bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the Combined Left Ventricular Systolic and Renal Dysfunction on One‐Year Outcomes after Primary Percutaneous Coronary Intervention
Authors: SAVIC LIDIJA , MRDOVIC IGOR , PERUNICIC JOVAN , ASANIN MILIKA , LASICA RATKO , MARINKOVIC JELENA , VASILJEVIC ZORANA , OSTOJIC MIODRAG
Published: November 2011

Background:

The aim of this study was to assess the impact of combined left ventricular systolic dysfunction (LVSD) and renal dysfunction (RD) on 1‐year overall mortality and major adverse cardiovascular events (MACEs) (comprising cardiovascular death, nonfatal renfarction, target vessel revascularization, and nonfatal stroke) in patients with ST‐elevation myocardial infarction undergoing primary percutaneous coronary intervention (pPCI).

Methods:

One thousand three hundred ninety eight patients with first myocardial infarction, undergoing pPCI were divided into four groups according to the presence of LVSD (ejection fraction [EF] <40%) and/or baseline RD (estimated glomerular filtration rate <60 mL/min per m2): Group I (no LVSD and no RD); Group II (LVSD, no RD); Group III (RD, no LVSD); Group IV (LVSD + RD).

Results:

One‐year mortality rates in Groups I, II, III, and IV were 2.6%, 15.2%, 10.6%, and 34.2% and 1‐year MACE rates were 5.7%, 19.5%, 17.1% and 35.7%, respectively. Patients in Groups II, III, and IV had an increased probability of 1‐year overall mortality and MACE as compared to Group I. Overall mortality: Group II HR 2.1 (95% CI 1.1–4.2); Group III HR 2.1 (95% CI 1.1–4.1); Group IV HR 4.8 (95% CI 2.4–9.4); MACE: Group II HR 2.2 (95% CI 1.1–4.2); Group III HR 2.2 (95% CI 1.1–4.3); Group IV HR 5.1 (95% CI 2.6–10.1). The LVSD‐RD combination was the strongest independent predictor for 1‐year outcomes.

Conclusions:

The LVSD‐RD combination is associated with an approximately five‐fold increase in 1‐year overall mortality and MACE after pPCI. The evaluation of the renal function in patients with LVSD represents a simple method which enables a more precise stratification of the risks related to the occurrence of adverse events in long‐term patient follow‐up. (J Interven Cardiol 2012;25:132–139)
Optical and Wetting Properties of CuAlO2 Films Prepared by Radio Frequency Magnetron Sputtering
Authors: Li Junlei , Wang Xian , Shi Shiwei , Song Xueping , Lv Jianguo , Cui Jingbiao , Sun Zhaoqi
Published: November 2011

The CuAlO2 films were prepared on glass and quartz substrates by radio frequency magnetron sputtering with a sintered target composed of Al(OH)3 and Cu2O powders. X‐ray diffraction analyses reveal that the as‐deposited films are amorphous structure and the as‐annealed films are predominated by the CuAlO2 phase along with the Al2O3 phase. Scanning electron microscope (SEM) measurements indicate that grains grow up and surface becomes rougher as a result of increasing temperature. The optical studies show that annealing leads to the reduction of the average transmittance of the films from 60% to 40% for the visible range and the decrease of the fitted refractive index from 2.0 to 1.5. Direct band gaps confirmed by the transmittance and reflectance measurements are estimated to be 3.86 and 3.50 eV for as‐deposited and as‐annealed films, respectively. As increasing exposure time, water contact angles of the as‐deposited films exposed under ultraviolet light source 365 nm or 254 nm decrease from 96.3° and 96.4° to 87.5° and 87.2°, respectively. The variation of contact angle can be attributed to the hydrophobic organic stains on the surface, surface roughness, the formation of Cu2+, and band gap variation of CuAlO2 film. The as‐annealed film becomes hydrophilic and its water contact angle is 31.1°. The wetting property of CuAlO2 films is very important for the wide spread application of this material.
Students’ perception of the prognosis for a single‐surface amalgam restoration
Authors: Devlin H.
Published: November 2011

The aim of the study was to assess the self‐rated skill, clinical judgement and competency of final‐year pre‐doctoral dental students. The study was also designed to determine whether the students’ estimated durability of their single‐surface restorations was determined by their confidence. Students were given a questionnaire and completed it anonymously. One hundred and ninety‐six forms were returned from the 238 students (82% return rate). Complete analysis was possible on 169 questionnaires. The students’ self‐assessed skill and judgement were a significant factor in predicting how long they would tell a patient that their restoration would last. Those ranking themselves below average were more likely to state that their amalgam restorations would have a shorter life (odds increased by 2.82 for those ranking themselves lower than most others). There was a significant association between the students’ self‐assessed skill and judgement and their confidence in dealing with both the initial management of patients’ medical emergencies (ρ = 0.244, P = 0.001, n = 191) and their general confidence in dealing with medical emergencies (ρ = 0.187, P = 0.01, n = 188). Given a conversational scenario with a patient, the treatment prognosis given by final‐year pre‐doctoral students for a single‐surface amalgam restoration was dependent on their self‐assessed competence, skill and judgement.
Memory Constructions and Their Limits
Authors: Larsen Svend Erik
Published: November 2011

In ‘Karl Jaspers: A citizen of the world’ (1957) Hannah Arendt points to the troubled role of memory in a globalized culture. She claims that world citizenship can harbour no reference to a shared local past or a collective vision of a shared future. In contrast, Caribbean authors like Derek Walcott or Édouard Glissant hold that on such conditions memory is of another kind: local experience is always a blend of various transcultural cultures and histories. At the same time, they are always constructed in a process of the present, and this presence reveals the composite and translocal nature of our experiences. Memories are therefore cultural sites for negotiations of cultural values and identities. The paper locates two processes in which literature plays an active role: travel across cultural boundaries of the images that mould our memories, and negotiations we carry out through the media of expression contrasting various possibilities for memory constructions. Core texts are Derek Walcott’s epic poem Omeros (1990), Imre Kertész’s essay ‘Who owns Auschwitz?’ (2001), Hans Staden’s travel account Warhaftig’ Historia (1557) and poems by Paul Celan (1952, 1967).
Noninvasive estimation of chronological and photoinduced skin damage using Raman spectroscopy and principal component analysis
Authors: González Francisco J. , Castillo‐Martínez Claudio , Martínez‐Escanamé Marcela , Ramírez‐Elías Miguel G. , Gaitan‐Gaona Francisco I. , Oros‐Ovalle Cuauhtémoc , Moncada Benjamín
Published: November 2011

Background

Skin aging can be attributed to endogenous and exogenous factors which modify the hydration and protein structure of the skin which can be measured using Raman spectroscopy.

Method

This study included 21 healthy adult volunteers, aged 32–81 years, Raman spectra were obtained from sun‐protected and sun‐exposed skin, also three millimeter punch biopsies of sun‐exposed skin were collected and analyzed. The Raman spectra were analyzed using principal component analysis and the results were correlated with clinical and histological findings.

Results

The principal component analysis of the Raman spectra shows that the first principal component (PC1) obtained from the sun‐protected skin is related to the age of the subject, which can be taken as a measure of chronological aging, the second (PC2) and fourth (PC4) principal components obtained from Raman spectra of sun‐exposed skin are related to the amount of solar elastosis and collagen, respectively.

Conclusion

In this work a relationship was found between histological properties of photoaged skin and noninvasive measurements based on Raman and principal components analysis (PCA). These relationships can be used to assess noninvasively the photoinduced damage and chronological characteristics of skin.
In Vivo Roles of the Basic Domain of Dynactin p150 in Microtubule Plus‐End Tracking and Dynein Function
Authors: Yao Xuanli , Zhang Jun , Zhou Henry , Wang Eric  , Xiang Xin
Published: November 2011

Microtubule (MT) plus‐end‐tracking proteins accumulate at MT plus ends for various cellular functions, but their targeting mechanisms are not fully understood (Akhmanova A and Steinmetz MO. Tracking the ends: a dynamic protein network controls the fate of microtubule tips. Nat Rev Mol Cell Biol 2008;9:309–322.). Here, we tested in the filamentous fungus Aspergillus nidulans the requirement for plus‐end localization of dynactin p150, a protein essential for dynein function. Deletion of the N‐terminal MT‐binding region of p150 significantly diminishes the MT plus‐end accumulation of both dynein heavy chain and p150, and causes a partial defect in nuclear distribution. Surprisingly, within the MT‐binding region, the basic domain is more critical than the CAP‐Gly (cytoskeleton‐associated protein glycine‐rich) domain for maintaining plus‐end tracking of p150, as well as for the functions of dynein in nuclear distribution and early endosome movement. Our results show that the basic domain of A. nidulans p150 is important for p150–MT interaction both in vivo and in vitro, and the basic amino acids within this domain are crucial for the plus‐end accumulation of p150 in the wild‐type background and for the p150–MT interaction in the ΔkinA (kinesin‐1) background. We suggest that the basic amino acids are required for the electrostatic interaction between p150 and MTs, which is important for kinesin‐1‐mediated plus‐end targeting of dynactin and dynein in A. nidulans.
Hereditary Thrombophilia, Anti‐Beta2 Glycoprotein 1 IgM, and Anti‐Annexin V Antibodies in Recurrent Pregnancy Loss
Authors: Karata Suat , Aydin Yavuz , Ocer Fahri , Buyru Aysenur , Balci Huriye
Published: November 2011

Citation Karata S, Aydin Y, Ocer F, Buyru A, Balci H. Hereditary Thrombophilia, anti‐beta2 glycoprotein 1 IgM, and anti‐annexin V antibodies in recurrent pregnancy loss. Am J Reprod Immunol 2012; 67: 251–255

Problem We investigated the beta2‐glycoprotein I and anti‐annexin V antibodies as anti‐phospholipid–cofactor antibodies; and factor V G1691A Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T mutations as hereditary thrombophilia in recurrent pregnancy losses (RPL).

Method of study Study group consisted of 84 women with recurrent pregnancy loss and control group consisted of 84 women having at least one live birth.

Results Methylenetetrahydrofolate reductase C677T homozygous mutation was detected in 28.5% of the study group and in 14.2% of the controls, and the difference was highly significant (P < 0.001). Heterozygous mutation of this gene was found in 64.3% of the study population and in 38.1% of the controls, and difference in heterozygous mutation frequency was also significant (P < 0.001). Both homozygous and heterozygous mutations of PT G20210A and factor V G1691A were not different between the groups. There was no significant difference in anti‐annexin V levels and anti‐beta2‐gp 1 levels of the groups.

Conclusion We concluded that both homozygous and heterozygous mutations of MTHFR C677T were related with RPL in Caucasian women.
Effects of fire, grazing and topographic variation on vegetation structure in tallgrass prairie
Authors: Collins Scott L. , Calabrese Laura B.
Published: November 2011

Questions

How do fire and grazing by bison affect the composition and structure of tallgrass prairie plant communities and their temporal stability? Are these responses modulated by topographic location?

Location

KonzaPrairie Biological Station,Kansas,USA.

Methods

Plant community composition was monitored in permanent plots in native grassland sites receiving different long‐term prescribed burning and bison grazing regimes across a topographic gradient (lowlands, slopes, uplands) following 20 yr of variable burning treatments and 13 yr of grazing by bison. A combination of multivariate analyses was used to determine how community structure, life forms and individual species responded to the accumulated effects of long‐term fire and grazing by native bison in upland, slope and lowland soils.

Results

Species diversity was maximized in sites that were infrequently burned and grazed by bison with the strongest response on infrequently burned slope sites, while diversity was lowest on frequently burned ungrazed sites and on frequently burned slope sites. In general, grass cover was highest in infrequently burned ungrazed sites and lowest on frequently burned grazed sites, while forb richness was highest in infrequently burned and grazed sites. Community response to fire and grazing differed across the topographic gradient. In general, frequent burning favouredC4grasses, which reduced the abundance ofC3forbs, especially in lowland sites. Responses of dominant grasses and forbs to fire and grazing varied depending on topographic position. Community stability was positively correlated with species richness.

Conclusions

Overall, we found that fire and grazing are the main determinants of plant community composition and structure in this grassland system, but that topography mediates these effects. A combination of bison grazing and periodic fire is necessary to maximize diversity and community stability across this native grassland landscape.
Damage Anchors on Real Juries
Authors: Diamond Shari Seidman , Rose Mary R. , Murphy Beth , Meixner John
Published: November 2011

Experiments reveal anchoring as a powerful force, even when participants see the anchor as irrelevant. Here, we examine the reactions of real deliberating jurors to attorney damage requests and concessions in 31 cases involving 33 plaintiffs in which the jury awarded damages. Jurors were critical consumers of attorney suggestions. They reacted more negatively to, and were less influenced by, plaintiff ad damnums for pain and suffering than to damage requests in categories grounded in more objective evidence. Deliberations revealed that jurors often perceive plaintiff ad damnums not only as irrelevant, but also as outrageous, impressions reflected in their verdicts. These findings suggest that extreme plaintiff ad damnums, including those without grounding in quantitative evidence from trial, may not exert substantial undue influence.
Anticancer Activity of an Imageable Curcuminoid 1‐[2‐Aminoethyl‐(6‐hydrazinopyridine‐3‐carbamidyl)‐3,5‐bis‐(2‐fluorobenzylidene)‐4‐piperidone (EFAH)
Authors: Lagisetty Pallavi , Subramaniam Dharmalingam , Sahoo Kaustuv , Anant Shrikant , Awasthi Vibhudutta
Published: November 2011

3,5‐Bis(2‐fluorobenzylidine)‐4‐piperidone or EF24 is a potent anticancer derivative of curcumin. Using an amine derivative of EF24, we synthesized a hydrazinonicotinic acid conjugate, EFAH, for Tc‐99m radiolabelling and single photon emission tomography imaging. The aqueous solubility of EFAH (3.5 mg/mL) was significantly more than that of EF24 (1.2 mg/mL); the octanol/water partition coefficient of EFAH was estimated at log P = 0.33. As an antiproliferative agent, EFAH was as effective as EF24 in suppressing the proliferation of H441, MiaPaCa‐2 and Panc‐1 cells. Daily intraperitoneal injection of EFAH (5 μg) for 3 weeks in mice carrying xenografts of Panc‐1 pancreatic cancer showed a mean tumour volume reduction of 79%; the tumour weight decreased by 82% in the treated group. For imaging and biodistribution, EFAH was labelled with Tc‐99m (98% RCY) and intravenously administered in rats. Approximately 23.7% and 14.3% of injected dose accumulated in liver and intestine, respectively, suggesting that EFAH is mostly eliminated by hepatobiliary route. The results indicate that HYNIC modification of EF24 for Tc‐99m radiolabelling does not affect its antiproliferative efficacy. For the first time, a visual biodisposition of EF24 in a live animal model has been demonstrated. Such knowledge could be of benefit in developing therapeutic curcuminoids, such as EF24.
Transnational Legal Process and State Change
Authors: Shaffer Gregory
Published: November 2011

This article applies a sociolegal approach to the study of transnational legal processes and their effects within countries. First, we clarify the concepts of transnational law, transnational legal process, and transnational legal order. Second, we provide a typology of five dimensions of state change that we can assess empirically. Third, we explain the factors that determine the variable effects of transnational legal processes and organize these factors into three clusters. Fourth, we introduce four empirical studies of transnational legal processes' differential effects in five regulatory areas in Asia, Africa, and South America that illustrate these points. Together, they provide a guide of how to study the interaction of transnational and national legal processes, and the extent and limits of transnational legal processes' effects.
Symptomatic treatment of ascites with a peritoneo‐vesical automated fluid shunt system in a dog
Authors: Venzin C. , Kook P. , Jenni S. , Wilhelm S. , Degen T. , Braun A. , Rütten M. , Glaus T. M.
Published: November 2011

A six‐year‐old Rottweiler with chronic ascites and moderate panhypoproteinaemia that had been treated with large volume paracentesis over several months duration was diagnosed with a large bi‐atrial mass and hepatic fibrosis. For palliative treatment, a peritoneo‐vesical automated fluid shunt system with an integrated chargeable battery and an integrated computer to control pump function and to transmit data transcutaneously was implanted by coeliotomy. The pump was left in place for 10 weeks, eliminating the need for further paracentesis during this time. At the end of this period, no ascites was discernible and serum protein concentrations had returned to their respective reference intervals. As a complication, decubitus with skin perforation had developed above the pump. Besides palliative treatment of chronic refractory ascites, this pump may have application in other conditions characterised by chronic cavity effusion or in peritoneal dialysis.
Localised Mycobacterium ulcerans infection in four dogs
Authors: O'Brien CR , McMillan E , Harris O , O'Brien DP , Lavender CJ , Globan M , Legione AR , Fyfe JA
Published: November 2011

Localised infection caused by Mycobacterium ulcerans is described in two Kelpies, a Whippet and a Koolie domiciled on the Bellarine Peninsula, Victoria, Australia. The diagnosis was confirmed using real‐time polymerase chain reaction (PCR) targeting the M. ulcerans‐specific insertion sequence (IS2404) in DNA extracted from swabs of ulcerated lesions in all cases. Where available, molecular typing confirmed that three of the dogs were infected with a strain of M. ulcerans that was indistinguishable from a disease‐causing strain in people and other animals in Victoria. One dog was still undergoing treatment at the time of writing, but the remaining three dogs were successfully treated with a combination of surgical debridement and medical therapy in one case, and medical therapy alone in the other two. Investigation of the home environs of three of the dogs using real‐time PCR revealed low amounts of M. ulcerans DNA in various environmental samples. Mycobacterium ulcerans infection should be included in the differential diagnoses of any ulcerated skin lesions in dogs that live in or visit endemic areas of Victoria and Queensland.
In this issue – December 2011
Authors: Jackson AE
Published: November 2011

Overview of the Australian sheep industry · The first incisor eruption in Angora goats · Hepatitis E in pigs in New Caledonia · Thromboelastography in neonatal foals · Mycobacterium ulcerans infection in dogs · Harmonic scalpel for soft palate surgery in dogs · Fungal dermatitis in coastal bearded dragons · Osteosarcoma in a python
Rectal single dose immunization of mice with Escherichia coli O157:H7 bacterial ghosts induces efficient humoral and cellular immune responses and protects against the lethal heterologous challenge
Authors: Mayr Ulrike Beate , Kudela Pavol , Atrasheuskaya Alena , Bukin Eugenij , Ignatyev Georgy , Lubitz Werner
Published: November 2011

Bacterial ghosts (BGs) have been applied through oral, aerogenic, intraocular or intranasal routes for mucosal immunization using a wide range of experimental animals. All these applications required a booster after primary immunization to achieve protective immunity against the lethal challenge. Here we report for the first time that a single rectal dose of BGs produced from enterohaemorrhagic Escherichia coli (EHEC) O157:H7 fully protects mice against a 50% lethal challenge with a heterologous EHEC strain given at day 55. BGs from EHEC O157:H7 were prepared by a combination of protein E‐mediated cell lysis and expression of staphylococcal nuclease A guaranteeing the complete degradation of pathogen residual DNA. The lack of genetic material in the EHEC BGs vaccine abolished any potential hazard for horizontal gene transfer of plasmid encoded antibiotic resistance genes or pathogenic islands to the recipient's gut flora. Single rectal immunization using EHEC O157:H7 BGs without any addition of adjuvant significantly stimulated efficient humoral and cellular immune responses, and was equally protective as two immunizations, which indicates the possibility to develop a novel efficacious single dose mucosal EHEC O157:H7 BGs vaccine using a simplified immunization regimen.
Transcriptional profiling of vaccine‐induced immune responses in humans and non‐human primates
Authors: Wang I‐Ming , Bett Andrew J. , Cristescu Razvan , Loboda Andrey , ter Meulen Jan
Published: November 2011

There is an urgent need for pre‐clinical and clinical biomarkers predictive of vaccine immunogenicity, efficacy and safety to reduce the risks and costs associated with vaccine development. Results emerging from immunoprofiling studies in non‐human primates and humans demonstrate clearly that (i) type and duration of immune memory are largely determined by the magnitude and complexity of the innate immune signals and (ii) genetic signatures highly predictive of B‐cell and T‐cell responses can be identified for specific vaccines. For vaccines with similar composition, e.g. live attenuated viral vaccines, these signatures share common patterns. Signatures predictive of vaccine efficacy have been identified in a few experimental challenge studies. This review aims to give an overview of the current literature on immunoprofiling studies in humans and also presents some of our own data on profiling of licensed and experimental vaccines in non‐human primates.
A Capacity Building Program to Promote CBPR Partnerships between Academic Researchers and Community Members
Authors: Allen Michele L. , Culhane‐Pera Kathleen A. , Pergament Shannon , Call Kathleen Thiede
Published: November 2011

Introduction: Community‐based participatory research (CBPR) adds community perspectives to research and aids translational research aims. There is a need for increased capacity in CBPR but few models exist for how to support the development of community/university partnerships.

Objective: Evaluate an approach to promote nascent CBPR partnerships.

Methods: Design was a mixed–methods evaluation using interviews, process notes, and open‐ and close‐ended survey questions. We trained 10 community scholars, matched them with prepared researchers to form seven partnerships, and supported their developing partnerships. Sequential mixed–methods analysis assessed research and partnership processes and identified integrated themes.

Results: Four of seven partnerships were funded within 15 months; all self‐reported their partnerships as successful. Themes were: (1) motivators contributed to partnership development and resiliency; (2) partners took on responsibilities that used individuals’ strengths; (3) partners grappled with communication, decision making, and power dynamics; and (4) community–university infrastructure was essential to partnership development.

Conclusions: This program for developing nascent partnerships between academicians and community members may guide others in increasing capacity for CBPR. Clin Trans Sci 2011; Volume 4: 428–433
Topographic relationship between frequency‐doubling technology threshold values
Authors: Fuertes‐Lazaro Isabel , Sanchez‐Cano Ana , Ferreras Antonio , Larrosa Jose M. , Garcia‐Martin Elena , Pablo Luis E.
Published: November 2011

Purpose:  To study the topographic relationship of retinal sensitivity evaluated by frequency‐doubling perimetry (FDT) in healthy subjects and patients with glaucoma.

Methods:  Hundred and thirty‐four eyes from 134 subjects (72 patients with glaucoma and 62 healthy controls) were prospectively and consecutively selected. Only one eye of each subject was randomly selected for evaluation. All subjects underwent a full ophthalmic examination and a reliable FDT (full‐threshold C‐20‐5 algorithm). Pearson correlation coefficients between threshold values within the same hemifield were calculated. Maps of related points were plotted according to these correlation coefficients.

Results:  In the control group, each FDT location strongly to moderately correlated with the other FDT locations in the same hemifield. In glaucoma subjects, only a few locations significantly correlated with other threshold values in the same hemifield. The strongest correlations were observed between neighbouring locations. The pairs of points with the strongest correlation corresponded to the inferior retinal regions. In general, perimetric maps showed the retinotopic distribution of ganglion cell axons in the retinal nerve fibre layer.

Conclusions:  The statistical correlations between the FDT threshold values in the same visual hemifield objectively highlight the structure–function relationship determined by the anatomic distribution of retinal nervous tissue. This structure is altered in patients with glaucoma.
Monitoring oxidative stress in acute‐on‐chronic liver failure by advanced oxidation protein products
Authors: Liu Hua , Han Tao , Tian Jie , Zhu Zheng‐Yan , Liu Ying , Li Yan , Xiao Shi‐Xiang , Li Ying , Feng Yu‐Ying
Published: November 2011

Aim:  Increased oxidative stress is important in the pathogenesis of acute‐on‐chronic liver failure (ACLF). This study aimed to investigate whether advanced oxidation protein products (AOPP) levels can monitor oxidative stress of ACLF patients. Furthermore, we aimed to study plasma exchange (PE) treatment and determine whether it can eliminate AOPP.

Methods:  We measured AOPP levels in 50 ACLF patients, 30 patients with compensated liver cirrhosis (CR), 30 patients with chronic hepatitis B (CHB) and 50 healthy controls by spectrophotometric assay. AOPP concentrations were also measured before and after PE treatment in ACLF patients. As an apoptosis marker, serum cytokeratin 18 (CK18 M 30) levels were detected to investigate the relationship between AOPP and apoptosis in ACLF patients.

Results:  Significantly higher AOPP levels at admission were found in patients with ACLF compared with CR, CHB and healthy controls (69.45 ± 29.04 µmol/L vs. 19.67 ± 7.02 µmol/L, 26.75 ± 5.21 µmol/L and 21.35 ± 6.15 µmol/L, respectively; P < 0.001). There was a positive relationship with total bilirubin, Child–Pugh, model for end‐stage liver disease scores and CK18 M 30. In ACLF patients, AOPP levels were higher in non‐survivors than survivors. An AOPP cut‐off of 74.21 µmol/L was used for predicting poor prognosis. Multivariate Cox regression analysis demonstrated that AOPP were independent risk factors for prognosis. Dynamic change of AOPP levels associated with prognosis appeared earlier than total bilirubin. Following PE treatment, AOPP levels reduced to 34.65 ± 18.14 µmol/L (P < 0.001).

Conclusions:  Advanced oxidation protein products were suitable for monitoring the levels of oxidative stress in ACLF patients. Increased AOPP may serve as an important biological marker of worse outcome. In addition, PE therapy was effective in reducing AOPP.
Protein‐energy malnutrition during early gestation in sheep blunts fetal renal vascular and nephron development and compromises adult renal function
Authors: Lloyd Louise J. , Foster Thomas , Rhodes Phillip , Rhind Stewart M. , Gardner David S.
Published: November 2011

Non‐technical summary  A poor diet during pregnancy has been linked to long‐term health outcomes for the baby, such as an increased risk of diseases of the heart and kidney. We show in an experimental model that recreates a poor diet during pregnancy, i.e. a diet low in protein with adequate energy, that kidney development in the baby is affected in such a way as to reduce the potential for new blood vessels to form. This results in a greater number of important, functional kidney cells spontaneously dying. Later in life, these effects in the kidney manifest as permanently reduced kidney function, especially if the baby subsequently becomes overweight as an adult. The research reinforces advice to pregnant mothers about the importance of eating a nutritionally balanced diet during pregnancy.
Sound‐evoked network calcium transients in mouse auditory cortex in vivo
Authors: Grienberger Christine , Adelsberger Helmuth , Stroh Albrecht , Milos Ruxandra‐Iulia , Garaschuk Olga , Schierloh Anja , Nelken Israel , Konnerth Arthur
Published: November 2011

Non‐technical summary  The coherent activity of a large number of neurons forming functional cell assemblies crucially contributes to neuronal information processing in the brain. It is believed that activity of such populations constitutes a key mechanism linking awareness, stimuli from the external world, memory and behaviour. In this study, we recorded population calcium signals in the auditory cortex of mice using an optical fibre. We found that the population activity was dominated by transients lasting ∼1 s. These calcium transients directly reflected the action potential firing of local clusters of neurons and occurred spontaneously as well as in response to sound stimulation. We characterized in detail the spontaneous and sound‐evoked calcium signals and the relation between the two. Thus, we were able to identify population calcium transients as an important element of sensory signalling.
Dose and dose averaged LET comparison of 1H, 4He, 6Li, 8Be, 10B, 12C, 14N, and 16O ion beams forming a spread‐out Bragg peak
Authors: Kantemiris I. , Karaiskos P. , Papagiannis P. , Angelopoulos A.
Published: November 2011

Purpose:

Modern clinical accelerators are capable of producing ion beams from protons up to neon. This work compares the depth dose distribution and corresponding dose averaged linear energy transfer (LET) distribution, which is related to the biological effectiveness, for different ion beams (1H, 4He, 6Li, 8Be, 10B, 12C, 14N, and 16O) using multi‐energetic spectra in order to configure spread‐out Bragg peaks (SOBP).

Methods:

Monte Carlo simulations were performed in order to configure a 5 cm SOBP at 8 cm depth in water for all the different ion beams. Physical dose and dose averaged LET distributions as a function of depth were then calculated and compared. The superposition of dose distribution of all ions is also presented for a two opposing fields configuration. Additional simulations were performed for12C beams to investigate the dependence of dose and dose averaged LET distributions on target depth and size, as well as beam configuration. These included simulations for a 3 cm SOBP at 7, 10, and 13 cm depth in water, a 6 cm SOBP at 7 depth in water, and two opposing fields of 6 cm SOBP.

Results:

Alpha particles and protons present superior physical depth dose distributions relative to the rest of the beams studied. Dose averaged LET distributions results suggest higher biological effectiveness in the target volume for carbon, nitrogen and oxygen ions. This is coupled, however, with relatively high LET values—especially for the last two ion species—outside the SOBP where healthy tissue would be located. Dose averaged LET distributions for8Be and 10B beams show that they could be attractive alternatives to 12C for the treatment of small, not deeply seated lesions. The potential therapeutic effect of different ion beams studied in this work depends on target volume and position, as well as the number of beams used.

Conclusions:

The optimization of beam modality for specific tumor cites remains an open question that warrants further investigation and clinically relevant results.
Jogging on a Carousel
Authors: Wilson Alpha E.
Published: November 2011

To jog around the periphery of a carousel at rest requires that the jogger experience a constant state of acceleration perpendicular to the direction of motion and directed toward the axis of rotation (centripetal). The jogger could achieve this centripetal acceleration by leaning inward, thereby using a horizontal weight component to provide the necessary centripetal force. There are two ordinary cases of circular motion involving the carousel that can be handled by the simple centripetal acceleration formula, where the joggers speed v is squared and then divided by the radius r of the path being followed (a = v2/r). One case would be as above, with the carousel at rest and the jogger moving on a circular path around it. The other case would be the jogger at rest on the carousel at a radial point r while it is moving with linear speed v. The situation can be made significantly more interesting and informative by letting the jogger be in motion while the carousel is in motion.
Pregnancy-Related Effects on Lamivudine Pharmacokinetics in a Population Study with 228 Women
Authors: Benaboud Sihem , Tréluyer Jean Marc , Urien Saik , Blanche Stéphane , Bouazza Naim , Chappuy Hélène , Rey Elisabeth , Pannier Emmanuelle , Firtion Ghislaine , Launay Odile , Hirt Déborah
Published: November 2011

The aim of this study was to describe lamivudine (3TC) pharmacokinetics (PK) in HIV-infected nonpregnant and pregnant women and their fetuses. Samples were collected according to therapeutic drug monitoring from 228 women treated with lamivudine and retrospectively analyzed by a population approach. The samples were also collected from cord blood and amniotic fluid at birth. Lamivudine pharmacokinetics were ascribed to an open two-compartment model with linear absorption and elimination. Mean population parameter estimates (intersubject variability) for women were an absorption rate constant of 1.04 h
−1
, an elimination clearance rate of 23.6 (0.266) liters · h
−1
, a central volume of distribution of 109 (0.897) liters, an intercompartmental clearance rate of 6.7 liters/h, and a peripheral volume of distribution of 129 liters. A fetal compartment was linked to maternal circulation by mother-to-cord (or fetus) and cord-to-mother rate constants of 0.463 h
−1
and 0.538 h
−1
, respectively. The amniotic fluid compartment was connected to the fetal compartment with an elimination rate constant of 0.163 h
−1
and a fixed-constant swallowing flow. The placental transfer expressed as fetal-to-maternal area under the concentration-time curve (AUC) ratio was 0.86, and the lamivudine amniotic fluid accumulation, expressed as the amniotic fluid-to-fetal AUC ratio, was 2.9. Pregnant women had a 22% higher apparent clearance than nonpregnant and parturient women; however, this increase did not lead to subexposure and should not require a dosage adjustment.
Overton's Rule Helps To Estimate the Penetration of Anti-Infectives into Patients' Cerebrospinal Fluid
Authors: Djukic Marija , Munz Martin , Sörgel Fritz , Holzgrabe Ulrike , Eiffert Helmut , Nau Roland
Published: November 2011

In 1900, Ernst Overton found that the entry of anilin dyes through the cell membranes of living cells depended on the lipophilicity of the dyes. The brain is surrounded by barriers consisting of lipid layers that possess several inward and outward active transport systems. In the absence of meningeal inflammation, the cerebrospinal fluid (CSF) penetration of anti-infectives in humans estimated by the ratio of the area under the concentration-time curve (AUC) in CSF (AUC
CSF
) to that in serum (AUC
CSF
/AUC
S
) correlated positively with the lipid-water partition coefficient at pH 7.0 (log
D
) (Spearman's rank correlation coefficient

r
S

= 0.40;
P
= 0.01) and negatively with the molecular mass (MM) (

r
S

= −0.33;
P
= 0.04). The ratio of AUC
CSF
to the AUC of the fraction in serum that was not bound (AUC
CSF
/AUC
S,free
) strongly correlated with log
D
(

r
S

= 0.67;
P
< 0.0001). In the presence of meningeal inflammation, AUC
CSF
/AUC
S
also correlated positively with log
D
(

r
S

= 0.46;
P
= 0.002) and negatively with the MM (

r
S

= −0.37;
P
= 0.01). The correlation of AUC
CSF
/AUC
S,free
with log
D
(

r
S

= 0.66;
P
< 0.0001) was as strong as in the absence of meningeal inflammation. Despite these clear correlations, Overton's rule was able to explain only part of the differences in CSF penetration of the individual compounds. The site of CSF withdrawal (lumbar versus ventricular CSF), age of the patients, underlying diseases, active transport, and alterations in the pharmacokinetics by comedications also appeared to strongly influence the CSF penetration of the drugs studied.
Influence of
NAT2
Polymorphisms on Sulfamethoxazole Pharmacokinetics in Renal Transplant Recipients
Authors: Kagaya Hideaki , Miura Masatomo , Niioka Takenori , Saito Mitsuru , Numakura Kazuyuki , Habuchi Tomonori , Satoh Shigeru
Published: November 2011

The sulfamethoxazole (SMX)-trimethoprim drug combination is routinely used as prophylaxis against
Pneumocystis
pneumonia during the first 3 to 6 months after renal transplantation. The objective of this study was to examine the impact of
N
-acetyltransferase 2 (
NAT2
) and
CYP2C9
polymorphisms on the pharmacokinetics of SMX in 118 renal transplant recipients. Starting on day 14 after renal transplantation, patients were administered 400 mg/day-80 mg/day of SMX-trimethoprim orally once daily. On day 14 after the beginning of SMX therapy, plasma SMX concentrations were determined by a high-performance liquid chromatography method. The SMX area under the concentration-time curve from 0 to 24 h (AUC
0-24
) for 15 recipients with the
NAT2
slow acetylator genotype (
NAT2*5/*6
, -*
6/*6
, -
*6/*7
, and -
*7/*7
) was significantly greater than that for 56 recipients with the
NAT2
rapid acetylator genotype (homozygous for
NAT2*4
) (766.4 ± 432.3 versus 537.2 ± 257.5 μg-h/ml, respectively;
P
= 0.0430), whereas there were no significant differences in the SMX AUC
0-24
between the
CYP2C9*1/*1
and -
*1/*3
groups. In a multiple regression analysis, the SMX AUC
0-24
was associated with
NAT2
slow acetylator polymorphisms (
P
= 0.0095) and with creatinine clearance (
P
= 0.0499). Hepatic dysfunction in
NAT2
slow acetylator recipient patients during the 6-month period after SMX administration was not observed. SMX plasma concentrations were affected by
NAT2
polymorphisms and renal dysfunction. Although standard SMX administration to patients with
NAT2
slow acetylator polymorphisms should be accompanied by monitoring for side effects and drug interaction effects from the inhibition of CYP2C9, SMX administration at a low dose (400 mg) as prophylaxis may not provide drug concentrations that reach the level necessary for the expression of side effects. Further studies with a larger sample size should be able to clarify the relationship between SMX plasma concentration and side effects.
Occidiofungin's Chemical Stability and
In Vitro
Potency against Candida Species
Authors: Ellis Dayna , Gosai Jiten , Emrick Charles , Heintz Rachel , Romans Lanette , Gordon Donna , Lu Shi-En , Austin Frank , Smith Leif
Published: November 2011

Occidiofungin is a cyclic glyco-lipopeptide produced by
Burkholderia contaminans
. MICs against
Candida
species were between 0.5 and 2.0 μg/ml. Occidiofungin retains its
in vitro
potency in the presence of 5% and 50% human serum with a minimal lethal concentration (MLC) of 2 and 4 μg/ml, respectively. Time-kill and postantifungal effect (PAFE) experiments of occidiofungin against
Candida albicans
were performed. The results demonstrate that occidiofungin is fungicidal. Occidiofungin was also found to be a very stable molecule. It is resistant to extreme temperatures and pH and maintains its activity following exposure to gastric proteases.
Possible Inhibitory Molecular Mechanism of Farnesol on the Development of Fluconazole Resistance in Candida albicans Biofilm
Authors: Yu Li-hua , Wei Xin , Ma Ming , Chen Xiao-jun , Xu Shuang-bo
Published: November 2011

Candida albicans
biofilm infections are usually treated with azole antifungals such as fluconazole. However, the development of resistance to this drug in
C. albicans
biofilms is very common, especially in immunocompromised individuals. The upregulation of the sterol biosynthetic pathway gene
ERG
and the efflux pump genes
CDR
and
MDR
may contribute to this azole tolerance in
Candida
species. We hypothesize that farnesol, an endogenous quorum sensing molecule with possible antimicrobial properties which is also the precursor of ergosterols in
C. albicans
, may interfere with the development of fluconazole resistance in
C. albicans
biofilms. To test this hypothesis, MICs were compared and morphology changes were observed by confocal laser scanning microscopy (CLSM) for farnesol-treated and -untreated and fluconazole-resistant groups. The expression of possible target genes (
ERG11
,
ERG25
,
ERG6
,
ERG5
,
ERG3
,
ERG1
,
MDR1
,
CDR1
, and
CDR2
) in biofilms was analyzed by reverse transcription-PCR (RT-PCR) and quantitative PCR (qPCR) to investigate the molecular mechanisms of the inhibitory effects of farnesol. The results showed a decreased MIC of fluconazole and thinner biofilms for the farnesol-treated group, indicating that farnesol inhibited the development of fluconazole resistance. The sterol biosynthetic pathway may contribute to the inhibitory effects of farnesol, as the transcription levels of the
ERG11
,
ERG25
,
ERG6
,
ERG3
, and
ERG1
genes decreased in the farnesol-treated group.
In Vivo
Activity of Aryl Ozonides against Schistosoma Species
Authors: Keiser Jennifer , Ingram Katrin , Vargas Mireille , Chollet Jacques , Wang Xiaofang , Dong Yuxiang , Vennerstrom Jonathan L.
Published: November 2011

We evaluated the
in vivo
antischistosomal activities of 11 structurally diverse synthetic peroxides. Of all compounds tested, ozonide (1,2,4-trioxolane) OZ418 had the highest activity against adult
Schistosoma mansoni
, with total and female worm burden reductions of 80 and 90% (
P
< 0.05), respectively. Furthermore, treatment of
S. haematobium
-infected mice with OZ418 reduced the total worm burden by 86%. In conclusion, OZ418 is a promising antischistosomal lead compound.
In Vitro
Evaluation of the Activities of the Novel Anticytomegalovirus Compound AIC246 (Letermovir) against Herpesviruses and Other Human Pathogenic Viruses
Authors: Marschall Manfred , Stamminger Thomas , Urban Andreas , Wildum Steffen , Ruebsamen-Schaeff Helga , Zimmermann Holger , Lischka Peter
Published: November 2011

AIC246 (letermovir) is a potent anticytomegalovirus drug in clinical development. Here, we report a consistent antiviral efficacy of AIC246 against human cytomegalovirus laboratory strains, clinical isolates, and virus variants resistant to approved drugs. Furthermore, we describe a remarkable selectivity of AIC246 for human cytomegaloviruses compared to that of other alpha-, beta-, or gammaherpesviruses or nonrelated pathogenic viruses, including adeno-, hepadna-, retro-, orthomyxo-, and flaviviruses. Our data confirm and support an excellent and selective anticytomegaloviral activity of AIC246.
Synergistic Interaction between Candida albicans and Commensal Oral Streptococci in a Novel
In Vitro
Mucosal Model
Authors: Diaz Patricia I. , Xie Zhihong , Sobue Takanori , Thompson Angela , Biyikoglu Basak , Ricker Austin , Ikonomou Laertis , Dongari-Bagtzoglou Anna
Published: November 2011

Candida albicans
is a commensal colonizer of the gastrointestinal tract of humans, where it coexists with highly diverse bacterial communities. It is not clear whether this interaction limits or promotes the potential of
C. albicans
to become an opportunistic pathogen. Here we investigate the interaction between
C. albicans
and three species of streptococci from the viridans group, which are ubiquitous and abundant oral commensal bacteria. The ability of
C. albicans
to form biofilms with
Streptococcus oralis
,
Streptococcus sanguinis
, or
Streptococcus gordonii
was investigated using flow cell devices that allow abiotic biofilm formation under salivary flow. In addition, we designed a novel flow cell system that allows mucosal biofilm formation under conditions that mimic the environment in the oral and esophageal mucosae. It was observed that
C. albicans
and streptococci formed a synergistic partnership where
C. albicans
promoted the ability of streptococci to form biofilms on abiotic surfaces or on the surface of an oral mucosa analogue. The increased ability of streptococci to form biofilms in the presence of
C. albicans
could not be explained by a growth-stimulatory effect since the streptococci were unaffected in their growth in planktonic coculture with
C. albicans
. Conversely, the presence of streptococci increased the ability of
C. albicans
to invade organotypic models of the oral and esophageal mucosae under conditions of salivary flow. Moreover, characterization of mucosal invasion by the biofilm microorganisms suggested that the esophageal mucosa is more permissive to invasion than the oral mucosa. In summary,
C. albicans
and commensal oral streptococci display a synergistic interaction with implications for the pathogenic potential of
C. albicans
in the upper gastrointestinal tract.
Establishment of a Real-Time, Quantitative, and Reproducible Mouse Model of Staphylococcus Osteomyelitis Using Bioluminescence Imaging
Authors: Funao Haruki , Ishii Ken , Nagai Shigenori , Sasaki Aya , Hoshikawa Tomoyuki , Aizawa Mamoru , Okada Yasunori , Chiba Kazuhiro , Koyasu Shigeo , Toyama Yoshiaki , Matsumoto Morio
Published: November 2011

Osteomyelitis remains a serious problem in the orthopedic field. There are only a few animal models in which the quantity and distribution of bacteria can be reproducibly traced. Here, we established a real-time quantitative mouse model of osteomyelitis using bioluminescence imaging (BLI) without sacrificing the animals. A bioluminescent strain ofStaphylococcus aureuswas inoculated into the femurs of mice. The bacterial photon intensity (PI) was then sequentially measured by BLI. Serological and histological analyses of the mice were performed. The mean PI peaked at 3 days, and stable signals were maintained for over 3 months after inoculation. The serum levels of interleukin-6, interleukin-1β, and C-reactive protein were significantly higher in the infected mice than in the control mice on day 7. The serum monocyte chemotactic protein 1 level was also significantly higher in the infected group at 12 h than in the control group. A significantly higher proportion of granulocytes was detected in the peripheral blood of the infected group after day 7. Additionally, both acute and chronic histological manifestations were observed in the infected group. This model is useful for elucidating the pathophysiology of both acute and chronic osteomyelitis and to assess the effects of novel antibiotics or antibacterial implants.