The effect of past use of oral contraceptive on bone mineral density, bone biochemical markers and muscle strength in healthy pre and post menopausal women

<p>Abstract</p> <p>Background</p> <p>during adulthood, most studies have reported that oral contraceptive (OC) pills had neutral, or possibly beneficial effect on bone health. We proposed this study of pre and post menopausal women assessing BMD, bone biochemical markers and physical performance among OC past users and comparable women who have never use Ocs.</p> <p>Methods</p> <p>A cross-sectional study comparing the bone density, bone biochemical markers (osteocalcin, CTX) and three measures to assess physical performance: timed get-up-and-go test "TGUG", five-times-sit-to-stand test "5 TSTS" and 8-feet speed walk "8 FSW" of users and never users OC. We were recruited 210 women who used OC for at least 2 years with that of 200 nonusers was carried out in pre and postmenopausal women (24-86 years).</p> <p>Results</p> <p>when analysing the whole population, BMD and biochemical markers values were similar for Ocs past users and control subjects. However when analysing the subgroup of premenopausal women, there was a statistically significant difference between users and never-users in osteocalcin (15,5 ± 7 ng/ml vs 21,6 ± 9 ng/ml; p = 0,003) and CTX (0,30 ± 0,1 ng/ml vs 0,41 ± 0,2 ng/ml; p = 0,025). This difference persisted after adjustment for age, BMI, age at menarche and number of pregnancies. In contrast, in post menopausal women, there was no difference in bone biochemical markers between OC users and the control. On the other hand OC past users had a significant greater performance than did the never users group. And when analysing the physical performance tests by quartile OC duration we found a significant negative association between the three tests and the use of OC more than 10 years.</p> <p>Conclusion</p> <p>the funding show no evidence of a significant difference in BMD between Ocs users and never user control groups, a decrease in bone turn over in OC pre menopausal users and a greater physical performances in patients who used OC up than 10 years.</p

Predictors of sun protection behaviours and sunburn among Australian adolescents

BACKGROUND: Excessive sun exposure and sunburn increase individuals' risk of skin cancer. It is especially important to prevent sunburn in childhood due to the higher relative risk of skin cancer across the life span compared to risk associated with sunburn episodes experienced later in life. This study examined demographic and attitudinal factors associated with engagement in a range of sun protection behaviours (wearing a hat, wearing protective clothing, staying in the shade, and staying indoors during the middle of the day) and the frequency of sunburn among Western Australian adolescents to provide insights of relevance for future sun protection campaigns. METHODS: Cross-sectional telephone surveys were conducted annually with Western Australians between 2005/06 and 2014/15. The results from 4150 adolescents aged 14-17 years were used to conduct a path analysis of factors predicting various sun protection behaviours and sunburn. RESULTS: Significant primary predictors of the sun protection behaviours included in the study were skin type (sun sensitivity), gender, tanning-related attitudes and behaviours, and perceived relevance of public service advertisements that advocate sun protection. Of the four sun protection behaviours investigated, staying in the shade and staying indoors during the middle of the day were associated with a lower frequency of sunburn. CONCLUSION: There is a particular need to target sun protection messages at adolescent males who are less likely to engage in the most effective sun protection behaviours and demonstrate an increased propensity to experience sunburn. The results suggest that such future sun protection messages should include a focus on the importance of staying in the shade or indoors during periods of high UV radiation to increase awareness of the efficacy of these methods of avoiding skin cancer

Genome-Wide Population-Based Association Study of Extremely Overweight Young Adults – The GOYA Study

Background: Thirty-two common variants associated with body mass index (BMI) have been identified in genome-wide association studies, explaining ~1.45% of BMI variation in general population cohorts. We performed a genome-wide association study in a sample of young adults enriched for extremely overweight individuals. We aimed to identify new loci associated with BMI and to ascertain whether using an extreme sampling design would identify the variants known to be associated with BMI in general populations. Methodology/Principal Findings: From two large Danish cohorts we selected all extremely overweight young men and women (n = 2,633), and equal numbers of population-based controls (n = 2,740, drawn randomly from the same populations as the extremes, representing ~212,000 individuals). We followed up novel (at the time of the study) association signals (

Diagnostic delay for giant cell arteritis – a systematic review and meta-analysis

Background Giant cell arteritis (GCA), if untreated, can lead to blindness and stroke. The study’s objectives were to (1) determine a new evidence-based benchmark of the extent of diagnostic delay for GCA and (2) examine the role of GCA-specific characteristics on diagnostic delay. Methods Medical literature databases were searched from inception to November 2015. Articles were included if reporting a time-period of diagnostic delay between onset of GCA symptoms and diagnosis. Two reviewers assessed the quality of the final articles and extracted data from these. Random-effects meta-analysis was used to pool the mean time-period (95% confidence interval (CI)) between GCA symptom onset and diagnosis, and the delay observed for GCA-specific characteristics. Heterogeneity was assessed by I 2 and by 95% prediction interval (PI). Results Of 4128 articles initially identified, 16 provided data for meta-analysis. Mean diagnostic delay was 9.0 weeks (95% CI, 6.5 to 11.4) between symptom onset and GCA diagnosis (I 2 = 96.0%; P < 0.001; 95% PI, 0 to 19.2 weeks). Patients with a cranial presentation of GCA received a diagnosis after 7.7 (95% CI, 2.7 to 12.8) weeks (I 2 = 98.4%; P < 0.001; 95% PI, 0 to 27.6 weeks) and those with non-cranial GCA after 17.6 (95% CI, 9.7 to 25.5) weeks (I 2 = 96.6%; P < 0.001; 95% PI, 0 to 46.1 weeks). Conclusions The mean delay from symptom onset to GCA diagnosis was 9 weeks, or longer when cranial symptoms were absent. Our research provides an evidence-based benchmark for diagnostic delay of GCA and supports the need for improved public awareness and fast-track diagnostic pathways

Steroid Concentrations in Plasma, Whole Blood and Brain: Effects of Saline Perfusion to Remove Blood Contamination from Brain

The brain and other organs locally synthesize steroids. Local synthesis is suggested when steroid levels are higher in tissue than in the circulation. However, measurement of both circulating and tissue steroid levels are subject to methodological considerations. For example, plasma samples are commonly used to estimate circulating steroid levels in whole blood, but steroid levels in plasma and whole blood could differ. In addition, tissue steroid measurements might be affected by blood contamination, which can be addressed experimentally by using saline perfusion to remove blood. In Study 1, we measured corticosterone and testosterone (T) levels in zebra finch (Taeniopygia guttata) plasma, whole blood, and red blood cells (RBC). We also compared corticosterone in plasma, whole blood, and RBC at baseline and after 60 min restraint stress. In Study 2, we quantified corticosterone, dehydroepiandrosterone (DHEA), T, and 17β-estradiol (E2) levels in the brains of sham-perfused or saline-perfused subjects. In Study 1, corticosterone and T concentrations were highest in plasma, significantly lower in whole blood, and lowest in RBC. In Study 2, saline perfusion unexpectedly increased corticosterone levels in the rostral telencephalon but not other regions. In contrast, saline perfusion decreased DHEA levels in caudal telencephalon and diencephalon. Saline perfusion also increased E2 levels in caudal telencephalon. In summary, when comparing local and systemic steroid levels, the inclusion of whole blood samples should prove useful. Moreover, blood contamination has little or no effect on measurement of brain steroid levels, suggesting that saline perfusion is not necessary prior to brain collection. Indeed, saline perfusion itself may elevate and lower steroid concentrations in a rapid, region-specific manner

A Kinome-wide screen identifies a CDKL5-SOX9 regulatory axis in epithelial cell death and kidney injury

© 2020, The Author(s). Renal tubular epithelial cells (RTECs) perform the essential function of maintaining the constancy of body fluid composition and volume. Toxic, inflammatory, or hypoxic-insults to RTECs can cause systemic fluid imbalance, electrolyte abnormalities and metabolic waste accumulation- manifesting as acute kidney injury (AKI), a common disorder associated with adverse long-term sequelae and high mortality. Here we report the results of a kinome-wide RNAi screen for cellular pathways involved in AKI-associated RTEC-dysfunction and cell death. Our screen and validation studies reveal an essential role of Cdkl5-kinase in RTEC cell death. In mouse models, genetic or pharmacological Cdkl5 inhibition mitigates nephrotoxic and ischemia-associated AKI. We propose that Cdkl5 is a stress-responsive kinase that promotes renal injury in part through phosphorylation-dependent suppression of pro-survival transcription regulator Sox9. These findings reveal a surprising non-neuronal function of Cdkl5, identify a pathogenic Cdkl5-Sox9 axis in epithelial cell-death, and support CDKL5 antagonism as a therapeutic approach for AKI

MEDEAS: a new modeling framework integrating global biophysical and socioeconomic constraints

Producción CientíficaA diversity of integrated assessment models (IAMs) coexists due to the different approaches developed to deal with the complex interactions, high uncertainties and knowledge gaps within the environment and human societies. This paper describes the open-source MEDEAS modeling framework, which has been developed with the aim of informing decision-making to achieve the transition to sustainable energy systems with a focus on biophysical, economic, social and technological restrictions and tackling some of the limitations identified in the current IAMs. MEDEAS models include the following relevant characteristics: representation of biophysical constraints to energy availability; modeling of the mineral and energy investments for the energy transition, allowing a dynamic assessment of the potential mineral scarcities and computation of the net energy available to society; consistent representation of climate change damages with climate assessments by natural scientists; integration of detailed sectoral economic structure (input–output analysis) within a system dynamics approach; energy shifts driven by physical scarcity; and a rich set of socioeconomic and environmental impact indicators. The potentialities and novel insights that this framework brings are illustrated by the simulation of four variants of current trends with the MEDEAS-world model: the consideration of alternative plausible assumptions and methods, combined with the feedback-rich structure of the model, reveal dynamics and implications absent in classical models. Our results suggest that the continuation of current trends will drive significant biophysical scarcities and impacts which will most likely derive in regionalization (priority to security concerns and trade barriers), conflict, and ultimately, a severe global crisis which may lead to the collapse of our modern civilization. Despite depicting a much more worrying future than conventional projections of current trends, we however believe it is a more realistic counterfactual scenario that will allow the design of improved alternative sustainable pathways in future work.Ministerio de Economía, Industria y Competitividad (Project CO2017-85110-R)Ministerio de Economía, Industria y Competitividad (Project JCI-2016–28833)MEDEAS project, funded by the European Union’s Horizon2020 research and innovation programme under grant agree-ment no. 691287.LOCOMOTION project, funded by the EuropeanUnion’s Horizon 2020 research and innovation programmeunder grant agreement no. 82110

Inhibition of the Progesterone Nuclear Receptor during the Bone Linear Growth Phase Increases Peak Bone Mass in Female Mice

Augmentation of the peak bone mass (PBM) may be one of the most effective interventions to reduce the risk of developing osteoporosis later in life; however treatments to augment PBM are currently limited. Our study evaluated whether a greater PBM could be achieved either in the progesterone nuclear receptor knockout mice (PRKO) or by using a nuclear progesterone receptor (nPR) antagonist, RU486 in mice. Compared to their wild type (WT) littermates the female PRKO mice developed significantly higher cancellous and cortical mass in the distal femurs, and this was associated with increased bone formation. The high bone mass phenotype was partially reproduced by administering RU486 in female WT mice from 1–3 months of age. Our results suggest that the inhibition of the nPR during the rapid bone growth period (1–3 months) increases osteogenesis, which results in acquisition of higher bone mass. Our findings suggest a crucial role for progesterone signaling in bone acquisition and inhibition of the nPR as a novel approach to augment bone mass, which may have the potential to reduce the burden of osteoporosis