Role of time from transplantation to biopsy in histologic ABMR: A single center report.

BACKGROUND: Allograft biopsies with lesions of Antibody-Mediated Rejection (ABMR) with Microvascular Inflammation (MVI) have shown heterogeneous etiologies and outcomes. METHODS: To examine factors associated with outcomes in biopsies that meet histologic ABMR criteria, we retrospectively evaluated for-cause biopsies at our center between 2011 and 2017. We included biopsies that met the diagnosis of ABMR by histology, along with simultaneous evaluation for anti-Human Leukocyte Antigen (HLA) donor-specific antibodies (DSA). We evaluated death-censored graft loss (DCGL) and used a principal component analysis (PCA) approach to identify key predictors of outcomes. RESULTS: Out of the histologic ABMR cohort (n = 118), 70 were DSA-positive ABMR, while 48 had no DSA. DSA(+)ABMR were younger and more often female recipients. DSA(+)ABMR occurred significantly later post-transplant than DSA(-)ABMR suggesting time-dependence. DSA(+)ABMR had higher inflammatory scores (i,t), chronicity scores (ci, ct) and tended to have higher MVI scores. Immunodominance of DQ-DSA in DSA(+)ABMR was associated with higher i+t scores. Clinical/histologic factors significantly associated with DCGL after biopsy were inputted into the PCA. Principal component-1 (PC-1), which contributed 34.8% of the variance, significantly correlated with time from transplantation to biopsy, ci/ct scores and DCGL. In the PCA analyses, i, t scores, DQ-DSA, and creatinine at biopsy retained significant correlations with GL-associated PCs. CONCLUSIONS: Time from transplantation to biopsy plays a major role in the prognosis of biopsies with histologic ABMR and MVI, likely due to ongoing chronic allograft injury over time.

Antioxidant activity of cod (Gadus morhua) protein hydrolysates: Fractionation and characterisation of peptide fractions.

This study aimed to characterise peptide fractions (>5kDa, 3-5kDa and <3kDa) with antioxidative activity obtained from a cod protein hydrolysate. The free amino acids in all fractions were dominated by Ala, Gly, Glu and Ser. The total amino acid composition had high proportions of Lys, Ala and Glu. The 3-5kDa and <3kDa fractions were further fractionated by size exclusion chromatography. All sub-fractions showed high Fe(2+) chelating activity. The DPPH radical-scavenging activity of the 3-5kDa fraction was exerted mainly by one sub-fraction dominated by peptides with masses below 600Da. The DPPH radical-scavenging activity of the <3kDa fraction was exerted by sub-fractions with low molecular weight. The highest reducing power was found in a sub-fraction containing peptides rich in Arg, Tyr and Phe. Both free amino acids and low molecular weight peptides thus seemed to contribute to the antioxidative activity of the peptide fractions, and Tyr seemed to play a major role in the antioxidant activity.

Antioxidant activity of Cod (Gadus morhua) protein hydrolysates: in vitro assays and evaluation in 5% fish oil-in-water emulsion.

Cod protein hydrolysates were fractionated according to the molecular mass into three fractions of >5 kDa, 3-5 kDa and <3 kDa using an ultrafiltration membrane system. The antioxidative activity of the crude hydrolysates and the fractions were investigated, both in in vitro assays (DPPH radical scavenging activity, reducing power, Fe²âº chelating activity and inhibition of lipid oxidation in liposome model system), and in 5% fish oil-in-water emulsions. The <3 kDa fractions had very good radical scavenging activity, Fe²âº chelating activity and reducing power while the fraction 3-5 kDa resulted in higher protection against oxidation in the liposome model system. When tested in 5% oil-in-water emulsions, all the fractions, including the crude protein hydrolysate, were able to protect fish oil against oxidation in an iron induced oxidation system. However, none of the peptide fractions were effective in preventing tocopherol loss and showed no tocopherol sparing property. Volatile oxidation products showed an interaction between the aldehydes and the protein/peptides added in the emulsions, and this needs further investigation.

RAADS-14 Screen: validity of a screening tool for autism spectrum disorder in an adult psychiatric population.

BACKGROUND: Autism spectrum disorder (ASD) can be difficult to distinguish from other psychiatric disorders. The clinical assessment of ASD is lengthy, and has to be performed by a specialized clinician. Therefore, a screening instrument to aid in the identification of patients who may have undiagnosed ASD should be useful. The purpose of this study was to develop such a screening instrument. METHODS: Based on the 80 item Ritvo Autism and Asperger Diagnostic Scale-Revised (RAADS-R), we developed a 14 item self-evaluation questionnaire, the RAADS-14 Screen. In total, 135 adults with ASD and 508 psychiatric controls completed the abridged version of the RAADS-R. RESULTS: The RAADS-14 Screen score was significantly higher in the ASD group than in the control samples, with a median score of 32 for ASD, 15 for attention deficit hyperactivity disorder, and 11 for other psychiatric disorders (P < 0.001). A cut-off score of 14 or above reached a sensitivity of 97% and a specificity of 46 to 64%. A factor analysis identified three factors consistent with mentalizing deficits, social anxiety, and sensory reactivity relevant for the diagnosis of ASD. The psychometric properties of RAADS-14 Screen were shown to be satisfactory. CONCLUSIONS: The results of this study indicate that RAADS-14 Screen is a promising measure in screening for ASD in adult psychiatric outpatients.

"Give the ladies a chance": gender and partisanship in the Prohibition Party, 1869-1912.

In the nineteenth-century Prohibition Party, American women ascribed new gendered meanings to party work traditionally performed by male partisans, and also drew upon their gendered roles as women, mothers, and wives to create new partisan strategies. This article investigates the political culture that sustained a remarkable departure from traditional Democratic and Republican practices, and further explores why women's contributions to the Prohibition Party declined in the early-twentieth century. In so doing, it traces how gender and gender roles shaped the meaning of party and politics, and elucidates the interplay between institutions, constituencies, and policy during one of America's most tumultuous political eras.

The Swedish version of the Ritvo autism and asperger diagnostic scale: revised (RAADS-R). A validation study of a rating scale for adults.

There is a paucity of diagnostic instruments for adults with autism spectrum disorder (ASD). This study evaluates the psychometric properties of the Swedish version of the Ritvo Autism and Asperger Diagnostic Scale-Revised (RAADS-R), an 80-item self-rating scale designed to assist clinicians diagnosing ASD in adults. It was administered to 75 adults with ASD and 197 comparison cases. Also, a subset completed the Autism Spectrum Quotient (AQ). Three out of four subscales had high internal consistency. Sensitivity was 91% and specificity was 93%. The ASD subjects had significantly higher mean scores on all subscales. ASD females had higher scores than ASD males on the sensory motor subscale, a dimension not included in the AQ. RAADS-R showed promising test re-test reliability.

Increased contractile response to phenylephrine in detrusor of patients with bladder outlet obstruction: effect of the alpha1A and alpha1D-adrenergic receptor antagonist tamsulosin.

PURPOSE: Alpha1-adrenergic receptor (alpha1-AR) antagonists are effective for treating patients with lower urinary tract symptoms associated with bladder outlet obstruction (BOO). In humans up-regulation of alpha1-AR function in the detrusor in patients with BOO has been suggested but to our knowledge it is not yet confirmed. We investigated the effect of phenylephrine, an alpha1-AR agonist, on isometric tension in small detrusor muscle biopsies from patients with lower urinary tract symptoms and BOO compared with controls. MATERIALS AND METHODS: Detrusor biopsies were obtained from 7 men with BOO undergoing prostatectomy and 7 undergoing cystectomy for bladder cancer (controls). Patients were characterized by symptom score and urodynamics. Isometric tension was measured in detrusor biopsies with an especially built mini myograph. RESULTS: Mean International Prostate Symptom Score +/- SEM in patients with BOO and controls were 22.3 +/- 2.3 and 4.0 +/- 0.8, respectively. Phenylephrine (10(-6) to 10(-3) M) induced a significant contractile response increase in detrusor biopsies from patients with BOO compared with controls at all concentrations. Tamsulosin (0.1 to 3.0 nM) inhibited phenylephrine induced contraction in a dose dependent manner. CONCLUSIONS: To our knowledge this functional study shows for the first time a highly significant increase in contractile force to phenylephrine in patients with BOO compared with controls. These results suggest up-regulation of alpha1-AR function in BOO since contractile responses were potently inhibited by the alpha1A/D-AR antagonist tamsulosin.

Monocyte chemoattractant protein-1 production by human detrusor smooth muscle cells.

PURPOSE: Most recently attention has turned to the secretory properties of smooth muscle cells. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that causes mast cells recruitment and provokes mast cells activation in vitro. We investigated whether MCP-1 is produced by human detrusor smooth muscle cells (HDSMCs) cultured under inflammatory conditions. MATERIALS AND METHODS: Using an explantation technique HDSMCs were isolated and short-term cultured. HDSMCs were incubated at 37C for 24 hours with the proinflammatory mediators interleukin-1 beta (IL-1 beta), tumor necrosis factor (TNF-alpha), lipopolysaccharide, histamine, leukotriene D4 and prostaglandin E2. The level of MCP-1 in cell supernatants were measured by enzyme linked immunoassay. RESULTS: There was basal secretion of MCP-1 in unstimulated cultures. Following 24-hour incubation with IL-1 beta or TNF-alpha (1 pg/ml to 100 ng/ml) the level of MCP-1 increased in a dose dependent manner. IL-1 beta was more potent at inducing MCP-1 release in 8 of 10 experiments. Lipopolysaccharide (10 microg/ml), histamine (100 microM), leukotriene D4 (50 nM), prostaglandin E2 (1 microM) and KCl (30 to 100 mM) failed to induce MCP-1 production. When IL-1 beta (10 ng/ml) and TNF-alpha (10 ng/ml) were given in combination, a highly synergistic effect on MCP-1 production was observed. CONCLUSIONS: To our knowledge this study shows for the first time that human detrusor smooth muscle cells cultivated under inflammatory conditions produce significant amounts of MCP-1. In addition to contractile function, HDSMCs have synthesis and secretory potential with the release of MCP-1. Thus, MCP-1 may contribute to the local inflammatory process by producing proinflammatory mediators. The release of cytokines and chemokines by human detrusor muscle even in small amounts may have important functional consequences.

The cysteinyl-leukotriene D4 induces cytosolic Ca2+ elevation and contraction of the human detrusor muscle.

PURPOSE: The role of intracellular Ca2+ in the activation of human detrusor smooth muscle cells (SMCs) is pivotal. Recently we showed that the mast cell derived pro-inflammatory mediator leukotriene D(4) (LTD(4)) induces increase in intracellular free Ca2+ ([Ca2+](i)) in human detrusor myocytes. In the current study we examined the mechanisms underlying LTD(4) induced increase in [Ca2+](i) and tested whether LTD(4) induces muscle contraction by measuring force development in human detrusor tissue. MATERIALS AND METHODS: Cultures of human detrusor SMCs were obtained from patients with benign bladder diseases undergoing cystoscopy. [Ca2+](i) was measured in fura-2 loaded SMCs using micro-spectrofluorometry and dynamic video imaging. Contractile force was monitored with an especially built mini-myograph. RESULTS: Spontaneous oscillations in [Ca2+](i) and force were observed. In the absence of calcium these oscillations were absent. LTD(4) caused a concentration dependent increase in [Ca2+](i) and isometric force. Calcium was released exclusively from intracellular stores. Increases in [Ca2+](i) and force were inhibited in dose dependent fashion by the LTD(4) receptor antagonists montelukast and zafirlukast. Likewise, LTC(4) and LTE(4) induced an increase in [Ca2+](i) and contractile force in the rank order LTD(4) >LTC(4) >LTE(4). Inhibition of Ca2+ induced Ca2+ release (CICR) with thapsigargin and ryanodine suggested the presence of a functional CICR in SMCs. CONCLUSIONS: To our knowledge this study demonstrates for the first time that the cysteinyl-leukotriene LTD(4) induces contraction in human detrusor SMCs. LTD(4) induced force and increased [Ca2+](i) were entirely dependent on Ca2+ release from intracellular stores. The action of LTD(4) on force development and increased [Ca2+](i) appeared to be specific, mediated by the binding and activation of specific LTD(4) receptors on SMCs. Also, to our knowledge this report is the first to show that human detrusor SMCs are sensitive to ryanodine, consistent with the hypothesis that a CICR is present and functional in these cells. The presence and role of endogenous cysteinyl leukotrienes for normal contractile functioning of the human detrusor during inflammation remains to be elucidated.