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Objectives To measure rates of potentially inappropriate pathology testing in the hospital setting. Methods Retrospective cross-sectional study in hospital setting from July 2021 to December 2021. We examined 3 potentially inappropriate uses: overordering, selection errors, and unnecessary repeat testing. Overordering included vitamin D and lipids (rarely required in acute hospital care). Selection error was the ratio of iron studies to standalone ferritin requests. Unnecessary repeats included any repeat vitamin D, lipids, iron, or ferritin in an episode of care or C-reactive protein (CRP) repeated within 3 days and N-terminal pro–brain natriuretic peptide (NT-proBNP) within 7 days and repeated previously abnormal CRP and NT-proBNP tests. Costs of inappropriate tests were estimated using the Australian Medicare Benefits Schedules. Results Among 55,904 test requests, 15% (n = 8120) were potentially inappropriate. Vitamin D was frequently ordered (n = 4498), as were lipids (n = 2872). Ratio of iron studies to standalone ferritin was 36. Of 19,233 repeat CRPs, 36% (n = 6947) were within 3 days and 62% (n = 179) of repeat NT-proBNPs were within 7 days of the first test. For initially abnormal tests, 89% of CRPs and 97% of NT-proBNPs remained abnormal. Inappropriate test costs accounted for 12% to 30% of costs. Conclusions Frequent potential inappropriate use and selection of pathology tests was observed in South Australian hospitals. [ABSTRACT FROM AUTHOR]

Both Google Android and Google Search (Shopping), along with other ongoing digital market antitrust enforcement actions like United States v. Google LLC, are based on foreclosure conduct that has raised difficult doctrinal questions for courts, regulators, and scholars. This emerging form of foreclosure, which some have termed "cognitive foreclosure" because of its behavioural economic foundations, has encountered difficulties in being conceptually subsumed under existing antitrust frameworks. Yet as a demand-side market failure, enforcers and scholars must be cautious about automatically categorising these market failures as antitrust issues, given that such market failures are usually governed by the more de-minimis consumer protection regime. This Article proffers a new legal test to aid courts and regulators in appropriately "identifying" behavioural market failures that would justify antitrust scrutiny. The test's limits are subsequently justified from moral hazard perspectives given the potential reduction in societal rationality due to antitrust over-enforcement. [ABSTRACT FROM AUTHOR]

Digital markets now fundamentally intertwine with our social and economic lives. International enforcement actions--the United States (U.S.) and European Union (E.U.) Google cases in particular--demonstrate from a behavioral economic perspective how digital platforms may be beginning to implicate antitrust's two most fundamental doctrinal components--conduct and market power--in nuanced ways. In short, the regulatory and policy landscape showcases that we may be moving closer towards an antitrust world whereby firms can manipulate consumers' psychological shortcomings to foreclose competition--a new form of nefarious conduct that might appropriately be termed "cognitive foreclosure." Yet as a demand-side market failure, one should be cautious about categorizing behavioral market failures as antitrust issues. The behavioral deviation from perfect competition, then, would need to be "substantial" and "sustainable" if such market failures are to justifiably attract antitrust scrutiny. [ABSTRACT FROM AUTHOR]

Digital markets now fundamentally intertwine with our social and economic lives. International enforcement actions--the United States (U.S.) and European Union (E.U.) Google cases in particular--demonstrate from a behavioral economic perspective how digital platforms may be beginning to implicate antitrust's two most fundamental doctrinal components--conduct and market power--in nuanced ways. In short, the regulatory and policy landscape showcases that we may be moving closer towards an antitrust world whereby firms can manipulate consumers' psychological shortcomings to foreclose competition--a new form of nefarious conduct that might appropriately be termed "cognitive foreclosure." Yet as a demand-side market failure, one should be cautious about categorizing behavioral market failures as antitrust issues. The behavioral deviation from perfect competition, then, would need to be "substantial" and "sustainable" if such market failures are to justifiably attract antitrust scrutiny. [ABSTRACT FROM AUTHOR]

Estrogen deficiency-induced bone loss is associated with complex changes in the calcium fluxes that constitute calcium balance. We studied the effects of oophorectomy on calcium balance and its components within the first 9 wk after the operation. Six-day calcium balance studies were performed on 30-wk-old female Sprague-Dawley rats before either sham operation or oophorectomy (oophx) and at 3-wk intervals for 9 wk postoperation. The rats were fed a diet containing 0.4g Ca/100 g diet and 0.3 g P/100 g diet throughout the study. The postoperative changes in calcium balance (P < 0.05) and net calcium absorption (P < 0.02) were negative in the oophx group compared with the ovary-intact group. The oophx group excreted more calcium via both the kidney (urine Ca, P < 0.05) and the gastrointestinal tract (endogenous fecal Ca, P < 0.05). The postoperation endogenous fecal calcium was higher at 3 wk postoophorectomy than at later times (P < 0.05). Oophorectomy did not affect true calcium absorption up to 9 wk postoophorectomy. Oophorectomy stimulates bone metabolism and our findings indicate that within the first 9 wk after oophorectomy, bone mineral loss is associated with a transient increase in the excretion of calcium by the gastrointestinal tract and the kidney. KEY WORDS: * oophorectomy * rat * calcium balance * calcium excretion.

Background: Isolation and social distancing restrictions due to COVID‐19 have the potential to impact access to healthcare services. Aims: To assess the use of pathology services during the COVID‐19 pandemic initial restrictions. Methods: Repeated cross‐sectional study of pathology tests utilisation during a baseline time period early in 2020 compared with pre‐lockdown and lockdown due to COVID‐19 in South Australia. The outcome measure was changed in a number of pathology tests compared to baseline period, particularly change in the number of troponin tests to determine potential impacts of lockdown on urgent care presentations. Results: In the community setting, the ratio of a number of pathology tests pre‐lockdown and post‐lockdown versus baseline period decreased from 1.02 to 0.53 respectively. The exception was microbiology molecular tests, where the number of tests was more than three times higher in the lockdown period. The number of troponin tests in emergency departments decreased in the lockdown period compared to the baseline time period; however, there was no evidence of an association between tests result (positive vs negative) and time period (odds ratio (OR) 1.09; 95% confidence interval (CI) 0.97–1.22). There was an inverse relationship between age and time period (OR 0.995; 95% CI 0.993–0.997), indicating that fewer troponin tests were conducted in older people during the lockdown compared with the baseline period. Conclusion: COVID‐19 restrictions had a significant impact on the use of pathology testing in both urgent and non‐urgent care settings. Further studies are needed to investigate the effect on health outcomes as a result of the COVID‐19 restrictions. [ABSTRACT FROM AUTHOR]

Calcium balance and its major components (true calcium absorption, urinary calcium excretion and intestinal calcium secretion) were assessed by a 6-d balance technique in young (6-wk-old) rats fed a diet containing 7.2 g Ca/kg diet. Following either oophorectomy (oophx) or sham operation, the balance study was repeated at 9, 12 and 15 wk of age. Calcium balance decreased with age but remained positive in each group (mean (pooled SEM): sham, (6 wk) 0.86 to (15 wk) 0.27 (0.03) mmol/d (P < 0.0001); oophx, (6 wk) 0.91 to (15 wk) 0.22 (0.03) mmol/d (P < 0.0001)). Analysis of variance of the change in calcium balance indicated that there was a significantly greater reduction in calcium balance in the oophx group compared with the sham-operated group. Intestinal calcium absorption decreased in each group with age (sham: (6 wk) 46.3% to (15 wk) 22.6% (1.5%) (P < 0.0001); oophx: (6 wk) 48.2% to (15 wk) 21.2% (1.5%) (P < 0.0001)). There was a marked rise in intestinal calcium secretion in the oophx group compared with the sham-operated group at 6 wk post-operation (12 wk of age) (oophx: 0.33 (0.02) mmol/d; sham: 0.23 (0.02) mmol/d (P < 0.01)). Urinary calcium excretion was not affected by either age or oophorectomy. We conclude that oophorectomy in young rats leads to a reduction in calcium accumulation, which is mainly the result of an increase in intestinal calcium secretion.

This study sought to determine patterns of multimorbidity and quantify their impact on use of primary health services in the presence and absence of anxiety and depression among a cohort of urban community-dwelling men in Australia. The analytic sample consisted of men (n = 2039; age 38–85) from the follow-up wave of a prospective cohort study of all participants of the Florey Adelaide Male Ageing Study (FAMAS; Stage 2 [2007–2010]) and age-matched men from the North-West Adelaide Health Study (NWAHS; Stage 3 [2008–2010]). Self-reported data and linkage with a national universal health coverage scheme (Medicare) provided information on the prevalence of eight chronic conditions and health service utilization information (including annual GP visits). Obesity and cardiovascular disease (CVD) were associated with the highest number of comorbid conditions. Two nonrandom multimorbidity “clusters” emerged: “CVD, Obesity, Diabetes” and “CVD, Obesity, Osteoarthritis.” Participants with conditions comorbid with CVD were more likely to have 10 or more annual GP visits, compared to multimorbidity involving other conditions. In comparison to participants without CVD, the presence of CVD increased the chance of having 10 or more annual GP visits (adjusted risk ratio: 3.7; 95% CI [2.8, 4.8]). When CVD was comorbid with anxiety and depression, having 10 or more annual GP visits was more common (adjusted risk ratio: 1.8; 95% CI [1.2, 2.5]). Multimorbidity patterns involving CVD, especially for multimorbidity that includes CVD with comorbid anxiety and depression, should be considered in developing clinical trials to better inform medical decision-making and care for patients with CVD and comorbid conditions. [ABSTRACT FROM AUTHOR]

Aims: Contrasting findings exist regarding the association between circulating sex hormone-binding globulin (SHBG) and testosterone levels and type 2 diabetes (T2D) in men. We examined prospective associations of SHBG and sex steroids with incident T2D in a cohort of community-dwelling men.Methods: Participants were from a cohort study of community-dwelling (n = 2563), middle-aged to elderly men (35-80 years) from Adelaide, Australia (the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study). The current study included men who were followed for 5 years and with complete SHBG and sex steroid levels (total testosterone (TT), dihydrotestosterone (DHT) and oestradiol (E2)), but without T2D at baseline (n = 1597). T2D was identified by either self-report, fasting glucose (≥ 7.0 mmol/L), HbA1c (≥ 6.5%/48.0 mmol/mol), and/or prescriptions for diabetes medications. Logistic binomial regression was used to assess associations between SHBG, sex steroids and incident T2D, adjusting for confounders including age, smoking status, physical activity, adiposity, glucose, triglycerides, symptomatic depression, SHBG and sex steroid levels.Results: During an average follow-up of 4.95 years, 14.5% (n = 232) of men developed new T2D. Multi-adjusted models revealed an inverse association between baseline SHBG, TT, and DHT levels, and incident T2D (odds ratio (OR) = 0.77, 95% CI [0.62, 0.95], p = 0.02; OR 0.70 [0.57, 0.85], p < 0.001 and OR 0.78 [0.63, 0.96], p = 0.02), respectively. However, SHBG was no longer associated with incident T2D after additional adjustment for TT (OR 0.92 [0.71, 1.17], p = 0.48; TT in incident T2D: OR 0.73 [0.57, 0.92], p = 0.01) and after separate adjustment for DHT (OR 0.83 [0.64, 1.08], p = 0.16; DHT in incident T2D: OR 0.83 [0.65, 1.05], p = 0.13). There was no observed effect of E2 in all models of incident T2D.Conclusions: In men, low TT, but not SHBG and other sex steroids, best predicts the development of T2D after adjustment for confounders. [ABSTRACT FROM AUTHOR]

Despite its widespread clinical use, there is little data available from population-based studies on the determinants of serum sex hormone binding globulin (SHBG). We aimed to examine multifactorial determinants of circulating SHBG levels in community-dwelling men. Study participants comprised randomly selected 35–80 y.o. men (n = 2563) prospectively-followed for 5 years (n = 2038) in the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study. After excluding men with illness or medications known to affect SHBG (n = 172), data from 1786 men were available at baseline, and 1476 at follow-up. The relationship between baseline body composition (DXA), serum glucose, insulin, triglycerides, thyroxine (fT4), sex steroids (total testosterone (TT), oestradiol (E2)), and pro-inflammatory cytokines and serum SHBG level at both baseline & follow-up was determined by linear and penalized logistic regression models adjusting for age, lifestyle & demographic, body composition, metabolic, and hormonal factors. Restricted cubic spline analyses was also conducted to capture possible non-linear relationships. At baseline there were positive cross-sectional associations between age (β = 0.409, p<0.001), TT (β = 0.560, p<0.001), fT4 (β = 0.067, p = 0.019) and SHBG, and negative associations between triglycerides (β = -0.112, p<0.001), abdominal fat mass (β = -0.068, p = 0.032) and E2 (β = -0.058, p = 0.050) and SHBG. In longitudinal analysis the positive determinants of SHBG at 4.9 years were age (β = 0.406, p = <0.001), TT (β = 0.461, p = <0.001), and fT4 (β = 0.040, p = 0.034) and negative determinants were triglycerides (β = -0.065, p = 0.027) and abdominal fat mass (β = -0.078, p = 0.032). Taken together these data suggest low SHBG is a marker of abdominal obesity and increased serum triglycerides, conditions which are known to have been associated with low testosterone and low T4. [ABSTRACT FROM AUTHOR]

The European Commission relies heavily on its leniency program for the public enforcement of Anti trust law, This program incentivizes a cartelist to come clean to the European Commission by offering immunity from. or a reduction in. sanctions that would otherwise be imposed for its participating in a cartel. The Commission is also keen to promote the private enforcement of Antitrust law, as evidenced by Council and Parliament Directive 2014/104/EU on certain rules governing actions for damages under national law for infringements of the competition law provisions of the Member States and of the European Union There are concerns. however. that tm increase in private enforcement will significantly curtail the efficacy of public enforcement. Indeed, if prospective leniency applicants anticipate that the evidence submitted for a leniency application will be used against them in a future damages action. the attractiveness of applying for leniency diminishes. Public antitrust enforcement's effectiveness would then be significantly reduced, Drawing on experiences from the United States and agency theory" from corporate governance, this note argues for the introduction of criminal penalties at the EU level as a solution to the public-private antitrust enforcement conflict. Specifically this note shows that the existence of individual criminal sanctions. coupled with the possibility of immunity from such sanctions. affects a firm's cost-benefit analysis when considering a leniency application--such that a firm is forced to come forward even if a damages action is likely, The note also analyses the possible legal bases for the introduction of antitrust criminalization at the EU level. [ABSTRACT FROM AUTHOR]

Background: Effective prevention of type 2 diabetes (T2D) requires early identification of high-risk individuals who might benefit from intervention. We sought to determine whether low serum testosterone, a novel risk factor for T2D in men, adds clinically meaningful information beyond current T2D risk models. Methods: The Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study population consists of 2563 community-dwelling men aged 35-80 years in Adelaide, Australia. Of the MAILES participants, 2038 (80.0 %) provided information at baseline (2002-2006) and follow-up (2007-2010). After excluding participants with diabetes (n = 317), underweight (n = 5), and unknown BMI status (n = 11) at baseline; and unknown diabetes status (n = 50) at follow-up; 1655 participants were followed for 5 years. T2D at baseline and follow-up was defined by self-reported diabetes, or fasting plasma glucose (FPG) ≥7.0 mmol/L (126.1 mg/dL), or glycated haemoglobin (HbA1c) ≥6.5 %, or diabetes medications. Risk models were tested using logistic regression models. Sensitivity, specificity, positive predictive values (PPV) were used to identify the optimal cut-off point for low serum testosterone for incident T2D and the area under the receiver operating characteristic (AROC) curve was used to summarise the predictive power of the model. 15.5 % of men had at least one missing predictor variable; addressed through multiple imputation. Results: The incidence rate of T2D was 8.9 % (147/1655) over a median follow-up of 4.95 years (interquartile range: 4.35-5.00). Serum testosterone level predicted incident T2D (relative risk 0.96 [95 % CI: 0.92,1.00], P = 0.032) independent of current risk models including the AUSDRISK, but did not improve corresponding AROC statistics. A cut-off point of <16 nmol/L for low serum testosterone, which classified about 43 % of men, returned equal sensitivity (61.3 % [95 % CI: 52.6,69.4]) and specificity (58.3 % [95 % CI: 55.6,60.9) for predicting T2D risk, with a PPV of 12.9 % (95 % CI: 10.4,15.8). Conclusions: Low serum testosterone predicts an increased risk of developing T2D in men over 5 years independent of current T2D risk models applicable for use in routine clinical practice. Screening for low serum testosterone in addition to risk factors from current T2D risk assessment models or tools, including the AUSDRISK, would identify a large subgroup of distinct men who might benefit from targeted preventive interventions. [ABSTRACT FROM AUTHOR]

Background: The relationship between lower urinary tract symptoms (LUTS) and common mental health disorders such as depression and anxiety in men remains unclear. Inflammation has recently been identified as an independent risk factor for LUTS and depression. This study aimed to assess the association between depression, anxiety and LUTS, and the moderating influence of systemic inflammation, in the presence of other biopsychosocial confounders. Methods: Participants were randomly-selected from urban, community-dwelling males aged 35–80 years at recruitment (n = 1195; sample response rate:67.8%). Of these, 730 men who attended baseline (2002–5) and follow-up clinic visits (2007–10), with complete outcome measures, and without prostate or bladder cancer and/or surgery, neurodegenerative conditions, or antipsychotic medications use, were selected for the present study. Unadjusted and multi-adjusted regression models of incident storage and voiding LUTS and incident depression and anxiety were combined with serum inflammatory markers (high-sensitive C-reactive protein (hsCRP), tumor necrosis factor-alpha (TNF-α), interleukin–6 (IL–6), myeloperoxidase (MPO), soluble e-selectin (e-Sel)) and socio-demographic, lifestyle, and health-related factors. Hierarchical multiple regression was used to assessed the moderating effect of inflammatory markers. Results: The incidence of storage, voiding LUTS, depression and anxiety was 16.3% (n = 108), 12.1% (n = 88), 14.5% (n = 108), and 12.2% (n = 107). Regression models demonstrated that men with depression and anxiety at baseline were more likely to have incident storage, but not voiding LUTS (OR: 1.26, 99%CI: 1.01–4.02; and OR:1.74; 99%CI:1.05–2.21, respectively). Men with anxiety and storage LUTS at baseline were more likely to have incident depression (OR: 2.77, 99%CI: 1.65–7.89; and OR:1.45; 99%CI:1.05–2.36, respectively), while men with depression and voiding LUTS were more likely to have anxiety at follow-up (OR: 5.06, 99%CI: 2.81–9.11; and OR:2.40; 99%CI:1.16–4.98, respectively). CRP, TNF-α, and e-Sel were found to have significant moderating effects on the development of storage LUTS (1.06, 0.91–1.96, R2 change: 12.7%), depression (1.17, 1.01–1.54, R2 change: 9.8%), and anxiety (1.35, 1.03–1.76, R2 change: 10.6%), respectively. Conclusions: There is a bidirectional relationship between storage, but not voiding, LUTS and both depression and anxiety. We observed variable moderation effects for selected inflammatory markers on the development of depression, anxiety and storage LUTS. [ABSTRACT FROM AUTHOR]

Background: We evaluated the recently released chemiluminescence assay for 25-hydroxy vitamin D (25-OHD) on the Immunodiagnostic Systems iSYS (IDS-iSYS) automated analyser. Methods: The IDS-iSYS comparison was performed using patient samples previously measured for 25-OHD by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method (n = 119) and an IDS enzyme immunoassy (IDS-EIA) method (n = 64). Limit of detection and limit of quantification were determined from a precision profile. Imprecision was assessed using quality control material and pooled serum. External QAP material (Vitamin D External Quality Assessment Scheme, UK) was analysed to establish inaccuracy. Linearity was assessed by two dilution studies. Cross-reactivity was determined by three serial dilution studies of patient samples with known 25-OHD2 concentrations. Results: The IDS-iSYS correlated well with both established methods (iSYS = 1.03LC-MS/MS 2 6.53, R² = 0.82 and iSYS = 1.07IDS-EIA 2 1.61, R² = 0.86). Imprecision of the iSYS assay for IDS control material was 13.4% at 32 nmol/L, 10% at 78 nmol/L, 9.4% at 161 nmol/L, and for the pooled material 9.3% at 72 nmol/L and 5.6% at 158 nmol/L. The evaluation found the assay to be highly accurate (IDS-iSYS = 0.93ALTM + 3.79, R² = 0.94) and linear (obs1 = 0.93exp1 2 5.05, R² = 0.99 (P = 0.256); and obs2 = 0.97exp2 + 6.07, R2 = 0.97 (P = 0.654); ALTM, all-laboratory trimmed mean). Cross-reactivity studies demonstrated no significant difference to the calculated total 25-OHD as measured by LC-MS/MS. Conclusions: Even though the imprecision of the iSYS was found to be greater than that of the LC-MS/MS and EIA methods, the performance characteristics of the IDS-iSYS 25-OHD assay are suitable for routine diagnostic purposes on a high throughput automated analyser. [ABSTRACT FROM AUTHOR]

Animal models fed low calcium diets demonstrate a negative calcium balance and gross bone loss while the combination of calcium deficiency and oophorectomy enhances overall bone loss. Following oophorectomy the dietary calcium intake required to remain in balance increases some 5 fold, estimated to be approximately 1.3% dietary calcium. In the context of vitamin D and dietary calcium depletion, osteomalacia occurs only when low dietary calcium levels are combined with low vitamin D levels and osteoporosis occurs with either a low level of dietary calcium with adequate vitamin D status or when vitamin D status is low in the presence of adequate dietary calcium intake. Maximum bone architecture and strength is only achieved when an adequate vitamin D status is combined with sufficient dietary calcium to achieve a positive calcium balance. This anabolic effect occurs without a change to intestinal calcium absorption, suggesting dietary calcium and vitamin D have activities in addition to promoting a positive calcium balance. Each of the major bone cell types, osteoblasts, osteoclasts and osteocytes are capable of metabolizing 25 hydroxyvitamin D (25D) to 1,25 dihydroxyvitamin D (1,25D) to elicit biological activities including reduction of bone resorption by osteoclasts and to enhance maturation and mineralization by osteoblasts and osteocytes. Each of these activities is consistent with the actions of adequate circulating levels of 25D observed in vivo. [ABSTRACT FROM AUTHOR]

Objective To assess if a cell-based readout of androgen action in serum demonstrates a closer association with recognized classical parameters of androgen action in men than current measures of serum testosterone (T). Design To develop, validate and utilize a mammalian cell-based assay to measure specifically bioactive T and determine if this measure is a physiologically relevant fraction of serum T. Measurements and participants We have developed a specific serum T bioassay using human prostate cancer cells. A rapid 5-min exposure to 100% serum followed by serum withdrawal confers specificity of the assay to serum T and provides sufficient sensitivity to measure T in male serum samples. Matrix effects were experimentally discounted as a confounding issue. A total of 960 male serum samples from the Florey Adelaide Male Ageing Study (FAMAS) with previous comprehensive cohort data and serum measurements were utilized. Results Bioassay T measurement in the 960 FAMAS serum samples returned a median of 10·7 nmol/l (1·7–45·4), and was most closely related to immunoassayed total T, but not immunoassayed bioavailable T or calculated free T. Immunoassayed total T demonstrated a positive association with isometric grip-strength ( R2 = 0·127, P < 0·001), self-reported sexual desire ( R2 = 0·113, P < 0·001) and erectile function ( R2 = 0·085, P < 0·05) while bioassay T did not. Conclusions While cellular bioassays offer a rapid and sensitive means of identifying the androgenic potential of complex environmental compounds, the utility of such assays in defining a clinically relevant fraction of serum T distinct from total T needs further investigation. [ABSTRACT FROM AUTHOR]

Objective Plasma androgen levels are inversely associated with health in men, the age-related decline of which may result from factors other than ageing per se. This study aimed to determine the effects of demographic, physical and lifestyle factors on age-related androgen status in men. Design An observational survey of a regionally representative male population residing in the North West regions of Adelaide, Australia. Participants Study sample includes 1195 men aged 35–81 years with a response rate of 45·1%. Measurements Plasma levels of total testosterone (TT), bioavailable testosterone (BT), SHBG, insulin-like peptide 3 (INSL3), and gonadotrophins were measured along with an extensive list of demographic, physical and lifestyle factors including body composition, muscle strength and biomarkers of chronic diseases, physical activity, nutrition and smoking behaviour. Results Low TT was mostly associated with high abdominal fat and triglycerides and low muscle strength rather than ageing per se. Low BT was associated with increased age followed by high whole body fat percentage. BT and TT levels were higher in unmarried men and smokers. SHBG levels increased with age, but were also inversely associated with insulin and triglycerides. The Leydig cell specific factor INSL3 was the strongest biomarker associated with both TT and BT. Conclusions Factors associated with low androgen status variably include high body fat percentage, low muscle strength and biomarkers of the metabolic syndrome. Reducing exposure to factors that adversely affect androgen status may improve the general health of ageing men by mechanisms yet to be defined. [ABSTRACT FROM AUTHOR]

The article discusses the results of a study on the role of CXCL12/CXCR4 chemokines in the activation and migration of osteoclast (OC) associated with bone loss in multiple myeloma (MM) in mice. The study found that overexpression of CXCL12 and RANKL genes in RPMI-8226 cells increased bone resorption mediated by OC. Implantation of RPMI-8226 cells led to osteolytic lesions. It concluded that mediated disruption of CXCL12/CXCR4 limits osteolysis in mice.

The article reports on the results of research which was done in an effort to define a serum 25(OH)D calcium level below which the serum 1,25(OH)D can no longer be sustained. researchers found that vitamin D deficiency does not reduce serum 1,25(OH)D or calcium absorption until the serum falls to the -10nM level.

The article reports on the results of research which was conducted in an effort to determine the levels of 25-hydoxyvitamin D that is needed for normal mineralization and to maintain bone strength in rats. Researchers found that vitamin D depletion induced osteoclastogenesis and bone loss in rats and that vitamin D levels also determined bone mineral volume.

Objective To determine the effects of menopause on bone-related variables in Indonesian women and to compare them with corresponding data in Caucasian Australian women. Design A study of bone-related variables in women aged 45–55 years in Jakarta compared with corresponding historical data from Caucasian Australian women. Measurements Dietary intakes, bone mineral density (BMD) and calcium-related variables in blood and urine. Results Dietary calcium, phosphorus and protein intakes were significantly lower in the women from Jakarta than in those from Adelaide (all P < 0·001), probably because of lower milk consumption, but energy intake was similar in the two cities. Indonesian women were shorter and lighter than Australian women ( P < 0·001) but had a comparable body mass index (BMI). The Indonesians also had a lower spinal BMD than the Australians but this was accounted for by the differences in height and weight between the two populations. The differences in serum and urinary calcium and phosphate and serum alkaline phosphatase across the menopause were comparable in Indonesian and Australian women but creatinine excretion was 25% lower in Jakarta than in Adelaide ( P < 0·001) and this was probably sufficient to account for higher ratios of some urinary solutes to urinary creatinine in the Indonesians. Serum 25-hydroxyvitamin D (25OHD) levels were significantly lower ( P < 0·001) and serum PTH levels significantly higher ( P = 0·0045) in Jakarta than in Adelaide. Conclusions The differences in bone-related biochemical variables across the menopause were similar in the two populations, but calcium and protein intake and urine creatinine were lower in Indonesian than in Australian women. Serum 25OHD was lower and PTH higher in the Indonesian women, probably because of their darker skin, their practice of avoiding direct sunlight and the heavy atmospheric pollution in Jakarta. [ABSTRACT FROM AUTHOR]

Objective To measure and contrast maternal cortisol and corticosteroid-binding globulin (CBG) levels in pregnancies with normal outcomes, pre-eclampsia, intrauterine growth restriction (IUGR) and in gamete recipients. Study design Prospective study of 93 women at high risk of pre-eclampsia, including gamete recipients ( n = 22) and 33 controls. Plasma total and free cortisol and CBG were measured every 2 weeks from 16 weeks’ gestation until delivery. Results Forty-two per cent of the high-risk group had complications, including pre-eclampsia ( n = 11), gestational hypertension ( n = 16) and small-for-gestational-age (SGA) neonates ( n = 12). There were no complications in the controls. In all groups, plasma CBG concentrations increased progressively across gestation ( P < 0·05), in parallel to total cortisol, but fell significantly from 36 weeks’ gestation onwards, with a corresponding rise in free cortisol concentrations. In pre-eclampsia and gestational hypertension, plasma CBG, and total and free cortisol concentrations were lower from 36 weeks onwards ( P < 0·05). In IUGR, plasma CBG concentrations were suppressed from 28 weeks’ gestation until delivery ( P < 0·05), but with no significant difference in plasma total and free cortisol. Gamete recipients had significantly lower plasma CBG from 20 weeks’ gestation onwards, and plasma total and free cortisol were reduced at 24 and 32 weeks onwards, respectively. Conclusions Maternal plasma CBG, total and free cortisol concentrations are reduced in pre-eclampsia/gestational hypertension, and markedly reduced in gamete recipients. Low CBG may be due to reduced synthesis or enhanced inflammation-driven degradation. Low maternal cortisol may be due to a lack of placental corticotropin-releasing hormone or reduced maternal ACTH, driving cortisol production. Low maternal cortisol may influence the foetal hypothalamic–pituitary–adrenal axis and disease patterns later in life following complicated pregnancy. [ABSTRACT FROM AUTHOR]

Because it has been reported that vitamin D, given to mother or infant, can prevent type I diabetes in children, that diabetes is more common in adults with low serum vitamin D and that insulin secretion and action are related to vitamin D levels in healthy young adults we examined the relationship between serum vitamin D metabolites and fasting serum glucose in patients attending our outpatient clinics.Retrospective examination of convenience sample of postmenopausal women attending our osteoporosis clinics.A total of 753 postmenopausal women attending a university hospital outpatient clinic and not on any treatment known to affect glucose metabolism.Body weight and height, serum 25-hydroxyvitamin D[25(OH)D], serum 1,25-dihydroxyvitamin D[1,25(OH)2D], serum PTH and fasting serum glucose.On simple correlation fasting serum glucose was a positive function of age (P < 0·05), weight (P < 0·001) and body mass index (BMI) (P < 0·001) and a negative function of serum 25(OH)D (P < 0·001), but it was not significantly related to either serum 1,25(OH)2D, PTH or creatinine. When fasting serum glucose was regressed simultaneously on age, BMI and 25(OH)D, glucose was still an inverse function of 25(OH)D (P = 0·006).Fasting serum glucose increased as 25(OH)D levels fell throughout the range of serum 25(OH)D measured but the greatest increase was observed in those with 25(OH)D below 40 nmol/l. [ABSTRACT FROM AUTHOR]

Abstract: Circulating levels of 1,25-dihydroxyvitamin D (1,25D) are determined by bioactivation catalyzed by the renal 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1) and degradation through the action of the renal 25-hydroxyvitamin D 24-hydroxylase (CYP24). CYP27B1 and CYP24 are also present in bone cells, but little is known of their physiological role. The purpose of this study was to determine the changes that occur with aging on the expression of CYP27B1 and CYP24 mRNA in whole kidney and femora of female Sprague–Dawley rats. Real-time RT-PCR was used to measure CYP27B1, CYP24 and vitamin D receptor (VDR) mRNA levels in the kidneys and bones of animals aged between 3 weeks and 2 years. Circulating 1,25D levels decreased exponentially with age which was correlated with both reduced kidney CYP27B1 mRNA (R 2 = 0.72) and increased CYP24 mRNA levels (R 2 = 0.71). In the bone, CYP27B1 mRNA levels were maintained at their highest level throughout the ages of 3 to 15 weeks before decreasing in adult animals (P &#60; 0.05). Bone CYP24 mRNA levels were positively correlated with bone CYP27B1 mRNA and not circulating 1,25D levels (R 2 = 0.74). Levels of bone CYP27B1 mRNA were positively correlated with distal femoral epiphyseal trabecular number (Tb.N) (R 2 = 0.74) and negatively with the trabecular thickness (Tb.Th) (R 2 = 0.56) in animals aged between 12 weeks and 2 years. These findings indicate that the regulation of CYP27B1 and CYP24 mRNA expression in the bone is unique from that in the kidney. The synthesis of 1,25D in bone tissue regulates bone CYP24 expression and is associated with bone mineralization suggesting that vitamin D metabolism has an autocrine or paracrine function. [Copyright &y& Elsevier]

Background: It is assumed that calcium absorption decreases with age, but this is not well documented. We report a study that addresses this issue. Objective: The aim was to establish the extent and timing of any age-related change in calcium absorption in postmenopausal women. Design: We measured radiocalcium absorption (α) in 262 healthy postmenopausal women aged 40 - 87 y. We also measured the serum vitamin D metabolites, parathyroid hormone (PTH), and other biochemical variables. Results: Radiocalcium absorption decreased with age (P = 0.018); it was 28% lower in the 25 women aged >75 y than in the rest (P < 0.001). Itwas significantly related to serum 1,25-dihydroxyvitamin D [1,25(OH)2D] in the whole set and in both the younger and older subsets, but it was not related to either 25-dihydroxyvitamin D [25(OH)D] or PTH or to any other measured variable. No decrease in 1,25(OH)2D was seen with age to account for the decrease in calcium absorption, so radiocalcium absorption corrected for serum 1,25(OH)2D decreased significantly after age 75 y. On multivariate analysis, the serum 1,25(OH)2D concentration was a positive function of 25(OH)D (P < 0.001), albumin (P = 0.010), and PTH (P = 0.012)andanegative function of serum creatinine (P = 0.003).PTH was a negative function of calculated ionized calcium (P = 0.004) and 25(OH)D (P = 0.009) and a positive function of weight (P = 0.011) and age (P = 0.028). Conclusions: A late age-related decrease in calcium absorption is seen in postmenopausal women in addition to the decline that occurs at menopause. This decrease could be due to a decline in either the active calcium transport or diffusion component of the calcium absorption system. [ABSTRACT FROM AUTHOR]

To evaluate the effects of the menopause on bone-related biochemical variables in a longitudinal study. Recruitment by advertisement of premenopausal women over the age of 44 for measurement of selected variables and collection of blood and urine samples for deep freezing, followed by annual check of menopausal status and repeat collection of blood and urine samples for deep freezing after the menopausal transition. A total of 104 women with confirmed premenopausal status and on no treatment likely to affect calcium or bone metabolism were admitted to the study over a period of 2 years. After 8 years, 43 of the volunteers had passed through the menopause and the study was closed. Radiocalcium absorption was measured at the first attendance and again after the menopausal transition. Calcium and other relevant variables were measured consecutively on paired thawed-out samples of blood and urine. The data were complete in 34 subjects. In these women, there were highly significant correlations between the first and second measurements of most variables – serum calcium and fractions, radiocalcium absorption, vitamin D metabolites, PTH and others – indicating significant ‘tracking’ of these variables across the menopause. Within that framework there were significant rises in serum total and calculated ionized calcium (both P < 0·001) without change in mean serum parathyroid hormone (PTH). Radiocalcium absorption fell ( P < 0·001) without change in serum 1,25D. There was a rise in fasting urinary calcium ( P < 0·001) which could not be explained by the rise in filtered load and therefore represented a fall in TmCa ( P < 0·001). There were significant rises in urinary bone resorption markers, pyridinoline and deoxypyridinoline ( P < 0·001). We conclude that the menopausal rise in calculated serum ionized calcium without fall in PTH, indicates a change in PTH set-point, and that the falls in gastrointestinal absorption and renal tubular reabsorption of calcium reflect the loss of an oestrogen action at these two sites. Although these changes are sufficient to explain the rise in calcium requirement at the menopause, the association of high bone resorption with normal serum PTH suggests also an increased sensitivity of bone to the action of parathyroid hormone. There is significant ‘tracking’ of many variables across the menopause despite very significant changes in their absolute values. [ABSTRACT FROM AUTHOR]

Details of the molecular mechanisms determining levels of the secosteroid, 1,25-dihydroxyvitamin D3 (1,25D) remain to be elucidated. The current paradigm for the control of serum 1,25D levels is the tight regulation of renal 25-hydroxyvitamin D-1α-hydroxlase (CYP27B1) activity by a number of physiological factors. 1,25D production is also regulated by the cytochrome P450 enzyme, 25-hydroxyvitamin D-24-hydroxylase (CYP24), which through side chain hydroxylation reactions, inactivates 1,25D. We have recently demonstrated that renal CYP27B1 and CYP24 expression contribute equally to regulating serum 1,25D levels. We now describe the contribution of renal Vitamin D receptor (VDR) expression in determining serum 1,25D levels. Serum 1,25D levels were decreased when the dietary calcium intake was increased. We measured mRNA levels for CYP27B1, CYP24 and VDR receptor in kidney RNA extracts from animals fed diets containing different levels of calcium, ranging from 0.05 to 1%. Serum 1,25D levels were negatively correlated with renal CYP24 mRNA levels (R2=0.35, P<0.01) while renal VDR is positively correlated with renal CYP24 mRNA (R2=0.80, P<0.001). However, only renal VDR mRNA remained a significant determinant of renal CYP24 expression when both these variables were included in multiple linear regression analysis (multiple R2=0.89, P<0.001). These findings suggest that kidney CYP24 activity acts in concert with kidney CYP27B1 to control serum 1,25D levels and that serum 1,25D stimulates renal CYP24 expression by acting through the renal VDR. [Copyright &y& Elsevier]