Variation in PTX3 Is Associated with Primary Graft Dysfunction after Lung Transplantation

Rationale: Elevated long pentraxin-3 (PTX3) levels are associated with the development of primary graft dysfunction (PGD) after lung transplantation. Abnormalities in innate immunity, mediated by PTX3 release, may play a role in PGD pathogenesis. Objectives: Our goal was to test whether variants in the gene encoding PTX3 are risk factors for PGD. Methods: We performed a candidate gene association study in recipients from the multicenter, prospective Lung Transplant Outcomes Group cohort enrolled between July 2002 and July 2009. The primary outcome was International Society for Heart and Lung Transplantation grade 3 PGD within 72 hours of transplantation. Targeted genotyping of 10 haplotype-tagging PTX3 single-nucleotide polymorphisms (SNPs) was performed in lung transplant recipients. The association between PGD and each SNP was evaluated by logistic regression, adjusting for pretransplantation lung disease, cardiopulmonary bypass use, and population stratification. The association between SNPs and plasma PTX3 levels was tested across genotypes in a subset of recipients with idiopathic pulmonary fibrosis. Measurements and Main Results: Six hundred fifty-four lung transplant recipients were included. The incidence of PGD was 29%. Two linked 5' region variants, rs2120243 and rs2305619, were associated with PGD (odds ratio, 1.5; 95% confidence interval, 1.1 to 1.9; P = 0.006 and odds ratio, 1.4; 95% confidence interval, 1.1 to 1.9; P = 0.007, respectively). The minor allele of rs2305619 was significantly associated with higher plasma PTX3 levels measured pretransplantation (P = 0.014) and at 24 hours (P = 0.047) after transplantation in patients with idiopathic pulmonary fibrosis. Conclusions: Genetic variants of PTX3 are associated with PGD after lung transplantation, and are associated with increased PTX3 plasma levels.     

Neuropsychological tools in hepatology: a survival guide for the clinician

Neuropsychological assessment has three main applications in clinical hepatology: (i) to detect, grade and monitor liver failure-related cognitive alterations in end-stage liver disease (hepatic encephalopathy), (ii) to substantiate complaints of attention or concentration difficulties in patients with non-cirrhotic chronic hepatitis C viral infection, and (iii) to screen patients who are being considered for liver transplantation for early signs of dementia. However, there is limited agreement on how cognitive assessment should be conducted in these patients, and how results should be interpreted and used to implement clinical decisions. In this review, we summarize the available literature on neuropsychological dysfunction in patients with cirrhosis and with chronic hepatitis C viral infection and provide some guidance on how to utilize neuropsychological assessment in practice.     

Early changes in retinal microcirculation after uncomplicated cataract surgery using an active-fluidics system

International Ophthalmology - To evaluate the early changes in retinal microcirculation after uncomplicated cataract surgery using an active-fluidics system. Patients underwent uncomplicated...     

A targeted neurotransmitter quantification and nontargeted metabolic profiling method for pharmacometabolomics analysis of olanzapine by using UPLC-HRMS

Neurotransmitters (NTs) are specific endogenous metabolites that act as “messengers” in synaptic transmission and are widely distributed in the central nervous system. Olanzapine (OLZ), a first-line antipsychotic drug, plays a key role in sedation and hypnosis, but, it presents clinical problems with a narrow therapeutic window, large individual differences and serious adverse effects, as well as an unclear mechanism in vivo. Herein, a simultaneous targeted NT quantification and nontargeted metabolomics method was developed and validated for pharmacometabolomics analysis of OLZ by using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS). Considering the low physiological concentrations of NTs, a full MS scan and target selective ion monitoring (tSIM) scan were combined for nontargeted metabolomics and targeted NT quantification, respectively. By using this strategy, NTs at a very low physiological concentration can be accurately detected and quantified in biological samples by tSIM scans. Moreover, simultaneously nontargeted profiling was also achieved by the full MS scan. The newly established UPLC-HRMS method was further used for the pharmacometabolomics study of OLZ. Statistical analysis revealed that tryptophan, 5-hydroxytryptophan, 5-hydroxytryptamine, γ-aminobutyric acid etc. were significantly downregulated, while tyrosine was significantly upregulated, which suggested that OLZ could promote the downstream phase II reaction of 5-hydroxytryptamine, inhibit tyrosine hydroxylase activity, and increase the activity of γ-aminobutyric acid transaminase. In conclusion, this method could provide novel insights for revealing the pharmacodynamic effect and mechanism of antipsychotic drugs.

We developed a method that would provide novel insights for revealing the pharmacodynamic effect and mechanism of antipsychotic drugs (olanzapine).     

Transport of nano zerovalent iron (nZVI) coupling with Alcaligenes sp. strain in porous media

Coupling nano zerovalent iron (nZVI) particles with anaerobic bacteria is a potentially powerful approach for remediating polluted groundwater. However, little is known about the transport of these mixed systems in porous media, which could potentially affect the system''s activity and half-life in aqueous environments. This study assessed the transport and stability of nZVI coupled with Alcaligenes sp. TB by column experiments and sedimentation tests. The results showed that combined bio-nZVI systems experienced significantly higher transport and lower sedimentation rates than stand-alone nZVI. The transmission electron microscopy (TEM) and scanning electron microscopy (SEM) images showed that Alcaligenes sp. TB reduced aggregation of nZVI to some extent, though slight toxicity to bacteria was observed. The results of ζ-potential measurements demonstrated that the presence of bacteria increased the electrostatic force between the particles. Voltammetry, X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) analysis confirmed that the bio-nZVI system undergoes different redox processes. The presence of bacteria favored the formation of FeOOH not Fe₂O₃ or Fe₃O₄, resulting in weaker surface magnetic properties.

Coupling nano zerovalent iron (nZVI) particles with anaerobic bacteria experienced significantly higher transport and lower sedimentation rates than stand-alone nZVI.     

Spinal infection: state of the art and management algorithm

Introduction

Spinal infection is a rare pathology although a concerning rising incidence has been observed in recent years. This increase might reflect a progressively more susceptible population but also the availability of increased diagnostic accuracy. Yet, even with improved diagnosis tools and procedures, the delay in diagnosis remains an important issue. This review aims to highlight the importance of a methodological attitude towards accurate and prompt diagnosis using an algorithm to aid on spinal infection management.

Methods

Appropriate literature on spinal infection was selected using databases from the US National Library of Medicine and the National Institutes of Health.

Results

Literature reveals that histopathological analysis of infected tissues is a paramount for diagnosis and must be performed routinely. Antibiotic therapy is transversal to both conservative and surgical approaches and must be initiated after etiological diagnosis. Indications for surgical treatment include neurological deficits or sepsis, spine instability and/or deformity, presence of epidural abscess and upon failure of conservative treatment.

Conclusions

A methodological assessment could lead to diagnosis effectiveness of spinal infection. Towards this, we present a management algorithm based on literature findings.     

Correlation between glycosylated hemoglobin and carotid intima-media thickness in non-diabetic peritoneal dialysis patients

Objective To investigate the correlation between glycosylated hemoglobin (HbA1c) and carotid intima?media thickness (CIMT) in non?diabetic peritoneal dialysis patients. Methods Forty?two non?diabetic peritoneal dialysis adult patients were enrolled in this study [mean age was (48.2±12.3) years, 50% was male]. CIMT was determined by carotid ultrasound. Patients were divided into two groups according to CIMT: CIMT normal group (CIMT＜0.9 mm) and CIMT thickening group (CIMT≥0.9 mm). HbA1c, 2?hour postprandial blood glucose (2hPBG) and other factors of the patients were analyzed with Spearman rank correlation and multiple linear regression. Results CIMT was correlated with age, 2hPBG, LDL?C, TG, TC, HbA1c in non?diabetic peritoneal dialysis patients (r＝0.355, 0.373, 0.416, 0.345, 0.351, 0.456, all P＜0.05). Multiple linear regression showed that HbA1c was the most powerful influence factor of CIMT（β＝0.459）. Conclusion HbA1c level is positively correlated with CIMT and may be a predictor of carotid atherosclerosis in non?diabetic peritoneal dialysis patients.