Exploring real-time functional magnetic resonance imaging neurofeedback in adolescents with disruptive behavior disorder and callous unemotional traits

Introduction: Adolescents with increased callous unemotional traits (CU traits) in the context of disruptive behavior disorder (DBD) show a persistent pattern of antisocial behavior with shallow affect and a lack of empathy or remorse. The amygdala and insula as regions commonly associated with emotion processing, empathy and arousal are implicated in DBD with high CU traits. While behavioral therapies for DBD provide significant but small effects, individualized treatments targeting the implicated brain regions are missing. Methods: In this explorative randomized controlled trial we randomly assigned twenty-seven adolescents with DBD to individualized real-time functional magnetic resonance neurofeedback (rtfMRI-NF) or behavioral treatment as usual (TAU). Visual feedback of either amygdala or insula activity was provided during rtfMRI-NF by gauges and included a simple and concurrent video run plus a transfer run. A linear mixed model (LMM) was applied to determine improvement of self-regulation. Specificity was assessed by correlating individual self-regulation improvement with clinical outcomes. Results: The rtfMRI-NF (n = 11) and TAU (n = 10) completers showed comparable and significant clinical improvement indicating neither superiority nor inferiority of rtfMRI-NF. The exploratory LMM revealed successful learning of self-regulation along the course of training for participants who received feedback from the amygdala. A significant exploratory correlation between individual target region activity in the simple run and clinical improvement was found for one dimension of DBD. Conclusions: This exploratory study demonstrated feasibility and suggests clinical efficacy of individualized rtfMRI-NF comparable to active TAU for adolescents with DBD and increased CU traits. Further studies are needed to confirm efficacy, specificity and to clarify underlying learning mechanisms

Tandem Mass Spectrometry Measurement of the Collision Products of Carbamate Anions Derived from CO2 Capture Sorbents: Paving the Way for Accurate Quantitation

The reaction between CO2 and aqueous amines to produce a charged carbamate product plays a crucial role in post-combustion capture chemistry when primary and secondary amines are used. In this paper, we report the low energy negative-ion CID results for several anionic carbamates derived from primary and secondary amines commonly used as post-combustion capture solvents. The study was performed using the modern equivalent of a triple quadrupole instrument equipped with a T-wave collision cell. Deuterium labeling of 2-aminoethanol (1,1,2,2,-d4-2-aminoethanol) and computations at the M06-2X/6-311++G(d,p) level were used to confirm the identity of the fragmentation products for 2-hydroxyethylcarbamate (derived from 2-aminoethanol), in particular the ions CN−, NCO− and facile neutral losses of CO2 and water; there is precedent for the latter in condensed phase isocyanate chemistry. The fragmentations of 2-hydroxyethylcarbamate were generalized for carbamate anions derived from other capture amines, including ethylenediamine, diethanolamine, and piperazine. We also report unequivocal evidence for the existence of carbamate anions derived from sterically hindered amines (Tris(2-hydroxymethyl)aminomethane and 2-methyl-2-aminopropanol). For the suite of carbamates investigated, diagnostic losses include the decarboxylation product (−CO2, 44 mass units), loss of 46 mass units and the fragments NCO− (m/z 42) and CN− (m/z 26). We also report low energy CID results for the dicarbamate dianion (−O2CNHC2H4NHCO2−) commonly encountered in CO2 capture solution utilizing ethylenediamine. Finally, we demonstrate a promising ion chromatography-MS based procedure for the separation and quantitation of aqueous anionic carbamates, which is based on the reported CID findings. The availability of accurate quantitation methods for ionic CO2 capture products could lead to dynamic operational tuning of CO2 capture-plants and, thus, cost-savings via real-time manipulation of solvent regeneration energies

Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms

Background: Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co‐occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. Methods and Results: We performed a mega‐analysis of 1000 Genomes Project‐imputed genome‐wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA‐, AAA‐, and TAA‐associated SNPs and tested these scores for association to case‐control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium–score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single‐nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]=1.11; P=4.1×10−5) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1×10−3). Conclusions: Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication

Mapping of specific sentinel node locations for skin cancer of the head.

In current dermatological practice lymphatic mapping and sentinel lymph node biopsy (SLNB) are frequently used in patients with cutaneous cancers, like malignant melanoma, squamous cell carcinoma and Merkel cell carcinoma. However, those tumors are often located on the head and neck, regions with notoriously variable lymphatic drainage patterns. Consequently, the incidence of successful SLNB in the head and neck is considerably lower compared to the SLNB on the trunk and extremities. Thus, there is a need to improve the hit rate of SLNB in this special area. Therefore, in the current study we analyzed SLNB of 149 patients treated for cutaneous tumors at the Department of Dermatology, University of Tuebingen, Germany. By mapping SLN (sentinel lymph node) locations to their specific tumor sites on the head and neck, we were able to calculate the frequency of SLN distribution to defined tumor locations. Furthermore, our analysis revealed that approximately 7% of tumors on the head and neck drain to contralateral SLN, which is of relevance for the classification in the current cancer TNM system. Thus, our mapping can predict SLN location in patients with cutaneous head and neck tumors and might help to further increase the rate of successful SLNB

Suppression of transforming growth factor β signalling aborts caerulein induced pancreatitis and eliminates restricted stimulation at high caerulein concentrations

BACKGROUND: Transforming growth factors betas (TGF-betas) are implicated in pancreatic tissue repair but their role in acute pancreatitis is not known. To determine whether endogenous TGF-betas modulate the course of caerulein induced acute pancreatitis, caerulein was administered to wild-type (FVB-/-) and transgenic mice that are heterozygous (FVB+/-) for expression of a dominant negative type II TGF-beta receptor. METHODS: After 7 hourly supramaximal injections of caerulein, the pancreas was evaluated histologically and serum was assayed for amylase and lipase levels. Next, the effects of caerulein on amylase secretion were determined in mouse pancreatic acini, and cholecystokinin (CCK) receptor expression was assessed. RESULTS: The normal mouse pancreas was devoid of inflammatory cells whereas the pancreas from transgenic mice contained lymphocytic infiltrates. Caerulein injection in wild-type mice resulted in 6- and 36-fold increases in serum amylase and lipase levels, respectively, increased serum trypsinogen activation peptide (TAP) levels, gross oedema and a marked inflammatory response in the pancreas that consisted mainly of neutrophils and macrophages. By contrast, FVB+/- mice exhibited minimal alterations in response to caerulein with attenuated neutrophil-macrophage infiltrates. Moreover, acini from FVB+/- mice did not exhibit restricted stimulation at high caerulein concentrations, even though CCK receptor mRNA levels were not decreased. CONCLUSION: Our findings indicate that a functional TGF-beta signalling pathway may be required for caerulein to induce acute pancreatitis and for the CCK receptor to induce acinar cell damage at high ligand concentrations. Our results also support the concept that restricted stimulation at high caerulein concentrations contributes to the ability of caerulein to induce acute pancreatitis