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Background: Reduced ankle dorsiflexion is associated with lower limb injury and dysfunction, with static stretching mostly used to increase ankle range of motion. Foam rolling is an alternative intervention, shown to immediately increase ankle range of motion, while the long-term application has conflicting evidence., Aims: To assess the effects of single and multiple foam rolling interventions on ankle dorsiflexion range of motion in healthy adults and appraise the methodological quality of the included studies., Design: Systematic literature review., Methods: Five electronic databases were systematically searched to identify randomised controlled trials reporting the effects of foam rolling on ankle dorsiflexion. Data was extracted from studies that met the inclusion criteria and independently appraised by each reviewer using the PEDro scale., Results: Thirty-two articles were identified; six studies included foam rolling compared to other interventions on ankle dorsiflexion range of motion. Five of the six studies reported a significant increase (p < 0.05) in ankle dorsiflexion within groups compared to baseline measurements, after a single foam rolling intervention. One study found a significant within group increase in long-term effects after foam rolling on ankle dorsiflexion over seven weeks. The mean PEDro score for all studies was 6/10 indicating a high-quality level of evidence., Conclusion: There is strong evidence suggesting that foam rolling may be effective in increasing range of motion in a healthy adult population in the short term up to 30 min; however, definitive conclusions on long-term effects cannot be drawn due to a lack of evidence, with further research recommended., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Congenital facial palsy is a rare medical condition that causes paralysis of the facial muscles, lack of facial expression, and an unusual appearance. Findings from developmental psychology suggest that the face plays a central role in the construction of self. Semi-structured interviews were conducted with 14 adults born with congenital facial palsy. Participant's constructions of self across the life span were explored and a grounded theory of this process was constructed. Theoretical sampling was conducted with two parents of children born with the condition. All participants reported "struggling to make connections," "experiencing invalidation," and "struggling to regulate affect," which lead to "constructing a defective sense of self." Alternatively, "making validating connections" facilitated the process of "constructing a validated sense of self." This study provides insight into the unique social and emotional challenges often experienced by those born with congenital facial palsy and highlights the need for early psychosocial intervention.

Background: Anisantha and Bromus spp. are widespread and difficult to control, potentially due to the evolution of herbicide resistance. In this study, UK populations of four brome species have been tested for the early development of resistance to acetolactate synthase (ALS)-inhibiting herbicides commonly used in their control., Results: Glasshouse assays confirmed reduced sensitivity to ALS-inhibiting herbicides in single populations of A. diandra, B. commutatus and B. secalinus, and in three populations of A. sterilis. By contrast, all 60 brome populations tested were sensitive to the ACCase-inhibiting herbicide propaquizafop and glyphosate. Dose-response with two ALS herbicides showed broad-ranging resistance in the A. diandra, A. sterilis and B. commutatus populations. In the B. commutatus population, this was associated with a point mutation in the ALS enzyme conferring target site resistance (TSR). Additionally, resistant populations of A. sterilis and B. commutatus populations contained enhanced amounts of an orthologue of the glutathione transferase phi (F) class 1 (GSTF1) protein, a functional biomarker of nontarget site resistance (NTSR) in Alopecurus myosuroides. There was further evidence of NTSR as these plants also demonstrated an enhanced capacity to detoxify herbicides., Conclusion: This study confirms the evolution of resistance to ALS inhibiting herbicides in brome species in the UK by mechanisms consistent with the evolution of both TSR and NTSR. These findings point to the need for increased vigilance in detecting and mitigating against the evolution of herbicide resistance in brome species in Northern Europe. © 2020 Society of Chemical Industry., (© 2020 Society of Chemical Industry.)

Objective: This study examined clinicians' views of the roles of two elements of cognitive behavioral therapy (CBT) in explaining treatment outcomes-CBT techniques and the therapeutic alliance., Method: Ninety-eight clinicians who reported delivering CBT for eating disorders completed measures addressing their beliefs about what is effective in CBT, their use of specific techniques, and their own anxiety levels., Results: Clinicians substantially overestimated the role of both therapeutic techniques and the alliance in explaining treatment outcomes in CBT. Weak but significant correlations were found between therapist anxiety levels and their beliefs about the value of therapeutic techniques or the alliance. However, these associations were in different directions, with higher levels of clinician anxiety associated with more belief in the effects of the alliance but with less belief in the role of CBT techniques. Belief in the role of the therapeutic alliance was associated with a lower likelihood of encouraging the patient to change their eating pattern, while belief in the role of techniques was linked to greater use of case formulation, cognitive restructuring, behavioral experiments and body image work., Discussion: Clinicians overestimate the value of both the alliance and therapy techniques in explaining treatment outcomes in CBT for eating disorders. Their beliefs about the strength of these factors are related to their own anxiety, and to their choice of techniques. Clinicians and supervisors should attend to the evidence regarding the impact of a range of elements of therapy, and work with all of those factors to enhance outcomes., (© 2019 Wiley Periodicals, Inc.)

Background/aims: Multiple sclerosis (MS) is one of the most common autoimmune disorders of the central nervous system (CNS) and the leading cause of neurological disability among young adults in the Western world. We have previously shown that the acid sphingomyelinase plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis., Methods: We induced adoptively transferred EAE in wildtype and acid sphingomyelinase-deficient mice. In addition, we immunized mice with MOG aa35-55 to induce active EAE and treated the mice with amitriptyline, a functional inhibitor of the acid sphingomyelinase. We investigated symptoms of EAE, blood-brain barrier integrity and neuroinflammation., Results: In the model of adoptively transferred EAE we demonstrate that expression of acid sphingomyelinase in the recipients rather than on transferred encephalitogenic T cells contributes to the clinical development of EAE symptoms. To test if pharmacological targeting of acid sphingomyelinase can be explored for the development of novel therapies for MS, we inhibited acid sphingomyelinase with amitriptyline in mice in which EAE was induced by active immunization. We demonstrate that pharmacological inhibition of acid sphingomyelinase using amitriptyline protects against the development of EAE and markedly attenuates the characteristic detrimental neuroinflammatory response., Conclusion: The studies identify the acid sphingomyelinase as a novel therapeutic target for treating MS patients., Competing Interests: The authors declare to have no conflict of interests., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

Background: Multiple sclerosis (MS) is a severe and common autoimmune disorder of the central nervous system. Despite the availability of several novel treatment options, the disease is still poorly controlled, since the pathophysiological mechanisms are not fully understood., Methods: We tested the role of the acid sphingomyelinase/ceramide system in a model of MS, i.e. experimental autoimmune encephalomyelitis (EAE). Mice were immunized with myelin-oligodendrocyte glycoprotein and the development of the disease was analyzed by histology, immunological tests and clinical assessment in wildtype and acid sphingomyelinase (Asm)-deficient mice., Results: Genetic deficiency of acid sphingomyelinase (Asm) protected against clinical symptoms in EAE and markedly attenuated the characteristic detrimental neuroinflammatory response. T lymphocyte adhesion, integrity of tight junctions, blood-brain barrier disruption and subsequent intracerebral infiltration of inflammatory cells were blocked in Asm-deficient mice after immunization. This resulted in an almost complete block of the development of disease symptoms in these mice, while wildtype mice showed severe neurological symptoms typical for EAE., Conclusion: Activation of the Asm/ceramide system is a central step for the development of EAE. Our findings may serve to identify novel therapeutic strategies for MS patients., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

Background: Low back pain (LBP) is the world's leading cause of disability and yet poorly understood. Cross-national comparisons may motivate hypotheses about outcomes being condition-specific or related to cultural differences and can inform whether observations from one country may be generalised to another. This analysis of data from three cohort studies explored whether characteristics and outcomes differed between LBP patients visiting chiropractors in Sweden, Denmark and the UK., Methods: LBP patients completed a baseline questionnaire and were followed up after 3, 5, 12 and 26 weeks. Outcomes were LBP intensity (0-10 scales) and LBP frequency (0-7 days the previous week). Cohort differences were tested in mixed models accounting for repeated measures. It was investigated if any differences were explained by different baseline characteristics, and interaction terms between baseline factors and nations tested if strength of prognostic factors differed across countries., Results: The study sample consisted of 262, 947 and 453 patients from Sweden, Denmark and the UK respectively. Patient characteristics were largely similar across cohorts although some statistically significant differences were observed. The clinical course followed almost identical patterns across nations and small observed differences were not present after adjusting for baseline factors. The associations of LBP intensity and episode duration with outcome differed in strength between countries., Conclusions: Chiropractic patients with low back pain had similar characteristics and clinical course across three Northern European countries. It is unlikely that culture have substantially different impacts on the course of LBP in these countries and the results support knowledge transfer between the investigated countries.

Key Message: Functional characterization of the Columbia root-knot nematode resistance gene R Mc1 ( blb ) in potato revealed the R gene-mediated resistance is dependent on a hypersensitive response and involves calcium. The resistance (R) gene R Mc1(blb) confers resistance against the plant-parasitic nematode, Meloidogyne chitwoodi. Avirulent and virulent nematodes were used to functionally characterize the R Mc1(blb)-mediated resistance mechanism in potato (Solanum tuberosum). Histological observations indicated a hypersensitive response (HR) occurred during avirulent nematode infection. This was confirmed by quantifying reactive oxygen species activity in response to avirulent and virulent M. chitwoodi. To gain an insight into the signal transduction pathways mediating the R Mc1(blb)-induced HR, chemical inhibitors were utilized. Inhibiting Ca(2+) channels caused a significant reduction in electrolyte leakage, an indicator of cell death. Labeling with a Ca(2+)-sensitive dye revealed high Ca(2+) levels in the root cells surrounding avirulent nematodes. Furthermore, the calcium-dependent protein kinase (CDPK), StCDPK4 had a higher transcript level in R Mc1(blb) potato roots infected with avirulent nematodes in comparison to roots infected with virulent M. chitwoodi. The results of this study indicate Ca(2+) plays a role in the R Mc1(blb)-mediated resistance against M. chitwoodi in potato.

A fluorescent tridentate phosphine, BodP3 (2), forms rhenium complexes which effectively image cancer cells. Related technetium analogues are also readily prepared and have potential as dual SPECT/fluorescent biological probes.

The syntheses of highly fluorescent analogues of PPh3 and PhPCy2 based on the Bodipy chromophore are described. The ligands have been incorporated into two- to four-coordinate group 11 metal complexes. The synthesis, characterisation and photophysical properties of the novel ligands and their metal complexes are reported; many of these compounds have also been characterised by single-crystal X-ray diffraction. Incorporation of the phosphino group and complexation to the group 11 metal centre has little effect on the absorption and emission profiles; high molar extinction coefficients and fluorescence quantum yields were still obtained. In particular, incorporation of the dicyclohexylphosphino substituent significantly increases the quantum yields relative to the parent dyes.

Sphingolipids, the main component of cellular membranes, are cellular 'jack-of-all-trades', influencing a variety of functions including signal transduction, cell activation, membrane fluidity and cell-cell interactions.In the last few years, sphingolipids have begun to be investigated in the pathophysiology of major diseases of the brain, e.g. multiple sclerosis and dementia. Modulation of neuroinflammatory responses, such as lymphocyte behaviour, is a chance to intervene in the pathways that cause disease. There is much research still to be done in this field, but the prospect of treating previously untreatable medical conditions compels us onwards. Here, we review the current knowledge of the link between sphingolipids and neuroinflammation.

The activity of the glucocorticoid receptor (GR) is modulated by posttranslational modifications, protein stability, and cofactor recruitment. In this report, we investigated the role of the stress-responsive activator of p300/tetratricopeptide repeat domain 5 (TTC5), in the regulation of the GR. TTC5 is a member of the TTC family of proteins and has previously been shown to participate in the cellular response to DNA damage and heat shock. Here, we demonstrate that TTC5 is an important cofactor for the nuclear hormone receptors GR and estrogen receptor. GR and TTC5 interact through multiple tetratricopeptide repeat and LXXLL motifs. TTC5 stabilizes GR and increases its half-life, through a proteasome-dependent process and by inhibiting the actions of the ubiquitin ligase murine double minute 2. Cellular stress, including DNA damage, proteasome inhibition, and heat shock, modulates the interaction pattern of GR/TTC5, thereby altering GR stability and transcriptional activity. Furthermore, GR transcriptional activity is regulated by TTC5 in both a positive and negative fashion under DNA damage conditions in a target gene-specific way. In this report we provide evidence supporting the notion that TTC5 is a novel cofactor regulating GR function in a stress-dependent manner.

Several posttranslational modifications including phosphorylation have been detected on the glucocorticoid receptor (GR). However, the interdependence and combinatorial regulation of these modifications and their role in GR functions are poorly understood. We studied the effects of c-Jun N-terminal kinase (JNK)-dependent phosphorylation of GR on its sumoylation status and the impact that these modifications have on GR transcriptional activity. GR is targeted for phosphorylation at serine 246 (S246) by the JNK protein family in a rapid and transient manner. The levels of S246 phosphorylation of endogenous GR increased significantly in cells treated with UV radiation that activates JNK. S246 GR phosphorylation by JNK facilitated subsequent GR sumoylation at lysines 297 and 313. GR sumoylation increased with JNK activation and was inhibited in cells treated with JNK inhibitor. GR sumoylation in cells with activated JNK was mediated preferentially by small ubiquitin-like modifier (SUMO)2 rather than SUMO1. An increase in GR transcriptional activity was observed after inhibition of JNK or SUMO pathways and suppression of GR transcriptional activity after activation of both pathways in cells transfected with GR-responsive reporter genes. Endogenous GR transcriptional activity was inhibited on endogenous target genes IGF binding protein (IGFBP) and glucocorticoid-induced leucine zipper (GILZ) when JNK and SUMO pathways were induced individually or simultaneously. Activation of both of these signals inhibited GR-mediated regulation of human inhibitor of apoptosis gene (hIAP), whereas simultaneous activation had no effect. We conclude that phosphorylation aids GR sumoylation and that cross talk of JNK and SUMO pathways fine tune GR transcriptional activity in a target gene-specific manner, thereby modulating the hormonal response of cells exposed to stress.