The human phosphotyrosine signaling network: Evolution and hotspots of hijacking in cancer

Phosphotyrosine (pTyr) signaling, which plays a central role in cell-cell and cell-environment interactions, has been considered to be an evolutionary innovation in multicellular metazoans. However, neither the emergence nor the evolution of the human pTyr signaling system is currently understood. Tyrosine kinase (TK) circuits, each of which consists of a TK writer, a kinase substrate, and a related reader, such as Src homology (SH) 2 domains and pTyr-binding (PTB) domains, comprise the core machinery of the pTyr signaling network. In this study, we analyzed the evolutionary trajectories of 583 literature-derived and 50,000 computationally predicted human TK circuits in 19 representative eukaryotic species and assigned their evolutionary origins. We found that human TK circuits for intracellular pTyr signaling originated largely from primitive organisms, whereas the inter- or extracellular signaling circuits experienced significant expansion in the bilaterian lineage through the back- wiring of newly evolved kinases to primitive substrates and SH2/PTB domains. Conversely, the TK circuits that are involved in tissue-specific signaling evolved mainly in vertebrates by the back-wiring of vertebrate substrates to primitive kinases and SH2/PTB domains. Importantly, we found that cancer signaling preferentially employs the pTyr sites, which are linked to more TK circuits. Our work provides insights into the evolutionary paths of the human pTyr signaling circuits and suggests the use of a network approach for cancer intervention through the targeting of key pTyr sites and their associated signaling hubs in the network. © 2012, Published by Cold Spring Harbor Laboratory Press

Bekkenplager og stabiliserende øvelser - hva vet vi egentlig?

A treatment program focusing on stabilising exercises for women with pelvic girdle pain after pregnancy showed a very good and long-lasting effect. Stabilising exercises are a common exercise and treatment modality. The aim of this article is to briefly present the treatment program and to review our knowledge concerning stabilising exercises for lumbopelvic pain, further to discuss aspects that may have a positive effect on the outcome. The treatment program consisted of following elements; joint mobilisation, motor control, muscle force, body and emotional awareness. The main focus was on exercises for control and stability of the pelvis. Stabilising exercises should not be at the expense of neuromuscular control and should not cause unnecessary compression forces which could result in increased pain. How the exercises is performed is equally as important as which exercise is chosen. The treatment program should be implemented in clinical practise, but not be limited to one exercise apparatus, one technique, one method, or only to stabilising exercises

Pelvic girdle pain affects the whole life—a qualitative interview study in Norway on women’s experiences with pelvic girdle pain after delivery

Background The aim of this study was to explore how pelvic girdle pain after delivery influences women’s daily life in Norway. Knowledge about living with post-partum pelvic girdle pain is lacking. Method A phenomenological–hermeneutical design with qualitative semi-structured interviews was used. A strategic selection procedure was chosen to recruit participants from physiotherapy clinics and a regional hospital in Norway. Five women with clinically verified pelvic girdle pain after delivery were included. Data were imported into NVivo9 and analysed in three steps: naïve reading, structural analysis and comprehensive understanding of the text. Results Three themes influencing the women’s daily life were identified: 1) activity and pain, 2) lack of acknowledgment of pain and disability, and 3) changed roles. A daily life with pain and limited physical activity was difficult to accept and made some of the women feel discouraged, isolated and lonely. Despite this, the women had a positive attitude to their problems, which may have positively increased their ability to cope. The findings also revealed the importance of a reciprocal influence between the woman and her environment, and that social support was crucial. Conclusions Pelvic girdle pain may influence women’s lives for months and years after delivery. Health care professionals should appreciate and focus on the patient’s knowledge and skills. Understanding the daily experiences of women with pelvic girdle pain might help improve rehabilitation strategies for these patients

Pelvic joint fusion in patients with severe pelvic girdle pain – a prospective single-subject research design study

Background The fusion of the pelvic joints in patients with severe pelvic girdle pain (PGP) is a controversial and insufficiently studied procedure. The aims of this study were to evaluate physical function and pain after sacroiliac joint (SIJ) fusion. Methods A single-subject research design study with repeated measurements was conducted; pre-operatively and at 3, 6 and 12 months post-operatively. The outcome measures considered were the Oswestry disability index (ODI), visual analogue scale (VAS), and SF-36. Eight patients with severe PGP received open-accessed unilateral anterior SIJ fusion and fusion of the pubic symphysis. Results Seven patients reported positive results from the surgery. At 1 year post-operation, significant (p < 0.001) reductions in ODI (54 to 37) and VAS (82 to 57) were reported. The physical functioning, bodily pain, and social functioning scores in the SF-36 were also improved. Conclusion Positive and significant changes in disability and pain at 1 year after SIJ fusion were observed. Despite these positive results, open accessed anterior fusion of the SIJ was associated with adverse events and complications such as infection and nerve damage

Reliability, validity and responsiveness of pelvic floor muscle surface electromyography and manometry

Introduction and hypothesis: Vaginal surface electromyography (sEMG) is commonly used to assess pelvic floor muscle (PFM) function and dysfunction but there is a lack of studies regarding the assessment properties. The aim of the study was to test the hypotheses that sEMG has good test-retest intratester reliability, good criterion validity and is responsive to changes compared to manometry. Methods: PFM resting tone, maximum voluntary contraction (MVC) and endurance were measured in 66 women with pelvic floor dysfunction. One assessment by manometry was followed by two testing sessions with sEMG at baseline. After 4 to 42 weeks of supervised PFM strength training, 29 participants were retested with both devices. Results: Median age of the participants was 41 years (range 24-83) and parity 2 (range 0-10). Very good test-retest intratester reliability was found for all three sEMG measurements. The correlation between sEMG and manometry was moderate for vaginal resting tone (r = 0.42, n = 66, p < 0.001) and strong for MVC (r = 0.66, n = 66, p < 0.001) and endurance (r = 0.67, n = 66, p < 0.001). Following the strength training period, participants demonstrated increased MVC and endurance measured with manometry, but not with sEMG. A significant reduction in resting tone was found only with sEMG. Conclusion: sEMG is reliable and correlates well with manometry. However, sEMG is not as responsive as manometry for changes in PFM MVC and endurance. For measurement of PFM resting tone, sEMG seems more responsive than manometry, but this requires further investigation

Reliability, validity and responsiveness of pelvic floor muscle surface electromyography and manometry

Introduction and hypothesis: Vaginal surface electromyography (sEMG) is commonly used to assess pelvic floor muscle (PFM) function and dysfunction but there is a lack of studies regarding the assessment properties. The aim of the study was to test the hypotheses that sEMG has good test-retest intratester reliability, good criterion validity and is responsive to changes compared to manometry. Methods: PFM resting tone, maximum voluntary contraction (MVC) and endurance were measured in 66 women with pelvic floor dysfunction. One assessment by manometry was followed by two testing sessions with sEMG at baseline. After 4 to 42 weeks of supervised PFM strength training, 29 participants were retested with both devices. Results: Median age of the participants was 41 years (range 24-83) and parity 2 (range 0-10). Very good test-retest intratester reliability was found for all three sEMG measurements. The correlation between sEMG and manometry was moderate for vaginal resting tone (r = 0.42, n = 66, p < 0.001) and strong for MVC (r = 0.66, n = 66, p < 0.001) and endurance (r = 0.67, n = 66, p < 0.001). Following the strength training period, participants demonstrated increased MVC and endurance measured with manometry, but not with sEMG. A significant reduction in resting tone was found only with sEMG. Conclusion: sEMG is reliable and correlates well with manometry. However, sEMG is not as responsive as manometry for changes in PFM MVC and endurance. For measurement of PFM resting tone, sEMG seems more responsive than manometry, but this requires further investigation

Pregnant women’s experiences with a pelvic floor muscle training program in Nepal

Background In Nepal, pelvic floor disorders affect about 24% of the women in reproductive age whereof 10% suffer from pelvic organ prolapse (POP). Still, many do not seek health care. Strengthening exercises for the pelvic floor muscles for prevention and treatment of POP has shown strong evidence internationally, but for women in Nepal surgery is primarily offered. To amend this, a novel pelvic floor muscle training (PFMT) program for pregnant women was introduced. Objective To learn about how the PFMT-program was received by the participating women, their understanding of the importance of doing the exercises, and the constraints of daily life for performing the program. Methods A qualitative study design based on a sub-sample (N = 10) from a strategic sample (N = 235) who participated in the PFMT-program. Ten semi-structured in-depth interviews were interpreted according to a phenomenological analytical tradition. Results The 10 women were representative for the women who had participated in the PFMT-program with regard to urban residence, socioeconomic, and educational standing. The program was well received and compliance satisfactory. In line with the PFMT’s learning outcomes, the women described risk factors, showed knowledge about the pelvic floor muscles, and understood the importance of doing the exercises. They had managed to fit the exercises into their busy daily routines. Meeting peers in exercise groups and understanding from family were positive factors for compliance. Conclusion The Nepalese women appear interested in self-care and are making an effort to fit the exercises into their busy schedule. Although the communicative validity was satisfactory, the pragmatic validity cannot be generalized to women in rural areas and under less fortunate socioeconomic and educational circumstances

The effect of minimally invasive sacroiliac joint fusion compared with sham operation: study protocol of a prospective double-blinded multicenter randomized controlled trial

Background and purpose — The sacroiliac joint is increasingly recognized as a cause of pain in 15–30% of patients with low back pain. Nonoperative management is not always successful and surgical treatment with fusion of the joint is increasingly recommended. According to the literature, minimally invasive fusion reduces pain and improves function compared with nonoperative treatment. It is, however, unclear to what extent the placebo effect influences these results. Patients and methods — The trial is designed as a prospective multi-center, double-blind, randomized sham-surgery controlled trial with 2 parallel groups. 60 patients with a suspected diagnosis of sacroiliac joint pain confirmed with sacroiliac joint injection are included according to the trial inclusion criteria. Patients are randomized with a 1:1 allocation into 2 groups of 30 patients each. The primary end-point is group difference in sacroiliac joint pain intensity on the operated side at 6 months postoperatively, measured by the Numeric Rating Scale. The main objective is to examine whether there is a difference in pain reduction between patients treated with a minimally invasive fusion of the sacroiliac joint compared with patients undergoing a sham operation. Results — Unblinding occurs after the completed 6-month follow-up. The primary analysis will be performed when all patients have completed 6 months’ follow-up. Follow-ups are continued to at least 2 years postoperatively. Data from the different groups will be compared based on the “intention to treat” principle