Nucleotide metabolic mismatches in mammalian hearts: implications for transplantation

Introduction

Human donor organ shortages have led surgeons and scientists to explore the use of animals as alternative organ sources. Acute thrombovascular rejection (AVR) is the main hurdle in xenotransplantation. Disparities in nucleotide metabolism in the vessels of different species may contribute significantly to the microvascular component of AVR.

Methods

We evaluated the extent of nucleotide metabolism mismatch in selected organs and endothelial cells of different mammals with particular focus on the changes in activity of ecto-5’-nucleotidase (E5’N) elicited by exposure of porcine hearts or endothelial cells to human blood (ex vivo) or human plasma (in vitro).

Results

E5’N activity in the rat heart was significantly higher than in other species. We noted a significant difference (p<0.001) in E5’N activity between human and pig endothelial cell lines. Initial pig aortic endothelial E5’N activity decreased in vitro after a three-hour exposure to human and porcine plasma while remaining constant in controls. Ex vivo perfusion with fresh human blood for four hours resulted in a significant decrease of E5’N activity in both wild type and transgenic pig hearts overexpressing human decay accelerating factor (p<0.001).

Conclusions

This study provides evidence that mismatches in basal mammalian metabolic pathways and humoral immunity interact in a xenogeneic environment. Understanding the role of nucleotide metabolism and signalling in xenotransplantation may identify new targets for genetic modifications and may lead to the development of new therapies extending graft survival.     

Medicaid and privately financed orthodontic patients have similar occlusal and psychosocial outcomes

Objective: This study compares occlusal and psychosocial outcomes from comprehensive orthodontic treatment in Medicaid (MC) and privately financed (private pay, PP) patients. Methods: Two cohorts received comprehensive orthodontics: MC (n = 66); PP (n = 60). A calibrated, blinded examiner scored dental casts at baseline (pretreatment, T1) and after completing 2 years of treatment (posttreatment, T2) using the Peer Assessment Rating (PAR) and the Index of Complexity, Outcome, and Need (ICON). The prevalence of patients in the validated ICON categories for treatment need, complexity, and improvement were calculated. Questionnaires to assess body image (BI) and expectations/experiences were administered. Occlusal measures at T2 were compared after adjustment for baseline characteristics. Psychosocial measures were compared between and within groups. Occlusal and psychosocial associations were evaluated. Results: MC was 1.3 years younger (P < 0.001) and had worse malocclusions at baseline (PAR 32 versus 25; P < 0.001); (ICON 64 versus 56; P = 0.06). After adjustment for age and initial severity, estimated average differences between groups at T2 (MC‐PP) were slight: 1.5 [95 percent confidence interval (CI) ?2.9, 5.9] and 2.4 (95 percent CI ?4.4, 8.9) for PAR and ICON, respectively. More PP completed treatment under 2 years (85 percent versus 62 percent; P = 0.03). At baseline, both groups needed treatment, but MC malocclusions were more complex (P = 0.05). At T2, both groups were acceptable and there were no differences in ICON improvement categories. Group differences in psychosocial measures and associations between psychosocial and occlusal measures were evident in the “teeth” domain but weak or lacking elsewhere. Conclusions: Occlusal and psychosocial outcomes from orthodontics in MC and PP were comparable, despite worse MC malocclusions at baseline.     

Modality shift effects mimic multisensory interactions: an event-related potential study

A frequent approach to study interactions of the auditory and the visual system is to measure event-related potentials (ERPs) to auditory, visual, and auditory-visual stimuli (A, V, AV). A nonzero result of the AV ? (A + V) comparison indicates that the sensory systems interact at a specific processing stage. Two possible biases weaken the conclusions drawn by this approach: first, subtracting two ERPs from one requires that A, V, and AV do not share any common activity. We have shown before (Gondan and Röder in Brain Res 1073–1074:389–397, 2006) that the problem of common activity can be avoided using an additional tactile stimulus (T) and evaluating the ERP difference (T + TAV) ? (TA + TV). A second possible confound is the modality shift effect (MSE): for example, the auditory N1 is increased if an auditory stimulus follows a visual stimulus, whereas it is smaller if the modality is unchanged (ipsimodal stimulus). Bimodal stimuli might be affected less by MSEs because at least one component always matches the preceding trial. Consequently, an apparent amplitude modulation of the N1 would be observed in AV. We tested the influence of MSEs on auditory-visual interactions by comparing the results of AV ? (A + V) using (a) all stimuli and using (b) only ipsimodal stimuli. (a) and (b) differed around 150 ms, this indicates that AV ? (A + V) is indeed affected by the MSE. We then formally and empirically demonstrate that (T + TAV) ? (TA + TV) is robust against possible biases due to the MSE.     

Outcomes of outpatient breast cancer surgery at a private breast clinic

Advances in surgical and anesthetic techniques have allowed for outpatient treatment of breast cancer. We evaluated the feasibility, safety, efficacy, and surgical outcomes of outpatient surgery in 370 patients with breast cancer who underwent breast‐conserving surgery (BCS)/axillar lymph node (ALN) management. There were no deaths or severe intraoperative complications, but 41 complications were observed and disease recurrence occurred in 18 patients. The cumulative overall survival rate was 95.2%. Outpatient surgery was well tolerated, feasible, and safe in patients receiving BCS/ALN management.