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BACKGROUND Regular physical activity is associated with reduced risk of chronic illnesses. Despite various types of successful physical activity interventions, maintenance of activity over the long term is extremely challenging. OBJECTIVE The aims of this original paper are to 1) describe physical activity engagement post intervention, 2) identify motivational profiles using natural language processing (NLP) and clustering techniques in a sample of women who completed the physical activity intervention, and 3) compare sociodemographic and clinical data among these identified cluster groups. METHODS In this cross-sectional analysis of 203 women completing a 12-month study exit (telephone) interview in the mobile phone-based physical activity education study were examined. The mobile phone-based physical activity education study was a randomized, controlled trial to test the efficacy of the app and accelerometer intervention and its sustainability over a 9-month period. All subjects returned the accelerometer and stopped accessing the app at the last 9-month research office visit. Physical engagement and motivational profiles were assessed by both closed and open-ended questions, such as “Since your 9-month study visit, has your physical activity been more, less, or about the same (compared to the first 9 months of the study)?” and, “What motivates you the most to be physically active?” NLP and cluster analysis were used to classify motivational profiles. Descriptive statistics were used to compare participants’ baseline characteristics among identified groups. RESULTS Approximately half of the 2 intervention groups (Regular and Plus) reported that they were still wearing an accelerometer and engaging in brisk walking as they were directed during the intervention phases. These numbers in the 2 intervention groups were much higher than the control group (overall P=.01 and P=.003, respectively). Three clusters were identified through NLP and named as the Weight Loss group (n=19), the Illness Prevention group (n=138), and the Health Promotion group (n=46). The Weight Loss group was significantly younger than the Illness Prevention and Health Promotion groups (overall P.05). CONCLUSIONS The findings could be relevant to tailoring a physical activity maintenance intervention. Furthermore, the findings from NLP and cluster analysis are useful methods to analyze short free text to differentiate motivational profiles. As more sophisticated NL tools are developed in the future, the potential of NLP application in behavioral research will broaden. CLINICALTRIAL ClinicalTrials.gov NCT01280812; https://clinicaltrials.gov/ct2/show/NCT01280812 (Archived by WebCite at http://www.webcitation.org/70IkGagAJ)

Unhealthy substance-use behaviors, including a heavy alcohol intake, illicit drug use, and cigarette smoking, are engaged in by many HIV-positive individuals, often as a way to manage their disease-related symptoms. This study, based on data from a larger randomized controlled trial of an HIV/AIDS symptom management manual, examines the prevalence and characteristics of unhealthy behaviors in relation to HIV/AIDS symptoms. The mean age of the sample (n = 775) was 42.8 years and 38.5% of the sample was female. The mean number of years living with HIV was 9.1 years. The specific self-reported unhealthy substance-use behaviors were the use of marijuana, cigarettes, a large amount of alcohol, and illicit drugs. A subset of individuals who identified high levels of specific symptoms also reported significantly higher substance-use behaviors, including amphetamine and injection drug use, heavy alcohol use, cigarette smoking, and marijuana use. The implications for clinical practice include the assessment of self-care behaviors, screening for substance abuse, and education of persons regarding the self-management of HIV.

Osseointegration is a new technique for prosthetic suspension in individuals with limb loss. The objective of this study was to determine perceptions and acceptance of osseointegration as a means of prosthetic suspension among individuals with lower limb amputations. A survey instrument was

Stress shielding from the presence of a femoral component can cause adverse changes to cortical bone geometry and porosity leading to increased fracture risk in the periprosthetic cortical bone. The objectives of this study were to determine if porosity increased after total hip arthroplasty along the principal axes, and to determine if a relationship existed between cortical bone porosity and geometry. Ten postmortem donors allowed comparisons of implanted femurs to the contralateral nonimplanted femurs. Transverse cross-sections of the femur were taken at 25, 45, 65, and 85% along the length of the femoral component. The cortical bone principal axes' location (degrees) and rigidity values (mm4) were based on cortical bone geometry by using digitized images of the cortical bone cross-sections. Percent porosity was measured along the principal axes using backscatter electron imaging. Cortical bone porosity increased in the more distal sections of the implanted femurs by ∼3%, but did not preferentially increase along a particular principal axis. No correlation was found between changes in porosity and rigidity values. In conclusion, the porosity increases in the implanted femurs may have regionally reduced cortical bone strength. The locations of higher porosity did not appear related to the cortical bone geometry. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008

Little is known regarding the specific managerial activities or best practices that nurse managers in outpatient hemodialysis settings use to achieve positive safety outcomes. The purpose of this study was to identify and describe specific managerial practices used by nurse managers in outpatient hemodialysis units to enhance patient safety and quality of care. A descriptive qualitative design was used. Seventeen nurse managers in outpatient hemodialysis units comprised the study sample. Telephone interviews were conducted, and qualitative content analysis was used to encode the data. Nurse managers identified patients, staff, the dialysis unit environment, and the dialysis organization as sources of safety risks. Nurse manager safety practices illuminated from the data were complex and multifaceted, and were aimed at reducing patient, staff environmental, and organization risks. The findings from this study offer a description and a better understanding of the practices in which nurse managers in outpatient hemodialysis units engage to keep patients safe in their units, and they underscore the critical role of nurse managers in creating and maintaining patient safety within outpatient hemodialysis settings.

When testing the effects of a femoral component on cortical bone following total hip arthroplasty, the patient's implanted femur is often compared with his/her contralateral nonimplanted femur, with differences attributed to the femoral component. However, if normal anatomical differences exist between bilateral femurs, they need to be quantified in order to validate whether the differences between implanted and nonimplanted bilateral femurs are due to the implant or possibility due to intrinsic differences before implantation. This study quantified the geometric properties of cortical bone shape between seven pairs of bilateral, cadaveric, human femurs. The null hypothesis tested stated that the bilateral femurs would not be significantly different in cortical bone geometry. Digitized images of cortical bone cross-sections taken at percent biomechanical lengths (levels 1–8) were used to calculate bone geometry measurements. The paired t-test showed that the only significant difference was in the location of principal axes at the most proximal location, level 1 (p = 0.015). All other measurements and levels were not significant with percent differences less than 6.6%. In conclusion, the data supports attributing cortical bone shape differences between implanted and contralateral nonimplanted femurs in levels 2–8 to the presence of the implant when the significant differences are greater than 6.6%. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006

Despite the widespread use of polypeptide growth factors as pharmacological agents, little is known about the extent to which these molecules regulate their cognate cell surface receptors and signal transduction pathways in vivo. We have addressed this issue with respect to the neurotrophic molecule ciliary neurotrophic factor (CNTF). Administration of CNTF in vivo resulted in modest decreases in levels of CNTFRα mRNA and protein in skeletal muscle. CNTF causes the rapid tyrosine phosphorylation of LIFRβ and gp130 and the induction of the immediate-early gene, tis11; injection of CNTF 3-7 h after an initial exposure failed to re-stimulate these immediate-early responses, suggesting a biochemical desensitization to CNTF not accounted for by decreased receptor protein. To determine whether the desensitization of immediate-early responses caused by CNTF resulted in a functional desensitization, we compared the efficacy of multiple daily injections versus a single daily dose of CNTF in preventing the denervation-induced atrophy of skeletal muscle. Surprisingly, injections of CNTF every 6 h, which falls within the putative refractory period for biochemical responses, resulted in efficacy equal to or greater than injections once daily. These results suggest that although much of the CNTF signal transduction machinery is down-regulated with frequent CNTF dosing, biological signals continue to be recognized and interpreted by the cell.

Alignment - the process and measured orientation of the prosthetic socket relative to the foot - is important for proper function of a transtibial prosthesis. Prosthetic alignment is performed by prosthetists using visual gait observation and amputees' feedback. The aim of this study was to investigate the effect of transtibial prosthesis malalignment on the moments measured at the base of the socket: the socket reaction moments. Eleven subjects with transtibial amputation were recruited from the community. An instrumented prosthesis alignment component was used to measure socket reaction moments during ambulation under 17 alignment conditions, including nominally aligned using conventional clinical methods, and angle perturbations of 3° and 6° (flexion, extension, abduction, and adduction) and translation perturbations of 5mm and 10mm (anterior, posterior, lateral, and medial) referenced from the nominal alignment. Coronal alignment perturbations caused systematic changes in the coronal socket reaction moments. All angle and translation perturbations revealed statistically significant differences on coronal socket reaction moments compared to the nominal alignment at 30% and 75% of stance phase (P

The differentiation of neuronal cell progenitors depends on complex interactions between intrinsic cellular programs and environmental cues. Such interactions have recently been explored using an immortalized sympathoadrenal progenitor cell line, MAH. These studies have revealed that depolarizing conditions, in combination with exposure to FGF, can induce responsiveness to NGF. Here we report that CNTF, which utilizes an intracellular signaling pathway distinct from that of both FGF and NGF, can collaborate with FGF to promote efficiently the differentiation of MAH progenitor cells to a stage remarkably reminiscent of NGF-dependent, postmitotic sympathetic neurons. We also find that similar collaborative interactions can occur during transdifferentiation of normal cultured chromaffin cells into sympathetic neurons.

Ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), oncostatin M (OSM), and interleukin-6 (IL6) compose a family of distantly related cytokines that initiate signaling by inducing either homodimerization of the "beta" signal transducing receptor component gp130 (in the case of IL6) or heterodimerization between gp130 and the gp130-related LIFR beta (in the case of CNTF, LIF, and OSM); dimerization of beta receptor components in turn activates members of the Jak/Tyk family of receptor-associated tyrosine kinases. Here we report that CNTF, LIF, OSM, and IL6 induce most of the same protein tyrosine phosphorylations, regardless of the cell type assayed or whether they initiate signaling by inducing homo- or heterodimerization of beta components. Although several of the protein tyrosine phosphorylations induced by the CNTF/LIF/OSM/IL6 family of factors may correspond to novel tyrosine kinase targets, we have been able to demonstrate the involvement of known signaling molecules, such as phospholipase C gamma, phosphoinositol 3-kinase, phosphotyrosine phosphatase (PTP1D), pp120, SHC, GRB2, STAT91, Raf-1, and the mitogen-activated protein kinases ERK1 and ERK2, revealing substantial convergence not only between the pathways activated by this cytokine family and other cytokines, but with pathways previously known to be activated only by factors that utilize receptor tyrosine kinases. Our data suggest the beta receptor components can form complexes with some of the signaling proteins identified and may play some role in their recruitment.

Extracellular signal-regulated kinases 1 and 2 are growth factor-sensitive serine/threonine kinases. cDNAs for both human kinases were isolated and sequenced. The nucleic acid and deduced protein sequences of human extracellular signal-regulated kinase 1 were 88% and 96% identical, respectively, to the homologous rat sequences. The nucleic acid and deduced protein sequences of human extracellular signal-regulated kinase 2 were 90% and 98% identical, respectively, to the corresponding rat sequences. A human extracellular signal-regulated kinase 2 specific probe was used to demonstrate that the mRNA for this kinase was present in T cells and did not change with activation. The deduced protein sequences of both human kinases were greater than 95% identical to two Xenopus kinase sequences, indicating that these enzymes are highly conserved across species.

Transcutaneous osseointegrated implants can improve function for select amputee patients, but infection serves as a significant limitation of implantable transcutaneous devices. This study examined the efficacy of an antimicrobial, pexiganan acetate (SUPONEX™), and a porous tantalum implant material (Trabecular Metal™) in preventing pin tract infection of osseointegrated implants in a rabbit model. Thirty-seven rabbits were randomized to three groups: Ti-control group (n = 11) with titanium alloy implant and no antimicrobial, Ti-Pexiganan group (n = 8) with titanium alloy implant and topical pexiganan acetate 1% applied daily at the skin/implant interface, and Ta-control group (n = 18) with porous tantalum implant and no antimicrobial. All implants were placed transcutaneously through skin, muscle, and bone. Rabbits were monitored for infection for 24 weeks. We observed a 75% reduction in rates of pin tract infection in the Ti-Pexiganan group compared to that observed in the Ti-control group (p = 0.019). No difference in rates of infection was observed between the Ta-control group and the Ti-control group (p = 0.230). In conclusion, pexiganan acetate may be an important antimicrobial for transcutaneous osseointegrated implants. Porous tantalum will not likely prevent pin tract infection without additional methods of soft tissue immobilization around the implant site. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010

A family of protein kinases, known alternatively as microtubule-associated protein-2/myelin basic protein kinases or extracellular signal-regulated kinases, is activated by numerous hormones, growth factors and other extracellular stimuli. At least two members of this family function as intermediate kinases in protein phosphorylation cascades. Their mechanisms of activation may involve autophosphorylation, which occurs on both threonine and tyrosine residues.

A protein kinase characterized by its ability to phosphorylate microtubule-associated protein-2 (MAP2) and myelin basic protein (MBP) is thought to play a pivotal role in the transduction of signals from many receptors in response to their ligands. A kinase with such activity, named extracellular signal-regulated kinase 1 (ERK1), is activated rapidly by numerous extracellular signals, requires phosphorylation on tyrosine to be fully active, and in vitro can activate a kinase (a ribosomal S6 protein kinase) that is downstream in phosphorylation cascades. From the protein sequence predicted by the rat ERK1 cDNA, peptides were synthesized and used to elicit antibodies. The antibodies recognize both ERK1; a closely related kinase, ERK2; and a third novel ERK-related protein. Using these antibodies we have determined that ERK1 and ERK2 are ubiquitously distributed in rat tissues. Both enzymes are expressed most highly in brain and spinal cord as are their mRNAs. The third ERK protein was found in spinal cord and in testes. The antibodies detect ERKs in cell lines from multiple species, including human, mouse, dog, chicken, and frog, in addition to rat, indicating that the kinases are conserved across species. ERK1 and ERK2 have been separated by chromatography on Mono Q. Stimulation by insulin increases the phosphorylation of both kinases on tyrosine residues, as assessed by immunoblotting with phosphotyrosine antibodies, and retards their elution from Mono Q. Each of these ERKs appears to account for a distinct peak of MBP kinase activity. The activity in each peak is diminished by incubation with either phosphatase 2a or CD45. Therefore, both enzymes have similar modes of regulation and appear to contribute to the growth factor-stimulated MAP2/MBP kinase activity measured in cell extracts.

In rat 1 fibroblasts, insulin has little or no stimulatory effect on the activities of either MAP2 protein kinase or ribosomal protein S6 kinase. In contrast, in rat 1 cells that overexpress the normal human insulin receptor (rat 1 HIRc B; McClain et al. (1987) J. Biol. Chem. 262, 14663-14671), insulin activates both MAP2 and S6 kinase activities close to 5-fold. A MAP2 kinase has been purified from insulin-treated rat 1 HIRc B cells over 6300-fold by chromatography on Q-Sepharose, phenyl-Sepharose, S-Sepharose, phosphocellulose, QAE-Sepharose, UltrogelAcA54, DEAE-cellulose, and a second Q-Sepharose. Its specific activity is approximately 0.8-1 mumol.min-1.mg-1 with MAP2 and 3 mumol.min-1.mg-1 with myelin basic protein. The enzyme preparation contains one major band of Mr = 43,000 upon SDS-polyacrylamide gel electrophoresis, which is immunoblotted by antibodies to phosphotyrosine. A sequence from the 43-kDa band led to the isolation of a cDNA encoding the enzyme, which we have named ERK1 for extracellular signal-regulated kinase (Boulton et al. (1990) Science 249, 64-67).

The abilities of a series of six mutants of the human insulin receptor, an insulin receptor/v-ros hybrid (IR-ros) and the P68gag-ros transforming protein to stimulate S6 protein kinase have been assessed. Insulin receptor mutants in which either 1 or 2 tyrosine residues have been replaced with phenylalanine (YF1, YF3) have lost some or all of the capacity to mediate the activation of S6 kinase in response to insulin. None of the four mutants that contain deletions (spBam, spBamYF3, iBgl, T-t) elicit an insulin-dependent stimulation of S6 kinase. A previous study of the IRros hybrid receptor demonstrated that it was unable to cause either insulin-stimulated thymidine incorporation or glucose uptake (Ellis, L., Morgan, D. O., Jong, S.-M., Wang, L.-H., Roth, R. A., and Rutter, W. J. (1987) Proc. Natl. Acad. Sci. U. S. A. 84, 5101-5105). In contrast, the IRros chimera appears to mediate the activation of S6 protein kinase by insulin. In further evaluating the biological activities of the IRros hybrid, we have examined its effects on a microtubule-associated protein-2 (MAP2) kinase that is thought to be an early target in the cascade of reactions leading to increased S6 phosphorylation (Sturgill, T. W., Ray, L. B., Erickson, E., and Maller, J. L. (1988) Nature 334, 715-718). We find that the IRros receptor stimulates the MAP2 protein kinase from 3- to 6-fold in insulin-treated cells, conferring more than a 30-fold increase in the insulin sensitivity of MAP2 kinase activation.

Our studies of the spatiotemporal availability of neurotrophic factors, coupled with tagged ligand binding assays that identify cell bearing receptors for these factors, should lead toward defining the physiological roles of these molecules in the animal. The use of the tagged ligands to identify factor-responsive cell lines has also provided new model systems for the examination of ligand-receptor interactions, as well as for the study of the subsequent induction of intracellular response pathways. To obtain insights into such intracellular pathways, we have molecularly cloned genes encoding a family of serine-threonine protein kinases, most closely related to kinases involved in the yeast response to pheromones. These kinases may be crucial regulators of early steps in the response of mammalian cells to neurotrophic factors as well as other extracellular signals.

Because periprosthetic bone loss impacts revision total hip arthroplasties and subsequent patient recovery, it is important to understand the consequences of stress shielding. We characterized bone loss attributed to stress shielding by investigating the influence of patient activity and demographics on reductions in cortical bone cross-sectional area, bone mineral density, and bone mineral content. Cortical bone shape, bone mineral content, and bone mineral density were measured in implanted and contralateral nonimplanted cadaveric femurs. Geometric measurements of transverse cross sections were measured with imaging software. Dual energy x-ray absorptiometry measured bone mineral content and bone mineral density. Patient activity was estimated by the mechanical usage score. The mechanical usage score was comprised of the ambulatory components of the Harris hip score. Regression analysis revealed a lower mechanical usage score and patient weight correlated with greater bone loss. Age, implant size, and time in situ did not correlate to bone loss. The implanted femurs were reduced in cross-sectional area and rigidity, and expanded endosteally and periosteally. Principal axis location did not change. Bone loss was more likely to occur uniformly than to change cortical bone distribution. Bone loss was minimized in patients with higher activity levels.

The standard technique for monitoring bone mineral in hip arthroplasty has been dual-energy x-ray absorptiometry (DEXA). The accuracy of DEXA in the cortical bone adjacent to femoral components has not been established. This study evaluated bone mineral in the cortical bone adjacent to the femoral component comparing DEXA and ashing. Seven pairs of human femora from postmortem donors with unilateral hip implants were examined. Twenty-eight ashed core specimens from both the medial and lateral sides were taken. Cortical bone loss was seen to be greater in the proximal and medial regions of the implanted femora. Dual-energy x-ray absorptiometry failed to show an acceptable level of accuracy compared with ash data (r = 0.56; P = .002). It did show relative patterns of bone loss. Bone loss was consistent with implant-induced stress shielding.