Efficacy and safety of adjunctive treatment with perampanel in epilepsy patients.

INTRODUCTION: Epilepsy is a neurological disease with high global prevalence. Almost one-third of epilepsy patients continue having seizures despite adequate treatment. Perampanel has been widely used in the Western countries as an adjunctive therapy for both generalized and focal seizures. Owing to its high cost, the use of perampanel is limited in our country. MATERIALS AND METHODS: We conducted a descriptive, retrospective study among epilepsy patients treated with perampanel. We aimed to assess the efficacy and safety of perampanel as an adjunctive in our hospital. RESULTS AND CONCLUSIONS: From our cohort of 25 patients, most of the patients were either on one or three anti-seizure medications (ASMs) prior to initiation of perampanel. Perampanel was added in 88% of them due to persistent seizures. Twenty-two (88%) patients experienced reduction in seizure frequency. 12% experienced mild side effects, which were leg cramps, hyponatremia and drowsiness. Only 1 patient stopped perampanel due to its side effects. CONCLUSION: Perampanel is a well-tolerated ASM that should be widely used as an adjunctive. More studies with regards to its efficacy and safety involving more centres are encouraged in Malaysia.

Aquatic disaster activation plan and tactic: The natural history and management conceptual framework of aquatic disasters.

INTRODUCTION: In the past decades, water-related disasters had been accounted for about three-quarters of all-natural disasters worldwide. Asia is the most affected region with more than 45% of fatalities and more than 90% of the victims affected by aquatic disasters. Aquatic events progress differently and rapidly as compared to inland disasters. Thus, apart from additional equipments and trained aquatic rescuers, aquatic disaster operation requires specific strategies and tactics. MATERIALS AND METHODS: This qualitative study was conducted using mixed methods involving the Delphi method and decision-conferencing approach. Two rounds of open-ended questionnaires were sent to subject matter experts from rescue agencies that involved in aquatic disaster rescue and management. Feedback from the panel was reviewed, the natural history of different aquatic disasters was appraised, and the decision-analysis model on the command, control and management of aquatic disaster was developed. The model was then reassessed through an iteration process at decision-conferencing among the expert panel until the final framework was accepted by all members of the panel. RESULTS: The fast progression of aquatic disasters with multiple hazards on the scene and unique technical challenges of the operation increase the risk of rescuers to become victims themselves. The developed conceptual framework, namely Aquatic Disaster Activation Plan and Tactic (ADAPT), was found able to guide rescuers in risk assessment, judgment, and response in aquatic disasters based on strategies and tactics for different phases along the natural history of aquatic disasters. CONCLUSION: With realistic scenario-based training and drills, ADAPT can be the blueprint in aquatic disaster management. It is designed to facilitate rescue agencies and organizations in preparing and executing the technical aquatic rescue operations safely, according to the resources available and the capability of the respective rescue organization.

Systematic review and meta-analysis of the prevalence of neuropathic-like pain and/or pain sensitization in people with knee and hip osteoarthritis.

OBJECTIVE: To determine the prevalence of neuropathic-like pain (NP) and pain sensitization (PS) defined by self-report questionnaires in knee and hip osteoarthritis, and whether prevalence is potentially explained by disease-severity or affected joint. DESIGN: MEDLINE, EMBASE, CINAHL were systematically searched (1990-April 2020) for studies describing the prevalence of NP and PS in knee and hip osteoarthritis using self-report questionnaires. Random-effects meta-analysis was performed. Statistical heterogeneity between studies and sub-groups (affected joint and population source as a proxy for disease severity) was assessed (I2 statistic and the Chi-squared test). RESULTS: From 2,706 non-duplicated references, 39 studies were included (2011-2020). Thirty-six studies reported on knee pain and six on hip pain. For knee osteoarthritis, the pooled prevalence of NP was: using PainDETECT, possible NP(score ≥13) 40% (95%CI 32-48%); probable NP(score >18) 20% (95%CI 15-24%); using Self-Report Leeds Assessment of Neuropathic Symptoms and Signs, 32% (95%CI 26-38%); using Douleur Neuropathique (DN4) 41% (95% CI 24-59%). The prevalence of PS using Central Sensitization Inventory (CSI) was 36% (95% CI 12-59%). For hip osteoarthritis, the pooled prevalence of NP was: using PainDETECT, possible NP 29% (95%CI 22-37%%); probable NP 9% (95%CI 6-13%); using DN4 22% (95%CI 12-31%) in one study. The prevalence of possible NP pain was higher at the knee (40%) than the hip (29%) (difference 11% (95% CI 0-22%), P = 0.05). CONCLUSIONS: Using self-report questionnaire tools, NP was more prevalent in knee than hip osteoarthritis. The prevalence of NP in knee and hip osteoarthritis were similar for each joint regardless of study population source or tool used. Whether defining NP using self-report questionnaires enables more effective targeted therapy in osteoarthritis requires investigation.

Does preoperative neuropathic-like pain and central sensitisation affect the post-operative outcome of knee joint replacement for osteoarthritis? A systematic review and meta analysis.

BACKGROUND: Almost a third of those undergoing knee replacement for osteoarthritis have poor outcomes despite technically successful surgery. Preoperative neuropathic-like pain and/or pain sensitisation may increase the risk of pain following joint replacement. OBJECTIVE: To examine whether preoperative neuropathic-like pain and pain sensitisation predicts pain, function and satisfaction following joint replacement for knee osteoarthritis. DESIGN: Systematic review with meta-analysis. METHODS: Medline, EMBASE and CINAHL were systematically searched until March 2020. Studies detecting neuropathic-like pain and/or sensitisation using self-report questionnaires prior to knee replacement for osteoarthritis, and relating this to post-operative outcomes were identified. Data extraction, risk of bias assessment and meta-analysis were performed, where appropriate. RESULTS: Five manuscripts, including one preprint, examining six cohorts were included: four used painDETECT or modified painDETECT, one the Self-Report Leeds Assessment of Neuropathic Symptoms and Signs, and another the Central Sensitisation Inventory to identify preoperative characteristics. Three studies showed preoperative neuropathic-like pain or sensitisation was associated with more intense post-operative pain. All four studies examining the risk of significant pain after knee replacement suggested it was increased after >3 months. The only study examining patient satisfaction and function found reduced satisfaction, but no difference in function in those with preoperative sensitisation. Meta-analysis found the relative risk of increased pain following knee replacement in those with neuropathic-like pain (painDETECT ≥13) to be 2.05 (95% confidence intervals 1.51, 2.79). CONCLUSION: These results provide consistent but limited evidence that self-report tools detecting neuropathic-like pain and/or pain sensitisation, predict patients at higher risk of pain following knee replacement.

High intensity non-invasive positive pressure ventilation for refractory decompensated acute hypercapnic respiratory failure in advanced chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a debilitating progressive lung disease characterised by irreversible airflow obstruction. In addition to an increase in morbidity and mortality, exacerbation also results in frequent hospital visits, which place a burden on healthcare systems. Non-invasive positive pressure ventilation (NPPV) with conventional inspiratory pressures is the standard ventilatory support for patients in exacerbation. At present, the use of higher inspiratory pressures through high intensity noninvasive positive pressure ventilation (Hi-NPPV) during an exacerbation remains unknown. We describe a novel application of Hi-NPPV in a patient with acute exacerbation who was refractory to conventional NPPV.

Mobilization of retrotransposons in synthetic allotetraploid tobacco.

Allopolyploidy is a major driving force in plant evolution and can induce rapid structural changes in the hybrid genome. As major components of plant genomes, transposable elements are involved in these changes. In a previous work, we observed turnover of retrotransposon insertions in natural allotretraploid tobacco (Nicotiana tabacum). Here, we studied the early stages of allopolyploid formation by monitoring changes at retrotransposon insertion sites in the Th37 synthetic tobacco. We used sequence-specific amplification polymorphism (SSAP) to study insertion patterns of two populations of the Tnt1 retrotransposon in Th37 S4 generation plants, and characterized the nature of polymorphic insertion sites. We observed significant amplification of young Tnt1 populations. Newly transposed copies were amplified from maternal elements and were highly similar to Tnt1A tobacco copies amplified in response to microbial factors. A high proportion of paternal SSAP bands were not transmitted to the hybrid, corresponding to various rearrangements at paternal insertion sites, including indels or the complete loss of the Tnt1/flanking junction. These data indicate that major changes, such as retrotransposon amplification and molecular restructuring in or around insertion sites, occur rapidly in response to allopolyploidy.

Effects of online augmented kinematic and perceptual feedback on treatment of speech movements in apraxia of speech.

Apraxia of speech (AOS) is a motor speech disorder characterized by disturbed spatial and temporal parameters of movement. Research on motor learning suggests that augmented feedback may provide a beneficial effect for training movement. This study examined the effects of the presence and frequency of online augmented visual kinematic feedback (AVKF) and clinician-provided perceptual feedback on speech accuracy in 2 adults with acquired AOS. Within a single-subject multiple-baseline design, AVKF was provided using electromagnetic midsagittal articulography (EMA) in 2 feedback conditions (50 or 100%). Articulator placement was specified for speech motor targets (SMTs). Treated and baselined SMTs were in the initial or final position of single-syllable words, in varying consonant-vowel or vowel-consonant contexts. SMTs were selected based on each participant's pre-assessed erred productions. Productions were digitally recorded and online perceptual judgments of accuracy (including segment and intersegment distortions) were made. Inter- and intra-judge reliability for perceptual accuracy was high. Results measured by visual inspection and effect size revealed positive acquisition and generalization effects for both participants. Generalization occurred across vowel contexts and to untreated probes. Results of the frequency manipulation were confounded by presentation order. Maintenance of learned and generalized effects were demonstrated for 1 participant. These data provide support for the role of augmented feedback in treating speech movements that result in perceptually accurate speech production. Future investigations will explore the independent contributions of each feedback type (i.e. kinematic and perceptual) in producing efficient and effective training of SMTs in persons with AOS.

Stress in Parents of Children With Genetically Determined Leukoencephalopathies: A Pilot Study.

Genetically determined leukoencephalopathies comprise a group of rare inherited white matter disorders. The majority are progressive diseases resulting in early death. We performed a cross-sectional pilot study including 55 parents from 36 families to assess the level of stress experienced by parents of patients with genetically determined leukoencephalopathies, aged 1 month to 12 years. Thirty-four mothers and 21 fathers completed the Parenting Stress Index-4th Edition. One demographic questionnaire was completed per family. Detailed clinical data was gathered on all patients. Statistical analysis was performed with total stress percentile score as the primary outcome. Mothers and fathers had significantly higher stress levels compared with the normative sample; 20% of parents had high levels of stress whereas 11% had clinically significant levels of stress. Mothers and fathers had comparable total stress percentile scores. We identified pediatric behavioral difficulties and gross motor function to be factors influencing stress in mothers. Our study is the first to examine parental stress in this population and highlights the need for parental support early in the disease course. In this pilot study, we demonstrated that using the Parenting Stress Index-4th Edition to assess stress levels in parents of patients with genetically determined leukoencephalopathies is feasible, leads to valuable and actionable results, and should be used in larger, prospective studies.

The ups and downs of genome size evolution in polyploid species of Nicotiana (Solanaceae).

BACKGROUND: In studies looking at individual polyploid species, the most common patterns of genomic change are that either genome size in the polyploid is additive (i.e. the sum of parental genome donors) or there is evidence of genome downsizing. Reports showing an increase in genome size are rare. In a large-scale analysis of 3008 species, genome downsizing was shown to be a widespread biological response to polyploidy. Polyploidy in the genus Nicotiana (Solanaceae) is common with approx. 40 % of the approx. 75 species being allotetraploid. Recent advances in understanding phylogenetic relationships of Nicotiana species and dating polyploid formation enable a temporal dimension to be added to the analysis of genome size evolution in these polyploids. METHODS: Genome sizes were measured in 18 species of Nicotiana (nine diploids and nine polyploids) ranging in age from <200,000 years to approx. 4.5 Myr old, to determine the direction and extent of genome size change following polyploidy. These data were combined with data from genomic in situ hybridization and increasing amounts of information on sequence composition in Nicotiana to provide insights into the molecular basis of genome size changes. KEY RESULTS AND CONCLUSIONS: By comparing the expected genome size of the polyploid (based on summing the genome size of species identified as either a parent or most closely related to the diploid progenitors) with the observed genome size, four polyploids showed genome downsizing and five showed increases. There was no discernable pattern in the direction of genome size change with age of polyploids, although with increasing age the amount of genome size change increased. In older polyploids (approx. 4.5 million years old) the increase in genome size was associated with loss of detectable genomic in situ hybridization signal, whereas some hybridization signal was still detected in species exhibiting genome downsizing. The possible significance of these results is discussed.

Rapid concerted evolution of nuclear ribosomal DNA in two Tragopogon allopolyploids of recent and recurrent origin.

We investigated concerted evolution of rRNA genes in multiple populations of Tragopogon mirus and T. miscellus, two allotetraploids that formed recurrently within the last 80 years following the introduction of three diploids (T. dubius, T. pratensis, and T. porrifolius) from Europe to North America. Using the earliest herbarium specimens of the allotetraploids (1949 and 1953) to represent the genomic condition near the time of polyploidization, we found that the parental rDNA repeats were inherited in roughly equal numbers. In contrast, in most present-day populations of both tetraploids, the rDNA of T. dubius origin is reduced and may occupy as little as 5% of total rDNA in some individuals. However, in two populations of T. mirus the repeats of T. dubius origin outnumber the repeats of the second diploid parent (T. porrifolius), indicating bidirectional concerted evolution within a single species. In plants of T. miscellus having a low rDNA contribution from T. dubius, the rDNA of T. dubius was nonetheless expressed. We have apparently caught homogenization of rDNA repeats (concerted evolution) in the act, although it has not proceeded to completion in any allopolyploid population yet examined.

Molecular cytogenetics and tandem repeat sequence evolution in the allopolyploid Nicotiana rustica compared with diploid progenitors N. paniculata and N. undulata.

Nicotiana rustica (2n = 4x = 48) is a natural allotetraploid composed of P and U genomes which are closely related to genomes of diploid species N. paniculata and N. undulata. Genomic in situ hybridization (GISH) also confirms that the diploid parents, or close relatives, are the ancestors of N. rustica. In order to study genetic interactions between ancestral genomes in the allotetraploid, we isolated three families of repetitive sequences, two from N. paniculata (NPAMBE and NPAMBO) and one from N. undulata (NUNSSP). Southern blot hybridization revealed that the sequences are digested with a range of restriction enzymes into regular ladder patterns indicating a tandem arrangement of high copy repeats possessing monomeric units of about 180 bp. The three-tandem sequences belong to a larger Nicotiana tandem repeat family called here the HRS-60 family. Members of this family are found in all Nicotiana species studied. Fluorescence in situ hybridization (FISH) analysis localized the satellite repeats to subtelomeric regions of most chromosomes of N. paniculata and N. undulata. The pattern of sequence distribution on the P- and U-genomes of N. rustica was similar to the putative parents N. paniculata and N. undulata respectively. However, NPAMBO repeats appear to be reduced and rearranged in N. rustica that may suggest evolution within the P genome. GISH and FISH with the tandem repeat probes failed to reveal intergenomic translocations as might be predicted from the nucleocytoplasmic interaction hypothesis.

Dynamic changes in the distribution of a satellite homologous to intergenic 26-18S rDNA spacer in the evolution of Nicotiana.

An approximately 135-bp sequence called the A1/A2 repeat was isolated from the transcribed region of the 26-18S rDNA intergenic spacer (IGS) of Nicotiana tomentosiformis. Fluorescence in situ hybridization (FISH) and Southern blot analysis revealed its occurrence as an independent satellite (termed an A1/A2 satellite) outside of rDNA loci in species of Nicotiana section Tomentosae. The chromosomal location, patterns of genomic dispersion, and copy numbers of its tandemly arranged units varied between the species. In more distantly related Nicotiana species the A1/A2 repeats were found only at the nucleolar organizer regions (NOR). There was a trend toward the elimination of the A1/A2 satellite in N. tabacum (tobacco), an allotetraploid with parents closely related to the diploids N. sylvestris and N. tomentosiformis. This process may have already commenced in an S(3) generation of synthetic tobacco. Cytosine residues in the IGS were significantly hypomethylated compared with the A1/A2 satellite. There was no clear separation between the IGS and satellite fractions in sequence analysis of individual clones and we found no evidence for CG suppression. Taken together the data indicate a dynamic nature of the A1/A2 repeats in Nicotiana genomes, with evidence for recurrent integration, copy number expansions, and contractions.

Anaesthesia for a patient with long QT syndrome undergoing renal transplantation.

Anaesthetizing patients with Long QT Syndrome is a major challenge, as the potential for sudden catastrophic cardiovascular collapse is well known. We present a 15-year-old boy with Long QT Syndrome who presented for an elective renal transplant. All electrolyte concentration abnormalities were corrected preoperative and adequate beta-blockade was maintained. The patient was given a target controlled infusion of propofol, together with opioids and atracurium. Anaesthesia was uneventful and the patient was extubated at the end of the surgical procedure.

Perceived skill and utilisation of information technology in medical education among final year medical students, Universiti Putra Malaysia.

The objective of this survey was to obtain a self-reported assessment of the use of information technology (IT) by final year medical students. Two hundred and sixty five students responded to a questionnaire survey. 81.5% of students considered their computer skills adequate, while 87.9% had access to computers outside the campus. Most students reported adequate skills at word processing, e-mailing and surfing the Internet. Fifty three percent of students spent three hours or more each week on the computer. While students indicated a general willingness to access Internet-based materials, further steps need to be taken to increase the use of this method of instruction.

cDNA cloning and characterization of human cardiac junctin.

Junctin is a calsequestrin binding protein detected in junctional sarcoplasmic reticulum of striated muscles. In the present study, the human cardiac junctin cDNA has been cloned by human heart cDNA library screening and RT-PCR, and the cDNA sequence has been determined. The deduced amino acid sequence of human junctin (210 aa) has 84% sequence identity to that of canine junctin identified previously. A human junctin isoform (isoform 1, 225 aa) was also identified and characterized. The isoform 1 has a 15 aa insertion at the amino acid residue 55 of the human junctin. Northern blot analysis revealed that the human junctin was present both in cardiac and skeletal muscles, and the sizes of the transcripts were approximately 3.0 and 4.2kb. Amino acid residues 6-78 of human junctin and 35-107 of human aspartyl beta-hydroxylase (hAspH) overlapped perfectly. The gene copy number of human junctin and hASPH was investigated by genomic Southern blot analysis using various restriction enzymes and a common DNA probe. The result showing a single hybridized DNA band at each restriction enzyme suggests that the same genomic region codes both junctin and hASPH.

Telomere variability in the monocotyledonous plant order Asparagales.

A group of monocotyledonous plants within the order Asparagales, forming a distinct clade in phylogenetic analyses, was reported previously to lack the 'typical' Arabidopsis-type telomere (TTTAGGG)(n). This stimulated us to determine what has replaced these sequences. Using slot-blot and fluorescent in situ hybridization (FISH) to species within this clade, our results indicate the following. 1. The typical Arabidopsis-type telomeric sequence has been partly or fully replaced by the human-type telomeric sequence (TTAGGG)(n). Species in Allium lack the human-type variant. 2. In most cases the human variant occurs along with a lower abundance of two or more variants of the minisatellite sequences (of seven types evaluated), usually these being the consensus telomeric sequence of Arabidopsis, Bombyx (TTAGG)(n) and Tetrahymena (TTGGGG)(n). FISH shows that the variants can occur mixed together at the telomere. 3. Telomerases generate products with a 6 base pair periodicity and when sequenced they reveal predominantly a reiterated human-type motif. These motifs probably form the 'true telomere' but the error rate of motif synthesis is higher compared with 'typical' plant telomerases. The data indicate that the Asparagales clade is unified by a mutation resulting in a switch from synthesis of Arabidopsis-like telomeres to a low-fidelity synthesis of human-like telomeres.

Loss and recovery of Arabidopsis-type telomere repeat sequences 5'-(TTTAGGG)(n)-3' in the evolution of a major radiation of flowering plants.

Fluorescent in situ hybridization and Southern blotting were used for showing the predominant absence of the Arabidopsis-type telomere repeat sequence (TRS) 5'-(TTTAGGG)(n)-3' (the 'typical' telomere) in a monocot clade which comprises up to 6300 species within Asparagales. Initially, two apparently disparate genera that lacked the typical telomere were identified. Here, we used the new angiosperm phylogenetic classification for predicting in which other related families such telomeres might have been lost. Our data revealed that 16 species in 12 families of Asparagales lacked typical telomeres. Phylogenetically, these were clustered in a derived clade, thereby enabling us to predict that the typical telomere was lost, probably as a single evolutionary event, following the divergence of Doryanthaceae ca. 80--90 million years ago. This result illustrates the predictive value of the new phylogeny, as the pattern of species lacking the typical telomere would be considered randomly placed against many previous angiosperm taxonomies. Possible mechanisms by which chromosome end maintenance could have evolved in this group of plants are discussed. Surprisingly, one genus, Ornithogalum (Hyacinthaceae), which is central to the group of plants that have lost the typical telomere, appears to have regained the sequences. The mechanism(s) by which such recovery may have occurred is unknown, but possibilities include horizontal gene transfer and sequence reamplification.

JSD and the design of user interface software.

Systems analysis and design methods (SADMs), such as Jackson system development (JSD), have been proposed as a means of improving software quality. This is contrasted with the role of improving software usability proposed for human factors (HF). The paper argues the need for an explicit user interface specification stage in system development to ensure the usability of proposed systems. It is suggested that JSD supplemented by the specialist knowledge of HF can support such a specification stage. For HF and JSD to be successfully integrated, contributions from both need to be appropriately timed and structured. A model of the system development process that incorporates HF contributions is proposed. A means by which the HF contributions, in the form of a user interface specification, can be integrated with the JSD specification is developed and illustrated through examples.

Yttrium-90 internal pair production imaging using first generation PET/CT provides high-resolution images for qualitative diagnostic purposes.

Yttrium-90 ((90)Y) internal pair production can be imaged by positron emission tomography (PET)/CT and is superior to bremsstrahlung single-photon emission CT/CT for evaluating hepatic (90)Y microsphere biodistribution. We illustrate a case of (90)Y imaging using first generation PET/CT technology, producing high-quality images for qualitative diagnostic purposes.

The impact of combined pulmonary fibrosis and emphysema on mortality.

SETTING: The impact on patient mortality of combined pulmonary fibrosis and emphysema (CPFE) compared with emphysema alone has never been investigated. OBJECTIVE: To elucidate whether CPFE has an impact on overall mortality over that of emphysema alone. DESIGN: We screened patients who underwent chest computed tomography (CT) scans during the period from 1 January 2001 to 31 December 2005 in a tertiary referral hospital. Patients who had both emphysema and pulmonary fibrosis, thus meeting the inclusion criteria, were defined as CPFE. Controls with emphysema alone who were matched for age, sex and the date of CT scan were randomly selected. Cox proportional regression analysis was performed to verify whether CPFE is associated with increased overall mortality. RESULTS: We found 135 CPFE cases. In the multivariable Cox regression stratified by the presence of comorbid malignancy, CPFE had five times higher mortality risk (adjusted HR 5.10, 95%CI 1.75-14.9) in non-malignant cases, and showed a statistically insignificant trend for higher mortality risk (adjusted HR 1.70, 95%CI 0.94-2.51) in the malignant cases after adjusting for forced vital capacity, height and hypertension. CONCLUSION: CPFE is not rare and CPFE patients had a higher overall mortality risk than emphysema-only patients.