Somatic hypermutation defects in two adult hyper immunoglobulin M patients

Immunologic Research - Hyper immunoglobulin M (HIGM) syndrome is a rare disorder of the immune system with impaired antibody functions. The clinical picture of the patients varies according to the...     

Postoperative pain in root canal treatment with ultrasonic versus conventional irrigation: a systematic review and meta-analysis of randomized controlled trials

Clinical Oral Investigations - The objective of this systematic review and meta-analysis (SRM) was to answer the question whether the use of ultrasonic irrigation (UI) results in less postoperative...     

Biomarkers for traumatic brain injury: a short review

Neurosurgical Review - Cellular response to TBI is a mixture of excitotoxicity, neuroinflammation, and cell death. Biomarkers that can track these lesions and inflammatory processes are being...     

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.     

Efficacy of the cognitive orientation to daily occupational performance with Brazilian children with developmental coordination disorder

Background: Children with Developmental Coordination Disorder (DCD) have difficulties performing daily activities which reflects negatively on participation, impacting their lives.

Objectives: To examine the effects of the cognitive orientation to daily occupational performance Approach (CO-OP Approach) protocol on occupational performance and satisfaction of Brazilian children who have DCD; to examine whether children could transfer strategies and skills learned during CO-OP to untrained goals.

Methods: A pre-post group comparison design with eight boys aged 6–10 years old. Children participated in 12 CO-OP sessions with their parents twice a week, with an extra session added to the protocol for parents´ orientation. The Canadian Occupational Performance Measure and the Performance Quality Rating Scale were used as outcome measures. The study was registered by the United States Institutes of Health at ClinicalTrials.gov (NCT03112746).

Results: Intervention resulted in higher, clinically and statistically significant, occupational performance measures according to parents, children’s, and external evaluators’ perspectives. All children improved occupational performance on their selected goals and five children could transfer the ability to use cognitive strategies to tasks not addressed in therapy.

Conclusions: This study provides initial directions for future research to investigate the applicability and to implement CO-OP approach on pediatric settings in Brazil.