Complete mitochondrial DNA sequences provide new insights into the Polynesian motif and the peopling of Madagascar

More than a decade of mitochondrial DNA (mtDNA) studies have given the 'Polynesian motif' renowned status as a marker for tracing the late-Holocene expansion of Austronesian speaking populations. Despite considerable research on the Polynesian motif in Oceania, there has been little equivalent work on the western edge of its expansion - leaving major issues unresolved regarding the motif's evolutionary history. This has also led to considerable uncertainty regarding the settlement of Madagascar. In this study, we assess mtDNA variation in 266 individuals from three Malagasy ethnic groups: the Mikea, Vezo, and Merina. Complete mtDNA genome sequencing reveals a new variant of the Polynesian motif in Madagascar; two coding region mutations define a Malagasy-specific sub-branch. This newly defined 'Malagasy motif' occurs at high frequency in all three ethnic groups (13-50%), and its phylogenetic position, geographic distribution, and estimated age all support a recent origin, but without conclusively identifying a specific source region. Nevertheless, the haplotype's limited diversity, similar to those of other mtDNA haplogroups found in our Malagasy groups, best supports a small number of initial settlers arriving to Madagascar through the same migratory process. Finally, the discovery of this lineage provides a set of new polymorphic positions to help localize the Austronesian ancestors of the Malagasy, as well as uncover the origin and evolution of the Polynesian motif itself

Combined vertebral fracture assessment and bone mineral density measurement: a new standard in the diagnosis of osteoporosis in academic populations

Vertebral Fracture Analysis enables the detection of vertebral fractures in the same session as bone mineral density testing. Using this method in 2,424 patients, we found unknown vertebral fractures in approximately one out of each six patients with significant impact on management. The presence of osteoporotic vertebral fractures (VF) is an important risk factor for all future fractures independent of BMD. Yet, determination of the VF status has not become standard practice. Vertebral Fracture Assessment (VFA) is a new feature available on modern densitometers. In this study we aimed to determine the prevalence of VF using VFA in all patients referred for BMD testing in a university medical center and to evaluate its added clinical value. Prospective diagnostic evaluation study in 2,500 consecutive patients referred for BMD. Patients underwent VFA in supine position after BMD testing. Questionnaires were used to assess perceived added value of VFA. In 2,424 patients (1,573 women), results were evaluable. In 541 patients (22%), VFA detected a prevalent VF that was unknown in 69%. In women, the prevalence was 20% versus 27% found in men (p <0.0001). The prevalence of VF was 14% in patients with normal BMD (97/678), increased to 21% (229/1,100) in osteopenia and to 26% in those with osteoporosis (215/646) by WHO criteria. After excluding mild fractures VF prevalence was 13% (322/2,424). In 468 of 942 questionnaires (50% response rate), 27% of the referring physicians reported VFA results to impact on patient management. VFA is a patient friendly new tool with a high diagnostic yield, as it detected unknown VF in one out of each six patients, with significant impact on management. We believe these findings justify considering VFA in all new patients referred for osteoporosis assessment in similar populations

Effectiveness of bisphosphonates on nonvertebral and hip fractures in the first year of therapy: The risedronate and alendronate (REAL) cohort study

INTRODUCTION: Randomized clinical trials have shown that risedronate and alendronate reduce fractures among women with osteoporosis. The aim of this observational study was to observe, in clinical practice, the incidence of hip and nonvertebral fractures among women in the year following initiation of once-a-week dosing of either risedronate or alendronate. METHODS: Using records of health service utilization from July 2002 through September 2004, we created two cohorts: women (ages 65 and over) receiving risedronate (n = 12,215) or alendronate (n = 21,615). Cox proportional hazard modeling was used to compare the annual incidence of nonvertebral fractures and of hip fractures between cohorts, adjusting for potential differences in risk factors for fractures. RESULTS: There were 507 nonvertebral fractures and 109 hip fractures. Through one year of therapy, the incidence of nonvertebral fractures in the risedronate cohort (2.0%) was 18% lower (95% CI 2% – 32%) than in the alendronate cohort (2.3%). The incidence of hip fractures in the risedronate cohort (0.4%) was 43% lower (95% CI 13% – 63%) than in the alendronate cohort (0.6%). These results were consistent across a number of sensitivity analyses. CONCLUSION: Patients receiving risedronate have lower rates of hip and nonvertebral fractures during their first year of therapy than patients receiving alendronate

Using vital statistics to estimate the population-level impact of osteoporotic fractures on mortality based on death certificates, with an application to France (2000-2004)

Abstract Background We developed a methodology using vital statistics to estimate the impact of osteoporotic fractures on the mortality of an entire population, and applied it to France for the period 2000-2004. Methods Current definitions of osteoporotic fractures were reviewed and their components identified. We used the International Classification of Diseases with national vital statistics data for the French adult population and performed cross-classifications between various components: age, sex, I-code (site) and E-code (mechanism of fracture). This methodology allowed identification of appropriate thresholds and categorization for each pertinent component. Results 2,625,743 death certificates were analyzed, 2.2% of which carried a mention of fracture. Hip fractures represented 55% of all deaths from fracture. Both sexes showed a similar pattern of mortality rates for all fracture sites, the rate increased with age from the age of 70 years. The E-high-energy code (present in 12% of death certificates with fractures) was found to be useful to rule-out non-osteoporotic fractures, and to correct the overestimation of mortality rates. Using this methodology, the crude number of deaths associated with fractures was estimated to be 57,753 and the number associated with osteoporotic fractures 46,849 (1.85% and 1.78% of all deaths, respectively). Conclusion Osteoporotic fractures have a significant impact on overall population mortality.</p

MicroRNA profiling of rhesus macaque embryonic stem cells

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) play important roles in embryonic stem cell (ESC) self-renewal and pluripotency. Numerous studies have revealed human and mouse ESC miRNA profiles. As a model for human-related study, the rhesus macaque is ideal for delineating the regulatory mechanisms of miRNAs in ESCs. However, studies on rhesus macaque (r)ESCs are lacking due to limited rESC availability and a need for systematic analyses of fundamental rESC characteristics.</p> <p>Results</p> <p>We established three rESC lines and profiled microRNA using Solexa sequencing resulting in 304 known and 66 novel miRNAs. MiRNA profiles were highly conserved between rESC lines and predicted target genes were significantly enriched in differentiation pathways. Further analysis of the miRNA-target network indicated that gene expression regulated by miRNAs was negatively correlated to their evolutionary rate in rESCs. Moreover, a cross-species comparison revealed an overall conservation of miRNA expression patterns between human, mouse and rhesus macaque ESCs. However, we identified three miRNA clusters (miR-467, the miRNA cluster in the imprinted Dlk1-Dio3 region and C19MC) that showed clear interspecies differences.</p> <p>Conclusions</p> <p>rESCs share a unique miRNA set that may play critical roles in self-renewal and pluripotency. MiRNA expression patterns are generally conserved between species. However, species and/or lineage specific miRNA regulation changed during evolution.</p

Biotic and abiotic retention, recycling and remineralization of metals in the ocean

Trace metals shape both the biogeochemical functioning and biological structure of oceanic provinces. Trace metal biogeochemistry has primarily focused on modes of external supply of metals from aeolian, hydrothermal, sedimentary and other sources. However, metals also undergo internal transformations such as abiotic and biotic retention, recycling and remineralization. The role of these internal transformations in metal biogeochemical cycling is now coming into focus. First, the retention of metals by biota in the surface ocean for days, weeks or months depends on taxon-specific metal requirements of phytoplankton, and on their ultimate fate: that is, viral lysis, senescence, grazing and/or export to depth. Rapid recycling of metals in the surface ocean can extend seasonal productivity by maintaining higher levels of metal bioavailability compared to the influence of external metal input alone. As metal-containing organic particles are exported from the surface ocean, different metals exhibit distinct patterns of remineralization with depth. These patterns are mediated by a wide range of physicochemical and microbial processes such as the ability of particles to sorb metals, and are influenced by the mineral and organic characteristics of sinking particles. We conclude that internal metal transformations play an essential role in controlling metal bioavailability, phytoplankton distributions and the subsurface resupply of metals

Progressive vertebral deformities despite unchanged bone mineral density in patients with sarcoidosis: a 4-year follow-up study

To evaluate the incidence of new and/or progressive vertebral deformities and changes in bone mineral density, we re-examined 66 patients with sarcoidosis after a follow-up period of four years. In 17 subjects (26%) new and/or progressive vertebral deformities were found, though BMD did not change significantly. INTRODUCTION: Previous studies from our group have shown that morphometric vertebral deformities suggestive of fractures can be found in 20% of patients with sarcoidosis, despite a normal bone mineral density (BMD). The aim of this study was to determine the incidence of new and/or progressive vertebral deformities and the evolution of BMD during the course of this disease. METHODS: BMD of the hip (DXA) and vertebral fracture assessment (VFA) with lateral single energy densitometry was performed at baseline and after 45 months in 66 patients with sarcoidosis. Potential predictors of new/ progressive vertebral deformities were assessed using logistic regression analysis. RESULTS: The BMD of the total group was unchanged after follow-up. The prevalence of vertebral deformities increased from 20 to 32% (p < 0.05); in 17 subjects (26%) new or progressive vertebral deformities were diagnosed. A lower T-score of the femoral neck [(OR = 2.5 (CI: 1.0-5.9), p < 0.05)] and mother with a hip fracture [(OR = 14.1 (CI: 1.4-142.6), p < 0.05)] were independent predictors of new/progressive deformities. CONCLUSIONS: In subjects with sarcoidosis the number of vertebral deformities increases in the course of this disease, despite unchanged BMD. The combination of low normal BMD and family history of fragility fractures confers an increased risk of the incidence of these deformities

The course of the acute vertebral body fragility fracture: its effect on pain, disability and quality of life during 12 months

The vertebral body fracture is the most frequent bone fragility fracture. In spite of this there is considerable uncertainty about the frequency, extent and severity of the acute pain and even more about the duration of pain, the magnitude of disability and how much daily life is disturbed in the post-fracture period. The aim of the present study was to follow the course of pain, disability, ADL and QoL in patients during the year after an acute low energy vertebral body fracture. The study design was a longitudinal cohort study with prospective data collection. All the patients over 40 years admitted to the emergency unit because of back pain with a radiologically acute vertebral body fracture were eligible. A total of 107 patients were followed for a year. The pain, disability (von Korff pain and disability scores), ADL (Hannover ADL score), and QoL (EQ-5D) were measured after 3 weeks, 3, 6 and 12 months. Two-thirds of the patients were women, and were similar in average age, as the men around 75 years. A total of 65.4% of the fractures were due to a level fall or a minor trauma, whereas 34.6% had no recollection of trauma or a specific event as the cause of the fracture. A total of 76.6% of the fractured patients were immediately mobilized and allowed to return home while the remaining were hospitalized. The average pain intensity score after 3 weeks was 70.9 (SD 19.3), the disability score 68.9 (SD 23.6), the ADL score 37.7 (SD 22.1) and EQ-5D score of 0.37 (SD 0.37). The largest improvements, 10–15%, occurred between the initial visit and the 3 months follow-up and were quite similar for all the measures. From 3 months, all the outcome measures leveled out or tended to deteriorate resulting in a mean pain intensity score of 60.5, disability score of 53.9, ADL score of 47.6, and EQ-5D score 0.52 after 12 months. After a whole year the fractured patients’ condition was similar to the preoperative condition of patients with a herniated lumbar disc, central lumbar spinal stenosis or in patients 100% work disabled due to back or neck problems. Instead of the generally believed good prognosis for the greater majority of those fractured, the acute vertebral body fracture was the beginning of a long-lasting severe deterioration of their health

Resistance Exercise Reverses Aging in Human Skeletal Muscle

Human aging is associated with skeletal muscle atrophy and functional impairment (sarcopenia). Multiple lines of evidence suggest that mitochondrial dysfunction is a major contributor to sarcopenia. We evaluated whether healthy aging was associated with a transcriptional profile reflecting mitochondrial impairment and whether resistance exercise could reverse this signature to that approximating a younger physiological age. Skeletal muscle biopsies from healthy older (N = 25) and younger (N = 26) adult men and women were compared using gene expression profiling, and a subset of these were related to measurements of muscle strength. 14 of the older adults had muscle samples taken before and after a six-month resistance exercise-training program. Before exercise training, older adults were 59% weaker than younger, but after six months of training in older adults, strength improved significantly (P<0.001) such that they were only 38% lower than young adults. As a consequence of age, we found 596 genes differentially expressed using a false discovery rate cut-off of 5%. Prior to the exercise training, the transcriptome profile showed a dramatic enrichment of genes associated with mitochondrial function with age. However, following exercise training the transcriptional signature of aging was markedly reversed back to that of younger levels for most genes that were affected by both age and exercise. We conclude that healthy older adults show evidence of mitochondrial impairment and muscle weakness, but that this can be partially reversed at the phenotypic level, and substantially reversed at the transcriptome level, following six months of resistance exercise training

Vitamin D inadequacy in Belgian postmenopausal osteoporotic women

BACKGROUND: Inadequate serum vitamin D [25(OH)D] concentrations are associated with secondary hyperparathyroidism, increased bone turnover and bone loss, which increase fracture risk. The objective of this study is to assess the prevalence of inadequate serum 25(OH)D concentrations in postmenopausal Belgian women. Opinions with regard to the definition of vitamin D deficiency and adequate vitamin D status vary widely and there are no clear international agreements on what constitute adequate concentrations of vitamin D. METHODS: Assessment of 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone was performed in 1195 Belgian postmenopausal women aged over 50 years. Main analysis has been performed in the whole study population and according to the previous use of vitamin D and calcium supplements. Four cut-offs of 25(OH)D inadequacy were fixed : < 80 nmol/L, <75 nmol/L, < 50 nmol/L and < 30 nmol/L. RESULTS: Mean (SD) age of the patients was 76.9 (7.5) years, body mass index was 25.7 (4.5) kg/m(2). Concentrations of 25(OH)D were 52.5 (21.4) nmol/L. In the whole study population, the prevalence of 25(OH)D inadequacy was 91.3 %, 87.5 %, 43.1 % and 15.9% when considering cut-offs of 80, 75, 50 and 30 nmol/L, respectively. Women who used vitamin D supplements, alone or combined with calcium supplements, had higher concentrations of 25(OH)D than non-users. Significant inverse correlations were found between age/serum PTH and serum 25(OH)D (r = -0.23/r = -0.31) and also between age/serum PTH and femoral neck BMD (r = -0.29/r = -0.15). There is a significant positive relation between age and PTH (r = 0.16), serum 25(OH)D and femoral neck BMD (r = 0.07). (P < 0.05) Vitamin D concentrations varied with the season of sampling but did not reach statistical significance (P = 0.09). CONCLUSION: This study points out a high prevalence of vitamin D inadequacy in Belgian postmenopausal osteoporotic women, even among subjects receiving vitamin D supplements