Effect of transcutaneous electrical nerve stimulation (TENS) on knee pain and physical function in patients with symptomatic knee osteoarthritis: the ETRELKA randomized clinical trial.

OBJECTIVE: To determine the effectiveness of TENS at relieving pain and improving physical function as compared to placebo TENS, and to determine its safety, in patients with knee osteoarthritis. METHODS: Multi-centre, parallel, 1:1 randomized, double-blind, placebo-controlled clinical trial conducted in six outpatient clinics in Switzerland. We included 220 participants with knee osteoarthritis recruited between October 15, 2012, and October 15, 2014. Patients were randomized to 3 weeks of treatment with TENS (n = 108) or placebo TENS (n = 112). Our pre-specified primary endpoint was knee pain at the end of 3-weeks treatment assessed with the WOMAC pain subscale. Secondary outcome measures included WOMAC physical function subscale and safety outcomes. RESULTS: There was no difference between TENS and placebo TENS in WOMAC pain at the end of treatment (mean difference -0.06; 95%CI -0.41 to 0.29; P = 0.74), nor throughout the trial duration (P = 0.98). Subgroup analyses did not indicate an interaction between patient/treatment characteristics and treatment effect on WOMAC pain at the end of treatment (P-interaction ≥0.22). The occurrence of adverse events was similar across groups, with 10.4% and 10.6% of patients reporting events in the TENS and placebo TENS groups, respectively (P = 0.95). No relevant differences were observed in secondary outcomes. CONCLUSIONS: TENS does not improve knee osteoarthritis pain when compared to placebo TENS. Therapists should consider other potentially more effective treatment modalities to decrease knee osteoarthritis pain and facilitate strengthening and aerobic exercise. Our findings are conclusive and further trials comparing TENS and placebo TENS in this patient population are not necessary.

Effects of high-intensity exercise training on physical fitness, quality of life and treatment outcomes after oesophagectomy for cancer of the gastro-oesophageal junction: PRESET pilot study.

BACKGROUND: Treatment for cancer of the gastro-oesophageal junction (GOJ) can result in considerable and persistent impairment of physical fitness and health-related quality of life (HRQoL). This controlled follow-up study investigated the feasibility and safety of postoperative exercise training. METHODS: Patients with stage I-III GOJ cancer were allocated to 12 weeks of postoperative concurrent aerobic and resistance training (exercise group) or usual care (control group). Changes in cardiorespiratory fitness, muscle strength and HRQoL were evaluated. Adherence to adjuvant chemotherapy, hospitalizations and 1-year overall survival were recorded to assess safety. RESULTS: Some 49 patients were studied. The exercise group attended a mean of 69 per cent of all prescribed sessions. After exercise, muscle strength and cardiorespiratory fitness were increased and returned to pretreatment levels. At 1-year follow-up, the exercise group had improved HRQoL (+13·5 points, 95 per cent c.i. 2·2 to 24·9), with no change in the control group (+3·7 points, -5·9 to 13·4), but there was no difference between the groups at this time point (+9·8 points, -5·1 to 24·8). Exercise was safe, with no differences in patients receiving adjuvant chemotherapy (14 of 16 versus 16 of 19; relative risk (RR) 1·04, 95 per cent c.i. 0·74 to 1·44), relative dose intensity of adjuvant chemotherapy (mean 57 versus 63 per cent; P = 0·479), hospitalization (7 of 19 versus 6 of 23; RR 1·41, 0·57 to 3·49) or 1-year overall survival (80 versus 79 per cent; P = 0·839) for exercise and usual care respectively. CONCLUSION: Exercise in the postoperative period is safe and may have the potential to improve physical fitness in patients with GOJ cancer. No differences in prognostic endpoints or HRQoL were observed. Registration number: NCT02722785 ( https://www.clinicaltrials.gov).

ANTECEDENTES: El tratamiento del cáncer de la unión gastroesofágica (gastroesophageal junction, GEJ) puede determinar un deterioro considerable y persistente de la condición física y de la calidad relacionada con la salud (health-related quality of life, HRQoL). El objetivo de este estudio controlado de seguimiento fue investigar la factibilidad y seguridad del entrenamiento físico postoperatorio. MÉTODOS: Pacientes con cáncer de GEJ en estadio I-III fueron asignados a 12 semanas de entrenamiento postoperatorio simultáneo aeróbico y de resistencia o a cuidados médicos habituales. Se evaluaron los cambios en el estado cardiorrespiratoria, fuerza muscular y HRQoL. Se recogieron datos de la adherencia a la quimioterapia adyuvante, hospitalizaciones y supervivencia global a 1 año para evaluar la seguridad. RESULTADOS: Se estudiaron un total de 49 pacientes. El grupo con ejercicio asistió al 69% de todas las sesiones planificadas. Después del ejercicio, la fuerza muscular y el estado cardiorrespiratorio aumentaron y volvieron a los niveles previos al tratamiento. Si bien al año de seguimiento, el grupo con ejercicio presentó una mejoría de la HRQoL (+13,5 puntos (i.c. del 95% 2,2 a 24,9)), sin cambios en el grupo con atención médica habitual (+3,7 puntos (i.c. del 95% −5,9 a 13,4)), no hubo diferencias entre los grupos en ese momento (+9,8 puntos (i.c. del 95% −5,1 a 24,8)). El ejercicio fue seguro, sin diferencias entre el ejercicio o la atención médica habitual en pacientes que recibían quimioterapia adyuvante 87,5% versus 84,2% (RR 1,04 (i.c. del 95% 0,74 a 1,44)), intensidad relativa de la dosis de quimioterapia adyuvante 56,8% versus 63,3% (P = 0,479), hospitalizaciones 36,8% versus 26,1% (RR 1,41 (i.c. del 95% 0,57 a 3,49)) o supervivencia global a 1 año 80,0% versus 79,3% (P = 0,839). CONCLUSIÓN: El ejercicio en el periodo postoperatorio es seguro y puede tener potencial para mejorar la condición física en pacientes con cáncer de GEJ. No se observaron diferencias en los resultados pronósticos o en la HRQoL.

Safety and feasibility of preoperative exercise training during neoadjuvant treatment before surgery for adenocarcinoma of the gastro-oesophageal junction.

Background: Neoadjuvant chemotherapy or chemoradiotherapy is used widely before tumour resection in cancer of the gastro-oesophageal junction (GOJ). Strategies to improve treatment tolerability are warranted. This study examined the safety and feasibility of preoperative exercise training during neoadjuvant treatment in these patients. Methods: Patients were allocated to a standard-care control group or an exercise group, who were prescribed standard care plus twice-weekly high-intensity aerobic exercise and resistance training sessions. The primary endpoint was the incidence of serious adverse events (SAEs) that prevented surgery, including death, disease progression or physical deterioration. Preoperative hospital admission, postoperative complications, changes in patient-reported quality of life and pathological treatment response were also recorded. In the exercise group, adherence to exercise and changes in aerobic fitness, muscle strength and body composition were measured. Results: The incidence of SAEs was not increased in the exercise group. The risk of failure to reach surgery was 5 versus 21 per cent in the control group (risk ratio (RR) 0·23, 95 per cent c.i. 0·04 to 1·29), the risk of preoperative hospital admission was 15 versus 38 per cent respectively (RR 0·39, 0·12 to 1·23) and the risk of postoperative complications was 58 versus 57 per cent (RR 1·06, 0·61 to 1·73). The exercise group attended a mean of 17·5 sessions, and improved fitness, muscle strength and Functional Assessment of Cancer Therapy - Esophageal (FACT-E) total score compared with the baseline level. Conclusion: Preoperative exercise training during neoadjuvant treatment in patients with GOJ cancer is safe and feasible, with improvements in fitness, strength and quality of life. Preoperative exercise training may be associated with a lower risk of critical SAEs that preclude surgery or result in hospitalization.

[Ultrasonographic findings for selected gastrointestinal tract diseases]. / Sonographische Befunde bei ausgewählten gastrointestinalen Erkrankungen von Hund und Katze.

OBJECTIVE: In addition to general and specific examinations, ultrasonographic and endoscopic examinations of the gastrointestinal tract may be necessary. This study aimed to determine possible relationships between the ultrasonographic and histopathological findings in the following diseases of the gastrointestinal tract: IBD (inflammatory bowel disease), FRD (food-responsive diarrhoea), ulcer and infection with GHLO (gastric Helicobacter-like organisms). MATERIAL AND METHODS: The data of 41 dogs and 19 cats were analysed. The inclusion criterion was the presence of acute or chronic gastrointestinal symptoms in patients that had also undergone the standard diagnostic tests to rule out extragastrointestinal diseases. The patients underwent ultrasonographic and endoscopic examinations of the gastrointestinal tract, and a histopathological examination of the tissue samples from the endoscopy was performed. Patients with intestinal foreign bodies, neoplasms of the gastrointestinal tract or inconclu- sive histopathological results were excluded. RESULTS: In a total of 41 dogs, 16 were diagnosed with IBD, 14 with FRD, 5 with ulceration and six with an infection with GHLO. Of the 19 cats, 12 had a diagnosis of IBD, 2 of FRD, 2 with ulceration and 3 with an infection with GHLO. In 26 dogs and 4 cats of the evaluated patients, the ultrasonographic examination did not show pathological changes, even though the patients had clinical symptoms and significant histopathological findings. However, in 14 dogs and 4 cats of the included patients, one or more pathological changes of the extragastrointestinal organs were found. In particular, cats with a diagnosis of IBD often presented lymphadenopathies (4 cats) or thickening of the zona muscularis (six cats). There were no specific ultrasonographic findings confirming an FRD or an infection with GHLO. Only 5 dogs and 1 cat without a primary diagnosis of infection with GHLO were positive for colonization with GHLO. The presence of ulcers was ultrasonographically indicated as areas showing a loss of wall layering with accumulation of gas. CONCLUSION AND CLINICAL RELEVANCE: Changes can be found during ultrasonographic examinations of patients with IBD and ulcer. However, the absence of findings in ultrasonographic examinations does not necessarily rule out serious gastrointestinal diseases. The histopathological examination still plays an important part in diagnosing the evaluated diseases.

[Automatic feeding systems for horses in group housing systems with regard to animal welfare. Part 2: Comparison of different automatic feeding systems]. / Tiergerechtheit von Futterabrufstationen in der Gruppenhaltung von Pferden. Teil 2: Abrufautomaten im Vergleich.

OBJECTIVE: Comparison with regard to animal welfare of different automatic feeding systems for hay and concentrate in group housing systems for horses using parameters of ethology and physiology. MATERIAL AND METHODS: Parameters of research comprised: duration of stay, frequency of visit, threatening behaviour with and without risk of injury, and avoiding behaviour as well as heart rate and injuries of the integument. 452 horses were observed at the feeding area of 32 run-out-sheds. Every group of horses was continuously observed following the pie chart system for 24 hours. RESULTS: The "walk-through" station significantly reduced the number of conflicts in the feeding area, whereas those systems which are appropriate for the feeding horses (feeding station with access barrier and without stimulation device by electric shock) led to a higher frequency of visits and a longer duration of stay resulting in more threatening gestures. However, the number of negative interactions in the feeding area of the feeding systems can all together be classified as relatively insignificant. The heart rate was within the physiological range (45.1 ± 12.42 beats/min) in the waiting area, but increased by approximately 20 beats/min on average within the feeding station. Some horses showed a very high heart rate (≥ 100 beats/min) while entering the feeding station, possibly stress-related. There were no injuries of the integument associated with the feeding systems. The most important factor of the observation criteria was the individual group housing system with its different dimensions, conception and management. CONCLUSION: "Walk-through" stations are better than "walk-back" stations with regard to animal welfare. Likewise, automatic feeding stations with a current-carrying stimulation device are not supportive of good welfare. The other differences between the constructions of feeding stations of present systems are probably of less importance, particularly as it was shown that the stable (management, stable area, conception) had a significant influence on the surveyed parameters. Investigations to obtain information on the cause for the sporadic occurrence of very high heart rate values should be undertaken.

AZGP1 is a tumor suppressor in pancreatic cancer inducing mesenchymal-to-epithelial transdifferentiation by inhibiting TGF-ß-mediated ERK signaling.

Epithelial-to-mesenchymal transdifferentiation (EMT) mediated by transforming growth factor-ß (TGF-ß) signaling leads to aggressive cancer progression. In this study, we identified zinc-α2-glycoprotein (AZGP1, ZAG) as a tumor suppressor in pancreatic ductal adenocarcinoma whose expression is lost due to histone deacetylation. In vitro, ZAG silencing strikingly increased invasiveness of pancreatic cancer cells accompanied by the induction of a mesenchymal phenotype. Expression analysis of a set of EMT markers showed an increase in the expression of mesenchymal markers (vimentin (VIM) and integrin-α5) and a concomitant reduction in the expression of epithelial markers (cadherin 1 (CDH1), desmoplakin and keratin-19). Blockade of endogenous TGF-ß signaling inhibited these morphological changes and the downregulation of CDH1, as elicited by ZAG silencing. In a ZAG-negative cell line, human recombinant ZAG (rZAG) specifically inhibited exogenous TGF-ß-mediated tumor cell invasion and VIM expression. Furthermore, rZAG blocked TGF-ß-mediated ERK2 phosphorylation. PCR array analysis revealed that ZAG-induced epithelial transdifferentiation was accompanied by a series of concerted cellular events including a shift in the energy metabolism and prosurvival signals. Thus, epigenetically regulated ZAG is a novel tumor suppressor essential for maintaining an epithelial phenotype.

The FGFR4 Y367C mutant is a dominant oncogene in MDA-MB453 breast cancer cells.

Mutational analysis of oncogenes is critical for our understanding of cancer development. Oncogenome screening has identified a fibroblast growth factor receptor 4 (FGFR4) Y367C mutation in the human breast cancer cell line MDA-MB453. Here, we investigate the consequence of this missense mutation in cancer cells. We show that MDA-MB453 cells harbouring the mutation are insensitive to FGFR4-specific ligand stimulation or inhibition with an antagonistic antibody. Furthermore, the FGFR4 mutant elicits constitutive phosphorylation leading to an activation of the mitogen-activated protein kinase cascade as shown by an enhanced Erk1/2 phosphorylation. Cloning and ectopic expression of the FGFR4 Y367C mutant in HEK293 cells revealed high pErk levels and enhanced cell proliferation. Based on these findings, we propose that FGFR4 may be a driver of tumour growth, particularly when highly expressed or stabilized and constitutively activated through genetic alterations. As such, FGFR4 presents an option for further mutational screening in tumours and is an attractive cancer target with the therapeutic potential.

Two-dimensional dynamics of metal nanoparticles on the surface of thin polymer films studied with coherent X rays.

X-ray photon-correlation spectroscopy is used to measure the dynamic structure factor f(q,tau) of gold particles moving on the surface of thin polymer films. Above the glass transition of the polymer the peculiar form f(q,tau) approximately exp[-(Gamma tau)(alpha)] is found with 0.7 < alpha < 1.5, depending on sample age and temperature. The relaxation rates Gamma scale linearly with q, excluding a simple Brownian diffusive motion. This type of behavior, already observed in aging bulk soft matter systems, is explained by a power law distribution of particle velocities due to ballistic motion.

FGFR4 Arg388 allele correlates with tumour thickness and FGFR4 protein expression with survival of melanoma patients.

A single nucleotide polymorphism in the gene for FGFR4 (-Arg388) has been associated with progression in various types of human cancer. Although fibroblast growth factors (FGFs) belong to the most important growth factors in melanoma, expression of FGF receptor subtype 4 has not been investigated yet. In this study, the protein expression of this receptor was analysed in 137 melanoma tissues of different progression stages by immunohistochemistry. FGFR4 protein was expressed in 45% of the specimens and correlated with pTNM tumour stages (UICC, P = 0.023 and AJCC, P = 0.046), presence of microulceration (P = 0.009), tumour vascularity (P = 0.001), metastases (P = 0.025), number of primary tumours (P = 0.022), overall survival (P = 0.047) and disease-free survival (P = 0.024). Furthermore, FGFR4 Arg388 polymorphism was analysed in 185 melanoma patients by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The Arg388 allele was detected in 45% of the melanoma patients and was significantly associated with tumour thickness (by Clark's level of invasion (P = 0.004) and by Breslow in mm (P = 0.02)) and the tumour subtype nodular melanoma (P = 0.002). However, there was no correlation of the FGFR4 Arg388 allele with overall and disease-free survival. In conclusion, the Arg388 genotype and the protein expression of FGFR4 may be potential markers for progression of melanoma.

The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification.

Homeostasis of multicellular organisms is critically dependent on the correct interpretation of the plethora of signals which cells are exposed to during their lifespan. Various soluble factors regulate the activation state of cellular receptors which are coupled to a complex signal transduction network that ultimately generates signals defining the required biological response. The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases represents both key regulators of normal cellular development as well as critical players in a variety of pathophysiological phenomena. The aim of this review is to give a broad overview of signal transduction networks that are controlled by the EGFR superfamily of receptors in health and disease and its application for target-selective therapeutic intervention. Since the EGFR and HER2 were recently identified as critical players in the transduction of signals by a variety of cell surface receptors, such as G-protein-coupled receptors and integrins, our special focus is the mechanisms and significance of the interconnectivity between heterologous signalling systems.

Estimate of the dose due to 90Sr to the Austrian population after the Chernobyl accident.

In order to estimate the contribution of 90Sr to the exposure of the Austrian population, the ratio of 90Sr to 137Cs in 126 food samples and nine drinking water samples was determined. From this and the average activity concentration of 137Cs in each type of food as obtained by the measurement of some 100,000 food samples after the Chernobyl accident, a good estimate of the average activity concentration of 90Sr in these food items could be obtained. Samples were investigated at various times after the accident to take into account possible changes with time in the 90Sr-activity concentration and its ratio to 137Cs. Also, pre-Chernobyl samples were measured to estimate the relative contribution of the reactor accident and the fallout of the atomic bomb testing to the intake of 90Sr. Assuming average food consumption, the intake of 90Sr for an adult person amounted to 168 Bq in the first year and 115 Bq in the second year after the accident, resulting in an effective dose equivalent of 5.9 muSv and 4.0 muSv, respectively. This is a minor fraction of the dose due to the ingestion of Cs isotopes, which amounted to 360 muSv in the first year and 97 muSv in the second year. For the one-year-old infant, a 90Sr intake of 96 Bq (10.5 muSv) in the first year and 65 Bq (7.1 muSv) in the second year is estimated. Approximately 50% of the intake in the first year and 70% of that in the second year are due to 90Sr from nuclear weapons testing.