Opposing activities of two novel members of the IL-1 ligand family regulate skin inflammation

The interleukin (IL)-1 family members IL-1α, -1β, and -18 are potent inflammatory cytokines whose activities are dependent on heterodimeric receptors of the IL-1R superfamily, and which are regulated by soluble antagonists. Recently, several new IL-1 family members have been identified. To determine the role of one of these family members in the skin, transgenic mice expressing IL1F6 in basal keratinocytes were generated. IL1F6 transgenic mice exhibit skin abnormalities that are dependent on IL-1Rrp2 and IL-1RAcP, which are two members of the IL-1R family. The skin phenotype is characterized by acanthosis, hyperkeratosis, the presence of a mixed inflammatory cell infiltrate, and increased cytokine and chemokine expression. Strikingly, the combination of the IL-1F6 transgene with an IL1F5 deficiency results in exacerbation of the skin phenotype, demonstrating that IL-1F5 has antagonistic activity in vivo. Skin from IL1F6 transgenic, IL1F5−/− pups contains intracorneal and intraepithelial pustules, nucleated corneocytes, and dilated superficial dermal blood vessels. Additionally, expression of IL1RL2, -1F5, and -1F6 is increased in human psoriatic skin. In summary, dysregulated expression of novel agonistic and antagonistic IL-1 family member ligands can promote cutaneous inflammation, revealing potential novel targets for the treatment of inflammatory skin disorders

Management of anterior cruciate ligament rupture in patients aged 40 years and older

The aim of anterior cruciate ligament (ACL) reconstruction is essentially to restore functional stability of the knee and to allow patients to return to their desired work and activities. While in the young and active population, surgery is often the best therapeutic option after an ACL tear, ACL reconstruction in middle-aged people is rather more controversial due to concerns about a higher complication rate. The purpose of our article is to establish, through a systematic review of the literature, useful decision-making criteria for the management of anterior cruciate ligament rupture in patients aged 40 years and older, guiding surgeons to the most appropriate therapeutic approach. Various reports have shown excellent results of ACL reconstruction in patients over the age of 40 in terms of subjective satisfaction, return to previous activity level, and reduced complication and failure rates. Some even document excellent outcomes in subjects of 50 years and older. Although there are limited high-level studies, data reported in the literature suggest that ACL reconstruction can be successful in appropriately selected, motivated older patients with symptomatic knee instability who want to return to participating in highly demanding sport and recreational activities. Deciding factors are based on occupation, sex, activity level of the subject, amount of time spent performing such highly demanding activities, and presence of associated knee lesions. Physiological age and activity level are more important than chronological age as deciding factors when considering ACL reconstruction

A Probabilistic Model of Glenohumeral External Rotation Strength for Healthy Normals and Rotator Cuff Tear Cases

The reigning paradigm of musculoskeletal modeling is to construct deterministic models from parameters of an “average” subject and make predictions for muscle forces and joint torques with this model. This approach is limited because it does not perform well for outliers, and it does not model the effects of population parameter variability. The purpose of this study was to simulate variability in musculoskeletal parameters on glenohumeral external rotation strength in healthy normals, and in rotator cuff tear case using a Monte Carlo model. The goal was to determine if variability in musculoskeletal parameters could quantifiably explain variability in glenohumeral external rotation strength. Multivariate Gamma distributions for musculoskeletal architecture and moment arm were constructed from empirical data. Gamma distributions of measured joint strength were constructed. Parameters were sampled from the distributions and input to the model to predict muscle forces and joint torques. The model predicted measured joint torques for healthy normals, subjects with supraspinatus tears, and subjects with infraspinatus–supraspinatus tears with small error. Muscle forces for the three conditions were predicted and compared. Variability in measured torques can be explained by differences in parameter variability.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44005/1/10439_2005_Article_9045.pd