Motor control or graded activity exercises for chronic low back pain? A randomised controlled trial

Background: Chronic low back pain remains a major health problem in Australia and around the world. Unfortunately the majority of treatments for this condition produce small effects because not all patients respond to each treatment. It appears that only 25-50% of patients respond to exercise. The two most popular types of exercise for low back pain are graded activity and motor control exercises. At present however, there are no guidelines to help clinicians select the best treatment for a patient. As a result, time and money are wasted on treatments which ultimately fail to help the patient

The differential effects of core stabilization exercise regime and conventional physiotherapy regime on postural control parameters during perturbation in patients with movement and control impairment chronic low back pain

<p>Abstract</p> <p>Background</p> <p>The purpose of the present study was to examine the differential effect of core stability exercise training and conventional physiotherapy regime on altered postural control parameters in patients with chronic low back pain (CLBP). As heterogeneity in CLBP population moderates the effect of intervention on outcomes, in this study, interventions approaches were used based on sub-groups of CLBP.</p> <p>Methods</p> <p>This was an allocation concealed, blinded, sequential and pragmatic control trial. Three groups of participants were investigated during postural perturbations: 1) CLBP patients with movement impairment (n = 15, MI group) randomized to conventional physiotherapy regime 2) fifteen CLBP patients with control impairment randomized to core stability group (CI group) and 3) fifteen healthy controls (HC).</p> <p>Results</p> <p>The MI group did not show any significant changes in postural control parameters after the intervention period however they improved significantly in disability scores and fear avoidance belief questionnaire work score (P < 0.05). The CI group showed significant improvements in Fx, Fz, and My variables (p < 0.013, p < 0.006, and p < 0.002 respectively with larger effect sizes: Hedges's g > 0.8) after 8 weeks of core stability exercises for the adjusted p values. Postural control parameters of HC group were analyzed independently with pre and post postural control parameters of CI and MI group. This revealed the significant improvements in postural control parameters in CI group compared to MI group indicating the specific adaptation to the core stability exercises in CI group. Though the disability scores were reduced significantly in CI and MI groups (p < 0.001), the post intervention scores between groups were not found significant (p < 0.288). Twenty percentage absolute risk reduction in flare-up rates during intervention was found in CI group (95% CI: 0.69-0.98).</p> <p>Conclusions</p> <p>In this study core stability exercise group demonstrated significant improvements after intervention in ground reaction forces (Fz, Mz; g > 0.8) indicating changes in load transfer patterns during perturbation similar to HC group.</p> <p>Trial registration</p> <p>UTRN095032158-06012009423714</p

Phytophthora species and oak decline - can a weak competitor cause significant root damage in a nonsterilized acidic forest soil?

Phytophthora species in general, and P. quercina in particular, have been suggested in several studies to be a contributing factor to the problem of oak decline in Europe. Although Phytophthora species are generally regarded as weak competitors, few studies of the pathogenicity of species causing root rot on oaks have hitherto been performed in natural, nonsterilized forest soils. This study describes the effects of seven southern Swedish isolates of P. quercina and one isolate of P. cactorum on root vitality of Quercus robur seedlings grown in a natural, nonsterilized, acidic forest soil. The pathogenicity of P. quercina and P. cactorum were tested using a soil infestation test. The climatic conditions applied were an attempt to simulate summer conditions in southern Sweden. Both species of Phytophthora caused a significant dieback of fine roots, and necrotic lesions on coarser roots, of Q. robur seedlings. Total and live root lengths were significantly lower in infected seedlings than in controls. No significant effects of Phytophthora on above-ground growth or leaf nutrient concentration were found. The results demonstrate that P. quercina and P. cactorum can cause substantial root dieback of seedlings of Q. robur in natural, acidic forest soils in competition with the inhabiting soil microflora under a mesic water regime

Upper limb impairments associated with spasticity in neurological disorders

<p>Abstract</p> <p>Background</p> <p>While upper-extremity movement in individuals with neurological disorders such as stroke and spinal cord injury (SCI) has been studied for many years, the effects of spasticity on arm movement have been poorly quantified. The present study is designed to characterize the nature of impaired arm movements associated with spasticity in these two clinical populations. By comparing impaired voluntary movements between these two groups, we will gain a greater understanding of the effects of the type of spasticity on these movements and, potentially a better understanding of the underlying impairment mechanisms.</p> <p>Methods</p> <p>We characterized the kinematics and kinetics of rapid arm movement in SCI and neurologically intact subjects and in both the paretic and non-paretic limbs in stroke subjects. The kinematics of rapid elbow extension over the entire range of motion were quantified by measuring movement trajectory and its derivatives; i.e. movement velocity and acceleration. The kinetics were quantified by measuring maximum isometric voluntary contractions of elbow flexors and extensors. The movement smoothness was estimated using two different computational techniques.</p> <p>Results</p> <p>Most kinematic and kinetic and movement smoothness parameters changed significantly in paretic as compared to normal arms in stroke subjects (p < 0.003). Surprisingly, there were no significant differences in these parameters between SCI and stroke subjects, except for the movement smoothness (p ≤ 0.02). Extension was significantly less smooth in the paretic compared to the non-paretic arm in the stroke group (p < 0.003), whereas it was within the normal range in the SCI group. There was also no significant difference in these parameters between the non-paretic arm in stroke subjects and the normal arm in healthy subjects.</p> <p>Conclusion</p> <p>The findings suggest that although the cause and location of injury are different in spastic stroke and SCI subjects, the impairments in arm voluntary movement were similar in the two spastic groups. Our results also suggest that the non-paretic arm in stroke subjects was not distinguishable from the normal, and might therefore be used as an appropriate control for studying movement of the paretic arm.</p

Clinical implications of novel activating EGFR mutations in malignant peritoneal mesothelioma

<p>Abstract</p> <p>Background</p> <p>There is a paucity of information about the molecular perturbations involved in MPM tumor formation. We previously reported that EGFR-TK mutations in MPM were predictive of achieving optimal surgical cytoreduction, but the status of EGFR pathway activation potential of these mutations was not known. Here we present the mutant EGFR activating potential and the matured survival data of the EGFR mutant(mut+) relative to wild type EGFR(mut-) mesothelioma.</p> <p>Methods</p> <p>Twenty-nine patients were evaluated and their tumors were probed for mutations in the catalytic TK-domain. Twenty-five patients were treated with cytoreductive surgery and complete clinical data was available for comparison of the mut+ and mut- groups. A COS-7 cell expression model was used to determine mutation activating profiles and response to erlotinib.</p> <p>Results</p> <p>Functional mutations were found in 31%(9/29) of patients; 7 of these mutations were novel and another was the L858R mutation. All missense mutations were found to be activating mutations and responsive to erlotinib. Of the 25 patients managed surgically, there were 7 mut+ and 18 mut-. Two of 7 (29%) mut+ developed progressive disease and died with a median follow-up time of 22 months; while 13/18 (72%) mut- developed progressive disease and 10/18 (56%) died with median TTP of 12 months and median survival of 14 months.</p> <p>Conclusions</p> <p>The novel EGFR mutations identified are activating mutations responsive to erlotinib. The mut+ subset have a 'relative' improved outcome. Erlotinib may have a role in MPM and exploration for mutations in a larger patient cohort is warranted.</p

Get Phases from Arsenic Anomalous Scattering: de novo SAD Phasing of Two Protein Structures Crystallized in Cacodylate Buffer

The crystal structures of two proteins, a putative pyrazinamidase/nicotinamidase from the dental pathogen Streptococcus mutans (SmPncA) and the human caspase-6 (Casp6), were solved by de novo arsenic single-wavelength anomalous diffraction (As-SAD) phasing method. Arsenic (As), an uncommonly used element in SAD phasing, was covalently introduced into proteins by cacodylic acid, the buffering agent in the crystallization reservoirs. In SmPncA, the only cysteine was bound to dimethylarsinoyl, which is a pentavalent arsenic group (As (V)). This arsenic atom and a protein-bound zinc atom both generated anomalous signals. The predominant contribution, however, was from the As anomalous signals, which were sufficient to phase the SmPncA structure alone. In Casp6, four cysteines were found to bind cacodyl, a trivalent arsenic group (As (III)), in the presence of the reducing agent, dithiothreitol (DTT), and arsenic atoms were the only anomalous scatterers for SAD phasing. Analyses and discussion of these two As-SAD phasing examples and comparison of As with other traditional heavy atoms that generate anomalous signals, together with a few arsenic-based de novo phasing cases reported previously strongly suggest that As is an ideal anomalous scatterer for SAD phasing in protein crystallography

Epstein-Barr Virus-Encoded LMP1 Interacts with FGD4 to Activate Cdc42 and Thereby Promote Migration of Nasopharyngeal Carcinoma Cells

Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC), a human malignancy notorious for its highly metastatic nature. Among EBV-encoded genes, latent membrane protein 1 (LMP1) is expressed in most NPC tissues and exerts oncogenicity by engaging multiple signaling pathways in a ligand-independent manner. LMP1 expression also results in actin cytoskeleton reorganization, which modulates cell morphology and cell motility— cellular process regulated by RhoGTPases, such as Cdc42. Despite the prominent association of Cdc42 activation with tumorigenesis, the molecular basis of Cdc42 activation by LMP1 in NPC cells remains to be elucidated. Here using GST-CBD (active Cdc42-binding domain) as bait in GST pull-down assays to precipitate active Cdc42 from cell lysates, we demonstrated that LMP1 acts through its transmembrane domains to preferentially induce Cdc42 activation in various types of epithelial cells, including NPC cells. Using RNA interference combined with re-introduction experiments, we identified FGD4 (FYVE, RhoGEF and PH domain containing 4) as the GEF (guanine nucleotide exchange factor) responsible for the activation of Cdc42 by LMP1. Serial deletion experiments and co-immunoprecipitation assays further revealed that ectopically expressed FGD4 modulated LMP1-mediated Cdc42 activation by interacting with LMP1. Moreover, LMP1, through its transmembrane domains, directly bound FGD4 and enhanced FGD4 activity toward Cdc42, leading to actin cytoskeleton rearrangement and increased motility of NPC cells. Depletion of FGD4 or Cdc42 significantly reduced (∼50%) the LMP1-stimulated cell motility, an effect that was partially reversed by expression of a constitutively active mutant of Cdc42. Finally, quantitative RT-PCR and immunohistochemistry analyses showed that FGD4 and LMP1 were expressed in NPC tissues, supporting the potential physiologically relevance of this mechanism in NPC. Collectively, our results not only uncover a novel mechanism underlying LMP1-mediated Cdc42 activation, namely LMP1 interaction with FGD4, but also functionally link FGD4 to NPC tumorigenesis

A randomised controlled trial among cleaners-Effects on strength, balance and kinesiophobia

<p>Abstract</p> <p>Background</p> <p>Cleaners constitute a job group with poor health and low socioeconomic resources. Therefore, there is a great need for scientifically documented health promoting initiatives for cleaners. However, both workplace initiatives and high quality intervention studies are lacking. The aim of this study was to evaluate the effects of a 3-month workplace trial with interventions to improve physical or cognitive behavioural resources among cleaners.</p> <p>Methods</p> <p>A cluster randomised controlled trial was conducted among 294 female cleaners from 9 workplaces. The participants were allocated to three groups: Physical coordination training (PCT, n = 95), Cognitive behavioural theory-based training (CBTr, n = 99) and Reference group (REF, n = 100). Interventions were conducted during work hours for an average of 1 hour/week. Muscle strength was measured by maximal voluntary contractions in trunk/extension, and shoulder abduction/elevation. Postural balance was measured on a force platform. Kinesiophobia was measured with Tampa Scale for Kinesiophobia. Test and questionnaires were completed at baseline and at 3-month follow-up and analyses followed the intention-to-treat (ITT) principle with last observation carried forward in case of missing data at follow-up. Reports and analyses are given on true observations as well.</p> <p>Results</p> <p>ITT-analyses revealed that PCT improved strength of the trunk (p < .05) and postural balance (p < .05) compared to CBTr and REF. Based on true observations the strength and balance improvements corresponded to ~20% and ~16%, respectively. ITT-analyses showed that CBTr reduced kinesiophobia compared to PCT and REF (p < .05). Based on true observations, the improvement corresponded to a ~16% improvement.</p> <p>Conclusion</p> <p>This workplace-based intervention study including PCT and CBTr among cleaners improved strength and postural balance from PCT, and kinesiophobia from CBTr. The improved strength, postural balance and kinesiophobia may improve the cleaners' tolerance for high physical work demands. Future studies should investigate the potential in the combination of PCT and CBTr in a workplace intervention.</p> <p>Trial registration</p> <p>Current controlled trials <a href="http://www.controlled-trials.com/ISRCTN96241850">ISRCTN96241850</a></p

Response of Quercus ilex seedlings to Phytophthora spp. root infection in a soil infestation test

[EN] Phytophthora species are the main agents associated with oak (Quercus spp.) decline, together with the changing environmental conditions and the intensive land use. The aim of this study was to evaluate the susceptibility of Quercus ilex to the inoculation with eight Phytophthora species. Seven to eight month old Q. ilex seedlings grown from acorns, obtained from two Spanish origins, were inoculated with P. cinnamomi, P. cryptogea, P. gonapodyides, P. megasperma, P. nicotianae, P. plurivora, P. psychrophila and P. quercina. All Phytophthora inoculated seedlings showed decline and symptoms including small dark necrotic root lesions, root cankers, and loss of fine roots and tap root. The most aggressive species were P. cinnamomi, P. cryptogea, P. gonapodyides, P. plurivora and P. psychrophila followed by P. megasperma., while Phytophthora quercina and P. nicotianae were the less aggressive species. 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Activity of the multikinase inhibitor dasatinib against ovarian cancer cells

BackgroundHere, we explore the therapeutic potential of dasatinib, a small-molecule inhibitor that targets multiple cytosolic and membrane-bound tyrosine kinases, including members of the Src kinase family, EphA2, and focal adhesion kinase for the treatment of ovarian cancer.MethodsWe examined the effects of dasatinib on proliferation, invasion, apoptosis, cell-cycle arrest, and kinase activity using a panel of 34 established human ovarian cancer cell lines. Molecular markers for response prediction were studied using gene expression profiling. Multiple drug effect/combination index (CI) isobologram analysis was used to study the interactions with chemotherapeutic drugs.ResultsConcentration-dependent anti-proliferative effects of dasatinib were seen in all ovarian cancer cell lines tested, but varied significantly between individual cell lines with up to a 3 log-fold difference in the IC(50) values (IC(50) range: 0.001-11.3 micromol l(-1)). Dasatinib significantly inhibited invasion, and induced cell apoptosis, but less cell-cycle arrest. At a wide range of clinically achievable drug concentrations, additive and synergistic interactions were observed for dasatinib plus carboplatin (mean CI values, range: 0.73-1.11) or paclitaxel (mean CI values, range: 0.76-1.05). In this study, 24 out of 34 (71%) representative ovarian cancer cell lines were highly sensitive to dasatinib, compared with only 8 out of 39 (21%) representative breast cancer cell lines previously reported. Cell lines with high expression of Yes, Lyn, Eph2A, caveolin-1 and 2, moesin, annexin-1, and uPA were particularly sensitive to dasatinib.ConclusionsThese data provide a clear biological rationale to test dasatinib as a single agent or in combination with chemotherapy in patients with ovarian cancer