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.     

Cataract Surgery in HIV Seropositive Patients: Long-Term Follow-Up

Purpose: To study epidemiology and clinical findings of cataract in HIV+ patients.

Methods: A total of 32 HIV+ patients, 11 with uveitis/retinitis before surgery and 21 without, mean follow-up 44.9 ± 36.6 months, and 114 HIV- patients, 57 with uveitis/retinitis before surgery and 57 without, were retrospectively compared.

Results: Visual acuity improved in all HIV+ patients (p < 0.001), who were younger (p = 0.01) and more frequently males (p = 0.027). HIV+ patients with uveitis prior surgery improved less (p = 0.046) than HIV- (p < 0.001); their anterior chamber inflammation was similar to baseline. Male sex (p = 0.005), younger age (p < 0.001), dyslipidaemia (p = 0.058), HBV+ (p = 0.037), and unilateral cataract (p = 0.001) were more frequent in HIV+ patients with senile cataract, but they showed the same postoperative course as HIV- patients.

Conclusion: Cataract surgery in HIV+ patients is safe and effective. Uveitis prior to surgery did not significantly affect the postoperative course. Systemic comorbidities are more frequent in HIV+ patients with senile cataract than in HIV- subjects.     

Adherence to the Mediterranean diet and weight status in children: the role of parental feeding practices

Abstract

The study examines Parental Feeding Practices (PFP) in relation to adherence to the Mediterranean Diet (MD) and children’s weight status. It’s a cross-sectional study of 402 parents (68.4% mothers), with children aged 2–12 years. Parents completed the Comprehensive Parental Feeding Questionnaire and the Mediterranean Diet Quality Index for children and adolescents (KIDMED), evaluating children’s adherence to the MD. Logistic regression showed that in children aged 2–<6 years, “emotion regulation/food as reward” and “pressure” decrease MD adherence (OR?=?0.186, p?<?0.0001 and OR?=?0.496, p?=?0.004), and “monitoring” decrease excess body weight (OR?=?0.284, p?=?0.009). In older children (6–12 years), “healthy eating guidance” and “monitoring” increase MD adherence (OR?=?3.262, p?=?0.001 and OR?=?3.147, p?<?0.0001), “child control” decreases MD adherence (OR?=?0.587, p?=?0.049), “pressure” decrease excess body weight (OR?=?0.495, p?<?0.0001) and “restriction” increase excess body weight (OR?=?1.784, p?=?0.015). “Healthy eating guidance” and “monitoring” seem to be the best PFP employed, in terms of children’s MD adherence and weight status.