The Psychedelic Future of Post-Traumatic Stress Disorder Treatment.

Post-traumatic stress disorder (PTSD) is a mental health condition that can occur following exposure to a traumatic experience. An estimated 12 million U.S. adults are presently affected by this disorder. Current treatments include psychological therapies (e.g., exposure-based interventions) and pharmacological treatments (e.g., selective serotonin reuptake inhibitors (SSRIs)). However, a significant proportion of patients receiving standard-of-care therapies for PTSD remain symptomatic, and new approaches for this and other trauma-related mental health conditions are greatly needed. Psychedelic compounds that alter cognition, perception, and mood are currently being examined for their efficacy in treating PTSD despite their current status as Drug Enforcement Administration (DEA)- scheduled substances. Initial clinical trials have demonstrated the potential value of psychedelicassisted therapy to treat PTSD and other psychiatric disorders. In this comprehensive review, we summarize the state of the science of PTSD clinical care, including current treatments and their shortcomings. We review clinical studies of psychedelic interventions to treat PTSD, trauma-related disorders, and common comorbidities. The classic psychedelics psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT) and DMT-containing ayahuasca, as well as the entactogen 3,4-methylenedioxymethamphetamine (MDMA) and the dissociative anesthetic ketamine, are reviewed. For each drug, we present the history of use, psychological and somatic effects, pharmacology, and safety profile. The rationale and proposed mechanisms for use in treating PTSD and traumarelated disorders are discussed. This review concludes with an in-depth consideration of future directions for the psychiatric applications of psychedelics to maximize therapeutic benefit and minimize risk in individuals and communities impacted by trauma-related conditions.

Early childhood fluoride exposure and preadolescent kidney function.

BACKGROUND: Early-life renal maturation is susceptible to nephrotoxic environmental chemicals. Given the widespread consumption of fluoride and the global obesity epidemic, our main aim was to determine whether childhood fluoride exposure adversely affects kidney function in preadolescence, and if adiposity status modifies this association. METHODS: Our study included 438 children from the PROGRESS cohort. Urinary fluoride (uF) was assessed at age 4 by diffusion analysis; outcomes studied included estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), selected kidney proteins and blood pressure measured at age 8-12 years. We modeled the relationship between uF and outcomes, and adjusted for body mass index (BMI), age, sex, and socioeconomic status. RESULTS: The median uF concentration was 0.67 µg/mL. We observed null associations between 4-year uF and preadolescent eGFR, although effect estimates were in the expected inverse direction. A single unit increase in ln-transformed uF was associated with a 2.2 mL/min decrease in cystatin C-based eGFR (95% CI: 5.8, 1.4; p = 0.23). We observed no evidence of sex-specific effects or effect modification by BMI status. Although uF was not associated with BMI, among children with obesity, we observed an inverse association (ß: 4.8; 95% CI: 10.2, 0.6; p = 0.08) between uF and eGFR. CONCLUSIONS: Low-level fluoride exposure in early childhood was not associated with renal function in preadolescence. However, given the adverse outcomes of chronic fluoride consumption it is possible that the preadolescent age was too young to observe any effects. Longitudinal follow-up in this cohort and others is an important next step.

Anti-Inflammatory Interleukin 10 Inversely Relates to Coronary Atherosclerosis in Persons With Human Immunodeficiency Virus.

Interleukin 10 (IL-10) is an anti-inflammatory cytokine that may be protective against coronary atherosclerosis. In an observational study of persons with human immunodeficiency virus (PWH) and uninfected controls, IL-10 was measured in serum samples by means of enzyme-linked immunosorbent assay, and coronary atherosclerosis was assessed using computed tomographic angiography. Among PWH, a 10-fold decrease in IL-10 was associated with a 2.6-fold increase in the odds of coronary plaque (P = .01), after controlling for traditional and nontraditional cardiovascular risk factors. IL-10 was also inversely associated with total coronary plaque (ρ = -0.19; P = .02) and noncalcified coronary plaque (ρ = -0.24; P = .004). Our findings suggest a role for IL-10 in mitigating atherosclerosis in PWH. Clinical Trials Registration. NCT00455793.

Low vitamin D is associated with coronary atherosclerosis in women with HIV.

BACKGROUND: Vitamin D deficiency is underdiagnosed and undertreated, especially among people living with HIV (PLWH). Recently, there has been an increased interest in the role of vitamin D in cardiovascular disease (CVD). While vitamin D deficiency has been associated with CVD in observational studies in the general population, there are limited data in PLWH. We therefore performed an analysis to assess the relationship of vitamin D and coronary atherosclerosis using coronary CT angiography (CCTA). METHODS: Women living with HIV (WLWH) without known CVD were included. Based on the median value of serum vitamin D levels, participants were dichotomized to either the <25 ng/ml (lower vitamin D group) or ≥25 ng/ml (higher vitamin D group). CCTA was used to assess plaque characteristics. RESULTS: Forty-three WLWH were included in the analyses (mean age 46 ±8 years, 56% African American, duration of HIV 15 ±6 years, 83% undetectable HIV viral load). WLWH in the lower vitamin D group (n=22) had significantly higher numbers of segments with any coronary plaque (2.27 ±3.01 versus 0.38 ±0.97; P=0.02) and segments with non-calcified coronary plaque (1.41 ±1.82 versus 0.29 ±0.64; P=0.03) compared with WLWH in the higher vitamin D group (n=21). After adjusting for Framingham CHD risk point score, body mass index, diabetes and race, the relationship remained significant. CONCLUSIONS: Our study demonstrates a significant, independent relationship between lower vitamin D status and higher numbers of noncalcified coronary plaque segments in WLWH. Further studies are warranted to evaluate the effect of vitamin D on CVD in PLWH. Trial Registration Identifier: NCT00455793.

Gastrointestinal Barrier Breakdown and Adipose Tissue Inflammation.

PURPOSE OF REVIEW: Obesity is a state of chronic inflammation. This review aims to summarize recent data supporting the role of the intestinal mucosal barrier and the microbiome in causing adipose tissue inflammation as well as metabolic factors that can affect the intestinal barrier. RECENT FINDINGS: Obesity and its metabolic consequences, such as diabetes mellitus, are associated with disruption of the intestinal barrier function. Intestinal microbiota and diet play a key role in the maintenance of a healthy intestinal epithelium. Intestinal barrier dysfunction can lead to heightened inflammation, which in turn can further damage the intestinal barrier through the disruption of tight junction proteins. Intestinal barrier breakdown is associated with adipose tissue inflammation in different disease states, such as obesity, diabetes mellitus, HIV, and inflammatory bowel disease. Future therapeutic strategies to ameliorate intestinal barrier function may help reduce inflammation in obesity and other chronic conditions of increased intestinal permeability.

Mild renal impairment is associated with calcified plaque parameters assessed by computed tomography angiography in people living with HIV.

OBJECTIVE: To investigate the association of mild renal impairment and coronary plaque in people living with HIV (PLHIV). METHODS: PLHIV and non-HIV controls with serum creatinine less than 1.5 mg/dl were investigated. Estimated glomerular filtration rate (eGFR) (calculated by CKD-EPI formula) was related to coronary plaque indices obtained by CT angiography. RESULTS: One hundred and eighty-four PLHIV [HIV viral load, 49 (47,49) copies/ml, CD4+ cell count, median 536 (370, 770) cells/µl, duration HIV, 15 ±â€Š7 years] and 72 HIV-negative controls without known cardiovascular disease (CVD) were studied. The two groups were well matched for traditional CVD risk factors. Serum creatinine (0.9 ±â€Š0.2 vs. 0.9 ±â€Š0.2 mg/dl, P = 0.96) and eGFR (96 ±â€Š22 vs. 96 ±â€Š24 ml/min per 1.73 m(2), P = 0.99) were similar between PLHIV and non-HIV, respectively. In PLHIV, eGFR inversely related to total severity of coronary plaque score (r = -0.27, P = 0.002), total coronary segments with plaque (r = -0.21, P = 0.005), calcified plaque segments (r = -0.15, P = 0.045), and Agatston score (r = -0.21, P = 0.006). Adjusting for total Framingham point score, BMI, and HIV parameters, eGFR remained significantly associated with calcified plaque and Agatston score in PLHIV. In HIV negative controls, eGFR did not correlate with calcified plaque (r = -0.20, P = 0.10) or Agatston score (r = -0.13, P = 0.29). Among PLHIV, those with eGFR less than 90 ml/min per 1.73 m(2) demonstrated increased total severity of coronary plaque score compared with those with eGFR greater than or equal to 90, P = 0.02). This relationship was stronger in PLHIV than the non-HIV group. CONCLUSION: Our data highlight a robust relationship between subclinical renal impairment and coronary artery disease among PLHIV. Further research is needed to understand the relationship between mild renal impairment and CVD in HIV.

I-FABP Is Higher in People With Chronic HIV Than Elite Controllers, Related to Sugar and Fatty Acid Intake and Inversely Related to Body Fat in People With HIV.

BACKGROUND: Intestinal fatty acid binding protein (I-FABP) has been shown to be a marker of intestinal damage among people living with HIV. We hypothesized that I-FABP would be increased in chronically HIV-infected patents more than elite controllers and would relate to specific nutrient intake and body composition. METHODS: In an observational study, serum I-FABP was measured by enzyme-linked immunosorbent assay. Anthropometric measurements, dual-energy x-ray absorptiometry, and single-slice abdominal computed tomography were obtained to assess body composition, as well as visceral and subcutaneous adipose tissue areas (VAT and SAT). Dietary intake was assessed using 4-day food records. RESULTS: One hundred forty-nine people with chronic HIV (65% male, 47 ± 7 years of age, 54.7% white, and 14 ± 6 years of known HIV), 10 elite controllers (60% male, 53 ± 8 years, 60% white, and 20 ± 7 years of known HIV), and 69 HIV-negative controls (59.4% male, 46 ± 7 years, and 52.2% white) were included in the analysis. I-FABP was significantly higher in HIV progressors relative to HIV-negative controls and elite controllers. In the chronic HIV group, I-FABP was positively associated with dietary intake of added sugar and with saturated fatty acids. I-FABP was inversely associated with body mass index, VAT, and SAT. I-FABP also correlated with MCP-1, CXCL10, sCD163, and lipopolysaccharide (LPS) among all participants. CONCLUSIONS: I-FABP was increased among chronically HIV-infected patients to a greater degree than in elite controllers and was related to nutrient intake and body composition in HIV progressors. Future studies to investigate the role of intestinal damage on nutrient absorption are needed to elucidate the mechanisms of these relationships. TRIAL REGISTRATION IDENTIFIER: NCT00455793.

A system for automated noise parameter measurements on MR preamplifiers and application to high B(0) fields.

A noise figure and noise parameter measurement system was developed that consists of a combination spectrum and network analyzer, preamplifier, programmable power supply, noise source, tuning board, and desktop computer. The system uses the Y-factor method for noise figure calculation and allows calibrations to correct for a decrease in excess noise ratio between the noise source and device under test, second stage (system) noise, ambient temperature variations, and available gain of the device under test. Noise parameters are extracted by performing noise figure measurements at several source impedance values obtained by adjusting an electronically controlled tuner. Results for several amplifiers at 128 MHz and 200 MHz agree with independent measurements and with the corresponding datasheets. With some modifications, the system was also used to characterize the noise figure of MRI preamplifiers in strong static magnetic fields up to 9.4 T. In most amplifiers tested the gain was found to be reduced by the magnetic field, while the noise figure increased. These changes are detrimental to signal quality (SNR) and are dependent on the electron mobility and design of the amplifier's semiconductor devices. Consequently, gallium arsenide (GaAs) field-effect transistors are most sensitive to magnetic fields due to their high electron mobility and long, narrow channel, while silicon-germanium (SiGe) bipolar transistor amplifiers are largely immune due to their very thin base.

SmartPhantom--an fMRI simulator.

Many informatics tools have emerged to process the voluminous and complex data generated by functional magnetic resonance imaging (fMRI). The interpretation of fMRI exams is largely determined by these tools. However, their performance is hard to evaluate because there is no independent means of calibration. A novel fMRI calibration system called SmartPhantom has been developed to simulate functional blood oxygen level dependent (BOLD) imaging. SmartPhantom contains a quadrature radio frequency coil, comprising two perpendicular planar loops that can be externally activated or deactivated. The system is able to produce reasonably uniform signal enhancements in a calibration sample surrounded by the two loops during an MRI scan. The enhancement is controlled well in both magnitude and predefined timing and produces BOLD-like signals. Characteristics of SmartPhantom are discussed in detail, followed by a comparison of fMRI informatics tools. Two fMRI data sets are acquired with the SmartPhantom. One with high signal-to-noise ratio provides the calibration. Another with lower SNR is input into three software packages (BrainVoyager, FSL and Statistical Parametric Mapping 2) for data preprocessing and statistical analysis. Results from the three packages are compared in both sensitivity of detecting the activation and correlation between the predicted activation and calibration.

Application of partial differential equation-based inpainting on sensitivity maps.

Inpainting is an image interpolation method. Partial differential equation (PDE)-based digital inpainting techniques are finding broad applications. In this paper, PDE-based inpainting techniques are applied to the field of MR parallel imaging. A novel model and its corresponding numerical method are introduced. This model is then applied to sensitivity maps. Coil sensitivity maps are important for parallel imaging, and they often require extrapolation and hole filling (holes being dark regions of low signal in MR images). These problems can be solved simultaneously by the application of inpainting techniques. Experiments for determining coil sensitivity maps for phantoms and cardiac MR images demonstrate the accuracy of the proposed model. Images generated using sensitivity encoding (SENSE) that utilizes inpainted sensitivity maps, thin-plate spline (TPS) estimated sensitivity maps, and Gaussian kernel smoothed (GKS) sensitivity maps are compared. From the experimental results, it can be seen that inpainted sensitivity maps produce better results than GKS sensitivity maps. The TPS method generates results similar to those of the inpainting technique but is much more time-consuming.

Observations of Surface Changes in Platinum Crucibles.

Iron which has been in solid solution in a platinum crucible will cause iron determinations in analyses to become high. Likewise the iron, oxidizing to ferric oxide during ignition, segregates along the boundaries between platinum crystals. It causes embrittlement and eventual crumbling of the crucible. During these studies it was observed that after heating in an electric muffle furnace the surface of a crucible was covered by tiny crystallographic faces. When, however, heating to the same temperature was carried out in a gas flame the facets almost smoothed out of existence.