Outcome of deceased donor renal transplantation in patients with an ileal conduit

Renal transplantation in recipients with an ileal conduit is uncommon and occasionally controversial as it has been associated with high morbidity and mortality rates. We report on 17 patients with an ileal conduit who received a deceased donor renal transplant at our institution between January 1986 and December 2012. We retrospectively reviewed their allograft and surgical outcome. There were four mortalities at five, five, 39, and 66 months post‐transplant. Sixteen of 17 grafts functioned immediately; one patient had primary non‐function secondary to vascular thrombosis. Thirteen of 17 (76.5%) grafts were functioning at a mean follow‐up period of 105 months. The mean serum creatinine at follow‐up was 111 μM (±38.62). Five patients had seven episodes of urosepsis requiring hospital admission, and five patients received treatment for renal stone disease. We conclude that given improvements in immunosuppression, surgical technique, infection treatment, and selection criteria, we believe that renal transplantation in the patient with an ileal conduit yields excellent graft survival, although there is a high morbidity rate in this cohort of patients in the long term.     

Colonisation with methicillin‐resistant Staphylococcus aureus prior to renal transplantation is associated with long‐term renal allograft failure

Renal transplant recipients are at an increased risk of developing Methicillin‐resistant Staphylococcus aureus due to their immunosuppressed status. Herein, we investigate the incidence of MRSA infection in patients undergoing renal transplantation and determine the effect of MRSA colonisation on renal allograft function and overall mortality. Between January 1st 2007 and December 31st 2012, 1499 consecutive kidney transplants performed in our transplant unit and a retrospective 1:2 matched case‐control study was performed on this patient cohort. The 1‐, 3‐ and 5‐year overall graft survival rates were 100%, 86% and 78%, respectively, in MRSA positive recipients compared with 100%, 100% and 93%, respectively, in the control group (P < 0.05). The 1‐, 3‐ and 5‐year overall patient survival rates were 100%, 97% and 79%, respectively, in MRSA positive recipients compared with 100%, 100% and 95%, respectively, in the control group (P = 0.1). In a multiple logistic regression analysis, colonisation with MRSA pre‐operatively was an independent predictor for renal allograft failure at 5 years (hazard ratio: 4.6, 95% confidence interval: 1–30.7, P = 0.048). These findings demonstrate that the incidence of long‐term renal allograft failure is significantly greater in this patient cohort compared with a matched control population.     

Signalling lymphocyte activation molecule family member 9 is found on select subsets of antigen-presenting cells and promotes resistance to Salmonella infection

Signalling lymphocyte activation molecule family member 9 (SLAMF9) is an orphan receptor of the CD2/SLAM family of leucocyte surface proteins. Examination of SLAMF9 expression and function indicates that SLAMF9 promotes inflammation by specialized subsets of antigen-presenting cells. Within healthy liver and circulating mouse peripheral blood mononuclear cells, SLAMF9 is expressed on CD11b⁺, Ly6C⁻, CD11c^low, F4/80^low, MHC-II⁺, CX₃CR1⁺ mononuclear phagocytes as well as plasmacytoid dendritic cells. In addition, SLAMF9 can be found on peritoneal B1 cells and small (F4/80^low), but not large (F4/80^high), peritoneal macrophages. Upon systemic challenge with Salmonella enterica Typhimurium, Slamf9^−/− mice were impaired in their ability to clear the infection from the liver. In humans, SLAMF9 is up-regulated upon differentiation of monocytes into macrophages, and lipopolysaccharide stimulation of PMA-differentiated, SLAMF9 knockdown THP-1 cells showed an essential role of SLAMF9 in production of granulocyte–macrophage colony-stimulating factor, tumour necrosis factor-α, and interleukin-1β. Taken together, these data implicate SLAMF9 in the initiation of inflammation and clearance of bacterial infection.     

In and out of synchrony—Behavioral and physiological dynamics of dyadic interpersonal coordination

Interpersonal synchrony, the temporal coordination of actions, emotions, thoughts and physiological processes, is a widely studied ubiquitous phenomenon. Research has already established that more synchrony is not always more beneficial, especially in the fields of emotional and physiological synchrony. Despite this fact, the dominant tone in the literature is that behavioral interpersonal synchrony is a pro-social phenomenon, and hence, in social contexts, more behavioral synchrony is generally considered better. In accordance with that tone, the naturally occurring dynamics of moving in and out of synchrony have rarely been studied or considered as an adaptive state. In the present article, we aim to present a new model of interpersonal synchrony, based on the existing literature assessing synchrony as well as the ideas of complex dynamical systems. At the core of our model is the idea that two tendencies exist simultaneously, one to synchronize with others and another to move out of synchrony and act independently. We suggest that an adaptive interpersonal system is a flexible one, able to continuously adjust itself to the social context. We suggest that the concept of meta-stability might be a marker of such a flexible interpersonal system. Moreover, the model considers both behavioral and physiological aspects in order to provide a more extensive account. We present research implications of the model, as well as a demonstration of the model's applicability to data, and provide code researchers can use to analyze their own data in these methods. Finally, we discuss future directions in detail.     

Perfectionistic traits and self‐presentation are associated with negative attitudes and concerns about seeking professional psychological help

Numerous factors influence whether an individual is able and willing to seek professional help for psychological difficulties. One of these may be perfectionism, a multidimensional personality construct that has been linked to poor psychological adjustment. The current study investigated whether perfectionism traits and self‐presentational facets were associated with negative help‐seeking attitudes and concerns about psychotherapy. Samples of university (N = 299) and community (N = 77) men and women completed the Multidimensional Perfectionism Scale, Perfectionistic Self‐Presentation Scale, Attitudes Towards Seeking Professional Help Scale, and Thoughts About Psychotherapy Survey. Various components of perfectionism were associated with both negative help‐seeking attitudes and concerns about psychotherapy. The findings suggest that perfectionistic behaviour may be an important dispositional factor that interferes with seeking and obtaining help for psychological difficulties. Theoretical and clinical implications are discussed.     

EFTUD2 missense variants disrupt protein function and splicing in mandibulofacial dysostosis Guion‐Almeida type

Pathogenic variants in the core spliceosome U5 small nuclear ribonucleoprotein gene EFTUD2/SNU114 cause the craniofacial disorder mandibulofacial dysostosis Guion‐Almeida type (MFDGA). MFDGA‐associated variants in EFTUD2 comprise large deletions encompassing EFTUD2, intragenic deletions and single nucleotide truncating or missense variants. These variants are predicted to result in haploinsufficiency by loss‐of‐function of the variant allele. While the contribution of deletions within EFTUD2 to allele loss‐of‐function are self‐evident, the mechanisms by which missense variants are disease‐causing have not been characterized functionally. Combining bioinformatics software prediction, yeast functional growth assays, and a minigene (MG) splicing assay, we have characterized how MFDGA missense variants result in EFTUD2 loss‐of‐function. Only four of 19 assessed missense variants cause EFTUD2 loss‐of‐function through altered protein function when modeled in yeast. Of the remaining 15 missense variants, five altered the normal splicing pattern of EFTUD2 pre‐messenger RNA predominantly through exon skipping or cryptic splice site activation, leading to the introduction of a premature termination codon. Comparison of bioinformatic predictors for each missense variant revealed a disparity amongst different software packages and, in many cases, an inability to correctly predict changes in splicing subsequently determined by MG interrogation. This study highlights the need for laboratory‐based validation of bioinformatic predictions for EFTUD2 missense variants.     

Tissue-resident T cells,in situ immunity and transplantation

T cells coordinate rejection of transplanted allografts and are key targets for depletion, immunosuppression, and tolerance induction to promote long-term graft survival. Studies in mouse models and humans generally focus on circulating T cells or those from lymphoid sites; however, vast numbers of T cells reside in multiple peripheral tissue sites including lungs, intestines, liver, and skin as non-circulating, tissue-resident memory T cells (Trm cells). In this review, we define the basic properties of Trm cells, the emerging evidence of their importance for protective immunity, and the potential role of resident versus circulating T cells in transplant rejection and in providing protection to prevalent infections posttransplantation. We also discuss potential susceptibilities and/or resistance of protective Trm to immunosuppression therapies, and how consideration of Trm, their compartmentalization, and specificity can enable improved therapies for targeted inhibition of pathogenic and preservation of protective T-cell subsets.