Stepping in time: Alpha-mu and beta oscillations during a walking synchronization task.

Interpersonal behavioral synchrony is defined as the temporal coordination of action between two or more individuals. Humans tend to synchronize their movements during repetitive movement tasks such as walking. Mobile EEG technology now allows us to examine how this happens during gait. 18 participants equipped with foot accelerometers and mobile EEG walked with an experimenter in three conditions: With their view of the experimenter blocked, walking naturally, and trying to synchronize their steps with the experimenter. The experimenter walked following a headphone metronome to keep their steps consistent for all conditions. Step behavior and synchronization between the experimenter and participant were compared between conditions. Additionally, event-related spectral perturbations (ERSPs) were time-warped to the gait cycle in order to analyze alpha-mu (7.5-12.5 Hz) and beta (16-32 Hz) rhythms over the whole gait cycle. Step synchronization was significantly higher in the synchrony condition than in the natural condition. Likewise regarding ERSPs, right parietal channel (C4, C6, CP4, CP6) alpha-mu and central channel (C1, Cz, C2) beta power were suppressed from baseline in the walking synchrony condition compared to the natural walking condition. The natural and blocked conditions were not found to be significantly different in behavioral or spectral comparisons. Our results are compatible with the view that intentional synchronization employs systems associated with social interaction as well as the central motor system.

"Schizophrenia past clozapine": reasons for clozapine discontinuation, mortality, and alternative antipsychotic prescribing.

INTRODUCTION: The clinical records of 190 patients with schizophrenia who discontinued clozapine between 1990 and 2012 in the county of Northamptonshire were examined, in an attempt to answer the following questions. Why do patients stop clozapine? What do physicians prescribe as an alternative? What is the mortality in this patient group? METHODS: Patients' data were extracted using their electronic records, then analysed using descriptive statistical methods. RESULTS: Non-compliance with treatment, or with the mandatory white blood cell monitoring, was the most common reason (55.3%) for clozapine cessation, followed by neutropaenia and other adverse effects (25.2%). Death (mean age 48 years) was the third most common reason (10%), with respiratory infections accounting for more than a quarter of the deaths. 13% of the patients had died (mean age 49 years) at some point following clozapine discontinuation. In terms of the alternative antipsychotic prescribing, olanzapine was the most commonly prescribed (37.1%) drug in patients who were still under the care of the local psychiatric service (n=121), at the time of data extraction. Clozapine had been reinstated in 19% of these patients. DISCUSSION: Our findings are generally consistent with previous studies, and they demonstrate the need for physicians to address their patients' concerns regarding clozapine treatment, and to effectively manage any adverse effects. Sialorrhea and constipation seem to be particularly of concern, as they may be linked to clozapine- related mortality. Olanzapine was the most commonly prescribed alternative to clozapine, which suggests that it may possibly have a role in refractory schizophrenia.

Pediatric intracranial aneurysms: new and enlarging aneurysms after index aneurysm treatment or observation.

BACKGROUND AND PURPOSE: Children with brain aneurysms may be at higher risk than adults to develop new or enlarging aneurysms in a relatively short time. We sought to identify comorbidities and angiographic features in children that predict new aneurysm formation or enlargement of untreated aneurysms. MATERIALS AND METHODS: Retrospective analysis of the University of California-San Francisco Pediatric Aneurysm Cohort data base including medical records and imaging studies was performed. RESULTS: Of 83 patients harboring 114 intracranial aneurysms not associated with brain arteriovenous malformations or intracranial arteriovenous fistulas, 9 (8.4%) developed new or enlarging brain aneurysms an average of 4.2 years after initial presentation. Comorbidities that may be related to aneurysm formation were significantly higher in patients who developed new aneurysms (89%) as opposed to patients who did not develop new or enlarging aneurysms (41%; RR, 9.5; 95% CI, 1.9%-48%; P = .0099). Patients with multiple aneurysms at initial presentation were more likely than patients with a single aneurysm at presentation to develop a new or enlarging aneurysm (RR, 6.2; 95% CI, 2.1%-185; P = .0058). Patients who initially presented with at least 1 fusiform aneurysm were more likely to develop a new or enlarging aneurysm than patients who did not present with a fusiform aneurysm (RR, 22; 95% CI, 3.6%-68%; P = .00050). Index aneurysm treatment with parent artery occlusion also was associated with higher risk of new aneurysm formation (RR, 4.2; 95% CI, 1.3%-13%; P = .024). New aneurysms did not necessarily arise near index aneurysms. The only fatality in the series was due to subarachnoid hemorrhage from a new posterior circulation aneurysm arising 20 months after index anterior circulation aneurysm treatment in an immunosuppressed patient. CONCLUSIONS: Patients who presented with a fusiform aneurysm had a significantly greater incidence of developing a new aneurysm or enlargement of an index aneurysm than did those who presented with a saccular aneurysm. In our patient cohort, 8 of the 9 children who eventually developed new or enlarging brain aneurysms initially presented with fusiform aneurysm morphology. Other comorbidities or multiple aneurysms were also common in these patients at initial presentation.

[Imaging of mild cognitive impairment]. / Exploracion del deterioro cognitivo leve por neuroimagen.

The refinement of in vivo imaging approaches to investigating the structure and function of the aging brain has provided the opportunity to strengthen our knowledge of the biological substrate of normal aging and late life neurological and psychiatric disorders. While postmortem studies are biased toward the end stages of disease, functional and structural imaging have permitted us to characterize the brain changes accompanying early Alzheimer s disease (AD). As more effective therapeutic approaches to slowing (and potentially reversing) disease progression are developed, the role of imaging in determining pre AD or high risk conditions becomes increasingly important. The goal of applying non invasive means to identify the transition state of mild cognitive impairment (MCI) is of considerable public health importance. Further, emerging imaging strategies may be used to monitor the efficacy of therapeutic regimens.

Parental reporting of smelly urine and urinary tract infection.

BACKGROUND: Parents often report that young children have "smelly urine" or a particular urinary odour. There is little evidence that these observations are relevant to the diagnosis of urinary tract infection (UTI). AIMS: To determine whether parental reporting of smelly urine is of any relevance to the diagnosis of UTI in children less than 6 years of age. METHODS: Parents whose children were having urine collected as part of their admission to a large district hospital were given a simple questionnaire to complete regarding the current smell of their child's urine. Parents were asked whether their child's urine smelled different from usual or had a particular smell. Microscopy and culture results of the child's urine were compared to their parent's questionnaire answers to see if there was a association between parental reporting of a different or particular urine smell and a diagnosis of UTI. RESULTS: One hundred and ten questionnaires and urine samples were obtained. Fifty two per cent of parents thought that their child's urine smelled different from usual or had a particular smell. Only 6.4% of children were diagnosed as having a UTI. There was no statistically significant association between parental reporting of abnormal urine smell and diagnosis of UTI. CONCLUSION: In determining whether a young child has a UTI, asking parents about urine smell is unlikely to be of benefit.

Selection criteria among gastroenterologists and surgeons for laparoscopic antireflux surgery.

BACKGROUND: Symptomatic gastroesophageal reflux disease (GERD) affects a substantial proportion of the American population. The diagnosis and treatment of GERD has advanced tremendously over the past 30 years. However, there remains a lack of understanding about the differences and advantages that laparoscopic antireflux surgery offers and a lack of agreement on the ideal surgical candidate. The purpose of this study was to determine whether a significant difference exists in the practice habits and selection criteria for surgery between gastroenterologists and laparoscopic surgeons. METHODS: Surveys were sent to 1,000 randomly selected members of the American Gastroenterological Association (AGA) and to 1,000 randomly selected members of the Society of American Gastrointestinal Endoscopic Surgeons (SAGES). As a result, 20% of the AGA surveys and 33% of the SAGES surveys were completed and returned. RESULTS: The AGA group considered patients whose symptoms are not well controlled, those who have complications of disease, and those who require significant lifestyle changes to control their symptoms as the best candidates for surgical evaluation. As a group, gastroenterologists remain somewhat hesitant to refer patients for laparoscopic antireflux surgery. Surgeons considered patients whose symptoms have been well controlled with medical therapy, those who have complications of disease, and those who require significant lifestyle changes to control their symptoms as ideal candidates for fundoplication. CONCLUSION: A consensus should be reached between surgeons and gastroenterologists in establishing criteria for surgical intervention to manage GERD.

Increasingly intolerable boundaries: future control of environmental pollution.

In recent years, there have been a number of toxic accidents on the sea and on land which have caused pollution down current, down wind and down stream. Four were dramatic and these four have led to substantial changes in the way we deal with risk to the environment. There have also been increasing concerns about a less spectacular but equally concerning problem, acid rain, though attempts to deal with this problem have been less successful. Perhaps the drama was lacking. In all these cases, unfortunately, the less developed countries can ill afford the costs of prevention and this means they are often the home of environmentally unfriendly development. While the current approaches to such problems will continue, it is likely that the countries on the receiving end of such pollution, especially if they have economic and military power, will seek more forceful solutions. One outcome may be a UN-sponsored environmental police force.

Pharmacological investigation of mitochondrial ca(2+) transport in central neurons: studies with CGP-37157, an inhibitor of the mitochondrial Na(+)-Ca(2+) exchanger.

Mitochondria buffer large changes in [Ca(2+)](i)following an excitotoxic glutamate stimulus. Mitochondrial sequestration of [Ca(2+)](i)can beneficially stimulate oxidative metabolism and ATP production. However, Ca(2+)overload may have deleterious effects on mitochondrial function and cell survival, particularly Ca(2+)-dependent production of reactive oxygen species (ROS) by the mitochondria. We recently demonstrated that the mitochondrial Na(+)-Ca(2+)exchanger in neurons is selectively inhibited by CGP-37157, a benzothiazepine analogue of diltiazem. In the present series of experiments we investigated the effects of CGP-37157 on mitochondrial functions regulated by Ca(2+). Our data showed that 25 microM CGP-37157 quenches DCF fluorescence similar to 100 microM glutamate and this effect was enhanced when the two stimuli were applied together. CGP-37157 did not increase ROS generation and did not alter glutamate or 3mM hydrogen-peroxide-induced increases in ROS as measured by DHE fluorescence. CGP-37157 induces a slight decrease in intracellular pH, much less than that of glutamate. In addition, CGP-37157 does not enhance intracellular acidification induced by glutamate. Although it is possible that CGP-37157 can enhance mitochondrial respiration both by blocking Ca(2+)cycling and by elevating intramitochondrial Ca(2+), we did not observe any changes in ATP levels or toxicity either in the presence or absence of glutamate. Finally, mitochondrial Ca(2+)uptake during an excitotoxic glutamate stimulus was only slightly enhanced by inhibition of mitochondrial Ca(2+)efflux. Thus, although CGP-37157 alters mitochondrial Ca(2+)efflux in neurons, the inhibition of Na(+)-Ca(2+)exchange does not profoundly alter glutamate-mediated changes in mitochondrial function or mitochondrial Ca(2+)content.

Astrocytes are more resistant than neurons to the cytotoxic effects of increased [Zn(2+)](i).

Increased intracellular free Zn(2+) ([Zn(2+)](i)) is toxic to neurons. Glia are more resistant to Zn(2+)-mediated toxicity; however, it is not known if this is because glia are less permeable to Zn(2+) or if glia possess intrinsic mechanisms that serve to buffer or extrude excess [Zn(2+)](i). We used the Zn(2+)-selective ionophore pyrithione to directly increase [Zn(2+)](i) in both neurons and astrocytes. In neurons, a 5-min exposure to 1 microM extracellular Zn(2+) in combination with pyrithione produced widespread toxicity, whereas extensive astrocyte injury was not observed until extracellular Zn(2+) was increased to 10 microM. Measurements with magfura-2 demonstrated that pyrithione increased [Zn(2+)](i) to similar levels in both cell types. We also measured how increased [Zn(2+)](i) affects mitochondrial membrane potential (Deltapsi(m)). In astrocytes, but not in neurons, toxic [Zn(2+)](i) resulted in an acute loss of Deltapsi(m), suggesting that mitochondrial dysregulation may be an early event in [Zn(2+)](i)-induced astrocyte but not neuronal death.

The Pleistocene serpent Wonambi and the early evolution of snakes.

The Madtsoiidae were medium sized to gigantic snakes with a fossil record extending from the mid-Cretaceous to the Pleistocene, and spanning Europe, Africa, Madagascar, South America and Australia. This widely distributed group survived for about 90 million years (70% of known ophidian history), and potentially provides important insights into the origin and early evolution of snakes. However, madtsoiids are known mostly from their vertebrae, and their skull morphology and phylogenetic affinities have been enigmatic. Here we report new Australian material of Wonambi, one of the last-surviving madtsoiids, that allows the first detailed assessment of madtsoiid cranial anatomy and relationships. Despite its recent age, which could have overlapped with human history in Australia, Wonambi is one of the most primitive snakes known--as basal as the Cretaceous forms Pachyrhachis and Dinilysia. None of these three primitive snake lineages shows features associated with burrowing, nor do any of the nearest lizard relatives of snakes (varanoids). These phylogenetic conclusions contradict the widely held 'subterranean' theory of snake origins, and instead imply that burrowing snakes (scolecophidians and anilioids) acquired their fossorial adaptations after the evolution of the snake body form and jaw apparatus in a large aquatic or (surface-active) terrestrial ancestor.

Relationship of the dimension of cardiac structures to body size: an echocardiographic study in normal infants and children.

Normalization of the dimensions of cardiac structures to the size of the body, using so-called Z scores, is becoming increasingly common in the management of infants and children with congenital heart disease. Current published nomograms for the ascertainment of Z scores for cardiac structures in childhood are based largely on normal data obtained in formalin-fixed hearts. Since decisions concerning management are frequently based on the findings of cross-sectional echocardiograms, the dimensions of 15 cardiac structures were measured using cross-sectional echocardiography in 125 normal infants and children. Regression equations were derived relating cardiac dimensions to the size of the body. The expression of size with the highest correlation to cardiac dimensions was body surface area. Nomograms were then developed from which the Z score of a cardiac structure could be estimated from a knowledge of the body surface area and the echocardiographically derived measurement.

Effects of oxidants and glutamate receptor activation on mitochondrial membrane potential in rat forebrain neurons.

Both glutamate and reactive oxygen species have been implicated in excitotoxic neuronal injury, and mitochondria may play a key role in the mediation of this process. In this study, we examined whether glutamate-receptor stimulation and oxidative stress interact to affect the mitochondrial membrane potential (delta psi). We measured delta psi in rat forebrain neurons with the ratiometric fluorescent dye JC-1 by using laser scanning confocal imaging. Intracellular oxidant levels were measured by using the oxidation-sensitive dyes 2',7'-dichlorodihydrofluorescein (DCFH2) and dihydroethidium (DHE). Application of hydrogen peroxide (0.3-3 mM) or 1 mM xanthine/0.06 U/ml xanthine oxidase decreased delta psi in a way that was independent of the presence of extracellular Ca2+ and was not affected by the addition of cyclosporin A, suggesting the presence of either a cyclosporin A-insensitive form of permeability transition, or a separate mechanism. tert-Butylhydroperoxide (730 microM) had less of an effect on delta psi than hydrogen peroxide despite similar effects on intracellular DCFH2 or DHE oxidation. Hydrogen peroxide-, tert-butylhydroperoxide-, and superoxide-enhanced glutamate, but not kainate, induced decreases in delta psi. The combined effect of peroxide or superoxide plus glutamate was Ca2+ dependent and was partially inhibited by cyclosporin A. These results suggest that oxidants and glutamate depolarize mitochondria by different mechanisms, and that oxidative stress may enhance glutamate-mediated mitochondrial depolarization.

Permanent presence of managed care and outcome of critically ill infants.

In the era of managed care, the potential for high-risk patients of all ages to receive less than optimal care exists because the mechanism for reimbursement is designed to promote savings. The specific ways managed care payment mechanisms actually differ from indemnity insurance or fee-for-service are conceptually quite simple. This article reviews mechanisms such as utilization review, setting length-of-stay bench marks, preapproval for referrals to specialists, specific treatments, procedures, and hospital days.

Effects of pyrroloquinoline quinone on glutamate-induced production of reactive oxygen species in neurons.

Pyrroloquinoline quinone may act as a free radical scavenger and also as a modulator of the NMDA receptor associated redox modulatory site. Using the oxidation sensitive dye dihydroethidium, we examined the effects of pyrroloquinoline quinone on free radical production in cultured forebrain neurons following glutamate receptor activation. Both glutamate (100 microM) and hydrogen peroxide (30 mM) produced a rapid increase in dihydroethidium fluorescence indicating dye oxidation. Pyrroloquinoline quinone (5-200 microM) effectively inhibited dihydroethidium fluorescence induced by glutamate but not by hydrogen peroxide. Glutamate-induced dihydroethidium fluorescence was inhibited by the thiol oxidant 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB). Pyrroloquinoline quinone (50 microM) inhibited glutamate responses in control and in dithiothreitol treated neurons. However, pyrroloquinoline quinone did not further decrease the response to glutamate in DTNB treated neurons. These results suggest that pyrroloquinoline quinone inhibits the free radical-generating response to glutamate by oxidizing the NMDA receptor redox site and not by scavenging reactive oxygen species.

Vagal regulation of heart rate in the prediction of developmental outcome for very low birth weight preterm infants.

To investigate heart rate and respiratory sinus arrhythmia (RSA) as markers of developmental outcome, infant ECG and 3 year outcome were assessed in 41 very low birth weight (< 1,500 g) infants. Measures of mean heart rate and RSA, and the maturational shifts in their values from 33 to 35 weeks gestational age, were recorded. RSA measures predicted 3 year outcome beyond the effects of birth weight, medical risk, and socioeconomic status. Higher RSA was associated with better social skills, whereas greater RSA maturation was associated with better mental processing and gross motor skills. Lower heart rate was associated with better behavior regulation and social skills, whereas greater maturational decreases were associated with better gross motor skills. Dividing the sample into groups of infants with birth weights less than 1,000 g and those with birth weights over 1,000 g, RSA maturation emerged a strong predictor of mental processing, knowledge base, and gross motor skills in the former. A measure of joint maturation of RSA and heart rate was associated with better behavior regulation at 3 years, as measured by Child Behavior Checklist and Parenting Stress Index scores, for this group. The findings directly respond to the need for physiological variables in the prediction of outcome in high-risk infants.

Pseudomeningocele/CSF fistula in a patient with lumbar spinal implants treated with epidural blood patch and a brief course of closed subarachnoid drainage. A case report.

STUDY DESIGN: This case report illustrates the development of a cerebrospinal fluid fistula and pseudomeningocele in a patient after lumbar discectomy and fusion with instrumentation. OBJECTIVE: The patient is treated successfully with a combined treatment protocol of epidural blood patch and brief course of spinal drainage. SUMMARY OF BACKGROUND DATA: Many surgeons advocate a trial of cerebrospinal fluid diversion for postoperative cerebrospinal fluid fistula. This treatment may be problematic in patients with spinal implants because a trial of cerebrospinal fluid diversion may not obliterate the extradural anatomic dead space that is created by instrumentation procedures and increases the rist of infection. A few case reports indicate that epidural blood patch also may be an effective management technique. A combined treatment protocol that may offer some advantages to either treatment alone is described METHODS: The patient was brought to the radiology department, and a lumbar spinal drain was placed at the L2-L3 interspace under fluoroscopic guidance with the patient in the prone position. A Tuohy needle was inserted into the pseudomeningocele, and the collection was drained. Thirty milliters of blood drawn from an antecubital vein was injected into the epidural space over the laminectomy site. Spinal drainage was continued for 4 days. RESULTS: The treatment protocol resulted in resolution of cerebrospinal fluid leakage in the patient. This result was confirmed by myelogram. CONCLUSIONS: Postoperative pseudomeningocele and cerebrospinal fluid fistula in patients with spinal instrumentation can be treated successfully with epidural blood patch and a brief course (4 days) of spinal drainage. This combined treatment protocol may have some advantages to treatment with 7 days of cerebrospinal fluid diversion or to percutaneous epidural blood patch alone.