bluuebunny/crossref_metadata_2025 huggingface dataset:
UK National Audit of Sexual History-taking: Clinic policies audit
Authors: McClean H , Carne C , Bhaduri S , Gokhale R , Sethi G , Daniels D
Published: April 2009

Provision of a confidential, private environment for sexual history-taking was provided in almost all clinics. However, less than half of the clinics had a policy displayed about their confidentiality policy in waiting areas, although more had this available by other means. About two-thirds of clinic information/advertising literature included information about the need to take a sexual history. Sixty percent of clinics assessed clinician communication skills as part of service quality. Most clinics had policies relating to patients whose first language is not English, but only around half of clinics had policies for hearing difficulties and learning difficulties. Policies are also lacking in some clinics for documentation of the offer of chaperones and assessment of the competency of under-16-year-olds to consent to history-taking and examination.
Nigeria's Energy Challenge and Power Development: The Way Forward
Authors: Ajayi Oluseyi O , Ajanaku Kolawole O
Published: April 2009

The ever increasing demand and meager supply of energy in Nigeria has been a great challenge to her development. This situation is becoming critical, with increasing population not balanced by an adequate energy development programme. The incessant power generation failure has grossly affected the economy, seriously slowing down development in rural and sub-rural settlements, with present energy policy mainly benefiting urban dwellers. Globally, energy projections stipulate that between 2002 and 2025, global energy needs may rise by over 34%, with that of developing nations doubling this percentage. A robust solution must be found to end the nation's energy crises. This Viewpoint compares the energy potential of Nigeria with the challenges faced. Nigeria receives a huge amount of solar radiation, has abundant wind energy resources, and large deposits of fossil fuel, as well as enormous hydro-power resources from Niger and Benue Rivers. However, of these about 80% of hydro-power remains untapped, the total 5.5KW-hr/m 2 /day of solar radiation is not utilized and wind energy resources remain unexploited. The solution lies in creating a mixed supply of energy in which as yet untapped renewable resources are combined with abundant non-renewable fossil fuel, including the massive quantities of gas wasted from crude oil exploitation.
Asian versus Global Strategies for Energy Fairness and Reduced Carbon Footprint — The Promise of the CDM
Authors: Wood David , Giri Jagdish P. N. , Mokhatab Saeid
Published: April 2009

Access to plentiful supplies of affordable energy is a key requirement for sustainable economic and social development in all emerging nations, and nowhere more so than in Asia. Global primary energy demand is expected in the reference scenario of the International Energy Agency (IEA) to increase by 1.6% per annum from 2004 to 2030, growing from 11.2 billion tones of oil equivalent (btoe) to 17.1 btoe in 2030, more than a 50% increase in total (IEA World Energy Outlook-WEO, 2006). 70% of this increase in energy demand is forecast to come from developing countries with 48.9% coming from developing nations in Asia (including China 30% and India 9.0%) with populations and economies growing much faster than OECD nations, shifting the focus of global energy demand to Asia. About 50% of the increase in global primary energy use is for electricity generation and one-fifth to meet transportation mainly in form of oil-based fuels.

The fossil fuels (oil, gas and coal) in the International Energy Agency's (IEA's) reference scenario continue to dominate primary energy supply over the next 25 years. Available fossil fuel reserves are just about adequate to meet that demand growth, but many doubt that they will be adequate to sustain energy demand growth much beyond 2030.

Such projections raise several concerns, including:

sufficient long-term energy supply, because of the finite nature of fossil fuel reserves; investment strategies to develop suitable and sustainable future energy infrastructure; environmental and climatic issues associated with the resulting carbon and other greenhouse gas (GHG) emissions from fossil fuel usage; increased competition for diminishing fossil fuel reserves; unequal access of the world's population to adequate energy supplies.

The Clean Development Mechanism (CDM) is a provision of the Kyoto Protocol to The United Nations Framework Convention on Climate Change (UNCCC) that offers a new pathway to encourage technology transfer, promote sustainable development in host countries, reduce greenhouse gases (GHG) emissions and assist Annex B countries (developed countries listed in Annex B of the Kyoto Protocol) to cost-effectively meet their commitments under the Kyoto Protocol.
Energy Efficiency: Temporal and Geographical Trends in Europe
Authors: Stead Dominic
Published: April 2009

Pan-European opinion surveys are carried out regularly in all European member states on behalf of the European Commission. From time to time, these ‘Eurobarometer’ surveys focus on energy related issues. This paper draws on three such surveys across a period of almost 20 years (1984, 1993 and 2002) in order to examine temporal trends in individual actions and intentions concerning energy efficiency across European member states. The main focus is on broad energy efficiency measures and the differences in stated actions and intentions over time and between countries. The paper examines whether actions and intentions differ according to socio-economic factors such as age, gender and education, and whether these differences are stable over time. Levels of public support for different types of energy efficiency instruments are also examined. The paper indicates that reported actions concerning energy efficiency have remained relatively stable over time in most European countries but intentions to do more have declined. Socio-economic variables such as age, gender and education appear to influence actions and intentions to save energy, suggesting that there is a social divide regarding energy conservation. Evidence suggests that many Europeans believe that they have already done what they can in terms of reducing their own energy consumption.
Basic Considerations for Loudness-Based Analysis of Room Impulse Responses
Authors: Lee Doheon , Cabrera Densil
Published: April 2009

Room impulse responses (RIRs) are used to characterise the acoustical conditions inside sound-critical rooms such as auditoria. The analysis of RIRs typically involves octave-band filtering, with parameters such as reverberation time, early decay time, temporal energy ratios and spatial parameters derived from this. This paper explores the potential for applying auditory models for the analysis of RIRs – incorporating auditory temporal integration (and masking), auditory filterbank analysis, and loudness calculation. The purpose of this is to produce analysis results that are closely related to the sound experienced by listeners. A preliminary step for such analysis is to filter RIRs so that their power spectrum is similar to that of typical material that would be listened to in the rooms (e.g. music or speech), and this paper proposes a music filter suitable for orchestral music, derived from long term power spectra of anechoic music recordings. Dynamic loudness analysis of RIRs yields loudness decay functions that are approximately exponential, which should provide a useful analogy with conventional analysis methods applied to RIRs.
Predicting the Sound Insulation of Walls
Authors: Davy John L.
Published: April 2009

Between 1990 and 1998, the author published five conference papers which described the gradual development of a simple theoretical model for predicting the sound insulation of building partitions. The first aim was to extend Sharp's model for cavity walls to cavities without sound absorption. The second aim was to remove the reported over prediction of Sharp's model for cavity walls. The third aim was to explain the five decibel empirical correction in Sharp's model for stud walls. The fourth aim was to produce a more theoretically valid model than Gu and Wang's steel stud wall model. Although the simple theoretical model has been reasonably successful, several concerns have since arisen. This paper describes how these concerns have been addressed and gives the current version of this theoretical model for predicting sound insulation. The theoretical model is compared with a number of experimental measurements and produces reasonable agreement.
Field Airborne Sound Insulation of Party Walls: A Means of Prediction Based on Statistical Analysis
Authors: Sullivan Michael , Beresford Tim , Finley Richard , Warren Thomas , Malone Jim
Published: April 2009

This review presents airborne noise test results collected over the last eight years during the Auckland apartment boom and aims to improve the industry's information base when considering the difference between walls of known laboratory performance and the measured field performance for the same nominal wall construction. Statistical analysis of the field results collected for various drywall constructions is presented in STC, R′w and DnT, w criteria with subsequent guidance when establishing and negotiating suitable on-site project criterion for multi-level construction contracts. Probabilities of achievement of various ratings are provided based on four projects using three wall types. Given the desire within the New Zealand industry to offer an upgrade on the existing site rating of FSTC 50, the authors suggest an R′w rating in the low 50 dB range is appropriate and achievable.
The C-terminal domains of human TNRC6A, TNRC6B, and TNRC6C silence bound transcripts independently of Argonaute proteins
Authors: Lazzaretti Daniela , Tournier Isabelle , Izaurralde Elisa
Published: April 2009

Proteins of the GW182 family are essential components of the miRNA pathway in animal cells. Vertebrate genomes encode three GW182 paralogs (TNRC6A, TNRC6B, and TNRC6C), which may be functionally redundant. Here, we show that the N-terminal GW-repeat-containing regions of all three TNRC6s interact with the four human Argonaute proteins (AGO1–AGO4). We also show that TNRC6A, TNRC6B, and TNRC6C silence the expression of bound mRNAs. This activity is mediated by their C-terminal silencing domains, and thus, is independent of the interaction with AGO1–AGO4. Silencing by TNRC6A, TNRC6B, and TNRC6C is effected by changes in protein expression and mRNA stability that can, in part, be attributed to deadenylation. Our findings indicate that TNRC6A, TNRC6B, and TNRC6C are recruited to miRNA targets through an interaction between their N-terminal domain and an Argonaute protein; the TNRC6s then promote translational repression and/or degradation of miRNA targets through a C-terminal silencing domain.
Hepatitis After Intravenous Injection of Sublingual Buprenorphine in Acute Hepatitis C Carriers: Report of Two Cases of Disappearance of Viral Replication After Acute Hepatitis
Authors: Peyrière Hélène , Tatem Ludmilla , Bories Camille , Pageaux Georges-Philippe , Blayac Jean-Pierre , Larrey Dominique
Published: April 2009

Objective

To report 2 cases of acute hepatitis related to intravenous administration of buprenorphine in hepatitis C–infected patients.

Case Summary

Two patients, aged 33 and 50 years, respectively, who were hepatitis C virus (HCV) carriers were treated with sublingual buprenorphine 8 mg/day for addiction. Several years after initiation of buprenorphine, they were hospitalized because of clinical hepatitis with jaundice that developed after intravenous injection of buprenorphine. Serum alanine aminotransferase rose to 100 times the upper limit of normal (ULN) in the first patient and to 21 times the ULN in the second. As cofactors, the first patient had consumed alcohol, and the second patient took aspirin 600 mg in addition to the injection of buprenorphine 20 mg 4 days before the onset of jaundice. After stopping the intravenous injections, both patients continued sublingual buprenorphine therapy, with no relapse of hepatitis. Interestingly, in these 2 patients, buprenorphine-induced hepatitis was followed by the disappearance of HCV RNA.

Discussion

Most cases of hepatotoxicity related to buprenorphine have occurred in hepatitis C–infected patients. The main mechanism for buprenorphine-induced hepatitis is a mitochondrial defect, exacerbated by cofactors with additional potential to induce mitochondria dysfunction (eg, HCV, alcohol, concomitant medications). According to the Naranjo probability scale, buprenorphine was found to be the probable cause of acute hepatitis in both patients. In addition, we assessed the relationship between intravenous buprenorphine and acute hepatitis using 2 scales for causality assessment of hepatotoxicity (the Council for International Organizations of Medical Sciences scale and the Maria & Victorino scale). The diagnosis of intravenous buprenorphine-induced hepatitis was classified as probable in both cases. In addition, these 2 cases illustrate that acute hepatitis in a carrier of chronic HCV may occasionally facilitate the clearance of virus.

Conclusions

Although buprenorphine is well tolerated when used at recommended sublingual doses, patients should be informed about the risk of acute hepatitis with misuse of the drug by the intravenous route. These cases illustrate that, in carriers of chronic HCV, acute hepatitis may modify the host's immunotolerance and facilitate clearance of the virus.
A Night in the Hospital: A Patient'sView
Authors: Van Eron-Sherman Kathleen
Published: April 2009

Hospital patients come in contact with a wide variety of equipment that is designed to administer health care as well as to make their stay more comfortable. Unfortunately, these devices are not always designed with patients in mind. This article presents a patient's perspective regarding her interactions with various products and how they may increase potential risks, such as falls, injury, contamination, discomfort, interrupted sleep, and false alarms to nurses.
Calling 911: Emergency Medical Services in Need of Human Factors
Authors: Feufel Markus A. , Lippa Katherine D. , Klein Helen Altman
Published: April 2009

Emergency medical services (EMS) play an important role in community health care systems. Paramedics provide basic life support, deliver babies, and transport critical patients to the hospital, among other services. We observed EMS units in action to learn about their underlying human factors/ergonomics (HF/E) and found that equipment and organizational systems were often difficult to use or poorly suited to task demands. Although HF/E professionals have the knowledge and tools to improve patient safety and occupational health, HF/E research on EMS is scarce. Our observations provide a systems overview pointing to needed improvements in equipment, decision making, and organizational coordination.
Nucleus Accumbens Deep Brain Stimulation Produces Region-Specific Alterations in Local Field Potential Oscillations and Evoked ResponsesIn Vivo
Authors: McCracken Clinton B. , Grace Anthony A.
Published: April 2009

Deep brain stimulation of the nucleus accumbens (NAC) region is an effective therapeutic avenue for several psychiatric disorders that are not responsive to traditional treatment strategies. Nonetheless, the mechanisms by which DBS achieves therapeutic effects remain unclear. We showed previously that high-frequency (HF) NAC DBS suppressed pyramidal cell firing and enhanced slow local field potential (LFP) oscillations in the orbitofrontal cortex (OFC) via antidromic activation of corticostriatal recurrent inhibition. Using simultaneous multisite LFP recordings in urethane-anesthetized rats, we now show that NAC DBS delivered for 90 min at high or low frequency (LF) selectively affects spontaneous and evoked LFP oscillatory power and coherence within and between the medial prefrontal cortex (mPFC), lateral OFC, mediodorsal thalamus (MD), and NAC. Compared with LF or sham DBS, HF DBS enhanced spontaneous slow oscillations and potentiated evoked LFP responses only in OFC. HF DBS also produced widespread increases in spontaneous beta and gamma power and enhanced coherent beta activity between MD and all other regions. In contrast, LF DBS elevated theta power in MD and NAC. Analysis of acute NAC-induced oscillations showed that HF DBS increased and LF DBS decreased induced relative gamma coherence compared with sham DBS. These data suggest that HF (therapeutic) and LF (possibly deleterious) NAC DBS produce distinct region-specific and frequency band-specific changes in LFP oscillations. NAC DBS may achieve therapeutic effects by enhancing rhythmicity and synchronous inhibition within and between afferent structures, thereby normalizing function of a neural circuit that shows aberrant activity in obsessive-compulsive disorder and depression.
Brain Injury Does Not Alter the Intrinsic Differentiation Potential of Adult Neuroblasts
Authors: Liu Fang , You Yan , Li Xiaosu , Ma Tong , Nie Yanzhen , Wei Bin , Li Tiejun , Lin Huanbing , Yang Zhengang
Published: April 2009

Neuroblasts produced by the neural stem cells of the adult subventricular zone (SVZ) migrate into damaged brain areas after stroke or other brain injuries, and previous data have suggested that they generate regionally appropriate new neurons. To classify the types of neurons produced subsequent to ischemic injury, we combined BrdU or virus labeling with multiple neuronal markers to characterize new cells at different times after the induction of stroke. We show that SVZ neuroblasts give rise almost exclusively to calretinin-expressing cells in the damaged striatum, resulting in the accumulation of these cells during long term recovery after stroke. The vast majority of SVZ neuroblasts as well as newly born young and mature neurons in the damaged striatum constitutively express the transcription factor Sp8, but do not express transcription factors characteristic of medium-sized spiny neurons, the primary striatal projection neurons lost after stroke. Our results suggest that adult neuroblasts do not alter their intrinsic differentiation potential after brain injury.
Fundamental Contribution by the Basolateral Amygdala to Different Forms of Decision Making
Authors: Ghods-Sharifi Sarvin , St. Onge Jennifer R. , Floresco Stan B.
Published: April 2009

Impairments in decision making about risks and rewards have been observed in patients with amygdala damage. Similarly, lesions of the basolateral amygdala (BLA) in rodents disrupts cost/benefit decision making, reducing preference for larger rewards obtainable after a delay or considerable physical effort. We assessed the effects of inactivation of the BLA on risk- and effort-based decision making, using discounting tasks conducted in an operant chamber. Separate groups of rats were trained on either a risk- or effort-discounting task, consisting of four blocks of 10 free-choice trials. Selection of one lever always delivered a smaller reward (one or two pellets), whereas responding on the other delivered a larger, four pellet reward. For risk discounting, the probability of receiving the larger reward decreased across trial blocks (100–12.5%), whereas on the effort task, the larger reward was delivered after a ratio of presses that increased across blocks (2–20). Infusions of GABA agonists baclofen/muscimol into the BLA disrupted risk discounting, inducing a risk-averse pattern of choice, and increased response latencies and trial omissions, most prominently during trial blocks that provided the greatest uncertainty about the most beneficial course of action. Similar inactivations also increased effort discounting, reducing the preference for larger yet more costly rewards, even when the relative delays to reward delivery were equalized across response options. These findings point to a fundamental role for the BLA in different forms of cost/benefit decision making, facilitating an organism's ability to overcome a variety of costs (work, uncertainty, delays) to promote actions that may yield larger rewards.
Rett Syndrome Astrocytes Are Abnormal and Spread MeCP2 Deficiency through Gap Junctions
Authors: Maezawa Izumi , Swanberg Susan , Harvey Danielle , LaSalle Janine M. , Jin Lee-Way
Published: April 2009

MECP2, an X-linked gene encoding the epigenetic factor methyl-CpG-binding protein-2, is mutated in Rett syndrome (RTT) and aberrantly expressed in autism. Most children affected by RTT are heterozygousMecp2−/+females whose brain function is impaired postnatally due to MeCP2 deficiency. While prior functional investigations of MeCP2 have focused exclusively on neurons and have concluded the absence of MeCP2 in astrocytes, here we report that astrocytes express MeCP2, and MeCP2 deficiency in astrocytes causes significant abnormalities in BDNF regulation, cytokine production, and neuronal dendritic induction, effects that may contribute to abnormal neurodevelopment. In addition, we show that the MeCP2 deficiency state can progressively spread at least in part via gap junction communications between mosaicMecp2−/+astrocytes in a novel non-cell-autonomous mechanism. This mechanism may lead to the pronounced loss of MeCP2 observed selectively in astrocytes in mouseMecp2−/+brain, which is coincident with phenotypic regression characteristic of RTT. Our results suggest that astrocytes are viable therapeutic targets for RTT and perhaps regressive forms of autism.
Selective Increase in Representations of Sounds Repeated at an Ethological Rate
Authors: Kim Heesoo , Bao Shaowen
Published: April 2009

Exposure to sounds during early development causes enlarged cortical representations of those sounds, leading to the commonly held view that the size of stimulus representations increases with stimulus exposure. However, representing stimuli based solely on their prevalence may be inefficient, because many frequent environmental sounds are behaviorally irrelevant. Here, we show that cortical plasticity depends not only on exposure time but also on the temporal modulation rate of the stimulus set. We examined cortical plasticity induced by early exposure to 7 kHz tone pips repeated at a slow (2 Hz), fast (15 Hz), or ethological (6 Hz) rate. Certain rat calls are modulated near 6 Hz. We found that spectral representation of 7 kHz increased only in the ethological-rate-reared animals, whereas improved entrainment of cortical neurons was seen in animals reared in the slow- and fast-rate condition. This temporal rate dependence of spectral plasticity may serve as a filtering mechanism to selectively enlarge representations of species-specific vocalizations. Furthermore, our results indicate that spectral and temporal plasticity can be separately engaged depending on the statistical properties of the input stimuli.
Phase-Resetting Curves Determine Synchronization, Phase Locking, and Clustering in Networks of Neural Oscillators
Authors: Achuthan Srisairam , Canavier Carmen C.
Published: April 2009

Networks of model neurons were constructed and their activity was predicted using an iterated map based solely on the phase-resetting curves (PRCs). The predictions were quite accurate provided that the resetting to simultaneous inputs was calculated using the sum of the simultaneously active conductances, obviating the need for weak coupling assumptions. Fully synchronous activity was observed only when the slope of the PRC at a phase of zero, corresponding to spike initiation, was positive. A novel stability criterion was developed and tested for all-to-all networks of identical, identically connected neurons. When the PRC generated usingN− 1 simultaneously active inputs becomes too steep, the fully synchronous mode loses stability in a network ofNmodel neurons. Therefore, the stability of synchrony can be lost by increasing the slope of this PRC either by increasing the network size or the strength of the individual synapses. Existence and stability criteria were also developed and tested for the splay mode in which neurons fire sequentially. Finally,N/Msynchronous subclusters ofMneurons were predicted using the intersection of parameters that supported both between-cluster splay and within-cluster synchrony. Surprisingly, the splay mode between clusters could enforce synchrony on subclusters that were incapable of synchronizing themselves. These results can be used to gain insights into the activity of networks of biological neurons whose PRCs can be measured.
Sleep Promotes the Neural Reorganization of Remote Emotional Memory
Authors: Sterpenich Virginie , Albouy Geneviève , Darsaud Annabelle , Schmidt Christina , Vandewalle Gilles , Dang Vu Thien Thanh , Desseilles Martin , Phillips Christophe , Degueldre Christian , Balteau Evelyne , Collette Fabienne , Luxen André , Maquet Pierre
Published: April 2009

Sleep promotes memory consolidation, a process by which fresh and labile memories are reorganized into stable memories. Emotional memories are usually better remembered than neutral ones, even at long retention delays. In this study, we assessed the influence of sleep during the night after encoding onto the neural correlates of recollection of emotional memories 6 months later. After incidental encoding of emotional and neutral pictures, one-half of the subjects were allowed to sleep, whereas the others were totally sleep deprived, on the first postencoding night. During subsequent retest, functional magnetic resonance imaging sessions taking place 3 d and 6 months later, subjects made recognition memory judgments about the previously studied and new pictures. Between these retest sessions, all participants slept as usual at home. At 6 month retest, recollection was associated with significantly larger responses in subjects allowed to sleep than in sleep-deprived subjects, in the ventral medial prefrontal cortex (vMPFC) and the precuneus, two areas involved in memory retrieval, as well as in the extended amygdala and the occipital cortex, two regions the response of which was modulated by emotion at encoding. Moreover, the functional connectivity was enhanced between the vMPFC and the precuneus, as well as between the extended amygdala, the vMPFC, and the occipital cortex in the sleep group relative to the sleep-deprived group. These results suggest that sleep during the first postencoding night profoundly influences the long-term systems-level consolidation of emotional memory and modifies the functional segregation and integration associated with recollection in the long term.
Biochemical Support for the “Threshold” Theory of Creativity: A Magnetic Resonance Spectroscopy Study
Authors: Jung Rex E. , Gasparovic Charles , Chavez Robert S. , Flores Ranee A. , Smith Shirley M. , Caprihan Arvind , Yeo Ronald A.
Published: April 2009

A broadly accepted definition of creativity refers to the production of something both novel and useful within a given social context. Studies of patients with neurological and psychiatric disorders and neuroimaging studies of healthy controls have each drawn attention to frontal and temporal lobe contributions to creativity. Based on previous magnetic resonance (MR) spectroscopy studies demonstrating relationships between cognitive ability and concentrations ofN-acetyl-aspartate (NAA), a common neurometabolite, we hypothesized that NAA assessed in gray and white matter (from a supraventricular slab) would relate to laboratory measures of creativity. MR imaging and divergent thinking measures were obtained in a cohort of 56 healthy controls. Independent judges ranked the creative products of each participant, from which a “Composite Creativity Index” (CCI) was created. Different patterns of correlations between NAA and CCI were found in higher verbal ability versus lower verbal ability participants, providing neurobiological support for a critical “threshold” regarding the relationship between intelligence and creativity. To our knowledge, this is the first report assessing the relationship between brain chemistry and creative cognition, as measured with divergent thinking, in a cohort comprised exclusively of normal, healthy participants.
Caenorhabditis elegansInnexins Regulate Active Zone Differentiation
Authors: Yeh Edward , Kawano Taizo , Ng Sharon , Fetter Richard , Hung Wesley , Wang Ying , Zhen Mei
Published: April 2009

In a genetic screen for active zone defective mutants inCaenorhabditis elegans, we isolated a loss-of-function allele ofunc-7, a gene encoding an innexin/pannexin family gap junction protein. Innexin UNC-7 regulates the size and distribution of active zones atC. elegansneuromuscular junctions. Loss-of-function mutations in another innexin, UNC-9, cause similar active zone defects asunc-7mutants. In addition to presumptive gap junction localizations, both UNC-7 and UNC-9 are also localized perisynaptically throughout development and required in presynaptic neurons to regulate active zone differentiation. Our mosaic analyses, electron microscopy, as well as expression studies suggest a novel and likely nonjunctional role of specific innexins in active zone differentiation in addition to gap junction formations.
NAD+Activates KNaChannels in Dorsal Root Ganglion Neurons
Authors: Tamsett Thomas J. , Picchione Kelly E. , Bhattacharjee Arin
Published: April 2009

Although sodium-activated potassium channels (KNa) have been suggested to shape various firing patterns in neurons, including action potential repolarization, their requirement for high concentrations of Na+to gate conflicts with this view. We characterized KNachannels in adult rat dorsal root ganglion (DRG) neurons. Using immunohistochemistry, we found ubiquitous expression of the Slack KNachannel subunit in small-, medium-, and large-diameter DRG neurons. Basal KNachannel activity could be recorded from cell-attached patches of acutely dissociated neurons bathed in physiological saline, and yet in excised inside-out membrane patches, the Na+EC50for KNachannels was typically high, ∼50 mm. In some cases, however, KNachannel activity remained considerable after initial patch excision but decreased rapidly over time. Channel activity was restored in patches with high Na+. The channel rundown after initial excision suggested that modulation of channels might be occurring through a diffusible cytoplasmic factor. Sequence analysis indicated that the Slack channel contains a putative nicotinamide adenine dinucleotide (NAD+)-binding site; accordingly, we examined the modulation of native KNaand Slack channels by NAD+. In inside-out-excised neuronal patch recordings, we found a decrease in the Na+EC50for KNachannels from ∼50 to ∼20 mmwhen NAD+was included in the perfusate. NAD+also potentiated recombinant Slack channel activity. NAD+modulation may allow KNachannels to operate under physiologically relevant levels of intracellular Na+and hence provides an explanation as to how KNachannel can control normal neuronal excitability.
Neuroprotection by the NR3A Subunit of the NMDA Receptor
Authors: Nakanishi Nobuki , Tu Shichun , Shin Yeonsook , Cui Jiankun , Kurokawa Toru , Zhang Dongxian , Chen H.-S. Vincent , Tong Gary , Lipton Stuart A.
Published: April 2009

Hyperactivation of NMDA-type glutamate receptors (NMDARs) results in excitotoxicity, contributing to damage in stroke and neurodegenerative disorders. NMDARs are generally comprised of NR1/NR2 subunits but may contain modulatory NR3 subunits. Inclusion of NR3 subunits reduces the amplitude and dramatically decreases the Ca2+permeability of NMDAR-associated channels in heterologous expression systems and in transgenic mice. Since excessive Ca2+influx into neurons is a crucial step for excitotoxicity, we asked whether NR3A subunits are neuroprotective. To address this question, we subjected neurons genetically lacking NR3A to various forms of excitotoxic insult. We found that cultured neurons prepared from NR3A knock-out (KO) mice displayed greater sensitivity to damage by NMDA application than wild-type (WT) neurons.In vivo, neonatal, but not adult, WT mice contain NR3A in the cortex, and neonatal NR3A KO mice manifested more damage than WT after hypoxia–ischemia. In adult retina, one location where high levels of NR3A normally persist into adulthood, injection of NMDA into the eye killed more retinal ganglion cells in adult NR3A KO than WT mice. These data suggest that endogenous NR3A is neuroprotective. We next asked whether we could decrease excitotoxicity by overexpressing NR3A. We found that cultured neurons expressing transgenic (TG) NR3A displayed greater resistance to NMDA-mediated neurotoxicity than WT neurons. Similarlyin vivo, adult NR3A TG mice subjected to focal cerebral ischemia manifested less damage than WT mice. These data suggest that endogenous NR3A protects neurons, and exogenously added NR3A increases neuroprotection and could be potentially exploited as a therapeutic.
Polarity-Sensitive Modulation of Cortical Neurotransmitters by Transcranial Stimulation
Authors: Stagg Charlotte J. , Best Jonathan G. , Stephenson Mary C. , O'Shea Jacinta , Wylezinska Marzena , Kincses Z. Tamas , Morris Peter G. , Matthews Paul M. , Johansen-Berg Heidi
Published: April 2009

Transcranial direct current stimulation (tDCS) modulates cortical excitability and is being used for human studies more frequently. Here we probe the underlying neuronal mechanisms by measuring polarity-specific changes in neurotransmitter concentrations using magnetic resonance spectroscopy (MRS). MRS provides evidence that excitatory (anodal) tDCS causes locally reduced GABA while inhibitory (cathodal) stimulation causes reduced glutamatergic neuronal activity with a highly correlated reduction in GABA, presumably due to the close biochemical relationship between the two neurotransmitters.
Dopamine Modulation of GABA Tonic Conductance in Striatal Output Neurons
Authors: Janssen Megan J. , Ade Kristen K. , Fu Zhanyan , Vicini Stefano
Published: April 2009

We previously reported greater GABAAreceptor-mediated tonic currents in D2+ striatopallidal than D1+ striatonigral medium spiny neurons (MSNs) are mediated by α5-subunit-containing receptors. Here, we used whole-cell recordings in slices from bacterial artificial chromosome transgenic mice to investigate the link between subunit composition, phosphorylation, and dopamine receptor activation. Whole-cell recordings in slices from δ-subunit knock-out mice demonstrate that while MSNs in wild-type mice do express δ-subunit-containing receptors, this receptor subtype is not responsible for tonic conductance observed in the acute slice preparation. We assessed the contribution of the β1- and β3-subunits expressed in MSNs by their sensitivity to etomidate, an agonist selective for β2- or β3-subunit-containing GABAAreceptors. Although etomidate produced substantial tonic current in D2+ neurons, there was no effect in D1+ neurons. However, with internal PKA application or dopamine modulation, D1+ neurons expressed tonic conductance and responded to etomidate application. Our results suggest that distinct phosphorylation of β3-subunits may cause larger tonic current in D2+ striatopallidal MSNs, and proper intracellular conditions can reveal tonic current in D1+ cells.
Frontal Eye Field Neurons with Spatial Representations Predicted by Their Subcortical Input
Authors: Crapse Trinity B. , Sommer Marc A.
Published: April 2009

The frontal eye field (FEF) is a cortical structure involved in cognitive aspects of eye movement control. Neurons in the FEF, as in most of cerebral cortex, primarily represent contralateral space. They fire for visual stimuli in the contralateral field and for saccadic eye movements made to those stimuli. Yet many FEF neurons engage in sophisticated functions that require flexible spatial representations such as shifting receptive fields and vector subtraction. Such functions require knowledge about all of space, including the ipsilateral hemifield. How does the FEF gain access to ipsilateral information? Here, we provide evidence that one source of ipsilateral information may be the opposite superior colliculus (SC) in the midbrain. We physiologically identified neurons in the FEF that receive input from the opposite SC, same-side SC, or both. We found a striking structure–function relationship: the laterality of the response field of an FEF neuron was predicted by the laterality of its SC inputs. FEF neurons with input from the opposite SC had ipsilateral fields, whereas neurons with input from the same-side SC had contralateral fields. FEF neurons with input from both SCs had lateralized fields that could point in any direction. The results suggest that signals from the two SCs provide each FEF with information about all of visual space, a prerequisite for higher level sensorimotor computations.
Long-Term Plasticity in Mouse Sensorimotor Circuits after Rhythmic Whisker Stimulation
Authors: Mégevand Pierre , Troncoso Edgardo , Quairiaux Charles , Muller Dominique , Michel Christoph M. , Kiss Jozsef Z.
Published: April 2009

Mice actively explore their environment by rhythmically sweeping their whiskers. As a consequence, neuronal activity in somatosensory pathways is modulated by the frequency of whisker movement. The potential role of rhythmic neuronal activity for the integration and consolidation of sensory signals, however, remains unexplored. Here, we show that a brief period of rhythmic whisker stimulation in anesthetized mice resulted in a frequency-specific long-lasting increase in the amplitude of somatosensory-evoked potentials in the contralateral primary somatosensory (barrel) cortex. Mapping of evoked potentials and intracortical recordings revealed that, in addition to potentiation in layers IV and II/III of the barrel cortex, rhythmic whisker stimulation induced a decrease of somatosensory-evoked responses in the supragranular layers of the motor cortex. To assess whether rhythmic sensory input-based plasticity might arise in natural settings, we exposed mice to environmental enrichment. We found that it resulted in somatosensory-evoked responses of increased amplitude, highlighting the influence of previous sensory experience in shaping sensory responses. Importantly, environmental enrichment-induced plasticity occluded further potentiation by rhythmic stimulation, indicating that both phenomena share common mechanisms. Overall, our results suggest that natural, rhythmic patterns of whisker activity can modify the cerebral processing of sensory information, providing a possible mechanism for learning during sensory perception.
Der echte Historiker als richtiger Kerl. Neue Veröffentlichungen (nicht nur) zum 200. Geburtstag von Johann Gustav DroysenThe authentic historian as a true guy. Current publications (not only) on the occasion of the 200th birthday of Johann Gustav Droysen
Authors: Welskopp Thomas
Published: April 2009

Zugleich Besprechung von: Wilfried Nippel, Johann Gustav Droysen. Ein Leben zwischen Wissenschaft und Politik
Vitamin D therapy in patients with primary hyperparathyroidism and hypovitaminosis D
Authors: Tucci J R
Published: April 2009

Objective

To determine whether vitamin D repletion of patients with primary hyperparathyroidism (PHPT) and vitamin D deficiency or insufficiency (hypovitaminosis D) has deleterious clinical and/or biochemical effects.

Design

Prospective audit of the effect of vitamin D repletion on biochemical data in 56 patients with PHPT. Patients were treated with 50 000 units of vitamin D2 weekly for 8 weeks with biochemical measurements at 5 and 10 weeks, and subsequently after 12 weeks on 800 units of vitamin D3 daily, and in those with hypovitaminosis D after 12 weeks of up to 100 000 units of vitamin D2 monthly.

Methods

Serum calcium, albumin, phosphorus, 25-OHD, intact parathyroid hormone (PTH) and urine calcium/creatinine (Ca/Cr) ratios were measured before and during vitamin D therapy.

Results

Patients treated with 50 000 units of vitamin D2 weekly for 8 weeks resulted in a significant increase in serum 25-OHD levels from 36.4 to 89.4 nmol/l at 5 weeks (P<0.0001) and 88.6 nmol/l at 10 weeks (P<0.0001). There were no significant changes in serum calcium. At 10 weeks, there was a non-significant decrease in serum PTH and in urine Ca/Cr ratios. None of the patients developed any calcium-related adverse events. Subsequently, patients with subnormal 25-OHD levels on 800 units of vitamin D daily were treated for the next 12 weeks with up to 100 000 units of vitamin D2 monthly with normalization of serum 25-OHD in all but 4 patients.

Conclusion

These data fail to demonstrate any adverse effects of vitamin D repletion in PHPT.
Improving glucocorticoid replacement therapy using a novel modified-release hydrocortisone tablet: a pharmacokinetic study
Authors: Johannsson Gudmundur , Bergthorsdottir Ragnhildur , Nilsson Anna G , Lennernas Hans , Hedner Thomas , Skrtic Stanko
Published: April 2009

Background

Endogenous plasma cortisol levels have a well-defined circadian rhythm. The aim of this project is to develop a once daily oral dual-release formulation for cortisol replacement therapy that mimics the diurnal variation in the plasma cortisol profile.

Objective

To determine single-dose plasma pharmacokinetics and dose-proportionality of oral 5 and 20 mg dual-release hydrocortisone tablets in healthy volunteers. In addition, the effect of food intake was investigated for the 20 mg dose.

Design

A randomised, controlled, two-way cross-over, double-blind, phase I study of oral hydrocortisone (modified (dual) release; 5 and 20 mg) with an open food-interaction arm.

Methods

The single dose pharmacokinetic studies were performed with betamethasone suppression. The two first study days were blinded and randomised between morning administration of 5 and 20 mg tablet in a fasting state. The third day was open with a 20 mg tablet taken 30 min after a high-calorie, high-fat meal. The plasma samples were assayed using both a validated LC–MS/MS and an immunoassay. The plasma pharmacokinetic variables were calculated using non-compartmental data analysis.

Results

The time to reach a clinically significant plasma concentration of cortisol (>200 nmol/l) was within 20 min and a mean peak of 431 (s.d. 126) nmol/l was obtained within 50 min after administration of the 20 mg tablet. Plasma cortisol levels remained above 200 nmol/l for around 6 h thereafter and all plasma concentrations 18–24 h after intake were below 50 nmol/l. In the fed state the time to reach 200 nmol/l was delayed by 28 and 9 min based on LC–MS/MS and immunoassay, respectively. The 5 and 20 mg tablets produced an increase in plasma exposure of cortisol that was not fully dose proportional.

Conclusion

The dual release hydrocortisone tablet with once-daily administration produced a diurnal plasma cortisol profile mimicking the physiological serum cortisol profile.
Childhood and adolescent obesity and adult mortality: a systematic review of cohort studies
Authors: Adami Fernando , Vasconcelos Francisco de Assis Guedes de
Published: April 2009

This systematic review addressed cohort studies on obesity in childhood and adolescence and adult mortality, published from January 1990 to March 2007. We searched the PubMed database with the following uniterms: obesity, mortality, child, adolescent; obesity and mortality; overweight and mortality. References were also analyzed. The age limit was 2 to 18 years. Quality of the articles was assessed, and eight were identified and reviewed. All used weight and stature for determination of obesity, and seven used body mass index (BMI). The quality score varied from 9 to 17. Evidence of association between obesity in childhood and adolescence and adult mortality should be viewed with caution. Use of BMI and potential confounders were discussed. Further research is needed to analyze the relationship between childhood and adolescent obesity and adult mortality.
Performance of cylindrical leaf wetness duration sensors in a tropical climate condition
Authors: Santos Eduardo Alvarez , Sentelhas Paulo Cesar , Gillespie Terry James , Lulu Jorge
Published: April 2009

Leaf wetness duration (LWD) measurements are required for disease warning in several agricultural systems, since it is an important variable for the diagnose of plant disease epidemiology. The cylindrical sensor is an inexpensive and simple electronic LWD sensor initially designed to measure this variable for onions, however some studies show that it may be helpful for standard measurements in weather stations and also for different crops. Therefore, the objective of this study was to assess their performance under tropical climate conditions, in Brazil, having as standard measurements those obtained by flat plate sensors, which have presented very good performance when compared with visual observations. Before field assessments, all LWD sensors used in our study (flat plates and cylinders) were white latex painted and submitted to a heat treatment. Laboratory tests were performed in order to determine the resistance threshold for the sensor to be considered wet and the time response of the sensors to wetness. In the field, all cylindrical sensors were initially deployed horizontally 30-cm above a turfgrass surface in order to assess the variability among them with respect to LWD measurements. The variability among the horizontal cylindrical sensors was reduced by using a specific resistance threshold for each sensor. The mean coefficient of variation (CV) of LWD data measured by the cylindrical sensors was 9.7%. After that, the cylindrical sensors were deployed at five different angles: 0º, 15º, 30º, 45º, and 60º. Data of measurements made at these angles were compared with the standard measurement, obtained by flat plate sensors at the same height and installed at 45º. The deployment angle had no systematic effect on LWD measurements for the local tropical conditions, since the correlations between flat plate and elevated cylinder measurements were very high (R² > 0.91), which differed from the results obtained under temperate climatic conditions, where LWD measured by cylinders were two hours longer than by flat plate sensors.
Climatic risk for potato late blight in the Andes region of Venezuela
Authors: Garcia Beatriz Ibet Lozada , Sentelhas Paulo Cesar , Tapia Luciano Roberto , Sparovek Gerd
Published: April 2009

Potato is an important crop for Venezuelan agriculture. However, its production is highly affected by late blight (Phytophtora infestans), since weather is commonly favorable for this disease. The aim of this study was to determine the sowing dates of low climatic risk for potato late blight in the Andes region of Venezuela, with an agrometeorological disease model and geographical information system (GIS) tools. The disease model used in this study was developed by Hyre (1954) which requires daily rainfall and temperature data which were obtained from 106 weather stations, located at the States of Mérida, Táchira, and Trujillo, for a period of 31 years. Hyre's model was applied for all stations obtainig the following variables: number of disease favorable days (DFD); number of periods with ten consecutive favorable days, named disease occurrence (O); and number of sprays required for disease control (S). These variables were used to calculate the Maximum Risk Index (MRI) and the Probable Risk Index (PRI). The interpolation of these indexes was used to generate maps of climatic risk for each sowing date. MRI and PRI maps showed that the highest climatic risk for potato late blight occurrence was during the rainy season, from May to July, decreasing during dry and mid seasons. However, high disease risk variability was observed for all seasons. The maps generated by coupling an agrometeorological disease model and GIS also show that in great part of potato areas of Andes region the number of sprays could be reduced, but more investigations about that must be carried out.