A phase 3 multicenter, prospective, open-label efficacy and safety study of immune globulin (human) 10% caprylate/chromatography purified in patients with myasthenia gravis exacerbations

Background: Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular transmission. Exacerbations may involve increasing bulbar weakness and/or sudden respiratory failure, both of which can be critically disabling. Management of MG exacerbations includes plasma exchange and intravenous immunoglobulin (IVIG); they are equally effective, but patients experience fewer side effects with IVIG. The objective of this study was to assess the efficacy and safety of immune globulin caprylate/chromatography purified (IGIV-C) in subjects with MG exacerbations. Methods: This prospective, open-label, non-controlled 28-day clinical trial was conducted in adults with MG Foundation of America class IVb or V status. Subjects received IGIV-C 2 g/kg over 2 consecutive days (1 g/kg/day) and were assessed for efficacy/safety on Days 7, 14, 21, and 28. The primary efficacy endpoint was the change from Baseline in quantitative MG (QMG) score to Day 14. Secondary endpoints of clinical response, Baseline to Day 14, included at least a 3-point decrease in QMG and MG Composite and a 2-point decrease in MG-activities of daily living (MG-ADL). Results: Forty-nine subjects enrolled. The change in QMG score at Day 14 was significant (p < 0.001) in the Evaluable (-6.4, n = 43) and Safety (-6.7, n = 49) populations. Among evaluable subjects, Day 14 response rates were 77, 86, and 88% for QMG, MG Composite, and MG-ADL, respectively. IGIV-C showed good tolerability with no serious adverse events. Conclusions: The results of this study show that IGIV-C was effective, safe, and well tolerated in the treatment of MG exacerbations

Gender and Age Dynamics in Future Educators\u27 Attitudes toward AI Integration in Education: A Sample from State-managed Universities in Zamboanga Peninsula, Philippines

Gender and age are critical factors in understanding attitudes toward artificial intelligence (AI) in education, yet limited research has directly explored their influence on teacher aspirants’ perspectives on AI integration. This study employed random sampling to select 603 respondents from two state-managed institutions. Findings indicate that prospective teachers generally hold neutral attitudes toward AI (M=2.84), reflecting uncertainty about preferring AI over human interaction in routine tasks, consistent with prior research. Male respondents (M=2.91) exhibited significantly more positive attitudes toward AI in education than females, as evidenced by a t value of -2.66 and a p value of 0.008. Additionally, adults (M=2.86) demonstrated significantly higher attitude scores than adolescents (M=2.80), with a t value of -2.05 and a p value of 0.040. These results highlight the role of demographic variables in shaping perceptions of AI in educational contexts, emphasizing the need for targeted interventions to address concerns and optimize AI adoption in teacher training programs

Quasi-BIC Modes in All-Dielectric Slotted Nanoantennas for Enhanced Er3+ Emission

In the quest for new and increasingly efficient photon sources, the engineering of the photonic environment at the subwavelength scale is fundamental for controlling the properties of quantum emitters. A high refractive index particle can be exploited to enhance the optical properties of nearby emitters without decreasing their quantum efficiency, but the relatively modest Q-factors (Q ∼ 5–10) limit the local density of optical states (LDOS) amplification achievable. On the other hand, ultrahigh Q-factors (up to Q ∼ 109) have been reported for quasi-BIC modes in all-dielectric nanostructures. In the present work, we demonstrate that the combination of quasi-BIC modes with high spectral confinement and nanogaps with spacial confinement in silicon slotted nanoantennas lead to a significant boosting of the electromagnetic LDOS in the optically active region of the nanoantenna array. We observe an enhancement of up to 3 orders of magnitude in the photoluminescence intensity and 2 orders of magnitude in the decay rate of the Er3+ emission at room temperature and telecom wavelengths. Moreover, the nanoantenna directivity is increased, proving that strong beaming effects can be obtained when the emitted radiation couples to the high Q-factor modes. Finally, via tuning the nanoanntenna aspect ratio, a selective control of the Er3+ electric and magnetic radiative transitions can be obtained, keeping the quantum efficiency almost unitary

Acute cerebral MCA ischemia with secondary severe head injury and acute intracerebral and subdural haematoma: Case report

Generally, according to international literature, cerebral ischemia is a secondary posttraumatic lesion produced by direct compression in the context of a cerebral herniation syndrome or indirect by vasospasm produced by posttraumatic subarachnoid, subdural or intraventricular hemorrhages. We present the case of a patient with an acute MCA ischemia with severe head injury due to a fall with subsequent intracranial acute intracerebral and subdural hematoma which evolved with acute left uncal, parahipocampal and subfalcinecerebral herniation (coma, GCS 6, left mydriasis, right severe hemiparesis). Surgical emergency aspiration of the hematomas was performed. Postoperative treatment of cerebral ischemia and residual hematomas was properly done. We consider important and underdiagnosed the association of cerebral ischemia and secondary posttraumatic brain injuries. Abbreviations: MCA-middle cerebral artery, GCS- Glasgow Coma Scale, ICA-internal carotid artery, PCA-posterior cerebral artery, ACA-anterior cerebral artery. Conclusion: We present a case of a patient with an acute MCA ischemia with secondary head injury due to a fall with subsequent intracranial acute intracerebral and subdural hematomas. Surgical emergency aspiration of the hematomas was performed. The treatment was performed for both lesions (cerebral ischemia and posttraumatic hematomas) with vitamins B, neurotrophycs, pain killers, antibiotics. Unfortunately, due to aggravation of the Mendelson syndrome, the patient died 7 days later

Primary tuberculomas of the thoracal spinal cord: Case report

The authors present an unusual case of intramedullary tuberculoma in a HIV-negative patient from the southeast part of Romania who demonstrated no other signs of tuberculous infection. Clinical exam: extreme spastic paraparesis in triple flexion, dorsal pain and bladder and bowel incontinence. Gd enhanced MRI revealed ring enhancing lesion with central hypointensity, suggesting granulomatous pathology. Surgical excision of the intramedullary lesions was carried out followed by anti-tuberculous chemotherapy and Baclofen tablets . !0 days postoperative MRI showed total resolution of the lesion. Two years follow up showed progressive resolution of spasticity. Following surgical excision, the patient improved significantly sensitive and modest the motility and spasticity. The management of this rare lesion is discussed and the literature reviewed

Misfolded α-Synuclein in Autosomal Dominant Alzheimer's Disease.

We analyzed Lewy body (LB) pathology in 18 autosomal dominant Alzheimer's disease (ADAD) brains via immunohistochemistry. Real-time quaking induced conversion was used to detect misfolded α-synuclein (α-syn) in 18 living ADAD cerebrospinal fluid (CSF) samples. Concomitant LB pathology was present in 44% ADAD brains. Only 6% CSF samples were positive for misfolded α-syn. In an additional AD sample, all patients with confirmed LB presented misfolded α-syn in postmortem CSF regardless of the LB staging. In conclusion, misfolded α-syn in CSF was scarce in symptomatic living ADAD individuals, in contrast to postmortem brain tissue. These results suggest late appearance of LB pathology in ADAD

Cortical thickness modeling and variability in Alzheimer's disease and frontotemporal dementia

Alzheimer's disease (AD) and frontotemporal dementia (FTD) show different patterns of cortical thickness (CTh) loss compared with healthy controls (HC), even though there is relevant heterogeneity between individuals suffering from each of these diseases. Thus, we developed CTh models to study individual variability in AD, FTD, and HC.We used the baseline CTh measures of 379 participants obtained from the structural MRI processed with FreeSurfer. A total of 169 AD patients (63 ± 9 years, 65 men), 88 FTD patients (64 ± 9 years, 43 men), and 122 HC (62 ± 10 years, 47 men) were studied. We fitted region-wise temporal models of CTh using Support Vector Regression. Then, we studied associations of individual deviations from the model with cerebrospinal fluid levels of neurofilament light chain (NfL) and 14-3-3 protein and Mini-Mental State Examination (MMSE). Furthermore, we used real longitudinal data from 144 participants to test model predictivity.We defined CTh spatiotemporal models for each group with a reliable fit. Individual deviation correlated with MMSE for AD and with NfL for FTD. AD patients with higher deviations from the trend presented higher MMSE values. In FTD, lower NfL levels were associated with higher deviations from the CTh prediction. For AD and HC, we could predict longitudinal visits with the presented model trained with baseline data. For FTD, the longitudinal visits had more variability.We highlight the value of CTh models for studying AD and FTD longitudinal changes and variability and their relationships with cognitive features and biomarkers.© 2023. The Author(s)

Classifying Alzheimer's disease and frontotemporal dementia using machine learning with cross-sectional and longitudinal magnetic resonance imaging data

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are common causes of dementia with partly overlapping, symptoms and brain signatures. There is a need to establish an accurate diagnosis and to obtain markers for disease tracking. We combined unsupervised and supervised machine learning to discriminate between AD and FTD using brain magnetic resonance imaging (MRI). We included baseline 3T-T1 MRI data from 339 subjects: 99 healthy controls (CTR), 153 AD and 87 FTD patients; and 2-year follow-up data from 114 subjects. We obtained subcortical gray matter volumes and cortical thickness measures using FreeSurfer. We used dimensionality reduction to obtain a single feature that was later used in a support vector machine for classification. Discrimination patterns were obtained with the contribution of each region to the single feature. Our algorithm differentiated CTR versus AD and CTR versus FTD at the cross-sectional level with 83.3% and 82.1% of accuracy. These increased up to 90.0% and 88.0% with longitudinal data. When we studied the classification between AD versus FTD we obtained an accuracy of 63.3% at the cross-sectional level and 75.0% for longitudinal data. The AD versus FTD versus CTR classification has reached an accuracy of 60.7%, and 71.3% for cross-sectional and longitudinal data respectively. Disease discrimination brain maps are in concordance with previous results obtained with classical approaches. By using a single feature, we were capable to classify CTR, AD, and FTD with good accuracy, considering the inherent overlap between diseases. Importantly, the algorithm can be used with cross-sectional and longitudinal data.© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC

Multifocal Transcranial Direct Current Stimulation in Primary Progressive Aphasia Does Not Provide a Clinical Benefit Over Speech Therapy

Primary progressive aphasia (PPA) is a group of neurodegenerative disorders including Alzheimer's disease and frontotemporal dementia characterized by language deterioration. Transcranial direct current stimulation (tDCS) is a non-invasive intervention for brain dysfunction.To evaluate the tolerability and efficacy of tDCS combined with speech therapy in the three variants of PPA. We evaluate changes in fMRI activity in a subset of patients.Double-blinded, randomized, cross-over, and sham-controlled tDCS study. 15 patients with PPA were included. Each patient underwent two interventions: a) speech therapy + active tDCS and b) speech therapy + sham tDCS stimulation. A multifocal strategy with anodes placed in the left frontal and parietal regions was used to stimulate the entire language network. Efficacy was evaluated by comparing the results of two independent sets of neuropsychological assessments administered at baseline, immediately after the intervention, and at 1 month and 3 months after the intervention. In a subsample, fMRI scanning was performed before and after each intervention.The interventions were well tolerated. Participants in both arms showed clinical improvement, but no differences were found between active and sham tDCS interventions in any of the evaluations. There were trends toward better outcomes in the active tDCS group for semantic association and reading skills. fMRI identified an activity increase in the right frontal medial cortex and the bilateral paracingulate gyrus after the active tDCS intervention.We did not find differences between active and sham tDCS stimulation in clinical scores of language function in PPA patients

Synaptic, axonal damage and inflammatory cerebrospinal fluid biomarkers in neurodegenerative dementias

INTRODUCTION: Synaptic damage, axonal neurodegeneration, and neuroinflammation are common features in Alzheimer's disease (AD), frontotemporal dementia (FTD), and Creutzfeldt-Jakob disease (CJD). METHODS: Unicentric cohort of 353 participants included healthy control (HC) subjects, AD continuum stages, genetic AD and FTD, and FTD and CJD. We measured cerebrospinal fluid neurofilament light (NF-L), neurogranin (Ng), 14-3-3, and YKL-40 proteins. RESULTS: Biomarkers showed differences in HC subjects versus AD, FTD, and CJD. Disease groups differed between them except AD versus FTD for YKL-40. Only NF-L differed between all stages within the AD continuum. AD and FTD symptomatic mutation carriers presented differences with respect to HC subjects. Applying the AT(N) system, 96% subjects were positive for neurodegeneration if 14-3-3 was used, 94% if NF-L was used, 62% if Ng was used, and 53% if YKL-40 was used. DISCUSSION: Biomarkers of synapse and neurodegeneration differentiate HC subjects from neurodegenerative dementias and between AD, FTD, and CJD. NF-L and 14-3-3 performed similar to total tau when AT(N) system was applied