The Transient Receptor Potential Ion Channel TRPV6 Is Expressed at Low Levels in Osteoblasts and Has Little Role in Osteoblast Calcium Uptake

Background: TRPV6 ion channels are key mediators of regulated transepithelial absorption of Ca2+ within the small intestine. Trpv6-/- mice were reported to have lower bone density than wild-type littermates and significant disturbances in calcium homeostasis that suggested a role for TRPV6 in osteoblasts during bone formation and mineralization. TRPV6 and molecules related to transepithelial Ca2+ transport have been reported to be expressed at high levels in human and mouse osteoblasts. Results: Transmembrane ion currents in whole cell patch clamped SaOS-2 osteoblasts did not show sensitivity to ruthenium red, an inhibitor of TRPV5/6 ion channels, and 45Ca uptake was not significantly affected by ruthenium red in either SaOS-2 (P = 0.77) or TE-85 (P = 0.69) osteoblastic cells. In contrast, ion currents and 45Ca uptake were both significantly affected in a human bronchial epithelial cell line known to express TRPV6. TRPV6 was expressed at lower levels in osteoblastic cells than has been reported in some literature. In SaOS-2 TRPV6 mRNA was below the assay detection limit; in TE-85 TRPV6 mRNA was detected at 6.90±1.9 × 10−5 relative to B2M. In contrast, TRPV6 was detected at 7.7±3.0 × 10−2 and 2.38±0.28 × 10−4 the level of B2M in human carcinoma-derived cell lines LNCaP and CaCO-2 respectively. In murine primary calvarial osteoblasts TRPV6 was detected at 3.80±0.24 × 10−5 relative to GAPDH, in contrast with 4.3±1.5 × 10−2 relative to GAPDH in murine duodenum. By immunohistochemistry, TRPV6 was expressed mainly in myleocytic cells of the murine bone marrow and was observed only at low levels in murine osteoblasts, osteocytes or growth plate cartilage. Conclusions: TRPV6 is expressed only at low levels in osteoblasts and plays little functional role in osteoblastic calcium uptake

Measurement theory and paleobiology

Measurement theory, a branch of applied mathematics, offers guiding principles for extracting meaning from empirical observations and is applicable to any science involving measurements. Measurement theory is highly relevant in paleobiology because statistical approaches assuming ratio-scaled variables are commonly used on data belonging to nominal and ordinal scale types. We provide an informal introduction to representational measurement theory and argue for its importance in robust scientific inquiry. Although measurement theory is widely applicable in paleobiology research, we use the study of disparity to illustrate measurement theoretical challenges in the quantitative study of the fossil record. Respecting the inherent properties of different measurements enables meaningful inferences about evolutionary and ecological processes from paleontological data

Mobility and other predictors of hospitalization for urinary tract infection: a retrospective cohort study

Abstract Background Many hospitalizations for residents of skilled nursing facilities are potentially avoidable. Factors that could prevent hospitalization for urinary tract infection (UTI) were investigated, with focus on patient mobility. Methods A retrospective cohort study was conducted using 2003–2004 data from the Centers for Medicare and Medicaid Services. The study included 408,192 residents of 4267 skilled nursing facilities in California, Florida, Michigan, New York, and Texas. The patients were followed over time, from admission to the skilled nursing facility to discharge or, for those who were not discharged, for 1 year. Cox proportional hazards regression was conducted with hospitalization for UTI as the outcome. Results The ability to walk was associated with a 69% lower rate of hospitalization for UTI. Maintaining or improving walking ability over time reduced the risk of hospitalization for UTI by 39% to 76% for patients with various conditions. For residents with severe mobility problems, such as being in a wheelchair or having a missing limb, maintaining or improving mobility (in bed or when transferring) reduced the risk of hospitalization for UTI by 38% to 80%. Other potentially modifiable predictors included a physician visit at the time of admission to the skilled nursing facility (Hazard Ratio (HR), 0.68), use of an indwelling urinary catheter (HR, 2.78), infection with Clostridium difficile or an antibiotic-resistant microorganism (HR, 1.20), and use of 10 or more medications (HR, 1.31). Patient characteristics associated with hospitalization for UTI were advancing age, being Hispanic or African-American, and having diabetes mellitus, renal failure, Parkinson's disease, dementia, or stroke. Conclusion Maintaining or improving mobility (walking, transferring between positions, or moving in bed) was associated with a lower risk of hospitalization for UTI. A physician visit at the time of admission to the skilled nursing facility also reduced the risk of hospitalization for UTI.http://deepblue.lib.umich.edu/bitstream/2027.42/112369/1/12877_2008_Article_125.pd

Simulation of gait asymmetry and energy transfer efficiency between unilateral and bilateral amputees

Efficient walking or running requires symmetrical gait. Gait symmetry is one of the key factors in efficient human dynamics, kinematics and kinetics. The desire of individuals with a lower-limb amputation to participate in sports has resulted in the development of energy-storing and-returning (ESR) feet. This paper analyses a case study to show the effect of symmetry and asymmetry as well as energy transfer efficiency during periodic jumping between simulated bilateral and unilateral runners. A custom gait analysis system is developed as part of this project to track the motion of the body of a physically active subject during a set of predefined motions. Stance and aerial times are accurately measured using a high speed camera. Gait frequency, the level of symmetry and the non-uniform displacement between left and right foot and their effects on the position of the Centre of Mass (CM) were used as criteria to calculate both peak energies and transformation efficiency. Gait asymmetry and discrepancy of energy transfer efficiency between the intact foot and the ESR are observed. It is concluded that unilateral runners require excessive effort to compensate for lack of symmetry as well as asymmetry in energy transfer, causing fatigue which could be a reason why bilateral amputee runners using ESR feet have a superior advantage over unilateral amputees

Evidence of Segregated Spawning in a Single Marine Fish Stock: Sympatric Divergence of Ecotypes in Icelandic Cod?

There is increasing recognition of intraspecific diversity and population structure within marine fish species, yet there is little direct evidence of the isolating mechanisms that maintain it or documentation of its ecological extent. We analyzed depth and temperature histories collected by electronic data storage tags retrieved from 104 Atlantic cod at liberty ≥1 year to evaluate a possible isolating mechanisms maintaining population structure within the Icelandic cod stock. This stock consists of two distinct behavioral types, resident coastal cod and migratory frontal cod, each occurring within two geographically distinct populations. Despite being captured together on the same spawning grounds, we show the behavioral types seem reproductively isolated by fine-scale differences in spawning habitat selection, primarily depth. Additionally, the different groups occupied distinct seasonal thermal and bathymetric niches that generally demonstrated low levels of overlap throughout the year. Our results indicate that isolating mechanisms, such as differential habitat selection during spawning, might contribute to maintaining diversity and fine-scale population structure in broadcast-spawning marine fishes

Temporal and Geographic variation in the validity and internal consistency of the Nursing Home Resident Assessment Minimum Data Set 2.0

<p>Abstract</p> <p>Background</p> <p>The Minimum Data Set (MDS) for nursing home resident assessment has been required in all U.S. nursing homes since 1990 and has been universally computerized since 1998. Initially intended to structure clinical care planning, uses of the MDS expanded to include policy applications such as case-mix reimbursement, quality monitoring and research. The purpose of this paper is to summarize a series of analyses examining the internal consistency and predictive validity of the MDS data as used in the "real world" in all U.S. nursing homes between 1999 and 2007.</p> <p>Methods</p> <p>We used person level linked MDS and Medicare denominator and all institutional claim files including inpatient (hospital and skilled nursing facilities) for all Medicare fee-for-service beneficiaries entering U.S. nursing homes during the period 1999 to 2007. We calculated the sensitivity and positive predictive value (PPV) of diagnoses taken from Medicare hospital claims and from the MDS among all new admissions from hospitals to nursing homes and the internal consistency (alpha reliability) of pairs of items within the MDS that logically should be related. We also tested the internal consistency of commonly used MDS based multi-item scales and examined the predictive validity of an MDS based severity measure viz. one year survival. Finally, we examined the correspondence of the MDS discharge record to hospitalizations and deaths seen in Medicare claims, and the completeness of MDS assessments upon skilled nursing facility (SNF) admission.</p> <p>Results</p> <p>Each year there were some 800,000 new admissions directly from hospital to US nursing homes and some 900,000 uninterrupted SNF stays. Comparing Medicare enrollment records and claims with MDS records revealed reasonably good correspondence that improved over time (by 2006 only 3% of deaths had no MDS discharge record, only 5% of SNF stays had no MDS, but over 20% of MDS discharges indicating hospitalization had no associated Medicare claim). The PPV and sensitivity levels of Medicare hospital diagnoses and MDS based diagnoses were between .6 and .7 for major diagnoses like CHF, hypertension, diabetes. Internal consistency, as measured by PPV, of the MDS ADL items with other MDS items measuring impairments and symptoms exceeded .9. The Activities of Daily Living (ADL) long form summary scale achieved an alpha inter-consistency level exceeding .85 and multi-item scale alpha levels of .65 were achieved for well being and mood, and .55 for behavior, levels that were sustained even after stratification by ADL and cognition. The Changes in Health, End-stage disease and Symptoms and Signs (CHESS) index, a summary measure of frailty was highly predictive of one year survival.</p> <p>Conclusion</p> <p>The MDS demonstrates a reasonable level of consistency both in terms of how well MDS diagnoses correspond to hospital discharge diagnoses and in terms of the internal consistency of functioning and behavioral items. The level of alpha reliability and validity demonstrated by the scales suggest that the data can be useful for research and policy analysis. However, while improving, the MDS discharge tracking record should still not be used to indicate Medicare hospitalizations or mortality. It will be important to monitor the performance of the MDS 3.0 with respect to consistency, reliability and validity now that it has replaced version 2.0, using these results as a baseline that should be exceeded.</p