Type 1 plasminogen activator inhibitor (PAI-1) in clear cell renal cell carcinoma (CCRCC) and its impact on angiogenesis, progression and patient survival after radical nephrectomy

<p>Abstract</p> <p>Background</p> <p>To examine the expression of type 1 plasminogen inhibitor (PAI-1) in clear cell renal cell carcinoma (CCRCC), and its possible association with microvessel density (MVD), the expression of thrombospondin-1 (TSP-1), nuclear grade, tumour stage, continuously coded tumour size (CCTS) and to assess the value of PAI as a prognostic marker in 162 patients with CCRCC treated with radical nephrectomy.</p> <p>Methods</p> <p>A total of 172 consecutive patients with CCRCC treated with radical nephrectomy were enrolled in the study. The expression of PAI-1, TSP-1 and factor VIII were analysed on formalin-fixed, paraffin-embedded tissues without knowledge of the clinical outcome. Ten cases, where PAI-1 immunohistochemistry was not possible due to technical problems and lack of material, were excluded. Sixty-nine patients (43%) died of RCC, while 47 patients (29%) died of other diseases. Median follow-up was 13.8 years for the surviving 46 patients (28%).</p> <p>Results</p> <p>Nine percent of the tumours showed PAI-1 positivity. High expression of PAI-1 was significantly inversely correlated with TSP-1 (p = 0.046) and directly with advanced stage (p = 0.008), high NG (3+4) (p = 0.002), tumour size (p = 0.011), microvessel density (p = 0.049) and disease progression (p = 0.002). In univariate analysis PAI-1 was a significant prognosticator of cancer-specific survival (CSS) (p < 0.001). Multivariate analysis revealed that TNM stage (p < 0.001), PAI-1 (p = 0.020), TSP-1 (p < 0.001) and MVD (p = 0.007) were independent predictors of CSS.</p> <p>Conclusions</p> <p>PAI-1 was found to be an independently significant prognosticator of CSS and a promoter of tumour angiogenesis, aggressiveness and progression in CCRCC.</p

Spin flop and crystalline anisotropic magnetoresistance in CuMnAs

Recent research works have shown that the magnetic order in some antiferromagnetic materials can be manipulated and detected electrically, due to two physical mechanisms: Neel-order spin-orbit torques and anisotropic magnetoresistance. While these observations open up opportunities to use antiferromagnets for magnetic memory devices, different physical characterization methods are required for a better understanding of those mechanisms. Here we report a magnetic field induced rotation of the antiferromagnetic Neel vector in epitaxial tetragonal CuMnAs thin films. Using soft x-ray magnetic linear dichroism spectroscopy, x-ray photoemission electron microscopy, integral magnetometry and magneto-transport methods, we demonstrate spin-flop switching and continuous spin reorientation in antiferromagnetic films with uniaxial and biaxial magnetic anisotropies, respectively. From field-dependent measurements of the magnetization and magnetoresistance, we obtain key material parameters including the anisotropic magnetoresistance coefficients, magnetocrystalline anisotropy, spin-flop and exchange fields.Comment: 26 pages, 6 figure

Assessment of Skeletal Muscle Contractile Properties by Radial Displacement: The Case for Tensiomyography

Skeletal muscle operates as a near-constant volume system; as such muscle shortening during contraction is transversely linked to radial deformation. Therefore, to assess contractile properties of skeletal muscle, radial displacement can be evoked and measured. Mechanomyography measures muscle radial displacement and during the last 20 years, tensiomyography has become the most commonly used and widely reported technique among the various methodologies of mechanomyography. Tensiomyography has been demonstrated to reliably measure peak radial displacement during evoked muscle twitch, as well as muscle twitch speed. A number of parameters can be extracted from the tensiomyography displacement/time curve and the most commonly used and reliable appear to be peak radial displacement and contraction time. The latter has been described as a valid non-invasive means of characterising skeletal muscle, based on fibre-type composition. Over recent years, applications of tensiomyography measurement within sport and exercise have appeared, with applications relating to injury, recovery and performance. Within the present review, we evaluate the perceived strengths and weaknesses of tensiomyography with regard to its efficacy within applied sports medicine settings. We also highlight future tensiomyography areas that require further investigation. Therefore, the purpose of this review is to critically examine the existing evidence surrounding tensiomyography as a tool within the field of sports medicine

Up in the air: Evidence of dehydration risk and long-haul flight on athletic performance

The microclimate of an airline cabin consists of dry, recirculated, and cool air, which is maintained at lower pressure than that found at sea level. Being exposed to this distinctive, encapsulated environment for prolonged durations, together with the short-term chair-rest immobilization that occurs during long-haul flights, can trigger distinct and detrimental reactions to the human body. There is evidence that long-haul flights promote fluid shifts to the lower extremity and induce changes in blood viscosity which may accelerate dehydration, possibly compromising an athlete\u2019s potential for success upon arrival at their destination. Surprisingly, and despite several recent systematic reviews investigating the effects of jet lag and transmeridian travel on human physiology, there has been no systematic effort to address to what extent hypohydration is a (health, performance) risk to travelers embarking on long journeys. This narrative review summarizes the rationale and evidence for why the combination of fluid balance and long-haul flight remains a critically overlooked issue for traveling persons, be it for health, leisure, business, or in a sporting context. Upon review, there are few studies which have been conducted on actual traveling athletes, and those that have provide no real evidence of how the incidence rate, magnitude, or duration of acute dehydration may affect the general health or performance of elite athletes

Erste Beobachtungen zur sexuellen Dysfunktion als Symptom einer Chemotherapie-induzierten Polyneuropathie

Introduction: Peripheral neuropathy (PNP) in feet and/or hands and sexual dysfunction are common side effects of cancer therapies. In patients with other diseases, there is evidence of an association between peripheral nervous system disorders and sexual dysfunction due to the impact of impaired neuronal control on genital organ sensitivity. In cancer patient interviews, it has now been observed that PNP and sexual dysfunction may be related. The aim of the study was to investigate the potential association between PNP, sexual dysfunction, and physical activity behavior.Methods: Ninety-three patients with PNP of the feet and/or hands were interviewed in August/September 2020 in a cross-sectional study regarding medical history, sexual dysfunction and functionality of the genital organs.Results: Thirty-one persons who participated in the survey provided seventeen evaluable questionnaires (four men, thirteen women). Nine women (69%) and three men (75%) reported sensory disorders of the genital organs. Three men (75%) had erectile dysfunction. All men who had sensory symptoms of the genital organs received chemotherapy, and one man also received immunotherapy. Eight women were sexually active. Five (63%) of them reported genital organ symptoms and mainly lubrication disorders. Four (80%) of the five sexually inactive women reported genital organ symptoms. Eight of the nine women with sensory symptoms of the genital organs received chemotherapy, and one woman received immunotherapy. Discussion: Our limited data suggest genital organ sensory symptoms in chemotherapy and immunotherapy patients. Genital organ symptoms do not appear to be directly related to sexual dysfunction, and the association between PNP and genital organ symptoms appears to be more pronounced in sexually inactive women. Chemotherapy could cause sensory symptoms of the genital organs and sexual dysfunction by damaging genital organ nerve fibers. Chemotherapy and anti-hormone therapy (AHT) could trigger a disturbance of the hormone balance, which in turn could be causative for sexual dysfunction. It remains open whether the cause of these disorders is the symptomatology of the genital organs or the altered hormone balance. The significance of the results is limited due to the small number of cases. To our knowledge, this study is the first of its kind in cancer patients and allows a better understanding of the association between PNP, sensory symptoms of the genital organs, and sexual dysfunction. Conclusion: In order to be able to narrow down the cause of these initial observations in cancer patients more precisely, larger studies are needed that can relate the influence of cancer therapy-induced PNP, physical activity level and hormone balance to sensory symptoms of the genital organs and sexual dysfunction. The methodology of further studies should take into account the frequent problem of low response rates in surveys on sexuality.Einleitung: Polyneuropathie (PNP) in Füßen und/oder Händen und sexuelle Dysfunktion sind häufige Nebenwirkungen von Krebstherapien. Bei Patient*innen mit anderen Erkrankungen gibt es Hinweise auf einen Zusammenhang zwischen Erkrankungen des peripheren Nervensystems und der sexuellen Dysfunktion aufgrund des Einflusses der gestörten neuronalen Kontrolle auf die Sensibilität der Genitalorgane. In Gesprächen mit Krebspatient*innen wurde nun beobachtet, dass die PNP und die sexuelle Dysfunktion möglicherweise zusammenhängen. Ziel der Studie war, den potentiellen Zusammenhang zwischen PNP, sexueller Dysfunktion und körperlichem Aktivitätsverhalten zu untersuchen.Methoden: Dreiundneunzig Patient*innen mit PNP der Füße und/oder Hände wurden im August/September 2020 in einer Querschnittuntersuchung bezüglich Krankengeschichte, sexueller Dysfunktion und Funktionalität der Genitalorgane befragt.Ergebnisse: Einunddreißig Personen, die an der Umfrage teilnahmen, lieferten siebzehn auswertbare Fragebögen (vier Männer, dreizehn Frauen). Neun Frauen (69%) und drei Männer (75%) berichteten über Gefühlsstörungen an den Geschlechtsorganen. Drei Männer (75%) hatten eine erektile Dysfunktion. Alle Männer, die sensorische Beeinträchtigungen der Genitalorgane aufwiesen, erhielten Chemotherapie, und ein Mann zudem Immuntherapie. Acht Frauen waren sexuell aktiv. Fünf (63%) von ihnen berichteten von Symptomen der Genitalorgane und hauptsächlich Lubrikationsstörungen. Vier (80%) der fünf sexuell inaktiven Frauen berichteten von Symptomen der Genitalorgane. Acht der neun Frauen mit sensorischen Symptomen der Genitalorgane erhielten Chemotherapie und eine Frau erhielt Immuntherapie.Diskussion: Unsere begrenzten Daten deuten auf sensorische Symptome der Genitalorgane bei Chemotherapie- und Immuntherapie-Patient*innen hin. Symptome der Genitalorgane scheinen nicht direkt mit sexueller Dysfunktion zusammenzuhängen und der Zusammenhang zwischen PNP und Symptomen der Genitalorgane scheint bei sexuell inaktiven Frauen ausgeprägter zu sein. Chemotherapie könnte durch Schädigung von Nervenfasern der Genitalorgane sensorische Symptome im Genitalbereich und eine sexuelle Dysfunktion verursachen. Chemotherapie und Anti-Hormontherapie (AHT) könnten eine Störung des Hormonhaushaltes auslösen, die wiederum ursächlich für eine sexuelle Dysfunktion sein könnte. Es bleibt offen, ob eine Symptomatik an den Genitalorganen oder der veränderte Hormonhaushalt Ursache dieser Störungen ist. Die Aussagekraft der Ergebnisse ist aufgrund der geringen Fallzahl eingeschränkt. Diese Untersuchung ist nach unserer Kenntnis die erste dieser Art bei Krebspatient*innen und ermöglicht ein besseres Verständnis für den Zusammenhang von PNP, sensorischen Symptomen der Genitalorgane und sexueller Dysfunktion. Fazit: Um die Ursache dieser ersten Beobachtungen bei Krebspatient*innen genauer eingrenzen zu können, sind größere Studien notwendig, die den Einfluss der Krebstherapie-induzierten PNP, des körperlichen Aktivitätsniveaus und des Hormonhaushalts auf die sensorischen Symptome der Genitalorgane und die sexuelle Dysfunktion in Beziehung setzen können. Bei der Methodik weiterer Studien sollte das häufig auftretende Problem der geringen Rücklaufquoten in Befragungen zur Sexualität berücksichtigt werden

Neuromuscular performance after rapid weight loss in Olympic-style boxers

The present study investigated the effect of a 3% rapid weight loss (RWL) procedure on neuromuscular performance in elite, Olympic-style boxers. Nine boxers were randomly assigned to two experimental procedures (RWL and control, in a randomized counter-balance order) to perform 5-s maximum isometric voluntary contractions (MVC) of the dominant leg knee extensors prior to (MVC1), and following (MVC2), a sustained, isometric contraction at 70% MVC until exhaustion. The voluntary activation (VA) was determined using percutaneous muscle stimulation and interpolated twitch technique. High (at 80 Hz) and low (at 20 Hz) frequency tetanic impulses were also delivered before and after the sustained 70% MVC to assess peripheral fatigue. Hydration status, hemodynamic parameters, and lactate concentration were assessed throughout the study. Body-mass was reduced by 3c3% (during RWL) compared to control (p =.001). As a result of the RWL protocol, MVC1 force output was 12% lower and VA deficits of 7% were observed after the fatigue protocol compared to control (p =.001). Following RWL, time to exhaustion for the sustained 70% MVC was 69 \ub1 20 s compared to 86 \ub1 34 s for control (p =.020). Peak lactate production was 53% lower in RWL compared to control (p =.001). In conclusion, the 3% RWL procedure translated into significant decline in neuromuscular performance for both brief and sustained contractions in competitive boxers