Preliminary Survey of Ectoparasites and Associated Pathogens from Norway Rats in New York City.

The Norway rat (Rattus norvegicus) is a reservoir of many zoonotic pathogens and lives in close proximity to humans in urban environments. Human infection with rodent-borne disease occurs either directly through contact with a rat or its excreta, or indirectly via arthropod vectors such as fleas and ticks. Here, we report on the diversity and abundance of ectoparasitic arthropod species and associated pathogenic bacteria from 133 Norway rats trapped over a 10-mo period in Manhattan, New York, NY. Norway rats were host to the tropical rat mite [Ornithonyssus bacoti (Hirst)], the spiny rat mite (Laelaps echidnina Berlese), Laelaps nuttalli Hirst, the spined rat louse [Polyplax spinulosa (Burmeister)], and the Oriental rat flea [(Xenopsylla cheopis) (Rothschild)], with an average of 1.7 species per individual. A flea index of 4.1 X. cheopis was determined, whereas previous studies in New York City reported 0.22 fleas per rat. Multiple species of pathogenic Bartonella were identified from Oriental rat fleas that were related to Bartonella tribocorum, Bartonella rochalimae, and Bartonella elizabethae. However, no evidence of Yersinia pestis or Rickettsia spp. infection was detected in fleas. The identification of multiple medically important ectoparasite species in New York City underscores the need for future efforts to fully characterize the diversity and distribution of ectoparasites on Norway rats, and assess the risk to humans of vector-borne disease transmission.

The impact of the pandemic influenza A(H1N1) 2009 virus on seasonal influenza A viruses in the southern hemisphere, 2009.

Data collected over winter 2009 by five World Health Organisation National Influenza Centres in the southern hemisphere were used to examine the circulation of pandemic and seasonal influenza A strains during the first pandemic wave in the southern hemisphere.There is compelling evidence that the pandemic influenza A(H1N1) 2009 virus significantly displaced seasonal influenza A(H1N1) and, to a lesser extent, A(H3N2) viruses circulating in the southern hemisphere. Complete replacement of seasonal influenza A strains, however, was not observed during the first pandemic wave.

Farm economic impacts of bovine Johne's disease in endemically infected Australian dairy herds.

OBJECTIVE: To determine the farm economic impact of bovine Johne's disease (BJD) infection and controls in commercial Victorian dairy herds. DESIGN: Benefit-cost analysis of BJD and various control methods in a Victorian dairy herd. RESULTS: Farm losses from BJD occurred from clinical disease. Clinical cases occur on average in 5-year-old cows, resulting in losses of A$1895 in the year of culling and A$221 in the year preceding culling, giving a total loss of A$2116. Early removal also resulted in loss of future profit equating to A$375 per year. This is the annualised value of foregone future income and costs expressed as a net present value (NPV). The total loss from removal of a clinical case was estimated as A$2491. The average clinical incidence in infected dairy herds prior to entry into the Victorian Bovine Johne's Test-and-Control Program (TCP) was 1.8% and the average Victorian dairy herd size was 262 cows in 2013-14, resulting in annual losses of 4.7 clinical cases if infected and implementing no BJD control. Farm annual loss of profit was estimated as A$11,748 ($44.84 per cow/year). Control of BJD using vaccination, test-and-cull or combined approaches was economical but the cost of implementation in initial years would exceed disease costs. Vaccination-based control provided minimal long-term losses and was the most cost-effective control over a 10-year planning horizon. CONCLUSION: Endemic BJD resulted in modest but persistent losses in typical infected dairy herds. Control of disease using test-and-cull, vaccination or combined test-and-cull with vaccination was cost-effective.

Quantitative effects of some muscarinic agonists on evoked surface-negative field potentials recorded from the guinea-pig olfactory cortex slice.

1. The effects of muscarinic receptor agonists on the electrically-evoked surface-negative field potential (N-wave) were measured in the guinea-pig olfactory cortex slice maintained in vitro. 2. Bath-superfusion of (+/-)-muscarine, acetylcholine (ACh), carbachol (CCh), or methacholine (MCh) (10-200 microM) produced reversible, dose-dependent depressions of the N-wave (ACh and MCh effects were observed in the presence of 10 microM neostigmine). The order of potencies (based on agonist dose causing 50% field depression: IC50) was: ACh greater than or equal to muscarine greater than CCh greater than MCh. All four agonists depressed the field potential by 100% at doses greater than 500 microM. 3. Pilocarpine and bethanechol were weak agonists and only produced measurable effects at high doses (1-2 mM). Neither agonist evoked a maximum response at doses up to 10 mM. 4. The muscarinic ganglion stimulant, McN-A-343 yielded inconsistent results, depressing the field potential in some slices, but having no effect in others. Pre-application of a conditioning dose (100 microM) of McN-A-343 reduced subsequent responses to CCh, suggesting possible partial agonist properties. 5. Oxotremorine (up to 100 microM) did not depress the field potential, but it reversibly antagonized the effects of CCh. 6. It is concluded that reproducible, quantifiable responses to muscarinic agonists can be evoked in the olfactory cortex slice. We suggest this preparation may be useful for conducting pharmacological studies of 'intact' central muscarinic receptors.

A quantitative study of the effects of some muscarinic antagonists on the guinea-pig olfactory cortex slice.

1. Muscarinic depression of the electrically-evoked surface-negative field potential (N-wave) was measured in guinea-pig olfactory cortex slices maintained in vitro. 2. The effects of three muscarinic receptor antagonists, pirenzepine, atropine and gallamine on this muscarinic response were analysed in detail. 3. Pirenzepine was a potent competitive antagonist of carbachol (CCh)-evoked responses. Schild plot analysis yielded a pA2 value of 7.9 (Schild slope constrained to unity). A similar analysis for atropine versus CCh responses gave a pA2 of 8.9. 4. Combination experiments using pirenzepine and atropine produced dose-ratio shifts close to those expected for two antagonists competing for a similar receptor site. 5. Gallamine was only a weak antagonist of responses to CCh. 6. Oxotremorine behaved as a competitive antagonist at this muscarinic receptor (pA2 = 6.1). 7. It is concluded that the presynaptic muscarinic receptor mediating depression of the N-wave in the olfactory cortex slice is of the M1-subtype.

Muscarinic depression of evoked surface-negative field potentials recorded from guinea-pig olfactory cortex in vitro.

The action of some cholinergic drugs has been studied on the field potentials evoked by orthodromic stimulation of the lateral olfactory tract (LOT) in guinea-pig olfactory cortex slices maintained in vitro. A reversible depression of the electrically evoked surface-negative field potential (N-wave) was seen following superfusion of muscarine (10-200 microM) or mixed-agonist choline esters but not nicotinic agonists. This depression was blocked by atropine and pirenzepine, but not d-tubocurarine or by antagonists active at gamma-aminobutyric acid or adenosine receptors. Little effect of muscarinic agonists was observed on the compound action potential recorded from the LOT, or on pial surface DC potential. A possible presynaptic site of action of muscarinic agonists in the olfactory cortex is discussed.

The Zimbabwe Rural Palliative Care Initiative: PCI-Z.

The Zimbabwe Rural Palliative Care Initiative is a program to increase access and expand palliative care in rural Zimbabwe. The goal was to add palliative care to existing home-based care teams comprising indigenous rural volunteers. Palliative care expertise is being developed through training and ongoing mentorship provided by Island Hospice Service, headquartered in the capital city of Harare. Specific outcomes relative to palliative care are reported, using the African Palliative Care Association African Palliative Outcome Scale, the Karnofsky Performance Scale, and a Supervision and Mentorship Checklist. Positive impact is documented, and there is significant opportunity for similar outcomes on a national scale.

Collaborative planning, forecasting, and replenishment.

This article highlights Procter & Gamble's (P&G's) current success and future direction of creating consumer value and improving trading partner relationships through electronic data communication, including the future vision of the company's ultimate supply system and CPFR--Collaborative Planning, Forecasting, and Replenishment.

Actions of endogenous opioids on NMDA receptor-independent long-term potentiation in area CA3 of the hippocampus.

The opioid peptides represent a major class of neurotransmitter in the vertebrate nervous system and are prevalent in the hippocampus. There is considerable interest in the physiological function of the opioids contained in the mossy fiber pathway. The release of opioids from mossy fibers shows a strong frequency dependence. Long-term potentiation (LTP) at this synapse, an NMDA receptor-independent form of LTP, also depends on high-frequency synaptic activity, and this has led to speculation that endogenous opioids may be a critical factor in LTP induction. Previous reports using extracellular recordings have provided evidence for and against a role for opioids in mossy fiber LTP. Using single-cell recording techniques, we have tested the hypothesis that endogenous opioids are required for mossy fiber LTP induction. We recorded from a defined population of synapses that had EPSCs with fast rise times, short latencies, and monophasic decays, consistent with a proximally terminating synapse. The opioid antagonist naloxone prevented mossy fiber LTP in the rat, but had no effect on the commissural/associational system, a nonopioid-containing pathway. The action of naloxone was not mediated through disinhibition because GABAA receptors were pharmacologically blocked in these experiments. We also tested the hypothesis that variations in postsynaptic receptor subtype distribution between species might explain previous controversies regarding the role of endogenous opioids. In contrast to the rat, LTP of the mossy fiber field potential in guinea pig was not blocked by naloxone. Our data suggest that opioids may be the presynaptically released, frequency-dependent, associative factor for mossy fiber LTP induction.

Kinetic properties of two anatomically distinct excitatory synapses in hippocampal CA3 pyramidal neurons.

1. We have investigated the kinetic properties of pharmacologically isolated excitatory synaptic currents in hippocampal CA3 neurons. Two distinct anatomic pathways, the commissural/associational (C/A) and the mossy fiber inputs, were compared to test the hypothesis derived from cable theory that distal inputs have slower kinetics than proximal inputs when measured at the soma. 2. Intracellular recordings were made from adult rat hippocampal slices using a single-electrode voltage clamp and low-resistance microelectrodes. A mixture of 10 microM picrotoxin and 10 microM bicuculine was used to block completely fast GABAergic inhibition. The slow inhibitory input was blocked by intracellular cesium. 3. The mean reversal potential of mossy fiber synaptic currents, -2.8 mV, was not significantly different from that of the C/A synaptic current, -1.4 mV. The mean 10-90% rise time of the mossy-fiber synaptic current [1.7 +/- 0.08 (SE) ms], however, was significantly faster than the C/A synaptic current (3.2 +/- 0.16 ms). Both mossy fiber and C/A synaptic-current decays were fit with a single exponential. The decay time constant of mossy fiber synaptic currents was also faster than that of the C/A excitatory postsynaptic current, 6.5 +/- 0.4 versus 10.1 +/- 0.8 ms. The mossy fiber synaptic current decay time constant showed little voltage dependence. 4. A modified shape index plot of synaptic current rise time versus decay time constant, normalized to membrane time constant, yielded a good linear relation for C/A synapses. A poorer correlation was observed for mossy fiber synapses. 5. Both synaptic currents could be fit by alpha functions. A representative value of alpha for the mossy fiber synapse was 295/s, and for the C/A was 172/s. 6. The rise time of the mossy fiber synaptic potential was significantly faster (5.3 ms) than the C/A (7.5 ms). The decay of both mossy fiber and C/A synaptic potentials was slower than the membrane time constant, suggesting that active currents may contribute to their falling phases. This prolongation was voltage dependent but insensitive to 2-amino-5-phosphonovaleric acid. 7. Our data provide a quantitative comparison of a proximal and a more distal synaptic input to CA3 hippocampal neurons. Distal inputs show slower kinetics than proximal synapses, as predicted. However, the voltage dependence of synaptic potential decays suggests that synaptic integration may be affected by active dendritic conductances.

Voltage- and space-clamp errors associated with the measurement of electrotonically remote synaptic events.

1. The voltage- and space-clamp errors associated with the use of a somatic electrode to measure current from dendritic synapses are evaluated using both equivalent-cylinder and morphologically realistic models of neuronal dendritic trees. 2. As a first step toward understanding the properties of synaptic current distortion under voltage-clamp conditions, the attenuation of step and sinusoidal voltage changes are evaluated in equivalent cylinder models. Demonstration of the frequency-dependent attenuation of voltage in the cable is then used as a framework for understanding the distortion of synaptic currents generated at sites remote from the somatic recording electrode and measured in the voltage-clamp recording configuration. 3. Increases in specific membrane resistivity (Rm) are shown to reduce steady-state voltage attenuation, while producing only minimal reduction in attenuation of transient voltage changes. Experimental manipulations that increase Rm therefore improve the accuracy of estimates of reversal potential for electrotonically remote synapses, but do not significantly reduce the attenuation of peak current. In addition, increases in Rm have the effect of slowing the kinetics of poorly clamped synaptic currents. 4. The effects of the magnitude of the synaptic conductance and its kinetics on the measured synaptic currents are also examined and discussed. The error in estimating parameters from measured synaptic currents is greatest for synapses with fast kinetics and large conductances. 5. A morphologically realistic model of a CA3 pyramidal neuron is used to demonstrate the generality of the conclusions derived from equivalent cylinder models. The realistic model is also used to fit synaptic currents generated by stimulation of mossy fiber (MF) and commissural/associational (C/A) inputs to CA3 neurons and to estimate the amount of distortion of these measured currents. 6. Anatomic data from the CA3 pyramidal neuron model are used to construct a simplified two-cylinder CA3 model. This model is used to estimate the electrotonic distances of MF synapses (which are located proximal to the soma) and perforant path (PP) synapses (which are located at the distal ends of the apical dendrites) and the distortion of synaptic current parameters measured for these synapses. 7. Results from the equivalent-cylinder models, the morphological CA3 model, and the simplified CA3 model all indicate that the amount of distortion of synaptic currents increases steeply as a function of distance from the soma. MF synapses close to the soma are likely to be subject only to small space-clamp errors, whereas MF synapses farther from the soma are likely to be substantially attenuated.(ABSTRACT TRUNCATED AT 400 WORDS)

Overexpression of a Shaker-type potassium channel in mammalian central nervous system dysregulates native potassium channel gene expression.

The nervous system maintains a delicate balance between excitation and inhibition, partly through the complex interplay between voltage-gated sodium and potassium ion channels. Because K+ channel blockade or gene deletion causes hyperexcitability, it is generally assumed that increases in K+ channel gene expression should reduce neuronal network excitability. We have tested this hypothesis by creating a transgenic mouse that expresses a Shaker-type K+ channel gene. Paradoxically, we find that addition of the extra K+ channel gene results in a hyperexcitable rather than a hypoexcitable phenotype. The presence of the transgene leads to a complex deregulation of endogenous Shaker genes in the adult central nervous system as well as an increase in network excitability that includes spontaneous cortical spike and wave discharges and a lower threshold for epileptiform bursting in isolated hippocampal slices. These data suggest that an increase in K+ channel gene dosage leads to dysregulation of normal K+ channel gene expression, and it may underlie a mechanism contributing to the pathogenesis of human aneuploidies such as Down syndrome.

Glutamate and gamma-aminobutyric acid neurotransmitter systems in the acute phase of maple syrup urine disease and citrullinemia encephalopathies in newborn calves.

Cerebral cortex tissue was obtained at autopsy from neonatal Poll Hereford calves with clinically confirmed maple syrup urine disease (MSUD), neonatal Holstein-Friesian calves with clinically confirmed citrullinemia, and matched controls. From this, synaptosomes were prepared for studies of neurotransmitter amino acid uptake and stimulus-induced release, and synaptic plasma membranes were obtained for studies of associated postsynaptic receptor binding sites. As well as having abnormal brain tissue concentrations of the pathognomic plasma amino acids (markedly increased levels of the branched-chain compounds valine, isoleucine, and leucine in MSUD; marked elevation of citrulline levels in citrullinemia), both groups of diseased animals showed reduced brain tissue concentrations of each of the transmitter amino acids glutamate, aspartate, and gamma-aminobutyric acid (GABA). Nontransmitter amino acids were generally unaffected in either disease. Citrullinemic calves showed a marked increase in brain glutamine concentration; in calves with MSUD, the glutamine concentration was raised, but to a much lesser extent. The Na(+)-dependent synaptosomal uptake of both glutamate and GABA was markedly reduced (to less than 50% of control values in both cases) in citrullinemic calves but was unaltered in calves with MSUD. Whereas synaptosomes from normal calves showed the expected stimulus-coupled release of transmitter amino acids, especially glutamate and aspartate, and no response to stimulus of nontransmitter amino acids, there was no increased release of transmitter amino acids in response to depolarization in synaptosomes from citrullinemic calves.(ABSTRACT TRUNCATED AT 250 WORDS)