Stromal Caveolin-1 and Caveolin-2 Expression in Primary Tumors and Lymph Node Metastases

The expression of caveolin-1 (CAV1) in both tumor cell and cancer-associated fibroblasts (CAFs) has been found to correlate with tumor aggressiveness in different epithelial tumor entities, whereas less is known for caveolin-2 (CAV2). The aim of this study was to investigate the clinicopathological significance and prognostic value of stromal CAV1 and CAV2 expression in lung cancer. The expression of these two genes was investigated at protein level on a tissue microarray (TMA) consisting of 161 primary tumor samples. 50.7% of squamous cell lung cancer (SCC) tumors showed strong expression of CAV1 in the tumor-associated stromal cells, whereas only 15.1% of adenocarcinomas (AC) showed a strong CAV1 expression (p <0 01). A strong CAV2 stromal expression was found in 46.0% of the lung tumor specimens, with no significant difference between the subtypes. Neither CAV1 nor CAV2 stromal expression was associated with any other clinicopathological factor including survival. When the stromal expression in matched primary tumors and lymph node metastases was compared, both CAV1 and CAV2 expressions were frequently found lost in the corresponding stroma of the lymph node metastasis (40.6%, p = 0 003 and 38.4%, p = 0 001, resp.). Loss of stromal CAV2 in the lymph node metastases was also significantly associated with earlier death (p = 0 011). In conclusion, in contrast to the expression patterns in the tumor tissue of lung cancer, stromal expression of CAV1 in primary tumors was not associated with clinical outcome whereas the stromal expression of especially CAV2 in the metastatic lymph nodes could be associated with lung cancer pathogenesis.Peer reviewe

Exercise-linked improvement in age-associated loss of balance is associated with increased vestibular input to motor neurons

Age-associated loss of muscle function is exacerbated by a concomitant reduction in balance, leading to gait abnormalities and falls. Even though balance defects can be mitigated by exercise, the underlying neural mechanisms are unknown. We now have investigated components of the proprioceptive and vestibular systems in specific motor neuron pools in sedentary and trained old mice, respectively. We observed a strong age-linked deterioration in both circuits, with a mitigating effect of exercise on vestibular synapse numbers on motor neurons, closely associated with an improvement in gait and balance in old mice. Our results thus describe how the proprioceptive and vestibular systems are modulated by age and exercise, and how these changes affect their input to motor neurons. These findings not only make a strong case for exercise-based interventions in elderly individuals to improve balance, but could also lead to targeted therapeutic interventions aimed at the respective neuronal circuitry

Effectiveness of individualized ressource-oriented joint protection education in people with rheumatoid arthritis : a randomized controlled trial

Objective: The modern joint protection (JP) concept for people with rheumatoid arthritis (RA) is an active coping strategy to improve daily tasks and role performance by changing working methods and using assistive devices. Effective group JP education includes psycho-educational interventions. The Pictorial Representation of Illness and Self Measure (PRISM) is an interactive hands-on-tool, assessing (a) the individual's perceived burden of illness and (b) relevant individual resources. Both issues are important for intrinsic motivation to take action and change behaviour. This study compared individual conventional JP education (C-JP) with PRISM-based JP education (PRISM-JP). Methods: An assessor-blinded multicentre randomized controlled trial, including four JP education sessions over 3 weeks, with assessments at baseline and 3 months. Results: In total 53 RA patients participated. At 3 months, the PRISM-JP (n = 26) participants did significantly better compared to the C-JP participants (n = 27) in JP behaviour (p = 0.02 and p = 0.008 when corrected for baseline values), Arthritis Self-efficacy (ASES, p = 0.015) and JP self-efficacy (JP-SES, p = 0.047). Within-group analysis also showed less hand pain (p < 0.001) in PRISM-JP group. Conclusion: PRISM-JP more effectively supported learning of JP methods, with meaningful occupations, resource activation and self-efficacy acting as important mediators. Practice implications: PRISM improved patient–clinician communication and is feasible for occupational therapy

Interleukin-6 potentiates endurance training adaptation and improves functional capacity in old mice

Interventions to preserve functional capacities at advanced age are becoming increasingly important. So far, exercise provides the only means to counteract age-related decrements in physical performance and muscle function. Unfortunately, the effectiveness of exercise interventions in elderly populations is hampered by reduced acceptance and compliance as well as disuse complications. We therefore studied whether application of interleukin-6 (IL-6), a pleiotropic myokine that is induced by skeletal muscle activity and exerts broad systemic effects in response to exercise, affects physical performance and muscle function alone or in combination with training in aged mice.; Sedentary old male mice (Sed+Saline, n = 15) were compared with animals that received recombinant IL-6 (rIL-6) in an exercise-mimicking pulsatile manner (Sed+IL-6, n = 16), were trained with a moderate-intensity, low-volume endurance exercise regimen (Ex+Saline, n = 13), or were exposed to a combination of these two interventions (Ex+IL-6, n = 16) for 12 weeks. Before and at the end of the intervention, mice underwent a battery of tests to quantify endurance performance, muscle contractility in situ, motor coordination, and gait and metabolic parameters.; Mice exposed to enhanced levels of IL-6 during endurance exercise bouts showed superior improvements in endurance performance (33% more work and 12% greater peak power compared with baseline), fatigue resistance in situ (P = 0.0014 vs. Sed+Saline; P = 0.0199 vs. Sed+IL-6; and P = 0.0342 vs. Ex+Saline), motor coordination (rotarod performance, P = 0.0428), and gait (gait speed, P = 0.0053) following training. Pulsatile rIL-6 treatment in sedentary mice had only marginal effects on glucose tolerance and some gait parameters. No increase in adverse events or mortality related to rIL-6 treatment was observed.; Administration of rIL-6 paired with treadmill running bouts potentiates the adaptive response to a moderate-intensity low-volume endurance exercise regimen in old mice, while being safe and well tolerated

Effect of suture technique on the occurrence of incisional hernia after elective midline abdominal wall closure: study protocol for a randomized controlled trial

Background: Based on a recent meta-analysis, a continuous suture technique with a suture to wound length ratio of at least 4: 1, using a slowly absorbable monofilament suture material, is recommended for primary median laparotomy closure. Incisional hernia, which develops in 9 to 20% of patients, remains the major complication of abdominal wall closure. Current clinical data indicate that the incidence of incisional hernias increases by 60% between the first and the third year after median laparotomy, implicating that a follow-up period of 1 year postoperatively is too short with regard to this common complication. Trauma to the abdominal wall can be reduced by improvements in suture technique as well as suture material. Several factors, such as stitch length, suture tension, elasticity, and tensile strength of the suture material are discussed and currently under investigation. A Swedish randomized controlled trial showed a significant reduction in the incisional hernia rate by shortening the stitch length. However, a non-elastic thread was used and follow-up ended after 12 months. Therefore, we designed a multicenter, international, double-blinded, randomized trial to analyze the influence of stitch length, using an elastic, extra-long term absorbable monofilament suture, on the long term clinical outcome of abdominal wall closure. Methods: In total, 468 patients undergoing an elective, median laparotomy will be randomly allocated to either the short stitch or the long stitch suture technique for abdominal wall closure in a 1: 1 ratio. Centers located in Germany and Austria will participate. The primary endpoint measure is the incisional hernia rate 1 year postoperatively, as verified by ultrasound. The frequency of short term and long term complications as well as costs, length of hospital stay and patients' quality of life (EQ-5D-5 L) will be considered as secondary parameters. Following hospital discharge, patients will be examined after 30 days and 1, 3, and 5 years after surgery. Discussion: This study will provide further evidence on whether a short stitch suture technique in combination with an elastic, extra-long term absorbable monofilament suture can prevent incisional hernias in the long term, compared with the long stitch suture technique

Remodeling of metabolism and inflammation by exercise ameliorates tumor-associated anemia

A considerable number of patients with cancer suffer from anemia, which has detrimental effects on quality of life and survival. The mechanisms underlying tumor-associated anemia are multifactorial and poorly understood. Therefore, we aimed at systematically assessing the patho-etiology of tumor-associated anemia in mice. We demonstrate that reduced red blood cell (RBC) survival rather than altered erythropoiesis is driving the development of anemia. The tumor-induced inflammatory and metabolic remodeling affect RBC integrity and augment splenic phagocyte activity promoting erythrophagocytosis. Exercise training normalizes these tumor-associated abnormal metabolic profiles and inflammation and thereby ameliorates anemia, in part, by promoting RBC survival. Fatigue was prevented in exercising tumor-bearing mice. Thus, exercise has the unique potential to substantially modulate metabolism and inflammation and thereby counteracts pathological remodeling of these parameters by the tumor microenvironment. Translation of this finding to patients with cancer could have a major impact on quality of life and potentially survival

Molecular control of endurance training adaptation in male mouse skeletal muscle

Skeletal muscle has an enormous plastic potential to adapt to various external and internal perturbations. Although morphological changes in endurance-trained muscles are well described, the molecular underpinnings of training adaptation are poorly understood. We therefore aimed to elucidate the molecular signature of muscles of trained male mice and unravel the training status-dependent responses to an acute bout of exercise. Our results reveal that, even though at baseline an unexpectedly low number of genes define the trained muscle, training status substantially affects the transcriptional response to an acute challenge, both quantitatively and qualitatively, in part associated with epigenetic modifications. Finally, transiently activated factors such as the peroxisome proliferator-activated receptor-γ coactivator 1α are indispensable for normal training adaptation. Together, these results provide a molecular framework of the temporal and training status-dependent exercise response that underpins muscle plasticity in training

Assessing Informal Social Learning at the Workplace – A Revalidation Case from Healthcare

This paper explores how informal learning can be assessed in the work environment which bears difficulties, as informal learning is largely invisible and people lack awareness of informal learning. We perform an exploratory case study involving 24 healthcare professionals representing small and medium sized enterprises (SME) in six healthcare networks in the UK. We use the existing revalidation procedure as implemented by the National Health Service (NHS) England to discuss our results. Our results comprise a description of six indicators, three of which can be used to assess informal learning activities and three of which can be used to assess informal learning outcomes. Our findings stress the importance of the social context of informal learning at the workplace. Finally, we discuss the implementation of these indicators to support informal social learning