Reliability of Achilles tendon resting angle and calf circumference measurement techniques.

BACKGROUND: The resting angle of the ankle joint may be altered following apparently successful management of Achilles tendon rupture. The reliability of the Achilles Tendon Resting Angle and Calf Circumference measurements was determined. METHODS: Three test-retest measurements for reliability assessment were performed on 16 healthy subjects: 10 males and 6 females. RESULTS: The mean left Achilles Tendon Resting Angle was mean 50.1° (range [26-61]), ICC 0.92 (CI [0.83-0.97]), SEM 2.4°. The mean right Achilles tendon resting angle was mean 49.9° (range [26-60]), ICC 0.91 (CI [0.80-0.96]), SEM 2.6°. The mean left calf circumference was mean 38.5cm (range [33.3-44.2]), ICC 0.97 (CI [0.94-0.98]), SEM 0.6cm, and the mean right calf circumference was mean 38.4cm (range [33.3-43.6]), ICC 0.97 (CI [0.94-0.99]), SEM 0.5cm. CONCLUSIONS: The Achilles Tendon Resting Angle and Calf Circumference at 15cm from the antero-medial joint line had excellent test-retest reliability. These are simple, quick and inexpensive measurements, which have the potential to correlate with tendon elongation and functional outcome. The Achilles tendon resting angle may be used as a guide to tendon length during intra-operative repair and rehabilitation.

Inhibition of the keratinolytic subtilisin protease Sub3 from Microsporum canis by its propeptide (proSub3) and evaluation of the capacity of proSub3 to inhibit fungal adherence to feline epidermis.

Microsporum canis is a pathogenic fungus that causes a superficial cutaneous infection called dermatophytosis, mainly in cats, dogs and humans. Proteolytic enzymes have been postulated to be key factors involved in the invasion of the stratum corneum and keratinized epidermal structures. Among these proteases, the secreted subtilisin protease Sub3 was found to be required for adherence of M. canis arthroconidia to feline epidermis. This protease is synthetized as a preproenzyme consisting of a signal peptide followed by the propeptide and the protease domain. In order to assess whether the enzymatic activity of Sub3 could be responsible for the role of the protease in the adherence process, we expressed and characterized the propeptide of Sub3 and demonstrated that this propeptide is a strong inhibitor of its mature enzyme. This propeptide acts as a noncompetitive inhibitor with dissociation constants, K(I) and [Formula: see text] of 170 and 130 nM respectively. When tested for its capacity to inhibit adherence of M. canis to feline epidermis using an ex vivo adherence model made of feline epidermis, the propeptide does not prevent adherence of M. canis arthroconidia because it loses its capacity to inhibit rSub3 following a direct contact with living arthroconidia, presumably through inactivation by fungal membrane-bound proteases.

Mechanisms of skin adherence and invasion by dermatophytes.

Dermatophytes are keratinophilic fungi that can be pathogenic for humans and animals by infecting the stratum corneum, nails, claws or hair. The first infection step consists of adherence of arthroconidia to the stratum corneum. The mechanisms and the kinetics of adherence have been investigated using different in vitro and ex vivo experimental models, most notably showing the role of a secreted serine protease from Microsporum canis in fungal adherence to feline corneocytes. After germination of the arthroconidia, dermatophytes invade keratinised structures that have to be digested into short peptides and amino acids to be assimilated. Although many proteases, including keratinolytic ones, have been characterised, the understanding of dermatophyte invasion mechanisms remains speculative. To date, research on mechanisms of dermatophyte infection focused mainly on both secreted endoproteases and exoproteases, but their precise role in both fungal adherence and skin invasion should be further explored.

Secreted subtilisin Sub3 from Microsporum canis is required for adherence to but not for invasion of the epidermis.

BACKGROUND: Microsporum canis is a pathogenic dermatophyte that causes a superficial cutaneous mycosis, mainly in cats and humans. Proteolytic enzymes, including subtilisins, have been postulated to be key factors involved in adherence and invasion of the stratum corneum and keratinized epidermal structures. OBJECTIVES: To evaluate the importance of Sub3 as a M. canis virulence factor using a SUB3 RNA-silenced strain. MATERIALS AND METHODS: The stability of a previously constructed RNA-silenced strain IHEM 22957 was tested in three different ways. The involvement of Sub3 in the adherence process was evaluated using a new ex vivo adherence model of M. canis arthroconidia to feline epidermis. In order to investigate the contribution of Sub3 in epidermal invasion, the pathogenicity of the SUB3 silenced strain was compared with that of the control strain in a guinea pig model of experimental M. canis dermatophytosis. RESULTS: The silenced strain was shown to be stable after four in vitro transfers and after the in vivo experimental infection. This strain has dramatic loss of adherence capacity to feline corneocytes when compared with the parental strain. In contrast, no significant differences were observed at any time during the infection between the control strain and the SUB3 silenced strain, indicating that Sub3 secretion is not required for invasion of epidermal structures. CONCLUSIONS: RNA interference is a useful tool to evaluate pathogenic mechanisms of M. canis. For the first time, a role in pathogenicity could be attributed to a protease of a dermatophyte, namely Sub3 from M. canis, which is required for adherence to but not for invasion of the epidermis.

The carriage of larval echinococcus multilocularis and other cestodes by the musk rat (Ondatra zibethicus) along the Ourthe River and its tributaries (Belgium).

In Belgium, the carriage of Echinococcus multilocularis by the red fox (Vulpes vulpes) can be very high in some areas. This study was designed to evaluate the carriage of the larval form of E. multilocularis and other cestodes in a musk rat (Ondatra zibethicus) population trapped along the Ourthe River (southeastern Belgium). Six hundred fifty-seven musk rats were necropsied, and the larval cestodes of the abdominal and pleural cavities were identified. For E. multilocularis, the fertility of the cysts was verified in 58 liver samples. The following species were found: Taenia taeniaeformis (65.8%), Taenia martis (22.2%), E. multilocularis (22.1%), Taenia polyacantha (2.6%), and Taenia crassiceps (0.9%). Results were analyzed according to the site of capture (upper, middle, and lower Ourthe). There was a highly significant relationship between the carriage of E. multilocularis and the site of capture (the prevalence being higher in the upper part of the river). This difference could be due to different geoclimatic conditions. All but one hepatic lesion were found to contain protoscoleces of E. multilocularis (98.8%). The musk rat is probably infected through the consumption of plant material contaminated by the fox's feces. The red fox can occasionally prey on musk rats, but the musk rat cadavers that are left on the river banks by the trappers are probably also consumed. This could favor the maintenance of E. multilocularis life cycle. In conclusion, the musk rat seems to be highly susceptible to E. multilocularis and in Belgium could play the role of reservoir; when present this species could represent an inexpensive and sensitive bioindicator for the study and monitoring of the zoonosis.

EGFR and KRAS mutations as criteria for treatment with tyrosine kinase inhibitors: retro- and prospective observations in non-small-cell lung cancer.

Results of individualized therapy guided by mutational tumor profile of patients with non-small-cell lung cancer are presented. After confirming the importance of epidermal growth factor receptor (EGFR) and KRAS mutations for (non)response on gefitinib in a retrospective series of patients, EGFR mutations were looked for before--and were a condition for--treatment with gefitinib or erlotinib. To increase the chance to find such a mutation, we selected patients on the basis of smoking status, gender and histopathology. Out of 41 patients selected, 13 (32%) were found to harbor an EGFR mutation. In nine of them it concerned deletions in exon 19 and in none of them KRAS mutations were detected. All nine patients with an exon 19 deletion had a favorable and continuing response to tyrosine kinase inhibitors (TKIs), while four other patients with point mutations responded less favorably: stable disease or a response of short duration. These observations confirm the potential role of EGFR and KRAS mutations in predicting (non)response to TKIs. Exon 19 deletions that are associated with the best responses might be used for first-line treatment selection, while KRAS mutations could play a role in excluding patients from treatment with TKIs.