44 ± 0.89 in those without fractures (p < 0.001). Mean height loss (HL) was 3.47 ± 2.11 cm in fractured subjects and 2.50 ± 2.47 cm in unfractured ones, and differed significantly, p < 0.01. Fracture incidence was significantly related to age, rheumatoid arthritis, falls, and previous fractures. In the multivariable analysis using logistic regression, FN BMD, baseline fracture, and HL were identified as the significant predictors of fractures of follow up. CONCLUSIONS: Osteoporotic fractures in postmenopausal women were predicted by FN BMD, prior fracture(s), and HL easily established during physical examination.

Functional status as a predictor of the incidence of falls in 10-year follow-up: results from the RAC-OST-POL study.

INTRODUCTION: The aim of this prospective study was to establish the influence of baseline functional status on the incidence of falls. MATERIAL AND METHODS: The study was performed in an epidemiological sample of postmenopausal women from the RAC-OST-POL study. At baseline there were 978 postmenopausal women with a mean age of 65.9 ± 7.6 years, and at the end of 10-year follow-up 640 patients with a mean age of 65.04 ± 6.95 years remained in observation. Functional status was established at baseline using a stand up and go test (SAG) and the Lawton Instrumental Activities of Daily Living (IADL) scale. Afterwards, data on fall incidence were updated annually using phone interviews. RESULTS: In a 10-year period of observation, in 384 (60%) women at least one fall occurred. At baseline, 90% of subjects achieved maximal value in the IADL scale (24 points). Although the difference between mean IADL score in those who fell and did not fall was noticeable (23.50 ± 1.68 vs. 23.65 ± 1.47, respectively), the category of any IADL score below 24 points was significantly more frequent in women with falls (71.9% vs. 28.1%; chi-square 4.2, p < 0.05). The SAG score in the subgroup with falls was (10.75 ± 3.39) and did not differ in comparison to subgroup without falls (10.27 ± 2.72). CONCLUSION: The baseline result of the IADL scale but not that of the SAG test are related to the incidence of falls in a 10-year prospective observation. Adequate correction of functional status may benefit patients and reduce the fall rate.

Incidence of Concomitant Neoplastic Diseases, Tumor Characteristics, and the Survival of Patients with Lung Adenocarcinoma or Squamous Cell Lung Carcinoma in Tobacco Smokers and Non-Smokers-10-Year Retrospective Single-Centre Cohort Study.

Changes in smoking trends and changes in lifestyle, together with worldwide data regarding the incidence of lung cancer in the group of patients with no previous history of smoking, leads to consideration of the differences in the course of the disease, the time of cancer diagnosis, the survival rate, and the occurrence of comorbidities in this group of patients. This study aimed to determine the occurrence of non-smokers among patients undergoing anatomical resection of the lung tissue due to lung carcinoma and to investigate the differences between the course of lung cancer, survival, and the comorbidities in the groups of patients with lung cancer depending on the history of tobacco smoking. The study included a cohort of 923 patients who underwent radical anatomical resection of the lung tissue with lung primary adenocarcinoma or squamous cell carcinoma. The Chi2 Pearson's test, the t-test, the Mann-Whitney U test, the Kaplan-Meier method, the Log-rank test with Mantel correction, and the Cox proportional hazard model were used for data analysis. We observed a significantly higher mean age of smoking patients compared to the mean age of non-smoking patients. The coexistence of former neoplastic diseases was significantly more frequent in the group of non-smokers compared to the group of smoking patients. We did not observe differences depending on smoking status in the tumor stage, grade, vascular and pleural involvement status in the diagnostic reports. We did not observe differences in the survival between smokers vs. non-smokers, however, we revealed better survival in the non-smoker women group compared to the non-smoker men group. In conclusion, 22.11% of the patients undergoing radical anatomical resection of the lung tissue due to lung cancers were non-smokers. More research on survival depending on genetic differences and postoperative treatment between smokers and non-smokers is necessary.

Does the Immunohistochemical Expression of CD44, MMP-2, and MMP-9 in Association with the Histopathological Subtype of Renal Cell Carcinoma Affect the Survival of Patients with Renal Cancer?

CD44, MMP-2, and MMP-9 are new potential molecular prognostic markers in renal cell carcinoma (RCC). The aim of the study was to analyze whether the expression of CD44, MMP-2, and MMP-9 in association with the histopathological subtype of RCC affects the survival of patients with renal cancer. The study population included 243 clear cell RCC (ccRCC) and 59 non-ccRCC cases. A total of 302 tumors were examined for CD44, MMP2, and MMP9 expression by immunohistochemistry. The expression levels of the proteins were scored by semi-quantitative methods, and the correlation with overall patient survival was verified. We found no significant differences in CD44 expression levels between cc-RCC and non-ccRCC cases; however, significant differences existed in the degree of MMP-2 and MMP-9 expression between cc-RCC and non-ccRCC cases. There was significantly higher MMP expression in non-ccRCC than in ccRCC cases. Univariate Cox regression analysis showed that increased CD44 expression and histopathological subtype of ccRCC were predictors of shorter overall survival. Moreover, MMP-2 overexpression slightly reduced the risk of patient death, while MMP-9 expression did not show an association with patients' survival. However, on multivariate analysis, only the histopathological subtypes of ccRCC and CD44 expression were independent risk factors for patient death.

Two Single Nucleotide Polymorphisms in the Von Hippel-Lindau Tumor Suppressor Gene in Patients with Clear Cell Renal Cell Carcinoma.

The most common subtype of renal cell carcinoma (RCC) is clear cell type (ccRCC), which accounts for approximately 75% of cases. von Hippel-Lindau (VHL) gene has been shown to be affected in more than half of ccRCC cases. Two single nucleotide polymorphisms (SNPs) located in VHL gene, rs779805 and rs1642742, are reported to be involved in the occurrence of ccRCC. The aim of this study was to assess their associations with clinicopathologic and immunohistochemical parameters, as well as risk and survival of ccRCC. The study population consisted of 129 patients. No significant differences in genotype or allele frequencies of VHL gene polymorphisms were observed between ccRCC cases and control population, and we have found that our results do not indicate a significant relationship of these SNPs with respect to ccRCC susceptibility. Additionally, we did not observe a significant association of these two SNPs with ccRCC survival. However, our results conclude that rs1642742 and rs779805 in the VHL gene are associated with increased tumor size, which is the most important prognostic indicator of renal cancer. Moreover, our analysis showed that patients with genotype AA of rs1642742 have a trend towards higher likelihood of developing ccRCC within their lifetime, while allele G of rs779805 can have a preventive effect against the development of renal cancer in stage 1. Therefore, these SNPs in VHL may be useful as genetic tumor markers for the molecular diagnostics for ccRCC patients.

POL-RISK: an algorithm for 10-year fracture risk prediction in postmenopausal women from the RAC-OST-POL study.

INTRODUCTION: Fragility fractures are the major consequence of osteoporosis. Thus, fracture risk assessment is an essential part of the diagnostic process in osteoporosis. OBJECTIVES: The aim of the study was to develop an algorithm for fracture risk prediction. PATIENTS AND METHODS: Bone status was evaluated in a population­basedcohort of postmenopausal women at a mean (SD) age of 66.4 (7.8) years. Subsequently, all participants were contacted by phone once a year (for 10 consecutive years) to update their history of fractures. At the end of the 10­year follow­up, the number of the study participants was 640, of whom 129 had a history of 190 osteoporotic fractures recorded during the study period. Statistical analysis included multistep data preprocessing, feature selection, identification of fracture risk factors, and design of the final model. Logistic regression models were fitted and used for the evaluation of variables from determined feature sets, including global fit measures, as well as individual parameters, such as the Wald statistic and P value, odds ratio, and 95% CI. RESULTS: The 10­year risk for any fracture depended on the age of the patient, the number of recorded fractures after the age of 40 years, femoral neck bone mass, and the occurrence of falls during the previous year. The achieved equation was incorporated into an algorithm, available at the www.fracture­risk.pl webpage. CONCLUSION: A fracture prediction algorithm was developed in a longitudinal study to enable calculation of the 10­year fracture risk. Identification of patients at a high risk of fracture should be followed by implementation of appropriate treatment strategy to reduce the number of future fractures.

Prognostic relevance of clinicopathological factors in sporadic and syndromic odontogenic keratocysts: A comparative study.

BACKGROUND: Current evidence suggests that nevoid basal cell carcinoma syndrome (NBCCS)-associated odontogenic keratocysts (OKCs) exhibit more aggressive clinical behavior and a higher tendency to relapse. The prognostic efficacy of various markers in sporadic and syndromic OKCs is unclear, and so are the results of studies on the usefulness of immunohistochemistry in distinguishing syndromic from sporadic OKCs. OBJECTIVES: This retrospective study aimed to compare the prognostic relevance of various clinicoradiological and histopathological features, as well as the immunoexpression of COX-2, Bcl-2, proliferating cell nuclear antigen (PCNA), p53, Ki-67, osteoprotegerin (OPG), receptor activator of nuclear factor κ B (RANK) and receptor activator of nuclear factor κ B ligand (RANKL), as well as RANKL/OPG balance between sporadic and syndromic OKCs, and to test their utility in distinguishing the 2 types of OKC. MATERIAL AND METHODS: We compared the immunoexpression of the aforementioned markers between 31 sporadic and 12 syndromic OKCs, and tested clinicopathological findings and levels of immunostaining against recurrence. RESULTS: We found a significant association between NBCCS and OKC recurrence. There were significant differences in PCNA, p53 and OPG immunoexpression between sporadic and syndromic OKCs. We also found that recurrent sporadic OKCs were significantly larger and markedly more often associated with cortical perforation. Recurrent sporadic OKCs exhibited COX-2 upregulation, but we failed to demonstrate its prognostic relevance. Recurrent syndromic OKCs showed a markedly higher RANKL > OPG ratio. CONCLUSIONS: The NBCCS-associated OKCs are significantly more prone to recur than their sporadic counterparts. Larger size and radiological signs of cortical perforation in sporadic OKCs may indicate a higher risk of recurrence. The COX-2 is upregulated in recurrent sporadic OKCs, whereas recurrent syndromic OKCs exhibit higher RANKL and lower OPG expression; however, these findings have no prognostic relevance. The immunoexpression of p53, PCNA and OPG may help to distinguish syndromic from sporadic OKCs.

Impaired Functional Status Increases Fracture Incidence in 10-year Follow-Up: The Results from RAC-OST-POL Study.

INTRODUCTION: The aim of study was to establish the influence of baseline functional status on fracture incidence. METHODOLOGY: In a prospective 10-years observation in epidemiological sample of postmenopausal women from RAC-OST-POL Study a thesis that affected functional status enhance fracture incidence was verified. At baseline, data were collected in 978 women at mean age 66.48±7.6 years and after 10 years of follow-up 640 subjects at mean age 75.04±6.95 years remained in the study. Functional status at baseline was established using Stand up and Go test (SAG) and Activity of Daily Living (IADL). Afterwards, annually data on fracture incidence were collected by phone interviews. RESULTS: In the period of observation 190 low-energy fractures in 129 women were noted. The whole group was divided into subgroups: without fracture (n=511), with one fracture (n=91) and those ones who had more than one fracture (n=38). In fractured and unfractured subgroup mean SAG results were 11.36±4.28 and 10.36±2.76, respectively and differed significantly (p<0.01). With increasing number of fractures the SAG time was longer - it was 11.15±4.49 in one fracture subgroup and 11.87±3.73 in multiple fractures subgroup, with both values significantly higher than in no fracture subjects. The mean value of IADL was 23.56±1.60. In 576 (90%) women IADL reached maximal value of 24 points. In the rest of them (n=64) IADL score was between 11 and 23 points. Mean value of IADL in fractured and unfractured subgroup were 23.27±1.97 and 23.64±1.47, respectively and differed significantly (p<0.01). CONCLUSION: The measures of functional status predict fractures in a prospective observation of representative epidemiological female sample.

Fracture risk and fracture prevalence in women from outpatient osteoporosis clinic and subjects from population-based sample: A comparison between GO Study and RAC-OST-POL cohorts.

BACKGROUND: The method of recruiting the study subjects is an important element of the study design. It can have a strong influence on the results. Different recruitment schedules can give a different picture of the studied phenomenon. OBJECTIVES: The aim of the study was to compare bone health in a group of female patients treated for osteoporosis with a population-based sample. MATERIAL AND METHODS: A cohort of women from GO Study from 1 outpatient osteoporotic clinic (n = 1442, mean age 65.8 ±6.7 years) and population-based female sample of RAC-OST-POL Study (n = 963, mean age 65.8 ±7.5 years) were studied. Mean age did not differ between groups. Mean weight, height and body mass index (BMI) in subjects from GO Study and RAC-OST-POL Study were 69.5 ±13.1 kg, 157.8 ±6.1 cm and 27.9 ±5.1 kg/m2, and 74.2 ±13.7 kg, 156.0 ±6.0 cm and 30.5 ±5.4 kg/m2, respectively, and differed significantly (p < 0.0001 for each variable). Data on clinical risk factors for osteoporosis and fractures were collected. Bone densitometry at hip was performed using a Prodigy or Lunar DPX device (GE Healthcare, Waukesha, USA). Fracture risk was established using FRAX, Garvan and POL-RISK. RESULTS: Mean values of T-score for femoral neck in subjects from GO Study and RAC-OST-POL Study were -1.67 ±0.91 and -1.27 ±0.91 and differed significantly (p < 0.0001). In GO Study and RAC-OST-POL Study, there were 518 (35.9%) and 280 (29.1%) subjects with fractures, respectively. The fracture frequency was significantly higher in the GO Study group (p < 0.001). Among clinical risk factors, only rheumatoid arthritis (p < 0.0001) secondary osteoporosis (p < 0.0001) and falls (p < 0.0001) were more frequent in RAC-OST-POL Study. Fracture risk established using FRAX, Garvan and POL-RISK calculators was significantly greater in patients enrolled in the GO Study than in subjects from the RAC-OST-POL population-based sample (p < 0.0001 for each variable). CONCLUSIONS: Differences noted between female patients treated for osteoporosis and population-based sample, especially in regard to fracture risk, reveal a strong influence of recruitment criteria on study results in the field of bone health and osteoporosis.

The Impact of Environmental and Genetic Factors on Bone Quality in Monozygotic and Dizygotic Twins.

The purpose of the research was to assess the genetic and environmental influences on bone properties. One hundred thirty-two pairs of twins (99/33 monozygotic/dizygotic) underwent anthropometric measurements and phalangeal quantitative ultrasound (DBM Sonic 1200, Igea, Italy) measuring the amplitude speed of sound (AD-SoS, m/s). The mean age was 16.78 ± 12.35 years for monozygotic twins and 14.30 ± 8 years for dizygotic. Interpair and intrapair correlations between twins were calculated. In the groups of monozygotic and dizygotic twins, Ad-SoS correlated significantly with age (r = 0.56−0.73, p < 0.05), weight (r = 0.73−0.78, p < 0.05), and height (r = 0.80−0.81, p < 0.05). The strongest intrapair correlation (r = 0.99−0.998) was noted in monozygotic females for Ad-SoS, weight, and height. There was a statistically significant correlation between the intrapair difference of Ad-SoS and age but only in the groups of monozygotic and dizygotic females (r = 0.281, r2 = 0.079, and p = 0.028; r = 0.544, r2 = 0.296, and p = 0.01, respectively). After age adjustment, it was estimated that 28.62% of Ad-SoS in women and 13.2% of Ad-SoS in men was explained by genetic influence, leading to the conclusion that Ad-SoS changed with age, weight, and height. The strongest correlation between pairs of twins was observed in monozygotic twins. The differences in bone values between female twins arose with age, which indicated the role of environmental factors.

Immunohistochemical Expression of CD44, MMP-2, MMP-9, and Ki-67 as the Prognostic Markers in Non-Clear Cell Renal Cell Carcinomas-A Prospective Cohort Study.

CD44 is the most frequently reported marker of the cancer stem cells in renal cell carcinoma (RCC). Matrix metalloproteinases MMP-2 and MMP-9 are key regulators of tumor invasion and metastasis. The aim of this study was to investigate the clinicopathologic and prognostic values of the immunohistochemical expression of CD44, MMP2, MMP9, and Ki-67 in papillary and chromophobe RCCs. In the case of papillary RCC, MMP-2 expression was positively correlated with patient age (p < 0.05), while CD44 expression was positively correlated with tumor stage (τ = 0.26, p < 0.05). Moreover, CD44 expression positively correlated with MMP-9 (τ = 0.39, p < 0.05). In the case of chromophobe RCC, only Ki-67 expression was negatively correlated with tumor stage (τ = −0.44, p < 0.05). During follow-up, a death was documented in 6 patients with papillary RCC. In these patients, CD44 expression was not a significant factor affecting the overall survival of patients (p > 0.05), whereas there was a positive correlation between increased MMP-9 expression and shorter overall survival (p < 0.05). Taken together, carcinogenesis in papillary RCC is probably dependent on both cancer stem cells and metalloproteinases activity. Expression of CD44 and MMP-9 can significantly improve the prediction of papillary RCC prognosis in the future.

Changes in osteoporosis therapy in postmenopausal women from the RAC­OST­POL study: a 10­year follow­up.

INTRODUCTION: Therapeutic regimens for osteoporosis are the key elements in the management of osteoporotic patients. OBJECTIVE: The aim of the study was to present data on changes in osteoporosis therapy in women during a 10­year follow­up. PATIENTS AND METHODS: We analyzed a population­based sample recruited in the RAC­OST­POL study. At baseline, the cohort included 978 women, of whom 541 remained in the follow­up. Mean (SD) age of the patients was 74.7 (6.6) years. RESULTS: The number of untreated women and those on alendronate decreased, while the number of patients receiving other forms of the antiresorptive therapy or calcium / vitamin D supplementation increased during the study. The percentage of untreated women in the rural areas and the urban areas was, respectively, 85% and 74.1% at baseline, and 74.3% and 63.3% at the end of the follow­up. The percentage of untreated women decreased significantly, both in rural and urban cohorts. It was accompanied by a significant increase in calcium / vitamin D supplementation in both subgroups. Regarding the antiresorptive therapy, there was a significant increase in the frequency of its use only in the rural cohort. The use of therapeutic strategies was determined by the level of education. The frequency of calcium and / or vitamin D supplementation increased significantly in all education-related categories during the follow­up. CONCLUSION: Changes in the therapy of postmenopausal women with osteoporosis, observed in a 10­year follow­up of the RAC­OST­POL study, indicated that the level of care did not improve in this group of patients.

Glucocorticoids Increase Fracture Risk and Fracture Prevalence Independently from Bone Mineral Density and Clinical Risk Factors: Results from the Gliwice Osteoporosis (GO) Study.

The aim of the study was to establish the influence of glucocorticoids (GC) on fracture risk, probability, and prevalence. A set of 1548 postmenopausal women were divided into study group - treated with GC (n=114, age 66.48±7.6 years) and controls (n=1434, age 66.46±6.83 years). Data on clinical risk factors for osteoporosis and fractures were collected. Hip bone densitometry was performed using a device Prodigy (GE, USA). Fracture probability was established by FRAX, and fracture risk by Garvan algorithm and POL-RISK. Fracture risk and fracture probability were significantly greater for GC-treated women in comparison to controls. In the study group, there were 24, 3, 24, and 6 fractures noted at spine, hip, forearm, and arm, respectively. The respective numbers of fractures reported in controls at those skeletal sites were: 186, 23, 240, and 25. The use of GCs increased significantly prevalence of all major, spine and arm fractures. Also the number of all fractures was affected by GC use. Following factors significantly increased fracture probability: age (OR 1.04 per each year; 95% CI: 1.03-1.06), GC use (OR 1.54; 95% CI: 1.03-2.31), falls (OR 2.09; 95% CI: 1.60-2.73), and FN T-score (OR 0.62 per each unit; 95% CI: 0.54-0.71). In conclusion, in patients treated with GCs the fracture risk, probability, and prevalence were increased. This effect was evident regardless of whether GC therapy is included in the algorithm as a risk factor (FRAX, POL-RISK) or not taken into consideration (Garvan nomogram).

Tracking of the biochemical changes upon pleomorphic adenoma progression using vibrational microspectroscopy.

Head and neck tumors can be very challenging to treat because of the risk of problems or complications after surgery. Therefore, prompt and accurate diagnosis is extremely important to drive appropriate treatment decisions, which may reduce the chance of recurrence. This paper presents the original research exploring the feasibility of Fourier transform infrared (FT-IR) and Raman spectroscopy (RS) methods to investigate biochemical alterations upon the development of the pleomorphic adenoma. Principal component analysis (PCA) was used for a detailed assessment of the observed changes and to determine the spectroscopic basis for salivary gland neoplastic pathogenesis. It is implied that within the healthy margin, as opposed to the tumoral tissue, there are parts that differ significantly in lipid content. This observation shed new light on the crucial role of lipids in tissue physiology and tumorigenesis. Thus, a novel approach that eliminates the influence of lipids on the elucidation of biochemical changes is proposed. The performed analysis suggests that the highly heterogeneous healthy margin contains more unsaturated triacylglycerols, while the tumoral section is rich in proteins. The difference in protein content was also observed for these two tissue types, i.e. the healthy tissue possesses more proteins in the anti-parallel ß-sheet conformation, whereas the tumoral tissue is dominated by proteins rich in unordered random coils. Furthermore, the pathogenic tissue shows a higher content of carbohydrates and reveals noticeable differences in nucleic acid content. Finally, FT-IR and Raman spectroscopy methods were proposed as very promising methods in the discrimination of tumoral and healthy tissues of the salivary gland.

Immunoexpression of RANK, RANKL and OPG in sporadic odontogenic keratocysts and their potential association with recurrence.

BACKGROUND: Odontogenic keratocysts (OKCs) are clinically aggressive lesions with relatively high recurrence rates. Dysregulation of functional equilibrium in the RANK/RANKL/OPG system is responsible for osteolysis associated with the development of OKCs. Previously published findings imply that immunoexpression of these 3 proteins may correlate with bone resorption activity in OKCs. OBJECTIVES: The rationale behind this study was to assess the potential for receptor activator of nuclear factor kappa-B (RANK), receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) expression, as well as RANKL/OPG expression ratio, to serve as prognostic indicators for OKC recurrence. MATERIAL AND METHODS: We investigated the immunoexpression patterns of RANK, RANKL and OPG, and their correlation with recurrence rates, in 41 patients with OKCs treated with enucleation. RESULTS: We found no statistically significant differences between recurrent and non-recurrent cysts in terms of either: epithelial (p = 0.404) and stromal (p = 0.469) immunoreactivity of RANK; epithelial (p = 0.649) and stromal (p = 0.198) immunoreactivity of RANKL; or epithelial (p = 1) and stromal (p = 0.604) immunoreactivity of OPG. We also did not find significant differences in the distribution of cases with respect to ratios of RANKL/OPG immunostaining scores between recurrent and non-recurrent OKCs, both in the epithelium and in the connective tissue (p = 1 and p = 0.237, respectively). CONCLUSIONS: Our results suggest that immunoexpression levels of RANK, RANKL and OPG at the time of pathological diagnosis, as well as the RANKL/OPG ratio, are not useful as prognostic markers for OKC recurrence.