Germline gain-of-function MMP11 variant results in an aggressive form of colorectal cancer

Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future.     

Treatment of muscle spasticity in patients with cerebral palsy using BTX-A: a pilot study

This study was designed to verify the safety and efficacy of botulinum toxin type A (BTX-A) used as a neuromuscular block on spastic masticatory musculature of children with cerebral palsy. Six patients who had spastic-tetraplegic cerebral-palsy, aged 5 to 20 years were selected. All patients had spasticity of the jaw muscles, bruxism, lower lip trauma, limited mouth opening, and difficulties in cleaning the oral cavity. The patients were sedated under general anesthesia, while the dentist injected the masseter and temporalis muscles bilaterally with 150 and 75 units of BTX-A each. Clinical examinations were conducted at 7, 14, 30, and 90 days after the initial appointment. We found statistically significant decreases in muscle spasticity and bruxism ( p = 0.002), improved inter-incisal opening ( p = 0.002), improved oral hygiene ( p = 0.031), and less lower lip trauma ( p = 0.060) after the neuromuscular blocking.     

Osteochondritis dissecans of the patella: 12 cases followed for 4 years

Osteochondritis dissecans of the patella in 9 patients (6 men, 3 women; mean age 19 years) was located in the median ridge and paramedial areas and was bilateral in 3 patients. All patients were initially treated conservatively with complete relief of symptoms in 5. In 7 patients fragments were excised and the crater was curetted and drilled. At follow-up after 4 (2-8) years, the patients had no restriction of activities and they had no pain.     

INVASIVE MUCORMYCOSIS WITH GASTRIC INVOLVEMENT IN A PATIENT WITH SEVERE ATHEROMATOUS VASCULAR DISEASE

Gastric mucormycosis involvement is a rare condition that usually occurs in inmunocompromised patients and frequently has a fatal outcome. We report the case of a 73‐year‐old woman admitted to the intensive care unit with severe bleeding after an acute pulmonary disease. Upper endoscopy disclosed wide and deep necrotic ulcers in the body and fundus of the stomach and greenish exudates with the antrum and the duodenum undamaged. Autopsy revealed an invasive mucormycosis and a severe atheromatosis. Several predisposing factors for mucormycosis infection have been reported until now. We postulate that ischemic gastritis could be a predisposing factor for colonization of zygomycete.     

Simple and rapid detection of Mycobacterium tuberculosis complex organisms in bovine tissue samples by PCR.

Mycobacterium bovis is a slowly growing microorganism, and confirmation of the diagnosis by conventional culture is a lengthy process. A simple, rapid method for the extraction of DNA from bovine tissue samples was developed and used in a PCR designed for the diagnosis of tuberculosis. Tissues from 81 cattle from tuberculosis-infected herds (group 1) and 19 cattle from tuberculosis-free herds (group 2) were tested in this PCR, and the results were compared with those of conventional culture. The PCR assay detected 71.4% of the culture-positive animals from group 1. Tissue from all animals in group 2 were negative in the PCR assay and by culture. The described method could be used as a rapid screening technique which would be complementary to culture of tissue specimens for the routine diagnosis of bovine tuberculosis. The PCR technique is much faster than culture and reduces the time for diagnosis from several months to 2 days. It also provides for the detection of M. bovis when rapidly growing Mycobacterium spp. are present in the sample and may be able to detect the presence of M. bovis in samples even when organisms have become nonviable.