The physiological lysophospholipids (LPLs), exemplified by lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), are omnific mediators of normal cellular proliferation, survival, and functions. Although both LPA and S1P attain micromolar concentrations in many biological fluids, numerous aspects of their biosynthesis, transport, and metabolic degradation are unknown. Eight members of a new subfamily of G protein-coupled LPA/S1P receptors, originally termed Edg Rs, bind either LPA or S1P with high affinity and transduce a series of growth-related and/or cytoskeleton-based functional responses. The most critical areas of LPL biology and pathobiology are neural development and neurodegeneration, immunity, atherosclerosis and myocardial injury, and cancer. Data from analyses of T cells established two basic points: (1) the plasticity and adaptability of expression of LPA/S1P Rs by some cells as a function of activation, and (2) the role of opposing signals from two different receptors for the same ligand as a mechanism for fine control of effects of LPLs. In the heart, LPLs may promote coronary atherosclerosis, but are effectively cytoprotective for hypoxic cardiac myocytes and those exposed to oxygen free radicals. The findings of production of LPA by some types of tumor cells, overexpression of selected sets of LPA receptors by the same tumor cells, and augmentation of the effects of protein growth factors by LPA have suggested pathogenetic roles for the LPLs in cancer. The breadth of physiologic and pathologic activities of LPLs emphasizes the importance of developing bioavailable nonlipid agonists and antagonists of the LPA/S1P receptors for diverse therapeutic applications.

A novel polyfluoranthene (PFA) exhibiting strong visual fluorescence emission, a highly amplified quenching effect, and widely controllable electrical conductivity is synthesized by the direct cationic oxidative polymerization of fluoranthene in a dynamic interface between n-hexane and nitromethane containing fluoranthene and FeCl₃, respectively. A full characterization of the molecular structure signifies that the PFAs have a degree of polymerization from 22-50 depending on the polymerization conditions. A polymerization mechanism at the interface of the hexane/nitromethane biphasic system is proposed. The conductivity of the PFA is tunable from 6.4 × 10^-6 to 0.074 S cm^-1 by doping with HCl or iodine. The conductivity can be significantly enhanced to 150 S cm^-1 by heat treatment at 1100 °C in argon. A PFA-based chemosensor shows a highly selective sensitivity for Fe³⁺ detection which is unaffected by other common metal ions. The detection of Fe³⁺ likely involves the synergistic effect of well-distributed π-conjugated electrons throughout the PFA helical chains that function as both the fluorophore and the receptor units.

The 70 kDa heat shock protein (HSP70) is a stress-inducible protein that has been shown to protect the brain from various nervous system injuries. It allows cells to withstand potentially lethal insults through its chaperone functions. Its chaperone properties can assist in protein folding and prevent protein aggregation following several of these insults. Although its neuroprotective properties have been largely attributed to its chaperone functions, HSP70 may interact directly with proteins involved in cell death and inflammatory pathways following injury. Through the use of mutant animal models, gene transfer, or heat stress, a number of studies have now reported positive outcomes of HSP70 induction. However, these approaches are not practical for clinical translation. Thus, pharmaceutical compounds that can induce HSP70, mostly by inhibiting HSP90, have been investigated as potential therapies to mitigate neurological disease and lead to neuroprotection. This review summarizes the neuroprotective mechanisms of HSP70 and discusses potential ways in which this endogenous therapeutic molecule could be practically induced by pharmacological means to ultimately improve neurological outcomes in acute neurological disease.

Background

Maintaining physical function is an important prerequisite for preserving independence in later life. Greater degrees of kyphosis in the thoracic spine are prevalent in older persons and accompanied by reduced physical function in multiple cross-sectional studies. It is unknown whether kyphosis predicts worse physical function over time.

Methods

We retrospectively assessed whether greater magnitude of kyphosis is associated with decline in self-reported and objectively measured physical function over 15 years. Digitized Cobb angle kyphosis (T4-T12) was derived from supine lateral thoracic spine radiographs in a cohort of 1,196 women aged 65 and older (mean = 69.3 years [SD = 4.0]). Using regression models, we evaluated associations of baseline kyphosis with both self-reported functional status and objectively measured gait speed, grip strength, and timed chair stands cross-sectionally and as change assessed over 15 years.

Results

In cross-sectional multivariate analyses, with each 10-degree increment of kyphosis, grip strength was 0.24 kg lower (p = .02), but there were no significant associations between kyphosis and functional status, gait speed, or timed chair stand, likely reflecting the high functioning study participants. In multivariate longitudinal analysis, with each 10-degree increment in baseline kyphosis, there was 0.07 point additional decline in functional status (p = .09), 0.01 m/s more decline in gait speed (p = .07), and 0.32 s greater decline in time to complete five chair stands (p = .004), but no association with decline in grip strength.

Conclusions

Greater magnitude of kyphosis may predict worsening lower extremity function over time in older women. Early recognition and preventative measures against kyphosis progression may help preserve physical function over the long term.

Strongly fluorescence-emitting oligofluoranthene (OFA) nanorods are readily synthesized by a direct template-free chemical oxidative oligomerization of fluoranthene in nitromethane containing ferric chloride as an oxidant. The OFAs likely consist of five fluoranthene units containing cyclic pentamers with crystalline order and tunable electrical conductivity across 12 orders of magnitude. The OFA nanorods are heat-resistant materials and efficient precursors for macroporous carbon materials with high carbon yield in argon at 1100 °C. In particular, the optimal ring-like pentamer shows 12.2 times stronger cyan fluorescence-emission than recognized highly fluorescent fluoranthene under the same conditions, which makes the OFAs into ideal strong fluorescent emitters, tunable conductors, and high carbon-yield precursors for the preparation of sensors and carbon materials. These findings demonstrate an advance in the direct synthesis of oligomers from fused-ring aromatic hydrocarbons and provide a potential direction to optimize the synthesis and functionalities of wholly aromatic nanomaterials.

Age-related hyperkyphosis is thought to be a result of underlying vertebral fractures, but studies suggest that among the most hyperkyphotic women, only one in three have underlying radiographic vertebral fractures. Although commonly observed, there is no widely accepted definition of hyperkyphosis in older persons, and other than vertebral fracture, no major causes have been identified. To identify important correlates of kyphosis and risk factors for its progression over time, we conducted a 15-year retrospective cohort study of 1196 women, aged 65 years and older at baseline (1986 to 1988), from four communities across the United States: Baltimore County, MD; Minneapolis, MN; Portland, OR; and the Monongahela Valley, PA. Cobb angle kyphosis was measured from radiographs obtained at baseline and an average of 3.7 and 15 years later. Repeated measures, mixed effects analyses were performed. At baseline, the mean kyphosis angle was 44.7 degrees (SE = 0.4, SD = 11.9) and significant correlates included a family history of hyperkyphosis, prevalent vertebral fracture, low bone mineral density, greater body weight, degenerative disc disease, and smoking. Over an average of 15 years, the mean increase in kyphosis was 7.1 degrees (SE = 0.25). Independent determinants of greater kyphosis progression were prevalent and incident vertebral fractures, low bone mineral density and concurrent bone density loss, low body weight, and concurrent weight loss. Thus, age-related kyphosis progression may be best prevented by slowing bone density loss and avoiding weight loss.

Age-related hyperkyphosis is thought to be a result of underlying vertebral fractures, but studies suggest that among the most hyperkyphotic women, only one in three have underlying radiographic vertebral fractures. Although commonly observed, there is no widely accepted definition of hyperkyphosis in older persons, and other than vertebral fracture, no major causes have been identified. To identify important correlates of kyphosis and risk factors for its progression over time, we conducted a 15-year retrospective cohort study of 1196 women, aged 65 years and older at baseline (1986 to 1988), from four communities across the United States: Baltimore County, MD; Minneapolis, MN; Portland, OR; and the Monongahela Valley, PA. Cobb angle kyphosis was measured from radiographs obtained at baseline and an average of 3.7 and 15 years later. Repeated measures, mixed effects analyses were performed. At baseline, the mean kyphosis angle was 44.7 degrees (SE = 0.4, SD = 11.9) and significant correlates included a family history of hyperkyphosis, prevalent vertebral fracture, low bone mineral density, greater body weight, degenerative disc disease, and smoking. Over an average of 15 years, the mean increase in kyphosis was 7.1 degrees (SE = 0.25). Independent determinants of greater kyphosis progression were prevalent and incident vertebral fractures, low bone mineral density and concurrent bone density loss, low body weight, and concurrent weight loss. Thus, age-related kyphosis progression may be best prevented by slowing bone density loss and avoiding weight loss.

Introduction

Hyperkyphosis commonly affects older people but is not widely acknowledged as a clinically actionable problem, especially in men. There are several techniques to quantify kyphosis including the blocks and Cobb angle measurements. This study includes both kyphosis measures to investigate whether older men with accentuated kyphosis may be at increased mortality risk.

Methods

Men aged ≥65 years (N = 5994) were recruited to participate in the MrOS prospective cohort study from 2000 to 2002 (baseline). Our primary cohort included 2931 enrollees (mean age 79.3 years; SD 5.2) who underwent blocks-measured kyphosis from 2006 to 2009. Our secondary cohort included 2351 participants who underwent radiographic Cobb angle measurements at baseline. Cox proportional hazards analyses were used to determine association between kyphosis and all-cause mortality while adjusting for prevalent radiographic vertebral fractures, bone mineral density, incident fractures, gait speed, timed chair stands, self-reported health, alcohol use, medical co-morbidities, and physical activity.

Results

During a mean follow-up of 8.3 (SD 3.2) years, 1393 participants died in the primary cohort. In this group, compared to men with 0-1 block kyphosis, increasing blocks-measured kyphosis was associated with increased mortality (HR: 1.26-1.53, p trend <0.001). With addition of prevalent vertebral fracture to adjusted models, the association remained significant in participants with severe kyphosis (3+ blocks-measured). Similarly, with addition of chair stand performance the association remained significant for 4+ blocks kyphosis. Walking speed did not attenuate the association of kyphosis and mortality. In the secondary cohort, there were no significant associations between radiographic Cobb angle kyphosis and mortality.

Conclusions

Increasing blocks-measured kyphosis was associated with a greater risk of mortality in older men, indicating that hyperkyphosis identified on physical exam should be considered a clinically significant finding that may warrant further evaluation and treatment.

Objective

This study aims to examine cross-sectional and longitudinal relations between dietary intake of isoflavones and bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN) in black, white, Chinese, and Japanese women during the menopausal transition.

Methods

We tested whether tertiles of isoflavone intake were associated with baseline BMD when all women were premenopausal or early perimenopausal. To analyze whether isoflavone intake was associated with longitudinal BMD, we fitted piecewise linear models to repeated measurements of baseline-normalized LS or FN BMD as functions of time before or after the final menstrual period (FMP) date.

Results

Multiply adjusted mean FN BMD values of premenopausal Japanese women were monotonically positively related to isoflavone consumption (P for trend = 0.0003). Otherwise, no statistically significant baseline associations were observed. During the period of 1 year before the FMP through 5 years after the FMP, all participants lost LS and FN BMD. Loss was unrelated to isoflavone intake, except for Japanese women during the period of 1 year before the FMP to 2 years after the FMP: higher tertiles of isoflavone intake were associated with greater annual LS BMD loss rates (P for trend = 0.01) and FN loss rates (P for trend = 0.04).

Conclusions

In Japanese women, higher isoflavone intake is associated with higher peak FN BMD but also with greater rates of LS and FN BMD loss during the menopausal transition. Results for the other racial/ethnic groups did not support a relation between dietary intake of isoflavones and either peak BMD or BMD loss during the menopausal transition.

Objectives

This research sought to assess racial and socioeconomic status (SES) differences in level and change in allostatic load (AL) over time in midlife women and to test whether psychosocial factors mediate these relationships. These factors were discrimination, perceived stress, and hostility.

Methods

Longitudinal data obtained from the Study of Women's Health Across the Nation were used (n = 2063; mean age at baseline = 46.0 years). Latent growth curve models evaluated the impact of demographic, menopausal, and psychosocial variables on level and change in AL for 8 years.

Results

Direct effects: high levels of discrimination and hostility significantly predicted higher AL (path coefficients = 0.05 and 0.05, respectively). High perceived stress significantly predicted a faster rate of increase of AL (path coefficient = 0.06). Racial and SES differentials were present, with African American race (path coefficient = 0.23), low income (path coefficient = -0.15), and low education (path coefficient = -0.08) significantly predicting high AL level. Indirect effects: significant indirect effects were found for African American race, less income, and lower education through higher discrimination, perceived stress, and hostility on level and rate of AL.

Conclusions

This was one of the first studies that investigated AL over multiple periods, and results supported AL as a cumulative phenomenon, affected by multiple psychosocial and demographic factors. The results suggest the complex ways in which race, SES, and psychosocial factors operate to influence AL.