Maternal Attachment Style, Interpersonal Trauma History, and Childbirth-Related Post-traumatic Stress

Childbirth-related post-traumatic stress has potentially negative and enduring consequences for the well-being of women and their families. Although research to date has identified attachment style and trauma history as individual risk factors, they have yet to be examined as integrative processes in the development and maintenance of childbirth-related post-traumatic stress. The current investigation aimed to examine whether attachment style may moderate the impact of a history of interpersonal trauma on initial levels and the rate of change in post-traumatic stress symptomatology across the first 6 months of the postpartum period. A large community sample of women were recruited from two Canadian urban hospitals. Childbirth-related post-traumatic stress symptoms were assessed longitudinally at 5 weeks, 2 months, and 6 months postpartum. Latent growth curve modeling (n = 251) revealed that attachment style moderated the impact of a history of interpersonal trauma on initial levels and the rate of change in post-traumatic stress symptomatology, while controlling for other well-established psychosocial (e.g., trait anxiety, previous psychopathology, lack of perceived support) and childbirth-related (e.g., mode of birth, labor pain, subjective experience) risk factors. More secure attachment conferred resiliency and more fearful attachment conferred vulnerability among women without a history of interpersonal trauma, while more preoccupied and more dismissing attachment conferred resiliency among women with a history of interpersonal trauma. These findings highlight the importance of understanding the integrative processes among risk and protective factors underlying the development of and ability to cope with childbirth-related post-traumatic stress. Attachment style and trauma history, which can be quickly measured, should be considered as targets in antenatal screening

Accepted: 2011-10-04.) © SAJEI South Afr

Original Research: GGSTM1, GSTP1 and NQO1 polymorphisms and susceptibility to asthma among South African children Gluthathione-S-transferase (GSTM1 and GSTP1) and nicotinamide quinone oxidoreductase (NQO1) genes play an important role in cellular protection against oxidative stress, which has been linked to asthma pathogenesis. We investigated whether common, functional polymorphisms in GSTM1, GSTP1, and NQO1 influence susceptibility to asthma among schoolchildren in South Africa. Genomic deoxyribonucleic acid (DNA) was extracted from 317 primary schoolchildren, aged 9-11 years, from the urban, underprivileged socio-economic communities of Durban. GSTM1 (null vs. present genotype), GSTP1 (Ile105Val; AA →AG+GG) and the NQO1 (Pro/Ser; CC →CT/TT) genotypes were determined using polymerase chain reaction. Among the children, 30% were GSTM1 null, 65% carried the G allele for GSTP1, and 36% carried the C allele for NQO1.There was a high prevalence of asthma of any severity (46.1%), with 20.4% reporting persistent asthma. The GSTP1 AG+GG polymorphic genotype was significantly associated with persistent asthma (adjusted OR = 3.98; CI = 1.39, 11.36, p-value = 0.01). Neither the GSTM1, nor the NQO1, genotype was a significant predictor of persistent asthma. Therefore, the GSTP1 A/G variant may modulate the risk of persistent asthma among our sample

Lymphocytic infiltration in stage II microsatellite stable colorectal tumors: A retrospective prognosis biomarker analysis

Background: Identifying stage II patients with colorectal cancer (CRC) at higher risk of progression is a clinical priority in order to optimize the advantages of adjuvant chemotherapy while avoiding unnecessary toxicity. Recently, the intensity and the quality of the host immune response in the tumor microenvironment have been reported to have an important role in tumorigenesis and an inverse association with tumor progression. This association is well established in microsatellite instable CRC. In this work, we aim to assess the usefulness of measures of T-cell infiltration as prognostic biomarkers in 640 stage II, CRC tumors, 582 of them confirmed microsatellite stable. Methods and findings: We measured both the quantity and clonality index of T cells by means of T-cell receptor (TCR) immunosequencing in a discovery dataset (95 patients with colon cancer diagnosed at stage II and microsatellite stable, median age 67, 30% women) and replicated the results in 3 additional series of stage II patients from 2 countries. Series 1 and 2 were recruited in Barcelona, Spain and included 112 fresh frozen (FF, median age 69, 44% women) and 163 formalin-fixed paraffin-embedded (FFPE, median age 67, 39% women) samples, respectively. Series 3 included 270 FFPE samples from patients recruited in Haifa, Northern Israel, as part of a large case-control study of CRC (median age 73, 46% women). Median follow-up time was 81.1 months. Cox regression models were fitted to evaluate the prognostic value of T-cell abundance and Simpson clonality of TCR variants adjusting by sex, age, tumor location, and stage (IIA and IIB). In the discovery dataset, higher TCR abundance was associated with better prognosis (hazard ratio [HR] for ≥Q1 = 0.25, 95% CI 0.10-0.63, P = 0.003). A functional analysis of gene expression on these tumors revealed enrichment in pathways related to immune response. Higher values of clonality index (lower diversity) were not associated with worse disease-free survival, though the HR for ≥Q3 was 2.32 (95% CI 0.90-5.97, P = 0.08). These results were replicated in an independent FF dataset (TCR abundance: HR = 0.30, 95% CI 0.12-0.72, P = 0.007; clonality: HR = 3.32, 95% CI 1.38-7.94, P = 0.007). Also, the association with prognosis was tested in 2 independent FFPE datasets. The same association was observed with TCR abundance (HR = 0.41, 95% CI 0.18-0.93, P = 0.03 and HR = 0.56, 95% CI 0.31-1, P = 0.042, respectively, for each FFPE dataset). However, the clonality index was associated with prognosis only in the FFPE dataset from Israel (HR = 2.45, 95% CI 1.39-4.32, P = 0.002). Finally, a combined analysis combining all microsatellite stable (MSS) samples demonstrated a clear prognosis value both for TCR abundance (HR = 0.39, 95% CI 0.26-0.57, P = 1.3e-06) and the clonality index (HR = 2.13, 95% CI 1.44-3.15, P = 0.0002). These associations were also observed when variables were considered continuous in the models (HR per log2 of TCR abundance = 0.85, 95% CI 0.78-0.93, P = 0.0002; HR per log2 or clonality index = 1.16, 95% CI 1.03-1.31, P = 0.016). Limitations: This is a retrospective study, and samples had been preserved with different methods. Validation series lack complete information about microsatellite instability (MSI) status and pathology assessment. The Molecular Epidemiology of Colorectal Cancer (MECC) study had information about overall survival instead of progression-free survival. Conclusion: Results from this study demonstrate that tumor lymphocytes, assessed by TCR repertoire quantification based on a sequencing method, are an independent prognostic factor in microsatellite stable stage II CRC

Proceedings of the third international molecular pathological epidemiology (MPE) meeting

Molecular pathological epidemiology (MPE) is a transdisciplinary and relatively new scientific discipline that integrates theory, methods and resources from epidemiology, pathology, biostatistics, bioinformatics and computational biology. The underlying objective of MPE research is to better understand the etiology and progression of complex and heterogeneous human diseases with the goal of informing prevention and treatment efforts in population health and clinical medicine. Although MPE research has been commonly applied to investigating breast, lung, and colorectal cancers, its methodology can be used to study most diseases. Recent successes in MPE studies include: 1) the development of new statistical methods to address etiologic heterogeneity; 2) the enhancement of causal inference; 3) the identification of previously unknown exposure-subtype disease associations; and 4) better understanding of the role of lifestyle/behavioral factors on modifying prognosis according to disease subtype. Central challenges to MPE include the relative lack of transdisciplinary experts, educational programs, and forums to discuss issues related to the advancement of the field. To address these challenges, highlight recent successes in the field, and identify new opportunities, a series of MPE meetings have been held at the Dana-Farber Cancer Institute in Boston, MA. Herein, we share the proceedings of the Third International MPE Meeting, held in May 2016 and attended by 150 scientists from 17 countries. Special topics included integration of MPE with immunology and health disparity research. This meeting series will continue to provide an impetus to foster further transdisciplinary integration of divergent scientific fields

Reconstructing Asian faunal introductions to eastern Africa from multi-proxy biomolecular and archaeological datasets

Human-mediated biological exchange has had global social and ecological impacts. In subS-aharan Africa, several domestic and commensal animals were introduced from Asia in the pre-modern period; however, the timing and nature of these introductions remain contentious. One model supports introduction to the eastern African coast after the mid-first millennium CE, while another posits introduction dating back to 3000 BCE. These distinct scenarios have implications for understanding the emergence of long-distance maritime connectivity, and the ecological and economic impacts of introduced species. Resolution of this longstanding debate requires new efforts, given the lack of well-dated fauna from high-precision excavations, and ambiguous osteomorphological identifications. We analysed faunal remains from 22 eastern African sites spanning a wide geographic and chronological range, and applied biomolecular techniques to confirm identifications of two Asian taxa: domestic chicken (Gallus gallus) and black rat (Rattus rattus). Our approach included ancient DNA (aDNA) analysis aided by BLAST-based bioinformatics, Zooarchaeology by Mass Spectrometry (ZooMS) collagen fingerprinting, and direct AMS (accelerator mass spectrometry) radiocarbon dating. Our results support a late, mid-first millennium CE introduction of these species. We discuss the implications of our findings for models of biological exchange, and emphasize the applicability of our approach to tropical areas with poor bone preservation

Germline Polymorphisms in MGMT Associated With Temozolomide-Related Myelotoxicity Risk in Patients With Glioblastoma Treated on NRG Oncology/RTOG 0825

Background: We sought to identify clinical and genetic predictors of temozolomide-related myelotoxicity among patients receiving therapy for glioblastoma. Methods: Patients (n = 591) receiving therapy on NRG Oncology/RTOG 0825 were included in the analysis. Cases were patients with severe myelotoxicity (grade 3 and higher leukopenia, neutropenia, and/or thrombocytopenia); controls were patients without such toxicity. A risk-prediction model was built and cross-validated by logistic regression using only clinical variables and extended using polymorphisms associated with myelotoxicity. Results: 23% of patients developed myelotoxicity (n = 134). This toxicity was first reported during the concurrent phase of therapy for 56 patients; 30 stopped treatment due to toxicity. Among those who continued therapy (n = 26), 11 experienced myelotoxicity again. The final multivariable clinical factor model included treatment arm, gender, and anticonvulsant status and had low prediction accuracy (area under the curve [AUC] = 0.672). The final extended risk prediction model including four polymorphisms in MGMT had better prediction (AUC = 0.827). Receiving combination chemotherapy (OR, 1.82; 95% CI, 1.02-3.27) and being female (OR, 4.45; 95% CI, 2.45-8.08) significantly increased myelotoxicity risk. For each additional minor allele in the polymorphisms, the risk increased by 64% (OR, 1.64; 95% CI, 1.43-1.89). Conclusions: Myelotoxicity during concurrent chemoradiation with temozolomide is an uncommon but serious event, often leading to treatment cessation. Successful prediction of toxicity may lead to more cost-effective individualized monitoring of at-risk subjects. The addition of genetic factors greatly enhanced our ability to predict toxicity among a group of similarly treated glioblastoma patients

Qualitative evaluation of a preventive intervention for the offspring of parents with a history of depression

Background: Meta-analyses of randomised controlled trials suggest that psychological interventions to reduce children’s risk of depression are effective. Nevertheless, these effects are modest and diminish over time. The Medical Research Council recommends a mixed-methods approach to the evaluation of complex interventions. By gaining a more thorough understanding of participants’ perspectives, qualitative evaluations of preventive interventions could improve their efficacy, longevity and transfer into clinical practice. Methods: 18 parents and 22 children who had received a 12-session family- and group-based cognitivebehavioural intervention to prevent youth depression as part of a randomised controlled trial took part in semistructured interviews or a focus group about aspects which had been perceived as helpful, elements they were still using after the intervention had ended, and suggestions they had for improving the intervention. Results: The chance to openly share and discuss their experiences of depression within and between families was considered helpful by both children and parents. Children benefitted the most from learning coping strategies for dealing with stress and many still used them in everyday life. Parents profited mostly from increasing positive family time, but noted that maintaining new routines after the end of the intervention proved difficult. Participants were generally content with the intervention but commented on how tiring and time consuming it was. Conclusions: Managing parents’ expectations of family-based interventions in terms of their own mental health needs (versus those of their children) and leaving more room for open discussions may result in interventions which are more appealing to participating families. Increasing intervals between sessions may be one means of improving the longevity of interventions. Trial registration: The original RCT this evaluation is a part of was registered under NCT02115880