A Fetal-Maternal Shift of Blood Oxygen Affinity in an Australian Viviparous Lizard, Sphenomorphus quoyii (Reptilia, Scincidae)

Compared to adults, the oxygen affinity of blood from fetal Sphenomorphus quoyii is very much higher: P50 is approximately 70 Torr in adults and 30 Torr in nearly full term embryos (PC02= 17 Torr, T=34 degrees C). Following birth, oxygen affinity decreases gradually and adult values are approached after about 15 weeks, with the onset of winter retreat. Electrophoresis revealed a multiple hemoglobin system in both adults and embryos, but there were no apparent differences between them

Interventions to support people exposed to adverse childhood experiences : systematic review of systematic reviews

BACKGROUND: Adverse Childhood Experiences (ACEs) such as abuse, neglect or household adversity may have a range of serious negative impacts. There is a need to understand what interventions are effective to improve outcomes for people who have experienced ACEs. METHODS: Systematic review of systematic reviews. We searched 18 database sources from 2007 to 2018 for systematic reviews of effectiveness data on people who experienced ACEs aged 3-18, on any intervention and any outcome except incidence of ACEs. We included reviews with a summary quality score (AMSTAR) of 5.5 or above. RESULTS: Twenty-five reviews were included. Most reviews focus on psychological interventions and mental health outcomes. The strongest evidence is for cognitive-behavioural therapy for people exposed to abuse. For other interventions - including psychological therapies, parent training, and broader support interventions - the findings overall are inconclusive, although there are some positive results. CONCLUSIONS: There are significant gaps in the evidence on interventions for ACEs. Most approaches focus on mitigating individual psychological harms, and do not address the social pathways which may mediate the negative impacts of ACEs. Many negative impacts of ACEs (e.g. on health behaviours, social relationships and life circumstances) have also not been widely addressed by intervention studies

Aging, lifestyle factors, hormones and bone health in Singaporean men

Purpose. The present study examined how age, bodyweight, body fat, regular exercise and some endocrine factors are associated with osteoporosis, spine bone mineral density (Sbmd) and femoral neck bone mineral density (Fnbmd) in Singaporean men. Methods. Body composition and bone scans of lumbar spine at L2-L4 and hip were carried out with duel-energy X-ray absorptiometry (DXA). Anthropometric parameters were measured and demographic data, medical history and exercise schedule were collected via a questionnaire. Results. Osteoporosis prevalence was higher and Sbmd and Fnbmd were lower in men with high percent body fat (PBF) and conversely osteoporosis prevalence was lower and Sbmd and Fnbmd were higher in men with higher body mass index (BMI). Age was negatively associated with Fnbmd but not Sbmd. On the other hand, PBF and insulin levels were negatively associated with both Sbmd and Fnbmd. Body mass index and exercise intensity were positively associated with both Sbmd and Fnbmd. Sex hormones were significantly associated with only Sbmd but not Fnbmd. Both estradiol and DHEAS were positively, while testosterone was negatively associated with Sbmd. Conclusion. The study shows that the prevalence of osteoporosis and some of the determinants of bone mineral density (BMD) in Singaporean men was site-specific. Further, BMI and PBF are opposing predictors of BMD. Therefore, any strategy for improving bone health should include modalities that increase lean and bone mass and decrease fat mass. The bone health of Singaporean men is comparable to non-Hispanic whites and better than some other Asian men

A three-year longitudinal evaluation of the forearm bone density of users of etonogestrel- and levonorgestrel-releasing contraceptive implants

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to evaluate bone mineral density (BMD) at baseline and at 18 and 36 months of use of etonogestrel (ENG)-and levonorgestrel (LNG)-releasing contraceptive implants. This is a continuation of a previous study in which BMD was evaluated at baseline and at 18 months of use.</p> <p>Methods</p> <p>A total of 111 women, 19–43 years of age, wererandomly allocated to use one of the two implants. At 36 months of follow-up, only 36 and 39 women were still using the ENG- and LNG-releasing implants, respectively. BMD was evaluated at the distal and at the ultra-distal radius of the non-dominant forearm using dual-energy X-ray absorptiometry.</p> <p>Results</p> <p>There was no difference in the BMD of users of either implant at 18 and at 36 months. BMD was significantly lower at 18 and at 36 months at the distal radius in both groups of users compared to pre-insertion values; however, no difference was found at the ultra-distal radius.</p> <p>Conclusion</p> <p>Women 19–43 years of age using either one of these two contraceptive implants for 36 months had lower BMD values at the distal radius compared to pre-insertion values; however, no difference was found at the ultra-distal radius.</p

Patient preference and acceptability of calcium plus vitamin D3 supplementation: a randomised, open, cross-over trial

Preference for a drug formulation is important in adherence to long-term medication for chronic illnesses such as osteoporosis. We investigated the preference for and acceptability of chewable tablet containing calcium and vitamin D (Calci Chew D3, Nycomed) compared to that of a sachet containing calcium and vitamin D3 (Cad, Will-Pharma). This open, randomised, cross-over trial was set up to compare the preference and acceptability of two calcium plus vitamin D3 formulations (both with 500 mg calcium and 400/440 IU vitamin D3), given twice a day in patients with osteoporosis. Preference and acceptability were assessed by means of questionnaires. Preference was determined by asking the question, which treatment the patient preferred, and acceptability was measured by scoring five variables, using rating scales. Of the 102 patients indicating a preference for a trial medication, 67% preferred the chewable tablet, 19% the sachet with calcium and vitamin D3, and 15% stated no preference. The significant preference for Calci Chew D3 (p < 0.0001) was associated with higher scores for all five acceptability variables. The two formulations were tolerated equally well. A significant greater number of patients considered the chewable tablet as preferable and acceptable to the sachet, containing calcium and vitamin D3. Trial registration: Current Controlled Trials ISRCTN18822358

Timing and risk factors for clinical fractures among postmenopausal women: a 5-year prospective study

BACKGROUND: Many risk factors for fractures have been documented, including low bone-mineral density (BMD) and a history of fractures. However, little is known about the short-term absolute risk (AR) of fractures and the timing of clinical fractures. Therefore, we assessed the risk and timing of incident clinical fractures, expressed as 5-year AR, in postmenopausal women. METHODS: In total, 10 general practice centres participated in this population-based prospective study. Five years after a baseline assessment, which included clinical risk factor evaluation and BMD measurement, 759 postmenopausal women aged between 50 and 80 years, were re-examined, including undergoing an evaluation of clinical fractures after menopause. Risk factors for incident fractures at baseline that were significant in univariate analyses were included in a multivariate Cox survival regression analysis. The significant determinants were used to construct algorithms. RESULTS: In the total group, 12.5% (95% confidence interval (CI) 10.1–14.9) of the women experienced a new clinical fracture. A previous clinical fracture after menopause and a low BMD (T-score <-1.0) were retained as significant predictors with significant interaction. Women with a recent previous fracture (during the past 5 years) had an AR of 50.1% (95% CI 42.0–58.1) versus 21.2% (95% CI 20.7–21.6) if the previous fracture had occurred earlier. In women without a fracture history, the AR was 13.8% (95% CI 10.9–16.6) if BMD was low and 7.0% (95% CI 5.5–8.5) if BMD was normal. CONCLUSION: In postmenopausal women, clinical fractures cluster in time. One in two women with a recent clinical fracture had a new clinical fracture within 5 years, regardless of BMD. The 5-year AR for a first clinical fracture was much lower and depended on BMD

Feasibility and acceptability of a multiple risk factor intervention: The Step Up randomized pilot trial

<p>Abstract</p> <p>Background</p> <p>Interventions are needed which can successfully modify more than one disease risk factor at a time, but much remains to be learned about the acceptability, feasibility, and effectiveness of multiple risk factor (MRF) interventions. To address these issues and inform future intervention development, we conducted a randomized pilot trial (n = 52). This study was designed to assess the feasibility and acceptability of the Step Up program, a MRF cognitive-behavioral program designed to improve participants' mental and physical well-being by reducing depressive symptoms, promoting smoking cessation, and increasing physical activity.</p> <p>Methods</p> <p>Participants were recruited from a large health care organization and randomized to receive usual care treatment for depression, smoking, and physical activity promotion or the phone-based Step Up counseling program plus usual care. Participants were assessed at baseline, three and six months.</p> <p>Results</p> <p>The intervention was acceptable to participants and feasible to offer within a healthcare system. The pilot also offered important insights into the optimal design of a MRF program. While not powered to detect clinically significant outcomes, changes in target behaviors indicated positive trends at six month follow-up and statistically significant improvement was also observed for depression. Significantly more experimental participants reported a clinically significant improvement (50% reduction) in their baseline depression score at four months (54% vs. 26%, OR = 3.35, 95% CI [1.01- 12.10], <it>p </it>= 0.05) and 6 months (52% vs. 13%, OR = 7.27, 95% CI [1.85 - 37.30], <it>p </it>= 0.004)</p> <p>Conclusions</p> <p>Overall, results suggest the Step Up program warrants additional research, although some program enhancements may be beneficial. Key lessons learned from this research are shared to promote the understanding of others working in this field.</p> <p>Trial registration</p> <p>The trial is registered with ClinicalTrials.gov (<a href="http://www.clinicaltrials.gov/ct2/show/NCT00644995">NCT00644995</a>).</p

Folding of Toll-like receptors by the HSP90 paralogue gp96 requires a substrate-specific cochaperone

Cytosolic HSP90 requires multiple cochaperones in folding client proteins. However, the function of gp96 (HSP90b1, grp94), an HSP90 paralogue in the endoplasmic reticulum (ER), is believed to be independent of cochaperones. Here, we demonstrate that gp96 chaperones multiple Toll-like receptors (TLRs), but not TLR3, in a manner that is dependent on another ER luminal protein, CNPY3. gp96 directly interacts with CNPY3, and the complex dissociates in the presence of adenosine triphosphate (ATP). Genetic disruption of gp96–CNPY3 interaction completely abolishes their TLR chaperone function. Moreover, we demonstrate that TLR9 forms a multimolecular complex with gp96 and CNPY3, and the binding of TLR9 to either molecule requires the presence of the other. We suggest that CNPY3 interacts with the ATP-sensitive conformation of gp96 to promote substrate loading. Our study has thus established CNPY3 as a TLR-specific cochaperone for gp96