Immunohistochemical expression and prognostic significance of MAGE-A in canine oral malignant melanoma.

Canine oral malignant melanoma (COMM) is considered a chemo-resistant cancer with a poor long-term prognosis. The melanoma-associated antigen A (MAGE-A) genes, which belong to the cancer-testis antigen family, are expressed in several different canine cancers but not in normal somatic tissue. This study evaluates the expression of MAGE-A proteins and their prognostic role in COMM. The study was conducted in 2 parts. During the first part, biopsies from oral malignant melanomas from 43 dogs were examined and immunohistochemically assessed for expression of MAGE-A proteins. For the second part, the association between MAGE-A expression and outcome was assessed using follow-up data which was available for 20 dogs whose primary tumour had been controlled with surgery +/- radiation therapy. MAGE-A proteins were expressed in 88.4% (38/43) of oral malignant melanomas and had a predominantly cytoplasmic expression pattern. Immunopositivity was observed in more than 50% of the cells in 21 dogs (48.8%). Immunostaining intensity was classified as weak, moderate and intense in 16 (37%), 16 (37%) and 6 (14%) cases, respectively. No staining for MAGE-A was seen in 5 dogs (11%). Dogs whose COMM had weak MAGE-A staining intensity had a median survival time (MST) of 320 days while this was 129 days for dogs with moderate and intense immunostaining (p = 0.161). Dogs whose COMM had >50% of positive staining neoplastic cells had an MST of 141 days and dogs with a staining <50% had an MST of 320 days (p = 0.164). MAGE-A expression did not influence survival in our cohort.

Adverse childhood experiences: Basics for the paediatrician.

In 1998, the Centers for Disease Control and Prevention Adverse Childhood Experiences study established the profound effects of early childhood adversity on life course health. The burden of cumulative adversities can affect gene expression, immune system development and condition stress response. A scientific framework provides explanation for numerous childhood and adult health problems and high-risk behaviours that originate in early life. In our review, we discuss adverse childhood experiences, toxic stress, the neurobiological basis and multigenerational and epigenetic transmission of trauma and recognized health implications. Further, we outline building resilience, screening in the clinical setting, primary care interventions, applying trauma-informed care and future directions. We foresee that enhancing knowledge of the far-reaching effects of adverse childhood events will facilitate mitigation of toxic stress, promote child and family resilience and optimize life course health trajectories.