Modulation of depth-dependent properties in tissue-engineered cartilage with a semi-permeable membrane and perfusion : a continuum model of matrix metabolism and transport

The functional properties of cartilaginous tissues are determined predominantly by the content, distribution, and organization of proteoglycan and collagen in the extracellular matrix. Extracellular matrix accumulates in tissue-engineered cartilage constructs by metabolism and transport of matrix molecules, processes that are modulated by physical and chemical factors. Constructs incubated under free-swelling conditions with freely permeable or highly permeable membranes exhibit symmetric surface regions of soft tissue. The variation in tissue properties with depth from the surfaces suggests the hypothesis that the transport processes mediated by the boundary conditions govern the distribution of proteoglycan in such constructs. A continuum model (DiMicco and Sah in Transport Porus Med 50:57-73, 2003) was extended to test the effects of membrane permeability and perfusion on proteoglycan accumulation in tissue-engineered cartilage. The concentrations of soluble, bound, and degraded proteoglycan were analyzed as functions of time, space, and non-dimensional parameters for several experimental configurations. The results of the model suggest that the boundary condition at the membrane surface and the rate of perfusion, described by non-dimensional parameters, are important determinants of the pattern of proteoglycan accumulation. With perfusion, the proteoglycan profile is skewed, and decreases or increases in magnitude depending on the level of flow-based stimulation. Utilization of a semi-permeable membrane with or without unidirectional flow may lead to tissues with depth-increasing proteoglycan content, resembling native articular cartilage.

Moving tele-monitoring and tele-treatment from promise to practice : a business model approach for a chronic lower back pain application

The availability of new information and communication technologies creates opportunities for new, mobile tele-health services. While many promising tele-health projects deliver working R&D prototypes, they often do not result in actual deployment. We aim to identify critical issues than can increase our understanding and enhance the viability of the mobile tele-health services beyond the R&D phase by developing a business model. The present study describes the systematic development and evaluation of a service-oriented business model for tele-monitoring and -treatment of chronic lower back pain patients based on a mobile technology prototype. We address challenges of multi-sector collaboration and disruptive innovation.

Plantar fasciitis : are pain and fascial thickness associated with arch shape and loading?

Background and Purpose Although plantar fascial thickening is a sonographic criterion for the diagnosis of plantar fasciitis, the effect of local loading and structural factors on fascial morphology are unknown. The purposes of this study were to compare sonographic measures of fascial thickness and radiographic measures of arch shape and regional loading of the foot during gait in individuals with and without unilateral plantar fasciitis and to investigate potential relationships between these loading and structural factors and the morphology of the plantar fascia in individuals with and without heel pain. Subjects The participants were 10 subjects with unilateral plantar fasciitis and 10 matched asymptomatic controls. Methods Heel pain on weight bearing was measured by a visual analog scale. Fascial thickness and static arch angle were determined from bilateral sagittal sonograms and weight-bearing lateral foot roentgenograms. Regional plantar loading was estimated from a pressure plate. Results On average, the plantar fascia of the symptomatic limb was thicker than the plantar fascia of the asymptomatic limb (6.1±1.4 mm versus 4.2±0.5 mm), which, in turn, was thicker than the fascia of the matched control limbs (3.4±0.5 mm and 3.5±0.6 mm). Pain was correlated with fascial thickness, arch angle, and midfoot loading in the symptomatic foot. Fascial thickness, in turn, was positively correlated with arch angle in symptomatic and asymptomatic feet and with peak regional loading of the midfoot in the symptomatic limb. Discussion and Conclusion The findings indicate that fascial thickness and pain in plantar fasciitis are associated with the regional loading and static shape of the arch.

Affect, attention, or anticipatory arousal? Human blink startle modulation in forward and backward affective conditioning

Affect modulates the blink startle reflex in the picture-viewing paradigm, however, the process responsible for reflex modulation during conditional stimuli (CSs) that have acquired valence through affective conditioning remains unclear. In Experiment 1, neutral shapes (CSs) and valenced or neutral pictures (USs) were paired in a forward (CS → US) manner. Pleasantness ratings supported affective learning of positive and negative valence. Post-acquisition, blink reflexes were larger during the pleasant and unpleasant CSs than during the neutral CS. Rather than affect, attention or anticipatory arousal were suggested as sources of startle modulation. Experiment 2 confirmed that affective learning in the picture–picture paradigm was not affected by whether the CS preceded the US. Pleasantness ratings and affective priming revealed similar extents of affective learning following forward, backward or simultaneous pairings of CSs and USs. Experiment 3 utilized a backward conditioning procedure (US → CS) to minimize effects of US anticipation. Again, blink reflexes were larger during CSs paired with valenced USs regardless of US valence implicating attention rather than anticipatory arousal or affect as the process modulating startle in this paradigm.

When does pain and distress relief hastening death become killing?

This paper discusses the question of when pain and distress relief known to hasten death would cross the line between permissible conduct and killing. The issue is discussed in the context of organ donation after cardiac death, and considers the administration of analgesics, sedatives, and the controversial use of paralysing agents in the provision and withdrawal of ventilation.

Modulation of the Chlamydia trachomatis In vitro transcriptome response by the sex hormones estradiol and progesterone

BACKGROUND:Chlamydia trachomatis is a major cause of sexually transmitted disease in humans. Previous studies in both humans and animal models of chlamydial genital tract infection have suggested that the hormonal status of the genital tract epithelium at the time of exposure can influence the outcome of the chlamydial infection. We performed a whole genome transcriptional profiling study of C. trachomatis infection in ECC-1 cells under progesterone or estradiol treatment.RESULTS:Both hormone treatments caused a significant shift in the sub-set of genes expressed (25% of the transcriptome altered by more than 2-fold). Overall, estradiol treatment resulted in the down-regulation of 151 genes, including those associated with lipid and nucleotide metabolism. Of particular interest was the up-regulation in estradiol-supplemented cultures of six genes (omcB, trpB, cydA, cydB, pyk and yggV), which suggest a stress response similar to that reported previously in other models of chlamydial persistence. We also observed morphological changes consistent with a persistence response. By comparison, progesterone supplementation resulted in a general up-regulation of an energy utilising response.CONCLUSION:Our data shows for the first time, that the treatment of chlamydial host cells with key reproductive hormones such as progesterone and estradiol, results in significantly altered chlamydial gene expression profiles. It is likely that these chlamydial expression patterns are survival responses, evolved by the pathogen to enable it to overcome the host's innate immune response. The induction of chlamydial persistence is probably a key component of this survival response.

The effect of emotional and attentional load on attentional startle modulation

The interactive effects of emotion and attention on attentional startle modulation were investigated in two experiments. Participants performed a discrimination and counting task with two visual stimuli during which acoustic eyeblink startle-eliciting probes were presented at long lead intervals. In Experiment 1, this task was combined with aversive Pavlovian conditioning. In Group Attend CS+, the attended stimulus was followed by an aversive unconditional stimulus (US) and the ignored stimulus was presented alone whereas the ignored stimulus was paired with the US in Group Attend CS−. In Experiment 2, a non-aversive reaction time task US replaced the aversive US. Regardless of the conditioning manipulation and consistent with a modality non-specific account of attentional startle modulation, startle magnitude was larger during attended than ignored stimuli in both experiments. Blink latency shortening was differentially affected by the conditioning manipulations suggesting additive effects of conditioning and discrimination and counting task on blink startle.

The relationship between self-reported animal fear and ERP modulation : Evidence for enhanced processing and fear of harmless invertebrates in snake- and spider-fearful individuals

The present study used ERPs to compare processing of fear-relevant (FR) animals (snakes and spiders) and non-fear-relevant (NFR) animals similar in appearance (worms and beetles). EEG was recorded from 18 undergraduate participants (10 females) as they completed two animal-viewing tasks that required simple categorization decisions. Participants were divided on a post hoc basis into low snake/spider fear and high snake/spider fear groups. Overall, FR animals were rated higher on fear and elicited a larger LPC. However, individual differences qualified these effects. Participants in the low fear group showed clear differentiation between FR and NFR animals on subjective ratings of fear and LPC modulation. In contrast, participants in the high fear group did not show such differentiation between FR and NFR animals. These findings suggest that the salience of feared-FR animals may generalize on both a behavioural and electro-cortical level to other animals of similar appearance but of a non-harmful nature.