Secretion,blood levels and cutaneous expression of TL1A in psoriasis patients

TL1A is a TNF‐like cytokine which has been shown to co‐stimulate TH1 and TH17 responses during chronic inflammation. The expression of this novel cytokine has been investigated in inflammatory disorders like rheumatoid arthritis and inflammatory bowel disease, but little is known about expression and induction in psoriasis. Indeed, the pathogenesis in psoriasis is still not fully understood and it is speculated that cytokines other than TNF‐α are important in subsets of patients. Also, for patients with severe disease that are treated with systemic anti‐TNF‐α blockade, novel candidates to be used as disease and response biomarkers are of high interest. Here, we demonstrate TL1A expression in biopsies from psoriatic lesions. Also, we investigated spontaneous and induced TL1A secretion from PBMCs and blood levels from a cohort of psoriasis patients. Here, increased spontaneous secretion from PBMCs was observed as compared to healthy controls and a small subset of patients had highly elevated TL1A in the blood. Interestingly, activation of PBMCs with various cytokines showed a decreased sensitivity for TL1A activation in psoriasis patients compared to healthy controls.TL1A levels in blood and biopsies could not be correlated with disease activity with this patient cohort. Thus, additional large‐scale studies are warranted to investigate TL1A as a biomarker.     

The practical assessment and management of bladder outflow obstruction

The initial management of bladder outflow obstruction typically related to benign prostatic hyperplasia (BPH) falls to a large extent within the remit of general practice. Referral onwards to secondary care typically arises following the failure to respond to conservative measures or when complications have supervened; the most significant of which is urinary retention. In the hospital setting, anaesthesia, constipation and immobility are the common precipitants. What follows is a practical guide to the management of these situations and provides an overview of the conservative, medical, minimally invasive and surgical treatments available.     

Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome

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International cancer patterns in men: geographical and temporal variations in cancer risk and the role of gender

The comparison of disease risk in populations stratified by certain demographic variables provides important clues as to the underlying causes of disease. There are fundamental variations in the risk of occurrence of different cancers by gender, area of residence, and time of diagnosis. Men are, for instance, at considerably higher risk of developing most of the common cancers that occur in both sexes, and there are substantial variations in the occurrence of particular cancers in different regions of the World. This paper attempts to highlight some of these remarkable variations using cancer incidence data by sex, area of residence and year of diagnosis, emphasising the strong evidence that many of the contrasts can be appropriated to a number of modifiable “environmental” factors.Rates of cancer occurrence in the developed world are double that of less developed regions, although risk patterns are of very different magnitude and direction depending on the cancer site examined. Lung cancer is the most common neoplasm in men globally, but is overshadowed by prostate cancer in certain westernised countries, notably in the U.S. Cancers of the colon and rectum are important in the developed world, whereas stomach and liver cancer are common in developing areas.Men have systematically higher rates than women for the vast majority of the tumours that develop in both sexes, with the exception of thyroid cancer. There are also huge variations in the extent of the inequality: men have notably elevated risks, relative to women, of developing tumours of the head and neck, bladder, lung, oral cavity and liver.In Europe, incidence trends of lung cancer tend to be declining in men, although there is substantial between-country variation. In women, lung cancer rates are systematically on the increase in most Western, Southern and European countries. Trends in prostate cancer are increasing, as are trends in colorectal cancer (in both sexes), although more noticeably in Southern and Eastern Europe. Stomach cancer continues to fall in most European areas. Bladder cancer is decreasing in both men and women, apart from in Eastern Europe, whereas cancers of the kidney and non-Hodgkin lymphoma are steadily increasing in both sexes.We have estimated that men have better and more readily achievable prospects of avoiding death from cancer since they have lower rates of gender specific cancers, that are probably hormonal in origin, then women. Tobacco consumption plays a dominating role in the excess risk of cancer in men but it is apparent that the male excess disease burden can be effectively reduced by various prevention measures. As well as avoiding (or quitting) smoking, these include, moderating alcohol consumption, avoiding obesity, undertaking regular physical exercise, and maintaining a diet high in fruit and vegetables. The adoption of a healthier lifestyle will be of considerable benefit to the general health of both men and women, with an expectation of a major reduction in the burden of cancer, as well as other major diseases.     

Functional anatomy and biomechanics of the meniscus

The meniscus is no longer considered the evolutionary remnant in the knee joint.Rather, it is now well established as an important structure that is integral to the complex biomechanics and proper functioning of the knee. The medial and lateral menisci form two crescent-shaped wedges of fibrocartilage between the femoral condyles and tibial plateaus.The knee joint biomechanics are based on a complex interaction of these intra-articular structures. The functions ascribed to the menisci include load transmission, shock absorption, stability, proprioception, joint lubrication, and joint nutrition. Load transmission generally is accepted as one of its primary functions. The menisci transmit a portion of the axial forces across the knee joint by converting this load into “hoop stresses.” This is accomplished by their unique shape, composition, and anatomic attachments. The menisci are relatively mobile structures and their motion during knee flexion also is determined by their shape and soft tissue attachments/constraints. Preservation of the meniscal functions is essential, and the authors review the basic anatomic and biomechanical concepts necessary to understand techniques for repair and restoration of these functions.     

In situ forces in the anterior cruciate ligament and its bundles in response to anterior tibial loads

The anterior cruciate ligament has a complex fiber anatomy and is not considered to be a uniform structure. Current anterior cruciate ligament reconstructions succeed in stabilizing the knee, but they neither fully restore normal knee kinematics nor reproduce normal ligament, function. To improve the outcome of the reconstruction, it may be necessary to reproduce the complex function of the intact anterior cruciate ligament in the replacement graft. We examined the in situ forces in nine human anterior cruciate ligaments as well as the force distribution between the anteromedial and posterolateral bundles of the ligament in response to applied anterioi tibial loads ranging from 22 to 110 N at knee flexion angles of 0–90°. The analysis was performed using a robotic manipulator in conjunction with a universal force-moment sensor. The in situ forces were determined with no device attached to the ligament, while the knee was permitted to move freely in response to the applied loads. We found that the in situ forces in the anterior cruciate ligament ranged from 12.8 ± 7.3 N under 22 N of anterior tibial load applied at 90° of knee flexion to 110.6 ± 14.8 N under 110 N of applied load at 15° of flexion. The magnitude of the in situ force in the posterolateral bundle was larger than that in the anteromedial bundle at knee flexion angles between 0 and 45°, reaching a maximum of 75.2 ± 18.3 N at 15° of knee flexion under an anterior tibial load of 110 N. The magnitude of the in situ force in the posterolateral bundle was significantly affected by knee flexion angle and anterior tibial load in a fashion remarkably similar to that seen in the anterior cruciate ligament. The magnitude of the in situ force in the anteromedial bundle, in contrast, remained relatively constant, not changing with flexion angle. Significant differences in the direction of the in situ force between the anteromedial bundle and the posterolateral bundle were found only at flexion angles of 0 and 60° and only under applied anterior tibial loads greater than 66 N. We have demonstrated the nonuniformity of the anterior cruciate ligament under unconstrained anterior tibial loads. Our data further suggest that in order for the anterior cruciate ligament replacement graft to reproduce the in situ forces of the normal anterior cruciate ligament, reconstruction techniques should take into account the role of the posterolateral bundle in addition to that of the anteromedial bundle.