bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibiotic Prophylaxis in Acute Necrotizing Pancreatitis Revisited
Authors: Segarra-Newnham Marisel , Hough Augustus
Published: August 2009

Objective:

To review studies of antibiotic prophylaxis in acute necrotizing pancreatitis published in the last decade and update recommendations.

Data Sources:

A search of PubMed (1998–July 2009) was conducted using the terms necrotizing pancreatitis, antibiotics, prophylaxis, and treatment. Clinical studies, meta-analyses, and review articles published in English were included. Additional references were obtained from article bibliographies. Randomized trials published before 1998 were included if indicated.

Study Selection and Data Extraction:

Relevant studies or meta-analyses on antibiotic prophylaxis since our previous review in 1998 were evaluated; older data were included if still relevant.

Data Synthesis:

Since our previous review, 4 more randomized trials, including 2 double-blind trials, have been conducted. The blinded studies found no significant difference in mortality with antibiotic prophylaxis compared with placebo, while the unblinded studies found a significant decrease in infections. Given these disparate results, available guidelines and meta-analyses provide different conclusions, usually based on exclusion or inclusion of a single trial. Based on all available data, antibiotic prophylaxis should not be used in patients with necrotizing pancreatitis. Instead, a more measured, on-demand use of antibiotics is preferred. Antibiotics should be added if signs and symptoms of infection are present (eg, fever, leukocytosis, positive results of cultures). Given improvements in intensive care and nutritional support, recent trials have found a lower incidence of infected necrotizing pancreatitis than before. Therefore, future trials are likely to need higher numbers of patients.

Conclusions:

Use of antibiotic prophylaxis for patients with necrotizing pancreatitis is not indicated, based on 2 blinded trials. Instead, on-demand use of antibiotics appears to be appropriate. Given progress in intensive care and the high crossover rate in studies, the need for antibiotic prophylaxis may continue to be debated for decades.
α2-Receptor Agonists for Treatment and Prevention of Iatrogenic Opioid Abstinence Syndrome in Critically Ill Patients
Authors: Honey Brooke L , Benefield Russell J , Miller Jamie L , Johnson Peter N
Published: August 2009

Objective:

To review the literature regarding the use of α2-agonists in the treatment and prevention of iatrogenic opioid abstinence syndrome (IOAS) in critically ill patients.

Data Sources:

Primary literature was identified through a search of MEDLINE (1950–June 2009), EMBASE (1988–June 2009), International Pharmaceutical Abstracts (1970–June 2009), and the Cochrane Library (1996–June 2009), using the names of individual α2-agonists and the following key words: children, opioid withdrawal, opioid, and adult. Relevant abstracts from the Society of Critical Care Medicine, reference citations from selected articles, and manufacturers’ product information were also reviewed.

Study Selection and Data Extraction:

All English-language articles identified from the data sources were evaluated. Three retrospective studies and 6 case reports/series representing 44 patients were included for analysis.

Data Synthesis:

Central α2-agonists are thought to minimize symptoms of IOAS by decreasing presynaptic outflow of catecholamines. Successful use of clonidine and dexmedetomidine for management of IOAS has been reported. Lofexidine, an α2-agonist not yet approved in the US, may offer similar withdrawal symptom relief but has yet to be studied in the intensive care setting. Although the quality of studies identified was limited, preliminary evidence does provide some support for the use of transdermal clonidine and injectable dexmedetomidine in the treatment and prevention of IOAS. These agents were shown to facilitate discontinuation of opioids and to minimize withdrawal symptoms with few reported adverse events.

Conclusions:

Central α2-agonists appear to be effective and safe second-line agents for treatment and prevention of IOAS. Further studies should be conducted to determine their role in the therapy of patients with IOAS.
Use of Subcutaneous Lepirudin in an Obese Surgical Intensive Care Unit Patient with Heparin Resistance
Authors: Inman Kristin R , Gerlach Anthony T
Published: August 2009

Objective:

To report the use of subcutaneous lepirudin in an obese patient with heparin resistance.

Case Summary:

A 34-year-old morbidly obese male (weight 145 kg) presented with hypoxia on postoperative day 1 following a sigmoid colectomy. A continuous unfractionated heparin infusion was started for a suspected pulmonary embolism. Doses were escalated without therapeutic activated partial thromboplastin time (aPTT) response and an antithrombin (AT) tevei was obtained. The AT level was reported as 78% (reference range 85–120%). Computed tomography angiography ruled out pulmonary embolism and lepirudin 50 mg administered subcutaneously twice daily was started (serum creatinine 1.3 mg/dL) for prevention of venous thromboembolism. The resulting aPTT values were therapeutic (63 and 60 sec, reference range 24–34, therapeutic heparin range 55–85). The dose was adjusted to 25 mg twice daily, aPTT values were 35 and 48 seconds. His serum creatinine increased to 1.6 mg/dL and minor bleeding was noted. The dose was decreased to 25 mg once daily, with resulting aPTT values of 31, 39, and 41 seconds. The patient was discharged to home without development of venous thromboembolism, as confirmed by duplex ultrasonography.

Discussion:

Commonly administered anticoagulants, such as unfractionated heparin, low-molecular-weight heparins, and fondaparinux, exert their effect by complexing with AT and thrombin (Factor IIa), activating AT and preventing thrombin from exerting coagulation effect. Without AT present, these drugs have little effect on inhibiting the coagulation cascade. Lepirudin is a synthetic irreversible direct thrombin inhibitor and does not rely on AT to exert its anticoagulation action. It can be given subcutaneously and is eliminated primarily by the kidneys, Dosage adjustments for both renal function and obesity need to be considered and aPTT should be monitored.

Conclusions:

In obese patients or those with heparin resistance, subcutaneous lepirudin can be monitored and the regimen adjusted based on aPTT values. Further studies are warranted to maximize efficacy and define dosing.
Regional Citrate Anticoagulation for PrismaFlex Continuous Renal Replacement Therapy
Authors: Burry Lisa D , Tung David D , Hallett David , Bailie Toni , Carvalhana Virginia , Lee David , Ramganesh Steve , Richardson Robert , Mehta Sangeeta , Lapinsky Stephen E
Published: August 2009

Background:

Since Mehta et al. reported the first successful use of regional citrate anticoagulation (RCA) for continuous renal replacement therapy (CRRT) in 1990, RCA is increasingly used for CRRT because it provides filter patency with minimal risk of bleeding. However, RCA has been associated with significant metabolic complications including hypocalcemia, hypernatremia, metabolic alkalosis, and citrate toxicity.

Objective:

To describe our experience with a newly implemented RCA protocol with acid citrate dextrose formula A (ACD-A) and intravenous calcium gluconate, for use with PrismaFlex CRRT in critically ill patients with acute kidney injury.

Methods:

A retrospective chart review was conducted from May 1, 2006, until May 1, 2007, in a 16-bed medical-surgical university-affiliated intensive care unit. Data collected included dialysis filter life, patient and circuit metabolic parameters, and units of packed red blood cells transfused.

Results:

Forty-eight patients received dialysis with citrate (n = 178 fitters). Circuit clotting occurred in 24% of all filters. Mean ± SD filter life was 38.4 ± 25.9 hours, and filter survival at 48 hours was 38.2%. Persistent metabolic alkalosis while on CRRT was identified in 6 of 45 (13.3%) patients. Mild hypocalcemia (ionized calcium <3.6 mg/dL) occurred in 11 (23%) patients, but no patient had an ionized calcium level less than 2.8 mg/dL. Six patients, 3 with acute leukemia, required transfusion of 2 or more units of packed red blood cells in 24 hours.

Conclusions:

We found that anticoagulation of PrismaFlex CRRT with ACD-A and intravenous calcium gluconate provided reasonable filter patency, but with minor metabolic complications. Close monitoring of electrolyte and acid–base balance is required to minimize metabolic derangements.
Sensitivity to differences between enjoyment and non‐enjoyment smiles in children with autism spectrum disorder
Authors: Blampied Meredith , Johnston Lucy , Miles Lynden , Liberty Kathleen
Published: August 2009

The sensitivity of male children (5–15 years) with and without autism spectrum disorder (ASD) to the affective state of others was tested using an emotion recognition task. Only children without ASD could reliably differentiate between enjoyment and non‐enjoyment smiles. Results are considered in terms of the social impairments of children with ASD.
Anger and childhood sexual abuse are independently associated with irritable bowel syndrome
Authors: Beesley Helen , Rhodes Jonathan , Salmon Peter
Published: August 2009

Objectives. Irritable bowel syndrome (IBS) presents in the absence of identifiable organic pathology. Clinical and research literature has suggested that both childhood abuse and anger are linked to functional gastrointestinal conditions including IBS. The present study tested the predictions that IBS patients, when compared to patients with an organic bowel disease (Crohn's disease), have higher levels of trait and suppressed anger, and that these mediate the link between abuse and IBS.

Design. The study was a cross‐sectional multivariate comparison between groups of patients with IBS and Crohn's disease.

Method. Levels of self‐reported trait and suppressed anger and recalled childhood abuse in patients with IBS (N =75) or Crohn's disease (N =76) were compared, using self‐report questionnaires and controlling for other psychological characteristics (anxiety, depression, and dissociation).

Results. Trait and suppressed anger were greater in IBS patients, and differences in trait anger remained significant after controlling for other psychological variables. Childhood sexual abuse was more prevalent in IBS than Crohn's disease patients but was unrelated to trait anger.

Conclusions. Higher levels of anger characterize IBS patients when compared to an organic bowel disease group, but do not explain the link between childhood abuse and IBS.
Shining light on supramolecular assemblies
Authors: Darcos Vincent , Huang Chih-Hao , McClenaghan Nathan , Molard Yann , Tucker James H. R. , Vida Pol Yolanda , Perez-Inestrosa Ezequiel , Bassani Dario M.
Published: August 2009

The organizational effect induced by noncovalent interactions such as hydrogen-bonding (H-B) and metal ion complexation on photoinduced processes is discussed. These include the intermolecular photodimerization of cinnamates, which is shown to occur under topochemical control within the supramolecular assemblies, and the intramolecular photodimerization of a bis-anthracene receptor where photoregulation of the recognition event is achieved. Progress in using supramolecular interactions toward the preparation of assemblies promoting charge separation and charge transport in all-organic photovoltaic devices rests on the preparation of materials that are adapted to the requirements of solid-state devices.
Interaction of UV radiation with DNA helices
Authors: Markovitsi Dimitra
Published: August 2009

Recent experimental and theoretical investigations dealing with model DNA double helices, composed of either adenine–thymine (A–T) or guanine–cytosine (G–C) base pairs, and G quadruplexes shed some light on the excited states populated by photon absorption and their relaxation, energy transfer among bases, and one-photon ionization. These studies revealed that the Franck–Condon excited states of DNA helices cannot be considered as the sum of their monomeric constituents because electronic coupling induces delocalization of the excitation over a few bases. Energy transfer takes place via intraband scattering in less than 100 fs. The fluorescence lifetimes of DNA helices detected by fluorescence upconversion and corresponding mainly to ππ* transitions are longer than that of an equimolar mixture of nucleotides; the only exception was observed for alternating G–C polymers. Moreover, nanosecond flash photolysis experiments showed that organization of bases within single and double helices may lead to a lowering of their ionization potential. Finally, the first determination regarding the time-scale needed for the formation of T dimers, the (6–4) adducts, was determined for the single strand (dT)20.
Modification of molecular organization of polymers by gas sorption: Thermodynamic aspects and industrial applications
Authors: Boyer Séverine A. E. , Yamada Takeshi , Yoshida Hirohisa , Grolier Jean-Pierre E.
Published: August 2009

In polymer science, gas–polymer interactions play a central role for the development of new polymeric structures for specific applications. This is typically the case for polymer foaming and for self-assembling of nanoscale structures where the nature of the gas and the thermodynamic conditions are essential to control. An important applied field where gas sorption in polymers has to be documented through intensive investigations concerns the (non)-controlled solubilization of light gases in the polymers serving, for example, in the oil industry for the transport of petroleum fluids. An experimental set-up coupling a vibrating-wire (VW) detector and apVTtechnique has been used to simultaneously evaluate the amount of gas entering a polymer under controlled temperature and pressure and the concomitant swelling of the polymer. Scanning transitiometry has been used to determine the interaction energy during gas sorption in different polymers; the technique was also used to determine the thermophysical properties of polymers submitted to gas sorption. The role of the pressurizing fluid has been documented in terms of the influence of pressure, temperature, and nature of the fluid.
Bicanonical map of surfaces with χ = 1 fibered by hyperelliptic curves of genus 3
Authors: Borrelli Giuseppe
Published: August 2009

We investigate surfaces of general type S with χ(S) = 1 that admit a fibration ƒ : S → ℙ1 whose general fiber is a hyperelliptic curve of genus 3. We show that the bicanonical map of S factors through a generically finite rational map of degree two onto a ruled surface.

Together with a previous result, this yields a characterization of surfaces with χ = 1 whose bicanonical map factors through a 2 : 1 map onto a ruled surface in terms of the existence of fibrations of small genus.
Presynaptic G-Protein-Coupled Receptors Dynamically Modify Vesicle Fusion, Synaptic Cleft Glutamate Concentrations, and Motor Behavior
Authors: Gerachshenko Tatyana , Schwartz Eric , Bleckert Adam , Photowala Huzefa , Seymour Andrew , Alford Simon
Published: August 2009

Understanding how neuromodulators regulate behavior requires investigating their effects on functional neural systems, but also their underlying cellular mechanisms. Utilizing extensively characterized lamprey motor circuits, and the unique access to reticulospinal presynaptic terminals in the intact spinal cord that initiate these behaviors, we investigated effects of presynaptic G-protein-coupled receptors on locomotion from the systems level, to the molecular control of vesicle fusion. 5-HT inhibits neurotransmitter release via a Gβγ interaction with the solubleN-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex that promotes kiss-and-run vesicle fusion. In the lamprey spinal cord, we demonstrate that, although presynaptic 5-HT receptors inhibit evoked neurotransmitter release from reticulospinal command neurons, their activation does not abolish locomotion but rather modulates locomotor rhythms. Liberation of presynaptic Gβγ causes substantial inhibition of AMPA receptor-mediated synaptic responses but leaves NMDA receptor-mediated components of neurotransmission mostly intact. Because Gβγ binding to the SNARE complex is displaced by Ca2+-synaptotagmin binding, 5-HT-mediated inhibition displays Ca2+sensitivity. We show that, as Ca2+accumulates presynaptically during physiological bouts of activity, 5-HT/Gβγ-mediated presynaptic inhibition is relieved, leading to a frequency-dependent increase in synaptic concentrations of glutamate. This frequency-dependent phenomenon mirrors a shift in the vesicle fusion mode and a recovery of AMPA receptor-mediated EPSCs from inhibition without a modification of NMDA receptor EPSCs. We conclude that activation of presynaptic 5-HT G-protein-coupled receptors state-dependently alters vesicle fusion properties to shift the weight of NMDA versus AMPA receptor-mediated responses at excitatory synapses. We have therefore identified a novel mechanism in which modification of vesicle fusion modes may profoundly alter locomotor behavior.
Executive Function and Attention Are Preserved in Older Surgically Menopausal Monkeys Receiving Estrogen or Estrogen Plus Progesterone
Authors: Voytko Mary Lou , Murray Rhonda , Higgs Casey J.
Published: August 2009

Animal models of menopause have been used to further define the cognitive processes that respond to hormone therapy and to investigate parameters that may influence the cognitive effects of estrogen. Many investigations in animals have focused on memory; however, the effects of hormone therapy on executive function and attention processes have not been well studied. Thus, the purpose of this set of investigations was to assess the effects of estrogen therapy alone or with progesterone on executive and attention processes in middle-aged ovariectomized monkeys. Monkeys were preoperatively trained on a modified version of the Wisconsin card sort task and on a visual cued reaction time task. Hormone therapy was initiated at the time of ovariectomy and cognitive function was reassessed at 2, 12, and 24 weeks postoperatively. Relative to monkeys receiving either of the estrogen therapies, monkeys receiving placebo were impaired in their ability to shift a cognitive set in the Wisconsin card sort task and were impaired in shifting visuospatial attention in the visual cued reaction time task. Our findings are consistent with clinical studies that indicate that hormone therapy can improve executive function and attention processes in postmenopausal women.
Intracellular Chloride Ions Regulate the Time Course of GABA-Mediated Inhibitory Synaptic Transmission
Authors: Houston Catriona M. , Bright Damian P. , Sivilotti Lucia G. , Beato Marco , Smart Trevor G.
Published: August 2009

The time-dependent integration of excitatory and inhibitory synaptic currents is an important process for shaping the input–output profiles of individual excitable cells, and therefore the activity of neuronal networks. Here, we show that the decay time course of GABAergic inhibitory synaptic currents is considerably faster when recorded with physiological internal Cl−concentrations than with symmetrical Cl−solutions. This effect of intracellular Cl−is due to a direct modulation of the GABAAreceptor that is independent of the net direction of current flow through the ion channel. As a consequence, the time window during which GABAergic inhibition can counteract coincident excitatory inputs is much shorter, under physiological conditions, than that previously measured using high internal Cl−. This is expected to have implications for neuronal network excitability and neurodevelopment, and for our understanding of pathological conditions, such as epilepsy and chronic pain, where intracellular Cl−concentrations can be altered.
Spatial Profile and Differential Recruitment of GABABModulate Oscillatory Activity in Auditory Cortex
Authors: Oswald Anne-Marie M. , Doiron Brent , Rinzel John , Reyes Alex D.
Published: August 2009

The interplay between inhibition and excitation is at the core of cortical network activity. In many cortices, including auditory cortex (ACx), interactions between excitatory and inhibitory neurons generate synchronous network gamma oscillations (30–70 Hz). Here, we show that differences in the connection patterns and synaptic properties of excitatory–inhibitory microcircuits permit the spatial extent of network inputs to modulate the magnitude of gamma oscillations. Simultaneous multiple whole-cell recordings from connected fast-spiking interneurons and pyramidal cells in L2/3 of mouse ACx slices revealed that for intersomatic distances <50 μm, most inhibitory connections occurred in reciprocally connected (RC) pairs; at greater distances, inhibitory connections were equally likely in RC and nonreciprocally connected (nRC) pairs. Furthermore, the GABAB-mediated inhibition in RC pairs was weaker than in nRC pairs. Simulations with a network model that incorporated these features showed strong, gamma band oscillations only when the network inputs were confined to a small area. These findings suggest a novel mechanism by which oscillatory activity can be modulated by adjusting the spatial distribution of afferent input.
An Intersegmental Neuronal Architecture for Spinal Wave Propagation under Deletions
Authors: Pérez Toni , Tapia Jesus A. , Mirasso Claudio R. , García-Ojalvo Jordi , Quevedo Jorge , Cuellar Carlos A. , Manjarrez Elias
Published: August 2009

Recent studies have established and characterized the propagation of traveling electrical waves along the cat spinal cord during scratching, but the neuronal architecture that allows for the persistence of such waves even during periods of absence of bursts of motoneuron activity (deletions) is still unclear. Here we address this problem both theoretically and experimentally. Specifically, we monitored during long lasting periods of time the global electrical activity of spinal neurons during scratching. We found clear deletions of unaltered cycle in extensor activity without associated deletions of the traveling spinal wave. Furthermore, we also found deletions with a perturbed cycle associated with a concomitant absence of the traveling spinal wave. Numerical simulations of an asymmetric two-layer model of a central-pattern generator distributed longitudinally along the spinal cord qualitatively reproduce the sinusoidal traveling waves, and are able to replicate both classes of deletions. We believe these findings shed light into the longitudinal organization of the central-pattern generator networks in the spinal cord.
γ-Secretase Inhibition Reduces Spine DensityIn Vivovia an Amyloid Precursor Protein-Dependent Pathway
Authors: Bittner Tobias , Fuhrmann Martin , Burgold Steffen , Jung Christian K. E. , Volbracht Christiane , Steiner Harald , Mitteregger Gerda , Kretzschmar Hans A. , Haass Christian , Herms Jochen
Published: August 2009

Alzheimer's disease (AD) represents the most common age-related neurodegenerative disorder. It is characterized by the invariant accumulation of the β-amyloid peptide (Aβ), which mediates synapse loss and cognitive impairment in AD. Current therapeutic approaches concentrate on reducing Aβ levels and amyloid plaque load via modifying or inhibiting the generation of Aβ. Based onin vivotwo-photon imaging, we present evidence that side effects on the level of dendritic spines may counteract the beneficial potential of these approaches. Two potent γ-secretase inhibitors (GSIs), DAPT (N-[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycinet-butyl ester) and LY450139 (hydroxylvaleryl monobenzocaprolactam), were found to reduce the density of dendritic spines in wild-type mice. In mice deficient for the amyloid precursor protein (APP), both GSIs had no effect on dendritic spine density, demonstrating that γ-secretase inhibition decreases dendritic spine density via APP. Independent of the effects of γ-secretase inhibition, we observed a twofold higher density of dendritic spines in the cerebral cortex of adult APP-deficient mice. This observation further supports the notion that APP is involved in the modulation of dendritic spine density—shown here for the first timein vivo.
Evidence for Developmentally Regulated Local Translation of Odorant Receptor mRNAs in the Axons of Olfactory Sensory Neurons
Authors: Dubacq Caroline , Jamet Sophie , Trembleau Alain
Published: August 2009

Odorant receptor mRNAs are transported within axons of olfactory sensory neurons that project into the olfactory bulb. Odorant receptor proteins have been identified along the distal part of these axons, which raises the possibility of their local synthesis in axons. We took advantage of the anatomical separation between the olfactory mucosa (which contains the sensory neuron cell bodies) and the bulb (which contains sensory axons but no sensory neuron cell bodies) to address this issue using a quantitative biochemical approach. Combining a method that separates polysome-associated mRNAs from untranslated mRNAs with a reverse transcription–quantitative PCR approach, we demonstrate that significant amounts of odorant receptor mRNAs are associated with polysomes in the sensory axons of the adult mouse bulb. We thus provide the first evidence for local synthesis of odorant receptor proteins in these axons. Interestingly, the rate of odorant receptor mRNA translation in axons is significantly greater during periods when the proportion of immature axons is higher (i.e., at postnatal day 4 or on regeneration after chemical lesion in adults). In contrast, the olfactory marker protein mRNA, which is restricted to mature axons, is translated at a low and constant level. Overall, we demonstrate that translation levels of odorant receptor mRNAs in axons are developmentally regulated, and positively correlated to the stage of axonal growth into the bulb. Given the established function of odorant receptors in the axonal wiring of sensory projections, we propose that this regulated axonal translation may play a role in the development and maintenance of the glomerular array.
Sonic Hedgehog Pathway Activation Is Induced by Acute Brain Injury and Regulated by Injury-Related Inflammation
Authors: Amankulor Nduka M. , Hambardzumyan Dolores , Pyonteck Stephanie M. , Becher Oren J. , Joyce Johanna A. , Holland Eric C.
Published: August 2009

The adult mammalian brain responds to injury by activating a program of cell proliferation during which many oligodendrocyte precursors, microglia, and some astrocytes proliferate. Another common response to brain injury is the induction of reactive gliosis, a process whereby dormant astrocytes undergo morphological changes and alter their transcriptional profiles. Although brain injury-induced reactive gliosis is concurrent with the proliferation of surrounding cells, a functional relationship between reactive gliosis and this cell proliferation has not been clearly demonstrated. Here, we show that the mitogen sonic hedgehog (SHH) is produced in reactive astrocytes after injury to the cerebral cortex and participates in regulating the proliferation of Olig2-expressing (Olig2+) cells after brain injury. Using a cortical freeze injury to induce reactive gliosis in a Gli–luciferase reporter mouse, we show that the SHH pathway is maximally active 3 d after brain injury and returns to baseline levels by 14 d. SHH expression parallels Gli activation and localizes to glial fibrillary acidic protein-expressing reactive astrocytes. Inhibition of the SHH pathway with cyclopamine blocks the Gli response and significantly reduces both the proliferating and overall number of Olig2+cells in the injured cortex. To provide mechanistic insight into SHH pathway activation in astrocytes, we show that proinflammatory stimuli activate SHH-expressing reactive astrocytes, whereas inhibition of inflammation-induced reactive gliosis by macrophage depletion abolishes SHH activation after brain injury and dampens cell proliferation after injury. Our data describes a unique reactive astrocyte-based, SHH-expressing niche formed in response to injury and inflammation that regulates the proliferation of Olig2+cells.
Subtype Specification of GABAergic Amacrine Cells by the Orphan Nuclear Receptor Nr4a2/Nurr1
Authors: Jiang Haisong , Xiang Mengqing
Published: August 2009

In the mammalian retina, amacrine cells (ACs) contain numerous subtypes with extremely diverse morphologies and physiological functions. To date, how these subtypes arise during retinogenesis remains largely unknown at the molecular level. The orphan nuclear receptor Nr4a2 plays an essential role in specifying ventral midbrain dopaminergic neurons, and its mutations are associated with familial Parkinson's disease. Here we show that Nr4a2 is also critically involved in the specification of AC subtype identity. During mouse retinogenesis, Nr4a2 is expressed in a subset of postmitotic GABAergic ACs and their precursors. Its targeted inactivation results in the loss of a subpopulation of GABAergic ACs that include all dopaminergic and p57Kip2+neurons as well as a simultaneous increase of calbindin+ACs. Misexpressed Nr4a2 can promote GABAergic AC differentiation and repress calbindin+ACs, whereas its dominant-negative form has the ability to suppress the GABAergic AC fate. Moreover, the expression of Nr4a2 is positively regulated by Foxn4 and negatively controlled by Brn3b, two retinogenic factors previously shown to promote and suppress GABAergic ACs, respectively. These data suggest that Nr4a2 is both necessary and sufficient to confer AC precursors with the identity of a GABAergic AC phenotype, and that it may network with multiple other retinogenic factors to ensure proper specification and differentiation of AC neurotransmitter subtypes.
Association between hepatic steatosis and serum IGF1 and IGFBP-3 levels in a population-based sample
Authors: Völzke Henry , Nauck Matthias , Rettig Rainer , Dörr Marcus , Higham Claire , Brabant Georg , Wallaschofski Henri
Published: August 2009

Context

It is assumed that hepatic steatosis plays a role in the development and progression of the metabolic syndrome and its cardiovascular sequelae. Low serum IGF1 levels might mediate these associations.

Objectives

The aims of this study were i) to investigate the associations of hepatic steatosis with serum IGF1 and IGF binding protein-3 (IGFBP-3) levels using ultrasound and serum alanine aminotransaminase (ALT) data to define hepatic steatosis, and ii) to analyze the specific role of alcohol consumption in this context.

Design

We analyzed data from the population-based Study of Health in Pomerania.

Methods

We used data from 3863 subjects (1971 women) aged 20–79 years who had no history of viral hepatitis, liver cirrhosis, or malignant diseases. Liver hyperechogenicity was diagnosed using ultrasound. Serum IGF1 and IGFBP-3 levels were determined by automated two-site chemiluminescence immunoassays.

Results

Hyperechogenic liver pattern was associated with low serum IGF1 levels and low serum IGF1/IGFBP-3 ratios. The lowest serum IGF1 and IGF1/IGFBP-3 values and highest IGFBP-3 levels were present in subjects who had a hyperechogenic liver pattern and increased serum ALT levels. All of these associations were independent of alcohol consumption.

Conclusions

Our data show that hepatic steatosis is associated with low serum IGF1 levels. This association is independent of alcohol consumption.
Melatonin regulates delayed embryonic development in the short-nosed fruit bat, Cynopterus sphinx
Authors: Banerjee Arnab , Meenakumari K J , Udin S , Krishna A
Published: August 2009

The aim of the present study was to evaluate the seasonal variation in serum melatonin levels and their relationship to the changes in the serum progesterone level, ovarian steroidogenesis, and embryonic development during two successive pregnancies of Cynopterus sphinx. Circulating melatonin concentrations showed two peaks; one coincided with the period of low progesterone synthesis and delayed embryonic development, whereas the second peak coincided with regressing corpus luteum. This finding suggests that increased serum melatonin level during November–December may be responsible for delayed embryonic development by suppressing progesterone synthesis. The study showed increased melatonin receptors (MTNR1A and MTNR1B) in the corpus luteum and in the utero–embryonic unit during the period of delayed embryonic development. The in vitro study showed that a high dose of melatonin suppressed progesterone synthesis, whereas a lower dose of melatonin increased progesterone synthesis by the ovary. The effects of melatonin on ovarian steroidogenesis are mediated through changes in the expression of peripheral-type benzodiazepine receptor, P450 side chain cleavage enzyme, and LH receptor proteins. This study further showed a suppressive impact of melatonin on the progesterone receptor (PGR) in the utero–embryonic unit; this effect might contribute to delayed embryonic development in C. sphinx. The results of the present study thus suggest that a high circulating melatonin level has a dual contribution in retarding embryonic development in C. sphinx by impairing progesterone synthesis as well as by inhibiting progesterone action by reducing expression of PGR in the utero–embryonic unit.
Regulatory Mechanisms for Adipose Tissue M1 and M2 Macrophages in Diet-Induced Obese Mice
Authors: Fujisaka Shiho , Usui Isao , Bukhari Agussalim , Ikutani Masashi , Oya Takeshi , Kanatani Yukiko , Tsuneyama Koichi , Nagai Yoshinori , Takatsu Kiyoshi , Urakaze Masaharu , Kobayashi Masashi , Tobe Kazuyuki
Published: August 2009

OBJECTIVE

To characterize the phenotypic changes of adipose tissue macrophages (ATMs) under different conditions of insulin sensitivity.

RESEARCH DESIGN AND METHODS

The number and the expressions of marker genes for M1 and M2 macrophages from mouse epididymal fat tissue were analyzed using flow cytometry after the mice had been subjected to a high-fat diet (HFD) and pioglitazone treatment.

RESULTS

Most of the CD11c-positive M1 macrophages and the CD206-positive M2 macrophages in the epididymal fat tissue were clearly separated using flow cytometry. The M1 and M2 macrophages exhibited completely different gene expression patterns. Not only the numbers of M1 ATMs and the expression of M1 marker genes, such as tumor necrosis factor-α and monocyte chemoattractant protein-1, but also the M1-to-M2 ratio were increased by an HFD and decreased by subsequent pioglitazone treatment, suggesting the correlation with whole-body insulin sensitivity. We also found that the increased number of M2 ATMs after an HFD was associated with the upregulated expression of interleukin (IL)-10, an anti-inflammatory Th2 cytokine, in the adipocyte fraction as well as in adipose tissue. The systemic overexpression of IL-10 by an adenovirus vector increased the expression of M2 markers in adipose tissue.

CONCLUSIONS

M1 and M2 ATMs constitute different subsets of macrophages. Insulin resistance is associated with both the number of M1 macrophages and the M1-to-M2 ratio. The increased expression of IL-10 after an HFD might be involved in the increased recruitment of M2 macrophages.
No Effect of the Altered Peptide Ligand NBI-6024 on β-Cell Residual Function and Insulin Needs in New-Onset Type 1 Diabetes
Authors: Walter Markus , Philotheou Areti , Bonnici François , Ziegler Anette-G. , Jimenez Roland ,   on behalf of the NBI-6024 Study Group
Published: August 2009

OBJECTIVE

This randomized, four-arm, placebo-controlled, dose-ranging phase 2 trial was conducted to determine whether repeated subcutaneous injections of the altered peptide ligand, NBI-6024, designed to inhibit autoreactive T-cells, improves β-cell function in patients with recently diagnosed type 1 diabetes.

RESEARCH DESIGN AND METHODS

A total of 188 patients, aged 10–35 years, with recently diagnosed type 1 diabetes were randomly assigned for a treatment consisting of the subcutaneous administration of placebo or 1, 0.5, or 0.1 mg NBI-6024 at baseline, weeks 2 and 4, and then monthly until month 24. Fasting, peak, and area under the curve (AUC) C-peptide concentrations during a 2-h mixed-meal tolerance test were measured at 3-month intervals during treatment. Immune function parameters (islet antibodies and CD4 and CD8 T-cells) were also studied.

RESULTS

The mean peak C-peptide concentration at 24 months after study entry showed no significant difference between the groups treated with 0.1 mg (0.59 pmol/ml), 0.5 mg (0.57 pmol/ml), and 1.0 mg NBI-6024 (0.48 pmol/ml) and the placebo group (0.54 pmol/ml). Fasting, stimulated peak, and AUC C-peptide concentrations declined linearly in all groups by ∼60% over the 24-month treatment period. The average daily insulin needs at month 24 were also comparable between the four groups. No treatment-related changes in islet antibodies and T cell numbers were observed.

CONCLUSIONS

Treatment with altered peptide ligand NBI-6024 at repeated doses of 0.1, 0.5, or 1.0 mg did not improve or maintain β-cell function.
Carbon sequestration potential of Alnus nepalensis in the mid hill of Nepal: A case study from Kaski district
Authors: Ranabhat S , Awasthi KD , Malla R
Published: August 2009

This study was carried out to analyze the carbon content in different parts of Alnus nepalensis, and to assess the effect of aspect and altitude in the carbon storage in Alnus nepalensis as well as to quantify the total carbon sequestration (stock) in Alnus nepalensis forest in the mid-hills of Kaski District. The inventory for estimating above and below ground biomass of forest was carried out using stratified random sampling technique. The carbon content in different parts of Alnus nepalensis was quantified using combustion method in the laboratory. For determining the soil carbon content, six soil profiles from each aspect were excavated and soil samples were taken from soil profile up to 1 m depth for deep soil and up to bedrock for shallow soils at the interval of 20 cm. Mean carbon content in stem, branches, leaves and bark of Alnus nepalensis were found to be 40.52%, 33%, 9.56% and 16.4%, respectively. Total biomass carbon sequestered in northern aspect was 30.20 t/ha while for southern aspect it was 39.00 t/ha. In both the aspects higher carbon sequestration was observed at an elevation range of 1200-1300m i.e. 34.8 t/ha and 45.6 t/ha in northern and southern aspects, respectively. Soil carbon sequestration in northern and southern aspects was found to be 113.4 t/ha and 169.30 t/ ha, respectively. The total carbon sequestration potential of Alnus nepalensis forest was estimated to be 186.05 t/ha. Key words: Alnus nepalensis, altitude, aspect, carbon sequestration, mid hills   doi: 10.3126/banko.v18i2.2167 Banko Janakari, Vol. 18, No. 2, 3-9
Challenges for service providers in community forestry governance: A case study of a community forest users group in Parbat, Nepal
Authors: Paudel A , Vogel S
Published: August 2009

This study was carried out in Bhodkhore Community Forest Users Group in Parbat district, Nepal with the overall objective to develop a clearer understanding of the challenges for service providers while working towards improving the Community Forestry governance. The primary data were collected through personal interviews, group discussions, key informant interviews and direct observations using a series of questionnaires and check lists. Similarly, the secondary data were gathered from reports and records from Community Forestry User Group and service providers, and from relevant scientific literature. The data were analyzed using qualitative and quantitative tools. The results show that the existing challenges for service providers mainly include financial resource management, time management and inadequate technical support for forest management. Key words: Community Forestry, Governance, Service Providers, Challenges   doi: 10.3126/banko.v18i2.2169 Banko Janakari, Vol. 18, No. 2, 18-24
Exploring the Relationship between Roadway Characteristics and Speed Variation
Authors: Ko Joonho , Guensler Randall , Hunter Michael
Published: August 2009

The degree of roadway service quality can be effectively related to individual vehicles’ degree of speed variation observed over roadway segments. In previous studies, the degree of speed variation, measured from the speed profiles of individual vehicles, has been proposed as a potential traffic parameter that may be effectively used to quantify driver, roadway, and traffic condition interactions. However, these relationships have not yet been extensively investigated because of the difficulty in collecting speed profile data. This study explores the relationship between acceleration noise–a speed variation measure defined as the standard deviation of the acceleration of a vehicle–and roadway characteristics. Data were gathered with the use of instrumented vehicles equipped with global positioning systems. The vehicles travel a freeway corridor over a 3-month period. Utilizing random intercept models that account for correlations from repeated measurements, the effects of roadway characteristics on acceleration noise are examined for each level-of-service condition. For the corridor studied, the results indicate that acceleration noise and thus the traffic conditions experienced by the driver are affected by the number of lanes, the speed limit, the facility type, and, to a lesser degree, by roadway curvature and grade.
Model for Predicting Speed along Horizontal Curves on Two-Lane Highways
Authors: Bonneson James A. , Pratt Michael P.
Published: August 2009

This paper describes the development and calibration of a curve speed prediction model. The model includes variables for curve radius, deflection angle, superelevation rate, and tangent speed. The model is based on the hypothesis that drivers modify their side friction demand because of a desire for both safe and efficient travel. One model component reflects a general desire by motorists to have lower side friction demand on higher speed curves. This trend likely reflects the driver's desire to maintain an acceptable margin of safety against sliding out or rolling over. A second model component reflects a willingness by drivers to tolerate slightly higher side friction demand on sharper curves in an effort to minimize the amount of speed reduction. The increase in side friction demand that a driver accepts is found to be proportional to the energy required to slow the vehicle to the curve speed.
Collision Prediction Models for Three-Dimensional Two-Lane Highways
Authors: Easa Said M. , You Qing Chong
Published: August 2009

Collision prediction models for three-dimensional (3-D) alignments of two-lane rural highways are lacking in the literature. This paper presents such models with vehicle collision data on 5,760 km (3,600 mi) of two-lane rural highways in Washington State collected from 2002 through 2005. Five statistical models were developed for different combinations of 3-D alignments to establish the relationship between collision frequency and the relevant variables. The alignment combinations are (a) horizontal curves combined with crest vertical curves, (b) horizontal curves combined with sag vertical curves, (c) horizontal curves combined with multiple vertical curves, (d) horizontal curves combined with grades of less than 5%, and (e) horizontal curves combined with grades of more than 5%. For each combination, four different statistical techniques were explored: Poisson, negative binomial, zero-inflated Poisson, and zero-inflated negative binomial. For validation, two models were selected and estimated by using the first 3 years of collision data and validated with the last-year data. The results show that the most significant predictors for collisions on horizontal curves on 3-D alignments are the degree of curvature, roadway width (lanes plus shoulders), access density, product of grade value and grade length, road section length, and average annual daily traffic. The results of this study should be useful in evaluating road safety on 3-D alignments and optimizing their design based on the substantive safety approaches.
Prioritizing Access Management Implementation
Authors: Schultz Grant G. , Braley Kordel T. , Boschert Tim
Published: August 2009

Traffic volumes and congestion continue to increase on arterial roads. Safety and performance on those roads are continual concerns. Transportation systems must be evaluated on an ongoing basis to ensure that people and goods can be moved as efficiently and safely as possible. Safety and performance indices provide a method to numerically measure given data about a system so that comparisons and rankings on safety and performance can be made as objectively as possible. One of the sets of tools that have proved successful in improving the safety and efficiency of arterial roads are access management techniques. To determine which roads can most benefit from access management techniques, a prioritization process was developed to guide decision makers in the implementation process. Recommendations were given in the form of a decision tree classifying existing or future road segments into subcategories based on volume, signal spacing, adjacent land use, and other criteria. The objective of this paper is to document the steps followed to develop a performance index-based prioritization process to target arterial roads that would benefit from the implementation of access management techniques. Using the results of the research, decision makers can better determine which sections of roadway may benefit from controlling driveway access, installing raised medians, providing future planning, or looking to a solution other than access management.
Calibration of Mechanistic–Empirical Pavement Design Guide Permanent Deformation Models
Authors: Banerjee Ambarish , Aguiar-Moya José P. , Prozzi Jorge A.
Published: August 2009

The performance models in the Mechanistic–Empirical Pavement Design Guide (MEPDG), developed under NCHRP 1-37A and 1-40D, are calibrated with sections throughout the United States. Hence, it is necessary to calibrate these models for specific states and regional conditions because of the differences in materials, environmental conditions, and construction practices. In general, a pavement design based on the nationally calibrated MEPDG will result in either an overestimate or underestimate of the pavement layer thicknesses because of systematic errors arising from local differences. This deficiency calls for local calibration of the performance models in the MEPDG so that they can be used to design pavements at a regional level. The calibration procedure described in this paper concentrates on finding two bias correction factors for the asphalt concrete (AC) permanent deformation performance model after values derived from expert knowledge have been assumed for the subgrade permanent deformation calibration factors. Pavement data from the Texas Specific Pavement Study (SPS)-1 and SPS-3 experiments of the Long-Term Pavement Performance database were used to run the MEPDG and calibrate the guide to Texas conditions. The regional calibration factors were obtained by minimizing the sum of squared errors between the observed and predicted surface permanent deformation. In this case, a simultaneous joint optimization routine was applied because it was theoretically sound. Finally, an average of the regional calibration coefficients for AC and subgrade permanent deformation was computed to obtain the set of state-default calibration coefficients for Texas.