The Role of Serotonin (5-HT) in Behavioral Control: Findings from Animal Research and Clinical Implications

The neurotransmitters serotonin and dopamine both have a critical role in the underlying neurobiology of different behaviors. With focus on the interplay between dopamine and serotonin, it has been proposed that dopamine biases behavior towards habitual responding, and with serotonin offsetting this phenomenon and directing the balance toward more flexible, goal-directed responding. The present focus paper stands in close relationship to the publication by Worbe et al. (2015), which deals with the effects of acute tryptophan depletion, a neurodietary physiological method to decrease central nervous serotonin synthesis in humans for a short period of time, on the balance between hypothetical goal-directed and habitual systems. In that research, acute tryptophan depletion challenge administration and a following short-term reduction in central nervous serotonin synthesis were associated with a shift of behavioral performance towards habitual responding, providing further evidence that central nervous serotonin function modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. In the present focus paper, we discuss the findings by Worbe and colleagues in light of animal experiments as well as clinical implications and discuss potential future avenues for related research.     

Development of decellularized conjunctiva as a substrate for the ex vivo expansion of conjunctival epithelium

This study was performed to develop a method to decellularize human conjunctiva and to characterize the tissue in terms of its deoxyribose nucleic acid (DNA) content, tensile strength, collagen denaturation, basement membrane, extracellular matrix components and its potential to support conjunctival epithelial growth. Human conjunctival tissues were subjected to a decellularization process involving hypotonic detergent and nuclease buffers. Variations in sodium dodecyl sulfate concentration (0.05–0.5%, w/v) were tested to determine the appropriate concentration of detergent buffer. DNA quantification, collagen denaturation, cytotoxicity and tensile strength were investigated. Human conjunctival cell growth by explant culture on the decellularized tissue substrate was assessed after 28 days in culture. Samples were fixed and paraffin embedded for immunohistochemistry including conjunctival epithelial cell markers and extracellular matrix proteins. Conjunctival tissue from 20 eyes of 10 donors (age range 65–92 years) was used. Decellularization of human conjunctiva was achieved to 99% or greater DNA removal (p < 0.001) with absence of nuclear staining. This was reproducible at the lowest concentration of sodium dodecyl sulfate (0.05% w/v). No collagen denaturation (p = 0.74) and no difference in tensile strength parameters was demonstrated following decellularization. No significant difference was noted in the immunolocalization of collagen IV, laminin and fibronectin, or in the appearance of periodic acid–Schiff‐stained basement membranes following decellularization. The decellularized tissue did not exhibit any cytotoxicity and explant culture resulted in the growth of stratified conjunctival epithelium. Allogeneic decellularized human conjunctiva can be successfully decellularized using the described protocol. It represents a novel substrate to support the expansion of conjunctival epithelium for ocular surface cellular replacement therapies. Copyright © 2017 John Wiley & Sons, Ltd.     

Clinical and patho-anatomical factors affecting expansion of thoracic aortic aneurysms

OBJECTIVE—To examine the expansion of aneurysmal aortic segments ( 35 mm) and to assess the impact of clinical and patho-anatomical factors on aneurysm expansion.
DESIGN—87 consecutive patients (mean age 63.6 years, range 22-84 years) were studied using serial (six month intervals) computed tomographic or magnetic resonance imaging to monitor progression of thoracic aortic aneurysms. Aortic diameter was measured at seven predetermined segments and at the site of maximum aortic dilatation (MAX).
RESULTS—780 segment intervals were identified. The median overall aneurysm expansion rate was 1.43 mm/year. This increased exponentially with incremental aortic diameter (p < 0.01) and varied by anatomical segment (p < 0.05). The presence of intraluminal thrombus (p < 0.01) but not dissection or calcification was associated with accelerated growth. Univariate analysis identified thrombus (p < 0.001), previous stroke (p < 0.002), smoking (p < 0.01), and peripheral vascular disease (p < 0.05) as factors associated with accelerated growth in MAX. Dissection, wall calcification, and history of hypertension did not affect expansion. β Blocker treatment was not associated with protection. Multivariate analysis confirmed the positive effect of intraluminal thrombus and previous cerebral ischaemia, and the negative effect of previous aortic surgery on aneurysm growth. These findings translated into a mathematical equation describing exponential aneurysm expansion.
CONCLUSIONS—Aneurysmal thoracic aortic segments expand exponentially according to their initial size and their anatomical position within the aorta. The presence of intraluminal thrombus, atherosclerosis, and smoking history is associated with accelerated growth and may identify a high risk patient group for close surveillance.


Keywords: thoracic aortic aneurysm; expansion rate     

Adoptive T-cell therapy for EBV-associated post-transplant lymphoproliferative disease

Increased understanding of the mechanisms by which T lymphocytes recognize virus and tumor-specific antigens has fueled the use of adoptive immunotherapy for viral and malignant diseases. An ideal candidate for such treatment is Epstein-Barr virus (EBV). EBV-associated post-transplant lymphoproliferative disorder (PTLD) is a serious complication post-solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT). The disease is essentially the result of suppression of cytotoxic T-cell function and despite various treatment strategies the course may still be fulminant and lethal. Therefore, an adoptive immunotherapeutic approach using ex vivo derived EBV-specific CTL offers a promising solution not only for the treatment but also as prophylaxis for PTLD. The infusion of EBV-CTL has been demonstrated to be safe and effective in allogeneic HSCT recipients and their use post-SOT is being evaluated.