Cutaneous Squamous Cell Carcinoma Outcomes in Solid Organ Transplant Recipients: A Matched Retrospective Cohort Study.

BACKGROUND: Solid organ transplant recipients with cutaneous squamous cell carcinoma (CSCC) have an increased risk of poor outcomes. However, a recent study demonstrated that immunosuppression is not an independent risk factor for these poor outcomes after controlling for primary tumor stage. OBJECTIVE: To evaluate whether transplant status is an independent risk factor for poor outcomes in CSCC. MATERIALS AND METHODS: A database of CSCCs treated at an academic center over 10 years was used to perform a retrospective cohort study comparing the risk of poor outcomes (local recurrence, regional and distant metastases, and disease-specific death) in solid organ transplant recipients and controls. Subjects were matched on age, tumor stage, sex, tumor site, and time to poor outcome. RESULTS: There were 316 tumors from 78 transplant patients and 316 tumors from 262 controls. On multivariate analysis, tumor stage and location on the head and neck were predictive of poor outcomes. There was no significant difference in the risk of poor outcomes in the transplant group versus the control group. CONCLUSION: Transplant status was not an independent risk factor for poor squamous cell carcinoma outcomes after controlling for stage, age, sex, site, and time to poor outcome.

Detection of advanced brain aging in schizophrenia and its structural underpinning by using normative brain age metrics.

Conceptualizing mental disorders as deviations from normative functioning provides a statistical perspective for understanding the individual heterogeneity underlying psychiatric disorders. To broaden the understanding of the idiosyncrasy of brain aging in schizophrenia, we introduced an imaging-derived brain age paradigm combined with normative modeling as novel brain age metrics. We constructed brain age models based on GM, WM, and their combination (multimodality) features of 482 normal participants. The normalized predicted age difference (nPAD) was estimated in 147 individuals with schizophrenia and their 130 demographically matched controls through normative models of brain age metrics and compared between the groups. Regression analyses were also performed to investigate the associations of nPAD with illness duration, onset age, symptom severity, and intelligence quotient. Finally, regional contributions to advanced brain aging in schizophrenia were investigated. The results showed that the individuals exhibited significantly higher nPAD (P < 0.001), indicating advanced normative brain age than the normal controls in GM, WM, and multimodality models. The nPAD measure based on WM was positively associated with the negative symptom score (P = 0.009), and negatively associated with the intelligence quotient (P = 0.039) and onset age (P = 0.006). The imaging features that contributed to nPAD mostly involved the prefrontal, temporal, and parietal lobes, especially the precuneus and uncinate fasciculus. This study demonstrates that normative brain age metrics could detect advanced brain aging and associated clinical and neuroanatomical features in schizophrenia. The proposed nPAD measures may be useful to investigate aberrant brain aging in mental disorders and their brain-phenotype relationships.

Considerations on the use of carbon and nitrogen isotopic ratios for sediment fingerprinting.

Carbon and nitrogen stable isotopic ratios are increasingly used in sediment fingerprinting studies. However, questions remain regarding tracer conservativeness during sediment transport and other error considerations. We investigate conservativeness processes, including carbon oxidation and nitrogen mineralization, using experiments. We also test how other considerations impact the isotopic ratios including algae accrual into temporary sediment deposits in the river, the physical loss of organic matter via disaggregation, concentration dependent mixing, and time-varying isotopic ratios of sediment sources. Results show all processes and considerations can change isotope abundance, however, significance varied. Carbon oxidation, nitrogen mineralization and upland seasonality of sediment sources did not significantly change isotopic ratios. Algae accrual, concentration dependency mixing, physical loss of organic matter during transport, and seasonality of the in-stream sediment source significantly changed the isotopic ratios for the conditions tested. Fertilization significantly impacted the stable carbon isotopic ratio in one case considered. Results from sediment fingerprinting simulations and testing how well the virtual mixture fits the mass balance equation agreed with significance results for tracer changes, and some uncertainty considerations changed fractional contribution of sources by as much as 50%. A noteworthy recommendation is the mean isotopic ratios of sediment sources should be separated by at least 1‰ to lessen tracer conservativeness concerns in fingerprinting simulation. We recommend concentration dependent mixing becomes the accepted practice when using isotopic ratios, however, we warn against using particle size corrections. We recommend the loss of organic matter during disaggregation be accounted for in fingerprinting estimates. We recommend algae accrual in in-stream sediment deposits should either be accounted for or in-stream sediment should be treated as a time-varying source in sediment fingerprinting simulations. Finally, we recommend both the carbon and nitrogen isotopic ratio should be tested as potential tracers because the two tracers performed similarly when testing how well the virtual mixture fits the mass balance equations.

Calling nurses to care for burn victims after color-dust explosion.

BACKGROUND: Healthcare professionals follow codes of ethics, making them responsible for providing holistic care to all disaster victims. However, this often results in ethical dilemmas due to the need to provide rapid critical care while simultaneously attending to a complex spectrum of patient needs. These dilemmas can cause negative emotions to accumulate over time and impact physiological and psychological health, which can also threaten nurse-patient relationships. AIM: This study aimed to understand the experience of nurses who cared for burn victims of the color-dust explosion and the meaning of ethical relationships between nurse and patient. RESEARCH DESIGN: A qualitative descriptive study using a phenomenological approach. PARTICIPANTS AND RESEARCH CONTEXT: Clinical nurses who provided care to the patients of the Formosa color-dust explosion of 2015 were selected by purposive sampling (N = 12) from a medical center in Taiwan. Data were collected using individual in-depth semi-structured interviews. Audiotaped interviews were transcribed and analyzed using Colaizzi's method. ETHICAL CONSIDERATIONS: This study was approved by the institutional review board of the study hospital. All participants provided written informed consent. FINDINGS: Three main themes described the essence of the ethical dilemmas experienced by nurses who cared for the burn-injured patients: (1) the calling must be answered, (2) the calling provoked my feelings, and (3) the calling called out my strengths. CONCLUSIONS: Healthcare providers should recognize that nurses believed they had an ethical responsibility to care for color-dust explosion burn victims. Understanding the feelings of nurses during the care of patients and encouraging them to differentiate between the self and the other by fostering patient-nurse relationships based on intersubjectivity could help nurses increase self-care and improve patient caregiving.

Dipeptidyl Peptidase-4 Inhibitor Decreases Allograft Vasculopathy Via Regulating the Functions of Endothelial Progenitor Cells in Normoglycemic Rats.

PURPOSE: Chronic rejection induces the occurrence of orthotopic allograft transplantation (OAT) vasculopathy, which results in failure of the donor organ. Numerous studies have demonstrated that in addition to regulating blood sugar homeostasis, dipeptidyl peptidase-4 (DPP-4) inhibitors can also provide efficacious therapeutic and protective effects against cardiovascular diseases. However, their effects on OAT-induced vasculopathy remain unknown. Thus, the aim of this study was to investigate the direct effects of sitagliptin on OAT vasculopathy in vivo and in vitro. METHODS: The PVG/Seac rat thoracic aorta graft to ACI/NKyo rat abdominal aorta model was used to explore the effects of sitagliptin on vasculopathy. Human endothelial progenitor cells (EPCs) were used to investigate the possible underlying mechanisms. RESULTS: We demonstrated that sitagliptin decreases vasculopathy in OAT ACI/NKyo rats. Treatment with sitagliptin decreased BNP and HMGB1 levels, increased GLP-1 activity and stromal cell-derived factor 1α (SDF-1α) expression, elevated the number of circulating EPCs, and improved the differentiation possibility of mononuclear cells to EPCs ex vivo. However, in vitro studies showed that recombinant B-type natriuretic peptide (BNP) and high mobility group box 1 (HMGB1) impaired EPC function, whereas these phenomena were reversed by glucagon-like peptide 1 (GLP-1) receptor agonist treatment. CONCLUSIONS: We suggest that the mechanisms underlying sitagliptin-mediated inhibition of OAT vasculopathy probably occur through a direct increase in GLP-1 activity. In addition to the GLP-1-dependent pathway, sitagliptin may regulate SDF-1α levels and EPC function to reduce OAT-induced vascular injury. This study may provide new prevention and treatment strategies for DPP-4 inhibitors in chronic rejection-induced vasculopathy.

Selenium removal by activated alumina in batch and continuous-flow reactors.

Selenium removal by activated alumina (AA) in batch and continuous-flow reactors was investigated in this study. The adsorption kinetics fitted pseudo-first as well as pseudo-second order models with equilibrium time for Se(VI) and Se(IV) adsorption of 8 and 12 hr, respectively. A significant higher adsorption capacity for Se(IV) than Se(VI) was observed in isothermal adsorption experiments. The adsorption isotherms of Se(VI) and Se(IV) agreed well with both Langmuir and Freundlich adsorption models. The results also showed that Se(VI) adsorption was adversely affected by NaHCO3 concentrations, while Se(IV) adsorption was not due to the selectivity of activated alumina for anions. In the continuous-flow reactor packed with AA and inoculated with Shigella fergusonii strain TB42616 under a hydraulic detention time of 3 days, approximately 74% and 70% Se(VI) were removed after 40 days at influent concentrations of 10 and 50 mg/L, respectively. Effluent concentrations of Se(IV) from the bioreactor were insignificant due to the combination of bioactivities and adsorption. The AA-packed bioreactor is promising in both Se(VI) and Se(IV) removal as better removal efficiency may be accomplished by increasing the liquid retention time. PRACTITIONER POINTS: The adsorption capacity for Se(IV) of activated alumina was significantly higher than that for Se(VI). Se(VI) adsorption was inhibited by NaHCO3 , while Se(IV) adsorption was not. Se(IV) formed by biological Se(VI) reduction was adsorbed by activated alumina in continuous-flow reactors. Both Se(VI) and Se(IV) were significantly removed by activated alumina-packed continuous-flow reactors.

Selenium reduction by a defined co-culture of Shigella fergusonii strain TB42616 and Pantoea vagans strain EWB32213-2.

Selenium reduction was evaluated with pure batch cultures of Shigella fergusonii strain TB42616 (TB) and Pantoea vagans strain EWB32213-2 (EWB), respectively. A two-stage process, from Se(VI) to Se(IV) and then from Se(IV) to Se(0), was observed. The second stage of reduction, from Se(IV) to Se(0), was observed as the rate-limiting step resulting in accumulation of the more toxic Se(IV). In order to facilitate Se(VI) reduction and reduce Se(IV) accumulation, the Se(VI)-reducing strain TB was co-cultured with a Se(IV)-reducing strain EWB. Although Se(VI) reduction rate was not affected, Se(IV) reduction was significantly enhanced with low Se(IV) accumulation in the defined co-culture. Effects of culture composition as well as nitrate and arsenate on Se(VI) reduction were also investigated. A co-culture composition of 10:1 (EWB:TB) ratio was observed to achieve the best total selenium reduction. In addition, nitrate at 50 mg/L was observed to inhibit Se(IV) reduction but not Se(VI) reduction, while arsenate at 200 mg/L exhibited slight inhibition on both Se(VI) and Se(IV) reduction.

Genetic associations and expression of extra-short isoforms of disrupted-in-schizophrenia 1 in a neurocognitive subgroup of schizophrenia.

Disrupted-in-schizophrenia 1 (DISC1) was reported to be associated with schizophrenia. In a previous study, we found significant association with schizophrenia patients with deficient sustained attention assessed by continuous performance test (CPT). This study aimed to identify risk polymorphisms in this specific neurocognitive subgroup and investigate the expression of different isoforms of DISC1. A total of 83 genetic variants were identified through direct sequencing in 50 controls and 100 schizophrenia patients. Fourteen variants were genotyped in 600 controls and 912 patients. Patients were subgrouped by familial loading (multiplex or simplex) and performance on CPT. The frequency of AA genotype of rs11122324 at the 3'-UTR of Es and Esv1 isoforms and of rs2793091 at intron 4 were significantly higher in multiplex schizophrenia patients than those in controls (corrected p < 0.05). In further subgrouping, the frequency of AA genotype of the two SNPs were significantly higher in multiplex schizophrenia patients with deficient sustained attention than those in controls (corrected p < 0.005). The mRNA expression levels of two extra-short isoforms (Es and Esv1) in the EBV-transformed lymphocytes of schizophrenia were significantly higher than those of controls. Luciferase reporter assays demonstrated that the A-allele of rs11122324 significantly upregulated DISC1 extra-short isoforms transcription compared with the G-allele. We found two SNPs (rs11122324 and rs2793091) of DISC1 may be specifically associated with multiplex schizophrenia patients with deficient sustained attention. The SNP rs11122324 may be a risk polymorphism, which may have functional influence on the transcription of Es and Esv1 through increasing their expression.

The germline-specific expression of Foxl3a and its paralogous Foxl3b are associated with male gonadal differentiation in the Japanese eel, Anguilla japonica.

Unlike its paralog Foxl2, which is well known for its role in ovarian development in vertebrates, the function of Foxl3 is still unclear. Foxl3 is an ancient duplicated copy of Foxl2. It is present as a single copy in ray-finned fish. But, due to repeated losses, it is absent in most tetrapods. Our transcriptomic data, however, show that two Foxl3s (Foxl3a and its paralog Foxl3b) are present in Japanese eel. Foxl3a is predominantly expressed in the pituitary, and Foxl3b is predominantly expressed in the gills. Both Foxl3s show a sex-dimorphic expression, being higher expression in testes than in ovaries. Moreover, Foxl3a and Foxl3b were exclusively expressed during gonadal differentiation in control eels (100% male). Conversely, Foxl3a and Foxl3b significantly decreased after gonadal differentiation in E2-treated eels (100% female). Furthermore, in accordance the difference in adhesive ability between somatic cells and germline cells in testes, Foxl3s showed a high expression in suspension cells (putative germline cells) and low expression in adhesive cells (putative somatic cells). In situ hybridization further showed that Foxl3a and Foxl3b were expressed in the testicular germline cells. In addition, Foxl3s expression was not changed by sex steroids in in vitro testes culture. Taken together, our results suggest that the teleost-specific Foxl3 paralog was repeatedly lost in most fish after the third round of whole genome duplication. The two germline-expressed Foxl3s had higher expression levels in males than in females during gonadal differentiation in Japanese eel. These results demonstrated that Foxl3s might play an important role in germline sexual fate determination from ancient fish to modern fish.

Shared and distinct alterations of white matter tracts in remitted and nonremitted patients with schizophrenia.

Patients with schizophrenia do not usually achieve remission state even after adequate antipsychotics treatment. Previous studies found significant difference in white matter integrity between patients with good outcomes and those with poor outcomes, but difference is still unclear at individual tract level. This study aimed to use a systematic approach to identify the tracts that were associated with remission state in patients with schizophrenia. We evaluated 91 patients with schizophrenia (remitted, 50; nonremitted, 41) and 50 healthy controls through diffusion spectrum imaging. White matter tract integrity was assessed through an automatic tract-specific analysis method to determine the mean generalized fractional anisotropy (GFA) values of the 76 white matter tract bundles in each participant. Analysis of covariance among the 3 groups revealed 12 tracts that were significantly different in GFA values. Post-hoc analysis showed that compared with the healthy controls, the nonremission group had reduced integrity in all 12 tracts, whereas the remission group had reduced integrity in only 4 tracts. Comparison between the remission and nonremission groups revealed 4 tracts with significant difference (i.e., the right fornix, bilateral uncinate fasciculi, and callosal fibers connecting the temporal poles) even after adjusting age, sex, education year, illness duration, and medication dose. Furthermore, all the 4 tracts were correlated with negative symptoms scores of the positive and negative syndrome scale. In conclusion, our study identified the tracts that were associated with remission state of schizophrenia. These tracts might be a potential prognostic marker for the symptomatic remission in patients with schizophrenia.

Individualized prediction of schizophrenia based on the whole-brain pattern of altered white matter tract integrity.

BACKGROUND: A schizophrenia diagnosis relies on characteristic symptoms identified by trained physicians, and is thus prone to subjectivity. This study developed a procedure for the individualized prediction of schizophrenia based on whole-brain patterns of altered white matter tract integrity. METHODS: The study comprised training (108 patients and 144 controls) and testing (60 patients and 60 controls) groups. Male and female participants were comparable in each group and were analyzed separately. All participants underwent diffusion spectrum imaging of the head, and the data were analyzed using the tract-based automatic analysis method to generate a standardized two-dimensional array of white matter tract integrity, called the connectogram. Unique patterns in the connectogram that most accurately identified schizophrenia were systematically reviewed in the training group. Then, the diagnostic performance of the patterns was individually verified in the testing group by using receiver-operating characteristic curve analysis. RESULTS: The performance was high in men (accuracy = 0.85) and satisfactory in women (accuracy = 0.75). In men, the pattern was located in discrete fiber tracts, as has been consistently reported in the literature; by contrast, the pattern was widespread over all tracts in women. These distinct patterns suggest that there is a higher variability in the microstructural alterations in female patients than in male patients. CONCLUSIONS: The individualized prediction of schizophrenia is feasible based on the different whole-brain patterns of tract integrity. The optimal masks and their corresponding regions in the fiber tracts could serve as potential imaging biomarkers for schizophrenia. Hum Brain Mapp 39:575-587, 2018. © 2017 Wiley Periodicals, Inc.

Urotensin II induces interleukin 8 expression in human umbilical vein endothelial cells.

BACKGROUND: Urotensin II (U-II), an 11-amino acid peptide, exerts a wide range of actions in cardiovascular systems. Interleukin-8 (IL-8) is secreted by endothelial cells, thereby enhancing endothelial cell survival, proliferation, and angiogenesis. However, the interrelationship between U-II and IL-8 as well as the detailed intracellular mechanism of U-II in vascular endothelial cells remain unclear. The aim of this study was to investigate the effect of U-II on IL-8 expression and to explore its intracellular mechanism in human umbilical vein endothelial cells. METHODS/PRINCIPAL FINDINGS: Primary human umbilical vein endothelial cells were used. Expression of IL-8 was determined by real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and luciferase reporter assay. Western blot analyses and experiments with specific inhibitors were performed to reveal the downstream signaling pathways as concerned. U-II increased the mRNA/protein levels of IL-8 in human umbilical vein endothelial cells. The U-II effects were significantly inhibited by its receptor antagonist [Orn(5)]-URP. Western blot analyses and experiments with specific inhibitors indicated the involvement of phosphorylation of p38 mitogen-activated protein kinase and extracellular signal-regulated kinase in U-II-induced IL-8 expression. Luciferase reporter assay further revealed that U-II induces the transcriptional activity of IL-8. The site-directed mutagenesis indicated that the mutation of AP-1 and NF-kB binding sites reduced U-II-increased IL-8 promoter activities. Proliferation of human umbilical vein endothelial cells induced by U-II could be inhibited significantly by IL-8 RNA interference. CONCLUSION/SIGNIFICANCE: The results show that U-II induces IL-8 expression in human umbilical vein endothelial cells via p38 mitogen-activated protein kinase and extracellular signal-regulated kinase signaling pathways and IL-8 is involved in the U-II-induced proliferation of human umbilical vein endothelial cells.

Modeling arsenite oxidation by chemoautotrophic Thiomonas arsenivorans strain b6 in a packed-bed bioreactor.

Arsenic is a major toxic pollutant of concern for the human health. Biological treatment of arsenic contaminated water is an alternative strategy to the prevalent conventional treatments. The biological treatment involves a pre-oxidation step transforming the most toxic form of arsenic, As (III), to the least toxic form, As (V), respectively. This intermediate process improves the overall efficiency of total arsenic removal from the contaminated water. As (III) oxidation by the chemoautotrophic bacterium Thiomonas arsenivorans strain b6 was investigated in a fixed-film reactor under variable influent As (III) concentrations (500-4000 mg/L) and hydraulic residence times (HRTs) (0.2-1 day) for a duration of 137 days. During the entire operation, seven steady-state conditions were obtained with As (III) oxidation efficiency ranging from 48.2% to 99.3%. The strong resilience of the culture was exhibited by the recovery of the bioreactor from an As (III) overloading of 5300±400 mg As (III)/L day operated at a HRT of 0.2 day. An arsenic mass balance revealed that As (III) was mainly oxidized to As (V) with unaccounted arsenic (≤4%) well within the analytical error of measurement. A modified Monod flux expression was used to determine the biokinetic parameters by fitting the model against the observed steady-state flux data obtained from operating the bioreactor under a range of HRTs (0.2-1 day) and a constant influent As (III) concentration of 500 mg/L. Model parameters, k=0.71±0.1 mg As (III)/mg cells h, and K(s)=13.2±2.8 mg As (III)/L were obtained using a non-linear estimation routine and employing the Marquardt-Levenberg algorithm. Sensitivity analysis revealed k to be more sensitive to model simulations of As (III) oxidation under steady-state conditions than parameter K(s).

Arsenite oxidation by immobilized cells of Alcaligenes faecalis strain O1201 in a fluidized-bed reactor.

Arsenic(III) oxidation was evaluated in a continuous-flow fluidized-bed reactor (FBR) with Alcaligenes faecalis strain 01201 immobilized in gel beads. The FBR was operated under 300 mg/L citrate and a range of influent As(III) concentrations (75 to 3000 mg/L) at short hydraulic retention times (1.06 to 3.17 hours). The pH and temperature in the FBR were maintained at optimal growth conditions for strain O1201 (pH 7 and 30 degrees C) throughout the study. A total of 10 quasi-steady-state operating conditions were obtained after 54 days of operation under an As(III) concentration of 441 mg/L (10 000 mg/L/d loading rate), with As (III) removal efficiency ranging from 76% to near complete. Material balance analysis over the FBR revealed that the difference between the cumulative influent As (III) and the sum of cumulative effluent As(III) and As(V) was insignificant. The major mechanism of As(III) removal from the FBR is biological oxidation to As(V).

Role of acid-sensing ion channel 3 in sub-acute-phase inflammation.

BACKGROUND: Inflammation-mediated hyperalgesia involves tissue acidosis and sensitization of nociceptors. Many studies have reported increased expression of acid-sensing ion channel 3 (ASIC3) in inflammation and enhanced ASIC3 channel activity with pro-inflammatory mediators. However, the role of ASIC3 in inflammation remains inconclusive because of conflicting results generated from studies of ASIC3 knockout (ASIC3-/-) or dominant-negative mutant mice, which have shown normal, decreased or increased hyperalgesia during inflammation. RESULTS: Here, we tested whether ASIC3 plays an important role in inflammation of subcutaneous tissue of paw and muscle in ASIC3-/- mice induced by complete Freund's adjuvant (CFA) or carrageenan by investigating behavioral and pathological responses, as well as the expression profile of ion channels. Compared with the ASIC3+/+ controls, ASIC3-/- mice showed normal thermal and mechanical hyperalgesia with acute (4-h) intraplantar CFA- or carrageenan-induced inflammation, but the hyperalgesic effects in the sub-acute phase (1-2 days) were milder in all paradigms except for thermal hyperalgesia with CFA-induced inflammation. Interestingly, carrageenan-induced primary hyperalgesia was accompanied by an ASIC3-dependent Nav1.9 up-regulation and increase of tetrodotoxin (TTX)-resistant sodium currents. CFA-inflamed muscle did not evoke hyperalgesia in ASIC3-/- or ASIC3+/+ mice, whereas carrageenan-induced inflammation in muscle abolished mechanical hyperalgesia in ASIC3-/- mice, as previously described. However, ASIC3-/- mice showed attenuated pathological features such as less CFA-induced granulomas and milder carrageenan-evoked vasculitis as compared with ASIC3+/+ mice. CONCLUSION: We provide a novel finding that ASIC3 participates in the maintenance of sub-acute-phase primary hyperalgesia in subcutaneous inflammation and mediates the process of granuloma formation and vasculitis in intramuscular inflammation.

Cilostazol attenuates MCP-1 and MMP-9 expression in vivo in LPS-administrated balloon-injured rabbit aorta and in vitro in LPS-treated monocytic THP-1 cells.

Monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) are involved in vascular inflammation. We tested the hypothesis, and explored the underlining mechanisms that cilostazol, a phosphodiesterase 3 inhibitor with antiplatelet and antithrombotic properties, inhibits lipopolysaccharide (LPS)-induced MCP-1 and MMP-9 expression. In a rabbit aorta balloon-injury model, administration of LPS increased macrophage infiltration and MCP-1 and MMP-9 expression; cilostazol supplementation prevented this phenomenon and reduced intimal hyperplasia. In contrast, the reverse zymography showed that cilostazol did not affect TIMP-1 expression in serum. In monocytic THP-1 cells, cilostazol and N6,O2'-dibutyryl-cAMP (dioctanoyl-cAMP, a cAMP analog) dose-dependently inhibited LPS-induced MCP-1 protein expression and MMP-9 activation, but did not affect the tissue inhibitor of metalloproteinase-1. Quantitative real-time polymerase chain reaction (PCR) showed that cilostazol inhibited MCP-1 and MMP-9 mRNA expression. Cilostazol significantly inhibited LPS-induced activation of p38, JNK, and nuclear factor-kappaB, and the respective inhibitors of p38 and JNK greatly reduced the level of LPS-induced MCP-1 and MMP-9, suggesting the involvement of the p38 and JNK pathways. In conclusion, cilostazol administered with LPS in vivo reduced neointimal hyperplasia and macrophage infiltration in the balloon-injured rabbit aorta; in vitro, cilostazol inhibits LPS-induced MCP-1 and MMP-9 expression. These data suggest that cilostazol may play an important role in preventing endotoxin- and injured-mediated vascular inflammation.

Modeling hexavalent chromium removal in a Bacillus sp. fixed-film bioreactor.

A one-dimensional diffusion-reaction model was developed to simulate Cr(VI) reduction in a Bacillus sp. pure culture biofilm reactor with glucose as a sole supplied carbon and energy source. Substrate utilization and Cr(VI) reduction in the biofilm was best represented by a system of (second-order) partial differential equations (PDEs). The PDE system was solved by the (fourth-order) Runge-Kutta method adjusted for mass transport resistance using the (second-order) Crank-Nicholson and Backward Euler finite difference methods. A heuristic procedure (genetic search algorithm) was used to find global optimum values of Cr(VI) reduction and substrate utilization rate kinetic parameters. The fixed-film bioreactor system yielded higher values of the maximum specific Cr(VI) reduction rate coefficient and Cr(VI) reduction capacity (kmc = 0.062 1/h, and Rc = 0.13 mg/mg, respectively) than previously determined in batch reactors (kmc = 0.022 1/h and Rc = 0.012 mg/mg). The model predicted effluent Cr(VI) concentration well with 98.9% confidence (sigmay2 = 2.37 mg2/L2, N = 119) and effluent glucose with 96.4 % confidence (sigmay(w)2 = 5402 mg2/L2, N = 121, w = 100) over a wide range of Cr(VI) loadings (10-498 mg Cr(VI)/L/d).