Highlightsd 20 inpatient adults received ultra-processed and unprocessed diets for 14 days each d Diets were matched for presented calories, sugar, fat, fiber, and macronutrients d Ad libitum intake was 500 kcal/day more on the ultraprocessed versus unprocessed diet d Body weight changes were highly correlated with diet differences in energy intake

Background Mutations in STAT1 cause a broad spectrum of disease, ranging from severe viral and bacterial infections (amorphic alleles), to mild disseminated mycobacterial disease (hypomorphic alleles), to chronic mucocutaneous candidiasis (hypermorphic alleles). The hypermorphic mutations are also associated with arterial aneurysms, autoimmunity and squamous cell cancers. Objective To investigate the role of STAT1 gain of function mutations in phenotypes other than CMC. Methods We initially screened patients with chronic mucocutaneous candidiasis and autoimmunity for STAT1 mutations. We functionally characterized mutations in vitro and studied immune profiles and regulatory T cells. After our initial case identifications we explored two large cohorts of FOXP3WT IPEX-like patients for STAT1 mutations. Results We identified 5 children with polyendocrinopathy, enteropathy, and dermatitis, reminiscent of IPEX syndrome, all but one had a variety of mucosal and disseminated fungal infections. All patients lacked FOXP3 mutations but had uniallelic STAT1 mutations [c.629 G>T, p.R210I; c.1073 T>G, p.L358W, c.796G>A; p.V266I; c.1154C>T, T385M (2 patients)]. STAT1 phosphorylation in response to IFN-γ, IL-6 and IL-21 was increased and prolonged. CD4+ IL-17 producing T cells were diminished. All patients had a normal percentage of regulatory T cells in the CD4+ T cell compartment and their function was intact in the two patients tested. Patients with cells available for study had normal levels of IL-2-induced STAT5 phosphorylation.. Conclusions Gain-of-function mutations in STAT1 can cause an IPEX-like syndrome with normal frequency and function of regulatory T cells.

Fibrous cap thickness is often considered as diagnostic of the degree of plaque instability. Necrotic core area (Core(area)) and the arterial remodeling index (Remod(index)), on the other hand, are difficult to use as clinical morphological indexes: literature data show a wide dispersion of Core(area) thresholds above which plaque becomes unstable. Although histopathology shows a strong correlation between Core(area) and Remod(index), it remains unclear how these interact and affect peak cap stress (Cap(stress)), a known predictor of rupture. The aim of this study was to investigate the change in plaque vulnerability as a function of necrotic core size and plaque morphology. Cap(stress) value was calculated on 5,500 idealized atherosclerotic vessel models that had the original feature of mimicking the positive arterial remodeling process described by Glagov. Twenty-four nonruptured plaques acquired by intravascular ultrasound on patients were used to test the performance of the associated idealized morphological models. Taking advantage of the extensive simulations, we investigated the effects of anatomical plaque features on Cap(stress). It was found that: 1) at the early stages of positive remodeling, lesions were more prone to rupture, which could explain the progression and growth of clinically silent plaques and 2) in addition to cap thickness, necrotic core thickness, rather than area, was critical in determining plaque stability. This study demonstrates that plaque instability is to be viewed not as a consequence of fibrous cap thickness alone but rather as a combination of cap thickness, necrotic core thickness, and the arterial remodeling index.

At 3 T, the effective wavelength of the RF field is comparable to the dimension of the human body, resulting in B 1 standing wave effects and extra variations in phase. This effect is accompanied by an increase in B 0 field inhomogeneity compared to 1.5 T. This combination results in nonuniform magnetization preparation by the composite MLEV weighted T 2 preparation (T 2 Prep) sequence used for coronary magnetic resonance angiography (MRA). A new adiabatic refocusing T 2 Prep sequence is presented in which the magnetization is tipped into the transverse plane with a hard RF pulse and refocused using a pair of adiabatic fast-passage RF pulses. The isochromats are subsequently returned to the longitudinal axis using a hard RF pulse. Coronary magnetic resonance angiography (MRA) at 1.5 T has shown promise for the assessment of significant coronary artery disease in proximal and mid segments of the coronary arteries (1). However, low signal-to-noise ratio (SNR) limits the utilization of this imaging technique for more distal and branching vessels at 1.5 T (1). At a higher magnetic field strength, an improved SNR is expected. However, the enhanced effect of magnetic field susceptibility leads to off-resonance effects, while B 1 inhomogeneity, tissue dielectric constants, body dielectric resonances, and increased specific absorption rate (SAR) are additional limitations that must be considered at higher magnetic field strength (2-8). Therefore, to take full advantage of higher field strength and clinically realize the improved SNR, a careful sequence design that minimizes these effects is necessary.Three-dimensional (3D), free-breathing coronary MRA techniques can be used to image the tortuous path of the coronary arterial tree with improved SNR relative to twodimensional (2D) approaches. However, 3D imaging results in a lower contrast between the coronary blood and the myocardium. To overcome this problem, the use of contrast agents (9 -12) or magnetization preparation schemes (13-17) have been proposed. T 2 Prep is used in 3D coronary imaging to increase the contrast between the coronary arterial blood-pool and the surrounding tissue (13,17,18). However, increased B 1 and B 0 inhomogeneities at higher magnetic field strength pose significant challenges to uniform T 2 preparation of the magnetization across the imaged volume, thereby limiting the value of coronary MRA in general. Therefore, a novel T 2 preparation scheme in which adiabatic pulses are used to achieve B 1 and B 0 insensitive contrast enhancement was developed. Numerical simulations and an in vivo study were performed to characterize the efficacy of the technique. METHODS Background

OBJECTIVEWe examined if chronic cannabis smoking is associated with hepatic steatosis, insulin resistance, reduced β-cell function, or dyslipidemia in healthy individuals.RESEARCH DESIGN AND METHODSIn a cross-sectional, case-control study, we studied cannabis smokers (n = 30; women, 12; men, 18; 27 ± 8 years) and control subjects (n = 30) matched for age, sex, ethnicity, and BMI (27 ± 6). Abdominal fat depots and intrahepatic fat content were quantified by magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively. Insulin-sensitivity indices and various aspects of β-cell function were derived from oral glucose tolerance tests (OGTT).RESULTSSelf-reported cannabis use was: 9.5 (2–38) years; joints/day: 6 (3–30) [median (range)]. Carbohydrate intake and percent calories from carbohydrates, but not total energy intake, were significantly higher in cannabis smokers. There were no group differences in percent total body fat, or hepatic fat, but cannabis smokers had a higher percent abdominal visceral fat (18 ± 9 vs. 12 ± 5%; P = 0.004). Cannabis smokers had lower plasma HDL cholesterol (49 ± 14 vs. 55 ± 13 mg/dL; P = 0.02), but fasting levels of glucose, insulin, total cholesterol, LDL cholesterol, triglycerides, or free fatty acids (FFA) were not different. Adipocyte insulin resistance index and percent FFA suppression during an OGTT was lower (P < 0.05) in cannabis smokers. However, oral glucose insulin sensitivity index, measures of β-cell function, or incretin concentrations did not differ between the groups.CONCLUSIONSChronic cannabis smoking was associated with visceral adiposity and adipose tissue insulin resistance but not with hepatic steatosis, insulin insensitivity, impaired pancreatic β-cell function, or glucose intolerance.

Objective To assess fetal and maternal outcomes of pregnancies in women with Turner syndrome (TS). Design Retrospective case series. Setting Clinical research center. Patients 276 adults with cytogenetically-proven TS participating in an intramural natural history protocol Interventions None. Main Outcome Measures Menstrual and obstetric histories, 50-cell karyotypes, and cardiovascular evaluation including aortic diameter measurements. Results Our cohort included five women with spontaneous pregnancies and five with pregnancies using assisted reproduction (ART). All five women with spontaneous pregnancies had spontaneous puberty, despite 45,X in ≥90% of their 50-cell karyotype. Participants had a total of 13 pregnancies and 14 live births. One child had cerebral palsy; the others were chromosomally and developmentally normal. Delivery was by Cesarean section in 4/7 spontaneous and 6/6 ART-related pregnancies. One mother experienced pre-eclampsia in an ART-related twin pregnancy requiring preterm delivery; she has marked but stable aortic dilation years later. Conclusions Approximately 2% of our study cohort experienced spontaneous pregnancies despite high grade X monosomy, and a similar number achieved pregnancy via oocyte donation and ART. The potential for life-threatening cardiovascular complications warrants comprehensive screening prior to conception, single embryo transfer, and caution regarding unintentional pregnancies for TS women.

HIV-infected adults with chronic aminotransferase elevations while receiving ART have a high rate of liver disease. Noninvasive testing can help identify liver disease in such patients, but liver biopsy is necessary to definitively identify those at risk for liver disease progression and complications. Longitudinal follow-up of this cohort will better characterize the natural history of aminotransferase elevations in this population and identify noninvasive biomarkers of liver disease progression.

No abstract