Can we more precisely classify exposure to antenatal depression and anxiety in multivariable prediction models of pregnancy and birth outcomes: a population-based cohort study.

BACKGROUND: Depression and anxiety are highly prevalent within the perinatal period and have been associated with myriad adverse pregnancy and birth outcomes. In this study, we sought to investigate whether population-based data can be used to build complex, longitudinal mental health histories that improve our ability to predict adverse pregnancy and birth outcomes. METHODS: Using population-based, administrative datasets, we examined individual-level mental health services use of all birth parents who delivered a live infant in British Columbia, Canada between April 1, 2000, and December 31, 2013, and who were registered with the provincial Medical Services Plan for over 100 days per year from 10-years preconception to 1-year postpartum. We operationalized variables to proxy severity, persistence, and frequency of depression/anxiety from preconception through pregnancy, then constructed predictive regression models for postpartum depression/anxiety and preterm birth. RESULTS: Predictive modeling of postpartum depression/anxiety and preterm birth revealed better predictions and stronger performance with inclusion of a more detailed preconception mental health history. Incorporating dichotomous indicators for depression/anxiety across preconception markedly improved predictive power and model fit. Our detailed measures of mental health service use predicted postpartum depression/anxiety much better than preterm birth. Variables characterizing use of outpatient psychiatry care and outpatient visit frequency within the first five years preconception were most useful in predicting postpartum depression/anxiety and preterm birth, respectively. CONCLUSION: We report a feasible method for developing and applying more nuanced definitions of depression/anxiety within population-based data. By accounting for differing profiles of mental health treatment, mental health history, and current mental health, we can better control for severity of underlying conditions and thus better understand more complex associations between antenatal mental health and adverse outcomes.

Preconception mental health and the relationship between antenatal depression or anxiety and gestational diabetes mellitus: a population-based cohort study.

BACKGROUND: Antenatal depression and anxiety are highly prevalent conditions that have been associated with increased risk for myriad adverse outcomes. Current literature exploring the connection between antenatal mental health and gestational diabetes mellitus (GDM) is limited, presenting conflicting evidence. We sought to evaluate the association between antenatal depression/anxiety (DEP-ANX) and GDM using population-based, administrative data, accounting for aspects of preconception mental health. METHODS: In this population-based retrospective cohort study, we included all singleton births in British Columbia, Canada from April 1, 2000, to December 31, 2014. We identified instances of DEP-ANX from outpatient and inpatient records that included relevant diagnostic codes and stratified our cohort by preconception DEP-ANX persistence. Logistic regression models were run to estimate odds of GDM given antenatal DEP-ANX. Models were adjusted for the birthing person's socio-demographics and pregnancy characteristics. Using an expanded cohort, we ran conditional logistic regression models that matched birthing people to themselves (in a subsequent pregnancy) based on discordance of exposure and outcome. RESULTS: Out of the 228,144 births included in this study, 43,664 (19.1%) were to birthing people with antenatal health service use for DEP-ANX. There were 4,180 (9.6%) cases of GDM among those antenatal exposure to DEP-ANX compared to 15,102 (8.2%) among those without exposure (SMD 0.049). We observed an unadjusted odds ratio (OR) of 1.19 (95% CI: 1.15 - 1.23) and fully adjusted OR of 1.15 (95% CI: 1.11 - 1.19) overall. Apparent risk for GDM given antenatal DEP-ANX was highest among the no DEP-ANX history stratum, with a fully adjusted OR of 1.24 (95% CI: 1.15 - 1.34). Associations estimated by matched sibling analysis were non-significant (fully adjusted OR 1.19 [95% CI: 0.86 - 1.63]). CONCLUSIONS: Results from this population-based study suggest an association between antenatal DEP-ANX and GDM that varied based on mental health history. Our analysis could suggest that incident cases of DEP-ANX within pregnancy are more closely associated with GDM compared to recurring or chronic cases.

Patient-reported outcomes in HCC: A scoping review by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.

BACKGROUND AND AIMS: HCC is a leading cause of mortality in patients with advanced liver disease and is associated with significant morbidity. Despite multiple available curative and palliative treatments, there is a lack of systematic evaluation of patient-reported outcomes (PROs) in HCC. APPROACH AND RESULTS: The American Association for the Study of Liver Diseases Practice Metrics Committee conducted a scoping review of PROs in HCC from 1990 to 2021 to (1) synthesize the evidence on PROs in HCC and (2) provide recommendations on incorporating PROs into clinical practice and quality improvement efforts. A total of 63 studies met inclusion criteria investigating factors associated with PROs, the relationship between PROs and survival, and associations between HCC therapy and PROs. Studies recruited heterogeneous populations, and most were cross-sectional. Poor PROs were associated with worse prognosis after adjusting for clinical factors and with more advanced disease stage, although some studies showed better PROs in patients with HCC compared to those with cirrhosis. Locoregional and systemic therapies were generally associated with a high symptom burden; however, some studies showed lower symptom burden for transarterial radiotherapy and radiation therapy. Qualitative studies identified additional symptoms not routinely assessed with structured questionnaires. Gaps in the literature include lack of integration of PROs into clinical care to guide HCC treatment decisions, unknown impact of HCC on caregivers, and the effect of palliative or supportive care quality of life and health outcomes. CONCLUSION: Evidence supports assessment of PROs in HCC; however, clinical implementation and the impact of PRO measurement on quality of care and longitudinal outcomes need future investigation.

The Effect of Divalent Cations on the Thermostability of Type II Polyketide Synthase Acyl Carrier Proteins.

The successful engineering of biosynthetic pathways hinges on understanding the factors that influence acyl carrier protein (ACP) stability and function. The stability and structure of ACPs can be influenced by the presence of divalent cations, but how this relates to primary sequence remains poorly understood. As part of a course-based undergraduate research experience, we investigated the thermostability of type II polyketide synthase (PKS) ACPs. We observed an approximate 40 °C range in the thermostability amongst the 14 ACPs studied, as well as an increase in stability (5 - 26 °C) of the ACPs in the presence of divalent cations. Distribution of charges in the helix II-loop-helix III region was found to impact the enthalpy of denaturation. Taken together, our results reveal clues as to how the sequence of type II PKS ACPs relates to their structural stability, information that can be used to study how ACP sequence relates to function.

Acyl Carrier Protein Cyanylation Delivers a Ketoacyl Synthase-Carrier Protein Cross-Link.

Acyl carrier proteins (ACPs) are central hubs in polyketide and fatty acid biosynthetic pathways, but the fast motions of the ACP's phosphopantetheine (Ppant) arm make its conformational dynamics difficult to capture using traditional spectroscopic approaches. Here we report that converting the terminal thiol of Escherichia coli ACP's Ppant arm into a thiocyanate activates this site to form a selective cross-link with the active site cysteine of its partner ketoacyl synthase (FabF). The reaction releases a cyanide anion, which can be detected by infrared spectroscopy. This represents a practical and generalizable method for obtaining and visualizing ACP-protein complexes relevant to biocatalysis and will be valuable in future structural and engineering studies.