Clinical targeting of HIV capsid protein with a long-acting small molecule.

Oral antiretroviral agents provide life-saving treatments for millions of people living with HIV, and can prevent new infections via pre-exposure prophylaxis1-5. However, some people living with HIV who are heavily treatment-experienced have limited or no treatment options, owing to multidrug resistance6. In addition, suboptimal adherence to oral daily regimens can negatively affect the outcome of treatment-which contributes to virologic failure, resistance generation and viral transmission-as well as of pre-exposure prophylaxis, leading to new infections1,2,4,7-9. Long-acting agents from new antiretroviral classes can provide much-needed treatment options for people living with HIV who are heavily treatment-experienced, and additionally can improve adherence10. Here we describe GS-6207, a small molecule that disrupts the functions of HIV capsid protein and is amenable to long-acting therapy owing to its high potency, low in vivo systemic clearance and slow release kinetics from the subcutaneous injection site. Drawing on X-ray crystallographic information, we designed GS-6207 to bind tightly at a conserved interface between capsid protein monomers, where it interferes with capsid-protein-mediated interactions between proteins that are essential for multiple phases of the viral replication cycle. GS-6207 exhibits antiviral activity at picomolar concentrations against all subtypes of HIV-1 that we tested, and shows high synergy and no cross-resistance with approved antiretroviral drugs. In phase-1 clinical studies, monotherapy with a single subcutaneous dose of GS-6207 (450 mg) resulted in a mean log10-transformed reduction of plasma viral load of 2.2 after 9 days, and showed sustained plasma exposure at antivirally active concentrations for more than 6 months. These results provide clinical validation for therapies that target the functions of HIV capsid protein, and demonstrate the potential of GS-6207 as a long-acting agent to treat or prevent infection with HIV.

Visual Stimuli Modulate Local Field Potentials But Drive No High-Frequency Activity in Human Auditory Cortex.

Neuroimaging studies suggest cross-sensory visual influences in human auditory cortices (ACs). Whether these influences reflect active visual processing in human ACs, which drives neuronal firing and concurrent broadband high-frequency activity (BHFA; >70 Hz), or whether they merely modulate sound processing is still debatable. Here, we presented auditory, visual, and audiovisual stimuli to 16 participants (7 women, 9 men) with stereo-EEG depth electrodes implanted near ACs for presurgical monitoring. Anatomically normalized group analyses were facilitated by inverse modeling of intracranial source currents. Analyses of intracranial event-related potentials (iERPs) suggested cross-sensory responses to visual stimuli in ACs, which lagged the earliest auditory responses by several tens of milliseconds. Visual stimuli also modulated the phase of intrinsic low-frequency oscillations and triggered 15-30 Hz event-related desynchronization in ACs. However, BHFA, a putative correlate of neuronal firing, was not significantly increased in ACs after visual stimuli, not even when they coincided with auditory stimuli. Intracranial recordings demonstrate cross-sensory modulations, but no indication of active visual processing in human ACs.

Development and construction of the Multidimensional Self-Efficacy Scale for Epilepsy (MSESE) and its psychometric properties.

PURPOSE: It has become evident that patients with epilepsy require strong self-efficacy support in various domains, including work, social interaction, and academic performance, to ensure their complete social functioning. Nevertheless, previous studies have predominantly assessed the self-efficacy of individuals with epilepsy from a singular perspective of disease management. This study aimed to develop the Multidimensional Self-Efficacy Scale for Epilepsy (MSESE) to assess multiple dimensions and establish its psychometric properties. METHODS: We compiled a total of 25 questions for the initial version of the questionnaire based on a review of the literature and insights from experts, patients, and family members. The study included 180 adult patients with epilepsy who met the research criteria, with 126 of them serving as pre-test samples. All participants completed the MSESE, Brief Symptom Rating Scale-50 (BSRS-50), Rosenberg Self-Esteem Scale-Chinese version (RSES-C), and General Self-Efficacy Scale (GSES). RESULTS: The final scale consisted of 12 items across four dimensions, with item factor loadings ranging from .51 to .90. Most of the fit indices indicated a good fit. Construct validity was established through significant correlations with the BSRS-50, RSES-C, and GSES (r = -0.51 to 0.69, p < 0.01). Internal consistency coefficients for the MSESE were strong at .90, with individual dimensions ranging from 0.71 to 0.89. The MSESE also demonstrated a satisfactory test-retest reliability of 0.72. CONCLUSIONS: The MSESE is a convenient, multidimensional, and easy-to-use scale with good psychometric properties, making it suitable for both clinical assessments and research purposes.

Frame-based versus robot-assisted stereo-electro-encephalography for drug-resistant epilepsy.

BACKGROUND: Stereoelectroencephalography (SEEG) is an effective presurgical invasive evaluation for drug-resistant epilepsies. The introduction of robotic devices provides a simplified, accurate, and safe alternative to the conventional SEEG technique. We report our institutional experience with robot-assisted SEEG and compare its in vivo accuracy, operation efficiency, and safety with the more traditional SEEG workflow. METHODS: All patients with medically refractory focal epilepsy who underwent SEEG depth electrode implantation between 2014 and 2022 were included in this study. Technical advancements of the robot-assisted technique are described. Analyses of patient demographics, electrode implantation accuracy, operation time, and procedure-related complications were performed. RESULTS: One hundred and sixty-six patients underwent 167 SEEG procedures. The first 141 procedures were performed using a conventional approach involving a Leksell stereotactic system, and the last 26 procedures were robot-assisted. Among the 1726 depth electrodes that were inserted, the median entry point localization error was as follows: conventional (1.0 mm; range, 0.1-33.5 mm) and robot-assisted (1.1 mm; range, 0-4.8 mm) (P = 0.17). The median target point localization error was as follows: conventional (2.8 mm; range, 0.1-49 mm) and robot-assisted (1.8 mm; range, 0-30.3 mm) (P < 0.001). The median operation time was significantly reduced with the robot-assisted workflow (90 min vs. 77.5 min; P < 0.01). Total complication rates were as follows: conventional (17.7%) and robot-assisted (11.5%) (P = 0.57). Major complication rates were 3.5% and 7.7% (P = 0.77), respectively. CONCLUSIONS: SEEG is a safe and highly accurate method that provides essential guidance for epilepsy surgery. Implementing SEEG in conjunction with multimodal planning systems and robotic devices can further increase safety margin, surgical efficiency, and accuracy.

The Association between Cholesterol Levels and Severity of Normal Tension Glaucoma.

Purpose: To evaluate the serum lipid levels, including total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) of patients with normal tension glaucoma (NTG) and to investigate the relationship between serum HDL levels and the severity of NTG. Methods: In this cross-sectional, case-control study, 282 NTG subjects and 202 control subjects were enrolled from the outpatient clinic of the Department of Ophthalmology at Taichung Veterans General Hospital in central Taiwan from 2015 to 2021. Fasting cholesterol, HDL, and LDL levels were evaluated using a biochemical analyzer (ARCHITECT c16000). Glaucoma severity was classified by visual field test as mild (mean deviation [MD] ≥ -6.0dB), moderate (-12dB ≤ MD < -6 dB), and severe (MD < -12dB), based on the mean deviation. Results: HDL levels were significantly lower in the NTG group compared with the control subjects (47 ± 18mg/dl versus 53 ± 18mg/dl; p = 0.03). There were no statistically significant differences in total cholesterol or LDL levels between the NTG and control subjects (total cholesterol levels: 194 ± 39mg/dl versus 190 ± 32mg/dl; p > 0.05; LDL levels: 113 ± 30mg/dl versus 110 ± 29mg/dl; p > 0.05). The mean serum HDL levels were lowest in the severe group (41 ± 11mg/dl) followed by the moderate (45 ± 16mg/dl) and mild (50 ± 15mg/dl) groups, with significant differences among the three groups (p = 0.02). The multivariate regression analysis revealed a statistically significant negative correlation between HDL and vertical cup-to-disc ratio (VCDR; B =-0.16, p = 0.03) among all NTG patients and a positive correlation between HDL and retinal nerve fiber layer (RNFL; r = 0.34, p = 0.03) among all NTG patients. Conclusions: A significantly lower serum HDL concentration was found in the NTG patients, which was negatively associated with disease severity. The findings warrant further study to elucidate the role of these phenomena in the pathogenesis of glaucoma.

Neuronal intranuclear inclusion disease in patients with adult-onset non-vascular leukoencephalopathy.

Neuronal intranuclear inclusion disease (NIID), caused by an expansion of GGC repeats in the 5'-untranslated region of NOTCH2NLC, is an important but underdiagnosed cause of adult-onset leukoencephalopathies. The present study aimed to investigate the prevalence, clinical spectrum and brain MRI characteristics of NIID in adult-onset nonvascular leukoencephalopathies and assess the diagnostic performance of neuroimaging features. One hundred and sixty-one unrelated Taiwanese patients with genetically undetermined nonvascular leukoencephalopathies were screened for the NOTCH2NLC GGC repeat expansions using fragment analysis, repeat-primed PCR, Southern blot analysis and/or nanopore sequencing with Cas9-mediated enrichment. Among them, 32 (19.9%) patients had an expanded NOTCH2NLC allele and were diagnosed with NIID. We enrolled another two affected family members from one patient for further analysis. The size of the expanded NOTCH2NLC GGC repeats in the 34 patients ranged from 73 to 323 repeats. Skin biopsies from five patients all showed eosinophilic, p62-positive intranuclear inclusions in the sweat gland cells and dermal adipocytes. Among the 34 NIID patients presenting with nonvascular leukoencephalopathies, the median age at symptom onset was 61 years (range, 41-78 years) and the initial presentations included cognitive decline (44.1%; 15/34), acute encephalitis-like episodes (32.4%; 11/34), limb weakness (11.8%; 4/34) and parkinsonism (11.8%; 4/34). Cognitive decline (64.7%; 22/34) and acute encephalitis-like episodes (55.9%; 19/34) were also the most common overall manifestations. Two-thirds of the patients had either bladder dysfunction or visual disturbance. Comparing the brain MRI features between the NIID patients and individuals with other undetermined leukoencephalopathies, corticomedullary junction curvilinear lesions on diffusion weighted images were the best biomarkers for diagnosing NIID with high specificity (98.4%) and sensitivity (88.2%). However, this diffusion weighted imaging abnormality was absent in 11.8% of the NIID patients. When only fluid-attenuated inversion recovery images were available, the presence of white matter hyperintensity lesions either in the paravermis or middle cerebellar peduncles also favoured the diagnosis of NIID with a specificity of 85.3% and sensitivity of 76.5%. Among the MRI scans of 10 patients, performed within 5 days of the onset of acute encephalitis-like episodes, five showed cortical hyperintense lesions on diffusion weighted images and two revealed focal brain oedema. In conclusion, NIID accounts for 19.9% (32/161) of patients with adult-onset genetically undiagnosed nonvascular leukoencephalopathies in Taiwan. Half of the NIID patients developed encephalitis-like episodes with restricted diffusion in the cortical regions on diffusion weighted images at the acute stage. Corticomedullary junction hyperintense lesions, white matter hyperintensities in the paravermis or middle cerebellar peduncles, bladder dysfunction and visual disturbance are useful hints to diagnosing NIID.

Cognitively engaging movement games improve interference control and academic performance in overweight children: A randomized control trial.

The purpose of this study was to determine the (a) dose-response effects of cognitively engaging movement games (CEMGs) designed to improve aerobic capacity, interference control (IC), and academic performance, (b) relationship between intervention-induced improvements in aerobic capacity, IC, and academic performance, and (c) moderation effect of IC on the relationship between aerobic capacity and academic performance in overweight children. Seventy-five overweight children (aged 11.23 ± 0.60 years; 48% males) participated in this study conducted in Taipei during the 2018/2019 academic year and were randomly assigned to the low-dose (20-min) intervention, high-dose (40-min) intervention, and control groups and completed a Stroop test, half-mile run, and language and mathematics tests before and after a 10-week afterschool program. Both intervention groups showed similar improvements in outcomes of aerobic capacity (ds > 0.80), IC (ds > 0.76), and academic performance (ds > 0.90) from the pretest to posttest, whereas these outcomes were unchanged for the control group. Furthermore, improved IC moderated the association between improvements in aerobic capacity and academic performance. Our findings suggest that CEMG with varying doses is feasible and effective for improving aerobic capacity, IC, and academic performance in overweight children and that the association between improvements in aerobic capacity and academic performance depends on the intervention effects on IC.

Non-meningeal, non-pulmonary cryptococcosis with limited posterior uveitis in a kidney organ transplant recipient with antibody-mediated rejection: a case report.

BACKGROUND: Cryptococcosis is one of the most frequent fungal eye infections in patients with immunosuppression. Currently, treatment approaches for non-meningeal, non-pulmonary cryptococcosis are based on those used for cryptococcal meningitis or pneumonia. CASE PRESENTATION: We present a rare case of non-meningeal, non-pulmonary cryptococcosis with clinical manifestations limited to one eye of a cadaveric kidney transplant recipient with chronic-active antibody-mediated rejection. Typical manifestations, diagnosis, and treatments, including antifungal therapies, adjunctive therapies, and immunosuppression reduction, are discussed. After timely diagnosis and treatment, her visual acuity recovered to baseline without recurrence or sequelae of cryptococcosis. CONCLUSIONS: Clinicians should be aware of rare presentations of fungal infections, especially when a kidney transplant recipient with rejection has been treated with intensive immunosuppressants. Early diagnosis with individualized therapies may have a favorable prognosis.

Pilot study of focused ultrasound for drug-resistant epilepsy.

OBJECTIVE: The neuromodulatory effects of focused ultrasound (FUS) have been demonstrated in animal epilepsy models; however, the safety and efficacy of FUS in humans with epilepsy have not been well established. Patients with drug-resistant epilepsy (DRE) undergoing stereo-electroencephalography (SEEG) provide an opportunity to investigate the neuromodulatory effects of FUS in humans. METHODS: Patients with DRE undergoing SEEG for localization of the seizure onset zone (SOZ) were prospectively enrolled. FUS was delivered to the SOZ using a neuronavigation-guided FUS system (ceiling spatial-peak temporal-average intensity level = 2.8 W/cm2 , duty cycle = 30%, modulating duration = 10 min). Simultaneous SEEG recordings were obtained during sonication and for 3 days after treatment. Seizures, interictal epileptiform discharges, and adverse events after FUS were monitored. RESULTS: Six patients met the eligibility criteria and completed FUS treatment. A decrease in seizure frequency was observed in two patients within the 3-day follow-up; however, one patient presented an increase in the frequency of subclinical seizures. Posttreatment magnetic resonance imaging revealed neither lesion nor brain edema. Significant changes in spectral power of SEEG were noted at the targeted electrodes during FUS treatment. One patient reported subjective scalp heating during FUS, and one patient developed transient naming and memory impairment that resolved within 3 weeks after FUS. SIGNIFICANCE: FUS can be safely delivered to the SOZ of patients with DRE, resulting in significant changes in spectral power of SEEG. A larger sample cohort and pursuing optimal sonication parameters will be required to elucidate the neuromodulatory effects of FUS when used for seizure control.

Clinical characteristics and long-term outcome of cerebral cavernous malformations-related epilepsy.

OBJECTIVE: Cerebral cavernous malformations (CCMs) present variably, and epileptic seizures are the most common symptom. The factors contributing to cavernoma-related epilepsy (CRE) and drug resistance remain inconclusive. The outcomes of CRE after different treatment modalities have not yet been fully addressed. This study aimed to characterize the clinical features of patients with CRE and the long-term seizure outcomes of medical and surgical treatment strategies. METHODS: This was a retrospective cohort of 135 patients with CCM who were diagnosed in 2007-2011 and followed up for 93.6 months on average. The patients were divided into drug-resistant epilepsy (DRE; n = 29), non-DRE (n = 45), and no epilepsy (NE; n = 61). RESULTS: Temporal CCM was the factor most strongly associated with the development of both CRE and DRE. The majority of patients with single temporal CCMs had CRE (86.8%, n = 33), and 50% had DRE, whereas only 14.7% (n = 5) with a nontemporal supratentorial CCM had DRE (p < .05). The most common lesion site in the DRE group was the mesiotemporal lobe (50%). Multiple CCMs were more frequently observed in the CRE (29.2%) than the NE (11.5%) group (p < .05). In patients with CRE, multiple lesions were associated with a higher rebleeding rate (odds ratio = 11.1), particularly in those with DRE (odds ratio = 15.4). The majority of patients who underwent resective surgery for DRE (76.5%, n = 13) achieved International League Against Epilepsy Class I and II seizure outcomes even after a long disease course. SIGNIFICANCE: Temporal CCM not only predisposes to CRE but also is a major risk factor for drug resistance. The mesiotemporal lobe is the most epileptogenic zone. Multiple CCMs are another risk factor for CRE and increase the rebleeding risk in these patients. Surgical resection could provide beneficial long-term seizure outcomes in patients with DRE.

Validation of the Taiwanese version of the Epilepsy Surgery Satisfaction Questionnaire (Tw-ESSQ-19).

OBJECTIVE: Satisfaction with epilepsy surgery in Mandarin-speaking countries remains unknown. We aimed to validate in our Taiwanese patients an existing instrument to measure patient satisfaction with epilepsy surgery, the 19-item Epilepsy Surgery Satisfaction Questionnaire (ESSQ-19). METHODS: Consecutive patients with epilepsy who received epilepsy surgery one year earlier in Taipei Veterans General Hospital were recruited and provided clinical and demographic data. The Mandarin version of the ESSQ-19 for the Taiwanese population and eight other questionnaires were completed to assess construct validity. To evaluate the validity and reliability of the tool, the data were analyzed by confirmatory factor analysis, Spearman's rank correlation, and internal consistency analysis. RESULTS: The study involved 120 patients (70 F/50 M, median age 35 years [IQR = 28-41]). The mean summary score (±SD) of the Tw-ESSQ-19 was 82.5 ±â€¯14.5. The mean scores of the four domains were 90.3 ±â€¯15.4 (surgical complications), 83.2 ±â€¯16.7 (seizure control), 80.1 ±â€¯17.3 (recovery from surgery), and 76.6 ±â€¯18.3 (psychosocial functioning). The questionnaire was shown to have good construct validity with satisfactory goodness-of-fit of the data (standardized root mean square residual = 0.0492; comparative fit index = 0.946). It also demonstrated good discriminant validity (being seizure free [AUC 0.78; 95% CI 0.68-0.89], endorsing depression [AUC 0.84; 95% CI 0.76-0.91], self-rating epilepsy as disabling [AUC 0.71; 95% CI 0.58-0.84], and self-rating epilepsy as severe [AUC 0.78; 95% CI 0.64-0.93]), high internal consistency in four domains (Cronbach's alpha = 0.83-0.96), and no significant floor/ceiling effects of the summary score. SIGNIFICANCE: The Mandarin version of the ESSQ-19 adapted for the Taiwanese population is a reliable and valid self-reported questionnaire for assessing patient satisfaction with epilepsy surgery.

Unexpected systolic anterior motion of the mitral valve-related hypoxemia during transurethral resection of the prostate under spinal anesthesia: a case report.

BACKGROUND: Dynamic obstruction of the left ventricular outflow tract resulting from systolic anterior motion of the mitral valve can be an unexpected cause of acute and severe perioperative hypotension in noncardiac surgery. We report a patient undergoing spinal anesthesia for transurethral resection of the prostate who experienced sudden hypoxemia caused by systolic anterior motion-induced mitral regurgitation but with a clinically picture simulating fluid overload. CASE PRESENTATION: An 83-year-old man with a history of hypertension was scheduled for transurethral resection of the prostate. One hour after spinal anesthesia, he developed acute restlessness and dyspnea, with pink frothy sputum and progressive hypoxemia. Slight hypertension was noted, and an electrocardiogram showed atrial fibrillation with a rapid ventricular response. Furosemide and nitroglycerin were thus administered for suspected fluid overload or transurethral resection of the prostate syndrome; however, he then became severely hypotensive. After tracheal intubation, intraoperative transesophageal echocardiography was promptly performed, which revealed an empty hypercontractile left ventricle, significant mitral regurgitation and mosaic flow signal in the left ventricular outflow tract. Following aggressive fluid therapy, his hemodynamic changes stabilized. Repeat echocardiography in intensive care unit confirmed the presence of systolic anterior motion of the anterior mitral leaflet obstructing the left ventricular outflow tract. We speculate that pulmonary edema was induced by systolic anterior motion-associated mitral regurgitation and rapid atrial fibrillation, and the initial management had worsened his hypovolemia and provoked left ventricular outflow tract obstruction and hemodynamic instability. CONCLUSIONS: Pulmonary edema caused by systolic anterior motion of the mitral valve can be difficult to clinically differentiate from that induced by fluid overload. Therefore, bedside echocardiography is paramount for timely diagnosis and prompt initiation of appropriate therapy in the perioperative care setting.

Reliability and validity of the traditional Chinese version of the GAD-7 in Taiwanese patients with epilepsy.

BACKGROUND: Generalized anxiety disorder (GAD) is the second most common psychiatric comorbidity of epilepsy. GAD has a negative impact on seizure control, and it is underrecognized. The Generalized Anxiety Disorder 7-item (GAD-7) questionnaire is useful for screening GAD in patients with epilepsy (PWE). This study aimed to validate the traditional Chinese version of the GAD-7 for Taiwanese patients by obtaining data on adult PWE from our hospital. METHOD: PWE were recruited from the Taipei Veterans General Hospital from April 2017 to January 2020. The mood disorder module of the Mini International Neuropsychiatric Interview (MINI) was used for the psychiatric assessment. The traditional Chinese version of the GAD-7 and the Beck Anxiety Inventory were included as self-rated psychiatric evaluation. To investigate the psychometric properties, internal consistency, external validation, and receiver operator characteristic (ROC) curve analysis were conducted to assess the utility of the Taiwanese version of the GAD-7. RESULTS: We recruited 109 patients in the present study. Seventeen patients (15.9%) had GAD according to the MINI. The mean GAD-7 score was 10.28 ± 10.68. All the GAD-7 items were significantly and positively associated with the corrected overall GAD-7 score (Cronbach's alpha = 0.928, p < 0.0001). The cut-off point for the GAD-7 in ROC curve analysis was 7. The patients with GAD were more likely to be female and single. CONCLUSION: The traditional Chinese version of the GAD-7 is a reliable and valid self-report questionnaire for detecting GAD in Taiwanese PWE.

The Development of a Literacy-Based Research Integrity Assessment Framework for Graduate Students in Taiwan.

Graduate education is a critical period in shaping and fostering graduate students' awareness about the importance of responsible conduct of research and knowledge and skills in doing good science. However, there is a lack of a standard curriculum and assessment framework for graduate students in Taiwan. The aim of this study was to develop a literacy-based research integrity (RI) assessment framework, including five core RI areas: (1) basic concepts in RI, (2) RI considerations in the research procedure, (3) research ethics and research subject protection, (4) publication and authorship, and (5) conflict of interest. The five areas were derived through a comprehensive review of major topics and areas covered in existing research integrity education and training programs and were rated by RI experts with adequate content validity. Test items on the five core areas were developed across three literacy levels: remembering and understanding, applying and analyzing, and evaluating and creating. Seven thousand and eighty-seven graduate-level trainees took an 18-unit RI course covering the five RI areas. Upon finishing the course, trainees completed a computer-based RI assessment randomly selected from 26 RI testing booklets. The design of test items followed the mastery-oriented assessment principles to promote trainees' learning of RI with adaptive assessment feedback. Results showed that the items in the RI assessment had adequate discrimination and low difficulty level. Thus, the RI assessment can be used to assess a range of trainees' RI literacy and can provide the most information in identifying trainees in need of more instruction or alternative training. The low guessing parameters also indicated the online RI assessment had an appropriate control of test exposure and cheating prevention. Higher education authorities can use this framework to assess graduate students' RI literacy based on a standard curriculum and prepare them for conversations about the responsible conduct of research for RI culture-building.

Distributed source modeling of intracranial stereoelectro-encephalographic measurements.

Intracranial stereoelectroencephalography (sEEG) provides unsurpassed sensitivity and specificity for human neurophysiology. However, functional mapping of brain functions has been limited because the implantations have sparse coverage and differ greatly across individuals. Here, we developed a distributed, anatomically realistic sEEG source-modeling approach for within- and between-subject analyses. In addition to intracranial event-related potentials (iERP), we estimated the sources of high broadband gamma activity (HBBG), a putative correlate of local neural firing. Our novel approach accounted for a significant portion of the variance of the sEEG measurements in leave-one-out cross-validation. After logarithmic transformations, the sensitivity and signal-to-noise ratio were linearly inversely related to the minimal distance between the brain location and electrode contacts (slope≈-3.6). The signa-to-noise ratio and sensitivity in the thalamus and brain stem were comparable to those locations at the vicinity of electrode contact implantation. The HGGB source estimates were remarkably consistent with analyses of intracranial-contact data. In conclusion, distributed sEEG source modeling provides a powerful neuroimaging tool, which facilitates anatomically-normalized functional mapping of human brain using both iERP and HBBG data.

Acute withdrawal of new-generation antiepileptic drugs in epilepsy monitoring units: Safety and efficacy.

INTRODUCTION: Acute withdrawal of antiepileptic drugs (AEDs) is a safe and effective approach to provoking seizures in order to complete video-electroencephalogram (V-EEG) studies in a timely manner. Previous studies have focused only on withdrawal from conventional AEDs, and the effects of withdrawal from new-generation AEDs have not been extensively studied. MATERIALS AND METHODS: This study examined adult patients with drug-resistant epilepsy admitted to an epilepsy monitoring unit between 2015 and 2018. Patients were classified according to whether they received conventional AEDs (Con; n = 13) or new-generation AEDs (N-Gen; n = 26). We then compared the effects of withdrawing these two types of AEDs over a period of one week in terms of efficacy (time to complete V-EEG monitoring) and safety, including the incidence of cluster seizures (CS), focal to bilateral tonic-clonic seizures (FBTCS) and status epilepticus (SE). RESULTS: In both groups, approximately one week was required to complete V-EEG analysis: N-Gen group (5.6 days) and Con group (6.3 days). No differences were observed between the two groups in terms of the median number of seizures, the onset of the 1st seizure, the distribution of CS, FBTCS, or SE. Following acute withdrawal of medication, a high percentage of patients with a history of CS or FBTCS, respectively, presented CS or FBTCS. CONCLUSIONS: We did not observe significant differences between patients taking new-generation AEDs and those taking conventional AEDs following withdrawal during V-EEG recording. In the current study, we employed a standard protocol for the rapid withdrawal of AEDs (daily dose reduction of 50%), which was sufficient for 80% of patients to complete V-EEG monitoring within one week.

Density-Functional Tight-Binding Parameters for Bulk Zirconium: A Case Study for Repulsive Potentials.

Density-functional tight-binding (DFTB) parameters are presented for the simulation of the bulk phases of zirconium. Electronic parameters were obtained using a band structure fitting strategy, while two-center repulsive potentials were created by particle swarm optimization. As objective functions for the repulsive potential fitting, we employed the Birch-Murnaghan equations of state for hexagonal close-packed (HCP), body-centered cubic (BCC) and ω phases of Zr from density-functional theory (DFT). When fractional atomic coordinates are not allowed to change in the generation of the equation-of-state curves, long-range repulsive DFTB potentials are able to almost perfectly reproduce equilibrium structures, relative DFT energies of the bulk phases, and bulk moduli. However, the same potentials lead to artifacts in the DFTB potential energy surfaces when atom positions in the unit cell are allowed to fully relax during the change of unit cell parameters. Conventional short-range repulsive DFTB potentials, while inferior in their ability to reproduce DFT bulk energetics, are able to correctly reproduce the qualitative shape of the DFT potential energy surfaces, including the location of global minima, and can therefore be considered more transferable.

A multigroup analysis of factors underlying teachers' technostress and their continuance intention toward online teaching.

Online teaching has been implemented in response to the COVID-19 pandemic. Nonetheless, teaching online consumes considerable time and adds pressure to teachers' daily lives. Teachers have to not only acquire technical skills but also provide engaging instruction online. Meanwhile, privacy breaches occasionally occur in online teaching. The objective of the current study is to analyze the factors underlying the continuance intention toward online teaching beyond the COVID-19 pandemic. We use the person-environment fit theory to develop the survey for investigation. An open-ended question appended to the survey helps to gather teachers' further thoughts on sustainable online teaching. The structural equation modeling reveals that teachers' technostress is associated with their privacy concerns and self-efficacy in delivering effective instruction amid online teaching. The multigroup analysis further demonstrates that technostress, self-efficacy and school support are related to the continuance intention to teach online for teachers at distinct teaching levels to different extents. The responses to the open-ended question reveal that teachers' preference for online instruction lies in wealthy teaching resources and flexibility. Students' learning performance and the effectiveness of assessments constitute a concern in conducting online teaching. The implications for policymakers and teachers are remarked upon at the end of this paper.

Social functioning and health-related quality of life trajectories in people with epilepsy after epilepsy surgery.

OBJECTIVE: An improvement in quality of life (QoL) over time after epilepsy surgery has been demonstrated in people with epilepsy; however, social functioning has been less investigated. We conducted this study to examine whether postsurgical improvement is parallel between QoL and social functioning in patients with epilepsy. METHODS: We retrospectively reviewed patients who underwent epilepsy surgery. All participants completed a comprehensive neuropsychological assessment, the Quality of Life in Epilepsy Inventory (QOLIE-89) questionnaire, and the Social and Occupational Functioning Scale for Epilepsy (SOFSE) before surgery and at 3 months, 6 months, and 1 year after surgery. Demographic and epilepsy-related information was also collected. Generalized estimating equations with identity links were used to model the QOLIE-89 and SOFSE over time and possible associated factors. A p < 0.05 was considered statistically significant. RESULTS: A total of 76 patients, including 36 males and 43 females aged 18 to 62 years were collected. Both total QOLIE-89 and overall SOFSE improved over time after epilepsy surgery (adjusted p value < 0.001 and 0.002, respectively, with Bonferroni's correction). Total QOLIE-89 improved 3 months after surgery, while overall SOFSE showed no significant improvement until 6 months after surgery. The presurgical Full-Scale Intelligence Quotient (FSIQ) of the Wechsler Adult Intelligence Scale-III and years of education were significantly associated with time-dependent improvement for both total QOLIE-89 and overall SOFSE (p value < 0.001). At one year after surgery, overall SOFSE and total QOLIE-89 scores were significantly higher in the seizure-free group than in the nonseizure-free group (p value = 0.040 and 0.032, respectively). CONCLUSION: Social functioning significantly improved in people with epilepsy after surgery as QoL, but it took more time to exhibit improvement. People with better FSIQ and more years of education had better improvement in social functioning over time. The early intervention of rehabilitation programs after epilepsy surgery might be necessary to facilitate the improvement in social functioning.

Polyketide Synthase Gene Expression in Relation to Chloromonilicin and Melanin Production in Monilinia fructicola.

Monilinia fructicola is a fungal pathogen of worldwide significance that causes brown rot of stone fruits. There are only few reports related to the production of biologically active polyketides by this pathogen. In this study, we examined an atypical M. fructicola strain TW5-4 that shows strong antimicrobial activity against various plant pathogens. TW5-4 also displays sparse growth in culture, low virulence, and higher levels of melanin compared with its albino mutant, TW5-4WM, and a wild-type strain Mf13-81. Antifungal compounds were extracted from TW5-4 and purified by thin-layer chromatography following visualization with an on-the-chromatogram inhibition assay. The principal antifungal compound was identified by linear ion trap mass spectrometry, high-resolution electro-spray ionization mass spectrometry, and proton nuclear magnetic resonance analyses as the polyketide chloromonilicin. Multiple M. fructicola polyketide synthase (PKS) sequences were then cloned by degenerate PCR and inverse PCR. Sequence analyses support presence of a 10-member PKS gene family in the M. fructicola genome. Analyses of PKS gene expression found no strong correlation between chloromonilicin production in culture and transcript levels of any of the PKS gene family members in mycelium of strains TW5-4, TW5-4WM, and Mf13-81. However, MfPKS12, a homolog of BcPKS12 involved in biosynthesis of 1,8-dihydroxynaphthalene (DHN)-melanin in Botrytis cinerea, was strongly expressed in mycelia of TW5-4 and Mf13-81. An MfPKS12-silenced mutant accumulated significantly less melanin in mycelia, had lower resistance to polyethylene glycol-induced osmotic stress, and displayed reduced virulence on nectarine fruit. The results suggest that DHN-melanin is required for tolerance to osmotic stress and full virulence in M. fructicola.