bluuebunny/crossref_metadata_2025 huggingface dataset:
New Evidence Supporting a Role for T-Type Ca2+ Channels in Absence Epilepsy and in the Action of Ethosuximide
Authors: Rogawski Michael A.
Published: December 2022

Lack of the Burst Firing of Thalamocortical Relay Neurons and Resistance to Absence Seizures in Mice Lacking α1G T-Type Ca2+ Channels

Kim D, Song I, Keum S, Lee T, Jeong MJ, Kim SS, McEnery MW, Shin HS

Neuron 2001;31:35–45

T-type Ca2+ currents have been proposed to be involved in the genesis of spike-and-wave discharges, a sign of absence seizures, but direct evidence in vivo to support this hypothesis has been lacking. To address this question, we generated a null mutation of the α1G subunit of T-type Ca2+ channels. The thalamocortical relay neurons of the α1G-deficient mice lacked the burst mode firing of action potentials, whereas they showed the normal pattern of tonic mode firing. The α1G-deficient thalamus was specifically resistant to the generation of spike-and-wave discharges in response to GABAB receptor activation. Thus, the modulation of the intrinsic firing pattern mediated by α1G T-type Ca2+ channels plays a critical role in the genesis of absence seizures in the thalamocortical pathway.

Block of Cloned Human T-Type Calcium Channels by Succinimide Antiepileptic Drugs

Gomora JC, Daud AN, Weiergraber M, Perez-Reyes E

Mol Pharmacol 2001;60:1121–1132

Inhibition of T-type Ca2+ channels has been proposed to play a role in the therapeutic action of succinimide antiepileptic drugs. Despite the widespread acceptance of this hypothesis, recent studies using rat and cat neurons have failed to confirm inhibition of T-type currents at therapeutically relevant concentrations. The present study re-examines this issue using the three cloned human channels that constitute the T-type family: α1G, α1H, and α1I. The cloned cDNAs were stably transfected and expressed into mammalian cells, leading to the appearance of typical T-type currents. The results demonstrate that both ethosuximide and the active metabolite of methsuximide, α-methyl-α-phenylsuccinimide (MPS), block human T-type channels in a state-dependent manner, with higher affinity for inactivated channels. In contrast, succinimide analogs that are not anticonvulsive were relatively poor blockers. The apparent affinity of MPS for inactivated states of the three channels was estimated using two independent measures: K1 for α1G and α1I was 0.3 to 0.5 mM and for α1H was 0.6 to 1.2 mM. T-type channels display current at the end of long pulses (persistent current), and this current was especially sensitive to block (ethosuximide IC50 = 0.6 mM). These drugs also reduced both the size of the T-type window current region and the currents elicited by a mock low threshold spike. We conclude that succinimide antiepileptic drugs are capable of blocking human T-type channels at therapeutically relevant concentrations.
Block of Thalamic T-Type Ca2+ Channels by Ethosuximide Is Not the Whole Story
Authors: Crunelli Vincenzo , Leresche Leresche
Published: December 2022

On the basis of more than a decade of studies on the cellular effects of ethosuximide, currently, the most prudent view is that together with a block of the low threshold, T-type Ca2+ current, a reduction both of the noninactivating Na+ current, and the Ca2+-activated K+ current in thalamic and cortical neurones contribute to the overall therapeutic action of this antiabsence medicine.
Prophylactic Anticonvulsants after Neurosurgery
Authors: Temkin Nancy R.
Published: December 2022

Six prospective, controlled trials have examined the effects of antiepileptic drugs (AEDs) given to prevent the occurrence of seizures following neurosurgery. Some studies have concentrated on specific reasons for the neurosurgery (brain tumor) while others have included people with a variety of indications for surgery. Phenytoin (PHT) has been studied most, but carbamazepine (CBZ) and phenobarbital (PB) have also been evaluated to some extent. Studies of people with traumatic brain injury (some of whom were operated on) provide some, but less direct, evidence of the prophylactic effects of AEDs after neurosurgery. Despite considerable variation in reasons for the neurosurgery, AEDs given, and study design, the overall conclusions are remarkably consistent. The seizure risk is reduced about 40%–50% for the first week after neurosurgery in those given the older AEDs compared with those given placebo or no treatment. After the first few weeks, none of the drugs has been proven to reduce the incidence of seizures and in most situations the best estimate is essentially no effect, but effects on the order of a 25%–50% reduction in late (epileptic) seizures cannot be ruled out. The new generation of AEDs have not been tested as prophylactic agents after neurosurgery. Although there are no guidelines for prophylaxis following neurosurgery in general, these results are consistent with the guidelines of professional organizations for subsets of neurosurgery cases. Those guidelines consider prophylaxis, especially using PHT, to be an option for the first week after surgery but that the routine use of prophylactic anticonvulsants after the first week is not warranted.
Negative Symptoms in Temporal Lobe Epilepsy
Authors: Kanner Andres M.
Published: December 2022

Negative Symptoms in Temporal Lobe Epilepsy

Getz K, Hermann B, Seidenberg M, Bell B, Dow C, Jones J, Woodard A, Rutecki P, Sheth R, O'Leary D, Magnotta V.

Am J Psychiatry 2002;159:644–651

Objective

This study examined the frequency of negative and positive symptoms in nonpsychotic patients with temporal lobe epilepsy and the relationship of negative and positive symptoms to cognition, quantitative magnetic resonance imaging (MRI) volumetrics, and depression.

Method

Eighty-four patients with temporal lobe epilepsy and 74 healthy comparison subjects were evaluated for negative and positive symptoms and underwent comprehensive neuropsychological evaluation, quantitative MRI volumetrics, and assessment of mood state and depression.

Results

Negative symptoms were significantly more prevalent in the patients with temporal lobe epilepsy (31%) than in the comparison subjects (8%). There was no difference between groups in the rate of positive symptoms. Although the epilepsy patients as a group exhibited generalized cognitive impairment relative to the comparison subjects, the epilepsy patients with negative symptoms performed significantly worse than patients without negative symptoms and comparison subjects across measures of nonverbal intelligence, visuoperception, speeded visuomotor processing, and memory. The epilepsy patients with negative symptoms exhibited significantly greater diffuse atrophy than the healthy comparison subjects and higher CSF volumes than the epilepsy patients without negative symptoms. The epilepsy patients with and without negative symptoms had statistically equivalent Beck Depression Inventory scores and lifetime history of mood disorders, including major depression.

Conclusions

Negative but not positive symptoms were more prevalent in temporal lobe epilepsy patients than in healthy comparison subjects. Negative symptoms were independent of current and past depression and were associated with neuropsychological deficits exceeding the general cognitive morbidity associated with temporal lobe epilepsy and with quantitative MRI indices, suggesting greater cerebral atrophy.
Poststroke Seizures and Epilepsy: Clinical Studies and Animal Models
Authors: Kelly Kevin M.
Published: December 2022

Poststroke seizures and epilepsy have been described in numerous clinical studies for many years. Most studies are retrospective in design, include relatively small numbers of patients, have limited periods of follow-up, and report a diversity of findings. Well-designed clinical trials and population studies in the recent past addressed several critical clinical issues and generated important findings regarding the occurrence of poststroke seizures and epilepsy. In contrast, the pathophysiologic events of injured brain that establish poststroke epileptogenesis are not well understood, and animal modeling has had limited development. Reviews of several important clinical studies and animal models that hold promise for a better understanding of poststroke epileptogenesis are presented.
Functional MRI for Language Localization
Authors: Cascino Gregory
Published: December 2022

Language Dominance in Partial Epilepsy Patients Identified with an fMRI Reading Task

Gaillard WD, Balsamo L, Xu B, Grandin CB, Braniecki SH, Papero PH, Weinstein S, Conry J, Pearl PL, Sachs B, Sato S, Jabbari B, Vezina LG, Frattali C, Theodore WH

Neurology 2002;59(2):256–265

Background

Functional magnetic resonance imaging (fMRI) language tasks readily identify frontal language areas; temporal activation has been less consistent. No studies have compared clinical visual judgment with quantitative region-of-interest (ROI) analysis.

Objective

To identify temporal language areas in patients with partial epilepsy by using a reading paradigm with clinical and ROI interpretation.

Methods

Thirty patients with temporal lobe epilepsy, aged 8 to 56 years, had 1.5-T fMRI. Patients silently named an object described by a sentence compared with a visual control. Data were analyzed with ROI analysis from t-maps. Regional asymmetry indices (AIs) were calculated ([L-R]/[L+R]), and language dominance defined as >0.20. t-Maps were visually rated by three readers at three t thresholds. Twenty-one patients had the intracarotid amobarbital test (IAT).

Results

The fMRI reading task provided evidence of language lateralization in 27 of 30 patients with ROI analysis. Twenty-five were left dominant, two right, one bilateral, and two were nondiagnostic; IAT and fMRI agreed in most patients; three had partial agreement, and none overtly disagreed. Interrater agreement ranged between 0.77 to 0.82 (Cramer V; p < 0.0001); agreement between visual and ROI reading with IAT was 0.71 to 0.77 (Cramer V; p < 0.0001). Viewing data at lower thresholds added interpretation to 12 patients on visual analysis and eight with ROI analysis.

Conclusions

An fMRI reading paradigm can identify language dominance in frontal and temporal areas. Clinical visual interpretation is comparable to quantitative ROI analysis.
The “Reel” Pathology of Temporal Lobe Epilepsy
Authors: Scharfman Helen
Published: December 2022

Role for Reelin in the Development of Granule Cell Dispersion in Temporal Lobe Epilepsy

Haas C, Dudeck O, Kirsch M, Huszka C, Kann G, Pollak S, Zentner J, Frotscher M

J Neurosci 2002;22:5797–5802

The reelin signaling pathway plays a crucial role during the development of laminated structures in the mammalian brain. Reelin, which is synthesized and secreted by Cajal–Retzius cells in the marginal zone of the neocortex and hippocampus, is proposed to act as a stop signal for migrating neurons. Here we show that a decreased expression of reelin messenger RNA (mRNA) by hippocampal Cajal–Retzius cells correlates with the extent of migration defects in the dentate gyrus of patients with temporal lobe epilepsy. These results suggest that reelin is required for normal neuronal lamination in humans, and that deficient reelin expression may be involved in migration defects associated with temporal lobe epilepsy.
Synaptic Reorganization in an Experimental Model of Posttraumatic Epilepsy
Authors: Dudek F. Edward , Shao Li-Rong
Published: December 2022

Synaptic Activity in Chronically Injured, Epileptogenic Sensorimotor Neocortex

Li H, Prince D

J Neurophysiol 2002;88:2–12

We recorded spontaneous and evoked synaptic currents in pyramidal neurons of layer V in chronically injured, epileptogenic neocortex to assess changes in the efficacy of excitatory and inhibitory neurotransmission that might promote cortical hyperexcitability. Partial sensory-motor neocortical isolations with intact blood supply (“undercuts”) were made in 20 rats on postnatal day 21–25 and examined 2–6 weeks later in standard brain slice preparations by using whole-cell patch-clamp techniques. Age-matched, uninjured naive rats (n = 20) were used as controls. Spontaneous and miniature excitatory and inhibitory postsynaptic currents (s- and mEPSCs; s- and mIPSCs) were recorded by using patch-clamp techniques. The average frequency of s- and mEPSCs was significantly higher, whereas that of s- and mIPSCs was significantly lower in neurons of undercuts versus controls. The increased frequency of excitatory events was due to an increase in both s- and mEPSC frequency, suggesting an increased number of excitatory contacts and/or increased release probability at excitatory terminals. No significant difference was observed in 10–90% rise time of these events. The input-output slopes of fast, short-latency, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate (AMPA/KA) receptor-mediated components of evoked EPSCs were steeper in undercuts than in controls. The peak amplitude of the AMPA/KA component of EPSCs evoked by suprathreshold stimuli was significantly greater in the partially isolated neocortex. In contrast, the N-methyl-d-aspartate receptor-mediated component of evoked EPSCs was not significantly different in neurons of injured versus control cortex, suggesting that the increased AMPA/KA component was due to postsynaptic alterations. Results support the conclusion that layer V pyramidal neurons receive increased AMPA/KA receptor-mediated excitatory synaptic drive and decreased γ-aminobutyric acid type A (GABAA) receptor-mediated inhibition in this chronically injured, epileptogenic cortex. This shift in the balance of excitatory and inhibitory synaptic activation of layer V pyramidal cells toward excitation might be maladaptive and play a critical role in epileptogenesis.
Prolonged Febrile Convulsions Produce More Severe Mesial Temporal Sclerosis
Authors: Theodore William H.
Published: December 2022

Quantitative Magnetic Resonance Characterization of Mesial Temporal Sclerosis in Childhood

Scott RC, Gadian DG, Cross JH, Wood SJ, Neville BG, Connelly A

Neurology 2001;56:1659–1665

Objective

To investigate whether quantitative magnetic resonance (MR) techniques can be used to distinguish between mesial temporal sclerosis in patients with a history of prolonged febrile convulsion and in patients without such a history.

Methods

Quantitative hippocampal T2 relaxometry, hippocampal volumetry, and single-voxel 1H-magnetic resonance spectroscopy (MRS) data were acquired from 16 children who subsequently underwent temporal lobe resections for intractable temporal lobe epilepsy and histologically were shown to have sclerosis of the horn of Ammon. Eight children had a history of prolonged febrile convulsion in early childhood, and eight children had other or no associations.

Results

Patients with a history of prolonged febrile convulsion had smaller hippocampi (p = 0.02) and prolonged T2 relaxation time (p = 0.03) ipsilateral to the seizure focus when compared with patients without such a history. There was also more side-to-side asymmetry of T2 relaxation time (p = 0.004) and hippocampal volume (p = 0.02) in the patients with a history of prolonged febrile convulsion than in those with other or no associations. No differences between the groups were identified by using 1H-MRS

Conclusions

These data support the view that there are at least two types of mesial temporal sclerosis. There may be several pathogenetic pathways from initial insult to later mesial temporal sclerosis, and these pathways are, at least in part, dependent on the initial insult.
Collective Data Supports Efficacy of Multiple Subpial Transection
Authors: Faught Edward
Published: December 2022

Multiple Subpial Transection for Intractable Partial Epilepsy: An International Meta-Analysis

Spencer SS, Schramm J, Wyler A, O'Connor M, Orbach D, Krauss G, Sperling M, Devinsky O, Elger C, Lesser R, Mulligan L, Westerveld M

Epilepsia 2002;43:141–145

Because the number and variety of patients at any single facility is not sufficient for clinical or statistical analysis, data from six major epilepsy centers that performed multiple subpial transections (MSTs) for medically intractable epilepsy were collected. A meta-analysis was performed to elucidate the indications and outcome, and to assess the results of the procedure. Overall, 211 patients were represented with data regarding preoperative evaluation, procedures, seizure types and frequencies before and after surgery, postoperative deficits, and demographic information. Fifty-three patients underwent MST without resection. In patients with MST plus resection, excellent outcome (>95% reduction in seizure frequency) was obtained in 87% of patients for generalized seizures, 68% for complex partial seizures, and 68% for simple partial seizures. For the patients who underwent MST without resection, the rate of excellent outcome was only slightly lower, at 71% for generalized, 62% for complex partial, and 63% for simple partial seizures. EEG localization, age at epilepsy onset, duration of epilepsy, and location of MST were not significant predictors of outcome for any kinds of seizures after MST, with or without resection. New neurologic deficits were found in 47 patients overall, comparable in MST with resection (23%) or without (19%). These preliminary results suggest that MST has efficacy by itself, with minimal neurologic compromise, in cases in which resective surgery cannot be used to treat uncontrolled epilepsy. MST should be investigated as a stand-alone procedure to allow further development of criteria and predictive factors for outcome.
Randomized Controlled Trial of Prophylactic Phenytoin after Neurosurgery for Brain Tumor
Authors: Penovich Patricia E.
Published: December 2022

Add-on Phenytoin Fails to Prevent Early Seizures after Surgery for Supratentorial Brain Tumors: A Randomized Controlled Study

De Santis A, Villani R, Sinisi M, Stocchetti N, Perucca E

Epilepsia 2002;43:175–182

Purpose

To determine the potential effectiveness of phenytoin (PHT) in preventing early postoperative seizures in patients undergoing craniotomy for supratentorial brain tumors. Two hundred patients requiring elective craniotomy for supratentorial brain tumors were randomized to two groups of equal size, with a prospective, open-label, controlled design. One group received PHT (18 mg/kg as an intravenous intraoperative load, followed by additional daily doses aimed at maintaining serum PHT concentrations within the 10- to 20-age/ml range) for 7 consecutive days. In the other group, PHT was not administered. More than 90% of patients in both groups continued to take preexisting anticonvulsant medication (AEDs) with carbamazepine or phenobarbital throughout the study. The primary efficacy end point was the number of patients remaining free from seizures during the 7-day period after the operation. Of 100 patients allocated to PHT, 13 experienced seizures during the 7-day observation period, compared with 11 of 100 patients in the placebo group (p > 0.05). Most seizures occurred in the first day after surgery in both groups. There were no differences between groups in the proportion of patients experiencing more than one seizure, but there was a trend for generalized seizures to be more common in PHT-treated patients than in controls (11 vs. five patients, respectively). Status epilepticus occurred in one patient in the PHT group and in two patients in the control group. Of the 13 PHT-treated seizure patients, 11 had serum PHT concentrations within the target range, and only two had concentrations below range on the days their seizures occurred. PHT, given at dosages producing serum concentrations within the target range, failed to prevent early postoperative seizures in patients treated with concomitant AEDs. Prophylactic administration of PHT cannot be recommended in these patients.
Animal Model of Cortical Dysplasia for Screening Candidate AEDs
Authors: Sankar Raman
Published: December 2022

Effects of Antiepileptic Drugs on Induced Epileptiform Activity in a Rat Model of Dysplasia

Smyth MD, Barbaro NM, Baraban SC

Epilepsy Res 2002;50:251–264

Seizure activity associated with cortical dysplasia (CD) is often resistant to standard pharmacologic treatments. Although several animal models exhibit CD, virtually nothing is known about antiepileptic drug (AED) responses in these animals. Here we used rats exposed to methylazoxymethanol acetate (MAM) in utero, an animal model featuring nodular heterotopia, to investigate the effects of AEDs in the dysplastic brain. 4-Aminopyridine (AP; 100 μM), a K+ channel blocker, was used to induce interictal epileptiform bursting in acute hippocampal slices from MAM-exposed and age-matched vehicle-injected control animals. Extracellular field recordings were used to monitor seizure activity in vitro. Five commonly used AEDs were tested: Phenobarbital (PB), 25–400 μM; carbamazepine (CBZ), 25–200 μM; valproate (VPA), 0.19–4 mM; ethosuximide (ESM), 0.5–8 mM; and lamotrigine (LTG), 49–390 μM. 4-AP-induced bursting occurred with shorter latencies in slices from MAM-exposed rats in comparison with slices from controls, confirming the intrinsic hyperexcitability of dysplastic tissue. Each AED tested demonstrated significant burst suppression in control slices, but interictal epileptiform bursting in MAM-exposed slices was resistant to these treatments. Even at the highest concentrations, VPA, ESM, and LTG had no effect on burst amplitude in slices from MAM-exposed rats. Pharmacoresistance was further tested by measuring seizure latencies in awake, freely moving rats after kainate administration (15 mg/kg, i.p.) with and without pretreatment with VPA (400 mg/kg, i.p.). Pretreatment with VPA prolonged seizure latency in control rats, but had no effect in MAM-exposed animals. These results suggest MAM-exposed rats exhibit a dramatically reduced sensitivity to commonly prescribed AEDs.
More Sensitive MRI Techniques for Detecting Focal Cortical Dysplasia
Authors: Cascino Gregory D.
Published: December 2022

Focal Cortical Dysplasia: Improving Diagnosis and Localization with Magnetic Resonance Imaging Multiplanar and Curvilinear Reconstruction

Montenegro MA, Li LM, Guerreiro MM, Guerreiro CA, Cendes F

J Neuroimaging 2002;12(3):224–230

Objective

To establish the contribution of multiplanar reconstruction (MPR) and curvilinear reformatting (CR) to the MRI investigation of focal cortical dysplasia (FCD).

Methods

From a group of patients with intractable frontal lobe epilepsy, we selected patients with neuroimaging diagnosis of FCD. The diagnosis of FCD was based on the neuroimaging findings after a three step evaluation, always in the same order: (a) plain MRI films, (b) MPR, and (c) CR. After the selection of patients, the process of reviewing all the images in the three stages described was performed by one of us, who did not take part on the selection of patients or on the initial evaluation, and who was blind to the clinical and EEG findings of the patients. For data analysis, we first assessed the contribution of the additional findings of MPR analysis compared with the results of the evaluation using only plain MRI films, as is usually done in routine practice. Second, we assessed the contribution of CR to the findings of plain MRI films plus MPR. After completing the multistep evaluation, we all went back to review the plain MRI films with knowledge of lesion topography, to identify possible subtle features associated with FCD.

Results

Seventeen patients met the inclusion criteria. Twelve had imaging diagnosis of FCD and were included in the second step of this project. Plain films of high-resolution MRI showed the lesion in six (50%) of the 12 patients. By adding MPR to the plain MRI films, we identified lesions in all 12 patients. Furthermore, we found that MPR provided a better lesion localization and ascertainment of its relation to other cerebral structures in five (83%) of six patients who had a lesion identified on plain films. By adding CR to the plain MRI films plus MPR analysis, we observed that (a) CR also allowed the identification of the dysplastic lesion in all patients, (b) CR improved lesion localization in one patient, and (c) CR provided a better visualization of the lesion extent in four patients (33%), showed a larger lesion in three, and demonstrated that part of the area suspected as abnormal was more likely volume averaging in two.

Conclusions

MPR and CR analysis add to the neuroimaging evaluation of FCD by improving the lesion diagnosis and localization. CR helps to establish the extent of the lesion more precisely, allowing the visualization of some areas not shown on high-resolution MRI and MPR. These techniques are complementary and do not replace the conventional wisdom of MRI analysis.
Neuropeptide Y and Epilepsy
Authors: Colmers William F. , Bahh Bouchaïb El
Published: December 2022

It is a central tenet of the epilepsy field that seizures result from the imbalance of excitation over inhibition ( 1 ). The bulk of excitation is mediated by the neurotransmitter glutamate, whereas inhibition results mainly from the actions of γ-aminobutyric acid (GABA). In the neocortex and hippocampus, the intrinsic sources of GABA are the interneurons, which lately have come under intense scrutiny. It has become clear that a large number of distinct types of interneurons can be differentiated in part by the array of neuropeptides they coexpress (cf. 2). Evidence is emerging that the neuropeptide complement of interneurons plays important roles in the way that interneurons regulate excitability. Here we discuss what is known about the relation of one well-characterized neuropeptide, neuropeptide Y (NPY), and epilepsy in experimental animals and humans, and suggest possible roles for the receptors as targets for the control of excessive excitation in epilepsy.
Does Neuroprotection Prevent Epileptogenesis?
Authors: Dudek F. Edward , Williams Philip A.
Published: December 2022

Delayed Sclerosis, Neuroprotection, and Limbic Epileptogenesis After Status Epilepticus in the Rat

Ebert U, Brandt C, Loscher W

Epilepsia 2002;43(suppl 5):86–95

Purpose

Hippocampal sclerosis and massive neurodegeneration in other parts of the limbic system are considered hallmarks of temporal lobe epilepsy. With the rat model of kainate-induced status epilepticus, we sought to determine if limbic sclerosis after an excitotoxic insult follows a delayed type of neurodegeneration and is thus accessible to neuroprotective intervention after the insult. Effective pharmacologic neuroprotection after status epilepticus also addresses the old question of whether degenerative morphologic changes after an epilepsy-inducing event like status epilepticus are the primary cause of epileptogenesis (i.e., the development of recurrent spontaneous seizures) during the following weeks.

Methods

Female Wistar rats after 90 minutes of generalized status epilepticus were used. Molecular biologic and histologic techniques were used to demonstrate markers of delayed cell death (apoptosis) 48 hours after the status. The neuroprotective effects of i.c.v. injections of caspase inhibitors and systemic injections of the anticonvulsant drugs (AEDs) dizocilpine and retigabine (RGB) after the status epilepticus were studied. The effect of neuroprotective intervention on the development of recurrent spontaneous seizures was investigated by behavioral observation of the rats.

Results

After generalized status epilepticus in Wistar rats, massive sclerosis of the hippocampus and the piriform cortex occurred. TUNEL labeling and electron microscopy revealed that apoptosis is involved in the degenerative processes. Immunohistochemical analysis of the time course of the expression of the proapoptotic protein Bax suggested a maximal induction of apoptosis 24 to 48 hours after the status. Application of caspase inhibitors before or after the status did not reduce lesions, although Bax labeling was reduced. Injection of dizocilpine and to a lower extent also of RGB after the status prevented limbic neurodegeneration and expression of markers of apoptosis. However, the neuroprotection by dizocilpine did not prevent the development of recurrent spontaneous seizures.

Conclusions

Prolonged seizure activity can induce delayed sclerosis in the hippocampus and other parts of the limbic system. This delayed cell loss can be prevented by neuroprotective drugs after status epilepticus. However, the damage in limbic brain regions is not the main reason for limbic epileptogenesis and the occurrence of recurrent spontaneous seizures.
Motivating nurses' coworker‐directed helping behaviour during the COVID‐19 pandemic: Role of managerial humour and nurses' power distance orientation
Authors: Han Chengfang , Jiang Ping
Published: December 2022

Aims

The aims of the research are to investigate (1) the influence of managerial humour on nurses' coworker‐directed helping behaviour, (2) the mediating effect of nurses' feelings of energy between managerial humour and nurses' coworker‐directed helping behaviour and (3) the moderating effect of nurses' power distance orientation.

Design

This is a quantitative study. A three‐wave survey design was conducted to collect data from direct managers to nurse dyads.

Methods

The random sampling method was employed. Data were collected from the supervisor to subordinate dyad at three time points during the first half of 2021. A total of 235 paired data sets of nurses and their direct managers were collected from a large state‐owned Chinese hospital. We used hierarchical regression analyses via SPSS 22.0 software to examine the hypotheses.

Results

(1) Managerial humour can foster nurses' coworker‐directed helping behaviour via accumulating their feelings of energy. (2) Power distance orientation moderates the effect of managerial humour on feelings of energy as well as the indirect effect of managerial humour on nurses' coworker‐directed helping behaviour via feelings of energy, in a way that these effects are stronger when nurses have higher (vs. lower) level of power distance orientation.

Conclusion

Managerial humour can increase nurses' feelings of energy, which in turn, motivates them to help their coworkers. Nurses' power distance orientation is an important boundary condition that constrains managerial humour effectiveness.

Impact

Hospital managers could use more humour during their interactions with nurses because managerial humour can promote nurses' feelings of energy and coworker‐directed helping behaviour. Hospitals can take humour into account during managers' selection and training to improve management effectiveness. Managers in eastern countries should use more humour during their interactions with followers.

Patient or public contribution

Nurses and their direct managers from a large state‐owned Chinese hospital contributed to this study by completing the survey.
The relationship between problem‐solving behaviour and performance – Analysing tool use and information retrieval in a computer‐based office simulation
Authors: Ludwig Sabrina , Rausch Andreas
Published: December 2022

Background

Problem‐solving competences have evolved into key skills for professionals. Computer‐based business simulations enable the analysis of problem‐solving processes beyond end results. An important aspect of successful problem‐solving is to systematically use built‐in tools and process the provided information efficiently.

Objectives

This investigation explores the relationship between students' tool use, information retrieval, and problem‐solving success in a computerized problem‐solving office simulation.

Methods

Around 30,000 recorded behavioural log data points of 432 German vocational students were analysed.

Results and Conclusion

Distinct user groups are identified and cognitive problem‐solving competences are assessed to draw a link between behaviour and performance. An explorative cluster analysis based on student behaviour revealed four clusters. Significant results support the use of two cognitive tools that lead to success. One successful behaviour is using a notepad, a domain‐general and voluntary tool. Another successful problem‐solving behaviour is the use of a domain‐specific and solution‐relevant spreadsheet program. Note‐taking organizes information and mental processes while the spreadsheet leads to efficient computing. In line with other studies, students with higher problem‐solving competences tend to access tools and documents providing information more frequently.

Takeaways

Domain‐general tool use differs from domain‐specific tool use over time. There are two different successful behaviour patterns in complex problem solving. Instructional and simulation designers should provide specific tools to support students as well as tackle problems.
IL‐33‐ST2 pathway regulates AECII transdifferentiation by targeting alveolar macrophage in a bronchopulmonary dysplasia mouse model
Authors: Zhu Yue , Yao Hui‐ci , Lu Hong‐yan , Hao Xiao‐bo , Xu Su‐qing
Published: December 2022

Evidence points to the indispensable function of alveolar macrophages (AMs) in normal lung development and tissue homeostasis. However, the importance of AMs in bronchopulmonary dysplasia (BPD) has not been elucidated. Here, we identified a significant role of abnormal AM proliferation and polarization in alveolar dysplasia during BPD, which is closely related to the activation of the IL‐33‐ST2 pathway. Compared with the control BPD group, AMs depletion partially abolished the epithelialmesenchymal transition process of AECII and alleviated pulmonary differentiation arrest. In addition, IL‐33 or ST2 knockdown has protective effects against lung injury after hyperoxia, which is associated with reduced AM polarization and proliferation. The protective effect disappeared following reconstitution of AMs in injured IL‐33 knockdown mice, and the differentiation of lung epithelium was blocked again. In conclusion, the IL‐33‐ST2 pathway regulates AECII transdifferentiation by targeting AMs proliferation and polarization in BPD, which shows a novel strategy for manipulating the IL‐33–ST2‐AMs axis for the diagnosis and intervention of BPD.
A theory of socially inefficient patent holdout
Authors: Llobet Gerard , Padilla Jorge
Published: December 2022

This paper proposes a framework to analyze holdout in patent licensing negotiations. We show that when the validity of a patent is probabilistic, a potential downstream user has incentives to shun to pay the price offered by a patent holder to license the technology and risk being brought to court. These incentives are exacerbated when jurisdictions are local, and the downstream producer can approach courts sequentially. The informational spillovers across trials imply that this firm often finds optimal to go to court aiming to invalidate the patent in a jurisdiction due to the knock‐on effect on future jurisdictions. This process results in excessive litigation compared to when the jurisdiction is global. The distortions from sequential litigation are likely to be aggravated when final competition is accounted for or when patent injunctions are not allowed.
Older adults and planning for firearm safety: A qualitative study of healthcare providers
Authors: Prater Laura C. , Simonetti Joseph A. , Knoepke Christopher E. , Polzer Evan R. , Nearing Kathryn A. , Lee Teresa , Betz Marian E.
Published: December 2022

Purpose/Background

Firearm injury, particularly self‐directed, is a major source of preventable morbidity and mortality among older adults. Older adults are at elevated risk of serious illness, cognitive impairment, and depression—all known risk factors for suicide and/or unintentional injury. Healthcare providers are often the first to identify these conditions and, although they commonly deliver safety guidance to such patients, little is known about how they approach firearm safety conversations with older adults.

Methods

We conducted semi‐structured interviews with healthcare providers who care for older adults (November 2020–May 2021). We used inductive and deductive thematic analyses to develop themes. We present themes and representative quotes from our analysis.

Results

We interviewed 13 healthcare providers who regularly care for older adult firearm owners. Emergent themes were: circumstances that prompt firearm safety conversations; strategies for addressing firearm safety in routine and acute circumstances; barriers to addressing firearm safety; and available or desired resources.

Conclusion

Planning for firearm safety should occur “early and often” as part of a longitudinal relationship with older adult patients. Age‐related safety issues such as driving are regularly addressed with older adult patients, likely because there are standard processes and established pathways. Establishing processes and provider/ patient resources would help improve provider efficacy to address firearm safety and relinquishment for older adult firearm owners. Integrating firearm safety conversations into routine encounters (e.g., Medicare Annual Wellness Visit, problem‐focused visits) templates could be a promising initial step but resources for follow‐up to the firearm screening must be available to both provider and patient.
Posttraumatic stress disorder, suicide, and unintended overdose death in later life: A national cohort study of veterans aged 50 and older
Authors: Clark Ryan , Kuffel Randall L. , Neylan Thomas C. , Maguen Shira , Li Yixia , Boscardin W. John , Byers Amy L.
Published: December 2022

Background/objectives

Although studies have shown posttraumatic stress disorder (PTSD) associated with risk of suicide, the relationship in later life, especially for overdose death, remains unclear. Thus, the aim of the current study was to determine associations between PTSD, suicide, and unintended overdose death in mid‐ to late‐life.

Methods

A nationwide cohort study integrating Department of Veterans Affairs' (VA) data, Centers for Medicare & Medicaid Services data, and national cause‐specific mortality data. Participants were US veterans aged ≥50 years with PTSD diagnoses at baseline (2012–2013) and were propensity‐matched 1:1 with patients without PTSD based on sociodemographics, Charlson Comorbidity Index, and neuropsychiatric disorders (N = 951,018). Information on suicide attempts and unintended death by overdose through December 31, 2017 was provided by the VA's National Suicide Prevention Applications Network (non‐fatal attempts) and Mortality Data Repository (death).

Results

Veterans with PTSD (N = 475,509) had increased risk of suicide attempt (Hazard Ratio [HR], 1.59; 95% CI, 1.54–1.65; p < 0.001), non‐fatal attempt (HR, 1.74; 95% CI, 1.67–1.81; p < 0.001), drug overdose death overall (HR, 1.32; 95% CI, 1.22–1.42; p < 0.001), and suicide overdose death (HR, 1.44; 95% CI, 1.15–1.80; p = 0.002), even after adjusting for sociodemographics, Charlson comorbidity index, and neuropsychiatric disorders. We found increased risk for overdose death by narcotics (HR, 1.30; 95% CI, 1.15–1.46; p < 0.001), antiepileptic/sedative‐hypnotics (HR, 1.29; 95% CI, 1.02–1.62; p = 0.032), and for other/unspecified drugs (HR, 1.35; 95% CI, 1.20–1.51; p < 0.001), the last category indicative of polydrug. Results remained robust when examined for unintentional, suicide, and undetermined intent for cause‐specific death by other/unspecified drugs.

Conclusions

PTSD persists throughout mid‐ to late‐life with considerable increased risk for non‐fatal suicide attempts and suicide overdose death. These findings suggest the importance of drug‐monitoring in preventing late‐life suicide.
Injury‐related emergency department use among assisted living residents with Alzheimer's disease and related dementias
Authors: Hua Cassandra L. , Cornell Portia Y. , White Elizabeth M. , Thomas Kali S.
Published: December 2022

Background

Injuries are a leading cause of emergency department (ED) visits among older adults, and individuals with Alzheimer's disease and related dementias (ADRD) may be at particular risk. We compared injury‐related ED use among assisted living (AL) residents with and without ADRD and assessed differences in the risk of injury‐related ED visits among individuals with ADRD residing in ALs with memory care designation versus general AL.

Methods

Using Medicare claims, we identified a cohort of fee‐for‐service beneficiaries who lived in AL in 2018 and resided in one of 20 states with site‐specific information on memory care designation (n = 116,754). Outcomes included all injury‐related ED visits and injury‐related ED visits resulting in hospitalization in the calendar year 2018. We fit multilevel models of the association between ADRD and outcomes, adjusting for resident demographic characteristics and chronic conditions, license type characteristics, and AL characteristics, with random intercepts at the AL and license type levels. Among residents with ADRD, we examined whether memory care licensure was associated with injury‐related ED visits.

Results

The adjusted risk of injury‐related ED use during the year was 20.1% (95% CI: 19.6%, 20.6%) for residents with ADRD compared to 16.1% for residents without ADRD (95% CI: 15.7%, 16.5%; p < 0.001). The adjusted risk of injury‐related ED use ending in hospitalization was 4.9% (95% CI: 4.6%, 5.1%) for AL residents with ADRD and 3.9% for residents without ADRD (95% CI: 3.8%, 4.1%; p < 0.001). There were no significant differences in injury‐related ED visits between residents with ADRD in ALs with memory care designation and residents in general AL.

Conclusions

Injury‐related ED visits are common among AL residents with ADRD and residents in memory care, but residents in memory care AL experienced similar risks of injury as those in general AL. Further research should identify modifiable factors that can prevent injury among AL residents with ADRD.
Cardiopulmonary resuscitation outcomes of dogs and cats at a veterinary teaching hospital before and after publication of the RECOVER guidelines
Authors: Dazio V. E. R. , Gay J. M. , Hoehne S. N.
Published: December 2022

Objectives

To describe and compare cardiopulmonary resuscitation outcomes at a Swiss veterinary teaching hospital before and after publication of the Reassessment Campaign on Veterinary Resuscitation guidelines.

Materials and Methods

Between 2018 and 2020, hospital staff underwent various types of yearly Reassessment Campaign on Veterinary Resuscitation‐based cardiopulmonary resuscitation trainings. Canine and feline cardiopulmonary resuscitation events during that period (post‐Reassessment Campaign on Veterinary Resuscitation) and between 2010 and 2012 (pre‐Reassessment Campaign on Veterinary Resuscitation) were identified and animal, arrest and outcome variables recorded retrospectively.

Results

Eighty‐one animals were included in the pre‐Reassessment Campaign on Veterinary Resuscitation group and 190 in the post‐Reassessment Campaign on Veterinary Resuscitation group. Twenty‐three percent in the pre‐Reassessment Campaign on Veterinary Resuscitation group and 28% in the post‐Reassessment Campaign on Veterinary Resuscitation group achieved return of spontaneous circulation and 1% and 4% survived to hospital discharge, respectively. Patients undergoing anaesthesia [odds ratio 4.26 (1.76 to 10.27)], elective [odds ratio 5.16 (1.06 to 25.02)] or emergent surgery [odds ratio 3.09 (1.20 to 8.00)], or experiencing cardiopulmonary arrest (CPA) due to arrhythmias [odds ratio 4.31 (1.44 to 12.93)] had higher odds of return of spontaneous circulation, while those with unknown cause of CPA [odds ratio 0.25 (0.08 to 0.78)] had lower odds. Undergoing cardiopulmonary resuscitation in the post‐Reassessment Campaign on Veterinary Resuscitation period was not statistically significantly associated with return of spontaneous circulation [odds ratio 1.38 (0.68 to 2.79)].

Clinical Significance

Unchanged odds of return of spontaneous circulation observed in this study could suggest that once‐yearly cardiopulmonary resuscitation training is insufficient, effects of animal and tertiary referral hospital variables confounded results, guideline benefit is limited, or that compliance during clinical cardiopulmonary resuscitation efforts is too poor for guideline recommendations to have a positive impact.
Association between sleep and problematic behaviours in gifted children: a polysomnographic study
Authors: Bastien Laurianne , Théoret Rachel , Godbout Roger
Published: December 2022

Neurological uniqueness, maladaptive behaviours, as well as atypical sleep patterns are reported to be defining characteristics of giftedness, but this has received little empirical support. We studied the polysomnography recorded sleep of gifted and typically‐developing children together with features of maladaptive behaviours. The association of sleep macrostructure and sleep instability with maladaptive behaviours was also investigated in gifted children. In all, 19 gifted children (74% boys) and 17 typically‐developing children (76% boys) aged 6–12 years were studied. Giftedness was identified using Renzulli's three‐factor definition. The microarousal index, number of awakenings, and number of Stage shifts between sleep stages throughout the night were computed as sleep instability parameters. Maladaptive behaviours were assessed using the Child Behaviour Checklist. We found significantly more Stage N1 and less Stage N3 in gifted children compared to typically‐developing children. More Stage N1 sleep was correlated with more externalising problems and less Stage N3 sleep was correlated with more internalising problems. Gifted children also displayed more rapid eye movement (REM) sleep, but this was not significantly correlated with behavioural scales. Gifted children displayed two opposing trends of sleep instability: more instability involving N1 sleep and less instability involving N2, N3 and REM sleep. More total Stage shifts were correlated with more internalising and externalising problems. The results of this study provide initial evidence of polysomnography‐based characteristics of giftedness. Further studies are needed to explore common pathways linking sleep alterations and maladaptive behaviours in children with giftedness.
The effect of wearable‐delivered sleep interventions on sleep outcomes among adults: A systematic review and meta‐analysis of randomized controlled trials
Authors: Lai Min Yi Calida , Mong Mei Siew Andrea , Cheng Ling Jie , Lau Ying
Published: December 2022

The aims of the review were to (i) evaluate the effectiveness of wearable‐delivered sleep interventions on sleep outcomes among adults, and (ii) explore the effect of factors affecting total sleep time. Eight databases were searched to identify relevant studies in English from inception until December 23, 2021. The Cochrane Risk of Bias tool version 2.0 and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria were used to assess the risk of bias and certainty of the evidence, respectively. Twenty randomized controlled trials (RCTs) were included, involving 1608 adults across nine countries. Wearable‐delivered sleep interventions elicited significant improvement of 1.96 events/h for the oxygen desaturation index and 3.13 events/h for the respiratory distress index. Meta‐analyses found that wearable‐delivered sleep interventions significantly decreased sleep disturbance (Hedges'g[g] = −0.37, 95% confidence interval [CI]: −0.59, −0.15) and sleep‐related impairment (g= −1.06, 95% CI: −1.99, −0.13) versus the comparators. The wearable‐delivered sleep interventions may complement usual care to improve sleep outcomes. More rigorous RCTs with a long‐term assessment in a wide range of populations are warranted.