Background Multimorbidity–having two or more coexisting chronic conditions–is highly prevalent, costly, and disabling to older adults. Questions remain regarding chronic diseases accumulation over time and whether this differs by racial and ethnic background. Answering this knowledge gap, this study identifies differences in rates of chronic disease accumulation and multimorbidity development among non-Hispanic white, non-Hispanic black, and Hispanic study participants starting in middle-age and followed up to 16 years. Methods and findings We analyzed data from the Health and Retirement Study (HRS), a biennial, ongoing, publicly-available, longitudinal nationally-representative study of middle-aged and older adults in the United States. We assessed the change in chronic disease burden among 8,872 non-Hispanic black, non-Hispanic white, and Hispanic participants who were 51–55 years of age at their first interview any time during the study period (1998–2014) and all subsequent follow-up observations until 2014. Multimorbidity was defined as having two or more of seven somatic chronic diseases: arthritis, cancer, heart disease (myocardial infarction, coronary heart disease, angina, congestive heart failure, or other heart problems), diabetes, hypertension, lung disease, and stroke. We used negative binomial generalized estimating equation models to assess the trajectories of multimorbidity burden over time for non-Hispanic black, non-Hispanic white, and Hispanic participants. In covariate-adjusted models non-Hispanic black respondents had initial chronic disease counts that were 28% higher than non-Hispanic white respondents (IRR 1.279, 95% CI 1.201, 1.361), while Hispanic respondents had initial chronic disease counts that were 15% lower than non-Hispanic white respondents (IRR 0.852, 95% CI 0.775, 0.938). Non-Hispanic black respondents had rates of chronic disease accumulation that were 1.1% slower than non-Hispanic whites (IRR 0.989, 95% CI 0.981, 0.998) and Hispanic respondents had rates of chronic disease accumulation that were 1.5% faster than non-Hispanic white respondents (IRR 1.015, 95% CI 1.002, 1.028). Using marginal effects commands, this translates to predicted values of chronic disease for white respondents who begin the study period with 0.98 chronic diseases and end with 2.8 chronic diseases; black respondents who begin the study period with 1.3 chronic diseases and end with 3.3 chronic diseases; and Hispanic respondents who begin the study period with 0.84 chronic diseases and end with 2.7 chronic diseases. Conclusions Middle-aged non-Hispanic black adults start at a higher level of chronic disease burden and develop multimorbidity at an earlier age, on average, than their non-Hispanic white counterparts. Hispanics, on the other hand, accumulate chronic disease at a faster rate relative to non-Hispanic white adults. Our findings have important implications for improving primary and secondary chronic disease prevention eff...

Clinicians stand to gain from a better understanding of which disease combinations are more and less disabling among older adults. Understanding how multimorbidity combinations relate to functional status is an important step towards reducing disability and sustaining independent living among older adults.

Balance assessment is an integral component of concussion evaluation and management. Although the modified balance error scoring system (mBESS) is the conventional clinical tool, objective metrics derived from wearable inertial sensors during the mBESS may increase sensitivity in detecting subtle balance deficits post-concussion. The aim of this study was to identify which stance condition and postural sway metrics obtained from an inertial sensor placed on the lumbar spine during the mBESS best discriminate athletes with acute concussion. Fifty-two college athletes in the acute phase of concussion and seventy-six controls participated in this study. Inertial sensor-based measures objectively detected group differences in the acutely concussed group of athletes while the clinical mBESS did not (p<0.001 and p = 0.06, respectively). Mediolateral postural sway during the simplest condition of the mBESS (double stance) best classified those with acute concussion. Inertial sensors provided a sensitive and objective measure of balance in acute concussion. These results may be developed into practical guidelines to improve and simplify postural sway analysis post-concussion.

Wu YJ, Muldoon LL, Varallyay C, Markwardt S, Jones RE, Neuwelt EA. In vivo leukocyte labeling with intravenous ferumoxides/protamine sulfate complex and in vitro characterization for cellular magnetic resonance imaging. Am J Physiol Cell Physiol 293: C1698-C1708, 2007. First published September 26, 2007; doi:10.1152/ajpcell.00215.2007.-Cellular labeling with ferumoxides (Feridex IV) superparamagnetic iron oxide nanoparticles can be used to monitor cells in vivo by MRI. The objective of this study was to use histology and MRI to evaluate an in vivo, as opposed to in vitro, technique for labeling of mononuclear leukocytes as a means of tracking inflammatory processes in the brain. Long-Evans rats were intravenously injected with 20 mg/kg ferumoxides, ferumoxtran-10, or ferumoxytol with or without protamine sulfate. Leukocytes and splenocytes were evaluated by cell sorting and iron histochemistry or were implanted into the brain for MRI. Injection of ferumoxides/ protamine sulfate complex IV resulted in iron labeling of leukocytes (ranging from 7.4 Ϯ 0.5% to 12.5 Ϯ 0.9% with average 9.2 Ϯ 0.8%) compared with ferumoxides (ranging from 3.9 Ϯ 0.4% to 6.3 Ϯ 0.5% with average 5.0 Ϯ 0.5%) or protamine sulfate alone (ranging from 0% to 0.9 Ϯ 0.7% with average 0.3 Ϯ 0.3%). Cell sorting analysis indicated that iron-labeled cells were enriched for cell types positive for the myelomonocytic marker (CD11b/c) and the B lymphocyte marker (CD45RA) and depleted in the T cell marker (CD3). Neither ferumoxtran-10 nor ferumoxytol with protamine sulfate labeled leukocytes. In vivo ferumoxides/protamine sulfate-loaded leukocytes and splenocytes were detected by MRI after intracerebral injection. Ferumoxides/protamine complex labeled CD45RA-positive and CD11b/c-positive leukocytes in vivo without immediate toxicity. The dose of feumoxides in this report is much higher than the approved human dose, so additional animal studies are required before this approach could be translated to the clinic. These results might provide useful information for monitoring leukocyte trafficking into the brain. leukocyte trafficking; brain; B lymphocyte; rat SUPERPARAMAGNETIC IRON OXIDE (SPIO) and ultra-small SPIO (USPIO) nanoparticle agents, consisting of an iron oxide core with a variable carbohydrate coating, are gaining use for MRI.

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Depression and/or cognitive impairment was identified in one-third of older adults with multimorbidity, and these combinations were associated with substantially greater prospective disability than combinations comprised exclusively of somatic conditions. This argues for identifying and managing mental health conditions that co-occur with somatic conditions.

Purpose The osteocyte exerts important effects on bone remodeling but its rhythmicity and effect on the rhythms of other bone cells are not fully characterized. The purpose of this study was to determine if serum sclerostin displays rhythmicity over a 24-hour (h) interval, similar to that of other bone biomarkers. Methods Serum sclerostin, FGF-23, CTX, and P1NP were measured every 2 hours over a 24-h interval on 10 healthy men aged 20-65 years. Maximum likelihood estimates of the parameters in a repeated measures model were used to determine if these biomarkers displayed a diurnal, sinusoidal rhythm. Results No discernible 24-h rhythm was identified for sclerostin (p = 0.99) or P1NP (p = 0.65). CTX rhythmicity was confirmed (p < 0.001), peaking at 05:30 (range 01:30–07:30). FGF-23 levels were also rhythmic (p < 0.001) but time of peak was variable (range 02:30-11:30). The only significant association identified between these four bone biomarkers was for CTX and P1NP mean 24-h metabolite levels (r = 0.65, p = 0.04). Conclusions Sclerostin levels do not appear to be rhythmic in men. This suggests that in contrast to CTX, serum sclerostin could be measured at any time of day. The 24-h profiles of FGF-23 suggest that a component of osteocyte function is rhythmic but its timing is variable. Our results do not support the hypothesis that osteocytes direct the rhythmicity of other bone turnover markers (CTX), at least not via a sclerostin mediated mechanism.

BACKGROUND: Older adults with diabetes rarely have only one chronic disease. As a result, there is a need to re-conceptualize research and clinical practice to address the growing number of older Americans with diabetes and concurrent chronic diseases (diabetes-multimorbidity). OBJECTIVE: To identify prevalent multimorbidity combinations and examine their association with poor functional status among a nationally representative sample of middle-aged and older adults with diabetes. DESIGN: A prospective cohort study of the 2012-2014 Health and Retirement Study (HRS) data. We identified the most prevalent diabetes-multimorbidity combinations and estimated negative binomial models of diabetes-multimorbidity on prospective disability. PARTICIPANTS: Analytic sample included 3841 HRS participants with diabetes, aged 51 years and older. MAIN MEASURES: The main outcome measure was the combined activities of daily living (ADL)-instrumental activities of daily living (IADL) index (range 0-11; higher index denotes higher disability). The main independent variables were diabetes-multimorbidity combination groups, defined as the co-occurrence of diabetes and at least one of six somatic chronic diseases (hypertension, cardiovascular disease, lung disease, cancer, arthritis, and stroke) and/or two mental chronic conditions (cognitive impairment and high depressive symptoms (CESD score ≥ 4). KEY RESULTS: The three most prevalent multimorbidity combinations were, in rank-order diabetes-arthritishypertension (n = 694, 18.1%); diabetes-hypertension (n = 481, 12.5%); and diabetes-arthritis-hypertensionheart disease (n = 383, 10%). Diabetes-multimorbidity combinations that included high depressive symptoms or stroke had significantly higher counts of ADL-IADL limitations compared with diabetes-only. In head-tohead comparisons of diabetes-multimorbidity combinations, high depressive symptoms or stroke added to somatic multimorbidity combinations was associated with a higher count of ADL-IADL limitations (diabetes-arthritishypertension-high depressive symptoms vs. diabetes-arthritis-hypertension: IRR = 1.95 [1.13, 3.38]; diabetesarthritis-hypertension-stroke vs. diabetes-arthritis-hypertension: IRR = 2.09 [1.15, 3.82]) even after adjusting for age, gender, education, race/ethnicity, BMI, baseline ADL-IADL, and diabetes duration. Coefficients were robust to further adjustment for diabetes treatment. CONCLUSIONS: Depressive symptoms or stroke added onto other multimorbidity combinations may pose a substantial functional burden for middle-aged and older adults with diabetes.