CAPG and GIPC1: Breast Cancer Biomarkers for Bone Metastasis Development and Treatment.

Background: Bone is the predominant site of metastasis from breast cancer, and recent trials have demonstrated that adjuvant bisphosphonate therapy can reduce bone metastasis development and improve survival. There is an unmet need for prognostic and predictive biomarkers so that therapy can be appropriately targeted.

Methods: Potential biomarkers for bone metastasis were identified using proteomic comparison of bone-metastatic, lung-metastatic, and nonmetastatic variants of human breast cancer MDA-MB-231 cells.

SEARCHBreast Workshop Proceedings: 3D Modelling of Breast Cancer.

SEARCHBreast, a UK initiative supported by the NC3Rs, organised a workshop entitled 3D Modelling of Breast Cancer. The workshop focused on providing researchers with solutions to overcome some of the perceived barriers to working with human-derived tumour cells, cell lines and tissues, namely: a) the limited access to human-derived material; and b) the difficulty in working with these samples. The workshop presentations provided constructive advice and information on how to best prepare human cells or tissues for further downstream applications.

Impact factor of medical education journals and recently developed indices: Can any of them support academic promotion criteria?

Journal Impact Factor (JIF) has been used in assessing scientific journals. Other indices, h- and g-indices and Article Influence Score (AIS), have been developed to overcome some limitations of JIF. The aims of this study were, first, to critically assess the use of JIF and other parameters related to medical education research, and second, to discuss the capacity of these indices in assessing research productivity as well as their utility in academic promotion.

Can we rely on simulated patients' satisfaction with their consultation for assessing medical students' communication skills? A cross-sectional study.

Background: In medical education, teaching methods offering intensive practice without high utilization of faculty resources are needed. We investigated whether simulated patients' (SPs') satisfaction with a consultation could predict professional observers' assessment of young doctors' communication skills.

Methods: This was a comparative cross-sectional study of 62 videotaped consultations in a general practice setting with young doctors who were finishing their internship.

Adjuvant bisphosphonates in early breast cancer: consensus guidance for clinical practice from a European Panel.

Bisphosphonates have been studied in randomised trials in early breast cancer to investigate their ability to prevent cancer treatment-induced bone loss (CTIBL) and reduce the risk of disease recurrence and metastasis. Treatment benefits have been reported but bisphosphonates do not currently have regulatory approval for either of these potential indications. This consensus paper provides a review of the evidence and offers guidance to breast cancer clinicians on the use of bisphosphonates in early breast cancer.

Reliability and Validity of a Nepali-language Version of the Hospital Anxiety and Depression Scale (HADS).

Background: In several languages and settings, the Hospital Anxiety and Depression Scale (HADS) has demonstrated reliable and valid screening properties in psychiatry.

Objective: To develop a Nepali version of HADS with acceptable reliability and construct validity for use among hospital patients and in the general population.

Method: The original English version was translated into Nepali using a forward-backward translation protocol.

Measuring Neuroticism in Nepali: Reliability and Validity of the Neuroticism Subscale of the Eysenck Personality Questionnaire.

Background: The Neuroticism subscale of the Eysenck Personality Questionnaire Revised Short Form (12 items) (EPQRS-N) has proven to be a reliable and valid measure in multiple languages.

Objective: To develop a single-factor Nepali-language version of the EPQRS-N for use in the adult population of Nepal.

Method: The original English version of EPQRS-N was translated into Nepali using a forward-backward translation protocol.

Undertreated Hypertension and its Implications for Public Health in Nepal: Nationwide Population-Based Survey.

Background: Hypertension (HTN), a major risk factor for cardiovascular diseases (CVDs), is a substantial global public health problem. Occasional studies indicate a high prevalence of HTN in the Nepalese population, but no nationwide population-based data exist so far. We opportunistically used a survey of major disorders of the brain in Nepal to measure blood pressure (BP) in participants selected randomly from the adult general population.

Oestrogen receptor positive breast cancer metastasis to bone: inhibition by targeting the bone microenvironment in vivo.

Clinical trials have shown that adjuvant Zoledronic acid (ZOL) reduces the development of bone metastases irrespective of ER status. However, post-menopausal patients show anti-tumour benefit with ZOL whereas pre-menopausal patients do not. Here we have developed in vivo models of spontaneous ER+ve breast cancer metastasis to bone and investigated the effects of ZOL and oestrogen on tumour cell dissemination and growth.

Mode of detection: an independent prognostic factor for women with breast cancer.

Objectives: To investigate breast cancer survival and risk of breast cancer death by detection mode (screen-detected, interval, and detected outside the screening programme), adjusting for prognostic and predictive tumour characteristics.

Methods: Information about detection mode, prognostic (age, tumour size, histologic grade, lymph node status) and predictive factors (molecular subtypes based on immunohistochemical analyses of hormone receptor status (estrogen and progesterone) and Her2 status) were available for 8344 women in Norway aged 50-69 at diagnosis of breast cancer, 2005-2011. A total of 255 breast cancer deaths were registered by the end of 2011.

Myostatin in relation to physical activity and dysglycaemia and its effect on energy metabolism in human skeletal muscle cells.

Aim: Some health benefits of exercise may be explained by an altered secretion of myokines. Because previous focus has been on upregulated myokines, we screened for downregulated myokines and identified myostatin. We studied the expression of myostatin in relation to exercise and dysglycaemia in skeletal muscle, adipose tissue and plasma.

A 15-Year Follow-Up Study of Sense of Humor and Causes of Mortality: The Nord-Trøndelag Health Study.

Background: Associations between the sense of humor and survival in relation to specific diseases has so far never been studied.

Methods: We conducted a 15-year follow-up study of 53,556 participants in the population-based Nord-Trøndelag Health Study, Norway. Cognitive, social, and affective components of the sense of humor were obtained, and associations with all-cause mortality, mortality due to cardiovascular diseases (CVD), infections, cancer, and chronic obstructive pulmonary diseases were estimated by hazard ratios (HRs).

The prevalence of primary headache disorders in Nepal: a nationwide population-based study.

Background: Headache disorders are among the most prevalent and burdensome global public-health problems. Within countries, health policy depends upon knowledge of health within the local populations, but the South-East Asia Region (SEAR), among WHO's six world regions, is the only one for which no national headache prevalence data are available.

Methods: In a cross-sectional population-based study, adults representative of the Nepali-speaking population aged 18-65 years and living in Nepal were randomly recruited using stratified multistage cluster sampling.

Hydrolyzed fish proteins reduced activation of caspase-3 in H2O2 induced oxidative stressed liver cells isolated from Atlantic salmon (Salmo salar).

Hydrolyzed fish proteins (H-pro) contains high concentrations of free amino acids and low molecular peptides that potentially benefit health. The following study aimed to test whether the water soluble phase of H-pro could reduce apoptosis and inflammation in primary liver cells isolated from Atlantic salmon following H2O2 provoked oxidative stress. Cells were grown as monocultures or co-cultured with head kidney cells to assess possible cross talk in inflammation and metabolism during treatments.

Parallel-hole collimator concept for stationary SPECT imaging.

Parallel-hole SPECT collimators have traditionally been manufactured by stacking sheets of lead foil or by casting. These techniques significantly restrict our options in terms of collimator geometry. However, recent developments in metal additive manufacturing are making novel collimator designs possible, giving rise to new opportunities in SPECT imaging.

Collimator design for a multipinhole brain SPECT insert for MRI.

Purpose: Brain single photon emission computed tomography (SPECT) imaging is an important clinical tool, with unique tracers for studying neurological diseases. Nowadays, most commercial SPECT systems are combined with x-ray computed tomography (CT) in so-called SPECT/CT systems to obtain an anatomical background for the functional information. However, while CT images have a high spatial resolution, they have a low soft-tissue contrast, which is an important disadvantage for brain imaging.

Obese, fat, or just overweight?

Background: Discussing obesity with the patient without this being perceived as offensive may represent a challenge. Prevention of lifestyle diseases requires that this topic be addressed with those concerned. In this study, we investigate the patients' sensitivity to expressions, i.

The frequency of osteolytic bone metastasis is determined by conditions of the soil, not the number of seeds; evidence from in vivo models of breast and prostate cancer.

Background: While both preclinical and clinical studies suggest that the frequency of growing skeletal metastases is elevated in individuals with higher bone turnover, it is unclear whether this is a result of increased numbers of tumour cells arriving in active sites or of higher numbers of tumour cells being induced to divide by the bone micro-environment. Here we have investigated how the differences in bone turnover affect seeding of tumour cells and/or development of overt osteolytic bone metastasis using in vivo models of hormone-independent breast and prostate cancer.

Methods: Cohorts of 6 (young) and 16 (mature)-week old BALB/c nude mice were culled 1, 7 and 21 days after received intracardiac injection of luciferase expressing human prostate (PC3) or breast cancer (MDA-MB-231) cell lines labelled with a fluorescent cell membrane dye (Vybrant DiD).

Safety, efficacy, and pharmacokinetics of navitoclax (ABT-263) in combination with irinotecan: results of an open-label, phase 1 study.

Purpose: The oral Bcl-2 inhibitor navitoclax demonstrated activity in solid and hematologic malignancies as monotherapy and in combination with other cytotoxic agents in preclinical and early clinical studies. We evaluated the safety, pharmacokinetics (PK), and antitumor activity of navitoclax plus irinotecan.

Methods: In this multicenter, open-label, phase 1 dose escalation study, adults with advanced solid tumors received navitoclax (starting dose 150 mg/day) in combination with 1 of 2 irinotecan schedules during a 21-day cycle: a once-every-3-week regimen (Q3W 180, 250, or 350 mg/m(2)) or a once-weekly regimen (QW 75 or 100 mg/m(2)).

Safety, efficacy, and pharmacokinetics of navitoclax (ABT-263) in combination with erlotinib in patients with advanced solid tumors.

Purpose: Navitoclax (ABT-263), a novel, oral Bcl-2 inhibitor, enhances the antitumor effects of chemotherapy in vitro by lowering the apoptotic threshold. This phase I study (NCT01009073) evaluated the safety, pharmacokinetics, and preliminary antitumor activity of navitoclax combined with erlotinib in patients with advanced solid tumors.

Patients And Methods: An open-label dose escalation study included an arm evaluating navitoclax combined with erlotinib, which included a dose escalation cohort and a planned safety expansion cohort.

Breech presentation is a risk factor for dysplasia of the femoral trochlea.

Background And Purpose: Instability of the patellofemoral joint is a common disorder in children and young adults. Although it has multifactorial causes, a shallow femoral trochlea is the single most important factor for instability. There is no consensus as to the etiology of trochlear dysplasia.

The exercise-regulated myokine chitinase-3-like protein 1 stimulates human myocyte proliferation.

Aim: Chitinase-3-like protein 1 (CHI3L1) is involved in tissue remodelling and inflammatory processes. Plasma levels are elevated in patients with insulin resistance and T2DM. We recently showed that CHI3L1 and its receptor protease-activated receptor 2 (PAR-2) are expressed in skeletal muscle.

The effect of acute and long-term physical activity on extracellular matrix and serglycin in human skeletal muscle.

Remodeling of extracellular matrix (ECM), including regulation of proteoglycans in skeletal muscle can be important for physiological adaptation to exercise. To investigate the effects of acute and long-term exercise on the expression of ECM-related genes and proteoglycans in particular, 26 middle-aged, sedentary men underwent a 12 weeks supervised endurance and strength training intervention and two acute, 45 min bicycle tests (70% VO2max), one at baseline and one after 12 weeks of training. Total gene expression in biopsies from m.

Rapid modification of the bone microenvironment following short-term treatment with Cabozantinib in vivo.

Introduction: Bone metastasis remains incurable with treatment restricted to palliative care. Cabozantinib (CBZ) is targeted against multiple receptor tyrosine kinases involved in tumour pathobiology, including hepatocyte growth factor receptor (MET) and vascular endothelial growth factor receptor 2 (VEGFR-2). CBZ has demonstrated clinical activity in advanced prostate cancer with resolution of lesions visible on bone scans, implicating a potential role of the bone microenvironment as a mediator of CBZ effects.