The role of 11-oxygenated androgens in prostate cancer

11-oxygenated androgens are a class of steroids capable of activating the androgen receptor (AR) at physiologically relevant concentrations. In view of the AR as a key driver of prostate cancer (PC), these steroids are potential drivers of disease and progression. The 11-oxygenated androgens are adrenal-derived, and persist after androgen deprivation therapy (ADT), the mainstay treatment for advanced PC. Consequently, these steroids are of particular interest in the castration-resistant prostate cancer (CRPC) setting. The principal androgen of the pathway, 11-ketotestosterone (11KT), is a potent AR agonist and the predominant circulating active androgen in CRPC patients. Additionally, several precursor steroids are present in the circulation which can be converted into active androgens by steroidogenic enzymes present in PC cells. In vitro evidence suggests that adaptations frequently observed in CRPC favour the intratumoral accumulation of 11-oxygenated androgens in particular. Still, apparent gaps in our understanding of the physiology and role of the 11-oxygenated androgens remain. In particular, in vivo and clinical evidence supporting these in vitro findings is limited. Despite recent advances, a comprehensive assessment of intratumoral concentrations has not yet been performed. The exact contribution of the 11-oxygenated androgens to CRPC progression therefore remains unclear. This review will focus on the current evidence linking the 11-oxygenated androgens to PC, will highlight current gaps in our knowledge, and will provide insight into the potential clinical importance of the 11-oxygenated androgens in the CRPC setting based on the current evidence.</p

Thyroid hormone status within the physiological range affects bone mass and density in healthy men at the age of peak bone mass

Context: The hormonal factors involved in the regulation of peak bone mass (PBM) in men have not been fully investigated. Apart from gonadal steroids and somatotropic hormones, thyroid hormones are known to affect bone maturation and homeostasis and are additional candidate determinants of adult bone mass. Objective: We aimed to investigate between-subject physiological variation in free and total thyroid hormone concentrations, TSH, and thyroid binding globulin (TBG) in relation to parameters of bone mass, geometry, and mineral density in healthy men at the age of PBM. Design and setting: We recruited 677 healthy male siblings aged 25-45 years in a cross-sectional, population-based study. Areal and volumetric bone parameters were determined using dual-energy x-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). Total and free thyroid hormones, TBG, and TSH were determined using immunoassays. Results: Free and total thyroid hormone concentrations were inversely associated with bone mineral density (BMD) and bone mineral content (BMC) at the hip and total body (free triiodothyronine (FT(3)), total T(3) (TT(3)), and total T(4) (TT(4))) and at the spine (FT(3)). TBG was negatively associated with BMC and areal BMD at all sites. At the radius, cortical bone area was inversely associated with TT(3), TT(4), and TBG, and trabecular bone density was inversely associated with free thyroxine, TT(4), and TBG. We observed inverse associations between cortical bone area at the mid-tibia and FT(3), TT(3), TT(4), and TBG. No associations between TSH and DXA or pQCT measurements were found. Conclusion: In healthy men at the age of PBM, between-subject variation in thyroid hormone concentrations affects bone density, with higher levels of FT(3), TT(3), TT(4), and TBG being associated with less favorable bone density and content

CABE : a cloud-based acoustic beamforming emulator for FPGA-based sound source localization

Microphone arrays are gaining in popularity thanks to the availability of low-cost microphones. Applications including sonar, binaural hearing aid devices, acoustic indoor localization techniques and speech recognition are proposed by several research groups and companies. In most of the available implementations, the microphones utilized are assumed to offer an ideal response in a given frequency domain. Several toolboxes and software can be used to obtain a theoretical response of a microphone array with a given beamforming algorithm. However, a tool facilitating the design of a microphone array taking into account the non-ideal characteristics could not be found. Moreover, generating packages facilitating the implementation on Field Programmable Gate Arrays has, to our knowledge, not been carried out yet. Visualizing the responses in 2D and 3D also poses an engineering challenge. To alleviate these shortcomings, a scalable Cloud-based Acoustic Beamforming Emulator (CABE) is proposed. The non-ideal characteristics of microphones are considered during the computations and results are validated with acoustic data captured from microphones. It is also possible to generate hardware description language packages containing delay tables facilitating the implementation of Delay-and-Sum beamformers in embedded hardware. Truncation error analysis can also be carried out for fixed-point signal processing. The effects of disabling a given group of microphones within the microphone array can also be calculated. Results and packages can be visualized with a dedicated client application. Users can create and configure several parameters of an emulation, including sound source placement, the shape of the microphone array and the required signal processing flow. Depending on the user configuration, 2D and 3D graphs showing the beamforming results, waterfall diagrams and performance metrics can be generated by the client application. The emulations are also validated with captured data from existing microphone arrays.</jats:p

The relationship between glycaemic variability and cardiovascular autonomic dysfunction in patients with type 1 diabetes : a systematic review

Rigorous glycaemic control-reflected by low HbA1c goals-is of the utmost importance in the prevention and management of complications in patients with type 1 diabetes mellitus (T1DM). However, previous studies suggested that short-term glycaemic variability (GV) is also important to consider as excessive glucose fluctuations may have an additional impact on the development of diabetic complications. The potential relationship between GV and the risk of cardiovascular autonomic neuropathy (CAN), a clinical expression of cardiovascular autonomic dysfunction, is of increasing interest. This systematic review aimed to summarize existing evidence concerning the relationship between GV and cardiovascular autonomic dysfunction in T1DM. An electronic database search of Medline (PubMed), Web of Science and Embase was performed up to October 2019. There were no limits concerning year of publication. Methodological quality was evaluated using the Newcastle Ottawa Scale for observational studies. Six studies (four cross-sectional and two prospective cohorts) were included. Methodological quality of the studies varied from level C to A2. Two studies examined the association between GV and heart rate variability (HRV), and both found significant negative correlations. Regarding cardiovascular autonomic reflex tests (CARTs), two studies did not, while two other studies did find significant associations between GV parameters and CART scores. However, associations were attenuated after adjusting for covariates such as HbA1c, age and disease duration. In conclusion, this systematic review found some preliminary evidence supporting an association between GV and cardiovascular autonomic dysfunction in T1DM. Hence, uncertainty remains whether high GV can independently contribute to the onset or progression of CAN. The heterogeneity in the methodological approach made it difficult to compare different studies. Future studies should therefore use uniformly evaluated continuous glucose monitoring-derived parameters of GV, while standardized assessment of HRV, CARTs and other potential cardiac autonomic function parameters is needed for an unambiguous definition of CAN

Association of jumping mechanography-derived indices of muscle function with tibial cortical bone geometry

Jumping mechanography has been developed to estimate maximum voluntary muscle forces. This study assessed associations of jumping mechanography-derived force and power measurements with tibial cortical bone geometry, compared to other estimates of muscle mass, size, and function. Healthy men (n = 181; 25–45 years) were recruited in a cross-sectional, population-based sibling-pair study. Muscle parameters include isokinetic peak torque of the quadriceps, DXA-derived leg lean mass, mechanography-derived peak jump force and power, and pQCT-derived mid-tibial (66 %) muscle cross-sectional area (CSA). Mid-tibial cortical bone parameters were assessed by pQCT. In age, height, and weight-adjusted analyses, jump force and power correlated positively with cortical bone area, cortical thickness, and polar strength–strain index (SSIp) (b = 0.23–0.34, p B 0.001 for force; b = 0.25–0.30, p B 0.007 for power) and inversely with endosteal circumference adjusted for periosteal circumference (ECPC) (b = -0.16, p\0.001 for force; b = -0.13, p = 0.007 for power). Force but not power correlated with cortical over total bone area ratio (b = 0.25, p = 0.002). Whereas leg lean mass correlated with all cortical parameters except cortical over total bone area ratio (b = 0.25–0.62, p B 0.004), muscle CSA only correlated with cortical bone area, periosteal circumference, and SSIp (b = 0.21–0.26, p B 0.001), and quadriceps torque showed no significant correlations with the bone parameters. Multivariate models indicated that leg lean mass was independently associated with overall bone size and strength reflected by periosteal and endosteal circumference and SSIp (b = 0.32–0.55, p B 0.004), whereas jump force was independently associated with cortical bone size reflected by ECPC, cortical thickness, and cortical over total bone area ratio (b = 0.13–0.28; p B 0.002). These data indicate that jumping mechanography provides relevant information about the relationship of muscle with bone geometry

Is type 1 diabetes mellitus more prevalent than expected in transgender persons? : a local observation

The International Diabetes Federation estimates that approximately 0.4% of the Belgian population is diagnosed with type 1 diabetes mellitus, which is similar to other industrialized countries. The prevalence of transgenderism is estimated at 0.6% to 0.7% of all adults in Western populations. In this study, we evaluated whether there was an increased prevalence of type 1 diabetes mellitus in transgender people in the local cohort. Medical records of transgender patients were analyzed retrospectively. From January 1, 2007 until October 10, 2016, 1,081 transgender patients presented at a tertiary reference center to start hormonal treatment. Nine of these 1,081 patients were previously diagnosed with type 1 diabetes mellitus and 1 was diagnosed with latent autoimmune diabetes in adults. A 2.3-fold higher prevalence of type 1 diabetes mellitus was observed in transgender patients. We concluded that type 1 diabetes mellitus was more prevalent in transgender patients than one would expect from population prevalences. This could be a spurious result in a local cohort, because a causal relation seems unlikely, but our finding might encourage other centers to investigate this putative association