Toward Mechanical Systems Biology in Bone

Cyclic mechanical loading is perhaps the most important physiological factor regulating bone mass and shape in a way which balances optimal strength with minimal weight. This bone adaptation process spans multiple length and time scales. Forces resulting from physiological exercise at the organ scale are sensed at the cellular scale by osteocytes, which reside inside the bone matrix. Via biochemical pathways, osteocytes orchestrate the local remodeling action of osteoblasts (bone formation) and osteoclasts (bone resorption). Together these local adaptive remodeling activities sum up to strengthen bone globally at the organ scale. To resolve the underlying mechanisms it is required to identify and quantify both cause and effect across the different scales. Progress has been made at the different scales experimentally. Computational models of bone adaptation have been developed to piece together various experimental observations at the different scales into coherent and plausible mechanisms. However additional quantitative experimental validation is still required to build upon the insights which have already been achieved. In this review we discuss emerging as well as state of the art experimental and computational techniques and how they might be used in a mechanical systems biology approach to further our understanding of the mechanisms governing load induced bone adaptation, i.e., ways are outlined in which experimental and computational approaches could be coupled, in a quantitative manner to create more reliable multiscale models of bon

John Archibald Campbell

From the Transactions, 1904, vol. V.https://scholarsjunction.msstate.edu/fvw-pamphlets/1659/thumbnail.jp

Mechanical loading of mouse caudal vertebrae increases trabecular and cortical bone mass-dependence on dose and genotype

Most in vivo studies addressing the skeletal responses of mice to mechanical loading have targeted cortical bone. To investigate trabecular bone responses also we have developed a caudal vertebral axial compression device (CVAD) that transmits mechanical loads to compress the fifth caudal vertebra via stainless steel pins inserted into the forth and sixth caudal vertebral bodies. Here, we used the CVAD in C57BL/6 (B6) and C3H/Hej (C3H) female mice (15weeks of age) to investigate whether the effect of regular bouts of mechanical stimulation on bone modeling and bone mass was dependent on dose and genotype. A combined micro-computed tomographic and dynamic histomorphometric analysis was carried out at the end of a 4-week loading regimen (3,000 cycles, 10 Hz, 3 xweek) for load amplitudes of 0N, 2N, 4N and 8N. Significant increases in trabecular bone mass of 9 and 21% for loads of 4N and 8N, respectively, were observed in B6 mice. A significant increase of 10% in trabecular bone mass occurred for a load of 8N in the C3H strain. For other loads, no significant increases were detected. Both mouse strains exhibited substantial increases in trabecular bone formation rates for all loads, B6: 111% (2N), 86% (4N), 164% (8N), C3H: 41% (2N), 38% (4N), 141% (8N). Significant decreases in osteoclast number of 146 and 93% for a load of 8N were detected in B6 and C3H mice, respectively. These findings demonstrate that the effect of loading on the structural and functional parameters of bone is dose and genotype dependent. The caudal vertebral loading model established here is proposed for further studies addressing the molecular processes involved in the skeletal responses to mechanical stimul

Q Fever Update, Maritime Canada

Since the 1990s, reports of Q fever in Nova Scotia, Canada, have declined. Passive surveillance for Q fever in Nova Scotia and its neighboring provinces in eastern Canada indicates that the clinical manifestation of Q fever in the Maritime provinces is pneumonia and that incidence of the disease may fluctuate

A Very Radio-Loud Narrow-Line Seyfert 1: PKS 2004-447

We have discovered a very radio-loud Narrow-Line Seyfert 1 candidate: PKS 2004-447. This Seyfert is consistent with the formal definition for NLS1s, although it does not have quite the same spectral features as some typical members of this subclass. Only ROSAT survey data is available at X-ray wavelengths, so it has not been possible to compare this source with other NLS1s at these wavelengths. A full comparison of this source with other members of the subclass will improve our physical understanding of NLS1s. In addition, using standard calculations, we estimate the central black hole to have a mass of $\sim 5 \times 10^6 M_{\odot}$. This does not agree with predictions in the literature, that radio-loud AGN host very massive black holes.Comment: 15 pages, 4 figures, accepted for publication in ApJ, minor typos change

Prolactin counteracts effects of short day lengths on pelage growth in the meadow vole, Microtus pennsylvanicus

To test whether growth of the winter coat in short day lengths is contingent on suppression of plama prolactin (Prl) levels, female meadow voles (Microtus pennsylvanicus) were kept in short day lengths for 12 weeks and were injected daily with saline or Prl; long-day animals were treated with either the dopamine agonist, bromocryptine (bromo), bromo plus Prl, or saline. Prl treatment prevented the growth of the winter coat normally observed after 12 weeks in short day lengths, but bromocryptine did not stimulate pelage growth in long-day voles. Pelage growth in short day lengths appears contingent upon decreased plasma prolactin levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60638/1/prolactin_counteracts_effects.pd

Social and structural determinants of injection drug use-associated bacterial and fungal infections: a qualitative systematic review and thematic synthesis

BACKGROUND AND AIMS: Injection drug use-associated bacterial and fungal infections are increasingly common, and social contexts shape individuals' injecting practices and treatment experiences. We sought to synthesize qualitative studies of social-structural factors influencing incidence and treatment of injecting-related infections. METHODS: We searched PubMed, EMBASE, Scopus, CINAHL, and PsycINFO from January 1, 2000, to February 18, 2021. Informed by Rhodes' "risk environment" framework, we performed thematic synthesis in three stages: (1) line-by-line coding; (2) organizing codes into descriptive themes, reflecting interpretations of study authors; (3) consolidating descriptive themes into conceptual categories to identify higher-order analytic themes. RESULTS: We screened 4,841 abstracts and included 26 qualitative studies on experiences of injecting-related bacterial and fungal infections. We identified six descriptive themes organized into two analytic themes. The first analytic theme, social production of risk, considered macro-environmental influences. Four descriptive themes highlighted pathways through which this occurs: (1) unregulated drug supply, leading to poor drug quality and solubility; (2) unsafe spaces, influenced by policing practices and insecure housing; (3) health care policies and practices, leading to negative experiences that discourage access to care; and (4) restrictions on harm reduction programs, including structural barriers to effective service provision. The second analytic theme, practices of care among people who use drugs, addressed protective strategies people employ within infection risk environments. Associated descriptive themes were: (5) mutual care, including assisted-injecting and sharing sterile equipment; and (6) self-care, including vein health and self-treatment. Within constraining risk environments, some protective strategies for bacterial infections precipitated other health risks (e.g., HIV transmission). CONCLUSIONS: Injecting-related bacterial and fungal infections are shaped by modifiable social-structural factors, including poor quality unregulated drugs, criminalization and policing enforcement, insufficient housing, limited harm reduction services, and harmful health care practices. People who inject drugs navigate these barriers while attempting to protect themselves and their community

What We Know about the Public’s Level of Concern for Farm Animal Welfare in Food Production in Developed Countries

Population growth and rising consumption of meat, dairy, eggs and fish are forcing the world to face the intersecting challenges of how to sustainably feed a population expected to exceed 9 billion by 2050, while also controlling the impact of food production on the planet, on people and on animals. This review acknowledges the absence of a globally accepted definition of animal welfare and then explores the literature regarding different levels of concern for animal welfare in food production by such stakeholders as veterinarians, farmers, and the general public. It focuses on the evidence that the general public’s level of concern for animal welfare is linked to various demographic and personal characteristics, such as age, gender, religion, location, meat eating, and knowledge of animal welfare. Certain animals have characteristics that influence concern for their welfare, with those species that are considered more intelligent being afforded more concern. There is compelling evidence that the general public’s understanding of animal welfare in food production is poor. Acknowledging that public concern can be a driving force to change current production methods, the authors suggest widespread consciousness raising to redefine socially acceptable methods of food production from animals and to ensure that it remains in step with societal concerns

Bias magnification in ecologic studies: a methodological investigation

<p>Abstract</p> <p>Background</p> <p>As ecologic studies are often inexpensive to conduct, consideration of the magnitude and direction of ecologic biases may be useful in both study design and sensitivity analysis of results. This paper examines three types of ecologic bias: confounding by group, effect measure modification by group, and non-differential exposure misclassification.</p> <p>Methods</p> <p>Bias of the risk difference on the individual and ecologic levels are compared using two-by-two tables, simple equations, and risk diagrams. Risk diagrams provide a convenient way to simultaneously display information from both levels.</p> <p>Results</p> <p>Confounding by group and effect measure modification by group act in the same direction on the individual and group levels, but have larger impact on the latter. The reduction in exposure variance caused by aggregation magnifies the individual level bias due to ignoring groups. For some studies, the magnification factor can be calculated from the ecologic data alone. Small magnification factors indicate little bias beyond that occurring at the individual level. Aggregation is also responsible for the different impacts of non-differential exposure misclassification on individual and ecologic studies.</p> <p>Conclusion</p> <p>The analytical tools developed here are useful in analyzing ecologic bias. The concept of bias magnification may be helpful in designing ecologic studies and performing sensitivity analysis of their results.</p