Association between serum resistin level and outcomes in kidney transplant recipients

Resistin is an adipocytokine that is associated with inflammation, coronary artery disease, and other types of cardiovascular disease among patients with normal kidney function. However, little is known about the association of resistin with outcomes in kidney transplant recipients. We collected socio‐demographic and clinical parameters, medical and transplant history, and laboratory data from 988 prevalent kidney transplant recipients enrolled in the Malnutrition‐Inflammation in Transplant—Hungary Study (MINIT‐HU study). Serum resistin levels were measured at baseline. Associations between serum resistin level and death with a functioning graft over a 6‐year follow‐up period were examined in unadjusted and adjusted models. The mean±SD age of the study population was 51 ± 13 years, among whom 57% were men and 21% were diabetics. Median serum resistin concentrations were significantly higher in patients who died with a functioning graft as compared to those who did not die during the follow‐up period (median [IQR]: 22[15–26] vs. 19[14–22] ng/ml, respectively; P < 0.001). Higher serum resistin level was associated with higher mortality risk in both unadjusted and fully adjusted models: HRs (95% CI): 1.33(1.16–1.54) and 1.21(1.01–1.46), respectively. In prevalent kidney transplant recipients, serum resistin was an independent predictor of death with a functioning graft.     

Evaluation of 660 nm LED light irradiation on the strategies for treating experimental periodontal intrabony defects

This study aims to investigate the therapeutic value of 660 nm light-emitting diode (LED) light irradiation on the strategies for treating experimental periodontal intrabony defects in vivo. Large-sized periodontal intrabony defects were created bilaterally on the mesial aspect of the maxillary second molars of 48 Sprague–Dawley rats, and the rats were equally divided into four treatment groups with primary wound intention (n?=?6/treatment/time point), including open flap debridement alone (OD), barrier membrane alone (MB), xenograft alone (BG), and xenograft plus barrier membrane (MG). Each group received daily 0 or 10 J/cm² LED light irradiation. The animals were sacrificed after 1 or 4 weeks. The treatment outcome was evaluated by gross observation of wound dehiscence and healing, micro-CT imaging for osteogenesis, and histological assessments for inflammatory cell infiltration and periodontal reattachment. With LED light irradiation, the extent of wound dehiscence was reduced, wound closure was accelerated, epithelial downgrowth was prevented, inflammation was reduced, and periodontal reattachment was promoted in all treatment strategies. Significant reduction of inflammation with LED light irradiation was noted at 1 week in the groups BG and MG (p?<?0.05). Osteogenesis was significantly promoted only in the group OD at both time points (p?<?0.05). Our study showed that 660 nm LED light accelerates mucoperiosteal flap healing and periodontal reattachment. However, the enhancement of osteogenesis appeared to be limited while simultaneously treating with a barrier membrane or xenograft.     

Memory CD4 T cells enhance primary CD8 T-cell responses

CD4 T-cell help is required for optimal memory CD8 T-cell responses. We have found that engaging preexisting CD4 Th1, but not Th2, memory cells at the time of CD8 T-cell priming results in increased CD8 effector responses to both bacterial and viral pathogens. The enhanced responses are characterized by increased numbers of cytokine-producing, antigen-specific cells. These findings suggest that engaging endogenous memory Th1 cells may increase cellular responses in an immunotherapy or vaccination setting.     

Enhanced creativity in bipolar disorder patients: a controlled study

OBJECTIVE: Associations between eminent creativity and bipolar disorders have been reported, but there are few data relating non-eminent creativity to bipolar disorders in clinical samples. We assessed non-eminent creativity in euthymic bipolar (BP) and unipolar major depressive disorder (MDD) patients, creative discipline controls (CC), and healthy controls (HC). METHODS: 49 BP, 25 MDD, 32 CC, and 47 HC (all euthymic) completed four creativity measures yielding six parameters: the Barron-Welsh Art Scale (BWAS-Total, and two subscales, BWAS-Dislike and BWAS-Like), the Adjective Check List Creative Personality Scale (ACL-CPS), and the Torrance Tests of Creative Thinking--Figural (TTCT-F) and Verbal (TTCT-V) versions. Mean scores on these instruments were compared across groups. RESULTS: BP and CC (but not MDD) compared to HC scored significantly higher on BWAS-Total (45% and 48% higher, respectively) and BWAS-Dislike (90% and 88% higher, respectively), but not on BWAS-Like. CC compared to MDD scored significantly higher (12% higher) on TTCT-F. For all other comparisons, creativity scores did not differ significantly between groups. CONCLUSIONS: We found BP and CC (but not MDD) had similarly enhanced creativity on the BWAS-Total (driven by an increase on the BWAS-Dislike) compared to HC. Further studies are needed to determine the mechanisms of enhanced creativity and how it relates to clinical (e.g. temperament, mood, and medication status) and preclinical (e.g. visual and affective processing substrates) parameters.     

Computational Modeling of Factor Xa Inhibition by Immobilized Tissue Factor Pathway Inhibitor

Coating surfaces of implanted devices with anticoagulants can reduce thrombosis and studies using a recombinant form of endogenous tissue factor pathway inhibitor (rTFPI) are promising. The anticoagulant function of immobilized rTFPI is thought to occur primarily by its inhibition of plasma clotting factor Xa (FXa); however the kinetics of this reaction at a surface are as yet unknown. To better understand the surface inhibition reaction under flow conditions, a theoretical model was developed delineating the roles of mass transport and reaction kinetics for an in vitro parallel plate device used in prior experimental studies [Hall et al., J. Biomech. Eng. 120:484–490, 1998]. As a first approximation, the kinetics of inhibition of FXa by rTFPI reported for static, homogeneous systems was considered. The unsteady convection–diffusion equation was solved for different wall-shear rates and inlet concentrations of FXa using the computational fluid dynamics software CFD-ACE (ESI Software Group). The results show that the heterogeneous inhibition reaction is diffusion controlled prior to saturation of the rTFPI. The experimental results compare favorably with the model at the lower shear rates (100–400 s⁻¹). At higher shear rates (>400 s⁻¹) the theoretical results follow the same trend as the experimental results but show a greater inhibition of FXa, implying an effect of flow or shear on the inhibition reaction.     

Cloning, sequence analysis and confirmation of derived gene sequences for three epitope-mapped monoclonal antibodies against human phagocyte flavocytochrome b

The integral membrane protein flavocytochrome b (Cyt b) is the catalytic core of the NADPH oxidase complex, a multicomponent enzyme system that initiates a cascade of reactive oxygen species that play a critical role in innate immunity and vascular physiology. Epitope-mapped, monoclonal antibodies (mAb) that recognize the large (gp91phox) and small (p22phox) subunits of Cyt b provide valuable reagents that have been used to examine structural and mechanistic aspects of oxidase function. In the present study, the heavy and light chain variable region genes of the Cyt b-specific mAbs 44.1, NS5, and NL7 have been amplified by RT-PCR, cloned and subject to DNA sequence analysis. Since the 5' degenerate primer sets used for mAb gene amplification were observed to introduce extensive heterogeneity into the heavy and light chain FR1 regions, N-terminal protein sequence analysis was also conducted to obtain the correct amino acid sequence of this region. In order to confirm the identity of the cloned genes, intact mAbs were resolved by two-dimensional electrophoresis and subject to in-gel tryptic digestion for analysis by both MALDI and nanospray LC-MS/MS. Databases searches using the derived mAb sequences predicted residues comprising CDR loops, identified candidate germline genes, and showed the respective germline genes to accurately predict the N-terminal amino acid residues for each variable region. The above studies report the amino acid sequence of Cyt b-specific mAb variable region genes with high confidence and provide essential information for future efforts at Cyt b structure analysis by resonance energy transfer and X-ray crystallography.     

Systemic absorption of nicotine following acute secondhand exposure to electronic cigarette aerosol in a realistic social setting

Evidence suggests exposure of nicotine-containing e-cigarette aerosol to nonusers leads to systemic absorption of nicotine. However, no studies have examined acute secondhand exposures that occur in public settings. Here, we measured the serum, saliva and urine of nonusers pre- and post-exposure to nicotine via e-cigarette aerosol. Secondarily, we recorded factors affecting the exposure.Six nonusers of nicotine-containing products were exposed to secondhand aerosol from ad libitum e-cigarette use by three e-cigarette users for 2?h during two separate sessions (disposables, tank-style). Pre-exposure (baseline) and post-exposure peak levels (Cmax) of cotinine were measured in nonusers’ serum, saliva, and urine over a 6-hour follow-up, plus a saliva sample the following morning. We also measured solution consumption, nicotine concentration, and pH, along with use behavior.Baseline cotinine levels were higher than typical for the US population (median serum session one?=?0.089?ng/ml; session two?=?0.052?ng/ml). Systemic absorption of nicotine occurred in nonusers with baselines indicative of no/low tobacco exposure, but not in nonusers with elevated baselines. Median changes in cotinine for disposable exposure were 0.007?ng/ml serum, 0.033?ng/ml saliva, and 0.316?ng/mg creatinine in urine. For tank-style exposure they were 0.041?ng/ml serum, 0.060?ng/ml saliva, and 0.948?ng/mg creatinine in urine. Finally, we measured substantial differences in solution nicotine concentrations, pH, use behavior and consumption.Our data show that although exposures may vary considerably, nonusers can systemically absorb nicotine following acute exposure to secondhand e-cigarette aerosol. This can particularly affect sensitive subpopulations, such as children and women of reproductive age.     

Peptidoglycan recognition protein genes and risk of Parkinson's disease

Increased gut permeability, inflammation, and colonic α‐synuclein pathology are present in early Parkinson's disease (PD) and have been proposed to contribute to PD pathogenesis. Peptidoglycan is a structural component of the bacterial cell wall. Peptidoglycan recognition proteins (PGRPs) maintain healthy gut microbial flora by regulating the immune response to both commensal and harmful bacteria. We tested the hypothesis that variants in genes that encode PGRPs are associated with PD risk. Participants in two independent case‐control studies were genotyped for 30 single‐nucleotide polymorphisms (SNPs) in the four PGLYRP genes. Using logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for potential confounding variables, we conducted analyses in each study, separately and pooled. One SNP failed the assay, and three had little to no variation. The ORs were similar in both study populations. In pooled analyses, three of seven PGLYRP2 SNPs (rs3813135, rs733731, rs892145), one of five PGLYRP3 SNPs (rs2987763), and six of nine PGLYRP4 SNPs (rs10888557, rs12063091, rs3006440, rs3006448, rs3006458, and rs3014864) were significantly associated with PD risk. Association was strongest for PGLYRP4 5'untranslated region (UTR) SNP rs10888557 (GG reference, CG OR 0.6 [95%CI 0.4‐0.9], CC OR 0.15 [95%CI 0.04‐0.6]; log‐additive P‐trend, 0.0004). Common variants in PGLYRP genes are associated with PD risk in two independent studies. These results require replication, but they are consistent with hypotheses of a causative role for the gut microbiota and gastrointestinal immune response in PD. © 2014 International Parkinson and Movement Disorder Society