Distribution, location, and transcriptional profile of Peyer's patch conventional DC subsets at steady state and under TLR7 ligand stimulation.

The initiation of the mucosal immune response in Peyer's patch (PP) relies on the sampling, processing, and efficient presentation of foreign antigens by dendritic cells (DCs). Among PP DCs, CD11b+ conventional DCs (cDCs) and lysozyme-expressing DCs (LysoDCs) have distinct progenitors and functions but share many cell surface markers. This has previously led to confusion between these two subsets. In addition, another PP DC subset, termed double-negative (DN), remains poorly characterized. Here we show that both DN and CD11b+ cDCs belong to a unique SIRPα+ cDC subset. At steady state, cDCs and TIM-4+ macrophages are mainly located in T-cell zones, i.e., interfollicular regions, whereas a majority of subepithelial phagocytes are monocyte-derived cells, namely, LysoDCs and TIM-4- macrophages. Finally, oral administration of a Toll-like receptor 7 ligand induces at least three TNF-dependent events: (i) migration of dome-associated villus cDCs in interfollicular regions, (ii) increase of CD8α+ interfollicular cDC number, and (iii) activation of both CD11b+ and CD8α+ interfollicular cDCs. The latter is marked by a genetic reprograming leading to the upregulation of type I interferon-stimulated and of both immuno-stimulatory and -inhibitory gene expression.

Early Low Urinary CXCL9 and CXCL10 Might Predict Immunological Quiescence in Clinically and Histologically Stable Kidney Recipients.

We monitored the urinary C-X-C motif chemokine (CXCL)9 and CXCL10 levels in 1722 urine samples from 300 consecutive kidney recipients collected during the first posttransplantation year and assessed their predictive value for subsequent acute rejection (AR). The trajectories of urinary CXCL10 showed an early increase at 1 month (p = 0.0005) and 3 months (p = 0.0009) in patients who subsequently developed AR. At 1 year, the AR-free allograft survival rates were 90% and 54% in patients with CXCL10:creatinine (CXCL10:Cr) levels <2.79 ng/mmoL and >2.79 ng/mmoL at 1 month, respectively (p < 0.0001), and 88% and 56% in patients with CXCL10:Cr levels <5.32 ng/mmoL and >5.32 ng/mmoL at 3 months (p < 0.0001), respectively. CXCL9:Cr levels also associate, albeit less robustly, with AR-free allograft survival. Early CXCL10:Cr levels predicted clinical and subclinical rejection and both T cell- and antibody-mediated rejection. In 222 stable patients, CXCL10:Cr at 3 months predicted AR independent of concomitant protocol biopsy results (p = 0.009). Although its positive predictive value was low, a high negative predictive value suggests that early CXCL10:Cr might predict immunological quiescence on a triple-drug calcineurin inhibitor-based immunosuppressive regimen in the first posttransplantation year, even in clinically and histologically stable patients. The clinical utility of this test will need to be addressed by dedicated prospective clinical trials.

Patient evaluation of prone carts used in spinal cord injury.

Prone carts are used for mobility by individuals with spinal cord injury who cannot use a wheelchair due to the risk of aggravating existing pressure ulcers. A prone cart is a flat/horizontal cart with a fixed height, propelled by the user while laying in a prone position. Patients reported that prolonged use of a prone cart resulted in chronic neck, shoulder and back pain. Additionally the existing prone carts lack user accessible angle adjustability, chest support area, as well as a storage, eating or working area. An interdisciplinary research team collaborated to address these concerns. Three prone carts were evaluated: E&J, Gendron, and a newly developed prototype, MIAD/PVA. Questionnaires were administered to caregivers and patients regarding usage and effectiveness of the prone carts as well as the features of an ideal cart. This data led to the design and refinement of a prototype prone cart which was tested on 20 patients and 19 caregivers at the SCI Centers of the Milwaukee and Tampa VAMC's from 1994-1995. The new prone cart enables the user to lie at an angle rather than laying flat. This position has been found to relieve back and neck pressure. With an hydraulic system, the the user can adjust both the front and rear angles of the cart to achieve desired comfort. In addition, a front deck provides an eating and working area. This study resulted in research-based information and criteria for the design of new prone carts. Findings of this pilot study will be incorporated in a development merit review proposal to the VA Rehabilitation Research & Development service for the design of a new manual and motorized prone cart. The researchers are collaborating with Ortho-Kinetics Inc. to promote ease in manufacturing.

Seasonal affective disorder in a spinal cord injury population.

Seasonal Affective Disorder (SAD) has received formal research attention only within the last eight years. Diagnostic criteria for SAD include many characteristics typical of depression: sadness, low self-esteem, lack of energy, social withdrawal, and suicide ideation, and features of atypical depression: carbohydrate craving, overeating, weight gain, and hypersomnia. Differential diagnosis of the disorder depends on an onset in fall/winter and remission in spring/summer. It was hypothesized that spinal cord injury (SCI) patients would have a higher incidence of the disorder in the northern latitudes because of decreased outdoor activities in winter and because of such light-depriving winter survival tactics as installing opaque plastic for storm windows. SCI patient responded to a postal survey which included Rosenthal's Seasonal Pattern Assessment Questionnaire (SPAQ) and the Beck Depression Inventory (BDI). Results showed a substantially higher rate of SAD among SCI patients than in the normative sample.