bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of a theory‐based exercise intervention on physical activity levels and health‐related outcomes in older people with chronic diseases
Authors: Li Qiyu , Cai Weiwei , Li Yanling , Zhang Ruixin , Zeng Chunlu , Ma Xiaoqing , Barka Catherine Katumu , Zhang Chu , Sun Ting , Xie Hui
Published: December 2022

Background

The benefits of physical activity are well‐documented, and the prevalence of physical inactivity is high in older patients with chronic diseases. This study aimed to investigate the impact of an aerobic exercise intervention based on the capacity, opportunity, motivation‐behavior (COM‐B) model on physical activity and health‐related outcomes in this population.

Methods

Thirty‐five participants were randomly assigned to the intervention group (IG) for an exercise intervention based on the COM‐B model, and 33 were assigned to the control group (CG) for usual care. Physical activity levels, daily steps and bone mineral density T‐value, body mass index, waist–hip ratio, subendocardial myocardial viability rate, central arterial pressure, growth index, brachial–ankle pulse wave velocity, ankle–arm index were measured at baseline, during the 12‐week intervention, and after the 12‐week follow‐up.

Results

Compared with the CG and pre‐intervention, total physical activity in the IG increased significantly (P < 0.05); however, after the 12‐week follow‐up, total physical activity decreased. At the same time, the average daily steps of the elderly in both groups increased. Compared with the CG, at the 12‐week follow‐up, the bone mineral density T‐value in the IG was significantly improved (P < 0.05). Compared with the pre‐intervention values, during the 12‐week intervention, bone mineral density T‐value, body mass index, waist–hip ratio, subendocardial myocardial viability rate and central arterial pressure were significantly improved (P < 0.05); after the 12‐week follow‐up, brachial–ankle pulse wave velocity and ankle–arm index were significantly improved (P < 0.05). No statistically significant changes in the growth index were detected, independent of the group and time.

Conclusion

Theory‐based exercise interventions can change the physical inactivity behavior of older people with chronic diseases, effectively promoting physical activity and improves bone mineral density T‐value, controls body weight, and reduces cardiovascular risk and physiological indicators related to atherosclerosis. Geriatr Gerontol Int 2023; 23: 78–84.
Training design enhancement through training evaluation: Effects on training transfer
Authors: Arabi Elham , Garza Tiberio
Published: December 2022

This research investigates the linkage between training evaluation, learning design and training transfer. A new training evaluation model, (i.e., learning‐transfer evaluation model [LTEM]), was used to examine its ability to provide evaluative evidence through robust assessments in pre‐, post‐ and delayed assessments. The model was used to improve the training design of a nursing training programme and to nudge the stakeholders to change their training practices. A mixed‐methods research approach, called convergent parallel, was employed to study the influence of the LTEM model in training design improvement by assessing the perceptions of nurse trainees, trainers and a nurse educator towards the instructional design of the training programme. A quantitative approach was used to examine the extent to which the improved programme using an iterative design cycle would result in improved performance among four groups (i.e., one baseline and three treatment groups). The integrated data showed that the LTEM model influenced the stakeholders to focus more on skills practice. With this shift of mindset, the training design was enhanced based on the principles of learning design, cognitive science and multimedia principles. Results of the pre‐, post‐ and delayed posttests showed higher mean scores in the three treatment groups compared to the baseline group. For the measure of transfer, while the treatment groups scored higher, there was no statistically significant difference among all four groups. This could be attributed to nurses’ varied levels of experience, negative transfer and the use of different evaluation matrices in the study and by the hospital.
First Randomized Study of Epilepsy Surgery
Authors: Marks William J.
Published: December 2022

A Randomized, Controlled Trial of Surgery for Temporal-Lobe Epilepsy

Wiebe S, Blume WT, Girvin JP, Eliasziw M

N Engl J Med 2001;345:311–318

Background

Randomized trials of surgery for epilepsy have not been conducted, because of the difficulties involved in designing and implementing feasible studies. The lack of data supporting the therapeutic usefulness of surgery precludes making strong recommendations for patients with epilepsy. We conducted a randomized, controlled trial to assess the efficacy and safety of surgery for temporal-lobe epilepsy.

Methods

Eighty patients with temporal-lobe epilepsy were randomly assigned to surgery (40 patients) or treatment with antiepileptic drugs for one year (40 patients). Optimal medical therapy and primary outcomes were assessed by epileptologists who were unaware of the patients’ treatment assignments. The primary outcome was freedom from seizures that impair awareness of self and surroundings. Secondary outcomes were the frequency and severity of seizures, the quality of life, disability, and death.

Results

At one year, the cumulative proportion of patients who were free of seizures impairing awareness was 58 percent in the surgical group and 8 percent in the medical group (P<0.001). The patients in the surgical group had fewer seizures impairing awareness and a significantly better quality of life (P<0.001 for both comparisons) than the patients in the medical group. Four patients (10 percent) had adverse effects of surgery. One patient in the medical group died.

Conclusions

In temporal-lobe epilepsy, surgery is superior to prolonged medical therapy. Randomized trials of surgery for epilepsy are feasible and appear to yield precise estimates of treatment effects.
Memory Function Related to Hippocampal Imaging Findings
Authors: Cascino Gregory D.
Published: December 2022

Bilateral Hippocampal Atrophy: Consequences to Verbal Memory Following Temporal Lobectomy

Martin RC, Sawrie SM, Knowlton RC, Bilir E, Gilliam FG, Faught E, Morawetz RB, Kuzniecky R

Neurology 2001;57:597–604

Background

Bilateral hippocampal damage is a risk factor for memory decline after anterior temporal lobectomy (ATL).

Objective

To investigate verbal memory outcome in patients with temporal lobe epilepsy (TLE) with either unilateral or bilateral hippocampal atrophy as measured by MRI.

Methods

The authors selected 60 patients with TLE who had undergone ATL (left = 31, right = 29). They determined normalized MRI hippocampal volumes by cursor tracing 1.5-mm slices from three-dimensional MRI acquisition. Hippocampal volumes were defined as atrophic if the volumes were below 2 SD for control subjects. Bilateral hippocampal atrophy was present in 10 patients with left TLE and 11 patients with right TLE. The authors assessed acquisition, retrieval, and recognition components of verbal memory both before and after ATL.

Results

Groups did not differ across age, education, intelligence, age at seizure onset, or seizure duration. Seizure-free rates after ATL were 70% or higher for all groups. Before surgery, patients with left TLE displayed worse verbal acquisition performance compared with patients with right TLE. Patients with left TLE with bilateral hippocampal volume loss displayed the lowest performance across all three memory components. After surgery, both groups of patients with left TLE exhibited worse verbal memory outcome compared with patients with right TLE. Bilateral hippocampal atrophy did not worsen outcome in the patients with right TLE. A higher proportion of patients with left TLE with bilateral hippocampal atrophy experienced memory decline compared with the other TLE groups.

Conclusion

Bilateral hippocampal atrophy in the presence of left TLE is associated with worse verbal memory before and after ATL compared with patients with unilateral hippocampal volume loss or right TLE with bilateral hippocampal volume loss.
Metabotropic Glutamate Receptors, PLCbeta 1 Signaling and Hippocampal Epileptiform Discharges
Authors: Benardo Larry S.
Published: December 2022

Group I Metabotropic Glutamate Receptors Elicit Epileptiform Discharges in the Hippocampus Through PLCbeta1 Signaling

Chuang SC, Bianchi R, Kim D, Shin HS, Wong RK

J Neurosci 2001;21:6387–6394

Activation of metabotropic glutamate receptors (mGluRs) produces multiple effects in cortical neurons, resulting in the emergence of network activities including epileptiform discharges. The cellular mechanisms underlying such network responses are largely unknown. We examined the properties of group I mGluR-mediated cellular responses in CA3 neurons and attempted to determine their role in the generation of the network activities. Group I mGluR stimulation causes depolarization of hippocampal neurons. This depolarization is primarily mediated by two sets of conductance change: the opening of a voltage-dependent cationic conductance (mediating I(mGluR(V))) and the closing of a voltage-independent (background) K(+) conductance. I(mGluR(V)) was no longer elicited by group I mGluR agonists in the presence of U73122, a phospholipase C (PLC) blocker. Also, the current could not be activated in hippocampal CA3 neurons from PLCbeta1 knock-out mice. In contrast, suppression of PLC signaling did not affect the group I mGluR-mediated suppression of background K(+) conductance. Thus, the suppression of the background K(+) conductance occurred upstream to PLC activation, whereas the generation of I(mGluR(V)) occurred downstream to PLC activation. Group I mGluR agonists normally elicited rhythmic single cell and population burst responses in the CA3 neurons. In the absence of an I(mGluR(V)) response, CA3 neurons in slices prepared from PLCbeta1–/– mutant mice could no longer generate these responses. The results suggest that I(mGluR(V)) expression in CA3 hippocampal neuron is PLCbeta1-dependent and that I(mGluR(V)) plays a necessary role in the generation of rhythmic single cell bursts and synchronized epileptiform discharges in the CA3 region of the hippocampus.
Excitatory Afferents to the Entorhinal Cortex Play a Role in Temporal Lobe Epileptogenesis
Authors: Benardo Larry S.
Published: December 2022

Ibotenate Injections into the Pre- and Parasubiculum Provide Partial Protection Against Kainate-Induced Epileptic Damage in Layer III of Rat Entorhinal Cortex

Eid T, Du F, Schwarcz R

Epilepsia 2001;42:817–824

Purpose

A loss of neurons in layer III of the entorhinal cortex (EC) is often observed in patients with temporal lobe epilepsy and in animal models of the disorder. We hypothesized that the susceptibility of layer III of the EC to prolonged seizure activity might be mediated by excitatory afferents originating in the presubiculum.

Methods

Experiments were designed to ablate the presubiculum unilaterally by focal ibotenate injections and to evaluate the effect of this deafferentation on the vulnerability of EC layer III neurons to the chemoconvulsant kainate (injected systemically 5 days later).

Results

After treatment with kainate, 11 of the 15 rats preinjected with ibotenate showed clear-cut, partial neuroprotection in layer III of the EC ipsilateral to the ibotenate lesion. Serial reconstruction of the ibotenate-induced primary lesion revealed that entorhinal neurons were protected only in animals that had lesions in the pre- and parasubiculum, especially in the deep layers (IV-VI).

Conclusions

The deep layers of the pre- and parasubiculum appear to control the seizure-induced damage of EC layer III. This phenomenon may be of relevance for epileptogenesis and for the pathogenesis of temporal lobe epilepsy.
Diuretics as Antiepileptic Drugs
Authors: Kanner Andres M.
Published: December 2022

Are Certain Diuretics Also Anticonvulsants?

Hesdorffer DC, Stables JP, Hauser WA, Annegers JF, Cascino G

Ann Neurol 2001;50:458–462

A history of diuretic use has been shown to be protective for first unprovoked seizure in adult patients. Recent animal studies suggest that certain diuretics have anticonvulsant activity. We evaluated the potential for the anticonvulsant activity of current diuretic use in a population-based, case-control study in older adults. We also tested chlorthiazide and furosemide for seizure protection in animal models of epilepsy. Concurrent medical prescription of any diuretic was protective for the development of epilepsy [odds ratio (OR) = 0.62, 95% confidence interval (CI) = 0.39–0.99]. A protective effect for current thiazide use was observed (OR = 0.53, CI = 0.31–0.90), and a protective effect for furosemide was suggested (OR = 0.44, CI = 0.1–1.9). In mice, both chlorthiazide and furosemide suppressed the occurrence of maximal electroshock-induced seizures in a dose-dependent manner. Chlorthiazide's toxic dose for 50% of animals tested (TD50) could not be achieved even with dosing as high as 1,500 mg/kg for furosemide; TD50 was 549 mg/kg. Results were similar in rats. Furosemide and chlorthiazide are protective for unprovoked seizures in an epidemiological study and in animal models. Given the potential therapeutic value for seizure control, low toxicity, and low cost, therapeutic efficacy should be explored in clinical studies.
Seizure-Induced Axonal Sprouting: Assessing Connections between Injury, Local Circuits, and Epileptogenesis
Authors: Sutula Thomas
Published: December 2022

Neurons and neural circuits undergo extensive structural and functional remodeling in response to seizures. Sprouting of axons in the mossy fiber pathway of the hippocampus is a prominent example of a seizure-induced structural alteration which has received particular attention because it is easily detected, is induced by intense or repeated brief seizures in focal chronic models of epilepsy, and is also observed in the human epileptic hippocampus. During the last decade the association of mossy fiber sprouting with seizures and epilepsy has been firmly established. Many anatomical features of mossy fiber sprouting have been described in considerable detail, and there is evidence that sprouting occurs in a variety of other pathways in association with seizures and injury. There is uncertainty, however, about how or when mossy fiber sprouting may contribute to hippocampal dysfunction and generation of seizures. Study of mossy fiber sprouting has provided a strong theoretical and conceptual framework for efforts to understand how seizures and injury may contribute to epileptogenesis and its consequences. It is likely that investigation of mossy fiber sprouting will continure to offer significant opportunities for insights into seizure-induced plasticity of neural circuits at molecular, cellular, and systems levels.
In Utero Effects of AEDs
Authors: Meador Kimford J.
Published: December 2022

Long-term Health and Neurodevelopment in Children Exposed to Antiepileptic Drugs Before Birth

Dean JC, Hailey H, Moore SJ, Lloyd DJ, Turnpenny PD, Little J.

J Med Genet 2002;39:251–259

Objective

To investigate the frequency of neonatal and later childhood morbidity in children exposed to antiepileptic drugs in utero.

Design

Retrospective population-based study. SETTING: Population of the Grampian region of Scotland.

Participants

Mothers taking antiepileptic drugs in pregnancy between 1976 and 2000 were ascertained from hospital obstetric records, and 149 (58% of those eligible) took part. They had 293 children whose health and neurodevelopment were assessed. Main outcome measures: Frequencies of neonatal withdrawal, congenital malformations, childhood-onset medical problems, developmental delay, and behaviour disorders.

Results

Neonatal withdrawal was seen in 20% of those exposed to antiepileptic drugs (AEDs). Congenital malformations occurred in 14% of exposed pregnancies, compared with 5% of nonexposed sibs, and developmental delay in 24% of exposed children, compared with 11% of nonexposed sibs. After excluding cases with a family history of developmental delay, 19% of exposed children and 3% of nonexposed sibs had developmental delay, 31% of exposed children had either major malformations or developmental delay, 52% of exposed children had facial dysmorphism compared with 25% of those not exposed, 31% of exposed children had childhood medical problems (13% of nonexposed sibs), and 20% had behaviour disorders (5% of nonexposed).

Conclusion

Prenatal AED exposure in the setting of maternal epilepsy is associated with developmental delay and later childhood morbidity in addition to congenital malformation.
Levetiracetam and Oral Contraceptives
Authors: Penovich Patricia E.
Published: December 2022

Levetiracetam Does Not Alter the Pharmacokinetics of an Oral Contraceptive in Healthy Women

Ragueneau-Majlessi I, Levy RH, Janik F

Epilepsia 2002;43(7):697–702

Purpose

This study was designed to evaluate whether levetiracetam (LEV), a novel antiepileptic drug (AED), influences the pharmacokinetics of steroid oral contraceptives.

Methods

During a run-in phase, 18 healthy female patients received an oral contraceptive containing ethinyl estradiol, 0.03 mg, and levonorgestrel, 0.15 mg, for the first 21 days of two consecutive menstrual cycles. In a subsequent double-blind, randomized, two-way crossover treatment phase, subjects received either LEV, 500 mg, or placebo twice daily concomitant with the oral contraceptive. Plasma concentrations of ethinyl estradiol and levonorgestrel were measured on days 14 and 15 of the two treatment periods for the evaluation of the 24-h kinetic parameters, and an additional sample was collected on day 21 to determine the trough plasma concentrations. Serum progesterone and luteinizing hormone (LH) levels were determined on days 13, 14, 15, and 21 of each cycle of the treatment phase.

Results

The plasma concentration–time curves and pharmacokinetic parameters of ethinyl estradiol and levonorgestrel were not statistically different during concomitant treatment with either LEV or placebo. The ratios of the log-transformed geometric mean areas under the plasma concentration–time curves (AUCs), maximal (Cmax) and minimal (Cmin) plasma concentrations, and trough concentrations on day 21 (C21) ranged from 99.12 to 99.96% for ethinyl estradiol and from 97.13 to 99.41% for levonorgestrel. The 90% confidence intervals of these ratios were well within the 80 to 125% acceptance range for lack of interaction. Serum progesterone and LH concentrations were fairly constant during the run-in and treatment phases and remained markedly below their respective physiologic levels. Safety and menstrual-bleeding patterns were comparable during LEV and placebo administration.

Conclusions

LEV does not affect the pharmacokinetics of an oral contraceptive containing ethinyl estradiol and levonorgestrel, and on the basis of serum progesterone and LH levels, it does not affect the contraceptive efficacy.
Sprouted Mossy Fibers Form Primarily Excitatory Connections
Authors: Coulter Douglas A.
Published: December 2022

Axon Sprouting in a Model of Temporal Lobe Epilepsy Creates a Predominantly Excitatory Feedback Circuit

Buckmaster PS, Zhang GF, Yamawaki R

J Neurosci 2002;22:6650–6658

The most common type of epilepsy in adults is temporal lobe epilepsy. After epileptogenic injuries, dentate granule cell axons (mossy fibers) sprout and form new synaptic connections. Whether this synaptic reorganization strengthens recurrent inhibitory circuits or forms a novel recurrent excitatory circuit is unresolved. We labeled individual granule cells in vivo, reconstructed sprouted mossy fibers at the electron-microscopic (EM) level, and identified postsynaptic targets with γ-aminobutyric acid (GABA) immunocytochemistry in the pilocarpine model of temporal lobe epilepsy. Granule cells projected an average of 1.0 and 1.1 mm of axon into the granule cell and molecular layers, respectively. Axons formed an average of one synapse every 7 μm in the granule cell layer and every 3 μm in the molecular layer. Most synapses were with spines (76 and 98% in the granule cell and molecular layers, respectively). Almost all of the synapses were with GABA-negative structures (93 and 96% in the granule cell and molecular layers, respectively). By integrating light microscopic and EM data, we estimate that sprouted mossy fibers form an average of >500 new synapses per granule cell, but <25 of the new synapses are with GABAergic interneurons. These findings suggest that almost all of the synapses formed by mossy fibers in the granule cell and molecular layers are with other granule cells; therefore after epileptogenic treatments that kill hilar mossy cells, mossy fiber sprouting does not simply replace one recurrent excitatory circuit with another. Rather, it replaces a distally distributed and disynaptic excitatory feedback circuit with one that is local and monosynaptic.
Flumazenil Binding and Cortical Malformations
Authors: Theodore William H.
Published: December 2022

Central Benzodiazepine Receptors in Malformations of Cortical Development: A Quantitative Study

Hammers A, Koepp MJ, Richardson MP, Labbe C, Brooks DJ, Cunningham VJ, Duncan J

Brain 2001;124:1555–1565

Purpose

We calculated [11C]flumazenil volume of distribution ([11C]FMZ-Vd] after correction for partial volume effect in 10 patients with malformations of cortical development (MCDs) and partial seizures, to quantify the γ-aminobutyric acid (GABAA)-central benzodiazepine receptor complex.

Methods

Abnormal grey matter and adjacent or overlying cortex were outlined individually and added to an individualized anatomic template for correction for partial volume effect.

Results

Nine of 10 patients showed single or multiple increases or decreases in [11C]FMZ-Vd in or around MCDs. Two of three patients with band heterotopia showed multiple increases in the overlying cortex. In three of four patients with subependymal nodular heterotopia, nodules had lower [11C]FMZ-Vd than the overlying cortex, which was normal. Decreases in [11C]FMZ-Vd were found in two of three clefts and one of six adjacent regions in one schizencephalic patient; another had normal [11C]FMZ-Vd in the thickened cortex itself but increases in all adjacent regions. Binding was reduced within focal cortical dysplasia but increased in adjacent cortex. [11C]FMZ-Vd was normal within one patient's polymicrogyric cortex but increased in one of six adjacent volumes of interest. The localization of abnormalities correlated with EEG and clinical data in cortical MCDs.

Conclusions

Flumazenil binding was decreased in some MCDs with increased grey-matter volume and increased in some adjacent or overlying areas of normal-appearing cortex, suggesting functional abnormalities beyond magnetic resonance imaging (MRI)-detectable structural changes.
Metabotropic Glutamate Receptors and Epileptiform Bursting
Authors: Benardo Larry S.
Published: December 2022

Differential Roles for mGluR1 and mGluR5 in the Persistent Prolongation of Epileptiform Bursts

Merlin LR

J Neurophysiol 2002;87:621–625

Purpose

Transient activation of group I metabotropic glutamate receptors (mGluRs) with the selective agonist (S)-3,5-dihydroxyphenylglycine (DHPG) produces persistent prolongation of epileptiform bursts in guinea-pig hippocampal slices, the maintenance of which can be reversibly suppressed with group I mGluR antagonists. To determine the relative roles of mGluR1 and mGluR5 in these group I mGluR-dependent induction and maintenance processes, subtype-selective antagonists were used. In the presence of picrotoxin, DHPG (50 μ M, 20–45 min) converted interictal bursts into 1- to 3-s discharges that persisted for hours after washout of the mGluR agonist. 2-Methyl-6–(phenylethynyl)-pyridine (MPEP, an mGluR5 antagonist; 25 μ M) and (+)-2-methyl-4-carboxy-phenylglycine (LY367385, an mGluR1 antagonist; 20–25 (μ M) each significantly suppressed the ongoing expression of the mGluR-induced prolonged bursts. However, LY367385 was more effective, reducing the burst prolongation by nearly 90%; MPEP produced only a 64% reduction in burst prolongation. Nevertheless, MPEP was more effective at preventing the induction of the burst prolongation; all 10 slices tested failed to express prolonged bursts both during and after coapplication of DHPG with MPEP. Coapplication of DHPG with LY367385, in contrast, resulted in significant burst prolongation (in 68% of slices tested) that was revealed on washout of the two agents. These results suggest that although both receptor subtypes participate in both the induction and maintenance of mGluR-mediated burst prolongation, mGluR1 activation plays a greater role in sustaining the expression of prolonged bursts, whereas mGluR5 activation may be a more critical contributor to the induction process underlying this type of epileptogenesis.
Responsiveness of Status Epilepticus to Treatment with Diazepam Decreases Rapidly as Seizure Duration Increases
Authors: Goodkin Howard P. , Kapur Jaideep
Published: December 2022

Characterization of Pharmacoresistance to Benzodiazepines in the Rat Li-pilocarpine Model of Status Epilepticus

Jones D, Esmaeil N, Maren S, Macdonald R

Epilepsy Res 2002;50(3):301

Status epilepticus is usually initially treated with a benzodiazepine (BZD) such as diazepam (DZP). During prolonged seizures, however, patients often lose their sensitivity to BZDs, thus developing pharmacoresistant seizures. In rats, administration of LiCl followed 20 to 24 hours later by pilocarpine induces a continuous, self-sustained, and reproducible form of status epilepticus that can be terminated with DZP when it is administered soon after the pilocarpine injection. However, when administered after a 45-minute delay, DZP is less effective. Previous findings suggested that the development of pharmacoresistance is related to the stage of status epilepticus. In this study, we characterized the seizure stage dependence of DZP pharmacoresistance. After administration of different doses of DZP at varying time intervals after specific behaviorally and electrographically defined seizure stages, stage-, time-, and dose-dependent pharmacoresistance to DZP developed. We also studied two other antiepileptic drugs (AEDs) commonly used in the treatment of status epilepticus, phenobarbital (PB) and phenytoin (PHT). Consistent with previous studies, our results indicated a similar relation between stage, time, and dose for PB, but not for PHT. Our data are consistent with rapid modulation of γ-aminobutyric acid subtype A (GABAA) receptors during status epilepticus that may result in pharmacoresistance to AEDs that enhance GABAA receptor-mediated inhibition.
Similarities in Mechanisms and Treatments for Epileptic and Nonepileptic Myoclonus
Authors: Krauss Gregory L. , Mathews Gregory C.
Published: December 2022

Myoclonus is a disordered movement that may be an ictal phenomenon or may be due to various injuries in brain and spinal cord motor structures. Many epileptic and nonepileptic myoclonic conditions are associated with abnormalities in inhibitory neurotransmission. γ-Aminobutyric acid type A (GABAA)-receptor antagonists may trigger myoclonus. Several antiepilepsy drugs (AEDs) effective against myoclonic seizures [valproic acid (VPA), clonazepam (CZP), levetiracetam (LEV)] enhance GABAergic neurotransmission and improve myoclonic movement disorders. Together these associations suggest links between episodic disorders involving synchronous cortical discharges (seizures) and hyperkinetic movement disorders.
Illnesses and Accidents in Epilepsy Patients
Authors: Berg Anne T.
Published: December 2022

Morbidity and Accidents in Patients with Epilepsy: Results of a European Cohort Study

Beghi E, Cornaggia C; The RESt-1 Group

Epilepsia 2002;43(9):1076–1083

Purpose

To assess the risk of illnesses and accidents in patients with epilepsy and to evaluate the proportion of those risks attributable to epilepsy.

Methods

Nine hundred fifty-one referral patients with idiopathic, cryptogenic, or remote symptomatic epilepsy and 909 matched controls (relatives or friends) were followed up prospectively for 1 to 2 years in eight European countries (Italy, Germany, Holland, England, Portugal, Russia, Estonia, and Slovenia). Each patient and control received a diary to keep notes regarding any illness or accident. Patients with epilepsy specifically recorded relations with seizures.

Results

Six hundred forty-four patients recorded 2,491 illnesses compared with 1,665 illnesses in 508 controls. The cumulative probability of illness in patients was 49% by 12 months and 86% by 24 months (controls, 39% and 75%; P < 0.0001). One hundred ninety-nine patients and 124 controls had 270 and 140 accidents, respectively. The cumulative probability of accident in the cases was 17% and 27% by 12 and 24 months (controls, 12% and 17%; P < 0.0001). The chance of two or more illnesses or accidents was modestly but significantly greater in the patients. Illnesses and accidents were mostly trivial. Thirty percent of illnesses and 24% of accidents were seizure related. When illnesses and accidents related to seizures were excluded, the chance of illnesses and accidents was fairly similar in the two groups.

Conclusions

Patients with idiopathic, cryptogenic, or remote symptomatic epilepsy have a moderately higher risk of illnesses and accidents than do the general population. With few exceptions, the events are trivial. When seizure-related events are excluded, patients with epilepsy are not at any significantly higher risk of illnesses and accidents.
Brain Stimulation for Temporal Lobe Epilepsy
Authors: Marks William J.
Published: December 2022

Long-term Amygdalohippocampal Stimulation for Refractory Temporal Lobe Epilepsy

Vonck K, Boon P, Achten E, De Reuck J, Caemaert J

Ann Neurol 2002;52(5):556–565

Short-term deep brain stimulation (DBS) recently has been shown to be efficacious in refractory temporal lobe epilepsy. We (a) evaluated long-term DBS in medial temporal lobe structures in patients with normal magnetic resonance imaging (MRI) findings and (b) investigated the use of long-term DBS electrodes for the localization of the ictal onset zone before DBS. In three patients with complex partial seizures (CPSs), DBS electrodes were implanted in the amygdalohippocampal region to identify and subsequently stimulate the ictal onset zone. CPSs were compared before and after prolonged DBS. Side effects were carefully monitored. DBS electrodes yielded high-quality electroencephalogram recordings showing unilateral seizure onset in medial temporal lobe structures. For all patients, unilateral amygdalohippocampal stimulation was performed. After a mean follow-up of 5 months (range, 3–6 months), all patients had a greater than 50% reduction in seizure frequency. In two patients, antiepileptic drugs could be tapered. None of the patients reported side effects. This open study demonstrates the feasibility of consecutive electroencephalographic recordings and DBS in medial temporal lobe structures using DBS electrodes. These results prompt further studies in a larger patient population to establish the efficacy and safety of long-term DBS as an alternative treatment for refractory temporal lobe epilepsy.
Contribution of Current and past Traumatic Events to Pseudoseizures and Epilepsy
Authors: Harden Cynthia L.
Published: December 2022

Comparative Study of Trauma-Related Phenomena in Subjects with Pseudoseizures and Subjects with Epilepsy

Fleisher W, Staley D, Krawetz P, Pillay N, Arnett JL, Maher J

Am J Psychiatry 2002;159:660–663

Purpose

The purpose of this study was to examine potential differences in measures of trauma-related phenomena between subjects with pseudoseizures and subjects with intractable epilepsy.

Methods

Thirty-one adult subjects with pseudoseizures and 32 subjects with intractable epilepsy (confirmed by video-EEG) were recruited from the epilepsy unit of a tertiary care hospital. Each participant completed the Impact of Event Scale, the Davidson Trauma Scale, the Mississippi Scale for Combat-Related Post-traumatic Stress Disorder (PTSD), the Dissociative Experience Scale, and the Pittsburgh Sleep Quality Index, as well as demographic, seizure history, and family-functioning measures.

Results

Subjects with pseudoseizures had significantly higher mean scores on the Davidson Trauma Scale, Mississippi Scale for Combat-Related PTSD, Impact of Event Scale, and Pittsburgh Sleep Quality Index than did subjects with epilepsy. In addition, a significantly higher percentage of subjects with pseudoseizures had scores above the clinical cutoff level of 30 on the Dissociative Experience Scale.

Conclusions

Subjects with pseudoseizures exhibited trauma-related profiles that differed significantly from those of epileptic comparison subjects and closely resembled those of individuals with a history of traumatic experiences. Interventions aimed at trauma-related issues may be beneficial for patients with pseudoseizures.
Uric acid relationships with lipid profile and adiposity indices: Impact of different hyperuricemic thresholds
Authors: Maloberti Alessandro , Vanoli Jennifer , Finotto Alessandra , Bombelli Michele , Facchetti Rita , Redon Pau , Mancia Giuseppe , Grassi Guido
Published: December 2022

Previous studies focused on the relationships between Serum Uric Acid (SUA) and lipids have found an association mainly with triglycerides. Furthermore, previous studies on adiposity indices have been focused on the evaluation of the Visceral Adiposity Index (VAI). The present study was aimed at providing within the same population a systematic evaluation of lipids and adiposity indices with SUA, employing both the classic cutoff for hyperuricemia and the newly one identified by the Uric Acid Right for Heart Health (URRAH) study. We analyzed data collected in 1892 subjects of the Pressioni Arteriose Monitorate E loro Associazioni (PAMELA) study with available SUA, lipid profile and variables necessary to calculate VAI, Cardio‐Metabolic Index (CMI) and Lipid Accumulation Product (LAP). At linear regression model (corrected for confounders) SUA correlated with all the lipids values (with the strongest β for triglycerides) and adiposity indices. When the two different cutoffs were compared, the URRAH one was significantly related to atherogenic lipids profile (OR 1.207 for LDL and 1.33 for non‐HDL, P < 0.001) while this was not the case for the classic one. Regarding adiposity indices the classic cutoff displays highest OR as compared to the URRAH one. In conclusions, newly reported URRAH cutoff for hyperuricemia better relate to atherogenic lipoprotein (LDL and non‐HDL) when compared to the classic one. The opposite has been found for adiposity indexes where the classic cut‐off seems to present highest performance. Among adiposity indexes, LAP present the highest OR for the relationship with hyperuricemia.
Multiple machine learning methods aided virtual screening of NaV1.5 inhibitors
Authors: Kong Weikaixin , Huang Weiran , Peng Chao , Zhang Bowen , Duan Guifang , Ma Weining , Huang Zhuo
Published: December 2022

Nav1.5 sodium channels contribute to the generation of the rapid upstroke of the myocardial action potential and thereby play a central role in the excitability of myocardial cells. At present, the patch clamp method is the gold standard for ion channel inhibitor screening. However, this method has disadvantages such as high technical difficulty, high cost and low speed. In this study, novel machine learning models to screen chemical blockers were developed to overcome the above shortage. The data from the ChEMBL Database were employed to establish the machine learning models. Firstly, six molecular fingerprints together with five machine learning algorithms were used to develop 30 classification models to predict effective inhibitors. A validation and a test set were used to evaluate the performance of the models. Subsequently, the privileged substructures tightly associated with the inhibition of the Nav1.5 ion channel were extracted using the bioalerts Python package. In the validation set, the RF‐Graph model performed best. Similarly, RF‐Graph produced the best result in the test set in which the Prediction Accuracy (Q) was 0.9309 and Matthew's correlation coefficient was 0.8627, further indicating the model had high classification ability. The results of the privileged substructures indicated Sulfa structures and fragments with large Steric hindrance tend to block Nav1.5. In the unsupervised learning task of identifying sulfa drugs, MACCS and Graph fingerprints had good results. In summary, effective machine learning models have been constructed which help to screen potential inhibitors of the Nav1.5 ion channel and key privileged substructures with high affinity were also extracted.
The main features of physician assistants/associates and insights for the development of similar professions in China
Authors: Jiang Huili , Zhao Qianqian , Chen Keyu , Yang Juntao , Li Qing
Published: December 2022

The physician assistant/associate (PA) profession originated in the United States; PAs play an active role in alleviating the shortage of health and medical resources and improving the quality of medical care. This position has been introduced in and developed by many countries. Based on extensive literature research, this article summarizes the three main features of PAs, namely, that there is professional education for training PAs, the PA is an independent and exclusive professional type and PAs assist doctors in completing medical work. With reference to the innovative concept of the PA profession, this article summarized the existing “assistant” position in China that is similar to the PA position, compared it with the three features of PAs, revealed the shortcomings of the existing “assistant” position in China, provided a reference for the development of relevant careers in China, and provided solutions for solving the problems of medical and health resources in China.
A double blind randomized controlled trial to assess efficacy of nutritional therapy for prevention of recurrence of hepatic encephalopathy in patients with cirrhosis
Authors: Ahuja Hardik , Sharma Barjesh Chander , Sachdeva Sanjeev , Mahajan Bhawna , Sharma Ashok , Bara Sushma , Srivastava Siddharth , Kumar Ajay , Dalal Ashok , Sonika Ujjwal
Published: December 2022

Background and Aim

Overt hepatic encephalopathy (OHE) has high risk of recurrence and is associated with poor survival. The role of nutrition therapy is well documented in cirrhosis, but its efficacy in preventing the recurrence of OHE has not been studied.

Methods

In double blind RCT, we randomly assigned 150 patients with liver cirrhosis, with history of OHE in recent past to receive nutrition therapy (group I) or no nutrition therapy (group II) and followed up for 6 months. The primary efficacy end points were occurrence of breakthrough episodes and time to breakthrough episode of OHE. Secondary end points were OHE related hospitalizations and time to hospitalization involving OHE. Other parameters included anthropometry, changes in serum cytokines (IL‐1, IL‐6, IL‐10, and TNF‐α), endotoxin and myostatin.

Results

There was significant reduction in occurrence of breakthrough episodes of OHE in group I [10 vs 36, hazard ratio 0.20; P < 0.001], OHE‐related hospitalization [8 vs 24, hazard ratio 0.27; P < 0.001)]. Times to breakthrough episode of OHE and OHE‐related hospitalization were longer in group I. At the end of 6 months, inflammatory and anthropometry parameters showed significant improvement in group I compared with worsening of serum albumin, anthropometric parameters, IL‐6, IL‐10 and TNF‐α in group II. At the end of 6 months, ascites (50 vs 66, P = 0.01), gastrointestinal bleed (2 vs 11, P = 0.007), and jaundice (16 vs 41, P < 0.001) were lower in group I.

Conclusions

Treatment with nutrition therapy prevented recurrence of OHE and decreased OHE‐related hospitalizations as compared with no nutrition therapy.
Ambulance use and subsequent fragmented hospital readmission among older adults
Authors: Turbow Sara D. , Culler Steven D. , Vaughan Camille P. , Rask Kimberly J. , Perkins Molly M. , Clevenger Carolyn K. , Ali Mohammed K.
Published: December 2022

Background

Interhospital care fragmentation, when a patient is readmitted to a different hospital than they were originally discharged from, occurs in 20%–25% of readmissions. Mode of transport to the hospital, specifically ambulance use, may be a risk factor for fragmented readmissions. Our study seeks to further understand the relationship between ambulance transport and fragmented readmissions in older adults, a population that is at increased risk for poor outcomes following fragmented readmissions.

Methods

We analyzed inpatient claims from Medicare beneficiaries in 2018 who had a hospital admission for select Hospital Readmission Reduction Program Conditions (acute myocardial infarction, congestive heart failure, chronic obstructive pulmonary disease, pneumonia) as well as dehydration, syncope, urinary tract infection, or behavioral issues. We evaluated the associations between ambulance transport and a fragmented readmission using logistic regression models adjusted for demographic, clinical, and hospital characteristics.

Results

The study included 1,186,600 30‐day readmissions. Of these, 46.8% (n = 555,847) required ambulance transport. In fully adjusted models, taking an ambulance to the readmission hospital increased the odds of a fragmented readmission by 38% (95% CI 1.32, 1.44). When this association was examined by readmission major diagnostic category (MDC), the strongest associations were seen for Factors Influencing Health Status and Other Contacts with Health Services (i.e., rehabilitation, aftercare) (AOR 3.66, 95% CI 3.11, 4.32), Mental Diseases and Disorders (AOR 2.69, 95% CI 2.44, 2.97), and Multiple Significant Trauma (AOR 2.61, 95% CI 1.56, 4.35). When the model was stratified by patient origin, ambulance use remained associated with fragmented readmissions across all locations.

Conclusions

Ambulance use is associated with increased odds of a fragmented readmission, though the strength of the association varies by readmission diagnosis and origin. Patient‐, hospital‐, and system‐level interventions should be developed, implemented, and evaluated to address this modifiable risk factor.
Glucocorticoid‐sensitive period of corticotroph development—Implications for mechanisms of early life stress
Authors: Peles Guy , Swaminathan Amrutha , Levkowitz Gil
Published: December 2022

Corticotrophs are intermediaries in the hypothalamic–pituitary–adrenal (HPA) axis, which plays a crucial role in stress response in vertebrates. The HPA axis displays an intricate mode of negative feedback regulation, whereby the peripheral effector, cortisol inhibits the secretion of its upstream regulator, adrenocorticotropic hormone (ACTH) from proopiomelanocortin (POMC)‐expressing cells in the pituitary. While the feedback regulation of the HPA axis is well characterized in the adult organism, the effect of feedback regulation on the development of corticotrophs is poorly understood. Here, we studied the effect of glucocorticoids on the development of POMC‐expressing cells in the zebrafish pituitary. The development of POMC cells showed a steady increase in numbers between 2–6 days post fertilization. Inhibition of endogenous glucocorticoid synthesis resulted in an increase in POMC cell number due to reduced developmental feedback inhibition of cortisol on POMC cells. Conversely, addition of exogenous dexamethasone at a critical developmental window led to a decrease in corticotroph cell number, mimicking greater feedback control due to increased cortisol levels. Finally, developmental dysregulation of ACTH levels resulted in impaired anxiety‐like and stress‐coping behaviours. Hence, we identified a sensitive developmental window for the effect of glucocorticoids on corticotrophs and demonstrate the downstream effect on stress‐responsive behaviour.
Parental protection in fathers with negative caregiving experiences: Heightened amygdala reactivity to infant threatening situations
Authors: Riem Madelon M. E. , Witte Annemieke M. , Lotz Anna M. , Cima Maaike , van IJzendoorn Marinus H. , Bakermans‐Kranenburg Marian J.
Published: December 2022

Parental protection is an important, yet understudied, aspect of parenting behavior. Predictors of the quality of protection and potential underlying neural mechanisms are still unknown. In this study, we examined whether negative caregiving experiences in fathers’ own childhood are related to protective behavior and neural reactivity to infant threatening situations. Paternal protective behavior was measured with self‐ and partner‐reported protective behavior and behavioral observations in an experimental set‐up (auditory startling task) in 121 first‐time fathers (mean age child = 19.35 weeks, SD = 11.27). Neural activation during exposure to videos of infant‐threatening (vs. neutral) situations was measured with functional magnetic resonance imaging (fMRI). We found a significant and positive association between negative caregiving experiences and amygdala reactivity to infant‐threatening situations. A history of negative caregiving experiences was not significantly related to reported or observed paternal protective behavior. Our findings suggest that fathers with negative caregiving experiences show emotional hyperreactivity to cues of infant threat.
Prolactin and glucocorticoid receptors in the prefrontal cortex are associated with anxiety‐like behavior in prenatally stressed adolescent offspring rats
Authors: Yao Dan , Lu Yong , Li Li , Wang Shan , Mu Yingjun , Ding Chenxi , Zhao Jing , Liu Mingzhe , Xu Meina , Wu Haoyue , Dou Chengyin , Zhu Zhongliang , Li Hui
Published: December 2022

Prenatal stress (PS) causes anxiety in mothers and their offspring and chewing is a commonly observed behavior during maternal stress. Prolactin (PRL) is an anti‐anxiety factor that suppresses the hypothalamic–pituitary–adrenal axis. Here, we studied the roles of PRL, corticosterone (CORT), and their receptors in PS‐induced anxiety‐like behavior in dams and their offspring. We further investigated whether chewing during maternal stress could prevent PS‐induced harmful consequences. Pregnant rats were randomly divided into PS, PS + chewing, and control groups. Anxiety‐like behaviors of dams and their adolescent offspring were assessed using the open field test and elevated plus maze. Serum levels of PRL and CORT were measured by ELISA. Expression of mRNA and protein of PRLR and glucocorticoid receptor (GR) in the prefrontal cortex (PFC) were evaluated by qRT‐PCR and western blotting, respectively. Compared to the control rats, dams and their female offspring, but not male offspring, in the PS group showed increased anxiety‐like behaviors. The PS‐affected rats had a lower serum PRL level and increased PRLR expression in the PFC. In contrast, these rats had a higher serum CORT level and decreased GR expression in the PFC. Chewing ameliorated anxiety‐like behaviors and counteracted stress‐induced changes in serum PRL and CORT, as well as the expression of their receptors in the PFC. Conclusion: PS‐induced anxiety‐like behavior is associated with changes in the serum levels of PRL and CORT and expression of their receptors in the PFC. Moreover, chewing blunts the hormonal and receptor changes and may serve as an effective stress‐coping method for preventing PS‐induced anxiety‐like behavior.