Gingival cell growth with antiresorptive treatment combined with corticosteroids or antiestrogen

Objectives: Antiresorptive treatment has been shown to impair mucosal cell proliferation, migration, and viability. However, in the clinic, antiresorptives are often used in combination with other drugs. We studied the effect of antiresorptives combined with a corticosteroid or antiestrogen on oral mucosal keratinocytes and fibroblasts.Material and methods: Human gingival keratinocyte and fibroblast cell lines were exposed to bisphosphonates (BPs) and denosumab in different concentrations and durations together with an antiestrogen or corticosteroid. Changes in cell viability, proliferation and migration after exposures were measured. Data were evaluated with hierarchical linear mixed model for repeated measurements.Results: Bisphosphonate exposure suppressed keratinocyte and fibroblast cell viability, proliferation, and migration in a time-dependent manner. Combining a corticosteroid or antiestrogen with BPs further increased this negative effect. Denosumab alone had a mild positive effect on keratinocyte and fibroblast growth. When denosumab was combined with a corticosteroid or antiestrogen, cell growth was suppressed.Conclusions: Our results show that coexisting medications may increase the negative impact of BPs or denosumab on oral mucosal cells

Awareness of hypertension and depressive symptoms: a cross-sectional study in a primary care population

Objective: To investigate the association of hypertension awareness and depressive symptoms, and to analyse factors predisposing aware hypertensives to depressive symptoms.Design: Cross-sectional study in a primary care population.Setting: Cardiovascular risk factor survey in two semi-rural towns in Finland.Subjects: Two thousand six hundred seventy-six middle-aged risk persons without an established cardiovascular or renal disease or type 2 diabetes.Main outcome measures: Depressive symptoms, previous and new diagnosis of hypertension.Results: Hypertension was diagnosed in 47.9% of the subjects, of whom 34.5% (442/1 282) had previously undetected hypertension. Depressive symptoms were reported by 14% of the subjects previously aware of their hypertension, and by 9% of both unaware hypertensives and normotensive subjects. In the logistic regression analysis, both the normotensive (OR 0.62, 95% CI 0.45–0.86) (p = 0.0038) and the unaware hypertensive subjects (OR 0.54, 95% CI 0.35–0.84) (p = 0.0067) had lower risk for depressive symptoms than the previously diagnosed hypertensives. Among these aware hypertensives, female gender (OR 3.61, 95% CI 2.06–6.32), harmful alcohol use (OR 2.55, 95% CI 1.40–4.64) and obesity (OR 2.50, 95% CI 1.01–6.21) predicted depressive symptoms. Non-smoking (OR 0.57, 95% Cl 0.33–0.99) and moderate leisure-time physical activity compared to low (OR 0.53, 95% CI 0.33–0.84) seemed to buffer against depressive symptoms.Conclusion: Depressive symptoms are common in hypertensive persons even without comorbidities, if the person is already aware of his/her hypertension. Many modifiable, lifestyle associated factors may contribute to the association of hypertension and depressive symptoms.</p

Associations Between Daytime Sleepiness, Psychological Symptoms, Headache, and Abdominal Pain in Schoolchildren

Daytime sleepiness and different symptoms are common problems affecting health and well-being of schoolchildren. This population-based cohort study included 568 children who were followed from ages 10 to 15 years. Daytime sleepiness, headache, abdominal pain, and psychological symptoms (depression, irritability or bad temper, nervousness, anxiety, and dejection) were assessed by self-administered questionnaires. The prevalence of frequent daytime sleepiness was 13% at the ages of 10 and 12 years and increased significantly up to 24% at the age of 15 (p </p

Staircase-pattern neonatal line in human deciduous teeth is associated with tooth type

ObjectiveThe staircase (Sc) pattern enamel microstructure is an expression of an impaired ameloblast function. It has been reported to appear in the neonatal line (NNL), the accentuated stria evincing live birth in deciduous tooth enamel. Our objective was to investigate the prevalence of Sc NNL in deciduous tooth types and its possible association with perinatal circumstances.DesignSc in the NNL of 88 teeth, a collection derived from a long-term, prospectively followed population cohort, was recorded with linear polarised transmitted light and analysed for tooth type, duration and mode of delivery, and pain medication used during labour.ResultsSc prevalence in the NNL differed highly significantly between tooth types (p ConclusionThis research indicates that the NNL location within tooth crown enamel has a strong impact on microstructural changes along the NNL. Considering our results of Sc prevalence, deciduous canines, having the least Sc appearance, could be used in studies that aim to investigate factors associated with NNL width. In addition, Sc prevalence variation in first deciduous molars might enable to investigation of physiological stressors strong enough to cause ameloblast impairment, such as Sc.</p

Ideal cardiovascular health and quality of life among Finnish municipal employees

Ideal cardiovascular health has been defined by the American Heart Association as the absence of clinically manifest cardiovascular disease together with the presence of favorable levels of cardiovascular health metrics. The ideal metrics are hard to achieve and the aim of this study was to assess the association between favorable cardiovascular health and perceived overall quality of life (QoL).A cross-sectional study was conducted in Finland among 836 employees in 2014 (732 women, 104 men, mean age 48 (SD 10) years) from ten municipal work units. The ideal metrics were evaluated with a physical examination, laboratory tests, medical history and self-administered questionnaires. The cardiovascular health was categorized into three groups by achievement of the ideal metrics. QoL was assessed with the EUROHIS-QOL 8-item index.The prevalence of having 5–7 of the ideal metrics was 25.1% (210), of having 3–4 it was 53.6% (448) and for 0–2 it was 21.3% (178). The EUROHIS-QOL mean score among all participants was 3.92 (SD 0.54). The EUROHIS-QOL mean score had a positive association with the sum of ideal metrics, and was 3.72, 3.91 and 4.10 among subjects with 0–2, 3–4 and 5–7 ideal metrics, respectively. Furthermore, poor sleep quality and disease burden had a significant negative association with QoL.A favorable cardiovascular health status together with good sleep quality seems to have a clear association with overall quality of life among employees in municipal work units.</p

Effect of Denosumab on Femoral Periprosthetic BMD and Early Femoral Stem Subsidence in Postmenopausal Women Undergoing Cementless Total Hip Arthroplasty

Antiresorptive denosumab is known to improve the quality and strength of cortical bone in the proximal femurs of osteoporotic women, but its efficacy in preventing periprosthetic bone loss and reducing femoral stem migration has not been studied in women undergoing cementless total hip arthroplasty. We conducted a single‐center, randomized, double‐blinded, placebo‐controlled trial of 65 postmenopausal women with primary hip osteoarthritis and Dorr type A or B proximal femur anatomy. The patients randomly received subcutaneous injections of denosumab 60 mg or placebo once every 6 months for 12 months, starting 1 month before surgery. The primary endpoint was the change in bone mineral density (BMD) of the proximal femur (Gruen zone 7) at week 48, and the secondary endpoint was stem subsidence measured by radiostereometric analysis (RSA) at week 48. Exploratory endpoints included changes in BMDs of the contralateral hip, lumbar spine and distal radius, serum levels of bone turnover markers, walking speed, walking activity, patient‐reported outcome measures, and radiographic assessment of stem osseointegration. The participants underwent vertebral‐fracture assessment in an extension safety study at 3 years. Denosumab significantly decreased bone loss in the medial femoral neck (zone 7) and increased periprosthetic BMD in the greater trochanteric region (zone 1) and lesser trochanteric region (zone 6). Denosumab did not reduce temporary femoral stem migration. The migration occurred mainly during the settling period (0 to 12 weeks) after implantation of the prosthesis. All of the stems osseointegrated, as evaluated by RSA and radiographs. There were no intergroup differences in functional recovery. Discontinuation of denosumab did not lead to any adverse events. In conclusion, denosumab increased periprosthetic BMD in the clinically relevant regions of the proximal femur, but the treatment response was not associated with any reduction of initial stem migration.

The Impact of a Web-Based Course Concerning Patient Education for Mental Health Care Professionals: Quasi-Experimental Study

Background: Continuing education has an important role in supporting the competence of health care professionals. Although Web-based education is a growing business in various health sectors, few studies have been conducted in psychiatric settings to show its suitability in demanding work environments.Objective: We aimed to describe the impact of a Web-based educational course to increase self-efficacy, self-esteem, and team climate of health care professionals. Possible advantages and disadvantages of the Web-based course are also described.Methods: The study used nonrandomized, pre-post intervention design in 1 psychiatric hospital (3 wards). Health care professionals (n=33) were recruited. Self-efficacy, self-esteem, and team climate were measured at 3 assessment points (baseline, 8 weeks, and 6 months). Possible advantages and disadvantages were gathered with open-ended questions at the end of the course.Results: Our results of this nonrandomized, pre-post intervention study showed that health care professionals (n=33) had higher self-efficacy after the course, and the difference was statistically significant (mean 30.16, SD 3.31 vs mean 31.77, SD 3.35; P=.02). On the other hand, no differences were found in the self-esteem or team climate of the health care professionals before and after the course. Health care professionals found the Web-based course useful in supporting their work and relationships with patients. The tight schedule of the Web-based course and challenges in recruiting patients to use the patient education program with health care professionals were found to be the disadvantages.Conclusions: Web-based education might be a useful tool to improve the self-efficacy of health care professionals even in demanding work environments such as psychiatric hospitals. However, more studies with robust and sufficiently powered data are still needed

Association of Early Beta-amyloid Accumulation and Neuroinflammation Measured with [11C]PBR28 in Elderly Individuals Without Dementia

OBJECTIVE: To examine whether early β-amyloid (Aβ) accumulation and metabolic risk factors are associated with neuroinflammation in elderly individuals without dementia. METHODS: We examined 54 volunteers (mean age 70.0, 56% women, 51% APOE ε4 carriers) with a TSPO-tracer [11C]PBR28 to assess neuroinflammation and with [11C]Pittsburgh compound B (PiB) to assess cerebral Aβ accumulation. [11C]PBR28 and [11C]PiB standardized uptake value ratios (SUVRs) were quantified in six regions of interests by using the cerebellar cortex as a pseudo-reference/reference region, respectively. Fasting venous glucose, insulin, and high sensitivity C-reactive protein (hs-CRP) values were determined. Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. A subset of individuals (n=11) underwent CSF sampling, and Aβ40, Aβ42, total-tau, phospho-tau, soluble TREM2 and YKL-40 levels were measured. RESULTS: Among the whole study group, no significant association was found between [11C]PiB and [11C]PBR28 SUVR composite scores (slope 0.02, p=0.30). However, higher [11C]PiB binding was associated with higher [11C]PBR28 binding among amyloid negative ([11C]PiB composite score ≤1.5) (TSPO-genotype, age and sex adjusted slope 0.26, p=0.008) but not among amyloid positive participants (slope: -0.004, p=0.88). Higher CSF sTREM2 (rs 0.72, p=0.01) and YKL-40 (rs=0.63, p=0.04) concentrations were associated with a higher [11C]PBR28 composite score. Higher body mass index, HOMA-IR, and hs-CRP were associated with higher [11C]PBR28 binding in brain regions where Aβ accumulation is first detected in Alzheimer's disease (AD). CONCLUSIONS: While there was no association between amyloid and neuroinflammation in the overall study group, neuroinflammation was associated with amyloid among the subgroup at early stages of amyloid pathology

Alendronate-induced disruption of actin cytoskeleton and inhibition of migration/invasion are associated with cofilin downregulation in PC-3 prostate cancer cells

Bisphosphonates are used for prevention of osteoporosis and metastatic bone diseases. Anti-invasive effects on various cancer cells have also been reported, but the mechanisms involved are not well-understood. We investigated the effects of the nitrogen-containing bisphosphonate alendronate (ALN) on the regulation of actin cytoskeleton in PC-3 cells. We analyzed the ALN effect on the organization and the dynamics of actin, and on the cytoskeleton-related regulatory proteins cofilin, p21-associated kinase 2 (PAK2), paxillin and focal adhesion kinase. Immunostainings of cofilin in ALN-treated PC-3 cells and xenografts were performed, and the role of cofilin in ALN-regulated F-actin organization and migration/invasion in PC-3 cells was analyzed using cofilin knockdown and transfection. We demonstrate that disrupted F-actin organization and decreased cell motility in ALN-treated PC-3 cells were associated with decreased levels of total and phosphorylated cofilin. PAK2 levels were also lowered but adhesion-related proteins were not altered. The knockdown of cofilin similarly impaired F-actin organization and decreased invasion of PC-3 cells, whereas in the cells transfected with a cofilin expressing vector, ALN treatment did not decrease cellular cofilin levels and migration as in mock transfected cells. ALN also reduced immunohistochemical staining of cofilin in PC-3 xenografts. Our results suggest that reduction of cofilin has an important role in ALN-induced disruption of the actin cytoskeleton and inhibition of the PC-3 cell motility and invasion. These data also support the idea that the nitrogen-containing bisphosphonates could be efficacious in inhibition of prostate cancer invasion and metastasis, if delivered in a pharmacological formulation accessible to the tumors.</p

Prospective study on the effect of short-term androgen deprivation therapy on PSMA uptake evaluated with 68Ga-PSMA-11 PET/MRI in men with treatment-naïve prostate cancer

PURPOSE: Based on in vitro studies, it is known that androgen deprivation therapy (ADT) increases prostate-specific membrane antigen (PSMA) expression. Therefore, we hypothesised that ADT improves the performance of PSMA-PET imaging in primary staging of prostate cancer. The purpose of the study was to demonstrate the time course effect of ADT on PSMA uptake in different types of metastatic lesions evaluated with 68Ga-PSMA-11 PET/MRI.METHODS: Nine men with treatment-naïve prostate cancer were enrolled to a prospective, registered (NCT03313726) clinical trial. A 68Ga-PSMA-11 PET/MRI was performed once before and 3 times post-ADT (degarelix, Firmagon). Change of maximum standardised uptake values (SUVmax) in prostate, lymph nodes, bone metastases, and physiologically PSMA-avid organs were evaluated in a time frame of 1-8 weeks.RESULTS: All patients reached castration levels within 10 days, and 50% decrease in prostate-specific antigen (PSA) concentration was observed 14 days post-ADT. A heterogeneous increase in PSMA uptake was observed 3 to 4 weeks post-ADT. This phenomenon was definitively more evident in bone metastases: 13 (57%) of the metastasis, with a mean (range) SUVmax increase of 77% (8-238%). In one patient, already having bone metastases at baseline, three new bone metastases were observed post-ADT. Of lesions with reduced SUVmax, none disappeared.CONCLUSIONS: Both in patient and region level, increase in PSMA uptake post-ADT is heterogenous and is seen most evidently in bone metastases. Preliminary results on a small cohort of patients suggest the clinical impact of ADT on improving the performance of 68Ga-PSMA PET in staging seems to be minor. However, the optimal imaging time point might be 3 to 4 weeks post-ADT. Since none of the metastases with decreasing SUVmax disappeared, it seems that short-term usage of ADT does not interfere with the interpretation of 68Ga-PSMA PET.TRIAL REGISTRATION: NCT03313726, registered 18 October 2017; EUDRA-CT, 2017-002345-29.</p