Lessons from history of socioeconomic improvements: a new approach to treating multi-drug-resistant tuberculosis

Summary This study investigated the trends in tuberculosis mortality through time in Switzerland. Information on the decline in mortality before chemotherapies were introduced may be useful in developing countries where drug-resistant tuberculosis is now becoming a major problem. Swiss data were collected from historical records and comparative data were obtained from the literature for England and Wales, New York, Japan, Brazil and Sierra Leone. Logistic curves were fitted to examine the rate of decline before introduction of pharmacotherapies and these show that the decline would have continued without the introduction of chemical therapies, including antibiotics. In Switzerland, England and Wales and New York, the decline had occurred long before the introduction of specific anti-tuberculosis agents. In Brazil and Japan, chemical therapy was co-incident with the decline in tuberculosis mortality rates. Overall, it is suggested that the effective control of tuberculosis can be achieved through a combination of chemical interventions, conservative therapy (rest, good nutrition, ventilation, etc.) as well as public health interventions addressing hygiene, nutrition, reducing exposure to infections and educating the population about tuberculosis

A Wasp Manipulates Neuronal Activity in the Sub-Esophageal Ganglion to Decrease the Drive for Walking in Its Cockroach Prey

BACKGROUND: The parasitoid Jewel Wasp hunts cockroaches to serve as a live food supply for its offspring. The wasp stings the cockroach in the head and delivers a cocktail of neurotoxins directly inside the prey's cerebral ganglia. Although not paralyzed, the stung cockroach becomes a living yet docile 'zombie', incapable of self-initiating spontaneous or evoked walking. We show here that such neuro-chemical manipulation can be attributed to decreased neuronal activity in a small region of the cockroach cerebral nervous system, the sub-esophageal ganglion (SEG). A decrease in descending permissive inputs from this ganglion to thoracic central pattern generators decreases the propensity for walking-related behaviors. METHODOLOGY AND PRINCIPAL FINDINGS: We have used behavioral, neuro-pharmacological and electrophysiological methods to show that: (1) Surgically removing the cockroach SEG prior to wasp stinging prolongs the duration of the sting 5-fold, suggesting that the wasp actively targets the SEG during the stinging sequence; (2) injecting a sodium channel blocker, procaine, into the SEG of non-stung cockroaches reversibly decreases spontaneous and evoked walking, suggesting that the SEG plays an important role in the up-regulation of locomotion; (3) artificial focal injection of crude milked venom into the SEG of non-stung cockroaches decreases spontaneous and evoked walking, as seen with naturally-stung cockroaches; and (4) spontaneous and evoked neuronal spiking activity in the SEG, recorded with an extracellular bipolar microelectrode, is markedly decreased in stung cockroaches versus non-stung controls. CONCLUSIONS AND SIGNIFICANCE: We have identified the neuronal substrate responsible for the venom-induced manipulation of the cockroach's drive for walking. Our data strongly support previous findings suggesting a critical and permissive role for the SEG in the regulation of locomotion in insects. By injecting a venom cocktail directly into the SEG, the parasitoid Jewel Wasp selectively manipulates the cockroach's motivation to initiate walking without interfering with other non-related behaviors

The Cercal Organ May Provide Singing Tettigoniids a Backup Sensory System for the Detection of Eavesdropping Bats

Conspicuous signals, such as the calling songs of tettigoniids, are intended to attract mates but may also unintentionally attract predators. Among them bats that listen to prey-generated sounds constitute a predation pressure for many acoustically communicating insects as well as frogs. As an adaptation to protect against bat predation many insect species evolved auditory sensitivity to bat-emitted echolocation signals. Recently, the European mouse-eared bat species Myotis myotis and M. blythii oxygnathus were found to eavesdrop on calling songs of the tettigoniid Tettigonia cantans. These gleaning bats emit rather faint echolocation signals when approaching prey and singing insects may have difficulty detecting acoustic predator-related signals. The aim of this study was to determine (1) if loud self-generated sound produced by European tettigoniids impairs the detection of pulsed ultrasound and (2) if wind-sensors on the cercal organ function as a sensory backup system for bat detection in tettigoniids. We addressed these questions by combining a behavioral approach to study the response of two European tettigoniid species to pulsed ultrasound, together with an electrophysiological approach to record the activity of wind-sensitive interneurons during real attacks of the European mouse-eared bat species Myotis myotis. Results showed that singing T. cantans males did not respond to sequences of ultrasound pulses, whereas singing T. viridissima did respond with predominantly brief song pauses when ultrasound pulses fell into silent intervals or were coincident with the production of soft hemi-syllables. This result, however, strongly depended on ambient temperature with a lower probability for song interruption observable at 21°C compared to 28°C. Using extracellular recordings, dorsal giant interneurons of tettigoniids were shown to fire regular bursts in response to attacking bats. Between the first response of wind-sensitive interneurons and contact, a mean time lag of 860 ms was found. This time interval corresponds to a bat-to-prey distance of ca. 72 cm. This result demonstrates the efficiency of the cercal system of tettigoniids in detecting attacking bats and suggests this sensory system to be particularly valuable for singing insects that are targeted by eavesdropping bats

Neural circuits controlling behavior and autonomic functions in medicinal leeches

In the study of the neural circuits underlying behavior and autonomic functions, the stereotyped and accessible nervous system of medicinal leeches, Hirudo sp., has been particularly informative. These leeches express well-defined behaviors and autonomic movements which are amenable to investigation at the circuit and neuronal levels. In this review, we discuss some of the best understood of these movements and the circuits which underlie them, focusing on swimming, crawling and heartbeat. We also discuss the rudiments of decision-making: the selection between generally mutually exclusive behaviors at the neuronal level

Nine-year comparison of presentation and management of acute coronary syndromes in Ireland: a national cross-sectional survey

BACKGROUND: Shorter time to treatment is associated with lower mortality in acute coronary syndromes (ACS). A previous (1994) survey showed substantial delays for acute myocardial infarction (AMI) in Ireland. The present study compared current practice with 1994 and surveyed acute coronary syndromes as a more complete contemporary evaluation of critical cardiac care than assessing AMI alone. METHODS: Following ethics committee approval, all centres (N = 39) admitting acute cardiac patients to intensive/coronary care unit provided information on 1365 episodes. A cross-sectional survey design was employed. RESULTS: Since 1994, median hospital arrival to thrombolysis time was reduced by 41% (76 to 45 minutes). Thrombolysis was delivered more often in the emergency department in 2003 (48% vs 2%). Thrombolysis when delivered in the emergency department was achieved faster than thrombolysis delivered in intensive/coronary care (35 mins v 60 mins; z = 5.62, p < .0001). Suspected AMI patients who did not subsequently receive thrombolysis took longer to present to hospital (5 h vs 2 h 34 mins; z = 7.33, p < .0001) and had longer transfer times to the intensive/coronary care unit following arrival (2 h 17 mins vs 1 h 10 mins; z = 8.92, p < .0001). Fewer confirmed AMI cases received thrombolysis in 2003 (43% vs 58%). There was an increase in confirmed cases of AMI from 1994 (70% to 87%). CONCLUSIONS: Substantial improvements in time to thrombolysis have occurred since 1994, probably relating to treatment provision in emergency departments. Patient delay pre-hospital is still the principal impediment to effective treatment of ACS. A recent change of definition of AMI may have precluded an exact comparison between 1994 and 2003 data

Information Transmission in Cercal Giant Interneurons Is Unaffected by Axonal Conduction Noise

What are the fundamental constraints on the precision and accuracy with which nervous systems can process information? One constraint must reflect the intrinsic “noisiness” of the mechanisms that transmit information between nerve cells. Most neurons transmit information through the probabilistic generation and propagation of spikes along axons, and recent modeling studies suggest that noise from spike propagation might pose a significant constraint on the rate at which information could be transmitted between neurons. However, the magnitude and functional significance of this noise source in actual cells remains poorly understood. We measured variability in conduction time along the axons of identified neurons in the cercal sensory system of the cricket Acheta domesticus, and used information theory to calculate the effects of this variability on sensory coding. We found that the variability in spike propagation speed is not large enough to constrain the accuracy of neural encoding in this system

Fluctuation-Driven Neural Dynamics Reproduce Drosophila Locomotor Patterns.

The neural mechanisms determining the timing of even simple actions, such as when to walk or rest, are largely mysterious. One intriguing, but untested, hypothesis posits a role for ongoing activity fluctuations in neurons of central action selection circuits that drive animal behavior from moment to moment. To examine how fluctuating activity can contribute to action timing, we paired high-resolution measurements of freely walking Drosophila melanogaster with data-driven neural network modeling and dynamical systems analysis. We generated fluctuation-driven network models whose outputs-locomotor bouts-matched those measured from sensory-deprived Drosophila. From these models, we identified those that could also reproduce a second, unrelated dataset: the complex time-course of odor-evoked walking for genetically diverse Drosophila strains. Dynamical models that best reproduced both Drosophila basal and odor-evoked locomotor patterns exhibited specific characteristics. First, ongoing fluctuations were required. In a stochastic resonance-like manner, these fluctuations allowed neural activity to escape stable equilibria and to exceed a threshold for locomotion. Second, odor-induced shifts of equilibria in these models caused a depression in locomotor frequency following olfactory stimulation. Our models predict that activity fluctuations in action selection circuits cause behavioral output to more closely match sensory drive and may therefore enhance navigation in complex sensory environments. Together these data reveal how simple neural dynamics, when coupled with activity fluctuations, can give rise to complex patterns of animal behavior