Central diabetes insipidus associated with impaired renal aquaporin-1 expression in mice lacking liver X receptor β

The present study demonstrates a key role for the oxysterol receptor liver X receptor β (LXRβ) in the etiology of diabetes insipidus (DI). Given free access to water, LXRβ(-/-) but not LXRα(-/-) mice exhibited polyuria (abnormal daily excretion of highly diluted urine) and polydipsia (increased water intake), both features of diabetes insipidus. LXRβ(-/-) mice responded to 24-h dehydration with a decreased urine volume and increased urine osmolality. To determine whether the DI was of central or nephrogenic origin, we examined the responsiveness of the kidney to arginine vasopressin (AVP). An i.p. injection of AVP to LXRβ(-/-) mice revealed a partial kidney response: There was no effect on urine volume, but there was a significant increase of urine osmolality, suggesting that DI may be caused by a defect in central production of AVP. In the brain of WT mice LXRβ was expressed in the nuclei of magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus. In LXRβ(-/-) mice the expression of AVP was markedly decreased in the magnocellular neurons as well as in urine collected over a 24-h period. The persistent high urine volume after AVP administration was traced to a reduction in aquaporin-1 expression in the kidney of LXRβ(-/-) mice. The LXR agonist (GW3965) in WT mice elicited an increase in urine osmolality, suggesting that LXRβ is a key receptor in controlling water balance with targets in both the brain and kidney, and it could be a therapeutic target in disorders of water balance.     

Complement activation products in liquid stored plasma and C3a kinetics after transfusion of autologous plasma

Background and Objectives Keeping a small stock of liquid plasma readily available for transfusion is common practise in Sweden. We report data on complement activation markers in plasma components during storage in the liquid state and the kinetics of C3a‐_desArg after transfusion of autologous plasma with high content of C3a‐_desArg. Material and Methods Plasma components were prepared by apheresis or from whole blood. C3 fragments (C3a‐_desArg, C3d,g, iC3), and soluble terminal complement complex (sC5b‐9) were investigated. C3a‐_desArg kinetics was investigated in regular apheresis donors. Results Apheresis plasma prepared by membrane centrifugation had significantly higher level of C3a‐_desArg, C3d,g and sC5b‐9 from day 0 and low iC3, than plasma prepared by other methods. By storage day 7, C3a‐_desArg ‐levels were above the reference value in 88% of all components. After re‐infusion of autologous plasma with high C3a‐_desArg content, there were rapid a₁ and a₂‐distribution followed by a slower b‐elimination phase. Conclusion Plasma components prepared by different methods and stored in the liquid phase differ significantly in the amount and timing of complement activation. C3a‐_desArg present in plasma is rapidly eliminated after transfusion. Autologous plasma could be used to study complement kinetics in different clinical situations.     

Perception of dental fluorosis amongst Ethiopian children and their mothers

This study was conducted in three Ethiopian Rift Valley villages known for endemic fluorosis. Three-hundred-and-six adolescents (12-15 years) and 233 mothers participated. The aim was to study dental fluorosis in the youngsters and to assess the extent of agreement between clinical and self-rated discoloration and pitting of teeth, and also the level at which dental fluorosis is perceived as a problem both by children and their mothers. The children (154 M and 152 F) gave a simple self-assessment of tooth-color and quality of their teeth, and were subsequently examined for dental fluorosis. Finally, four color photographs of teeth with dental fluorosis (TF-scores 2, 3, 5, and 7) were used as references during a structured oral interview of the children, as well as their mothers. At TF score &#83 2, the prevalence of dental fluorosis on maxillary central incisors was 72% and 37% at TF score &#83 4. The mean TF score was significantly higher among boys than among girls of unemployed fathers compared to children of employed fathers. The likelihood of reporting problems with dental appearance increased with increasing individual TF scores. The child/mother pairs found teeth with TF scores 2 and 3 esthetically acceptable, while teeth with TF scores 5 and 7 were considered unacceptable. Mothers were more critical of severe fluorosis than were their children.     

Dental treatment need among 20 to 25‐year‐old Swedes: discrepancy between subjective and objective need

Abstract

Objective. This methodological study aimed to determine whether the mandibular trabecular bone assessment from panoramic radiographs, using a visual index, corresponds to the evaluation obtained from periapical radiographs. Material and methods. A panoramic radiograph and corresponding periapical radiographs of the region of the lower premolars and molars were collected from each of 32 patients (mean age 18.5 ± 5.5 years). Two calibrated observers assessed randomly the interdental sites between the first molar and second premolar and between the two premolars on all the radiographs using a visual index. Evaluations were repeated with an interval of 60 days. The results of the repeated evaluations were used to assess intra- and inter-observer agreements, employing Kappa statistics. Spearman's correlation was used to determine the association between assessments of panoramic and periapical radiographs. Results. In total, 79 interdental sites were evaluated on the panoramic and periapical radiographs. The visual analysis of periapical radiographs revealed intra-observer agreements of 0.88 for observer 1 and 0.93 for observer 2, and an inter-observer agreement of 0.82. The intra-observer agreement for panoramic radiographs was 0.79 and 0.83 for observers 1 and 2, respectively, and the inter-observer agreement was 0.79. A substantial correlation was found between periapical and panoramic radiographs (rho = 0.737, p = 0.001). Conclusions. Although panoramic radiographs are less reliable than periapical radiographs, they can be used for assessment of the trabecular bone pattern with the aid of a visual index. Training on the method is recommended to obtain results with a high reproducibility.     

Capture the Fracture: a Best Practice Framework and global campaign to break the fragility fracture cycle

Summary

The International Osteoporosis Foundation (IOF) Capture the Fracture Campaign aims to support implementation of Fracture Liaison Services (FLS) throughout the world.

Introduction

FLS have been shown to close the ubiquitous secondary fracture prevention care gap, ensuring that fragility fracture sufferers receive appropriate assessment and intervention to reduce future fracture risk.

Methods

Capture the Fracture has developed internationally endorsed standards for best practice, will facilitate change at the national level to drive adoption of FLS and increase awareness of the challenges and opportunities presented by secondary fracture prevention to key stakeholders. The Best Practice Framework (BPF) sets an international benchmark for FLS, which defines essential and aspirational elements of service delivery.

Results

The BPF has been reviewed by leading experts from many countries and subject to beta-testing to ensure that it is internationally relevant and fit-for-purpose. The BPF will also serve as a measurement tool for IOF to award ‘Capture the Fracture Best Practice Recognition’ to celebrate successful FLS worldwide and drive service development in areas of unmet need. The Capture the Fracture website will provide a suite of resources related to FLS and secondary fracture prevention, which will be updated as new materials become available. A mentoring programme will enable those in the early stages of development of FLS to learn from colleagues elsewhere that have achieved Best Practice Recognition. A grant programme is in development to aid clinical systems which require financial assistance to establish FLS in their localities.

Conclusion

Nearly half a billion people will reach retirement age during the next 20 years. IOF has developed Capture the Fracture because this is the single most important thing that can be done to directly improve patient care, of both women and men, and reduce the spiralling fracture-related care costs worldwide.     

Degenerative changes at the lumbar spine—implications for bone mineral density measurement in elderly women

Summary

Degenerative changes of the lumbar spine may lead to misinterpretation of bone mineral density (BMD) measurements and cause underdiagnosis of osteoporosis. This longitudinal study of 1,044 women, 75 years at inclusion and followed for 10 years, shows that identification of apparent degenerative changes on the dual energy X-ray absorptiometry (DXA) scan can increase the proportion diagnosed.

Introduction

In the elderly, degenerative manifestations in the lumbar spine may result in falsely elevated BMD values, consequently missing a large proportion of those with osteoporosis. Our aim was to determine the distribution and impact of degenerative changes on lumbar spine DXA over time and its clinical implications.

Methods

Participants were 1,044 women from the population-based Osteoporosis Risk Assessment cohort. All women were 75 years old at invitation and followed up after 5 years (n?=?715) and 10 years (n?=?382). Degenerative changes were evaluated visually on the DXA image for each vertebra L1 to L4 (intraobserver precision kappa values of 0.66–0.70).

Results

At baseline, apparent degenerative changes were more frequent in the inferior segments of the lumbar spine [5 % (L1), 15 % (L2), 26 % (L3), and 36 % (L4)] and increased over time. At 10 years, the prevalences were 20 % (L1), 39 % (L2), 59 % (L3), 72 % (L4), resulting in a significant increase in overall BMD. In women without apparent degenerative changes, BMD remained stable between 75 and 85 rather than an expected bone loss. At baseline, 37 % had osteoporosis (BMD?<??2.5) at L1–L4; exclusion of women with apparent degenerative changes increased this proportion to 47 %. Using L1–L2, which was less prone to degenerative changes, 46 % of women were classified as osteoporotic regardless of degenerative changes.

Conclusion

Degenerative changes were very common in elderly women, accelerated disproportionately over time, were increasingly frequent from vertebrae L1 to L4, and had significant impact on diagnosing osteoporosis. This suggests that routine reporting of spine BMD at L1–L2 would add valuable information for reassessment and monitoring.     

Birth weight is more important for peak bone mineral content than for bone density: the PEAK-25 study of 1,061 young adult women

Summary

Lower birth weight has a negative association with adult BMC and body composition in young adult Swedish women.

Introduction

The aim of this study was to evaluate the influence of birth weight on peak bone mass and body composition in a cohort of 25-year-old women.

Methods

One thousand sixty-one women participated in this cross-sectional population-based study using dual energy X-ray absorptiometry (DXA) to assess bone mineral content (BMC), bone mineral density (BMD), and body composition (total body (TB), femoral neck (FN), total hip (TH), lumbar spine L1–L4 (LS), and lean and fat mass). Birth weight data was available for 1,047 women and was categorized into tertiles of low (≤3,180 g), intermediate (3,181–3,620 g), and high (≥3,621 g) birth weight.

Results

Significant correlations were observed between birth weight and TB-BMC (r?=?0.159, p?<?0.001), FN-BMC (r?=?0.096, p?<?0.001), TH-BMC (r?=?0.102, p?=?0.001), LS-BMC (r?=?0.095, p?=?0.002), and lean mass (r?=?0.215, p?<?0.001). No correlation was observed between birth weight and BMD. The estimated magnitude of effect was equivalent to a 0.3–0.5 SD difference in BMC for every 1 kg difference in birth weight (151 g (TB); 0.22 g (FN); 1.5 g (TH), 2.5 kg TB lean mass). The strongest correlations between birth weight and BMC occurred in women with lowest birth weights, although excluding women who weighed <2,500 g at birth, and the correlation remained significant although slightly weaker.

Conclusions

Women with lower birth weight have lower BMC and less lean and fat mass at the age of 25, independent of current body weight. Lower birth weight has a greater negative influence on bone mass than the positive influence of higher birth weight.     

Inclusion of CYP3A5 genotyping in a nonparametric population model improves dosing of tacrolimus early after transplantation

Following organ engraftment, initial dosing of tacrolimus is based on recipient weight and adjusted by measured C₀ concentrations. The bioavailability and elimination of tacrolimus are affected by the patients CYP3A5 genotype. Prospective data of the clinical advantage of knowing patient's CYP3A5 genotype prior to transplantation are lacking. A nonparametric population model was developed for tacrolimus in renal transplant recipients. Data from 99 patients were used for model development and validation. A three‐compartment model with first‐order absorption and lag time from the dosing compartment described the data well. Clearances and volumes of distribution were allometrically scaled to body size. The final model included fat‐free mass, body mass index, hematocrit, time after transplantation, and CYP3A5 genotype as covariates. The bias and imprecision were 0.35 and 1.38, respectively, in the external data set. Patients with functional CYP3A5 had 26% higher clearance and 37% lower bioavailability. Knowledge of CYP3A5 genotype provided an initial advantage, but only until 3‐4 tacrolimus concentrations were known. After this, a model without CYP3A5 genotype predicted just as well. The present models seem applicable for clinical individual dose predictions but need a prospective evaluation.     

Fundamentals of randomized clinical trials in wound care: Reporting standards

In wound care research, available high‐level evidence according to the evidence pyramid is rare, and is threatened by a poor study design and reporting. Without comprehensive and transparent reporting, readers will not be able to assess the strengths and limitations of the research performed. Randomized clinical trials (RCTs) are universally acknowledged as the study design of choice for comparing treatment effects. To give high‐level evidence the appreciation it deserves in wound care, we propose a step‐by‐step reporting standard for comprehensive and transparent reporting of RCTs in wound care. Critical reporting issues (e.g., wound care terminology, blinding, predefined outcome measures, and a priori sample size calculation) and wound‐specific barriers (e.g., large diversity of etiologies and comorbidities of patients with wounds) that may prevent uniform implementation of reporting standards in wound care research are addressed in this article. The proposed reporting standards can be used as guidance for authors who write their RCT, as well as for peer reviewers of journals. Endorsement and application of these reporting standards may help achieve a higher standard of evidence and allow meta‐analysis of reported wound care data. The ultimate goal is to help wound care professionals make better decisions for their patients in clinical practice.