Connexin communication compartments and wound repair in epithelial tissue

Epithelial tissues line the lumen of tracts and ducts connecting to the external environment. They are critical in forming an interface between the internal and external environment and, following assault from environmental factors and pathogens, they must rapidly repair to maintain cellular homeostasis. These tissue networks, that range from a single cell layer, such as in airway epithelium, to highly stratified and differentiated epithelial surfaces, such as the epidermis, are held together by a junctional nexus of proteins including adherens, tight and gap junctions, often forming unique and localised communication compartments activated for localised tissue repair. This review focuses on the dynamic changes that occur in connexins, the constituent proteins of the intercellular gap junction channel, during wound-healing processes and in localised inflammation, with an emphasis on the lung and skin. Current developments in targeting connexins as corrective therapies to improve wound closure and resolve localised inflammation are also discussed. Finally, we consider the emergence of the zebrafish as a concerted whole-animal model to study, visualise and track the events of wound repair and regeneration in real-time living model systems

Post-1995 French cinema: return of the social, return of the political?

A key trend in post-1995 French cinema has been the return of the social. Analysing this trend, this article seeks to evaluate its politic impact. Using Hervé Le Roux’s Reprise (1997) and Agnès Varda’s Les Glaneurs et la glaneuse (2000) as key meta-texts, it suggests that the current wave of politically engaged cinema needs to be approached in new ways that recognise how films trace the impact of a politically unmediated, ‘raw’ real on groups or individuals. It further suggests that the withdrawal of political mediation gives the films an essential ambiguity and a melodramatic quality that, rather than mere cliché, may be a privileged way to engage with the violence of the real. Film is now not so much in the van but dans le bain of a diverse socio-political stirring

Chiropractic management of patients post-disc arthroplasty: eight case reports

<p>Abstract</p> <p>Background</p> <p>When conservative therapies for low back pain (LBP) are not effective, elective surgery may be proposed to these patients. Over the last 20 years, a new technology, disc replacement, has become increasingly popular because it is believed to maintain or restore the integrity of spinal movement and minimize the side-effects compared to fusion. Although disc replacement may relieve a patient from pain and related disability, soreness and stiffness of the lumbopelvic region seem to be common aftermaths of the surgery. This prospective case series was undertaken to identify and describe potential adverse events of lumbar spinal manipulation, a common therapy for low back pain, in a group of patients with symptoms after disc prostheses.</p> <p>Cases presentation</p> <p>Eight patients who underwent lumbar spine total disc replacement were referred by an orthopaedic surgeon for chiropractic treatments. These patients had 1 or 2 total lumbar disc replacements and were considered stable according to the surgical protocol but presented persistent, post-surgical, non-specific LBP or pelvic pain. They were treated with lumbar spine side posture manipulations only and received 8 to 10 chiropractic treatments based on the clinical evolution and the chiropractor's judgment. Outcome measures included benign, self-limiting, and serious adverse events after low back spinal manipulative therapy. The Oswestry Disability Index, a pain scale and the fear avoidance belief questionnaire were administered to respectively assess disability, pain and fear avoidance belief about work and physical activity. This prospective case series comprised 8 patients who all had at least 1 total disc replacement at the L4/L5 or L5/S1 level and described persistent post-surgical LBP interfering with their daily activities. Commonly-reported side-effects of a benign nature included increased pain and/or stiffness of short duration in nearly half of the chiropractic treatment period. No major or irreversible complication was noted.</p> <p>Conclusions</p> <p>During the short treatment period, no major complication was encountered by the patients. Moreover, the benign side-effects reported after lumbar spine manipulation were similar in nature and duration to those frequently experienced by the general population.</p

Connexins and the epithelial tissue barrier: a focus on Connexin 26

Epithelial tissue responds rapidly to environmental triggers and is constantly renewed. This tissue is also highly accessible for therapeutic targeting. This review highlights the role of connexin mediated communication in avascular epithelial tissue. These proteins form communication conduits with the extracellular space (hemichannels) and between neighboring cells (gap junctions). Regulated exchange of small metabolites less than 1kDa aide the co-ordination of cellular activities and in spatial communication compartments segregating tissue networks. Dysregulation of connexin expression and function has profound impact on physiological processes in epithelial tissue including wound healing. Connexin 26, one of the smallest connexins, is expressed in diverse epithelial tissue and mutations in this protein are associated with hearing loss, skin and eye conditions of differing severity. The functional consequences of dysregulated connexin activity is discussed and the development of connexin targeted therapeutic strategies highlighted

Changes in flexion-relaxation phenomenon and lumbo-pelvic kinematics following lumbar disc replacement surgery

Background: A single group prospective study. Disc prostheses are believed to contribute to the restoration of the segmental movement and the preservation of the adjacent segments. The study's main objective was to determine if changes in neuromuscular patterns assessed using the flexion-relaxation phenomenon (FRP) can be observed following disc replacement surgery. Methods: Fifteen subjects participated in this study they were evaluated before and after lumbar disc replacement surgery. Both assessments included ten repetitions of a trunk flexion and extension movement (with and without a load), where the surface electromyography (EMG) and kinematic data were recorded. Results: Following the disc replacement procedure (17.3 weeks plus or minus 8.4), participants reported a significant reduction in their ODI and FABQ - physical activity scores. Increases in pelvic flexion as well as in erector spinae (ES) muscle activity at L5 in the flexion phase were observed. Following the disc replacement surgery, ES activity at L2 decreased during the quiet standing position. Conclusion: The results of this study suggest that although improvements in disability scores and fear-avoidance related to physical activities scores were noted after a disc replacement surgery, the lumbar ROM was not modified. Nevertheless, a significant increase in the hip ROM during the flexion-extension task as well as an increase in ES muscle activity in flexion was observed following surgery. The VAS, FABQ I and ODQ scores were positively correlated with change in the muscular activities during the FRP

STarT Back Tool risk stratification is associated with changes in movement profile and sensory discrimination in low back pain: A study of 290 patients

Background: Investigation of movement and sensory profiles across STarT Back risk subgroups. Methods: A chronic low back pain cohort (n = 290) were classified as low, medium or high risk using the STarT Back Tool, and completed a repeated spinal bending task and quantitative sensory testing. Pain summation, time taken and the number of protective behaviours with repeated bending were measured. Sensory tests included two-point discrimination, temporal summation, pressure/thermal pain thresholds and conditioned pain modulation. Subgroups were profiled against movement and sensory variables. Results: The high-risk subgroup demonstrated greater pain summation following repeated forward bending (p &lt; 0.001). The medium-risk subgroup demonstrated greater pain summation following repeated backward bending (p = 0.032). Medium- and high-risk subgroups demonstrated greater forward/backward bend time compared to the low-risk subgroup (p = 0.001, p = 0.005, respectively). Medium- and high-risk subgroups demonstrated a higher number of protective behaviours per forward bend compared to the low-risk subgroup (p = 0.008). For sensory variables, only two-point discrimination differed between subgroups, with medium- and high-risk subgroups demonstrating higher thresholds (p = 0.016). Conclusions: This study showed altered movement characteristics and sensory discrimination across SBT risk subgroups in people with CLBP. Membership of the high SBT risk subgroup was associated with greater pain and disability levels, greater pain summation following repeated bending, slower bending times, a greater number of protective behaviours during forward bending, and a higher TPD threshold. Treatment outcomes for higher risk SBT subgroups may be enhanced by interventions specifically targeting movement and sensory alterations. Significance: In 290 people with chronic low back pain movement profile and two-point discrimination threshold differed across risk subgroups defined by the STarT Back Tool. Conversely, pain sensitivity did not differ across these subgroups. These findings may add further guidance for targeted care in these subgroups

The silence of self-knowledge

Gareth Evans famously affirmed an explanatory connection between answering the question whether p and knowing whether one believes that p. This is commonly interpreted in terms of the idea that judging that p constitutes an adequate basis for the belief that one believes that p. This paper formulates and defends an alternative, more modest interpretation, which develops from the suggestion that one can know that one believes that p in judging that p

Dysregulation of Connexin expression plays a pivotal role in psoriasis

Background: Psoriasis, a chronic inflammatory disease affecting 2–3% of the population, is characterised by epidermal hyperplasia, a sustained pro-inflammatory immune response and is primarily a T-cell driven disease. Previous work determined that Connexin26 is upregulated in psoriatic tissue. This study extends these findings. Methods: Biopsies spanning psoriatic plaque (PP) and non-involved tissue (PN) were compared to normal controls (NN). RNA was isolated and subject to real-time PCR to determine gene expression profiles, including GJB2/CX26, GJB6/CX30 and GJA1/CX43. Protein expression was assessed by immunohistochemistry. Keratinocytes and fibroblasts were isolated and used in 3D organotypic models. The pro-inflammatory status of fibroblasts and 3D cultures was assessed via ELISA and RnD cytokine arrays in the presence or absence of the connexin channel blocker Gap27. Results: Connexin26 expression is dramatically enhanced at both transcriptional and translational level in PP and PN tissue compared to NN (&gt;100x). In contrast, CX43 gene expression is not affected, but the protein is post-translationally modified and accumulates in psoriatic tissue. Fibroblasts isolated from psoriatic patients had a higher inflammatory index than normal fibroblasts and drove normal keratinocytes to adopt a “psoriatic phenotype” in a 3D-organotypic model. Exposure of normal fibroblasts to the pro-inflammatory mediator peptidoglycan, isolated from Staphylococcus aureus enhanced cytokine release, an event protected by Gap27. Conclusion: dysregulation of the connexin26:43 expression profile in psoriatic tissue contributes to an imbalance of cellular events. Inhibition of connexin signalling reduces pro-inflammatory events and may hold therapeutic benefit

Chronic low back pain clinical outcomes present higher associations with the STarT Back Screening Tool than with physiologic measures: a 12-month cohort study

Stratification strategies based on identifying patient's prognosis in order to guide patient care constitute one of the most prominent and recent approach in low back pain research. The STarT Back Screening Tool (SBST) although promising, has not been studied in patients with chronic low back pain (cLBP). Considering how challenging it is to translate research into practice, the value of integrating a new tool should be thoroughly assessed. The purpose was therefore to assess associations between the short- and long-terms clinical status and two types of variables, physiologic measures and the SBST, in participants with cLBP. The ability of both types of variables to discriminate between participants with and without higher levels of disability, pain, fear of movement and patient's global impression of change was also investigated