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With an aging population, numerous assistive and monitoring technologies are under development to enable older adults to age in place. To facilitate aging in place predicting risk factors such as falls, and hospitalization and providing early interventions are important. Much of the work on ambient monitoring for risk prediction has centered on gait speed analysis, utilizing privacy-preserving sensors like radar. Despite compelling evidence that monitoring step length, in addition to gait speed, is crucial for predicting risk, radar-based methods have not explored step length measurement in the home. Furthermore, laboratory experiments on step length measurement using radars are limited to proof of concept studies with few healthy subjects. To address this gap, a radar-based step length measurement system for the home is proposed based on detection and tracking using radar point cloud, followed by Doppler speed profiling of the torso to obtain step lengths in the home. The proposed method was evaluated in a clinical environment, involving 35 frail older adults, to establish its validity. Additionally, the method was assessed in people's homes, with 21 frail older adults who had participated in the clinical assessment. The proposed radar-based step length measurement method was compared to the gold standard Zeno Walkway Gait Analysis System, revealing a 4.5cm/8.3% error in a clinical setting. Furthermore, it exhibited excellent reliability (ICC(2,k)=0.91, 95% CI 0.82 to 0.96) in uncontrolled home settings. The method also proved accurate in uncontrolled home settings, as indicated by a strong agreement (ICC(3,k)=0.81 (95% CI 0.53 to 0.92)) between home measurements and in-clinic assessments.

Objective To evaluate the pattern of frailty across several of social stratifiers associated with health inequalities. Design, setting and participants Cross-sectional baseline data on 51 338 community-living women and men aged 45-85 years from the population-based Canadian Longitudinal Study on Aging (collected from September 2011 to May 2015) were used in this study. Primary outcomes and measures A Frailty Index (FI) was constructed using self-reported chronic conditions, psychological function and cognitive status and physical functioning variables. Social stratifiers were chosen based on the Pan-Canadian Health Inequalities Reporting Initiative, reflecting key health inequalities in Canada. Unadjusted and adjusted FIs and domain-specific FIs (based on chronic conditions, physical function, psychological/cognitive deficits) were examined across population strata. Results The overall mean FI was 0.13±0.08. It increased with age and was higher in women than men. Higher mean FIs were found among study participants with low income (0.20±0.10), who did not complete secondary education (0.17±0.09) or had low perceived social standing (0.18±0.10). Values did not differ by Canadian province of residence or urban/rural status. After simultaneously adjusting for population characteristics and other covariates, income explained the most heterogeneity in frailty, especially in younger age groups; similar patterns were found for men and women. The average frailty for people aged 45-54 in the lowest income group was greater than that for those aged 75-85 years. The heterogeneity in the FI among income groups was greatest for the psychological/cognitive domain. Conclusions Our results suggest that especially in the younger age groups, psychological/cognitive deficits are most highly associated with both overall frailty levels and the gradient in frailty associated with income. If this is predictive of later increases in the other two domains (and overall frailty), it raises

Objective To evaluate the pattern of frailty across several of social stratifiers associated with health inequalities. Design, setting and participants Cross-sectional baseline data on 51 338 community-living women and men aged 45-85 years from the population-based Canadian Longitudinal Study on Aging (collected from September 2011 to May 2015) were used in this study. Primary outcomes and measures A Frailty Index (FI) was constructed using self-reported chronic conditions, psychological function and cognitive status and physical functioning variables. Social stratifiers were chosen based on the Pan-Canadian Health Inequalities Reporting Initiative, reflecting key health inequalities in Canada. Unadjusted and adjusted FIs and domain-specific FIs (based on chronic conditions, physical function, psychological/cognitive deficits) were examined across population strata. Results The overall mean FI was 0.13±0.08. It increased with age and was higher in women than men. Higher mean FIs were found among study participants with low income (0.20±0.10), who did not complete secondary education (0.17±0.09) or had low perceived social standing (0.18±0.10). Values did not differ by Canadian province of residence or urban/rural status. After simultaneously adjusting for population characteristics and other covariates, income explained the most heterogeneity in frailty, especially in younger age groups; similar patterns were found for men and women. The average frailty for people aged 45-54 in the lowest income group was greater than that for those aged 75-85 years. The heterogeneity in the FI among income groups was greatest for the psychological/cognitive domain. Conclusions Our results suggest that especially in the younger age groups, psychological/cognitive deficits are most highly associated with both overall frailty levels and the gradient in frailty associated with income. If this is predictive of later increases in the other two domains (and overall frailty), it raises

Alexandra O Kobza,1 Deena Herman,1 Alexandra Papaioannou,2,3 Arthur N Lau,1 Jonathan D Adachi1 1Division of Rheumatology, Department of Medicine, McMaster University, Hamilton, ON, Canada; 2Division of Geriatric Medicine, Department of Medicine, McMaster University, Hamilton, ON, Canada; 3Department of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, ON, CanadaCorrespondence: Jonathan D Adachi 501-25 Charlton Avenue East, Hamilton, Ontario, L8N 1Y2, CanadaTel +1 905-529-1317Fax +1 905-521-1297Email jd.adachi@sympatico.caAbstract: Glucocorticoids are effective immunosuppressants used in a wide variety of diseases. Their use results in secondary osteoporosis in about 30– 50% of chronic glucocorticoid users. Glucocorticoids cause a rapid decline in bone strength within the first 3– 6 months mostly due to increased bone resorption by osteoclasts. This is followed by a more gradual loss of bone partly due to decreased osteoblastogenesis and osteoblast and osteocyte apoptosis. The loss of bone strength induced by glucocorticoids is not fully captured by bone mineral density measurements. Other tools such as the trabecular bone score and advanced imaging techniques give insight into bone quality; however, these are not used widely in clinical practice. Glucocorticoid-induced osteoporosis should be seen as a widely preventable disease. Currently, only about 15% of chronic glucocorticoid users are receiving optimal care. Glucocorticoids should be prescribed at the lowest dose and shortest duration. All patients should be counselled on lifestyle measures to maintain bone strength including nutrition and weight-bearing exercise. Pharmacological therapy should be considered for all patients at moderate to high risk of fracture as there is evidence for the prevention of bone loss and fractures with a favourable safety profile. Oral bisphosphonates are the current mainstay of therapy, whereas osteoanabolic agents may be considered for those at hi

The mobility of the spine and the change in the angle of the curvatures are directly related to spinal pain and spinal stenosis. The aim of the study was the evaluation of morphology and mobility of the spine in patients who were subjected to decompression and posterior fusion with pedicle screws. The treatment group consisted of 20 patients who underwent posterior fixation of lumbar spine (one and two level fusion). The control group consisted of 39 healthy subjects. Mobility and curvatures of the spine were measured with a non-invasive device, the Spinal Mouse. Pain was evaluated with the Visual Analogue Scale (VAS). The Oswestry Disability Index (ODI) and the SF-36 were used to evaluate the degree of the functional disability and the quality of life, respectively. The measurements were recorded preoperatively and at 3, 6 and 12 months postoperatively. The mobility of the lumbar spine in the sagittal plane increased (p = 0.009) at 12 months compared to the measurements at 3 months. The mobility of the thoracic spine in the frontal plane increased (p = 0.009) at 12 months compared to the preoperative evaluation. The results of VAS, ODI and SF-36 PCS improved significantly (p<0.001). The levels of fusion exhibited a strong linear correlation (r = 0.651, p = 0.002) with the total trunk inclination in the upright position. Although pain, quality of life and spinal mobility in the sagittal and frontal planes significantly improved in the treatment group, these patients still had limited mobility and decreased curves/angles values compared to control group.

The mobility of the spine and the change in the angle of the curvatures are directly related to spinal pain and spinal stenosis. The aim of the study was the evaluation of morphology and mobility of the spine in patients who were subjected to decompression and posterior fusion with pedicle screws. The treatment group consisted of 20 patients who underwent posterior fixation of lumbar spine (one and two level fusion). The control group consisted of 39 healthy subjects. Mobility and curvatures of the spine were measured with a non-invasive device, the Spinal Mouse. Pain was evaluated with the Visual Analogue Scale (VAS). The Oswestry Disability Index (ODI) and the SF-36 were used to evaluate the degree of the functional disability and the quality of life, respectively. The measurements were recorded preoperatively and at 3, 6 and 12 months postoperatively. The mobility of the lumbar spine in the sagittal plane increased (p = 0.009) at 12 months compared to the measurements at 3 months. The mobility of the thoracic spine in the frontal plane increased (p = 0.009) at 12 months compared to the preoperative evaluation. The results of VAS, ODI and SF-36 PCS improved significantly (p<0.001). The levels of fusion exhibited a strong linear correlation (r = 0.651, p = 0.002) with the total trunk inclination in the upright position. Although pain, quality of life and spinal mobility in the sagittal and frontal planes significantly improved in the treatment group, these patients still had limited mobility and decreased curves/angles values compared to control group.

The mobility of the spine and the change in the angle of the curvatures are directly related to spinal pain and spinal stenosis. The aim of the study was the evaluation of morphology and mobility of the spine in patients who were subjected to decompression and posterior fusion with pedicle screws. The treatment group consisted of 20 patients who underwent posterior fixation of lumbar spine (one and two level fusion). The control group consisted of 39 healthy subjects. Mobility and curvatures of the spine were measured with a non-invasive device, the Spinal Mouse. Pain was evaluated with the Visual Analogue Scale (VAS). The Oswestry Disability Index (ODI) and the SF-36 were used to evaluate the degree of the functional disability and the quality of life, respectively. The measurements were recorded preoperatively and at 3, 6 and 12 months postoperatively. The mobility of the lumbar spine in the sagittal plane increased (p = 0.009) at 12 months compared to the measurements at 3 months. The mobility of the thoracic spine in the frontal plane increased (p = 0.009) at 12 months compared to the preoperative evaluation. The results of VAS, ODI and SF-36 PCS improved significantly (p<0.001). The levels of fusion exhibited a strong linear correlation (r = 0.651, p = 0.002) with the total trunk inclination in the upright position. Although pain, quality of life and spinal mobility in the sagittal and frontal planes significantly improved in the treatment group, these patients still had limited mobility and decreased curves/angles values compared to control group.

The mobility of the spine and the change in the angle of the curvatures are directly related to spinal pain and spinal stenosis. The aim of the study was the evaluation of morphology and mobility of the spine in patients who were subjected to decompression and posterior fusion with pedicle screws. The treatment group consisted of 20 patients who underwent posterior fixation of lumbar spine (one and two level fusion). The control group consisted of 39 healthy subjects. Mobility and curvatures of the spine were measured with a non-invasive device, the Spinal Mouse. Pain was evaluated with the Visual Analogue Scale (VAS). The Oswestry Disability Index (ODI) and the SF-36 were used to evaluate the degree of the functional disability and the quality of life, respectively. The measurements were recorded preoperatively and at 3, 6 and 12 months postoperatively. The mobility of the lumbar spine in the sagittal plane increased (p = 0.009) at 12 months compared to the measurements at 3 months. The mobility of the thoracic spine in the frontal plane increased (p = 0.009) at 12 months compared to the preoperative evaluation. The results of VAS, ODI and SF-36 PCS improved significantly (p<0.001). The levels of fusion exhibited a strong linear correlation (r = 0.651, p = 0.002) with the total trunk inclination in the upright position. Although pain, quality of life and spinal mobility in the sagittal and frontal planes significantly improved in the treatment group, these patients still had limited mobility and decreased curves/angles values compared to control group.

The mobility of the spine and the change in the angle of the curvatures are directly related to spinal pain and spinal stenosis. The aim of the study was the evaluation of morphology and mobility of the spine in patients who were subjected to decompression and posterior fusion with pedicle screws. The treatment group consisted of 20 patients who underwent posterior fixation of lumbar spine (one and two level fusion). The control group consisted of 39 healthy subjects. Mobility and curvatures of the spine were measured with a non-invasive device, the Spinal Mouse. Pain was evaluated with the Visual Analogue Scale (VAS). The Oswestry Disability Index (ODI) and the SF-36 were used to evaluate the degree of the functional disability and the quality of life, respectively. The measurements were recorded preoperatively and at 3, 6 and 12 months postoperatively. The mobility of the lumbar spine in the sagittal plane increased (p = 0.009) at 12 months compared to the measurements at 3 months. The mobility of the thoracic spine in the frontal plane increased (p = 0.009) at 12 months compared to the preoperative evaluation. The results of VAS, ODI and SF-36 PCS improved significantly (p<0.001). The levels of fusion exhibited a strong linear correlation (r = 0.651, p = 0.002) with the total trunk inclination in the upright position. Although pain, quality of life and spinal mobility in the sagittal and frontal planes significantly improved in the treatment group, these patients still had limited mobility and decreased curves/angles values compared to control group.

The mobility of the spine and the change in the angle of the curvatures are directly related to spinal pain and spinal stenosis. The aim of the study was the evaluation of morphology and mobility of the spine in patients who were subjected to decompression and posterior fusion with pedicle screws. The treatment group consisted of 20 patients who underwent posterior fixation of lumbar spine (one and two level fusion). The control group consisted of 39 healthy subjects. Mobility and curvatures of the spine were measured with a non-invasive device, the Spinal Mouse. Pain was evaluated with the Visual Analogue Scale (VAS). The Oswestry Disability Index (ODI) and the SF-36 were used to evaluate the degree of the functional disability and the quality of life, respectively. The measurements were recorded preoperatively and at 3, 6 and 12 months postoperatively. The mobility of the lumbar spine in the sagittal plane increased (p = 0.009) at 12 months compared to the measurements at 3 months. The mobility of the thoracic spine in the frontal plane increased (p = 0.009) at 12 months compared to the preoperative evaluation. The results of VAS, ODI and SF-36 PCS improved significantly (p<0.001). The levels of fusion exhibited a strong linear correlation (r = 0.651, p = 0.002) with the total trunk inclination in the upright position. Although pain, quality of life and spinal mobility in the sagittal and frontal planes significantly improved in the treatment group, these patients still had limited mobility and decreased curves/angles values compared to control group.

Dedicated to the memory of Dr. Colin E. Webber, This comparative study of peripheral (p) QCT, high-resolution pQCT (hr-pQCT) and 1.0 Tesla pMRI technologies quantified short-term test-retest reproducibility, validity, one-year detection limit and clinical sensitivity of each modality’s derived bone measures. Select bone outcomes were evaluated from scans performed on Hamiltonian women above 50 years old and externally validated in a population-based cohort. In the local cohort (age: 74 ± 9 years and BMI 27.65 ± 5.74 kg/m2), Tb.Sp measured on pMRI, Ct.Th and vBMD from pQCT showed significant correlations (r2=0.52-0.85) with hr-pQCT, yielding slopes near unity. Bland-Altman analyses revealed significant relationships between pQCT and pMRI bone outcome values (Tb.Th(-), Tb.N(+), BV/TV(-)) and agreement with hr-pQCT. Short-term reproducibility was < 5% for pQCT but only BV/TV was < 5% for pMRI. Co-registration and excluding individuals with fractures mildly reduced precision error and one-year change. In the local cohort, only Ct.Th and cortical vBMD associated with fractures (OR: 1.09-3.28) using hr-pQCT, which was externally validated in the national cohort. Certain trabecular measures on pMRI and pQCT erred towards increased odds for fractures locally. For pQCT, these became significant in the national cohort (OR:1.04-3.81). This Canadian reference dataset for hr-pQCT showed larger Tb.Sp and smaller Tb.N compared to Americans but age-related decline in Ct.Th and BV/TV was faster in Europeans. This study demonstrated validity of pMRI and pQCT-derived volumetric bone outcomes and reasonable short- and long-term precision error for pQCT but not 1.0T pMRI. A single CT slice from pQCT was comparable to 110 slices from hr-pQCT in associations with fractures., Doctor of Philosophy (Medical Science)

Although it is known that a change in any level of the spine alters biomechanics, there aren’t many studies to evaluate the spine as a whole both in sagittal and frontal planes. This prospective cohort study evaluates the morphology and mobility of the entire spine in patients with vertebral fractures. The treatment group consisted of 43 patients who underwent percutaneous balloon kyphoplasty or percutaneous balloon kyphoplasty plus fixation. The Control Group consisted of 39 healthy subjects. Spinal mouse was used for the assessment of the curvatures and the mobility of the spine. Clinical outcomes were evaluated by Visual-Analogue Scale and Oswestry Disability Index. The measurements were recorded at 15 days, 3, 6 and 12 months postoperatively. Regarding the curvatures and mobility in sagittal plane, a statistically significant increase appeared early at 3 months, for lumbar curve, spinopelvic angulation and overall trunk inclination. In the frontal plane, most of the improvements were recorded after 6 months. Patients with osteoporotic fracture showed statistically significant lower mean value than patients with traumatic fracture. Pain and disability index showed early improvements. This study provides a comprehensive and complete picture of the functionality of the spine in patients treated with percutaneous balloon kyphoplasty.

Although it is known that a change in any level of the spine alters biomechanics, there aren’t many studies to evaluate the spine as a whole both in sagittal and frontal planes. This prospective cohort study evaluates the morphology and mobility of the entire spine in patients with vertebral fractures. The treatment group consisted of 43 patients who underwent percutaneous balloon kyphoplasty or percutaneous balloon kyphoplasty plus fixation. The Control Group consisted of 39 healthy subjects. Spinal mouse was used for the assessment of the curvatures and the mobility of the spine. Clinical outcomes were evaluated by Visual-Analogue Scale and Oswestry Disability Index. The measurements were recorded at 15 days, 3, 6 and 12 months postoperatively. Regarding the curvatures and mobility in sagittal plane, a statistically significant increase appeared early at 3 months, for lumbar curve, spinopelvic angulation and overall trunk inclination. In the frontal plane, most of the improvements were recorded after 6 months. Patients with osteoporotic fracture showed statistically significant lower mean value than patients with traumatic fracture. Pain and disability index showed early improvements. This study provides a comprehensive and complete picture of the functionality of the spine in patients treated with percutaneous balloon kyphoplasty.

Although it is known that a change in any level of the spine alters biomechanics, there aren’t many studies to evaluate the spine as a whole both in sagittal and frontal planes. This prospective cohort study evaluates the morphology and mobility of the entire spine in patients with vertebral fractures. The treatment group consisted of 43 patients who underwent percutaneous balloon kyphoplasty or percutaneous balloon kyphoplasty plus fixation. The Control Group consisted of 39 healthy subjects. Spinal mouse was used for the assessment of the curvatures and the mobility of the spine. Clinical outcomes were evaluated by Visual-Analogue Scale and Oswestry Disability Index. The measurements were recorded at 15 days, 3, 6 and 12 months postoperatively. Regarding the curvatures and mobility in sagittal plane, a statistically significant increase appeared early at 3 months, for lumbar curve, spinopelvic angulation and overall trunk inclination. In the frontal plane, most of the improvements were recorded after 6 months. Patients with osteoporotic fracture showed statistically significant lower mean value than patients with traumatic fracture. Pain and disability index showed early improvements. This study provides a comprehensive and complete picture of the functionality of the spine in patients treated with percutaneous balloon kyphoplasty.

Paschalia Pantazi,1,2 Amelia Acha-Sagredo,1,3,4 Alexandra Papaioannou,2 Georgios Nikolaidis,1,2 Triantafillos Liloglou1 1Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK; 2Division of Basic Science, University of Crete Medical School, Heraklion, Greece; 3Department of Stomatology II, Oral Medicine and Pathology UFI 11/25, University of the Basque Country, Leioa, Spain; 4IKERBASQUE, Basque Foundation for Science, Bilbao, Spain Abstract: DNA methylation is a fundamental biochemical modification that in conjunction with noncoding RNAs, histone modifications, and chromatin remodeling institutes the epigenetic machinery of mammalian cells. As a result of the second decade of intense epigenetic research and its role in human disease, substantial new mechanisms have been uncovered. However, it is well acknowledged that we have just scratched the tip of the iceberg. Epigenetic deregulation appears to be one of the foundations of major human diseases, including lung cancer, which is the most frequent cause of cancer-related deaths. Currently, significant effort is made to dissect the role of epigenetic deregulation in the development of lung cancer and utilize this knowledge in diagnostic and therapeutic applications. Taking advantage of the recent technologies in genomic research, many studies have been conducted to discover and validate abnormal DNA methylation patterns that may shed light on cancer development pathways and open new areas of potential clinical exploitation. In this article, we provide basic information of the DNA methylation involved in gene regulation and review the latest literature on potential relevant translational applications in lung cancer. Particular emphasis is given to the development and validation of DNA methylation biomarkers that may assist in the clinical management of lung cancer. Keywords: epigenetics, biomarkers, body fluids

Although it is known that a change in any level of the spine alters biomechanics, there aren’t many studies to evaluate the spine as a whole both in sagittal and frontal planes. This prospective cohort study evaluates the morphology and mobility of the entire spine in patients with vertebral fractures. The treatment group consisted of 43 patients who underwent percutaneous balloon kyphoplasty or percutaneous balloon kyphoplasty plus fixation. The Control Group consisted of 39 healthy subjects. Spinal mouse was used for the assessment of the curvatures and the mobility of the spine. Clinical outcomes were evaluated by Visual-Analogue Scale and Oswestry Disability Index. The measurements were recorded at 15 days, 3, 6 and 12 months postoperatively. Regarding the curvatures and mobility in sagittal plane, a statistically significant increase appeared early at 3 months, for lumbar curve, spinopelvic angulation and overall trunk inclination. In the frontal plane, most of the improvements were recorded after 6 months. Patients with osteoporotic fracture showed statistically significant lower mean value than patients with traumatic fracture. Pain and disability index showed early improvements. This study provides a comprehensive and complete picture of the functionality of the spine in patients treated with percutaneous balloon kyphoplasty.

Although it is known that a change in any level of the spine alters biomechanics, there aren’t many studies to evaluate the spine as a whole both in sagittal and frontal planes. This prospective cohort study evaluates the morphology and mobility of the entire spine in patients with vertebral fractures. The treatment group consisted of 43 patients who underwent percutaneous balloon kyphoplasty or percutaneous balloon kyphoplasty plus fixation. The Control Group consisted of 39 healthy subjects. Spinal mouse was used for the assessment of the curvatures and the mobility of the spine. Clinical outcomes were evaluated by Visual-Analogue Scale and Oswestry Disability Index. The measurements were recorded at 15 days, 3, 6 and 12 months postoperatively. Regarding the curvatures and mobility in sagittal plane, a statistically significant increase appeared early at 3 months, for lumbar curve, spinopelvic angulation and overall trunk inclination. In the frontal plane, most of the improvements were recorded after 6 months. Patients with osteoporotic fracture showed statistically significant lower mean value than patients with traumatic fracture. Pain and disability index showed early improvements. This study provides a comprehensive and complete picture of the functionality of the spine in patients treated with percutaneous balloon kyphoplasty.

Although it is known that a change in any level of the spine alters biomechanics, there aren’t many studies to evaluate the spine as a whole both in sagittal and frontal planes. This prospective cohort study evaluates the morphology and mobility of the entire spine in patients with vertebral fractures. The treatment group consisted of 43 patients who underwent percutaneous balloon kyphoplasty or percutaneous balloon kyphoplasty plus fixation. The Control Group consisted of 39 healthy subjects. Spinal mouse was used for the assessment of the curvatures and the mobility of the spine. Clinical outcomes were evaluated by Visual-Analogue Scale and Oswestry Disability Index. The measurements were recorded at 15 days, 3, 6 and 12 months postoperatively. Regarding the curvatures and mobility in sagittal plane, a statistically significant increase appeared early at 3 months, for lumbar curve, spinopelvic angulation and overall trunk inclination. In the frontal plane, most of the improvements were recorded after 6 months. Patients with osteoporotic fracture showed statistically significant lower mean value than patients with traumatic fracture. Pain and disability index showed early improvements. This study provides a comprehensive and complete picture of the functionality of the spine in patients treated with percutaneous balloon kyphoplasty.

Paschalia Pantazi,1,2 Amelia Acha-Sagredo,1,3,4 Alexandra Papaioannou,2 Georgios Nikolaidis,1,2 Triantafillos Liloglou1 1Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK; 2Division of Basic Science, University of Crete Medical School, Heraklion, Greece; 3Department of Stomatology II, Oral Medicine and Pathology UFI 11/25, University of the Basque Country, Leioa, Spain; 4IKERBASQUE, Basque Foundation for Science, Bilbao, Spain Abstract: DNA methylation is a fundamental biochemical modification that in conjunction with noncoding RNAs, histone modifications, and chromatin remodeling institutes the epigenetic machinery of mammalian cells. As a result of the second decade of intense epigenetic research and its role in human disease, substantial new mechanisms have been uncovered. However, it is well acknowledged that we have just scratched the tip of the iceberg. Epigenetic deregulation appears to be one of the foundations of major human diseases, including lung cancer, which is the most frequent cause of cancer-related deaths. Currently, significant effort is made to dissect the role of epigenetic deregulation in the development of lung cancer and utilize this knowledge in diagnostic and therapeutic applications. Taking advantage of the recent technologies in genomic research, many studies have been conducted to discover and validate abnormal DNA methylation patterns that may shed light on cancer development pathways and open new areas of potential clinical exploitation. In this article, we provide basic information of the DNA methylation involved in gene regulation and review the latest literature on potential relevant translational applications in lung cancer. Particular emphasis is given to the development and validation of DNA methylation biomarkers that may assist in the clinical management of lung cancer. Keywords: epigenetics, biomarkers, body fluids

The risk of fracture is higher in adults with type 2 diabetes compared to controls without type 2 diabetes, despite normal or higher than normal bone mineral density (BMD). In addition to BMD, bone strength depends on other factors such as structural and material bone qualities, which are not accounted for in BMD measurements. The objective was to determine whether structural and material bone qualities are different in adults with type 2 diabetes compared to controls without type 2 diabetes. First, a cross-sectional study was undertaken using MRI to investigate distal radius trabecular bone microarchitecture, a structural bone quality. In women with type 2 diabetes, trabecular bone holes were larger compared to controls, which is important because greater trabecular bone hole size is related to reduced bone strength. Next, a two year prospective study was conducted with the participants involved in the cross-sectional study to determine whether changes in trabecular bone microarchitecture are different in women with type 2 diabetes compared to controls. There was a greater increase in the number of trabecular bone holes in women with type 2 diabetes compared to controls, which provides early evidence of trabecularization of cortical bone in women with type 2 diabetes. In the third study, quantitative backscattered electron imaging (qBEI) was used to derive bone mineralization density distribution (BMDD) outcomes for bone samples from adults with and without type 2 diabetes to compare material bone quality. There was evidence of elevated bone calcium concentration and reduced mineralization heterogeneity in bone samples from adults with type 2 diabetes compared to controls, which may contribute to bone brittleness. In summary, differences in structural and material bone qualities identified in this body of work provide explanations for elevated fracture risk in adults with type 2 diabetes., Doctor of Science (PhD)

Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancer-associated bone disease. This has led to the development of guidelines by several societies and workin, SCOPUS: ar.j, info:eu-repo/semantics/published

Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancer-associated bone disease. This has led to the development of guidelines by several societies and workin, SCOPUS: ar.j, info:eu-repo/semantics/published

Teriparatide (rDNA origin) injection [recombinant human PTH (1-34)] stimulates bone formation, increases bone mineral density (BMD), and restores bone architecture and integrity. In contrast, bisphosphonates reduce bone resorption and increase BMD. We compared the effects of teriparatide and alendronate sodium on BMD, nonvertebral fracture incidence, and bone turnover in 146 postmenopausal women with osteoporosis. Women were randomized to either once-daily sc injections of teriparatide 40 micro g plus oral placebo (n = 73) or oral alendronate 10 mg plus placebo injection (n = 73). Median duration of treatment was 14 months. At 3 months, teriparatide increased lumbar spine BMD significantly more than did alendronate (P < 0.001). Lumbar spine-BMD increased by 12.2% in the teriparatide group and 5.6% in the alendronate group (P < 0.001 teriparatide vs. alendronate). Teriparatide increased femoral neck BMD and total body bone mineral significantly more than did alendronate, but BMD at the one third distal radius decreased, compared with alendronate (P < or = 0.05). Nonvertebral fracture incidence was significantly lower in the teriparatide group than in the alendronate group (P < 0.05). Both treatments were well tolerated despite transient mild asymptomatic hypercalcemia with teriparatide treatment. In conclusion, teriparatide, a bone formation agent, increased BMD at most sites and decreased nonvertebral fractures more than alendronate., Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

Teriparatide (rDNA origin) injection [recombinant human PTH (1-34)] stimulates bone formation, increases bone mineral density (BMD), and restores bone architecture and integrity. In contrast, bisphosphonates reduce bone resorption and increase BMD. We compared the effects of teriparatide and alendronate sodium on BMD, nonvertebral fracture incidence, and bone turnover in 146 postmenopausal women with osteoporosis. Women were randomized to either once-daily sc injections of teriparatide 40 micro g plus oral placebo (n = 73) or oral alendronate 10 mg plus placebo injection (n = 73). Median duration of treatment was 14 months. At 3 months, teriparatide increased lumbar spine BMD significantly more than did alendronate (P < 0.001). Lumbar spine-BMD increased by 12.2% in the teriparatide group and 5.6% in the alendronate group (P < 0.001 teriparatide vs. alendronate). Teriparatide increased femoral neck BMD and total body bone mineral significantly more than did alendronate, but BMD at the one third distal radius decreased, compared with alendronate (P < or = 0.05). Nonvertebral fracture incidence was significantly lower in the teriparatide group than in the alendronate group (P < 0.05). Both treatments were well tolerated despite transient mild asymptomatic hypercalcemia with teriparatide treatment. In conclusion, teriparatide, a bone formation agent, increased BMD at most sites and decreased nonvertebral fractures more than alendronate., Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published