Renoprotective effect of combining pentoxifylline with angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker in advanced chronic kidney disease.

BACKGROUND/PURPOSE: Several studies have shown the renoprotective effects of pentoxifylline in the treatment of chronic kidney disease (CKD). This study was conducted to examine whether there was an increased benefit of including pentoxifylline with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in the treatment of CKD. METHODS: A single-center retrospective analysis was conducted. A total of 661 Stage 3B-5 CKD patients who received ACEI or ARB treatment were recruited. The patients were divided into the pentoxifylline use group and the no pentoxifylline group. Renal survival analysis of the two groups was compared. Subgroup analysis was performed by dividing the patients into lower [urine protein to creatinine ratio (UPCR)<1 g/g] and higher (UPCR ≥ 1 g/g) proteinuria subgroups. RESULTS: There was no between-groups difference regarding mortality and cardiovascular events. Addition of pentoxifylline showed a better renal outcome (p = 0.03). The protective effect of add-on pentoxifylline was demonstrated in the higher proteinuria subgroup (p = 0.005). In the multivariate Cox regression model, pentoxifylline use also showed a better renal outcome [hazard ratio (HR): 0.705; 95% confidence interval (CI): 0.498-0.997; p = 0.048]. This effect was more prominent in the higher proteinuria subgroup (HR: 0.602; 95% CI: 0.413-0.877; p = 0.008). CONCLUSION: In the advanced stages of CKD, patients treated with a combination of pentoxifylline and ACEI or ARB had a better renal outcome than those treated with ACEI or ARB alone. This effect was more prominent in the higher proteinuria subgroup. More large randomized control trials are needed to provide concrete evidence of the add-on effect of pentoxifylline.

Measuring the environmental efficiency of countries: a directional distance function metafrontier approach.

This paper measures environmental efficiency (EE) in 63 countries over the period 1981-2005 and analyzes whether the adoption of the Kyoto Protocol is accompanied by an increase in environmental efficiency during the same period. Differences in EE across countries under distinct country-specific production frontiers are measured using a directional distance function model, which incorporates a desirable output (GDP) and an undesirable output (CO2 emissions). It is further assumed that a stochastic meta-technology-frontier exists and represents potential outputs available to all countries given inputs. The metafrontier for four country groups, high income countries, upper-middle income countries, low-middle income countries, and low income countries, are estimated using balanced panel data for the sample countries over the study period. The overall results indicate that the four country groups operated under distinct stochastic production frontiers and therefore used different production technologies. It is found that high income countries achieved the highest progress in their average environmental efficiency relative to the metafrontier, while lower-middle income countries and low income countries recorded negative growth in their average EE relative to the metafrontier.

EPR-ENDOR characterization of (17O, 1H, 2H) water in manganese catalase and its relevance to the oxygen-evolving complex of photosystem II.

The synthesis of efficient water-oxidation catalysts demands insight into the only known, naturally occurring water-oxidation catalyst, the oxygen-evolving complex (OEC) of photosystem II (PSII). Understanding the water oxidation mechanism requires knowledge of where and when substrate water binds to the OEC. Mn catalase in its Mn(III)-Mn(IV) state is a protein model of the OEC's S(2) state. From (17)O-labeled water exchanged into the di-µ-oxo di-Mn(III,IV) coordination sphere of Mn catalase, CW Q-band ENDOR spectroscopy revealed two distinctly different (17)O signals incorporated in distinctly different time regimes. First, a signal appearing after 2 h of (17)O exchange was detected with a 13.0 MHz hyperfine coupling. From similarity in the time scale of isotope incorporation and in the (17)O µ-oxo hyperfine coupling of the di-µ-oxo di-Mn(III,IV) bipyridine model (Usov, O. M.; Grigoryants, V. M.; Tagore, R.; Brudvig, G. W.; Scholes, C. P. J. Am. Chem. Soc. 2007, 129, 11886-11887), this signal was assigned to µ-oxo oxygen. EPR line broadening was obvious from this (17)O µ-oxo species. Earlier exchange proceeded on the minute or faster time scale into a non-µ-oxo position, from which (17)O ENDOR showed a smaller 3.8 MHz hyperfine coupling and possible quadrupole splittings, indicating a terminal water of Mn(III). Exchangeable proton/deuteron hyperfine couplings, consistent with terminal water ligation to Mn(III), also appeared. Q-band CW ENDOR from the S(2) state of the OEC was obtained following multihour (17)O exchange, which showed a (17)O hyperfine signal with a 11 MHz hyperfine coupling, tentatively assigned as µ-oxo-(17)O by resemblance to the µ-oxo signals from Mn catalase and the di-µ-oxo di-Mn(III,IV) bipyridine model.

Safety and immunogenicity of 2009 pandemic influenza A H1N1 vaccines in China: a multicentre, double-blind, randomised, placebo-controlled trial.

BACKGROUND: The current influenza pandemic calls for a safe and effective vaccine. We assessed the safety and immunogenicity of eight formulations of 2009 pandemic influenza A H1N1 vaccine produced by ten Chinese manufacturers. METHODS: In this multicentre, double-blind, randomised trial, 12 691 people aged 3 years or older were recruited in ten centres in China. In each centre, participants were stratified by age and randomly assigned by a random number table to receive one of several vaccine formulations or placebo. The study assessed eight formulations: split-virion formulation containing 7.5 microg, 15 microg, or 30 microg haemagglutinin per dose, with or without aluminium hydroxide adjuvant, and whole-virion formulation containing 5 microg or 10 microg haemagglutinin per dose, with adjuvant. All formulations were produced from the reassortant strain X-179A (A/California/07/2009-A/PR/8/34). We analysed the safety (adverse events), immunogenicity (geometric mean titre [GMT] of haemagglutination inhibition antibody), and seroprotection (GMT >or=1:40) of the formulations. Analysis was by per protocol. Two sites registered their trial with ClinicalTrials.gov, numbers NCT00956111 and NCT00975572. The other eight studies were registered with the State Food and Drug Administration of China. FINDINGS: 12 691 participants received the first dose on day 0, and 12 348 participants received the second dose on day 21. The seroprotection rate 21 days after the first dose of vaccine ranged from 69.5% (95% CI 65.9-72.8) for the 7.5 microg adjuvant split-virion formulation to 92.8% (91.9-93.6) for the 30 microg non-adjuvant split-virion formulation. The seroprotection rate was 86.5% (796 of 920; 84.1-88.7) in recipients of one dose of the 7.5 microg non-adjuvant split-virion vaccine compared with 9.8% (140 of 1432; 8.3-11.4) in recipients of placebo (p<0.0001). One dose of the 7.5 microg non-adjuvant split-virion vaccine induced seroprotection in 178 of 232 children (aged 3 years to <12 years; 76.7%, 70.7-82.0), 211 of 218 adolescents (12 years to <18 years; 96.8%, 93.5-98.7), 289 of 323 adults (18-60 years; 89.5%, 85.6-92.6), and 118 of 147 adults older than 60 years (80.3%, 72.9-86.4), meeting the European Union's licensure criteria for seroprotection in all age-groups. In children, a second dose of the 7.5 microg formulation increased the seroprotection rate to 97.7% (215 of 220, 94.8-99.3). Adverse reactions were mostly mild or moderate, and self-limited. Severe adverse effects occurred in 69 (0.6%, 0.5-0.8) recipients of vaccine compared with one recipient (0.1%, 0-0.2) of placebo. The most common severe adverse reaction was fever, which occurred in 25 (0.22%; 0.14-0.33) recipients of vaccine after the first dose and four (0.04%; 0.01-0.09) recipients of vaccine after the second dose compared with no recipients of placebo after either dose. INTERPRETATION: One dose of non-adjuvant split-virion vaccine containing 7.5 microg haemagglutinin could be promoted as the formulation of choice against 2009 pandemic influenza A H1N1 for people aged 12 years or older. In children (aged <12 years), two 7.5 mug doses might be needed. FUNDING: Sinovac Biotech, Hualan Biological Bacterin, China National Biotec Group, Beijing Tiantan Biological Products, Changchun Institute of Biological Products, Changchun Changsheng Life Sciences, Jiangsu Yanshen Biological Technology Stock, Zhejiang Tianyuan Bio-Pharmaceutical, Lanzhou Institute of Biological Products, Shanghai Institute of Biological Products, and Dalian Aleph Biomedical.

Contemporary Policies Regarding Alcohol and Marijuana Use Among Liver Transplant Programs in the United States.

BACKGROUND: Alcoholic liver disease is a common indication for orthotopic liver transplantation (OLT). Although OLT has been shown to confer survival benefit to patients with acute alcoholic hepatitis (AAH), historically most programs require a 6-month abstinence period before OLT which excludes patients with AAH. Marijuana has become legal in more than half the states in the United States. This survey of liver transplant programs was conducted to evaluate current policies regarding alcohol, marijuana and methadone use. METHODS: A questionnaire was distributed to 100 United Network for Organ Sharing-approved liver transplant programs in North America that have performed at least 30 liver transplants/year in the last 5 years. RESULTS: Forty-nine programs responded. Only 43% of the programs required a specific period of abstinence before transplant for alcoholic liver disease and only 26% enforced 6-month abstinence policy. For patients with AAH, 71% programs waived the 6-month abstinence requirement and considered psychosocial factors, such as family support, patient's motivation, or commitment to rehabilitate. Few programs used validated instruments to assess risk of relapse in AAH patients. Fourteen percent of programs transplant patients actively using marijuana and an additional 28% of programs listed patients using marijuana provided they discontinue by the time of OLT. Active methadone users were accepted in 45% of the programs. CONCLUSIONS: Policies regarding alcohol use have become more flexible particularly toward patients with AAH. Marijuana use is also more accepted. Although policies regarding alcohol and marijuana have changed significantly in the last decade, they remain highly variable among programs.

Green synthesis of carbon quantum dots embedded onto titanium dioxide nanowires for enhancing photocurrent.

The green synthesis of nanowired photocatalyst composed of carbon quantum dots-titanium hybrid-semiconductors, CQDs/TiO2, are reported. Where graphite-based CQDs with a size less than 5 nm are directly synthesized in pure water electrolyte by a one-step electrochemistry approach and subsequently electrodeposited onto as-prepared TiO2 nanowires through a voltage-driven reduction process. Electron paramagnetic resonance studies show that the CQDs can generate singlet oxygen and/or oxygen radicals to decompose the kinetic H2O2 intermediate species upon UV light illumination. With the effect of peroxidase-like CQDs, photocurrent density of CQDs/TiO2 is remarkably enhanced by a 6.4 factor when compared with that of as-prepared TiO2.

The Management of Hepatitis B in Liver Transplant Recipients.

Liver transplant (LT) is now an established indication for patients with chronic hepatitis B, mainly because of the development and use of hepatitis B immunoglobulin (HBIG) and oral antivirals for prophylaxis. The combination of low-dose HBIG and antivirals has been considered the standard prophylaxis regimen to prevent post-LT recurrence of hepatitis B. The important remaining issues are related to the long-term cost of HBIG and the risk of escape hepatitis B virus (HBV) mutants. Strategies for prevention of HBV after LT are constantly improving. With the availability of new nucleoside/nucleotide analogues, new post-LT strategies also should emerge.

An unexpected bonding interaction between dxy and a1u orbitals mediated by porphyrin deformation.

Through density functional calculation and NMR spectroscopy, an unusual intermediate-spin electronic structure (d(xz)d(yz))3(d(xy))1(d(z)2)1 has been assigned to the six-coordinate saddled [Fe(OETPP)(THF)2]+ complex instead of the corresponding ruffled [Fe(TiPrP)(THF)2]+ complex.

Multidisciplinary care program for advanced chronic kidney disease: reduces renal replacement and medical costs.

BACKGROUND: Multidisciplinary care is advocated as an effective chronic kidney disease treatment program in a few, but not all, studies. Our study aimed to evaluate the effect of multidisciplinary care on renal outcome and patient survival using a larger cohort. METHOD: A total 1382 chronic kidney disease patients, ages 18-80 years, with chronic kidney disease stage 3B-5, in nephrology outpatient clinics were enrolled. Using age, sex, chronic kidney disease stage, and diabetes mellitus as variables, 592 multidisciplinary care program participants were matched with 614 nonmultidisciplinary care patients. The primary outcomes were long-term renal replacement therapy and mortality. Secondary outcomes included changes of biochemical markers and blood pressure, infection hospitalization, cardiovascular events, and emergent start of long-term dialysis. Annual medical costs were compared. RESULTS: There were no between-group differences regarding mortality. In the multivariate competing-risk regression model, the multidisciplinary care group had a better renal survival (hazard ratio 0.640; 95% confidence interval, 0.484-0.847; P = .002). This effect was most prominent in stage 4 (hazard ratio 0.375; 95% confidence interval, 0.219-0.640; P < .001), but not in stage 3B and 5 patients. The multidisciplinary care group showed a slower estimated glomerular filtration rate decline (-2.57 vs -3.74 mL/min/1.73 m(2), P = .021), and a smaller increase in phosphate (+ 0.03 vs + 0.33 mg/dL, P = .013). Cardiovascular and infection events were both decreased in the multidisciplinary care group (P < .001). There was also less requirement of emergent start dialysis (39.6% vs 54.5%, P = .001). The annual cost for the multidisciplinary care group was lower than the nonmultidisciplinary care group (US $2372 vs $3794, P < .001). In addition, considering the reduction of patients requiring renal replacement therapy, the multidisciplinary care program saved a total US $1931 per patient annually. CONCLUSIONS: Our analysis demonstrated that the multidisciplinary care program provided better health care and reduced renal replacement therapy in patients with advanced chronic kidney disease. By decreasing hospitalizations, emergent start, and the need for renal replacement therapy, the multidisciplinary care program was cost-effective.

Anion reduction dominated cathodic limit of metal-free ionic liquid: experimental and theoretical proofs.

The cathodic limit of the electrochemical window in the second-generation ionic liquids (composed of air- and water-stable metal-free cations and anions) is traditionally believed to be determined by the reduction of the cation. More and more exceptions, however, were found in various ionic liquids. In this study, the cathodic limit of the electrochemical window in 1-butyl-1-methylpyrrolidinium salicylate ionic liquid (BMP-SAL IL) was studied. It has been found that the cathodic limit of BMP-SAL is determined by the reduction of SAL(-) anion rather than the reduction of BMP(+) cation. The cyclic voltammetric behavior, NMR spectra, and MALDI-TOF MS spectra of BMP-SAL recorded before and after the IL was electrolyzed at the cathodic limit provide sufficient evidence that the major reaction at the cathodic limit of BMP-SAL is the reduction of SAL(-) anion. The theoretical calculations support the experimental data, and the results indicate that anion reduction dominated cathodic limit should be a common phenomenon in ionic liquids.

Design Challenges and Guidelines for Persuasive Technologies that Facilitate Healthy Lifestyles.

Many diseases and health risks are the result of unhealthy lifestyles and technology could be used as an intervention. However, designing healthy lifestyle technologies is challenging, as the technology should be able to influence user behavior. In this case study, the design and evaluation process of a persuasive healthy lifestyle assistance technology was investigated. The iterative design and evaluation process included: contextual inquiry, storyboarding, concept generation, paper prototyping, video prototyping, interactive prototyping and user testing. Several design challenges are identified and guidelines are described for designing a technological intervention to encourage healthy lifestyles.

Modeling eye gaze patterns in clinician-patient interaction with lag sequential analysis.

OBJECTIVE: The aim of this study was to examine whether lag sequential analysis could be used to describe eye gaze orientation between clinicians and patients in the medical encounter. This topic is particularly important as new technologies are implemented into multiuser health care settings in which trust is critical and nonverbal cues are integral to achieving trust. This analysis method could lead to design guidelines for technologies and more effective assessments of interventions. BACKGROUND: Nonverbal communication patterns are important aspects of clinician-patient interactions and may affect patient outcomes. METHOD: The eye gaze behaviors of clinicians and patients in 110 videotaped medical encounters were analyzed using the lag sequential method to identify significant behavior sequences. Lag sequential analysis included both event-based lag and time-based lag. RESULTS: Results from event-based lag analysis showed that the patient's gaze followed that of the clinician, whereas the clinician's gaze did not follow the patient's. Time-based sequential analysis showed that responses from the patient usually occurred within 2 s after the initial behavior of the clinician. CONCLUSION: Our data suggest that the clinician's gaze significantly affects the medical encounter but that the converse is not true. APPLICATION: Findings from this research have implications for the design of clinical work systems and modeling interactions. Similar research methods could be used to identify different behavior patterns in clinical settings (physical layout, technology, etc.) to facilitate and evaluate clinical work system designs.

A novel network module for medical devices.

In order to allow medical devices to upload the vital signs to a server on a network without manually configuring for end-users, a new network module is proposed. The proposed network module, called Medical Hub (MH), functions as a bridge to fetch the data from all connecting medical devices, and then upload these data to the server. When powering on, the MH can immediately establish network configuration automatically. Network Address Translation (NAT) traversal is also supported by the MH with the UPnP Internet Gateway Device (IGD) methodology. Besides the network configuration, other configuration in the MH is automatically established by using the remote management protocol TR-069. On the other hand, a mechanism for updating software automatically according to the variant connected medical device is proposed. With this mechanism, newcome medical devices can be detected and supported by the MH without manual operation.

Symmetry and bonding in metalloporphyrins. A modern implementation for the bonding analyses of five- and six-coordinate high-spin iron(III)-porphyrin complexes through density functional calculation and NMR spectroscopy.

Bonding interactions between the iron and the porphyrin macrocycle of five- and six-coordinate high-spin iron(III)-porphyrin complexes are analyzed within the framework of approximate density functional theory with the use of the quantitative energy decomposition scheme in combination with removal of the vacant pi orbitals of the porphyrin from the valence space. Although the relative extent of the iron-porphyrin interactions can be evaluated qualitatively through the spin population and orbital contribution analyses, the bond strengths corresponding to different symmetry representations can be only approximated quantitatively by the orbital interaction energies. In contrast to previous suggestions, there are only limited Fe --> P pi back-bonding interactions in high-spin iron(III)-porphyrin complexes. It is the symmetry-allowed bonding interaction between d(z)2 and a(2u) orbitals that is responsible for the positive pi spin densities at the meso-carbons of five-coordinate iron(III)-porphyrin complexes. Both five- and six-coordinate complexes show significant P --> Fe pi donation, which is further enhanced by the movement of the metal toward the in-plane position for six-coordinate complexes. These bonding characteristics correlate very well with the NMR data reported experimentally. The extraordinary bonding interaction between d(z)2 and a(2u) orbitals in five-coordinate iron(III)-porphyrin complexes offers a novel symmetry-controlled mechanism for spin transfer between the axial ligand sigma system and the porphyrin pi system and may be critical to the electron transfer pathways mediated by hemoproteins.