Preventing distracted driving: A program from initiation through to evaluation

BackgroundDistracted driving(DD) is a public health threat. We initiated a DD program where the objective was to attract parents to a website to download a parent tool box. We report the effectiveness of media strategy.MethodsAn evidence based interactive DD website was developed which provided a parent tool box. Two different digital media strategies were used. Parent(P)/Teen(T) focus groups were used. Analytics, orders during each media strategy are reported as well the results of the focus group.ResultsThere were 73972 visits (>2 min) to the site. The tool box was downloaded/ordered from 10 different countries and 50 states. There were 603 requests via the internet for tools kits, 159 in the first campaign and 444 in the second campaign. Average website time increased from 2.33 min in media campign 1–5.29 min in campaign 2. The focus groups reported the: website was “very useful” in 9/15-P vs 10/15- T.ConclusionContextual placement digital advertising and focused social media was more effective in attracting parents to the website, and increased downloads.Level of evidenceIII.Type of studyprospective/retrospective study with economic and valued based evaluations.     

Behavioral influences on cortical neuronal responses to optic flow

Optic flow selectively activates neurons in medial superior temporal (MST) cortex. We find that many MST neurons yield larger and more selective responses when the optic flow guides a subsequent eye movement. Smaller, less selective responses are seen when optic flow is preceded by a flashed precue that guides eye movements. Selectivity can decrease by a third (32%) after a flashed precue is presented at a peripheral location as a small spot specifying the target location of the eye movement. Smaller decreases in selectivity (18%) occur when the precue is presented centrally with its shape specifying the target location. Shape precues presented centrally, but not linked to specific target locations, do not appear to alter optic flow selectivity. The effects of spatial precueing can be reversed so that the precue leads to larger and more selective optic flow responses: A flashed precue presented as a distracter before behaviorally relevant optic flow is associated with larger optic flow responses and a 45% increase in selectivity. Together, these findings show that spatial precues can decrease or increase the size and selectivity of optic flow responses depending on the associated behavioral contingencies.     

Persistent cortical activity: mechanisms of generation and effects on neuronal excitability

Local cortical networks in the prefrontal cortex and visual cortex are capable of spontaneously generating sustained activity for periods of seconds or longer. This sustained activity is generated through recurrent excitation between pyramidal cells that is controlled by feedback inhibition and can have both a rapid onset and a rapid offset. The period of activity is associated with a marked increase in neuronal responsiveness to the intracellular injection of current pulses, especially those of smaller amplitude. Independently mimicking the depolarization, increase in membrane conductance and increase in noise associated with sustained activity revealed that the depolarization is largely responsible for the increase in neuronal responsiveness, although an increase in membrane noise also facilitates responses to small inputs. These results indicate that the persistent activity associated with the performance of working memory tasks may be generated largely through recurrent networks. They also suggest that feedback pathways, such as those involved in selective attention, may exert a powerful influence on neuronal responsiveness through synaptic bombardment.     

Human cerebral cortical responses to contralateral transcranial stimulation

We wished to develop a noninvasive electrophysiological measure of functioning of human cerebral cortex. The response chosen was that elicited by a corticocortical afferent input, specifically the transcallosal response (TCR). We used ourselves as subjects. The large shock artifacts associated with passing large currents through the head were reduced by: stimulating percutaneously with a focal anode (5 cm2) situated midway between F4 and C4 (i.e., frontal region, standard 10-20 nomenclature) and a medially located, semicircular grounded cathode (26 cm2) no closer than 3 to 4 cm away; and recording with the focal scalp electrode over homologous left frontal cortex vs. two or more reference electrodes interconnected through variable resistors and at least 6 cm away. Transcranial stimulation with pulses of 80 to 140 mA and lasting 100 microseconds elicited a brief diphasic deflection (latency, 2 to 4 ms), followed by an initially positive, often bifid wave with a latency of 9 to 14 ms, lasting 18 to 44 ms and reaching 5 to 10 microV. The initial diphasic deflection greatly increased when the stimulating anode was moved laterally over temporalis muscle, indicating an electromyographic (EMG) origin. The EMG, but not the positive wave, was elicited when the interpolar distance was reduced to 1 cm, which greatly reduced the fraction of current traversing the cortex (epicranial stimulation); furthermore, occluding the circulation to the scalp for 30 minutes by rubber tubing above the zygomas and brows dulled sensation, reduced the EMG, but did not alter the latency or rising phase of the positive wave. Early somatosensory components, if present, were small compared with the positive wave.(ABSTRACT TRUNCATED AT 250 WORDS)     

Driving plastered: driving habits of orthopaedic outpatients and the medico-legal implications

Driving in cast impairs driving ability. We surveyed driving behaviour of orthopaedic trauma patients. Fifteen percent admitted that they drove while in cast. In a national context, this would mean that over 500 people drive every year on Irish roads while still wearing a forearm or below knee cast. In reality, this is probably a gross underestimation.     

In vitro networks: cortical mechanisms of anaesthetic action

Br J Anaesth 2002; 89: 102–11     

Transplantation of osteoblast-like cells to the distracted callus in rabbits

We carried out limb lengthening in rabbits and then transplanted osteoblast-like cells derived from the tibial periosteum to the centres of distracted callus immediately after distraction had been terminated. Two weeks later the transaxial area ratio at the centre of the distracted callus and the bone mineral density (BMD) were significantly higher in the transplanted group, by 21% and 42%, respectively, than in the non-injected group or the group injected with physiological saline (p < 0.05). Callus BMD as a percentage of density in uninvolved bone was also significantly higher in the transplanted group (p < 0.05) than in the other two groups, by 27% and 20% in the second and fourth weeks, respectively (p < 0.05). Mechanically, the callus in the transplanted group tended to be stronger as shown by the three-point bending test although the difference in fracture strength was not statistically significant. Our results show that transplantation of osteoblast-like cells promotes maturity of the distracted callus as observed at the second and fourth weeks after lengthening. The method appears promising as a means of shortening the consolidation period of callus distraction and decreasing complications during limb lengthening with an external fixator.     

Chronic furosemide treatment alters renal responses to furosemide in conscious lambs

Despite the widespread chronic use of furosemide in the clinical management of a variety of fluid and electrolyte disorders in human infants, the physiological responses to furosemide in the newborn after chronic furosemide treatment are not known. The present experiments were conducted to determine the effects of chronic furosemide treatment on renal responses to acute furosemide challenge in conscious, chronically instrumented lambs. Experiments were carried out on day 1 (before chronic treatment) and on day 7 (after chronic treatment) in lambs given intravenous injections of either furosemide (1 mg/kg per 12 h for 5 days, n=9) or vehicle (0 mg/kg per 12 h for 5 days, n=4). Furosemide-treated animals responded to acute furosemide challenge on day 7 with attenuation of natriuresis and diuresis, and augmentation of kaliuresis compared with responses on day 1. Baseline renin production was elevated, although the renin response to furosemide was similar in chronic furosemide-treated and vehicle-treated lambs. Baseline aldosterone levels were not altered by chronic furosemide treatment, but the aldosterone response to acute furosemide injection was decreased after chronic furosemide treatment. Therefore, chronic furosemide treatment alters renal responses to furosemide in conscious lambs, and alters the aldosterone response to acute furosemide challenge.     

Subarachnoid blockade alters homeostasis by modifying compensatory splanchnic responses to hemorrhagic hypotension

To demonstrate that sympathetic responses transmitted by the splanchnic nerve help maintain intravascular stability, 12 mongrel dogs (35-45 kg each), anesthetized with pentobarbital, were given two separate but identical hypotensive stimuli (mean arterial blood pressure of 60 mm Hg for 15 min) by the withdrawal of appropriate amounts of blood. The first stimulus was performed in the absence of drug or surgical manipulation. The second stimulus was performed after animals were subjected to no intervention (n = 4), bilateral splanchnic nerve section (n = 4), or spinal anesthesia (n = 4). Before and 10 min after the onset of hypotension, arterial epinephrine concentration and adrenal medullary and abdominal organ blood flow were measured. In the group without intervention, the second hypotensive stimulus (like the first) elicited 3-fold increases in adrenal medullary blood flow, 40-fold increases in arterial epinephrine concentration, and a 61% reduction in abdominal organ blood flow (P greater than 0.002). The volume of blood withdrawn to produce hypotension was similar (approximately 21 ml.kg-1). Bilateral splanchnic nerve section attenuated the adrenal medullary blood flow, arterial epinephrine concentration, and abdominal organ blood flow responses to hypotension by 86, 64, and 66%, respectively (P less than 0.008), and the blood volume withdrawn was reduced by 42% (P less than 0.02). Spinal anesthesia eliminated the adrenal medullary blood flow response to hypotension, attenuated the arterial epinephrine concentration and abdominal organ blood flow responses by 78 and 57%, respectively (P less than 0.01), and decreased the blood volume extracted by 55% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pregnancy alters adrenergic mechanisms in uterine arterioles of rats

Pregnancy is associated with altered vascular reactivity. However, the effect of pregnancy on the alpha- and beta-adrenergic responses in the uterine microcirculation remains to be determined. In late-pregnant (Day 20-21, n = 6) and virgin (n = 6) Sprague-Dawley rats, uterine radial arterioles (70-120 microm in internal diameter) were isolated. We studied in vitro arteriolar responses in a pressurized, no-flow state with videomicroscopy. alpha(2)-Adrenergic activation relaxed uterine arterioles; this relaxation was increased with pregnancy and was inhibited after endothelial denudation or inhibition of nitric oxide synthase. Pregnancy significantly increased the contractile response to the alpha(1)-adrenoceptor agonist phenylephrine but decreased the relaxation to the beta-adrenoceptor agonist isoproterenol. The contractile response to the protein kinase C activator phorbol ester and relaxation responses to both the adenylate cyclase activator forskolin and the endothelium-independent cyclic guanosine monophosphate-mediated vaso- dilator nitroprusside were preserved. These results suggest that pregnancy enhances the alpha(2)-adrenoceptor-mediated relaxation of uterine arterioles, probably because of an increase in the release of nitric oxide. The alpha(1)-adrenergic response is upregulated, whereas the beta-adrenergic response is impaired, in the uterine microcirculation of pregnant rats. IMPLICATIONS: Both alpha- and beta-adrenergic responses are important mechanisms for the regulation of uteroplacental perfusion. By use of an in vitromicrovascular technique, we have shown pregnancy-associated alteration in adrenergic responses in the uterine microcirculation of the rat.     

短期使用齐多夫定抑制p53R2表达及诱导小鼠神经元凋亡的研究

目的探讨齐多夫定(AZT)的中枢神经毒性及其相关机制。方法原代培养小鼠大脑皮层神经元,分别用0 mmol/L、50 mmol/L、100 mmol/L的AZT作用于细胞,TUNEL法检测细胞凋亡,免疫荧光观察细胞形态,实时定量PCR(qPCR)检测依赖p53的p53R2、抑癌基因p21、胸苷激酶(TK2)mRNA表达及线粒体DNA含量,蛋白印迹检测p53R2与p21蛋白的表达。结果 AZT 0mmol/L组(对照组)、50 mmol/L组和100 mmol/L组细胞凋亡率分别为(11.9±3.37)%、(24.3±8.94)%和(54.7±17.9)%,差异具有统计学意义(χ2=5.19、19.33,P均0.01);突起长度分别为(869.21±177.75)mm、(495.76±175.20)mm和(120.38±47.12)mm,且差异均具有统计学意义(F=19.558,P=0.002);real-time qPCR检测结果显示AZT 50 mmol/L和100 mmol/L组p53R2、TK2 mRNA拷贝数分别是对照组的0.42和0.04倍、0.52和0.29倍,组间差异均具有统计学意义(Z=-4.54、-6.65、-4.33和-5.24,P均0.01);AZT 50 mmol/L和100 mmol/L组p21 mRNA拷贝数分别是对照组的0.98和0.86倍,差异无统计学意义(P0.05)。线粒体含量用环氧化酶2(COX-2)拷贝数评估,AZT 50 mmol/L组和100 mmol/L组分别是对照组的0.92和0.87倍,差异无统计学意义(P0.05)。蛋白印迹显示对照组、AZT 50 mmol/L组和100 mmol/L组p53R2蛋白含量依次降低,而p21蛋白含量无差异。结论 AZT可诱导神经元凋亡,抑制突起形成,推测其机制与p53R2表达降低有关。短期接触AZT可抑制TK2的表达,但对线粒体DNA含量无影响。     

Face recognition and cortical responses show similar sensitivity to noise spatial frequency

To find cortical correlates of face recognition, we manipulatedthe recognizability of face images in a parametric manner bymasking them with narrow-band spatial noise. Face recognitionperformance was best at the lowest and highest noise spatialfrequencies (NSFs, 2 and 45 c/image, respectively), and degradedgradually towards central NSFs (11–16 c/image). The strengthof the 130–180 ms neuromagnetic response (M170) in thetemporo-occipital cortex paralleled the recognition performance,whereas the mid-occipital response at 70–120 ms actedin the opposite manner, being strongest for the central NSFs.To noise stimuli without faces, M170 was small and rather insensitiveto NSF, whereas the mid-occipital responses resembled closelythe responses to the combined face and noise stimuli. Theseresults suggest that the 100 ms mid-occipital response is sensitiveto the central spatial frequencies that are critical for facerecognition, whereas the M170 response is sensitive to the visibilityof a face and closely related to face recognition.     

Differential behavioral and histopathological responses to graded cortical impact injury in mice

Controlled cortical impact (CCI) injury, a model of contusive brain injury in humans, is being used with increasing frequency in mice to investigate post-traumatic cell damage and death and to evaluate treatment strategies. Because cellular injury mechanisms and therapeutic approaches may depend on the severity of the initial insult, it is important to utilize a model in which outcomes are sensitive to injury severity. Adult male C57Bl/6 mice were anesthetized and subjected to sham injury (n = 23) or CCI injury at either 0.5 mm (n = 22) or 1.0 mm (n = 22) depth of impact at a velocity of 5 m/sec. At 2 days, brain-injured mice exhibited significant memory (p < 0.05) and motor function (p < 0.001) deficits compared to sham-injured mice; furthermore, mice subjected to an impact of 1.0 mm were significantly more impaired in both outcome measures than those injured at 0.5 mm (p < 0.05). The cortical lesion increased in size between 24 h and 7 days in both injury groups, but was significantly larger in the 1.0 mm group. Hippocampal cell loss was observed in the hilar and CA3 regions in both groups, and in the CA1 and dentate granule cell layers in the 1.0 mm group. Regional patterns of IgG extravasation and reactive astrocytosis were similar in the two injured groups, but changes were more persistent in the 1.0 mm group. Both levels of injury resulted in acute loss of neuronal MAP-2 immunoreactivity in the cortex and sub-region specific changes in the hippocampus. Thus, increasing the depth of impact led to similar structural alterations in neurons, astrocytes and the vasculature, but resulted in greater behavioral deficits and cortical and hippocampal cell death.     

Acute responses to experimental blunt head trauma. Topography of cerebral cortical edema

Anesthetized cats subjected to impact followed by acceleration and rotation of the skull were sacrificed at 15 minutes or 6 hours after injury and were selected for study if unilateral cerebral contusion was present. Widespread areas of cerebral cortex were examined bilaterally for edema, using measurement of tissue density with an organic gradient, and for breakdown of the blood-brain barrier to plasma protein tagged with Evans blue dye. At both times tested, a halo of vasogenic edema (Evans blue stain plus decreased density) was present in the cortex surrounding areas of contusion. At 15 minutes after injury, animals with deep contusions also had a slight decrease in density without Evans blue staining, interpreted as cytotoxic edema, in some gyri neighboring the contusion. At 6 hours, cytotoxic edema was not evident, but some animals had vasogenic edema in the gyri adjoining the contusion. Most gyri contralateral to contused areas had neither Evans blue staining nor changes in tissue density. These findings suggest that, with the present head-injury model, acute changes in tissue density and vascular permeability occur in the cerebral cortex of hemispheres with contusion. These responses are related topographically to contusion sites, and change over the two times studied. The authors conclude that events in addition to spread of fluid from areas of contusion contribute to the edema of head injury, and that more than one form of edema can follow mechanical trauma to the brain.     

Auditory cortical responses to the interactive effects of interaural intensity disparities and frequency

Under natural conditions, stimuli reaching the two ears contain multiple acoustic components. Rarely does a stimulus containing only one component (e.g. pure tone burst) exist outside the realm of the laboratory. For example, in sound localization the simultaneous presence of multiple cues (spectral content, level, phase, etc.) serves to increase the number of available cues and provide the listener with more information, thereby helping to reduce errors in locating the sound source. The present study was designed to explore the relationship between two acoustic parameters: stimulus frequency and interaural intensity disparities (IIDs). By varying both stimulus frequency and IIDs for each cell, we hoped to gain insight into how multiple cues are processed. To this end, we examined the responses of neurons in cat primary auditory cortex (AI) to determine if their sensitivity to IIDs changed as a function of stimulus frequency. IIDs ranging from +30 to -30 dB were presented at different frequencies (frequency was always the same in the two ears). We found that approximately half of the units examined exhibited responses to IIDs that varied as a function of stimulus frequency (i.e. displayed some form of IID x Freq dependency). The remaining units displayed IID responses that were not clearly related to stimulus frequency.     

Intrathecal picrotoxin minimally alters electro-encephalographic responses to noxious stimulation during halothane and isoflurane anesthesia

BACKGROUND: Isoflurane and halothane act in the spinal cord to blunt ascending transmission of impulses to the brain resulting from noxious stimulation. Because intrathecal picrotoxin (an antagonist at the gamma-aminobutyric acid-A receptor) partially reverses the immobilizing effect of isoflurane and halothane, we hypothesized that the electroencephalographic response to noxious stimulation would likewise be partially reversed by intrathecal picrotoxin. METHODS: Rats were anesthetized with isoflurane (n = 8) or halothane (n = 8) and a laminectomy performed. Following determination of minimum alveolar concentration (MAC), the electroencephalogram (EEG) was recorded during separate applications of a hindpaw clamp, tail clamp and electrical current to the tail at 0.8 and 1.2 MAC. Picrotoxin was then applied to the exposed spinal cord and the EEG response to noxious stimulation again determined. RESULTS: The EEG was more active during halothane anesthesia than isoflurane (spectral edge frequency for 95% power: 25.6 +/- 2.1 Hz vs. 23.1 +/- 1.6 Hz, P < 0.05). Noxious stimulation usually caused the EEG to shift to higher frequencies (e.g. for 0.8 MAC halothane, median edge frequency for 50% power: from 7.6 +/- 3.1 Hz to 10.7 +/- 2.6 Hz, P < 0.05). Picrotoxin minimally affected this response. CONCLUSIONS: Noxious stimulation evokes an EEG response that is minimally altered by intrathecal picrotoxin. This suggests that isoflurane and halothane do not have GABAergic actions in the spinal cord that indirectly suppress the EEG response.     

Neonatal hippocampal damage alters electrophysiological properties of prefrontal cortical neurons in adult rats

A neonatal excitotoxic lesion of the ventral hippocampus in the rat produces a variety of behavioral and cellular changes that remain latent until early adulthood. These delayed effects resemble many phenomena observed in schizophrenia, a neuropsychiatric disorder of early adult onset in which abnormal development of the hippocampus and prefrontal cortex has been postulated. Here we investigated the impact of this neonatal hippocampal lesion on the response of medial prefrontal cortical pyramidal neurons to specific afferent stimulation. Neonatal hippocampal damage altered the physiological responses of these neurons to electrical stimulation of midbrain dopaminergic-GABAergic projections, but not thalamic glutamatergic afferents. The lesion resulted in excessive firing of pyramidal neurons in response to mesocortical stimulation and this effect was not observed before adulthood or after similar hippocampal damage produced in adult rats. These data show that neonatal damage to the ventral hippocampus changes, in a developmentally specific manner, the nature of prefrontal cortical neuron responses to activation of projections from the ventral tegmental area, an effect that may explain the adverse impact of stress in schizophrenia.     

Propofol directly depresses lumbar dorsal horn neuronal responses to noxious stimulation in goats

PURPOSE: We tested the hypothesis that propofol, acting in the brain, would either enhance, or have no effect, on lumbar dorsal horn neuronal responses to a noxious mechanical stimulus applied to the hindlimb. We recorded the response of lumbar dorsal horn neurons during differential delivery of propofol to the brain and torso of goats. METHODS: Goats were anesthetized with isoflurane and neck dissections performed which permitted cranial bypass. A laminectomy was made to allow microelectrode recording of lumbar dorsal horn neuronal activity. Isoflurane was maintained at 0.8+/-0.1% to both head and torso throughout the study. During cranial bypass propofol was separately administered to the torso (1 mg x kg(-1), n = 7; 3.75 mg x kg(-1), n = 8) or cranial (0.04 mg x kg(-1), n = 7; 0.14 mg kg(-1), n = 8) circulations. RESULTS: Propofol administered to the torso depressed dorsal horn neuronal responses to noxious stimulation: low dose: 500+/-243 to 174+/-240 impulses x min(-1) at one minute post-injection, P<0.001; high dose: 478+/-204 to 91+/-138 impulses x min(-1) at one minute post-injection, P<0.05). Propofol administered to the cranial circulation had no effect: low dose: 315+/-150 to 410+/-272 impulses x min(-1), P>0.05; high dose: 462+/-261 to 371+/-196 impulses x min(-1), P>0.05. CONCLUSIONS: These data indicate that propofol has a direct depressant effect on dorsal horn neuronal responses to noxious stimulation, with little or no indirect supraspinal effect.