bluuebunny/crossref_metadata_2025 huggingface dataset:
A lethal ovitrap‐based mass trapping scheme for dengue control in Australia: I. Public acceptability and performance of lethal ovitraps
Authors: RITCHIE S. A. , RAPLEY L. P. , WILLIAMS C. , JOHNSON P. H. , LARKMAN M. , SILCOCK R. M. , LONG S. A. , RUSSELL R. C.
Published: November 2009

We report on the first field evaluation of the public acceptability and performance of two types of lethal ovitrap (LO) in three separate trials in Cairns, Australia. Health workers were able to set standard lethal ovitraps (SLOs) in 75 and 71% of premise yards in the wet and dry season, respectively, and biodegradable lethal ovitraps (BLOs) in 93% of yards. Public acceptance, measured as retention of traps by residents, was high for both trap types, with <9% of traps missing after 4 weeks. Traps retaining water after 4 weeks were 78 and 34% for the two SLO trials and 58% for the BLOs. The ‘failure rate’ in the 535 BLOs set in the field for 4 weeks was 47%, of which 19% were lost, 51% had holes from probable insect chewing, 23% were knocked over, 7% had dried by evaporation and 1% were split. There was no significant difference in the failure rate of BLOs set on porous (grass, soil and mulch) versus solid (tiles, concrete, wood and stone) substrates. The SLOs and the BLOs were readily acceptable to ovipositing Aedes aegypti L. (Diptera: Culicidae); the mean number of eggs/trap was 6 and 15, for the dry season and wet season SLO trial, respectively, and 15 for the BLO wet season trial. Indeed, 84–94% of premise yards had egg positive SLOs or BLOs. A high percentage of both wet and dry season SLOs (29 and 70%, respectively) and BLOs (62%) that were dry after 4 weeks were egg positive, indicating the traps had functioned. Lethal strips from SLOs and BLOs that had been exposed for 4 weeks killed 83 and 74%, respectively, of gravid Ae. aegypti in laboratory assays. These results indicate that mass trapping schemes using SLOs and BLOs are not rejected by the public and effectively target gravid Ae. aegypti. The impact of the interventions on mosquito populations is described in a companion paper.
Effects of dexmedetomidine sedation on the EEG in children
Authors: MASON KEIRA P. , O’MAHONY ELIZABETH , ZURAKOWSKI DAVID , LIBENSON MARK H.
Published: November 2009

Objectives: To examine the effects of dexmedetomidine sedation on EEG background and epileptiform activity in children, comparing it to natural sleep.

Aim: To provide quantitative and qualitative descriptions of the effect of dexmedetomidine sedation on the EEG of children.

Background: Children with intractable epilepsy admitted for surgery undergo 5 days of continuous EEG monitoring as well as nuclear medicine imaging studies with dexmedetomidine for sedation. Continuous EEG monitoring of each child during both natural sleep and dexmedetomidine‐induced sedation provides a unique opportunity to evaluate the effects of dexmedetomidine on the EEG of children.

Materials/methods: Sixteen children undergoing dexmedetomidine sedation for nuclear medicine studies and simultaneous continuous EEG monitoring were studied. EEG segments during sedation were compared to samples of naturally occurring stage II sleep from the same child. Standard visual EEG analysis, quantification of delta, theta, alpha, beta, and total RMS power, number and location of spike foci, and frequency of spike activity were compared.

Results: The EEG during dexmedetomidine sedation resembled stage II sleep. During sedation, statistically significant increases in power of 16% for theta (P = 0.01), 21% for alpha (P = 0.03), and 40% for beta (P < 0.01) were observed, but not for delta (P = 0.63) or total EEG power (P = 0.61). Spike frequency increased by 47% during sedation but no new spike foci or seizures were observed.

Conclusion: Dexmedetomidine sedation elicited an EEG pattern similar to that of Stage II sleep with modest increases in theta, alpha, and beta activity. Dexmedetomidine does not hinder interpretation of the EEG, suggesting that it may be a uniquely useful agent for EEG sedation in children.
Presurgical fentanyl vs caudal block and the incidence of adverse respiratory events in children after orchidopexy
Authors: KHALIL SAMIA N. , MATUSZCZAK MARIA E. , MAPOSA DOUGLAS , BOLOS MARIANA E. , LINGADEVARU HEMANETH S. , CHUANG ALICE Z.
Published: November 2009

Background:  There is controversy about the etiology of early postoperative hypoxemia. Age, weight, intubation, surgical procedure, use of muscle relaxants, and/or administration of opioids may affect the incidence of early postoperative hypoxemia. In this prospective, randomized, and single‐blinded study, we evaluated whether the administration of caudal analgesia vs i.v. fentanyl affected the number of children who develop postextubation adverse upper airway respiratory events, (upper airway obstruction, laryngospasm) and/or early postoperative hypoxemia.

Methods/materials:  Institutional approval and written parental informed consents were obtained. Thirty‐eight healthy outpatient boys, aged 1–6 years, scheduled for elective orchidopexy were randomized to receive pain relief either with a presurgical caudal block or by i.v. fentanyl. The primary outcome of the study was the number of children who developed postextubation adverse upper airway respiratory events and/or early postoperative hypoxemia.

Results:  The number of boys who developed postextubation adverse upper airway respiratory events and/or early postoperative hypoxemia in the caudal group was less compared with those in the fentanyl group (P = 0.04).

Conclusions:  Compared to fentanyl, placement of a presurgical caudal block in boys scheduled for orchidopexy was associated with a lower incidence of postextubation adverse upper airway respiratory events and/or early postoperative hypoxemia.
Reduction of fumarate, mesaconate and crotonate by Mfr, a novel oxygen‐regulated periplasmic reductase in Campylobacter jejuni
Authors: Guccione Edward , Hitchcock Andrew , Hall Stephen J. , Mulholland Francis , Shearer Neil , Van Vliet Arnoud H. M. , Kelly David J.
Published: November 2009

Methylmenaquinol : fumarate reductase (Mfr) is a newly recognized type of fumarate reductase present in some ε‐proteobacteria, where the active site subunit (MfrA) is localized in the periplasm, but for which a physiological role has not been identified. We show that the Campylobacter jejuni mfrABE operon is transcribed from a single promoter, with the mfrA gene preceded by a small open reading‐frame (mfrX) encoding a C. jejuni‐specific polypeptide of unknown function. The growth characteristics and enzyme activities of mutants in the mfrA and menaquinol : fumarate reductase A (frdA) genes show that the cytoplasmic facing Frd enzyme is the major fumarate reductase under oxygen limitation. The Mfr enzyme is shown to be necessary for maximal rates of growth by fumarate respiration and rates of fumarate reduction in intact cells measured by both viologen assays and 1H‐NMR were slower in an mfrA mutant. As periplasmic fumarate reduction does not require fumarate/succinate antiport, Mfr may allow more efficient adaptation to fumarate‐dependent growth. However, a further rationale for the periplasmic location of Mfr is suggested by the observation that the enzyme also reduces the fumarate analogues mesaconate and crotonate; fermentation products of anaerobes with which C. jejuni shares its gut environment, that are unable to be transported into the cell. Both MfrA and MfrB subunits were localized in the periplasm by immunoblotting and 2D‐gel electrophoresis, but an mfrE mutant accumulated unprocessed MfrA in the cytoplasm, suggesting a preassembled MfrABE holoenzyme has to be recognized by the TAT system for translocation to occur. Gene expression studies in chemostat cultures following an aerobic‐anaerobic shift showed that mfrA is highly upregulated by oxygen limitation, as would be experienced in vivo. Our results indicate that in addition to a role in fumarate respiration, Mfr allows C. jejuni to reduce analogous substrates specifically present in the host gut environment.
Complex regulatory network encompassing the Csr, c‐di‐GMP and motility systems of Salmonella Typhimurium
Authors: Jonas Kristina , Edwards Adrianne N. , Ahmad Irfan , Romeo Tony , Römling Ute , Melefors Öjar
Published: November 2009

Bacterial survival depends on the ability to switch between sessile and motile lifestyles in response to changing environmental conditions. In many species, this switch is governed by (3′‐5′)‐cyclic‐diguanosine monophosphate (c‐di‐GMP), a signalling molecule, which is metabolized by proteins containing GGDEF and/or EAL domains. Salmonella Typhimurium contains 20 such proteins. Here, we show that the RNA‐binding protein CsrA regulates the expression of eight genes encoding GGDEF, GGDEF‐EAL and EAL domain proteins. CsrA bound directly to the mRNA leaders of five of these genes, suggesting that it may regulate these genes post‐transcriptionally. The c‐di‐GMP‐specific phosphodiesterase STM3611, which reciprocally controls flagella function and production of biofilm matrix components, was regulated by CsrA binding to the mRNA, but was also indirectly regulated by CsrA through the FlhDC/FliA flagella cascade and STM1344. STM1344 is an unconventional (c‐di‐GMP‐inactive) EAL domain protein, recently identified as a negative regulator of flagella gene expression. Here, we demonstrate that CsrA directly downregulates expression of STM1344, which in turn regulates STM3611 through fliA and thus reciprocally controls motility and biofilm factors. Altogether, our data reveal that the concerted and complex regulation of several genes encoding GGDEF/EAL domain proteins allows CsrA to control the motility‐sessility switch in S. Typhimurium at multiple levels.
Microclimate and limits to photosynthesis in a diverse community of hypolithic cyanobacteria in northern Australia
Authors: Tracy Christopher R. , Streten‐Joyce Claire , Dalton Robert , Nussear Kenneth E. , Gibb Karen S. , Christian Keith A.
Published: November 2009

Hypolithic microbes, primarily cyanobacteria, inhabit the highly specialized microhabitats under translucent rocks in extreme environments. Here we report findings from hypolithic cyanobacteria found under three types of translucent rocks (quartz, prehnite, agate) in a semiarid region of tropical Australia. We investigated the photosynthetic responses of the cyanobacterial communities to light, temperature and moisture in the laboratory, and we measured the microclimatic variables of temperature and soil moisture under rocks in the field over an annual cycle. We also used molecular techniques to explore the diversity of hypolithic cyanobacteria in this community and their phylogenetic relationships within the context of hypolithic cyanobacteria from other continents. Based on the laboratory experiments, photosynthetic activity required a minimum soil moisture of 15% (by mass). Peak photosynthetic activity occurred between approximately 8°C and 42°C, though some photosynthesis occurred between −1°C and 51°C. Maximum photosynthesis rates also occurred at light levels of approximately 150–550 μmol m−2 s−1. We used the field microclimatic data in conjunction with these measurements of photosynthetic efficiency to estimate the amount of time the hypolithic cyanobacteria could be photosynthetically active in the field. Based on these data, we estimated that conditions were appropriate for photosynthetic activity for approximately 942 h (∼75 days) during the year. The hypolithic cyanobacteria community under quartz, prehnite and agate rocks was quite diverse both within and between rock types. We identified 115 operational taxonomic units (OTUs), with each rock hosting 8–24 OTUs. A third of the cyanobacteria OTUs from northern Australia grouped with Chroococcidiopsis, a genus that has been identified from hypolithic and endolithic communities from the Gobi, Mojave, Atacama and Antarctic deserts. Several OTUs identified from northern Australia have not been reported to be associated with hypolithic communities previously.
Semiparametric regression models and sensitivity analysis of longitudinal data with non‐random dropouts
Authors: Todem David , Kim KyungMann , Fine Jason , Peng Limin
Published: November 2009

We propose a family of regression models to adjust for non‐random dropouts in the analysis of longitudinal outcomes with fully observed covariates. The approach conceptually focuses on generalized linear models with random effects. A novel formulation of a shared random effects model is presented and shown to provide a dropout selection parameter with a meaningful interpretation. The proposed semiparametric and parametric models are made part of a sensitivity analysis to delineate the range of inferences consistent with observed data. Concerns about model identifiability are addressed by fixing some model parameters to construct functional estimators that are used as the basis of a global sensitivity test for parameter contrasts. Our simulation studies demonstrate a large reduction of bias for the semiparametric model relative to the parametric model at times where the dropout rate is high or the dropout model is mis‐specified. The methodology's practical utility is illustrated in a data analysis.
EFNS guidelines on the molecular diagnosis of mitochondrial disorders
Authors: Finsterer J. , Harbo H. F. , Baets J. , Van Broeckhoven C. , Di Donato S. , Fontaine B. , De Jonghe P. , Lossos A. , Lynch T. , Mariotti C. , Schöls L. , Spinazzola A. , Szolnoki Z. , Tabrizi S. J. , Tallaksen C. M. E. , Zeviani M. , Burgunder J.‐M. , Gasser T.
Published: November 2009

Objectives:  These European Federation of Neurological Sciences (EFNS) guidelines are designed to provide practical help for the general neurologist to make appropriate use of molecular genetics for diagnosing mitochondrial disorders (MIDs), which gain increasing attention and are more frequently diagnosed due to improved diagnostic tools.

Background:  Since the publication of the first EFNS guidelines on the molecular diagnosis of inherited neurological diseases in 2001, rapid progress has been made in this field, necessitating the creation of an updated version.

Search strategy:  To collect data about the molecular diagnosis of MIDs search for literature in various electronic databases, such as Cochrane library, MEDLINE, OMIM, GENETEST or Embase, were carried out and original papers, meta‐analyses, review papers, and guideline recommendations were reviewed.

Results:  The guidelines summarise the possibilities and limitations of molecular genetic diagnosis of MIDs and provide practical recommendations and diagnostic criteria in accordance with the EFNS Scientific Committee to guide the molecular diagnostic work‐up of MIDs.

Recommendations:  The proposed guidelines suggest an approach to the molecular diagnosis of MIDs in a manner accessible to general neurologists.
Restenosis after carotid endarterectomy: significance of newly acquired risk factors
Authors: Fluri F. , Hatz F. , Voss B. , Lyrer P. A. , Engelter S. T.
Published: November 2009

Background:  In patients who had carotid endarterectomy (CEA), the significance of newly acquired cerebrovascular risk factors (CRFs) is unknown. Newly acquired CRFs are defined as CRFs not present prior to CEA (baseline CRFs) but acquired during long‐term follow‐up.

Objective:  We sought to determine the significance of newly acquired CRFs in CEA patients with regard to progressive ICA disease (≥50% restenosis; occurrence or progression of contralateral stenosis).

Methods:  In a single‐center CEA‐registry, 361 CEA patients with annual follow‐up visits for 7 years were identified. Hazard ratios (HR) were calculated for (i) any baseline CRF (hypertension, diabetes, hypercholesterolemia, coronary heart disease (CHD), peripheral artery disease (PAD), smoking), (ii) any newly acquired CRF, and (iii) for the use of statins and antihypertensives.

Results:  No baseline CRF was associated with progressive ICA disease (unadjusted analysis). After adjustment for age and gender, smoking (HR 1.52, 95%CI 1.02–2.26), diabetes (HR 1.64, 95%CI 1.00–2.68), and hypercholesterolemia (HR 1.61, 95%CI 1.03–2.52) were weakly related to progressive ICA disease. Newly acquired hypertension (HR 2.44, 95%CI 1.57‐3.79), CHD (HR 2.73, 95%CI 1.81–4.11), diabetes (HR 2.30, 95%CI 1.39‐3.80), and PAD (HR 3.94, 95%CI 2.69–5.76) were associated with progressive ICA disease; also, after adjustment for baseline CRFs. Acquisition of at least one new CRF was related to progressive ICA disease (HRadjusted 8.07, 95%CI 4.97–13.12). Neither statins nor antihypertensive drugs did alter the odds for progressive ICA disease.

Conclusion:  CRFs acquired during long‐term follow‐up after CEA may independently contribute to progressive ICA stenosis after endarterectomy. Newly acquired CRFs might be more hazardous than CRFs present prior to CEA.
Therapeutic potential for novel drugs targeting the type 1 cholecystokinin receptor
Authors: Cawston Erin E , Miller Laurence J
Published: November 2009

Cholecystokinin (CCK) is a physiologically important gastrointestinal and neuronal peptide hormone, with roles in stimulating gallbladder contraction, pancreatic secretion, gastrointestinal motility and satiety. CCK exerts its effects via interactions with two structurally related class I guanine nucleotide‐binding protein (G protein)‐coupled receptors (GPCRs), the CCK1receptor and the CCK2receptor. Here, we focus on the CCK1receptor, with particular relevance to the broad spectrum of signalling initiated by activation with the natural full agonist peptide ligand, CCK. Distinct ligand‐binding pockets have been defined for the natural peptide ligand and for some non‐peptidyl small molecule ligands. While many CCK1receptor ligands have been developed and have had their pharmacology well described, their clinical potential has not yet been fully explored. The case is built for the potential importance of developing more selective partial agonists and allosteric modulators of this receptor that could have important roles in the treatment of common clinical syndromes.

This article is part of a themed section on Molecular Pharmacology of GPCR. To view the editorial for this themed section visithttp://dx.doi.org/10.1111/j.1476‐5381.2010.00695.x
Medieval Sicily and Southern Italy in Recent Historiographical Perspective
Authors: Davis‐Secord Sarah C.
Published: November 2009

Sicily and southern Italy during the Middle Ages have been a neglected area of study for many years, primarily due to the general belief that the area fell into decline after the ‘fall’ of Rome. Recently, however, there has been growing interest in the Muslims of medieval Sicily and Italy, as well as the Jewish and Greek populations that lived under Latin Christian rule for many centuries. There has also been a rise in scholarship on the medieval Mediterranean region as a whole, which has caused a re‐evaluation not only of the role and importance of the Mediterranean world, but also of how the medieval European system worked, how Latin Christendom related to the Muslim states on its southern borders, and what roles Muslim cultures and settlements played in the development of Italy’s society.
Limbic Encephalitis Investigated by 18FDG‐PET and 3D MRI
Authors: Kassubek Jan , Juengling Freimut D. , Nitzsche Egbert U. , Lücking Carl H.
Published: November 2009

Two patients with clinically probable or possible limbic encephalitis (LE) are reported, both cases with typical findings in clinical symptoms (severe neuropsychological deficits and complex partial seizures) and in routine magnetic resonance imaging (MRI) (hyperintense mesiotemporal lesions). Underlying malignancy was identified (rectal carcinoma) in one case but could not be detected in the other patient. The 2 patients were investigated by cerebral 18F‐fluoro‐2‐deoxy‐D‐glucose—positron emission tomography (FDG‐PET) and 3‐dimensional (3D) MRI, and abnormalities in metabolic activity were mapped using coregistration of spatially normalized PET and MRI. Highly significant focal hypermetabolism in bilateral hippocampal areas was found in both cases. The authors' findings support FDG‐PET coregistered to 3D MRI as a potentially valuable additional tool in the imaging diagnostics of LE. Results are discussed with respect to the clinical symptoms and previously reported imaging findings in the disease.
Weapon Usage in Attempted and Completed Parricides in Nineteenth‐Century America: An Archival Exploration of the Physical Strength Hypothesis
Authors: Shon Phillip C. H.
Published: November 2009

Abstract:  The “physical strength hypothesis” (PSH) predicts that where there is the greatest discrepancy in size and strength between offenders and victims, the former will use superior weaponry (e.g., firearms) to overcome structural imbalances against the latter. Using archival data from the New York Times and the Chicago Tribune, 1851–1899, this paper examines the weapons used in attempted and completed parricides in nineteenth‐century America. Findings indicate that parricide offenders used firearms most frequently against their fathers while intimate contact methods were used against mothers. When gun usage was combined with level of intent in male offender patricides, where the greatest discrepancy in strength was expected, results indicate that spontaneous gun usage outnumbered premeditated gun usage, thus challenging the assumptions of the PSH. The data suggest that cultural factors such as methods of dispute resolution, weapon carrying, and alcohol consumption may be important factors in understanding parricides.
“Lateral Angle” of the Internal Auditory Canal: Non‐Association with Temporal Bone Pneumatization
Authors: Wendell Todd Norman , Graw Matthias , Dietzel Maria
Published: November 2009

Abstract:  The “lateral angle,” the angle with which the posterior wall of the internal auditory canal meets the posterior fossa plate, is arguably wider in females (>45°) than males (<45°). Not previously addressed, however, are repeatability of angle determination, and whether the extent of temporal bone pneumatization is a confounder. Forty‐one adult human cranial specimens (82 clinically normal temporal bones) were studied; no sex information was available for this United States sample. Two casts were created from each ear; each cast was independently categorized twice. No association of lateral angle with mastoid size was found. Repeatability was good. Although bilateral symmetry was suggested (phi = 0.60, p = 0.05), two crania had oppositely categorized right‐left angles. We observed a new finding: narrowed but clinically normal canals in 10% of crania. The lateral angle is a good candidate to be a morphological method in determination of sex.
The contribution of active medication to combined treatments of psychotherapy and pharmacotherapy for adult depression: a meta‐analysis
Authors: Cuijpers P. , Van Straten A. , Hollon S. D. , Andersson G.
Published: November 2009

Cuijpers P, van Straten A, Hollon SD, Andersson G. The contribution of active medication to combined treatments of psychotherapy and pharmacotherapy for adult depression: a meta‐analysis.

Objective:  Although there is sufficient evidence that combined treatments of psychotherapy and pharmacotherapy are more effective for depression in adults than each of the treatments alone, it remains unclear what the exact contribution of active medication is to the overall effects of combined treatments. This paper examines the contribution of active medication to combined psychotherapy and pharmacotherapy treatments.

Method:  Meta‐analysis of randomised controlled trials comparing the combination of psychotherapy and pharmacotherapy with the combination of psychotherapy and placebo.

Results:  Sixteen identified studies involving 852 patients met our inclusion criteria. The standardised mean difference indicating the differences between the combination of psychotherapy and pharmacotherapy and the combination of psychotherapy and placebo was 0.25 (95% CI: 0.03–0.46), which corresponds to a numbers‐needed‐to‐be‐treated of 7.14. No significant differences between subgroups of studies were found.

Conclusion:  Active medication has a small but significant contribution to the overall efficacy of combined treatments.
Clinical Inertia and Blood Pressure Goal Attainment
Authors: Basile Jan
Published: November 2009

Optimal blood pressure (BP) control is still not being achieved for the majority of patients with hypertension.  Although the topic of patient adherence to health care practitioner recommendations is less than desirable and medication noncompliance adds to the cost of health care, another issue that affects the ability to attain optimal BP control is therapeutic, or clinical, inertia, which is the failure of health care providers to initiate or intensify therapy when indicated.  This paper will discuss therapeutic inertia and other issues that prevent BP goal attainment.
Endothelial Dysfunction: Do Angiotensin Receptor Blockers Have a Role?
Authors: Mason R. Preston
Published: November 2009

Endothelial dysfunction, oxidative stress, and inflammation are several destructive mechanisms of disease, including hypertension, atherosclerosis, and type 2 diabetes.  There is clear evidence linking endothelial dysfunction to abnormal vasodilation with these well‐known risk factors.  This paper will discuss the understanding of endothelial dysfunction as it applies to both hypertension and dyslipidemia models and the pharmacologic approaches available to improve endothelial dysfunction.
Renin‐Angiotensin‐Aldosterone System Inhibition and Improvement in Glucose Tolerance
Authors: Whaley‐Connell Adam , Kurukulasuriya L. Romayne , Sowers James R.
Published: November 2009

A linchpin of the cardiometabolic syndrome is insulin resistance, an important cardiovascular and chronic kidney disease risk factor. Activation of the renin‐angiotensin‐aldosterone system (RAAS) has been shown to impair insulin metabolic signaling and insulin‐stimulated glucose uptake as well as pancreatic secretion of insulin. Recent work has highlighted the role of aldosterone as an important component of the RAAS and may play a role in not only altering glucose uptake in skeletal muscle but in normal liver metabolism as well. Like angiotensin II, aldosterone may promote hepatosteatosis and impact pancreatic β‐cells. By blocking the effects of angiotensin II with a RAAS blocker or aldosterone with a mineralocorticoid inhibitor, the effects may be reversed. Therefore, it appears that the RAAS and aldosterone are important in generation of reactive oxygen species in the β‐cell and increased apoptosis. It is clear that preclinical evidence has demonstrated a role for the RAAS and glucose metabolism. While there is sufficient clinical data to support RAAS inhibition with either an angiotensin‐converting enzyme inhibitor or an angiotensin receptor blocker, it is important to note none of these studies were powered to address glucose tolerance as a primary end point. Thereby, to complement preclinical studies, more randomized multicenter outcomes evidence is needed to fully elucidate the impact that RAAS inhibition and, specifically, the use of angiotensin receptor blockers have on glucose tolerance. Nonetheless, the weight of evidence suggests that inhibition of the RAAS vs other antihypertensive agents, whether calcium channel blockers, thiazide diuretics, or β‐blockade, improve glucose tolerance.
Does Renin‐Angiotensin‐Aldosterone System Inhibition Impact Obesity as a Co–Risk Factor?
Authors: Hsueh Willa A. , Wyne Kathleen L.
Published: November 2009

Obesity is an independent risk factor for cardiovascular disease (CVD).  When combined with smoking, diabetes, and hypertension (HTN), obesity has a synergistic effect to increase CVD risk 21‐fold.  Obesity damages multiple target organs, which are targets of “angry fat”, to increase risk of diabetes and fatty liver.  Many of these effects are due to ectopic fat deposition, increased oxidative stress, and inflammation. Importantly, the adipocyte is a source of angiotensinogen, potentially leading to renin‐angiotensinogen‐aldosterone system (RAAS) activation and HTN, which is 3‐fold more prevalent in obese compared with nonobese populations.  Emerging evidence suggests that the RAAS may also play a role in metabolism and the complications of obesity. Further research is needed to determine whether RAAS modulation with angiotensin receptor blockers will be useful not only for treating obesity‐associated HTN, but also for the metabolic and other complications of obesity, particularly by reducing damage from oxidative stress.
Single‐port surgery: Current applications and limitations
Authors: Rao GV , Mansard MJ , Ravula PK , Rebala P , Dama RR , Reddy DN
Published: November 2009

Introduction: In an attempt to further enhance the benefits of cosmesis and reduced morbidity of minimally invasive surgery, single‐port (incision) laparoscopic surgery (SPS) has emerged as a bridge between conventional laparoscopy and natural orifice transluminal endoscopic surgery. As the expertise and instrumentation required are an extension of standard laparoscopic techniques, SPS has been adapted for a variety of procedures and specialties in a short span of time.

Discussion: In this article, we discuss the various SPS techniques, as well as the new devices and instrumentation available for facilitating SPS. We also review current applications reported for SPS in various surgical specialties. We present a comprehensive review of the potential benefits, limitations and risks of these novel techniques.

Conclusion: Initial reports have demonstrated the technical feasibility and safety of SPS for a wide range of surgical applications. With specialized instrumentation and refinement of technique, its role will increase in coming years. Future work is necessary to improve existing instrumentation, to increase clinical experience and to assess the benefits of this surgical approach.
Those wonderful elastic waves
Authors: Ignatovich Vladimir K. , Phan Loan T. N.
Published: November 2009

We consider elastic waves in isotropic and anisotropic media and discuss their polarization, speeds, reflection from interfaces with mode conversion, and surface waves. The waves are represented by a wave function. For isotropic media this representation greatly simplifies the theory. The reflection of quasitransverse waves in anisotropic media from a free surface is shown to be characterized by three critical angles.
Equilibrium charge density on a thin curved wire
Authors: Partovi M. Hossein , Griffiths David J.
Published: November 2009

We address the electrostatic problem of a thin, curved, and cylindrical conductor (a conducting filament) and show that the corresponding linear charge density slowly tends to uniformity as the inverse of the logarithm of a characteristic parameter, which is the ratio of the diameter to the smaller of the length and minimum radius of curvature of the filament. An alternative derivation of this result based on energy minimization is given. These results follow from a general asymptotic analysis of the electric field components and potential near a charged filament in the limit of vanishing diameter. It is found that the divergent parts of the radial and azimuthal electric field components are determined by the local charge density, while the axial component is determined by the local dipole density. For a straight filament our results reduce to those known for conducting needles. For curved filaments, the configuration of charges and fields is no longer azimuthally symmetric, and there is an additional length scale arising from the finite radius of curvature of the filament. The basic uniformity result survives the added complications, which include an azimuthal variation in the surface charge density of the filament. As with the variations in linear charge density along the filament, the azimuthal variations vanish with the characteristic parameter, only more rapidly. These findings allow us to derive an asymptotic formula for the capacitance of a curved filament that generalizes a result first obtained by Maxwell. The examples of a straight filament with uniform and linearly varying charge densities and a circular filament with a uniform charge distribution are treated analytically and found to agree with the general analysis. Numerical calculations illustrating the slow convergence of linear charge distribution to uniformity for an elliptical filament are presented. An interactive computer program implementing and animating the numerical calculations is available.
Super paramagnetic iron oxide MRI shows defective Kupffer cell uptake function in non-alcoholic fatty liver disease
Authors: Asanuma Taketoshi , Ono Masafumi , Kubota Kei , Hirose Akira , Hayashi Yoshihiro , Saibara Toshiji , Inanami Osamu , Ogawa Yasuhiro , Enzan Hideaki , Onishi Saburo , Kuwabara Mikinori , Oben Jude A
Published: November 2009

Background

The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is incompletely understood. Kupffer cells (KCs), phagocytic liver-resident macrophages, provide a protective barrier against egress of endotoxin from the portal to the systemic circulation. It is not known if KC phagocytic function is impaired in NAFLD. Super-paramagnetic iron oxide (SPIO) magnetic resonance imaging is a comparative technology dependent on KC phagocytic function.

Objective

To evaluate KC uptake function, in patients and experimental animals with NAFLD, using SPIO.

Methods

Abdominal CT and histological examination of liver biopsy specimens were used to estimate the degree of steatosis in patients with NAFLD and controls with chronic hepatitis C. SPIO-MRI was then performed in all patients. Normal rats fed a methionine-choline-deficient diet to induce non-alcoholic steatohepatitis (NASH), the more severe stage of NAFLD, and obese, insulin resistant, Zucker fa/fa rats with steatohepatitis, were also studied with SPIO-MRI and analysed for hepatic uptake of fluorescent microbeads. Immunohistochemical analysis evaluated the numbers of KCs in patients and rat livers.

Results

Relative signal enhancement (RSE), inversely proportional to KC function, was higher in patients with NAFLD than in controls and with the degree of steatosis on CT. RSE also positively correlated with the degree of steatosis on histology and was similarly higher in rats with induced severe NAFLD (NASH). On immunohistochemistry, defective phagocytic function was the result of reduced phagocytic uptake and not due to reduced KC numbers in rats or patients with NAFLD.

Conclusions

KC uptake function is significantly impaired in patients with NAFLD and experimental animals with NASH, worsens with the degree of steatosis and is not due to a reduction of KC numbers.
Patterns of Aggressive Attack in Juvenile Steelhead Trout (Salmo gairdneri)
Authors: Abbott Jeremy C. , Dill Lawrence M.
Published: November 2009

Nipping is a potentially damaging aggressive behavior of juvenile steelhead trout (Salmo gairdneri). By analyzing videotaped interactions of pairs of fish we determined where nips were aimed and where they contacted the opponent's body. Patterns of fin damage were also assessed. Aims and nips (contacts) were distributed differently in reciprocal and nonreciprocal aggressive bouts. In nonreciprocal bouts, aims were directed mainly at the dorsal fin, central body section, and caudal fin. Nip contact was biased towards the caudal fin. In reciprocal bouts, both aims and nips were concentrated on the dorsal fin and anterior portions of the body. We suggest that juvenile steelhead adjust their fighting tactics in response to opponent behavior. Mouth fighting, a novel behavior in juvenile trout, was observed in some reciprocal bouts. The dorsal fin incurred the greatest damage. We conclude that aggression (nipping) is responsible for the dorsal fin damage commonly observed in hatchery-reared salmonids.
Fish Hepatocytes: A Model Metabolic System
Authors: Moon T. W. , Walsh P. J. , Mommsen T. P.
Published: November 2009

The hepatocyte or liver cell preparation is a standard metabolic model in mammalian physiology/biochemistry. This paper presents a basic method for the isolation of viable fish hepatocytes, reviews specifically the literature available on hepatic function and adaptation using the preparation, and examines those areas where this preparation could contribute to our understanding of basic and applied fisheries biology. Viable liver cells are prepared by collagenase perfusion and collected by low-speed centrifugation. Buffered salines employed for cell isolation must be consistent with the normal plasma constituents of the species. Recent studies have established that a variety of fish hepatocytes remain metabolically active in suspension and perform a variety of anabolic tasks, including gluconeogenesis, lipogenesis, ketogenesis, sterol biosynthesis, synthesis of export and mitochondrial proteins, and nucleic acid biosynthesis. New techniques, including cell culture, will provide biologists with a tool to study the more long-term effects of hormones, xenobiotics, and micronutrient requirements under controlled laboratory conditions. The use of fish hepatocytes to reduce the necessity of whole animal models in pharmacological and toxicological studies is particularly promising. The fish hepatocyte preparation represents an important tool to further our understanding of the role of the liver in the biology of fish species.
Impaired oxidative metabolism and inflammation are associated with insulin resistance in ERα-deficient mice
Authors: Ribas Vicent , Nguyen M. T. Audrey , Henstridge Darren C. , Nguyen Anh-Khoi , Beaven Simon W. , Watt Matthew J. , Hevener Andrea L.
Published: November 2009

Impaired estrogen action is associated with the metabolic syndrome in humans. We sought to determine whether impaired estrogen action in female C57Bl6 mice, produced by whole body Esr1 ablation, could recapitulate aspects of this syndrome, including inflammation, insulin resistance, and obesity. Indeed, we found that global knockout (KO) of the estrogen receptor (ER)α leads to reduced oxygen uptake and caloric expenditure compared with wild-type (WT) mice. In addition, fasting insulin, leptin, and PAI-1 levels were markedly elevated, whereas adiponectin levels were reduced in normal chow-fed KO. Furthermore, ERα-KO mice exhibited impaired glucose tolerance and marked skeletal muscle insulin resistance that was accompanied by the accumulation of bioactive lipid intermediates, inflammation, and diminished PPARα, PPARδ, and UCP2 transcript levels. Although the relative glucose intolerance and insulin resistance phenotype in KO mice became more severe with high-fat feeding, WT mice were refractory to these dietary-induced effects, and this protection coincided with a marked increase in circulating adiponectin and heat shock protein 72 levels in muscle, liver, and fat. These data indicate that ERα is critical for the maintenance of whole body insulin action and protection against tissue inflammation during both normal chow and high-fat feeding.
Procalcitonin as a Biomarker for a Bacterial Infection on Hospital Admission: A Critical Appraisal in a Cohort of Travellers with Fever after a Stay in (Sub)tropics
Authors: Hesselink Dennis A. , Bosmans-Timmerarends Hanna , Burgerhart Jan-Steven , Petit Pieter L. , van Genderen Perry J.
Published: November 2009

Fever in a returned traveller may be the manifestation of a self-limiting, trivial infection but it can also presage an infection that can be rapidly progressive and lethal. We studied the diagnostic accuracy of procalcitonin (PCT) as a biomarker for a bacterial cause of fever in a cohort of 157 consecutive travellers with fever after a stay in the (sub)tropics. Elevated procalcitonin levels were observed not only in about 50% of travellers with proven bacterial infection, but also in a significant proportion of travellers with a likely infection. Using a cutoff point of 0.5 ng/mL, procalcitonin had a sensitivity of 0.52 and a specificity of 0.76 for a bacterial cause of fever on admission. Interestingly, only 1 out of 16 patients with a proven viral infection had a marginally elevated PCT concentration on admission, suggesting that an increased PCT level likely excludes a viral infection as the cause of fever. However, the diagnostic accuracy of this semiquantitative procalcitonin test for a bacterial cause of fever on admission is too poor to advocate its use in the initial clinical evaluation of fever in a setting of ill-returned travellers.
Some Computational Formulas forD‐Nörlund Numbers
Authors: Liu Guodong
Published: November 2009

The author establishes some identities involving theDnumbers, Bernoulli numbers, and central factorial numbers of the first kind. A generating function and several computational formulas forD‐Nörlund numbers are also presented.
Optimal On‐Off Attitude Control for the Brazilian Multimission Platform Satellite
Authors: Arantes Gilberto , Martins-Filho Luiz S. , Santana Adrielle C.
Published: November 2009

This work deals with the analysis and design of a reaction thruster attitude control for the Brazilian Multimission platform satellite. The three‐axis attitude control systems are activated in pulse mode. Consequently, a modulation of the torque command is compelling in order to avoid high nonlinear control action. This work considers the Pulse‐Width Pulse‐Frequency (PWPF) modulator which is composed of a Schmidt trigger, a first‐order filter, and a feedback loop. PWPF modulator holds several advantages over classical bang‐bang controllers such as close to linear operation, high accuracy, and reduced propellant consumption. The Linear Gaussian Quadratic (LQG) technique is used to synthesize the control law during stabilization mode and the modulator is used to modulate the continuous control signal to discrete one. Numerical simulations are
used to analyze the performance of the attitude control. The LQG/PWPF approach achieves good stabilization‐mode requirements as disturbances rejection and regulation performance.
Human Bone Marrow–Derived Mesenchymal Stem Cells for Intravascular Delivery of Oncolytic Adenovirus Δ24-RGD to Human Gliomas
Authors: Yong Raymund L. , Shinojima Naoki , Fueyo Juan , Gumin Joy , Vecil Giacomo G. , Marini Frank C. , Bogler Oliver , Andreeff Michael , Lang Frederick F.
Published: November 2009

Δ24-RGD is an infectivity-augmented, conditionally replicative oncolytic adenovirus with significant antiglioma effects. Although intratumoral delivery of Δ24-RGD may be effective, intravascular delivery would improve successful application in humans. Due to their tumor tropic properties, we hypothesized that human mesenchymal stem cells (hMSC) could be harnessed as intravascular delivery vehicles of Δ24-RGD to human gliomas. To assess cellular events, green fluorescent protein–labeled hMSCs carrying Δ24-RGD (hMSC-Δ24) were injected into the carotid artery of mice harboring orthotopic U87MG or U251-V121 xenografts and brain sections were analyzed by immunofluorescence for green fluorescent protein and viral proteins (E1A and hexon) at increasing times. hMSC-Δ24 selectively localized to glioma xenografts and released Δ24-RGD, which subsequently infected glioma cells. To determine efficacy, mice were implanted with luciferase- labeled glioma xenografts, treated with hMSC-Δ24 or controls, and imaged weekly by bioluminescence imaging. Analysis of tumor size by bioluminescence imaging showed inhibition of glioma growth and eradication of tumors in hMSC-Δ24-treated animals compared with controls (P < 0.0001). There was an increase in median survival from 42 days in controls to 75.5 days in hMSC-Δ24-treated animals (P < 0.0001) and an increase in survival beyond 80 days from 0% to 37.5%, respectively. We conclude that intra-arterially delivered hMSC-Δ24 selectively localize to human gliomas and are capable of delivering and releasing Δ24-RGD into the tumor, resulting in improved survival and tumor eradication in subsets of mice. [Cancer Res 2009;69(23):8932–40]
Acyl-CoA Synthetase VL3 Knockdown Inhibits Human Glioma Cell Proliferation and Tumorigenicity
Authors: Pei Zhengtong , Sun Peng , Huang Ping , Lal Bachchu , Laterra John , Watkins Paul A.
Published: November 2009

The contribution of lipid metabolic pathways to malignancy is poorly understood. Expression of the fatty acyl-CoA synthetase ACSVL3 was found to be markedly elevated in clinical malignant glioma specimens but nearly undetectable in normal glia. ACSVL3 levels correlated with the malignant behavior of human glioma cell lines and glioma cells propagated as xenografts. ACSVL3 expression was induced by the activation of oncogenic receptor tyrosine kinases (RTK) c-Met and epidermal growth factor receptor. Inhibiting c-Met activation with neutralizing anti–hepatocyte growth factor monoclonal antibodies reduced ACSVL3 expression concurrent with tumor growth inhibition in vivo. ACSVL3 expression knockdown using RNA interference, which decreased long-chain fatty acid activation, inhibited anchorage-dependent and anchorage-independent glioma cell growth by ∼70% and ∼90%, respectively. ACSVL3-depleted cells were less tumorigenic than control cells, and subcutaneous xenografts grew ∼60% slower than control tumors. Orthotopic xenografts produced by ACSVL3-depleted cells were 82% to 86% smaller than control xenografts. ACSVL3 knockdown disrupted Akt function as evidenced by RTK-induced transient decreases in total and phosphorylated Akt, as well as glycogen synthase kinase 3β, via a caspase-dependent mechanism. Expressing constitutively active myr-Akt rescued cells from the anchorage-dependent and anchorage-independent growth inhibitory effects of ACSVL3 depletion. These studies show that ACSVL3 maintains oncogenic properties of malignant glioma cells via a mechanism that involves, in part, the regulation of Akt function. [Cancer Res 2009;69(24):9175–82]
Absence of Both CytochromeP450 3A and P-glycoprotein Dramatically Increases Docetaxel Oral Bioavailability and Risk of Intestinal Toxicity
Authors: van Waterschoot Robert A.B. , Lagas Jurjen S. , Wagenaar Els , van der Kruijssen Cornelia M.M. , van Herwaarden Antonius E. , Song Ji-Ying , Rooswinkel Rogier W. , van Tellingen Olaf , Rosing Hilde , Beijnen Jos H. , Schinkel Alfred H.
Published: November 2009

Docetaxel is one of the most widely used anticancer drugs. A major problem with docetaxel treatment, however, is the considerable interpatient variability in docetaxel exposure. Another disadvantage of the drug is that it has a very low oral bioavailability and can therefore only be administered i.v. The drug-metabolizing enzyme cytochrome P450 3A (CYP3A) and the drug transporter P-glycoprotein (P-gp; MDR1) are considered to be major determinants of docetaxel pharmacokinetics. It has been hypothesized that CYP3A and P-gp work synergistically in limiting the systemic exposure to many orally ingested drugs. However, it has been difficult to examine this interplay in vivo. We therefore generated mice lacking all CYP3A and P-gp genes. Although missing two primary detoxification systems, Cyp3a/Mdr1a/1b−/− mice are viable, fertile, and without spontaneous abnormalities. When orally challenged with docetaxel, a disproportionate (>70-fold) increase in systemic exposure was observed compared with the increases in single Cyp3a−/− (12-fold) or Mdr1a/1b−/− (3-fold) mice. Unexpectedly, although CYP3A and P-gp collaborated extremely efficiently in lowering docetaxel exposure, their individual efficacy was not dependent on activity of the other protein. On reflection, this absence of functional synergism makes biological sense, as synergism would conflict with a robust detoxification defense. Importantly, the disproportionate increase in docetaxel exposure in Cyp3a/Mdr1a/1b−/− mice resulted in dramatically altered and lethal toxicity, with severe intestinal lesions as a major cause of death. Simultaneous inhibition of CYP3A/P-gp might thus be a highly effective strategy to improve oral drug bioavailability but with serious risks when applied to drugs with narrow therapeutic windows. [Cancer Res 2009;69(23):8996–9002]