Subject(s)
Granulomatosis with Polyangiitis/diagnosis , Laryngostenosis/diagnosis , Methotrexate/administration & dosage , alpha 1-Antitrypsin Deficiency/diagnosis , alpha 1-Antitrypsin Deficiency/drug therapy , Administration, Oral , Child, Preschool , Dexamethasone/therapeutic use , Diagnosis, Differential , Emergency Service, Hospital , Female , Granulomatosis with Polyangiitis/complications , Humans , Laryngostenosis/drug therapy , Laryngostenosis/etiology , Rare Diseases , Recurrence , Risk Assessment , Treatment Outcome , alpha 1-Antitrypsin Deficiency/complicationsABSTRACT
OBJECTIVE: To identify psychosocial challenges facing pregnant women with intellectual and developmental disabilities (IDD) using retrospective, routinely collected electronic medical record data. DESIGN: A retrospective qualitative study using narratives and supporting documents found in the electronic medical record of an academic family health team (FHT). SETTING: Academic FHT in southeastern Ontario. PARTICIPANTS: A sample of 10 women with a diagnosis of IDD, rostered to physicians at the academic FHT, who delivered a child between January 2010 and June 2015 (14 pregnancies). Exclusion criteria included women who received prenatal care from a midwife and women for whom no delivery or antenatal records were available. METHODS: Thematic analysis of data collected from a retrospective chart review. MAIN FINDINGS: Many women with IDD had yes marked on their antenatal records for poor social supports, family violence, and parenting concerns. Women with IDD had pregnancies that were characterized by complex social environments, financial instability, discord between their perceptions and their physicians' perceptions, and stressful encounters with Child and Family Services. CONCLUSION: Findings in this study support previous research that pregnant women with IDD are a vulnerable population, at higher risk of adverse health outcomes. There is a need for specific care guidelines for health care providers, as well as additional resources and social supports.
Subject(s)
Developmental Disabilities/psychology , Intellectual Disability/psychology , Pregnancy Complications/psychology , Prenatal Care/psychology , Adult , Developmental Disabilities/therapy , Domestic Violence/statistics & numerical data , Female , Humans , Intellectual Disability/therapy , Ontario , Pregnancy , Pregnancy Complications/therapy , Primary Health Care/methods , Qualitative Research , Retrospective Studies , Social Support , Vulnerable PopulationsABSTRACT
Activation-induced cytidine deaminase (AID) is essential for class-switch recombination (CSR) and somatic hypermutation (SHM) of Ig genes. The AID C terminus is required for CSR, but not for S-region DNA double-strand breaks (DSBs) during CSR, and it is not required for SHM. AID lacking the C terminus (ΔAID) is a dominant negative (DN) mutant, because human patients heterozygous for this mutant fail to undergo CSR. In agreement, we show that ΔAID is a DN mutant when expressed in AID-sufficient mouse splenic B cells. To have DN function, ΔAID must have deaminase activity, suggesting that its ability to induce DSBs is important for the DN function. Supporting this hypothesis, Msh2-Msh6 have been shown to contribute to DSB formation in S regions, and we find in this study that Msh2 is required for the DN activity, because ΔAID is not a DN mutant in msh2(-/-) cells. Our results suggest that the DNA DSBs induced by ΔAID are unable to participate in CSR and might interfere with the ability of full-length AID to participate in CSR. We propose that ΔAID is impaired in its ability to recruit nonhomologous end joining repair factors, resulting in accumulation of DSBs that undergo aberrant resection. Supporting this hypothesis, we find that the S-S junctions induced by ΔAID have longer microhomologies than do those induced by full-length AID. In addition, our data suggest that AID binds Sµ regions in vivo as a monomer.
