Lithium pollution of a white dwarf records the accretion of an extrasolar planetesimal.

Tidal disruption and subsequent accretion of planetesimals by white dwarfs can reveal the elemental abundances of rocky bodies in exoplanetary systems. Those abundances provide information on the composition of the nebula from which the systems formed, which is analogous to how meteorite abundances inform our understanding of the early Solar System. We report the detection of lithium, sodium, potassium, and calcium in the atmosphere of the white dwarf Gaia DR2 4353607450860305024, which we ascribe to the accretion of a planetesimal. Using model atmospheres, we determine abundance ratios of these elements, and, with the exception of lithium, they are consistent with meteoritic values in the Solar System. We compare the measured lithium abundance with measurements in old stars and with expectations from Big Bang nucleosynthesis.

The contribution of the pericanalicular matrix to mineral content in human osteonal bone.

The osteocyte lacunar-canalicular network (LCN) penetrates bone and houses the osteocytes and their processes. Despite its rather low volume fraction, the LCN represents an outstanding large surface that is possibly used by the osteocytes to interact with the surrounding mineralized bone matrix thereby contributing to mineral homeostasis. The aim of this study was to quantitatively describe such contributions by spatially correlating the local density of the LCN with the mineral content at the same location in micrometer-sized volume elements in human osteons. For this purpose, 65 osteons from the femur midshaft from healthy adults (n = 4) and children (n = 2) were structurally characterized with two different techniques. The 3D structure of the LCN in the osteons was imaged with confocal laser scanning microscopy after staining the bone samples with rhodamine. Subsequent image analysis provided the canalicular length density, i.e. the total length of the canaliculi per unit volume (µm/µm3). Quantitative information on the mineral content (wt%Ca) from the identical regions was obtained using quantitative backscattered electron imaging. As the LCN-porosity lowers the mineral content, a negative correlation between Ca content and network density was expected. Calculations predict a reduction of around -0.97 fmol Ca per µm of network. However, the experiment revealed for 62 out of 65 osteons a positive correlation resulting in an average additional Ca loading of +1.15 fmol per µm of canalicular network, i.e. an accumulation of mineral has occurred at dense network regions. We hypothesize that this accumulation happens in the close vicinity of canaliculi forming mineral reservoirs that can be utilized by osteocytes. Significant differences found between individuals indicate that the extent of mineral loading of the reservoir zone reflects an important parameter for mineral homeostasis.

Cortical bone properties in the Brtl/+ mouse model of Osteogenesis imperfecta as evidenced by acoustic transmission microscopy.

Higher skeletal fragility has been established for the Brtl/+ mouse model of osteogenesis imperfecta at the whole bone level, but previous investigations of mechanical properties at the bone material level were inconclusive. Bone material was analyzed separately at endosteal (ER) and periosteal regions (PR) on transverse femoral midshaft sections for 2-month old mice (wild-type n = 6; Brtl/+ n = 6). Quantitative backscattered electron imaging revealed that the mass density computed from mineral density maps was higher in PR than in ER for both wild-type (+2.1%, p < 0.05) and Brtl/+ mice (+1.8%, p < 0.05). Electron induced X-ray fluorescence analysis indicated significantly lower atomic Ca/P ratios and higher Na/Ca, Mg/Ca and K/Ca ratios in PR bone compared to ER independently of genotype. Second harmonic generation microscopy indicated that the occurrence of periodically alternating collagen orientation in ER of Brtl/+ mice was strongly reduced compared to wild-type mice. Scanning acoustic microscopy in time of flight mode revealed that the sound velocity and Young's modulus (estimated based on sound velocity and mass density maps) were significantly greater in PR (respectively +6% and +15%) compared to ER in wild-type mice but not in Brtl/+ mice. ER sound velocity and Young's modulus were significantly increased in Brtl/+ mice (+9.4% and +22%, respectively) compared to wild-type mice. These data demonstrate that the Col1a1 G349C mutation in Brtl/+ mice affects the mechanical behavior of bone material predominantly in the endosteal region by altering the collagen orientation.

A cluster-randomized trial to reduce major perinatal morbidity among women with one prior cesarean delivery in Québec (PRISMA trial): study protocol for a randomized controlled trial.

BACKGROUND: Rates of cesarean delivery are continuously increasing in industrialized countries, with repeated cesarean accounting for about a third of all cesareans. Women who have undergone a first cesarean are facing a difficult choice for their next pregnancy, i.e.: (1) to plan for a second cesarean delivery, associated with higher risk of maternal complications than vaginal delivery; or (b) to have a trial of labor (TOL) with the aim to achieve a vaginal birth after cesarean (VBAC) and to accept a significant, but rare, risk of uterine rupture and its related maternal and neonatal complications. The objective of this trial is to assess whether a multifaceted intervention would reduce the rate of major perinatal morbidity among women with one prior cesarean. METHODS/DESIGN: The study is a stratified, non-blinded, cluster-randomized, parallel-group trial of a multifaceted intervention. Hospitals in Quebec are the units of randomization and women are the units of analysis. As depicted in Figure 1, the study includes a 1-year pre-intervention period (baseline), a 5-month implementation period, and a 2-year intervention period. At the end of the baseline period, 20 hospitals will be allocated to the intervention group and 20 to the control group, using a randomization stratified by level of care. Medical records will be used to collect data before and during the intervention period. Primary outcome is the rate of a composite of major perinatal morbidities measured during the intervention period. Secondary outcomes include major and minor maternal morbidity; minor perinatal morbidity; and TOL and VBAC rate. The effect of the intervention will be assessed using the multivariable generalized-estimating-equations extension of logistic regression. The evaluation will include subgroup analyses for preterm and term birth, and a cost-effectiveness analysis. DISCUSSION: The intervention is designed to facilitate: (1) women's decision-making process, using a decision analysis tool (DAT), (2) an estimate of uterine rupture risk during TOL using ultrasound evaluation of low-uterine segment thickness, (3) an estimate of chance of TOL success, using a validated prediction tool, and (4) the implementation of best practices for intrapartum management. TRIAL REGISTRATION: Current Controlled Trials, ID: ISRCTN15346559 . Registered on 20 August 2015.

Baseline mineralizing surface determines the magnitude of the bisphosphonate effect on cortical bone mineralization in postmenopausal osteoporotic patients.

PURPOSE: To determine the effect of short- or long-term bisphosphonate treatment on cortical bone mineralization density distribution (BMDD). METHODS: BMDD was assessed by quantitative backscatter electron imaging in postmenopausal osteoporosis: in paired transiliac biopsy samples (n=36) at baseline and after 3 years risedronate treatment from a clinical study, in transiliac biopsy samples from patients who were treated with either risedronate (n=31) or alendronate (n=68) for 3 to 7 years from an observational study. Outcomes were related to premenopausal reference data (n=73) and to histomorphometric mineralizing surface per bone surface (MS/BS). RESULTS: In the clinical study, patients with lower (below cohort median) MS/BS had normal cortical CaMean at baseline. After 3 years risedronate, their CaMean was not different versus baseline but increased versus reference (+2.9%, p=0.003). Among the groups of the observational study, CaMean did not exceed reference level, was similar for alendronate versus risedronate and similar between 3 to 5 years versus longer than 5 years treatment duration. CONCLUSION: Baseline bone mineralizing surface appears to be important for the effect of bisphosphonate on cortical bone mineralization. In patients with lower baseline MS/BS, level of mineralization after treatment can exceed reference level. Whether this is beneficial in the long-term is unknown.

Bone matrix mineralization is preserved during early perimenopausal stage in healthy women: a paired biopsy study.

UNLABELLED: Bone matrix mineralization based on quantitative backscatter electron imaging remained unchanged during the first year of menopause in paired transiliac biopsy samples from healthy women. This suggests that the reported early perimenopausal reductions in bone mineral density are caused by factors other than decreases in the degree of mineralization. INTRODUCTION: It is unknown whether perimenopausal loss of bone mass is associated with a drop in bone matrix mineralization. METHODS: For this purpose, we measured the bone mineralization density distribution (BMDD) by quantitative backscatter electron imaging (qBEI) in n = 17 paired transiliac bone biopsy samples at premenopausal baseline and 12 months after last menses (obtained at average ages of 49 ± 2 and 55 ± 2 years, respectively) in healthy women. For interpretation of BMDD outcomes, previously measured bone mineral density (BMD) and biochemical and histomorphometric markers of bone turnover were revisited for the present biopsy cohort. RESULTS: Menopause significantly decreased BMD at the lumbar spine (-4.5 %) and femoral neck (-3.8 %), increased the fasting urinary hydroxyproline/creatinine ratio (+60 %, all p < 0.01) and histomorphometric bone formation rate (+25 %, p < 0.05), but affected neither cancellous nor cortical BMDD variables (paired comparison p > 0.05). Mean calcium concentrations of cancellous (Cn.CaMean) and cortical bone (Ct.CaMean) were within normal range (p > 0.05 compared to established reference data). Ct.CaMean was significantly correlated with Cn.CaMean before (R = 0.81, p < 0.001) and after menopause (R = 0.80, p < 0.001) and to cortical porosity of mineralized tissue (Ct.Po.) after menopause (R = -0.57, p = 0.02). CONCLUSIONS: Surprisingly, the BMDD was found not affected by the changes in bone turnover rates in this cohort. This suggests that the substantial increase in bone formation rates took place shortly before the second biopsy, and the bone mineralization changes lag behind. We conclude that during the first year after the last menses, the degree of bone matrix mineralization is preserved and does not contribute to the observed reductions in BMD.

Bone matrix quality and plasma homocysteine levels.

It has recently been reported in the clinical literature that blood homocysteine levels correlate well with fracture risk, although a couple of reports exist to the opposite. Bone strength depends on both bone quantity and quality. The purpose of the present study was to investigate possible correlations between plasma homocysteine levels and bone material properties (Bone Mineral Density Distribution; BMDD, and collagen cross-link ratio). In the present study, femoral heads from subjects (N=19, females, age range 70-95 years old) with known homocysteine plasma levels were investigated. The bone material was collected during hemiarthroplasty surgery. We have determined collagen cross-link ratio and bone mineralization density distribution (BMDD) in bone tissue from patients with acute femoral neck fractures, by Fourier Transform Infrared Imaging (FTIRI) and quantitative Backscattered Electron Imaging (qBEI), respectively. The collagen cross-link ratio that was spectroscopically determined was pyridinoline/divalent cross-links (pyr/divalent). The BMDD variables quantified were: CaMean: the weighted mean calcium concentration; CaPeak: the most frequent Ca concentration; CaWidth: the width of the distribution, a measure of the mineralization homogeneity; CaLow: the percentage of bone area that is mineralized below the 5th percentile in the reference range; CaHigh: the percentage of bone area that is mineralized above the 95th percentile in the reference range. There was a significant correlation between plasma homocysteine levels and collagen cross-link ratio in areas of primary mineralized bone (p<0.0001), unlike the case of trabecular bone surfaces undergoing resorption (p>0.05). On the other hand there was no correlation in any of the BMDD parameters and plasma homocysteine levels (p>0.05). The results are consistent with the known effect of homocysteine on collagen post-translational modifications. These changes were independent of bone mineral characteristics. The results of the present study offer a mechanism by which homocysteine affects bone quality, but caution should be exercised since all patients examined had sustained fracture.

Interactions between microenvironment and cancer cells in two animal models of bone metastasis.

The preferential proliferation of cancer cells in the bone microenvironment is poorly characterised. Expression pattern of bone marrow and other organ microenvironment in contact with osteolytic (Walker W256) and osteoblastic (MatLyLu MLL) metastases were investigated. Fisher and Copenhagen rats received, respectively, W256 and MLL cells injection. Bone and soft tissues were analysed by immunochemistry for DKK1, cathepsin K, RANKL, MCSF or IL6 expression. Tartrate-resistant acid phosphatase (TRAcP)-positive cells were detected by a histoenzymatic technique. In bone, expressions of MCSF and DKK1 were shown in stromal cells of the bone marrow, in contact with metastatic foci of both tumours. Many stromal cells were found RANKL positive in the vicinity of the tumours. Cells expressing cathepsin K and multinucleated TRAcP+ cells were found in direct contact with trabeculae but also in bone marrow spaces near metastatic cells. In extraosseous tumours, cells in contact with malignant cells did not expressed DKK1, MCSF, cathepsin K and IL6. Some RANKL+ cells were found in the periphery of subcutaneous tumours but may represent Langerhans cells. Abnormal presence of TRAcP+ cells was never observed in the vicinity of malignant cells. Interaction between stromal and cancer cells induces the expression on the formers of characteristics leading to osteoclastogenesis only in the bone microenvironment.

Disuse and orchidectomy have additional effects on bone loss in the aged male rat.

INTRODUCTION: A severely osteopenic rat model was obtained by combining orchidectomy (ORX) and disuse (due to local paralysis induced by botulinum toxin [BTX] in the quadriceps muscle). METHODS: Forty-two aged male rats (5-6 months old) were randomized into three groups: 18 were SHAM operated; 6 were ORX; and 18 were ORX and BTX injected in the right hindlimb. One, two, and three months after surgery, bone mass (BV/TV) and microarchitectural parameters (Tb.Th, Tb.N, Tb.Sp, Tb.Pf, and structure model index [SMI]) were measured by microcomputed tomography (microCT) on the primary and secondary spongiosa of the femur. Osteoid parameters (OS/BS, O.Th), the number of osteoclasts (Nb.Oc), and the mineral apposition rate (Ct.MAR, Cn.MAR) were measured by histology. The serum tartrate-resistant acid phosphatase (TRAcP) 5b activity was measured by immunoassay. RESULTS: ORX induced a decrease of BV/TV, Tb.N and an increase of Tb.Sp, Tb.Pf, and SMI on both primary and secondary spongiosa. ORX and BTX had cumulative effects on bone loss, since differences were maximized on the right femur. The decrease in BV/TV reached -65%. Osteoid parameters and mineral apposition rate increased during the time course of the study. A peak of serum TRAcP was found at 7 days post-ORX. TRAcP levels reached the highest values in the ORX-BTX groups and the effect lasted longer than in the group with ORX alone. The association of ORX-BTX induced a greater bone resorption, due to the removal of complete trabeculae, compared to ORX alone. CONCLUSION: This model induced a severe and rapid bone loss and can be used to explore pharmacological- and biomaterial-based countermeasures.

Relations between radiograph texture analysis and microcomputed tomography in two rat models of bone metastases.

AIMS: Osteolytic (Walker 256, W256) and osteoblastic (MatLyLu, MLL) metastases were induced to investigate their effect on bone architecture by microcomputed tomography (microCT) and texture analysis of radiographs. METHODS: Fischer and Copenhagen rats received an intracardiac injection with W256/MLL cells, respectively. Femur and tibia radiographs were analyzed by texture analysis with run lengths and fractal algorithms. Microarchitecture was analyzed on primary and secondary spongiosa by microCT. RESULTS: W256 and MLL induced a decrease of trabecular bone mass, a disconnection of trabeculae and an increased conversion of plates into pillars. On radiographs and 3-dimensional models of W256 rats, a disappearance of the primary spongiosa was observed. On radiographs and 3-dimensional models of MLL rats, osteolytic lesions were observed as disseminated dark areas. Run length and fractal analyses were altered in both metastases. CONCLUSION: W256 and MLL cells induced two different patterns of osteolysis. Texture analysis of radiographs is a useful technique to explore trabecular bone changes.

Evaluation of an injectable bone substitute (betaTCP/hydroxyapatite/hydroxy-propyl-methyl-cellulose) in severely osteopenic and aged rats.

The use of injectable biomaterials is of interest in osteoporotic patients to locally restore bone mass in sites at risk of fracture. An injectable bone substitute (IBS1 made of betaTCP/hydroxyapatite as a calcium phosphate substitute and hydroxy-propyl-methyl-cellulose as a polymer carrier) was used in a severely osteopenic rat model obtained by combining orchidectomy (ORX) and disuse (paralysis induced by botulinum toxin - BTX). Fifty-six aged male rats were randomized into three groups: 18 were SHAM operated; 38 were ORX and BTX injected in the right hindlimb; they constituted the OP (osteoporotic) group. One month after ORX-BTX surgery, 20 of these OP rats received a IBS1 injection in the right femur (OP-IBS1 rats). Animals were studied at the time of IBS1 injection 1 month post ORX-BTX (M1), 1 month (M2) and 2 months (M3) after IBS1 injection. Bone mass (BV/TV) and microarchitectural parameters were measured by microCT. BV/TV was decreased after ORX-BTX; ORX and BTX had cumulative effects on bone loss (differences maximized on the right femur). BV/TV (combining the volume of both bone and material in OP-IBS1 rats) was elevated at M1 but decreased at M2. Marked bone formation was found onto the biomaterial granules but bone had a woven texture. A marked increase in the number of nonosteoclastic TRAcP+ cells was found in the implanted area. IBS1 induced new bone formation shortly after implantation but both IBS1 and woven bone were resorbed without inducing lamellar bone. Biomaterial trials must be conducted with long-term implantation periods, in aged osteoporotic animals.

Serum thyroid hormone concentrations and thyrotropin responsiveness in dogs with generalized dermatologic disease.

Fifty-eight dogs with generalized dermatologic disease that had not been given glucocorticoids systemically or topically within 6 weeks of entering the study were evaluated for thyroid function by use of the thyrotropin-response test. Dogs were classified as euthyroid or hypothyroid on the basis of test results and response to thyroid hormone replacement therapy. Baseline serum thyroxine (T4), free T4 (fT4), and triiodothyronine (T3) concentrations were evaluated in the 58 dogs. Serum T4, fT4, and T3 concentrations were evaluated in 200 healthy dogs to establish normal values. Hormone concentrations were considered low if they were less than the mean -2 SD of the values for control dogs. Specificity of T4 and fT4 concentrations was 100% in predicting hypothyroidism; none of the euthyroid dogs with generalized skin disease had baseline serum T4 or fT4 concentration in the low range. Sensitivity was better for fT4 (89%) than for T4 (44%) concentration. Significant difference was not observed in serum T4 and fT4 concentrations between euthyroid dogs with generalized skin disease and healthy control dogs without skin disease. Serum T3 concentration was not accurate in predicting thyroid function; most of the euthyroid and hypothyroid dogs with skin disease had serum T3 concentration within the normal range.

Inbreeding avoidance behaviors.

Inbreeding is defined as mating between individuals related by common ancestry. Thus, the degree to which a particular mating is inbred depends on how far back in a pedigree one begins counting common ancestors. In general practice, the term inbreeding is used to describe mating between close relatives (first cousins or closer). Animal breeders have known for centuries that inbreeding causes a loss of constitutional vigor and fertility in domestic livestock. A growing literature now demonstrates that the offspring of matings between close relatives in species of undomesticated birds and mammals are less fit than outbred offspring. The deleterious consequences of inbreeding suggest the possibility that many species have evolved behaviors that lower the frequency of inbreeding.

High affinity Ca2+ -Mg2+ ATPase in the distal tubule of the mouse kidney.

The purpose of this study was to investigate whether Ca2+ -Mg2+ ATPase in the distal tubule (where calcium transport is active, against a gradient, and hormone dependent) presents some characteristics different from those observed in the proximal tubule, and whether these characteristics are likely to shed light on the respective roles of this enzyme at the two sites of the nephron. The Ca2+ - and Mg2+-dependent ATP hydrolysis was measured in microdissected segments of the distal nephron, the kinetic parameters were determined, and the influence of magnesium upon the sensitivity to calcium was examined. Results were compared with those obtained in the proximal tubule, and in purified membranes as reported by others. In the distal tubule, low concentrations of Mg2+ (less than 10(-7) M) did not influence ATP hydrolysis. At concentrations above 10(-7) M, Mg2+ increased ATP hydrolysis according to Michaelis kinetics (apparent Km = 11.3 +/- 2.4 microM, Vmax = 219 +/- 26 pmol.mm-1.20 min-1). The addition of 1 microM Ca2+ decreased the apparent Km for Mg2+ and the Vmax for Mg2+. Similar results were obtained in the proximal tubule. At low Mg2+ concentrations, Ca2+ also stimulated ATP hydrolysis according to Michaelis kinetics with an apparent Km value for Ca2+ of 0.18 +/- 0.06 and 0.10 +/- 0.03 microM Ca2+ (ns) and a Vmax of 101 +/- 12 and 89 +/- 9 pmol.mm-1.20 min-1 (ns) in the distal and proximal tubules, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of practolol on exercise tolerance and cardiac haemodynamics and metabolism in patients with coronary artery disease.

Sixteen male patients with typical angina pectoris secondary to coronary atherosclerosis performed two daily standardized exercise tests during two consecutive days. Three hours before each exercise they received placebo or 400 mg practolol administered orally in double-blind fashion in order to complete a cross-over design. Practolol significantly prolonged the exercise duration by 30.6% and delayed the appearance time of ischaemic electrocardiographic changes by 67.7%. Maximal heart rate, systolic pressure, and pressure-rate product were also reduced after medication. In order to investigate further the effects of this beta blocking agent, myocardial function and metabolism at rest and during supine exercise were assessed in 12 male patients with coronary artery disease before and after practolol 30 mg, iv. At rest, practolol produced a decrease in tension-time index (18%), cardiac index (17%), heart rate (10%), and stroke index (7%). A significant reduction was also observed in resting stroke work index (14%) and systolic and mean aortic pressure (6%). Left ventricular end-diastolic pressure remained unchanged. During supine exercise, only time-tension index (12%), heart rate (12%), and cardiac index (10%) were significantly reduced after the beta blocking agent. Practolol did not significantly change the arterial glucose, lactate, inorganic phosphate, potassium, calcium, magnesium, pH, PCO2, or PO2. The beta blocking agent did not modify the myocardial extraction of any of these substrates at rest or during exercise. In the dosage used in both studies, practolol significantly improved the exercise tolerance and reduced the ischaemic manifestations. The efficacy of practolol in angina pectoris may result mostly from its ability to decrease heart rate and systolic pressure during exercise.