Lipo-pam™ adjuvanted herpes zoster vaccine induces potent gE-specific cellular and humoral immune responses.

Herpes zoster (HZ), also known as shingles, is caused by the reactivation of latent varicella-zoster virus (VZV). Decreased VZV-specific T-cell immune responses significantly contribute to the development of HZ. Shingrix is a recombinant zoster vaccine that is currently used to prevent HZ. However, Shingrix has high reactogenicity and pain at the injection site due to QS21, one of the adjuvant components. In this study, we developed a new herpes zoster vaccine formulation called CVI-VZV-001, containing gE protein and a novel liposome-based adjuvant Lipo-pam™, which consists of two TLR agonists. We evaluated the immunogenicity of CVI-VZV-001 in mouse and rabbit models. CVI-VZV-001 elicited robust gE-specific T-cell immune responses and gE-specific antibody production. Specifically, CVI-VZV-001 induced polyfunctional CD4+ T cell populations that secrete multiple cytokines. Furthermore, CVI-VZV-001 sustained the gE-specific immune responses for up to six months after immunization. To ensure CVI-VZV-001's safety for further development, we conducted a good laboratory practice (GLP) toxicity test, which confirmed that CVI-VZV-001 is safe for use. At present, CVI-VZV-001 is undergoing phase I clinical trials. This study suggests that CVI-VZV-001 can be a potent candidate for the HZ vaccine with high immunogenicity and safety.

Static and dynamic brain morphological changes in isolated REM sleep behavior disorder compared to normal aging.

Objective/background: To assess whether cerebral structural alterations in isolated rapid eye movement sleep behavior disorder (iRBD) are progressive and differ from those of normal aging and whether they are related to clinical symptoms. Patients/methods: In a longitudinal study of 18 patients with iRBD (age, 66.1 ± 5.7 years; 13 males; follow-up, 1.6 ± 0.6 years) and 24 age-matched healthy controls (age, 67.0 ± 4.9 years; 12 males; follow-up, 2.0 ± 0.9 years), all participants underwent multiple extensive clinical examinations, neuropsychological tests, and magnetic resonance imaging at baseline and follow-up. Surface-based cortical reconstruction and automated subcortical structural segmentation were performed on T1-weighted images. We used mixed-effects models to examine the differences between the groups and the differences in anatomical changes over time. Results: None of the patients with iRBD demonstrated phenoconversion during the follow-up. Patients with iRBD had thinner cortices in the frontal, occipital, and temporal regions, and more caudate atrophy, compared to that in controls. In similar regions, group-by-age interaction analysis revealed that patients with iRBD demonstrated significantly slower decreases in cortical thickness and caudate volume with aging than that observed in controls. Patients with iRBD had lower scores on the Korean version of the Mini-Mental Status Examination (p = 0.037) and frontal and executive functions (p = 0.049) at baseline than those in controls; however, no significant group-by-age interaction was identified. Conclusion: Patients with iRBD show brain atrophy in the regions that are overlapped with the areas that have been documented to be affected in early stages of Parkinson's disease. Such atrophy in iRBD may not be progressive but may be slower than that in normal aging. Cognitive impairment in iRBD is not progressive.

White matter microstructure and connectivity changes after surgery in male adults with obstructive sleep apnea: recovery or reorganization?

Study objectives: Obstructive sleep apnea (OSA) is a prevalent clinical problem significantly affecting cognitive functions. Surgical treatment is recommended for those unable to use continuous positive airway pressure. We aimed to investigate the therapeutic effect of upper airway surgery on the white matter (WM) microstructure and brain connectivity in patients with OSA. Methods: Twenty-one male patients with moderate-to-severe OSA were recruited for multi-level upper airway surgery. Overnight polysomnography (PSG), neuropsychiatric tests, and brain MRI scans were acquired before and 6.1 ± 0.8 months after surgery. Nineteen male patients with untreated OSA were also included as a reference group. We calculated the longitudinal changes of diffusion tensor imaging (DTI) parameters, including fractional anisotropy (ΔFA) and mean/axial/radial diffusivity (ΔMD/AD/RD). We also assessed changes in network properties based on graph theory. Results: Surgically treated patients showed improvement in PSG parameters and verbal memory after surgery. Globally, ΔFA was significantly higher and ΔRD was lower in the surgery group than in the untreated group. Especially ΔFA of the tracts involved in the limbic system was higher after surgery. In network analysis, higher Δbetweenness and lower Δclustering coefficients were observed in the surgical group than in the untreated group. Finally, the improvement of verbal memory after surgery positively correlated with ΔFA in superior thalamic radiation (p = 0.021), fronto aslant tracts (p = 0.027), and forceps minor tracts (p = 0.032). Conclusion: Surgical treatment of OSA can alleviate alterations in WM integrity and disruptions in local networks, particularly for the tracts involved in the limbic system. These findings may further explain the cognitive improvement observed after the treatment of OSA.

Identifying important factors for successful surgery in patients with lateral temporal lobe epilepsy.

OBJECTIVE: Lateral temporal lobe epilepsy (LTLE) has been diagnosed in only a small number of patients; therefore, its surgical outcome is not as well-known as that of mesial temporal lobe epilepsy. We aimed to evaluate the long-term (5 years) and short-term (2 years) surgical outcomes and identify possible prognostic factors in patients with LTLE. METHODS: This retrospective cohort study was conducted between January 1995 and December 2018 among patients who underwent resective surgery in a university-affiliated hospital. Patients were classified as LTLE if ictal onset zone was in lateral temporal area. Surgical outcomes were evaluated at 2 and 5 years. We subdivided based on outcomes and compared clinical and neuroimaging data including cortical thickness between two groups. RESULTS: Sixty-four patients were included in the study. The mean follow-up duration after the surgery was 8.4 years. Five years after surgery, 45 of the 63 (71.4%) patients achieved seizure freedom. Clinically and statistically significant prognostic factors for postsurgical outcomes were the duration of epilepsy before surgery and focal cortical dysplasia on postoperative histopathology at the 5-year follow-up. Optimal cut-off point for epilepsy duration was eight years after the seizure onset (odds ratio 4.375, p-value = 0.0214). Furthermore, we propose a model for predicting seizure outcomes 5 years after surgery using the receiver operating characteristic curve and nomogram (area under the curve = 0.733; 95% confidence interval, 0.588-0.879). Cortical thinning was observed in ipsilateral cingulate gyrus and contralateral parietal lobe in poor surgical group compared to good surgical group (p-value < 0.01, uncorrected). CONCLUSIONS: The identified predictors of unfavorable surgical outcomes may help in selecting optimal candidates and identifying the optimal timing for surgery among patients with LTLE. Additionally, cortical thinning was more extensive in the poor surgical group.

Enhancement of galactose uptake for bioethanol production from Eucheuma denticulatum hydrolysate using galactose-adapted yeasts.

Eucheuma denticulatum is a red macroalgae with a high carbohydrate content. The fermentable sugars from E. denticulatum were obtained through sequential thermal acid hydrolysis, enzymatic saccharification, and detoxification. Thermal acid hydrolysis of E. denticulatum was optimized under the condition of 10% (w/v) slurry content and 300 mM HNO3 at 121 â„ƒ for 90 min. The maximum monosaccharide concentration after thermal acid hydrolysis was 31.0 g/L with an efficiency (ETAH) of 44.7%. By further enzymatic hydrolysis of pretreated biomass solution under 20 U/mL Cellic CTec2 at 50 â„ƒ and 160 rpm for 72 h, the maximum monosaccharide concentration reached 79.9 g/L with an efficiency of 66.2% (ES). To remove 5-hydroxymethylfurfural (5-HMF), a fermentation inhibitor, absorption using 2% activated carbon was performed for 2 min. Ethanol fermentation was performed using wild-type and high galactose-adapted strains of Saccharomyces cerevisiae, Kluyveromyces marxianus, and Candida lusitaniae. As a result, galactose-adapted strains showed higher ethanol production than wild-type strains. Especially, the fermentation result by adaptively evolved S. cerevisiae produced the highest ethanol of 37.6 g/L and with YEtOH of 0.48 g/g. Moreover, the transcript level of MIG1 in the galactose-adapted strain was slightly lower than that in the wild-type strain. The application of adaptive evolution of microorganisms was efficient for bioethanol production.

Environmental factors affecting akinete germination and resting cell awakening of two cyanobacteria.

Globally, cyanobacteria frequently cause blooms that outcompete other species in the waterbody, affecting the diversity, decreasing water exchange rates, and promoting eutrophication that leads to excessive algal growth. Here, Dolichospermum circinale (akinetes) and Microcystic aeruginosa (resting cells), were isolated from the sediment in the Uiam Dam in the North Han River and near Ugok Bridge in the Nakdong River, respectively. The morphology, germination process and rates, and growth was evaluated in different environmental conditions. D. cercinalis germination began on day two of culturing, with maximum cell growth observed on day ten. In contrast, M. aeruginosa exhibited daily increase in cell density and colony size, with notable density increase on day six. Next, different environmental conditions were assessed. Akinetes exhibited high germination rates at low light intensity (5-30 µmol/m2/s), whereas resting cells exhibited high growth rates at high light intensity (50-100 µmol/m2/s). Furthermore, both cell types exhibited optimum germination and growth in media containing N and P at 20-30° at a pH of 7-9. Our study reveals the optimum conditions for the germination and growth of cyanobacterial akinetes and resting cells isolated from river sediment, respectively, and will assist in predicting cyanobacterial blooms for appropriate management.

Effects of Obstructive Sleep Apnea on Epilepsy, and Continuous Positive Airway Pressure as a Treatment Option.

Purpose: To compare the characteristics of obstructive sleep apnea (OSA) between patients with epilepsy and patients without epilepsy and to investigate CPAP (Continuous Positive Airway Pressure) effect on seizures. Methods: Medical and polysomnography (PSG) data from 235 adult OSA patients with epilepsy (OE; 183 males; mean age, 49.8 years) and 268 age- and sex-matched OSA patients without epilepsy (OSE; 216 males; mean age, 51.3 years), obtained between March 2014 and May 2020 and housed in a database in a university-affiliated hospital, were retrospectively reviewed. All subjects completed surveys addressing comorbidities and medications, and sleep-related questionnaires including the Insomnia Severity Index, Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, and Beck Depression Inventory-II. Results: Compared with the OSE group, the OE group reported fewer sleep-related complaints and less severe OSA-related PSG parameters, with a lower apnea-hypopnea index (24.9 vs. 33.4 events/h; p < 0.003), arousal index (23.3 vs. 30.8 events/h; p < 0.001), and oxygen desaturation index (19.6 vs. 28.8; p < 0.002). The OE group had fewer smokers and lower alcohol consumption but a higher body mass index (27.0 vs. 25.9 kg/m2; p < 0.001). No correlations were observed between OSA-related PSG parameters and epilepsy-related factors, such as age at seizure onset, seizure type, frequency of seizures, presence of nocturnal seizures, and number of antiseizure medications, in the OE group. Patients with OE who demonstrated good compliance with CPAP therapy exhibited a decrease in seizure frequency. Conclusions: The OE group exhibited less severe disease characteristics than their age- and sex-matched OSE counterparts. Nevertheless, because the coexistence of OSA and epilepsy is high, CPAP therapy can reduce the frequency of seizures. Therefore, it is important to evaluate the presence of OSA in patients with epilepsy and to treat the conditions concurrently.

Lateralizing Characteristics of Morphometric Changes to Hippocampus and Amygdala in Unilateral Temporal Lobe Epilepsy with Hippocampal Sclerosis.

Background andObjective: In the present study, a detailed investigation of substructural volume change in the hippocampus (HC) and amygdala (AMG) was performed and the association with clinical features in patients with mesial temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) determined. Methods: The present study included 22 patients with left-sided TLE-HS (LTLE-HS) and 26 patients with right-sided TLE-HS (RTLE-HS). In addition, 28 healthy controls underwent high-resolution T2-weighted image (T2WI) and T1-weighted image (T1WI) MRI scanning. Subfield analysis of HC and AMG was performed using FreeSurfer version 6.0. Results: Patients with TLE-HS showed a decrease in the volume of substructures in both HC and AMG, and this change was observed on the contralateral side and the ipsilateral side with HS. The volume reduction pattern of substructures showed laterality-dependent characteristics. Patients with LTLE-HS had smaller volumes of the ipsilateral subiculum (SUB), contralateral SUB, and ipsilateral cortical nucleus of AMG than patients with RTLE-HS. Patients with RTLE-HS had reduced ipsilateral cornu ammonis (CA) 2/3 and contralateral cortico-amygdaloid transition area (CAT) volumes. The relationship between clinical variables and subregions was different based on the lateralization of the seizure focus. Focal to bilateral tonic-clonic seizures (FTBTCS) was associated with contralateral and ipsilateral side subregions only in LTLE-HS. The abdominal FAS was associated with the volume reduction of AMG subregions only in LTLE-HS, but the volume reduction was less than in patients without FAS. Conclusions: The results indicate that unilateral TLE-HS is a bilateral disease that shows different laterality-dependent characteristics based on the subfield analysis of HC and AMG. Subfield volumes of HC and AMG were associated with clinical variables, and the more damaged substructures depended on laterality in TLE-HS. These findings support the evidence that LTLE-HS and RTLE-HS are disparate epilepsy entities rather than simply identical syndromes harboring a mesial temporal lesion. In addition, the presence of FAS supports good localization value, and abdominal FAS has a high localization value, especially in patients with LTLE-HS.

Associations of actigraphy derived rest activity patterns and circadian phase with clinical symptoms and polysomnographic parameters in chronic insomnia disorders.

We explored the associations of actigraphy-derived rest-activity patterns and circadian phase parameters with clinical symptoms and level 1 polysomnography (PSG) results in patients with chronic insomnia to evaluate the clinical implications of actigraphy-derived parameters for PSG interpretation. Seventy-five participants underwent actigraphy assessments and level 1 PSG. Exploratory correlation analyses between parameters derived from actigraphy, PSG, and clinical assessments were performed. First, participants were classified into two groups based on rest-activity pattern variables; group differences were investigated following covariate adjustment. Participants with poorer rest-activity patterns on actigraphy (low inter-day stability and high intra-daily variability) exhibited higher insomnia severity index scores than participants with better rest-activity patterns. No between-group differences in PSG parameters were observed. Second, participants were classified into two groups based on circadian phase variables. Late-phase participants (least active 5-h and most active 10-h onset times) exhibited higher insomnia severity scores, longer sleep and rapid eye movement latency, and lower apnea-hypopnea index than early-phase participants. These associations remained significant even after adjusting for potential covariates. Some actigraphy-derived rest-activity patterns and circadian phase parameters were significantly associated with clinical symptoms and PSG results, suggesting their possible adjunctive role in deriving plans for PSG lights-off time and assessing the possible insomnia pathophysiology.

Sleep Disturbances and Phenoconversion in Patients with REM Sleep Behavior Disorder.

OBJECTIVE: We aimed to investigate relationships between sleep disturbances and phenoconversion to neurodegenerative diseases in patients with REM sleep behavior disorder (RBD). METHOD: Using a comprehensive sleep database in a university-affiliated hospital between December 2014 and March 2021, we reviewed the data of 226 patients with RBD (182 patients with idiopathic RBD (iRBD) and 44 patients with symptomatic RBD (sRBD) with a neurodegenerative disease). RESULTS: Among 226 patients with RBD (male, 61.5%), the mean age at RBD onset and mean disease duration were 59.4 ± 10.5 and 5.9 ± 5.6 years, respectively. Further, 111 (49.1%) patients had periodic limb movements during sleep (PLMS, PLM index ≥ 15/h), while 110 patients (48.7%) had comorbid obstructive sleep apnea (OSA, respiratory disturbance index ≥ 15/h). There was a positive correlation between age at RBD onset and the apnea-hypopnea index and Pittsburgh Sleep Quality Index. Compared to patients with iRBD, patients with sRBD showed a lower N3 sleep (3.3 ± 5.0 vs. 1.6 ± 3.1%, p = 0.004) and higher periodic limb movement index (36.3 ± 31.8 vs. 56.9 ± 47.5/h, p = 0.021) at the baseline. Among the 186 patients with iRBD, 18 (8.0%) developed neurodegenerative diseases (converters, mean follow-up duration: 2.5 ± 1.6 years) and 164 did not (non-converters, mean follow-up 2.4 ± 2.2 years). There was no significant between-group difference in the demographics and baseline clinical features. Continuous positive airway pressure (CPAP) therapy was prescribed in 101 patients with OSA; among them, 71 (70%) patients agreed to use it. CPAP improved dream enactment behaviors. CONCLUSION: In our study, 8.0% of patients with iRBD showed phenoconversion within a mean follow-up duration of 2.5 years. Polysomnographic parameters could not predict phenoconversion to neurodegenerative disease. However, approximately half of the patients with RBD presented with significant sleep disorders, including OSA or PLMS. CPAP therapy may alleviate RBD symptoms in patients with RBD-OSA.

Survey on Antiepileptic Drug Therapy in Patients with Drug Resistant Epilepsy.

BACKGROUND AND PURPOSE: Individualized anti-epileptic drug (AED) selection in patient with epilepsy is crucial. However, there is no unified opinion in treating patients with drug resistant epilepsy (DRE). This survey aimed to make a consolidate consensus with epileptologists' perspectives of the treatment for Korean DRE patients by survey responses. METHODS: The survey was conducted with Korean epilepsy experts who have experience prescribing AEDs via e-mail. Survey questionnaires consisted of six items regarding prescription patterns and practical questions in treating patients with DRE in Korea. The research period was from February 2021 to March 2021. RESULTS: The survey response rate was 83.3% (90/108). Most (77.8%) of the responders are neurologists. The proportion of patients whose seizures were not controlled by the second AED was 26.9%. The proportion of patients who had taken five or more AEDs is 13.9%, and those who are currently taking five or more AEDs are 7.3%, of which 54.5% and 37.9% reported positive effects on additional AED, respectively. The majority (91.1%) of respondents answered that the mechanism of action was the top priority factor when adding AED. Regarding data priority, responders considered that expert opinion should have the top priority, followed by clinical experiences, reimbursement guidelines and clinical evidence. Responders gave 64.9 points (range from 0 to 100) about overall satisfaction on reimbursement system of Health Insurance Review and Assessment Service for AED. CONCLUSIONS: This study on AED therapy for DRE patients is the first nationwide trial in Korean epilepsy experts. In five drug failure, the top priorities on AED selection are mechanism of action and expert opinion. These findings might help to achieve consensus and recognize the insight on optimal therapy of AED in DRE.

Comparing Ictal Cardiac Autonomic Changes in Patients with Frontal Lobe Epilepsy and Temporal Lobe Epilepsy by Ultra-Short-Term Heart Rate Variability Analysis.

Background and Objectives: Abnormal epileptic discharges in the brain can affect the central brain regions that regulate autonomic activity and produce cardiac symptoms, either at onset or during propagation of a seizure. These autonomic alterations are related to cardiorespiratory disturbances, such as sudden unexpected death in epilepsy. This study aims to investigate the differences in cardiac autonomic function between patients with temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE) using ultra-short-term heart rate variability (HRV) analysis around seizures. Materials and Methods: We analyzed electrocardiogram (ECG) data recorded during 309 seizures in 58 patients with epilepsy. Twelve patients with FLE and 46 patients with TLE were included in this study. We extracted the HRV parameters from the ECG signal before, during and after the ictal interval with ultra-short-term HRV analysis. We statistically compared the HRV parameters using an independent t-test in each interval to compare the differences between groups, and repeated measures analysis of variance was used to test the group differences in longitudinal changes in the HRV parameters. We performed the Tukey-Kramer multiple comparisons procedure as the post hoc test. Results: Among the HRV parameters, the mean interval between heartbeats (RRi), normalized low-frequency band power (LF) and LF/HF ratio were statistically different between the interval and epilepsy types in the t-test. Repeated measures ANOVA showed that the mean RRi and RMSSD were significantly different by epilepsy type, and the normalized LF and LF/HF ratio significantly interacted with the epilepsy type and interval. Conclusions: During the pre-ictal interval, TLE patients showed an elevation in sympathetic activity, while the FLE patients showed an apparent increase and decrease in sympathetic activity when entering and ending the ictal period, respectively. The TLE patients showed a maintained elevation of sympathetic and vagal activity in the pos-ictal interval. These differences in autonomic cardiac characteristics between FLE and TLE might be relevant to the ictal symptoms which eventually result in SUDEP.

Regional Ictal Hyperperfusion in the Contralateral Occipital Area May Be a Poor Prognostic Marker of Anterior Temporal Lobectomy: A SISCOM Analysis of MTLE Cases.

BACKGROUND AND OBJECTIVE: Subtraction of ictal SPECT coregistered to MRI (SISCOM) provides complementary information for detecting the ictal onset zone, especially in patients with MRI-negative focal epilepsy, and provides additional useful information for predicting long-term postresection outcomes. This study sought to investigate the relationship between surgical failure and increased cerebral blood flow (CBF) pattern using SPECT in patients with mesial temporal lobe epilepsy with unilateral hippocampal sclerosis (MTLE-HS). METHODS: Among 42 subjects who underwent anterior temporal lobectomy with amygdalohippocampectomy (ATL-AH) for MTLE-HS, 29 (69.0%) were seizure-free (SF group). Hyperperfusion was compared in 14 ipsilateral and contralateral brain regions in SISCOM images between the two groups. RESULTS: The pattern of ictal hyperperfusion in temporal regions did not vary significantly between the SF and non-seizure-free (NSF) groups. However, CBF increases in the contralateral occipital area was more frequent in the NSF group than in the SF group. Furthermore, ictal hyperperfusion of the ipsilateral occipital and contralateral parietal areas tended to be more frequent in the NSF group. CONCLUSION: The results indicate that poor ATL-AH surgical outcome is associated with a tendency of ictal hyperperfusion of the contralateral occipital cortex based on SISCOM analysis. The pattern of early ictal CBF changes implicating the propagation from temporal to occipital cortices can be considered a marker of poor surgical outcomes of ATL-AH in MTLE-HS patients.

Effects of Organic Light-Emitting Diodes on Circadian Rhythm and Sleep.

OBJECTIVE: Organic light-emitting diodes (OLEDs) emit less blue light than traditional light-emitting diodes (LEDs), and we previously found that early-night OLED light exposure (LE) delays the melatonin phase by less than LED at a color temperature of 4,000 K. As a follow-up study, we investigated the effects of OLED and LED at a different color temperature (3,000 K) on melatonin profile, sleep, and vigilance. METHODS: 24 healthy subjects (27.5±5.1 years) were exposed to three light conditions [OLED, LED, and dim light (DL)] from 17:30 to 24:00, in a random order and with a 1-week interval. Saliva samples for melatonin were taken every hour from 18:00 to 24:00. Polysomnography (PSG) and a psychomotor vigilance test (PVT) were performed. RESULTS: Melatonin onset time was significantly delayed under OLED and LED compared with DL, with no significant difference between OLED and LED. The mean melatonin level at 24:00 under LED was lower than that under DL, but there was no significant difference between OLED LE and DL. The percentage of slow wave sleep (N3) in LED was significantly lower than in OLED. CONCLUSION: Exposure to light in the evening can suppress melatonin secretion late at night and disturb deep sleep, and those effects are slightly worse under LED than OLED.

Effects of Evening Exposure to Light from Organic Light-Emitting Diodes on Melatonin and Sleep.

BACKGROUND AND PURPOSE: Organic light-emitting diodes (OLEDs) emit less blue light than traditional light-emitting diodes (LEDs), but the effects of OLED light exposure (LE) on melatonin and sleep have not been evaluated. METHODS: Twenty-four healthy subjects (age 26.9±5.7 years; including 18 females) with the intermediate chronotype were exposed to three different light conditions [4,000 K 150 lux OLED LE, 4,000 K 150 lux LED LE, and dim light (DL) at <10 lux] for 6.5 h from 17:30 to 24:00, in a random order and with a 1-week interval. Participants entered the unit for the experiment at 16:00, and their daylight was measured by actigraphy from 8:00 to 16:00 during each session. Saliva samples for melatonin were taken every hour from 18:00 to 24:00. Sleep was monitored by polysomnography, and vigilance was evaluated by psychomotor vigilance test upon awakening. RESULTS: Melatonin onset occurred at 21:11±01:24, 21:20±01:19, and 21:36±01:16 in the DL, OLED, and LED conditions, respectively. Melatonin onset was significantly delayed under LED LE compared to DL (p=0.007) but did not differ under OLED LE (p=0.245). Melatonin suppression, sleep parameters, and vigilance were similar among the three light conditions. The accumulated amount of daytime light in each session was negatively correlated with the melatonin onset time under the DL (rho=-0.634, p=0.002) and OLED (rho=-0.447, p=0.029) conditions, not under the LED condition (p=0.129). CONCLUSIONS: Melatonin onset under OLED LE was not significantly delayed compared to DL. Exposure to sufficient daylight may advance melatonin onset even when a subject is exposed to OLED LE in the evening.

Identifying a subtype of Alzheimer's disease characterised by predominant right focal cortical atrophy.

We aimed to identify an Alzheimer's disease (AD) subtype with right predominant focal atrophy. We recruited 17 amyloid PET positive logopenic variant primary progressive aphasia (lvPPA) and 226 amyloid PET positive AD patients. To identify AD with right focal atrophy (Rt-AD), we selected cortical areas that showed more atrophy in lvPPA than in AD and calculated an asymmetry index (AI) for this area in each individual. Using a receiver operating characteristic curve, we found that the optimal AI cut-off to discriminate lvPPA from AD was -3.1 (mean AI - 1.00 standard deviation) (sensitivity 88.2, specificity 89.8). We identified 32 Rt-AD patients whose AI was above mean AI + 1.00 standard deviation, 38 Lt-AD patients whose AI was lower than mean AI - 1.00 standard deviation, and 173 Symmetric-AD patients whose AI was within mean AI ± 1.00 standard deviation. We characterized clinical and cognitive profiles of Rt-AD patients by comparing with those of Lt-AD and Symmetric-AD patients. Compared to Symmetric-AD patients, Rt-AD patients had asymmetric focal atrophy in the right temporoparietal area and showed poor performance on visuospatial function testing (p = 0.009). Our findings suggested that there is an AD variant characterized by right focal atrophy and visuospatial dysfunction.

Dopa Responsive Parkinsonism in an Early Onset Alzheimer's Disease Patient with a Presenilin 1 Mutation (A434T).

Alzheimer's disease patients with presenilin 1 (PSEN1) mutations commonly show parkinsonism in addition to dementia. Yet, whether these patients show dopaminergic deficit and response to L-dopa is largely unknown. We report a 43-year-old woman with a PSEN1 mutation (A434T) who showed right side dominant parkinsonism. As disease progressed, she developed bilateral parkinsonism which was markedly relieved by L-dopa. Amyloid (Florbetaben) positron-emission tomography (PET) showed cortical florbetaben uptake, relatively sparing the striatum. Initial dopamine transporter (FP-CIT) PET showed asymmetrically decreased FP-CIT uptake in the left striatum. We suggest that in Alzheimer's disease patients with PSEN1 mutation, parkinsonism may be relieved by L-dopa when it is associated with presynaptic dopaminergic deficit.

Outcomes of Minimally Invasive Oblique Lumbar Interbody Fusion in Patients with Lumbar Degenerative Disease with Rheumatoid Arthritis.

PURPOSE OF STUDY: Standard treatment protocols for lumbar degenerative lesions in the setting of rheumatoid arthritis (RA) are lacking. The purpose of this study was to evaluate the clinical and radiologic outcomes of minimally invasive oblique lumbar interbody fusion (MI-OLIF) in RA patients having degenerative lumbar spine lesions. METHODS: This was a retrospective hospital-based case series (evidence level 4). Eight patients with degenerative lumbar disease with significant back pain and neurologic claudication underwent MI-OLIFwith polyetheretherketone cage insertion and posterior pedicle screw instrumentation. The clinical outcomes were measured by the numerical rating scale (NRS) for back and leg pain and the Oswestry Disability Index (ODI), and radiologic outcomes were studied on radiographs, computed tomography, and magnetic resonance imaging. Minimum follow-up duration was 1 year. RESULTS: Mean NRS results for back and leg pain preoperatively were 6.3 and 7.1 that improved to 2.6 and 2 for back and leg pain, respectively, at last follow-up. The mean ODI scores preoperatively were 58.02 that improved to 39.06 at last follow-up. All patients had good functional outcomes, good fusion rates, and were able to continue their activities of daily living without much disability at last follow-up. CONCLUSION: MI-OLIF in patients with symptomatic lumbar spine degenerative lesions with RA seems to provide good short-term clinical and radiologic outcomes.