GABA-receptor activation in the globus pallidus and entopeduncular nucleus: opposite effects on reaction time performance in the cat

The possible role of GABAergic mechanisms in the control of the basal ganglia output structures, the globus pallidus (GP) and the entopeduncular nucleus (EP), was studied in cats performing a conditioned flexion movement triggered by an auditory stimulus. The effects of discrete unilateral microinjections of low doses of the GABA_A receptor agonist (muscimol 5–100 ng/ 0.5 l) and antagonist (bicuculline methiodide 25–150 ng/0.5 l) in the GP and the EP were tested on the motor performance of eight animals trained to release a lever in a simple reaction time (RT) schedule after an auditory stimulus. Control injections in neighboring structures did not induce any effect except with five- to tenfold higher doses in the closest injection sites. The dose of 20 ng muscimol injected into the ventral and medial part of the GP produced an arrest of the performance after a few unsuccessful trials (over the RT reinforcement limit of 500 ms), while muscimol injected in sites located in the lateral GP resulted in a dose-dependent lengthening in RTs, with a concomitant increase in the force change latency. In most of the subjects, the force exerted on the lever was higher after muscimol than after vehicle injection. Force change velocity was then significantly increased. In contrast, muscimol injected in the ventral and rostral region of the EP produced a decrease in RTs or a complete cessation of responding after a high number of anticipatory responses (release of the lever before the trigger stimulus). No significant changes in the force change latency could be observed while there was a non-significant tendency for the force levels to be lowered. Bicuculline injections in the EP were found to increase RTs with a concomitant increase in force change latency and a slowness of velocity, while no significant effect was observed following injections in the GP. These results suggest that a balance between GABAergic activity in the two output nuclei of the basal ganglia, the GP and the EP, is crucial for the correct initiation and execution of the conditioned motor task.     

The relative effects of external spatial and motoric factors on the bimanual coordination of discrete movements

The ability to coordinate the two hands effectively is a fundamental requirement for many everyday tasks. To investigate how bimanual coordination is achieved we asked subjects to perform discrete bimanual key-press responses under conditions in which the motoric (i.e., muscles employed) and external spatial (i.e., direction of movement in external space) relationships between the actions of the left and right index fingers were systematically varied. Subjects made simultaneous right and left index finger key-presses in response to an auditory tone. The right finger always made downward flexion movements whilst the left finger either flexed in a downward/upward direction, or extended in a downward/upward direction. Unimanual control trials of each movement type for both hands were also performed. Reaction times for each hand (RTs) and the inter-response interval (IRI) were recorded . Right hand RTs were significantly affected only when the left finger performed motorically different actions, but were unaffected by the external spatial direction in which the left hands actions were made. The IRI results followed a similar pattern with the worst coordination (highest IRI) occurring when the left finger performed different motor actions to the right finger regardless of the direction of the left hand movement. In contrast to other recent results from experiments examining oscillatory tasks (e.g., Mechsner et al. 2001), our results suggest that in discrete tasks there is a dominance of the motor relationship between the hands over the external spatial relationship.     

Ballistic reactions under different motor sets

In preparation for performing task specific ballistic movements, subjects may choose among different possibilities for setting up their motor apparatus, ranging from quiet resting to different types of muscle activation. In the study presented here, we investigated whether differences in the motor set modify either the reaction time or the kinematic characteristics of the movement. Subjects wearing surface EMG recording electrodes in the wrist extensor (WE) and wrist flexor (WF) muscles were requested to react to the presentation of a visual stimulus by performing a ballistic wrist extension movement of an amplitude of about 50° in the following experimental conditions: resting quietly, which was considered as the control condition (CC); isometric contraction (IC), in which subjects were required to activate WE and WF muscles isometrically; rapid oscillations (RO), in which subjects were requested to make a fast oscillatory wrist movement; and slow oscillations (SO), in which subjects were maintaining a slow oscillatory motion of the wrist. To constrain the movement to the wrist joint and limit the action of postural muscles, the subjects forearm and hand were attached to joined non-resistive metallic platforms, allowing for free non-frictional displacement. In the EMG recordings, we measured the size of the EMG bursts in agonist and antagonist muscles, and the inter-burst intervals. In movement recordings, we measured movement onset latency and the velocity profile. Movement onset was delayed in SO with respect to all other conditions. Conversely, peak velocity was larger in all test conditions in comparison to CC. There were no differences in the size of the first EMG burst of the agonist muscle, but significant changes occurred in the subsequent bursts recorded in the agonist and antagonist muscles. Our study indicates that the motor program used to execute a ballistic voluntary movement is influenced by the conditions of the motor system. The configuration of the motor set should be specifically considered in the search for improving the speed of the reaction and the kinematics of ballistic movements.JMC and MTS were funded by the Spanish Ministry of Education, Culture and Sport, with grant numbers PR 2003-0212 and AP2000-0913     

Cocaine's effects on speech sound identification and reaction times in baboons

The effects of cocaine on speech sound discriminations was examined to determine whether cocaine's previously demonstrated effect in reducing speech sound discriminability was dependent upon either the type of stimuli employed (simple tones versus complex speech) or the procedure (stimulus detection versus stimulus discrimination). Because of demonstrated similarities in the way that baboons and humans discriminate speech, and in the way the CNS is thought to encode and process speech sounds in these two species, baboons were trained to perform a choice procedure to identify the occurrence of different synthetic vowel sounds (/a/, /æ/, //, /U/, and /љ/). Animals held down a lever and released the lever only when one of four target vowels sounded, and not when a fifth, standard vowel sounded. Acute IM administration of cocaine (0.0032–1.0 mg/kg) produced dose-dependent decreases in vowel discriminability that were mostly due to elevations in false alarms (i.e., releases to the standard vowel) following cocaine. Cocaine also shortened reaction times to the stimuli in two of three baboons, but to a much lesser extent than observed previously. These results suggest that cocaine may interfere with the ability of the CNS to process the acoustic cues in speech sounds, and that the effects of cocaine on reaction times may depend upon the complexity of the reaction time procedure employed.     

Responses of the human auditory cortex to changes in one versus two stimulus features

Neuromagnetic responses were recorded with a 24 SQUID magnetometer in two oddball experiments to determine whether mismatch responses to changes in single stimulus features are additive. In experiment 1, the one feature deviants differed from standards in interstimulus interval (ISI) or frequency, and the two feature deviants in both ISI and frequence. In experiment 2, deviants differed in duration, frequency, or both. All deviants evoked a mismatch field (MMF) with sources close to each other in the supratemporal auditory cortex. Except for the ISI deviants, the MMF sources were about 1 cm anterior to the source of the 100ms response, N100m, to the standards. In the two experiments, MMFs obtained in response to the two feature deviants resembled closely the sum of MMFs in response to one feature deviants. The results suggest that the standards leave a multiple neuronal representation in the human auditory cortex. The particular neuronal traces of the representation react independently to changes in different features of sound stimuli.     

MYCN AMPLIFICATION IN MEDULLOBLASTOMA

Prominent neuronal differentiation and MYCN amplification occur only in a small percentage of medulloblastomas (primitive neuroectodermal tumor of the cerebellum). In this article, we describe two medulloblastomas that showed a striking degree of neuronal differentiation with islands of mature neurons associated with abundant neuropil. In these differentiated foci, there were no mitoses or atypia, and the histology was reminiscent of a malformative or hamartomatous lesion. Both tumors were assessed for MYCN amplification by the novel technique of differential polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH). In case 1, MYCN amplification was in the 10 - fold range determined by differential PCR, while in case 2 the level of amplification was marked, with 20 - 30 copies compared with diploid controls. FISH analysis also confirmed the presence of MYCN amplification in both tumors. These two cases are of great interest, especially as they show MYCN amplification in medulloblastomas with marked degree of neuronal differentiation. Furthermore, in both cases, there was evidence of a slower and more indolent clinical course, suggesting a more favorable outcome in medulloblastoma with this degree of neuronal differentiation.     

Diagnosing Respiratory Events and Tracing Air Flow by Internal Thermistors

We have developed a new method to measure flow in patients with sleep-related breathing disorders (SRBD). These flow sensors are modified thermistors located in the same sensors we use for pressure measurement in the upper airways to find the obstructive segments during apnoeas. The aim of this study was to test if using internal thermistors as indicator of air flow has advantages compared with the external thermistor method in detecting respiratory events. A total of 50 consecutive patients with an apnoea-hypopnoea index (AHI) of more than 15 were studied. A standard nocturnal polysomnography (PSG) with both internal and external thermistors was performed in all patients. To estimate the patients' AHI, a detailed analysis viewing all parameters except external and internal thermistors was performed. This was followed by an analysis viewing only internal thermistors signals indicating airflow in the pharynx, and finally an analysis viewing only external thermistor signals indicating air flow at the mouth and nose. Mean AHI measured by the three methods showed 49.8 (SD 23.4) by the PSG, 47.8 (SD 24.9) by internal thermistors alone, and 31.5 (SD 22.2) by external thermistors. There was no statistical difference between AHI detected by PSG and internal thermistors, but highly significant differences between PSG and external thermistors (p<0.001). The external thermistors missed an average of almost 20 respiratory events per hour.     

Respiratory syncytial virus and influenza hospitalizations in Danish children 2010–2016

ObjectiveTo pave the way for universal or risk factor-based vaccination strategies, the present study aimed to describe the epidemiology and compare risk factors for hospitalization associated with respiratory syncytial virus (RSV) and influenza virus infections in Danish children.MethodsNational register-based cohort study among 403,422 Danish children born 2010–2016.ResultsPrior asthma hospitalization, number of children in the household, chronic disease and maternal history of asthma hospitalization were the most important risk factors for both RSV and influenza hospitalization. The incidence of influenza increased at school start.ConclusionsOur findings enable targeted vaccination programs for high-risk children with asthma-like disease, chronic disease, siblings in the household, or maternal history of asthma hospitalization.     

某院392例不良反应报告分析

目的：分析探讨某院药物不良反应产生的原因和类型,为合理用药提供指导,促进用药安全,减轻患者痛苦.方法：利用回顾性分析方法,分析患者在治疗期间产生的不良反应类型及其原因,统计分析,得出结论.结果：患者所发生的不良反应中抗菌药比例高达59.95%,相比于其它种类的药物,不良反应发生率明显升高,P＜0.05,具有统计学意义.在各种不良反应之中,消化系统和全身性系统的不良反应种类所占比例相较于其他种类明显增多,P＜0.05,具有统计学意义.结论：在临床用药的过程中,要做到合理用药,尽量减少抗菌药物的应用,同时要建立监测和预防机制,减少不良反应的发生,使患者平安度过病程,恢复健康.     

What about doctors? The impact of medical errors

Medical error is a distressing event to the patient and the health care providers. The impact of such events has been well studied on patients but poorly on health professionals. These events are still considered as a taboo in the medical culture and hence missed as great learning opportunities. They have negative impact on doctors' emotional wellbeing, general quality of life, and their professional practice and conduct. Medical errors and adverse events also affect the quality and cost of the health service. Health service administrations should provide healthcare professionals involved in such events with professional support and counselling services, and should consider and treat them as second victims.