Integrating neuroimaging biomarkers into the multicentre, high-dose erythropoietin for asphyxia and encephalopathy (HEAL) trial: rationale, protocol and harmonisation.

INTRODUCTION: MRI and MR spectroscopy (MRS) provide early biomarkers of brain injury and treatment response in neonates with hypoxic-ischaemic encephalopathy). Still, there are challenges to incorporating neuroimaging biomarkers into multisite randomised controlled trials. In this paper, we provide the rationale for incorporating MRI and MRS biomarkers into the multisite, phase III high-dose erythropoietin for asphyxia and encephalopathy (HEAL) Trial, the MRI/S protocol and describe the strategies used for harmonisation across multiple MRI platforms. METHODS AND ANALYSIS: Neonates with moderate or severe encephalopathy enrolled in the multisite HEAL trial undergo MRI and MRS between 96 and 144 hours of age using standardised neuroimaging protocols. MRI and MRS data are processed centrally and used to determine a brain injury score and quantitative measures of lactate and n-acetylaspartate. Harmonisation is achieved through standardisation-thereby reducing intrasite and intersite variance, real-time quality assurance monitoring and phantom scans. ETHICS AND DISSEMINATION: IRB approval was obtained at each participating site and written consent obtained from parents prior to participation in HEAL. Additional oversight is provided by an National Institutes of Health-appointed data safety monitoring board and medical monitor. TRIAL REGISTRATION NUMBER: NCT02811263; Pre-result.

High urea induces depression and LTP impairment through mTOR signalling suppression caused by carbamylation.

BACKGROUND: Urea, the end product of protein metabolism, has been considered to have negligible toxicity for a long time. Our previous study showed a depression phenotype in urea transporter (UT) B knockout mice, which suggests that abnormal urea metabolism may cause depression. The purpose of this study was to determine if urea accumulation in brain is a key factor causing depression using clinical data and animal models. METHODS: A meta-analysis was used to identify the relationship between depression and chronic diseases. Functional Magnetic Resonance Imaging (fMRI) brain scans and common biochemical indexes were compared between the patients and healthy controls. We used behavioural tests, electrophysiology, and molecular profiling techniques to investigate the functional role and molecular basis in mouse models. FINDINGS: After performing a meta-analysis, we targeted the relevance between chronic kidney disease (CKD) and depression. In a CKD mouse model and a patient cohort, depression was induced by impairing the medial prefrontal cortex. The enlarged cohort suggested that urea was responsible for depression. In mice, urea was sufficient to induce depression, interrupt long-term potentiation (LTP) and cause loss of synapses in several models. The mTORC1-S6K pathway inhibition was necessary for the effect of urea. Lastly, we identified that the hydrolysate of urea, cyanate, was also involved in this pathophysiology. INTERPRETATION: These data indicate that urea accumulation in brain is an independent factor causing depression, bypassing the psychosocial stress. Urea or cyanate carbamylates mTOR to inhibit the mTORC1-S6K dependent dendritic protein synthesis, inducing impairment of synaptic plasticity in mPFC and depression-like behaviour. CKD patients may be able to attenuate depression only by strict management of blood urea.

Test-Retest Reliability of Graph Theoretic Metrics in Adolescent Brains.

Graph theory analysis of structural brain networks derived from diffusion tensor imaging (DTI) has become a popular analytical method in neuroscience, enabling advanced investigations of neurological and psychiatric disorders. The purpose of this study was to investigate (1) the effects of edge weighting schemes and (2) the effects of varying interscan periods on graph metrics within the adolescent brain. We compared a binary (B) network definition with three weighting schemes: fractional anisotropy (FA), streamline count, and streamline count with density and length correction (SDL). Two commonly used global and two local graph metrics were examined. The analysis was conducted with two groups of adolescent volunteers who received DTI scans either 12 weeks apart (16.62 ± 1.10 years) or within the same scanning session (30 min apart) (16.65 ± 1.14 years). The intraclass correlation coefficient was used to assess test-retest reliability and the coefficient of variation (CV) was used to assess precision. On average, each edge scheme produced reliable results at both time intervals. Weighted measures outperformed binary measures, with SDL weights producing the most reliable metrics. All edge schemes except FA displayed high CV values, leaving FA as the only edge scheme that consistently showed high precision while also producing reliable results. Overall findings suggest that FA weights are more suited for DTI connectome studies in adolescents.

Preoperative Assessment of the Pregnant Patient Undergoing Nonobstetric Surgery.

The anesthetic management of pregnant patients can present a variety of challenges and a thorough preoperative assessment is necessary before initiating any anesthetic services. Both the mother and the fetus need to be considered when formulating an anesthetic plan and discussing informed consent. The overall aims in assessing a pregnant patient are to identity potential issues that can lead to catastrophic complications, provide adequate information allowing the mother to make informed decisions, and to obtain knowledge for tailoring an anesthetic that maintains maternal and fetal homeostasis.

The Louisiana Mental and Behavioral Health Capacity Project Trauma-Informed Integrated Care Model and Improved Posttraumatic Stress Outcomes.

OBJECTIVE: The Mental and Behavioral Health Capacity Project in Louisiana has been addressing health disparities by increasing accessibility and availability through integrating services into primary care clinics. Integrated health is becoming the standard of care, providing an opportunity to address the trauma-specific needs of communities, and allowing for informed and less stigmatized services. The purpose of this study is to test the efficacy of the Mental and Behavioral Health Capacity Project in Louisiana model in the primary care settings to reduce posttraumatic stress symptoms and physical health complaints. DESIGN: A pre-experimental time series design was used on the basis of participants self-reporting at least 1 trauma at intake and follow-up collected at 1-, 3-, and 6-month intervals. The hypotheses were that posttraumatic stress and physical health complaints would significantly decrease over the course of treatment. SETTING: This study was part of a larger study to evaluate the effectiveness of the Mental and Behavioral Health Capacity Project in Louisiana-integrated health efforts. Sample parameters included (1) intake date from January 2013 through December 2015; (2) at least 18 years of age; and (3) presented at 1 of 5 primary health care clinics in Southeast Louisiana. PARTICIPANTS: A total of 235 patients were selected; the mean age was 44.7 years (SD = 13.6) and the majority were white (68%) and female (76%). INTERVENTION: Brief behavioral-based trauma treatment was delivered using both on-site and telemedicine therapies provided by a psychologist, psychiatrist, or through a combined treatment model. MAIN OUTCOME MEASURE: The main outcome measures were the Posttraumatic Stress Civilian Checklist (PCL-C) and the Patient Health Questionnaire (PHQ-15). RESULTS: The hypothesis was supported. Statistically significant decreases in posttraumatic stress symptoms and physical health complaints were shown over the course of treatment, with 63% of the group demonstrating clinically significant change. CONCLUSIONS: This study supports brief trauma treatment in primary care clinics as an effective method of reducing trauma and physical health symptoms in postdisaster environments.