Effortless awareness: using real time neurofeedback to investigate correlates of posterior cingulate cortex activity in meditators' self-report

Neurophenomenological studies seek to utilize first-person self-report to elucidate cognitive processes related to physiological data. Grounded theory offers an approach to the qualitative analysis of self-report, whereby theoretical constructs are derived from empirical data. Here we used grounded theory methodology to assess how the first-person experience of meditation relates to neural activity in a core region of the default mode network –the posterior cingulate cortex. We analyzed first-person data consisting of meditators’ accounts of their subjective experience during runs of a real-time fMRI neurofeedback study of meditation, and third-person data consisting of corresponding feedback graphs of posterior cingulate cortex activity during the same runs. We found that for meditators, the subjective experiences of ‘undistracted awareness’ such as ‘concentration’ and ‘observing sensory experience’, and ‘effortless doing’ such as ‘observing sensory experience’, ‘not efforting’, and ‘contentment’, correspond with posterior cingulate cortex deactivation. Further, the subjective experiences of ‘distracted awareness’ such as ‘distraction’ and ‘interpreting’, and ‘controlling’ such as ‘efforting’ and ‘discontentment’, correspond with posterior cingulate cortex activation. Moreover, we derived several novel hypotheses about how specific qualities of cognitive processes during meditation relate to posterior cingulate cortex activity, such as the difference between meditation and ‘trying to meditate’. These findings offer novel insights into the relationship between meditation and self-related thinking and neural activity in the default mode network, driven by the first-person experience

High abundance synovial fluid proteome: distinct profiles in health and osteoarthritis

The development of increasingly high-throughput and sensitive mass spectroscopy-based proteomic techniques provides new opportunities to examine the physiology and pathophysiology of many biologic fluids and tissues. The purpose of this study was to determine protein expression profiles of high-abundance synovial fluid (SF) proteins in health and in the prevalent joint disease osteoarthritis (OA). A cross-sectional study of 62 patients with early OA (n = 21), patients with late OA (n = 21), and control individuals (n = 20) was conducted. SF proteins were separated by using one-dimensional PAGE, and the in-gel digested proteins were analyzed by electrospray ionization tandem mass spectrometry. A total of 362 spots were examined and 135 high-abundance SF proteins were identified as being expressed across all three study cohorts. A total of 135 SF proteins were identified. Eighteen proteins were found to be significantly differentially expressed between control individuals and OA patients. Two subsets of OA that are not dependent on disease duration were identified using unsupervised analysis of the data. Several novel SF proteins were also identified. Our analyses demonstrate no disease duration-dependent differences in abundant protein composition of SF in OA, and we clearly identified two previously unappreciated yet distinct subsets of protein profiles in this disease cohort. Additionally, our findings reveal novel abundant protein species in healthy SF whose functional contribution to SF physiology was not previously recognized. Finally, our studies identify candidate biomarkers for OA with potential for use as highly sensitive and specific tests for diagnostic purposes or for evaluating therapeutic response

Participation in physical activity in patients 1–4 years post total joint replacement in the Dominican Republic

Background: To address both the growing burden of joint disease and the gaps in medical access in developing nations, medical relief organizations have begun to launch programs to perform total joint replacement (TJR) on resident populations in developing countries. One outcome of TJR of particular interest is physical activity (PA) since it is strongly linked to general health. This study evaluates the amount of postoperative participation in PA in low-income patients who received total joint replacement in the Dominican Republic and identifies preoperative predictors of postoperative PA level. Methods: We used the Yale Physical Activity Survey (YPAS) to assess participation in postoperative PA 1–4 years following total knee or hip replacement. We compared the amount of aerobic PA reported by postoperative TJR patients with the levels of PA recommended by the CDC and WHO. We also analyzed preoperative determinants of postoperative participation in aerobic PA in bivariate and multivariate analyses. Results: 64 patients out of 170 eligible subjects (52/128 TKR and 14/42 THR) who received TJR between 2009–2012 returned for an annual follow-up visit in 2013, with a mean treatment-to-follow-up time of 2.1 years. 43.3% of respondents met CDC/WHO criteria for sufficient participation in aerobic PA. Multivariate analyses including data from 56 individuals identified that patients who were both younger than 65 and at least two years postoperative had an adjusted mean activity dimensions summary index (ADSI) 22.9 points higher than patients who were 65 or older and one year postoperative. Patients who lived with friends or family had adjusted mean ADSI 17.2 points higher than patients living alone. Patients who had the most optimistic preoperative expectations of outcome had adjusted mean ADSI scores that were 19.8 points higher than those who were less optimistic. Conclusion: The TJR patients in the Dominican cohort participate in less PA than recommended by the CDC/WHO. Additionally, several associations were identified that potentially affect PA in this population; specifically, participants who are older than 65, recently postoperative, less optimistic about postoperative outcomes and who live alone participate in less PA

Placing a Price on Medical Device Innovation: The Example of Total Knee Arthroplasty

Background: Total knee arthroplasty (TKA) is common, effective, and cost-effective. Innovative implants promising reduced long-term failure at increased cost are under continual development. We sought to define the implant cost and performance thresholds under which innovative TKA implants are cost-effective. Methods: We performed a cost-effectiveness analysis using a validated, published computer simulation model of knee osteoarthritis. Model inputs were derived using published literature, Medicare claims, and National Health and Nutrition Examination Survey data. We compared projected TKA implant survival, quality-adjusted life expectancy (QALE), lifetime costs, and cost-effectiveness (incremental cost-effectiveness ratios or ICERs) of standard versus innovative TKA implants. We assumed innovative implants offered 5–70% decreased long-term TKA failure rates at costs 20–400% increased above standard implants. We examined the impact of patient age, comorbidity, and potential increases in short-term failure on innovative implant cost-effectiveness. Results: Implants offering ≥50% decrease in long-term TKA failure at ≤50% increased cost offered ICERs <$100,000 regardless of age or baseline comorbidity. An implant offering a 20$150,000 per QALY gained only among healthy 50–59-year-olds. Increasing short-term failure, consistent with recent device failures, reduced cost-effectiveness across all groups. Increasing the baseline likelihood of long-term TKA failure among younger, healthier and more active individuals further enhanced innovative implant cost-effectiveness among younger patients. Conclusions: Innovative implants must decrease actual TKA failure, not just radiographic wear, by 50–55% or more over standard implants to be broadly cost-effective. Comorbidity and remaining life span significantly affect innovative implant cost-effectiveness and should be considered in the development, approval and implementation of novel technologies, particularly in orthopedics. Model-based evaluations such as this offer valuable, unique insights for evaluating technological innovation in medical devices

First observations of SPEAR-induced artificial backscatter from CUTLASS and the EISCAT Svalbard radars

Results are presented from the first two active experimental campaigns undertaken by the new SPEAR (Space Plasma Exploration by Active Radar) high-power system that has recently become operational on Spitzbergen, in the Svalbard archipelago. SPEAR&apos;s high-power beam was used to excite artificial enhancements in the backscatter detected by the ESR (EISCAT Svalbard Radar) parallel to the geomagnetic field, as well as coherent backscatter detected by both of the CUTLASS (Co-operative UK Twin Located Auroral Sounding System) coherent radars, in directions orthogonal to the geomagnetic field. The ESR detected both enhanced ion-lines as well as enhanced plasma-lines, that were sustained for the whole period when SPEAR was transmitting ordinary mode radio waves, at frequencies below the maximum F-region plasma frequency. On a number of occasions, coherent backscatter was also observed in one or in both of the CUTLASS radars, in beams that intersected the heated volume. Although the levels of enhanced backscatter varied considerably in time, it appeared that ion-line, plasma-line and coherent backscatter were all excited simultaneously, in contrast to what has typically been reported at Troms&amp;#248;, during EISCAT heater operations. A description of the technical and operational aspects of the new SPEAR system is also included

A Connection between Colony Biomass and Death in Caribbean Reef-Building Corals

Increased sea-surface temperatures linked to warming climate threaten coral reef ecosystems globally. To better understand how corals and their endosymbiotic dinoflagellates (Symbiodinium spp.) respond to environmental change, tissue biomass and Symbiodinium density of seven coral species were measured on various reefs approximately every four months for up to thirteen years in the Upper Florida Keys, United States (1994–2007), eleven years in the Exuma Cays, Bahamas (1995–2006), and four years in Puerto Morelos, Mexico (2003–2007). For six out of seven coral species, tissue biomass correlated with Symbiodinium density. Within a particular coral species, tissue biomasses and Symbiodinium densities varied regionally according to the following trends: Mexico≥Florida Keys≥Bahamas. Average tissue biomasses and symbiont cell densities were generally higher in shallow habitats (1–4 m) compared to deeper-dwelling conspecifics (12–15 m). Most colonies that were sampled displayed seasonal fluctuations in biomass and endosymbiont density related to annual temperature variations. During the bleaching episodes of 1998 and 2005, five out of seven species that were exposed to unusually high temperatures exhibited significant decreases in symbiotic algae that, in certain cases, preceded further decreases in tissue biomass. Following bleaching, Montastraea spp. colonies with low relative biomass levels died, whereas colonies with higher biomass levels survived. Bleaching- or disease-associated mortality was also observed in Acropora cervicornis colonies; compared to A. palmata, all A. cervicornis colonies experienced low biomass values. Such patterns suggest that Montastraea spp. and possibly other coral species with relatively low biomass experience increased susceptibility to death following bleaching or other stressors than do conspecifics with higher tissue biomass levels

Analogues of Marine Guanidine Alkaloids Are in Vitro Effective against Trypanosoma cruzi and Selectively Eliminate Leishmania (L.) infantum Intracellular Amastigotes

Synthetic analogues of marine sponge guanidine alkaloids showed in vitro antiparasitic activity against Leishmania (L.) infantum and Trypanosoma cruzi. Guanidines 10 and 11 presented the highest selectivity index when tested against Leishmania. The antiparasitic activity of 10 and 11 was investigated in host cells and in parasites. Both compounds induced depolarization of mitochondrial membrane potential, upregulation of reactive oxygen species levels, and increased plasma membrane permeability in Leishmania parasites. Immunomodulatory assays suggested an NO-independent effect of guanidines 10 and 11 on macrophages. The same compounds also promoted anti-inflammatory activity in L. (L.) infantum-infected macrophages cocultived with splenocytes, reducing the production of cytokines MCP-1 and IFN-γ. Guanidines 10 and 11 affect the bioenergetic metabolism of Leishmania, with selective elimination of parasites via a host-independent mechanism

Anti-tumor necrosis factor-Α antibody treatment reduces pulmonary inflammation and methacholine hyper-responsiveness in a murine asthma model induced by house dust

Background/Aims Recent studies documented that sensitization and exposure to cockroach allergens significantly increase children's asthma morbidity as well as severity, especially among inner city children. TNF-Α has been postulated to be a critical mediator directly contributing to the bronchopulmonary inflammation and airway hyper-responsiveness in asthma. This study investigated whether an anti-TNF-Α antibody would inhibit pulmonary inflammation and methacholine (Mch) hyper-responsiveness in a mouse model of asthma induced by a house dust extract containing both endotoxin and cockroach allergens. Methods A house dust sample was extracted with phosphate-buffered saline and then used for immunization and two additional pulmonary challenges of BALB/c mice. Mice were treated with an intravenous injection of anti-TNF-Α antibody or control antibody 1  h before each pulmonary challenge. Results In a kinetic study, TNF-Α levels within the bronchoalveolar lavage (BAL) fluid increased quickly peaking at 2 h while BAL levels of IL-4, IL-5, and IL-13 peaked at later time-points. Mch hyper-responsiveness was measured 24 h after the last challenge, and mice were killed 24 h later. TNF inhibition resulted in an augmentation of these Th2 cytokines. However, the allergic pulmonary inflammation was significantly reduced by anti-TNF-Α antibody treatment as demonstrated by a substantial reduction in the number of BAL eosinophils, lymphocytes, macrophages, and neutrophils compared with rat IgG-treated mice. Mch hyper-responsiveness was also significantly reduced in anti-TNF-Α antibody-treated mice and the pulmonary histology was also significantly improved. Inhibition of TNF significantly reduced eotaxin levels within the lung, suggesting a potential mechanism for the beneficial effects. These data indicate that anti-TNF-Α antibody can reduce the inflammation and pathophysiology of asthma in a murine model of asthma induced by a house dust extract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73609/1/j.1365-2222.2005.02407.x.pd

Patient Disease Perceptions and Coping Strategies for Arthritis in a Developing Nation: A Qualitative Study

<p>Abstract</p> <p>Background</p> <p>There is little prior research on the burden of arthritis in the developing world. We sought to document how patients with advanced arthritis living in the Dominican Republic are affected by and cope with their disease.</p> <p>Methods</p> <p>We conducted semi-structured, one-to-one interviews with economically disadvantaged Dominican patients with advanced knee and/or hip arthritis in the Dominican Republic. The interviews, conducted in Spanish, followed a moderator's guide that included topics such as the patients' understanding of disease etiology, their support networks, and their coping mechanisms. The interviews were audiotaped, transcribed verbatim in Spanish, and systematically analyzed using content analysis. We assessed agreement in coding between two investigators.</p> <p>Results</p> <p>18 patients were interviewed (mean age 60 years, median age 62 years, 72% women, 100% response rate). Patients invoked religious and environmental theories of disease etiology, stating that their illness had been caused by God's will or through contact with water. While all patients experienced pain and functional limitation, the social effects of arthritis were gender-specific: women noted interference with homemaking and churchgoing activities, while men experienced disruption with occupational roles. The coping strategies used by patients appeared to reflect their beliefs about disease causation and included prayer and avoidance of water.</p> <p>Conclusions</p> <p>Patients' explanatory models of arthritis influenced the psychosocial effects of the disease and coping mechanisms used. Given the increasing reach of global health programs, understanding these culturally influenced perceptions of disease will be crucial in successfully treating chronic diseases in the developing world.</p