Characterization of electrospun nanocomposite scaffolds and biocompatibility with adipose-derived human mesenchymal stem cells

Electrospun nanocomposite scaffolds were fabricated by encapsulating multi-walled carbon nanotubes (MWNT) in poly (lactic acid) (PLA) nanofibers. Scanning electron microscopy (SEM) confirmed the fabrication of nanofibers, and transmission electron microscopy identified the alignment and dispersion of MWNT along the axis of the fibers. Tensile testing showed an increase in the tensile modulus for a MWNT loading of 0.25 wt% compared with electrospun nanofibrous mats without MWNT reinforcement. Conductivity measurements indicated that the confined geometry of the fibrous system requires only minute doping to obtain significant enhancements at 0.32 wt%. Adipose-derived human mesenchymal stem cells (hMSCs) were seeded on electrospun scaffolds containing 1 wt% MWNT and 0 wt% MWNT, to determine the efficacy of the scaffolds for cell growth, and the effect of MWNT on hMSC viability and proliferation over two weeks in culture. Staining for live and dead cells and DNA quantification indicated that the hMSCs were alive and proliferating through day 14. SEM images of hMSCs at 14 days showed morphological differences, with hMSCs on PLA well spread and hMSCs on PLA with 1% MWNT closely packed and longitudinally aligned

Patients affected with Fabry disease have an increased incidence of progressive hearing loss and sudden deafness: an investigation of twenty-two hemizygous male patients

BACKGROUND: Fabry disease (FD, OMIM 301500) is an X-linked inborn error of glycosphingolipid metabolism due to the deficient activity of alpha-galactosidase A, a lysosomal enzyme. While the progressive systemic deposition of uncleaved glycosphingolipids throughout the body is known to have protean clinical manifestations, few data are available regarding the cochlear involvement. METHODS: We non-invasively investigated cochlear functions in 22 consecutive hemizygous males (age 19–64 years, mean 39) affected with classic FD. Conventional audiometry, tympanometry, ABR audiometry, otoacoustic emissions were performed in all patients, together with medical history record and physical examination as part of an exhaustive baseline evaluation prior to enzyme replacement therapy. RESULTS: A total of 12 patients (54.5%) with classic FD were found to have abnormal audition. Five patients had progressive hearing loss and seven patients (32%) experienced sudden deafness. In addition, a hearing loss on high-tone frequencies was found in 7 out of the 10 remaining patients without clinical impairment, despite their young age at time of examination. The incidence of hearing loss appeared significantly increased in FD patients with kidney failure (P < 0.01) or cerebrovascular lesions (P < 0.01), whereas there was no correlation with left ventricular hypertrophy. In addition, tinnitus aurium was also found in six patients (27%). CONCLUSION: This is the first evidence of a high incidence of both progressive hearing loss and sudden deafness in a cohort of male patients affected with classic Fabry disease. The exact pathophysiologic mechanism(s) of the cochlear involvement deserves further studies

A prospective cohort study of postoperative complications in the management of perforated peptic ulcer

BACKGROUND: With dwindling rates of postoperative mortality in perforated peptic ulcer that is attributable to H(2)-receptor blocker usage, there is a need to shift the focus towards the prevention of postoperative morbidity. Further, the simultaneous contribution of several putative clinical predictors to this postoperative morbidity is not fully appreciated. Our objective was to assess the predictors of the risk, rate and number of postoperative complications in surgically treated patients of perforated peptic ulcer. METHODS: In a prospective cohort study of 96 subjects presenting as perforated peptic ulcer and treated using Graham's omentoplatsy patch or gastrojejunostomy (with total truncal vagotomy), we assessed the association of clinical predictors with three domains of postoperative complications: the risk of developing a complication, the rate of developing the first complication and the risk of developing higher number of complications. We used multiple regression methods – logistic regression, Cox proportional hazards regression and Poisson regression, respectively – to examine the association of the predictors with these three domains. RESULTS: We observed that the risk of developing a postoperative complication was significantly influenced by the presence of a concomitant medical illness [odds ratio (OR) = 8.9, p = 0.001], abdominal distension (3.8, 0.048) and a need of blood transfusion (OR = 8.2, p = 0.027). Using Poisson regression, it was observed that the risk for a higher number of complications was influenced by the same three factors [relative risk (RR) = 2.6, p = 0.015; RR = 4.6, p < 0.001; and RR = 2.4, p = 0.002; respectively]. However, the rate of development of complications was influenced by a history suggestive of shock [relative hazards (RH) = 3.4, p = 0.002] and A(- )blood group (RH = 4.7, p = 0.04). CONCLUSION: Abdominal distension, presence of a concomitant medical illness and a history suggestive of shock at the time of admission warrant a closer and alacritous postoperative management in patients of perforated peptic ulcer

Proteomic Analysis of Polypeptides Captured from Blood during Extracorporeal Albumin Dialysis in Patients with Cholestasis and Resistant Pruritus

Albumin dialysis using the molecular adsorbent recirculating system (MARS) is a new therapeutic approach for liver diseases. To gain insight into the mechanisms involved in albumin dialysis, we analyzed the peptides and proteins absorbed into the MARS strong anion exchange (SAX) cartridges as a result of the treatment of patients with cholestasis and resistant pruritus. Proteins extracted from the SAX MARS cartridges after patient treatment were digested with two enzymes. The resulting peptides were analyzed by multidimensional liquid chromatography coupled to tandem mass spectrometry. We identified over 1,500 peptide sequences corresponding to 144 proteins. In addition to the proteins that are present in control albumin-derived samples, this collection includes 60 proteins that were specific to samples obtained after patient treatment. Five of these proteins (neutrophil defensin 1 [HNP-1], secreted Ly-6/uPAR-related protein 1 [SLURP1], serum amyloid A, fibrinogen alpha chain and pancreatic prohormone) were confirmed to be removed by the dialysis procedure using targeted selected-reaction monitoring MS/MS. Furthermore, capture of HNP-1 and SLURP1 was also validated by Western blot. Interestingly, further analyses of SLURP1 in serum indicated that this protein was 3-fold higher in cholestatic patients than in controls. Proteins captured by MARS share certain structural and biological characteristics, and some of them have important biological functions. Therefore, their removal could be related either to therapeutic or possible adverse effects associated with albumin dialysis

Neural correlates of indicators of sound change in Cantonese: evidence from cortical and subcortical processes

Across time, languages undergo changes in phonetic, syntactic and semantic dimensions. Social, cognitive and cultural factors contribute to sound change, a phenomenon in which the phonetics of a language undergo changes over time. Individuals who misperceive and produce speech in a slightly divergent manner (called innovators) contribute to variability in the society, eventually leading to sound change. However, the cause of variability in these individuals is still unknown. In this study, we examined whether such misperceptions are represented in neural processes of the auditory system. We investigated behavioral, subcortical (via FFR), and cortical (via P300) manifestations of sound change processing in Cantonese, a Chinese language in which several lexical tones are merging. Across the merging categories, we observed a similar gradation of speech perception abilities in both behavior and the brain (subcortical and cortical processes). Further, we also found that behavioral evidence of tone merging correlated with subjects’ encoding at the subcortical and cortical levels. These findings indicate that tone-merger categories, that are indicators of sound change in Cantonese, are represented neurophysiologically with high fidelity. Using our results, we speculate that innovators encode speech in a slightly deviant neurophysiological manner, and thus produce speech divergently that eventually spreads across the community and contributes to sound change

Nitration of the Pollen Allergen Bet v 1.0101 Enhances the Presentation of Bet v 1-Derived Peptides by HLA-DR on Human Dendritic Cells

Nitration of pollen derived allergens can occur by NO2 and ozone in polluted air and it has already been shown that nitrated major birch (Betula verrucosa) pollen allergen Bet v 1.0101 (Bet v 1) exhibits an increased potency to trigger an immune response. However, the mechanisms by which nitration might contribute to the induction of allergy are still unknown. In this study, we assessed the effect of chemically induced nitration of Bet v 1 on the generation of HLA-DR associated peptides. Human dendritic cells were loaded with unmodified Bet v 1 or nitrated Bet v 1, and the naturally processed HLA-DR associated peptides were subsequently identified by liquid chromatography-mass spectrometry. Nitration of Bet v 1 resulted in enhanced presentation of allergen-derived HLA-DR-associated peptides. Both the copy number of Bet v 1 derived peptides as well as the number of nested clusters was increased. Our study shows that nitration of Bet v 1 alters antigen processing and presentation via HLA-DR, by enhancing both the quality and the quantity of the Bet v 1-specific peptide repertoire. These findings indicate that air pollution can contribute to allergic diseases and might also shed light on the analogous events concerning the nitration of self-proteins