Striatal structure and its association with N-Acetylaspartate and glutamate in autism spectrum disorder and obsessive compulsive disorder

Autism spectrum disorders (ASD) and obsessive compulsive disorder (OCD) are often comorbid and are associated with changes in striatal volumes and N-Acetylaspartate (NAA) and glutamate levels. Here, we investigated the relation between dorsal striatal volume and NAA and glutamate levels. We additionally compared striatal volume and shape between ASD, OCD and controls. T1-weighted magnetic resonance (MR) images, proton spectra (1H-MRS) in the left striatum, and phenotypic information were collected from 54 children with ASD, 32 with OCD, and 56 controls (aged 8–13 years) in a four-site study. Dorsal striatal volume and shape were determined using the FMRIB integrated registration and segmentation tool (FIRST). Spectra were processed with Linear Combination Model. The relationship of left striatal volume with NAA and glutamate was investigated, and group comparisons were performed for NAA levels and for bilateral striatal volume and shape. NAA levels were lower in subjects with ASD compared with controls (t=2.86, p=0.005) and were associated with striatal volume (β=0.37, t=2.78, p=0.008). Glutamate levels were also associated with volume in the ASD group (β=0.38, t=2.46, p=0.018). No group differences were found for striatal volume or shape, but a post-hoc diagnosis-by-hemisphere interaction (F_(2,129)=3.86, p=0.024) revealed greater asymmetry (right>left) in striatal volume for the disorder-groups compared with controls. Our findings show involvement of NAA and glutamate in striatal volume in ASD and suggest greater asymmetry in paediatric ASD and OCD compared with controls, pointing to overlapping subcortical abnormalities. The lower NAA in ASD reflects reduced neuronal integrity or impaired neuronal functioning.     

Automated preparation of 2‐[18F]fluoropropionate labeled peptides using a flexible,multi‐stage synthesis platform (iPHASE Flexlab)

Radiolabelled peptides are vital tools used in positron emission tomography imaging for the diagnosis of disease, drug discovery, and biomedical research. Peptides are typically labeled through conjugation to a radiolabelled prosthetic group, which usually necessitates complex, multi‐step procedures, especially for fluorine‐18 labeled peptides. Herein, we describe the automated synthesis and formulation of 2‐[¹⁸F]fluoropropionate labeled RGD‐peptides through use of the iPHASE Flexlab as an effective dual‐stage radiochemical synthesis module. The fully automated preparation of the monomeric RGD‐peptides, [¹⁸F]FP‐GalactoRGD and [¹⁸F]FP‐c(RGDy(SO₃)K), was accomplished in under 90 minutes with n.d.c. radiochemical yields ca. 7% from fluoride. Similarly, the automated preparation of the dimeric RGD‐peptides, [¹⁸F]F‐PRGD₂ and [¹⁸F]FP‐E(RGDy(SO₃)K)₂, was accomplished in under 105 minutes with n.d.c. yields ca. 4% from fluoride.     

Contingency Management Versus Psychotherapy for Prenatal Smoking Cessation: A Meta-Analysis of Randomized Controlled Trials

Objectives

Prenatal smoking is the leading preventable cause of poor obstetric outcomes, yet treatment options are limited. Past reviews of prenatal smoking cessation have often grouped all counseling into a single category, which ignores the fact that psychotherapy is distinct from brief counseling. The objective of this study was to compare the effect sizes of two intensive interventions for prenatal smoking cessation: contingency management (i.e., financial incentives for abstinence) and psychotherapy.

Three‐month pancreas graft function significantly influences survival following simultaneous pancreas‐kidney transplantation in type 2 diabetes patients

Successful simultaneous pancreas‐kidney transplantation (SPK) improves quality‐of‐life and prolongs kidney allograft and patient survival in type‐1 diabetic (T1DM) patients. However, the use of SPK in type‐2 diabetic (T2DM) patients remains limited. We examined a national transplant registry for 35 849 T2DM kidney disease patients who received transplant between 2000 and 2016 and survived the first 3 months with a functioning kidney, and categorized as: deceased‐donor kidney transplant alone (DD‐KA, 68%), living‐donor kidney transplant alone (LD‐KA, 30%), or SPK (2%). Among SPK recipients, 6% had pancreas allograft failure within 3 months (SPK,P‐) and 94% had a functional pancreas (SPK,P+). Associations of transplant type with kidney allograft failure and death (multivariable‐adjusted hazard ratio, _95%LCLaHR_95%UCL), over follow‐up through December 2018, were quantified by multivariable inverse probability of treatment weighted survival analyses. SPK recipients had better kidney graft and patient survival than LD‐KA or DD‐KA recipients. Compared to SPK,P+, DD‐KA, or LD‐KA recipients had significantly higher risk of kidney allograft failure (DD‐KA: aHR _1.532.20_3.17; LD‐KA: aHR _1.291.87_2.71) and death (DD‐KA: aHR _2.123.25_5.00; LD‐KA: aHR _1.542.35_3.59). SPK,P‐ recipients had significantly higher risk of death (aHR _1.683.30_6.50). Similar to T1DM, T2DM patients with SPK have a survival benefit compared to those with kidney transplant alone, but this benefit depends upon successful early pancreas function.     

Application of a Penrose Drain Guide for Vascular Stapling During Hepatic Surgery: How I Do It

The use of stapling devices to manage vascular pedicles during hepatic surgery has been a significant advance in the field. However, insertion and application of the stapler in vascular dissection planes can be associated with injury to adjacent structures. We describe a five-step technique using a silicone Penrose drain to aid in the positioning of an endovascular stapling device to obtain vascular control during hepatectomy. The use is described here for hepatic vein management during right hepatectomy. The technique can be also used for other applications when transecting major vessels during major liver surgery. The use of this silicone Penrose-guided endovascular stapler technique is a simple, cost-effective maneuver that can be used to improve control and prevent vascular injury during the division of major vascular structures when performing hepatic surgery.     

Fasting and exercise increase plasma cannabinoid levels in THC pre-treated rats: an examination of behavioural consequences

Rationale

Δ⁹-Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, accumulates in fat tissue where it can remain for prolonged periods. Under conditions of increased fat utilisation, blood cannabinoid concentrations can increase. However, it is unclear whether this has behavioural consequences.

Objectives

Here, we examined whether rats pre-treated with multiple or single doses of THC followed by a washout would show elevated plasma cannabinoids and altered behaviour following fasting or exercise manipulations designed to increase fat utilisation.

Methods

Behavioural impairment was measured as an inhibition of spontaneous locomotor activity or a failure to successfully complete a treadmill exercise session. Fat utilisation was indexed by plasma free fatty acid (FFA) levels with plasma concentrations of THC and its terminal metabolite (-)-11-nor-9-carboxy-?⁹-tetrahydrocannabinol (THC-COOH) also measured.

Results

Rats given daily THC (10 mg/kg) for 5 days followed by a 4-day washout showed elevated plasma THC-COOH when fasted for 24 h relative to non-fasted controls. Fasted rats showed lower locomotor activity than controls suggesting a behavioural effect of fat-released THC. However, rats fasted for 20 h after a single 5-mg/kg THC injection did not show locomotor suppression, despite modestly elevated plasma THC-COOH. Rats pre-treated with THC (5 mg/kg) and exercised 20 h later also showed elevated plasma THC-COOH but did not differ from controls in their likelihood of completing 30 min of treadmill exercise.

Conclusions

These results confirm that fasting and exercise can increase plasma cannabinoid levels. Behavioural consequences are more clearly observed with pre-treatment regimes involving repeated rather than single THC dosing.     

Immune responses to major histocompatibility complex homozygous lymphoid cells in murine F1 hybrid recipients: implications for transfusion-associated graft-versus-host disease

Graft-versus-host disease (GVHD) is currently encountered after bone marrow transplantation and transfusion. GVHD associated with transfusion (TA-GVHD) in apparently immunocompetent recipients has been recently reported with increasing frequency. A consistent finding in many of these cases is that the recipient received blood from a donor homozygous for one of the recipient's HLA haplotypes. However, the observed frequency of TA-GVHD is much lower than the estimated probability of this donor/recipient combination. The potential role of recipient immune responses in controlling TA-GVHD was investigated using an analogous murine model in which GVHD is induced by the injection of parental lymphoid cells into unirradiated F1 hybrid recipients. The effect of various immune manipulations of the recipient of GVHD induction was assessed by determining the number of donor lymphoid cells required to induce GVHD responses. Whereas depletion of recipient CD4+ cells increased the number of donor cells needed to induce GVHD, depletion of recipient CD8+ and natural killer cells resulted in fewer donor cells being needed to induce a GVHD response. These studies suggest a central role for functioning recipient CD8 and natural killer cells in the down-regulation of TA-GVHD development in recipients.