296 research outputs found
Domains of Chronic Stress, Lifestyle Factors, and Allostatic Load in Middle-Aged Mexican-American Women
Abstract available at publisher's website
Microarchitecture and Nanomechanical Properties of Trabecular Bone After Strontium Administration in Osteoporotic Goats
Strontium (Sr) ralenate is a new agent used for the prevention and treatment of osteoporosis. As a bone-seeking element, 98% of Sr is deposited in the bone and teeth after oral ingestion. However, the effect of Sr treatment on bone microarchitecture and bone nanomechanical properties remains unclear. In this study, 18 osteoporotic goats were divided into four groups according to the treatment regimen: control, calcium alone (Ca), calcium and Sr at 24 mg/kg (Ca + 24Sr), and calcium and Sr at 40 mg/kg (Ca + 40Sr). The effects of Sr administration on bone microarchitecture and nanomechanical properties of trabecular bones were analyzed with micro-CT and nanoindentation test, respectively. Serum Sr levels increased six- and tenfold in the Ca + 24Sr and Ca + 40Sr groups, respectively. Similarly, Sr in the bone increased four- and sixfold in these two groups. Sr administration significantly increased trabecular bone volume fraction, trabecular thickness, and double-labeled new bone area. Sr administration, however, did not significantly change the nanomechanical properties of trabecular bone (elastic modulus and hardness). The data suggested that Sr administration increased trabecular bone volume and improved the microarchitecture while maintaining the intrinsic tissue properties in the osteoporotic goat model
Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses
The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined
Bone refilling in cortical bone multicellular units: Insights into tetracycline double labelling from a computational model
Bone remodelling is carried out by `bone multicellular units' (BMUs) in which
active osteoclasts and active osteoblasts are spatially and temporally coupled.
The refilling of new bone by osteoblasts towards the back of the BMU occurs at
a rate that depends both on the number of osteoblasts and on their secretory
activity. In cortical bone, a linear phenomenological relationship between
matrix apposition rate (MAR) and BMU cavity radius is found experimentally. How
this relationship emerges from the combination of complex, nonlinear
regulations of osteoblast number and secretory activity is unknown.
Here, we extend our previous mathematical model of cell development within a
single BMU to investigate how osteoblast number and osteoblast secretory
activity vary along the BMU's closing cone. MARs predicted by the model are
compared with data from tetracycline double labelling experiments. We find that
the linear phenomenological relationship observed in these experiments between
MAR and BMU cavity radius holds for most of the refilling phase simulated by
our model, but not near the start and end of refilling. This suggests that at a
particular bone site undergoing remodelling, bone formation starts and ends
rapidly. Our model also suggests that part of the observed cross-sectional
variability in tetracycline data may be due to different bone sites being
refilled by BMUs at different stages of their lifetime. The different stages of
a BMU's lifetime depend on whether the cell populations within the BMU are
still developing or have reached a quasi-steady state while travelling through
bone. We find that due to their longer lifespan, active osteoblasts reach a
quasi-steady distribution more slowly than active osteoclasts. We suggest that
this fact may locally enlarge the Haversian canal diameter (due to a local lack
of osteoblasts compared to osteoclasts) near the BMU's point of origin.Comment: 16 pages, 6 figures, 3 tables. V3: minor changes: added 2 paragraphs
(BMU cavity in Section 2 and Model Robustness in Section 4), references
[52,54
The Boston Puerto Rican Health Study, a longitudinal cohort study on health disparities in Puerto Rican adults: challenges and opportunities
BACKGROUND: The Boston Puerto Rican Health Study is an ongoing longitudinal cohort study designed to examine the role of psychosocial stress on presence and development of allostatic load and health outcomes in Puerto Ricans, and potential modification by nutritional status, genetic variation, and social support.
METHODS: Self-identified Puerto Ricans, aged 45-75 years and residing in the Boston, MA metro area, were recruited through door-to-door enumeration and community approaches. Participants completed a comprehensive set of questionnaires and tests. Blood, urine and salivary samples were extracted for biomarker and genetic analysis. Measurements are repeated at a two-year follow-up.
RESULTS: A total of 1500 eligible participants completed baseline measurements, with nearly 80% two-year follow-up retention. The majority of the cohort is female (70%), and many have less than 8th grade education (48%), and fall below the poverty level (59%). Baseline prevalence of health conditions is high for this age range: considerable physical (26%) and cognitive (7%) impairment, obesity (57%), type 2 diabetes (40%), hypertension (69%), arthritis (50%) and depressive symptomatology (60%).
CONCLUSIONS: The enrollment of minority groups presents unique challenges. This report highlights approaches to working with difficult to reach populations, and describes some of the health issues and needs of Puerto Rican older adults. These results may inform future studies and interventions aiming to improve the health of this and similar communities
Diffraction techniques and vibrational spectroscopy opportunities to characterise bones
From a histological point of view, bones that allow body mobility and protection of internal organs consist not only of different organic and inorganic tissues but include vascular and nervous elements as well. Moreover, due to its ability to host different ions and cations, its mineral part represents an important reservoir, playing a key role in the metabolic activity of the organism. From a structural point of view, bones can be considered as a composite material displaying a hierarchical structure at different scales. At the nanometre scale, an organic part, i.e. collagen fibrils and an inorganic part, i.e. calcium phosphate nanocrystals are intimately mixed to assure particular mechanical properties
Therapeutic approach to FSGS in children
Therapy of primary focal segmental glomerulosclerosis (FSGS) in children incorporates conservative management and immunosuppression regimens to control proteinuria and preserve kidney function. In long-term cohort studies in adults and children with primary FSGS, renal survival has been directly associated with degree of proteinuria control. This educational article reviews the current therapeutic approach toward children with primary FSGS
Management of osteoporosis in patients hospitalized for hip fractures
Hip fracture is associated with high morbidity, mortality, and economic burden worldwide. It is also a major risk factor for a subsequent fracture. A literature search on the management of osteoporosis in patients with hip fracture was performed on the Medline database. Only one clinical drug trial was conducted in patients with a recent hip fracture. Further studies that specifically address post-fracture management of hip fracture are needed. The efficacy of anti-osteoporosis medication in older individuals and those at high risk of fall is reviewed in this paper. Adequate nutrition is vital for bone health and to prevent falls, especially in malnourished patients. Protein, calcium, and vitamin D supplementation is associated with increased hip BMD and a reduction in falls. Fall prevention, exercise, and balance training incorporated in a comprehensive rehabilitation program are essential to improve functional disability and survival. Exclusion of secondary causes of osteoporosis and treatment of coexistent medical conditions are also vital. Such a multidisciplinary team approach to the management of hip fracture patients is associated with a better clinical outcome. Although hip fracture is the most serious of all fractures, osteoporosis management should be prioritized to prevent deterioration of health and occurrence of further fracture
Scientific assessment of the use of sugars as cigarette tobacco ingredients: A review of published and other publicly available studies
Sugars, such as sucrose or invert sugar, have been used as tobacco ingredients in American-blend cigarettes to replenish the sugars lost during curing of the Burley component of the blended tobacco in order to maintain a balanced flavor. Chemical-analytical studies of the mainstream smoke of research cigarettes with various sugar application levels revealed that most of the smoke constituents determined did not show any sugar-related changes in yields (per mg nicotine), while ten constituents were found to either increase (formaldehyde, acrolein, 2-butanone, isoprene, benzene, toluene, benzo[k]fluoranthene) or decrease (4-aminobiphenyl, N-nitrosodimethylamine, N-nitrosonornicotine) in a statistically significant manner with increasing sugar application levels. Such constituent yields were modeled into constituent uptake distributions using simulations of nicotine uptake distributions generated on the basis of published nicotine biomonitoring data, which were multiplied by the constituent/nicotine ratios determined in the current analysis. These simulations revealed extensive overlaps for the constituent uptake distributions with and without sugar application. Moreover, the differences in smoke composition did not lead to relevant changes in the activity in in vitro or in vivo assays. The potential impact of using sugars as tobacco ingredients was further assessed in an indirect manner by comparing published data from markets with predominantly American-blend or Virginia-type (no added sugars) cigarettes. No relevant difference was found between these markets for smoking prevalence, intensity, some markers of dependence, nicotine uptake, or mortality from smoking-related lung cancer and chronic obstructive pulmonary disease. In conclusion, thorough examination of the data available suggests that the use of sugars as ingredients in cigarette tobacco does not increase the inherent risk and harm of cigarette smoking
An Integration of Genome-Wide Association Study and Gene Expression Profiling to Prioritize the Discovery of Novel Susceptibility Loci for Osteoporosis-Related Traits
Osteoporosis is a complex disorder and commonly leads to fractures in elderly persons. Genome-wide association studies (GWAS) have become an unbiased approach to identify variations in the genome that potentially affect health. However, the genetic variants identified so far only explain a small proportion of the heritability for complex traits. Due to the modest genetic effect size and inadequate power, true association signals may not be revealed based on a stringent genome-wide significance threshold. Here, we take advantage of SNP and transcript arrays and integrate GWAS and expression signature profiling relevant to the skeletal system in cellular and animal models to prioritize the discovery of novel candidate genes for osteoporosis-related traits, including bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), as well as geometric indices of the hip (femoral neck-shaft angle, NSA; femoral neck length, NL; and narrow-neck width, NW). A two-stage meta-analysis of GWAS from 7,633 Caucasian women and 3,657 men, revealed three novel loci associated with osteoporosis-related traits, including chromosome 1p13.2 (RAP1A, p = 3.6×10−8), 2q11.2 (TBC1D8), and 18q11.2 (OSBPL1A), and confirmed a previously reported region near TNFRSF11B/OPG gene. We also prioritized 16 suggestive genome-wide significant candidate genes based on their potential involvement in skeletal metabolism. Among them, 3 candidate genes were associated with BMD in women. Notably, 2 out of these 3 genes (GPR177, p = 2.6×10−13; SOX6, p = 6.4×10−10) associated with BMD in women have been successfully replicated in a large-scale meta-analysis of BMD, but none of the non-prioritized candidates (associated with BMD) did. Our results support the concept of our prioritization strategy. In the absence of direct biological support for identified genes, we highlighted the efficiency of subsequent functional characterization using publicly available expression profiling relevant to the skeletal system in cellular or whole animal models to prioritize candidate genes for further functional validation
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