Impaired glycaemic control is a major risk factor for developing type 2 diabetes (T2D), a worldwide health epidemic intrinsically linked to diet and obesity. Whey proteins (WP) are increasingly popular supplements that are a rich source of branched-chain amino acids (BCAA), essential for muscle protein synthesis and metabolic regulation. In humans, fasting plasma concentrations of BCAA are maintained around 350 µM but become chronically elevated by 10–25% in persons with T2D. Little is known about whether BCAA from WP impacts circulating BCAA concentrations and contributes to this phenomenon. This narrative review used a systematic search approach with relevant keywords to identify evidence from randomised controlled trials in normoglycaemic humans and those with insulin resistance or T2D, on the effects of WP intake on plasma BCAA and glycaemic control. This review is, to the authors’ knowledge, the first to specifically examine the effects of WP intake on plasma BCAA concentrations in relation to glycaemic control. Whilst the majority of acute studies identified (n = 6) reported that WP consumption between 10 and 50 g significantly elevates postprandial BCAA and insulin responses (as evidenced by peak concentration and/or area under the curve), evidence from chronic studies (n = 3) report inconsistent findings on the impact of 9–51 g of WP/d on fasting BCAA and glycaemic control (for example, fasting glucose and insulin, insulin clearance). Findings from this literature review highlight the need for further studies that investigate the relationship between WP consumption with BCAA and glycaemic control, and to determine underlying mechanisms of action.

Background: Fluorescence-guided surgery (FGS) with 5-aminolevulinic acid (5-ALA) is a well-established tool for improving tumor visualization in glioma surgery. However, its applications in non-glioma pathologies remain underexplored and require further investigation. Methods: A retrospective review of patients who underwent FGS with 5-ALA between January 2022 and September 2024 was conducted to assess its utility in non-glioma tumors. Results: Among 232 FGS procedures, 13 (5.6%) involved non-glioma pathologies. We categorized our patients into three different levels: high, moderate, and no response based on intra-operative 5-ALA fluorescence visualization. Our patients showed a high 5-ALA fluorescence in 10 cases (77%), mainly in the following tumors: choroid plexus papilloma, atypical teratoid rhabdoid tumor, metastatic adenocarcinoma as well as atypical meningiomas. Moderate 5-ALA fluorescence was seen in 2 cases (15%). While no 5-ALA fluorescence was seen in one case of CNS lymphoma. 90% of procedures with high response had total resection. Conclusions: Fluorescence-guided surgery (FGS) using 5-ALA has demonstrated effectiveness in enhancing tumor visualization beyond gliomas. This retrospective review highlights the potential applications of 5-ALA in various non-glioma pathologies. These findings emphasize the need for further research to refine the use of 5-ALA FGS in diverse pathologies, optimize patient selection, and expand its utility in neurosurgical oncology.

Background: While developing a differentiation therapy for Sonic Hedgehog Medulloblastoma (MB), we discovered a potential paradoxical feedback cycle between Ezh2, a protein that temporarily keeps differentiation genes silenced via trimethylating H3K27, and Cyclin D1, a protein that regulates cell cycle entry. Methods: We quantified H3K27me3 in P7 purified cerebral GNPs using chromatin immunoprecipitation sequencing and correlated it with gene expression via RNA sequencing (RNAseq). To assess transcriptional effects of Ezh2 loss, we purified P7 GNPs from Math1-Cre, Ezh2-flox knockout mice. MB cells were cultured in suspension spheres and imaged using the ImageXpress Micro XLS system, with nuclei segmented based on DAPI staining. Results: Cyclin D1 ranked among the top 7.37% of expressed genes but was heavily marked by the repressive histone mark H3K27me3 (top 5.5%) in GNPs. Ezh2 overexpression increased G0-arrested MB cells 2.7-fold, while, in GNPs, RNAseq showed significant Cyclin D1 upregulation in Ezh2 knockout mice (Log2FC: 1.301). Cyclin D1 regulates the pRb/E2F1 complex, and we observe that Ezh2 expression depends on pRb/E2F1 complex abundance, forming a feedback loop. Notably, combining the Hedgehog inhibitor Vismodegib with an Ezh2 inhibitor rescued MB cells from Vismodegib-induced death. Conclusions: Our study introduces a model that promotes GNP differentiation, leading tumor cells to differentiate into neurons.

International human rights law (IHRL) provides extensive protections for the living, but little in the way of direct protections for the dead. International humanitarian law (IHL) has more detailed protections for the dead, but is only triggered during armed conflicts. At first glance, this seems to create a protection gap for the dead during peacetime. This article explores how the Convention on the Rights of Persons with Disabilities (CRPD) creates a connection between IHL, IHRL and transitional justice to fill in this perceived gap in protections for the dead. While the CRPD does not explicitly address the dead, IHL contains several specific rules to guide how dead bodies are to be handled. When read together with the CRPD framework, these rules provide ample guidance on the treatment of individuals with disabilities after death. Some IHL protections of the dead extend temporally beyond the conflict, when transitional justice mechanisms should be in play, although neither the CRPD nor IHL address with any specificity how the five pillars of transitional justice – truth, justice, reparation, memorialization and guarantees of non-recurrence – might apply in relation to IHL rules regarding dead bodies. Nonetheless, Article 11 of the CRPD forges a bidirectional link to IHL protections and obligations supporting transitional justice. Accordingly, there is a legal framework for examining the interrelationships between rules in the CRPD, IHL and human rights law writ large, and for how we think about dead bodies under the various regimes of international law. Each ought to inform the others if the implications of CRPD Article 11 are to be fully realized and the siloing and fragmentation of international law avoided.

Background: Diffusion tensor imaging (DTI) tractography enables detailed visualization of white matter tracts (WMT) relevant to surgical planning. Head-to-head performance of clinically available DTI software has not been assessed. We retrospectively compared Synaptive’s Modus Plan™(vers. 2.0.1.1743) and Medtronic’s StealthViz™(vers. 1.4) software, focusing on workflow, usability, stability, and capacity to generate WMT reconstructions. Methods: Retrospective evaluation of patients (n=13) with intrinsic brain lesions (01/2021-12/2023) with MP and SV software. Corticospinal and optic radiation WMT reconstruction was attempted according to the manufacturers specifications and was rated as clinically useful or not, based on anatomic plausibility. Duration of each analysis step (image importing, post-processing, segmentation, fine-tuning and tract export) was recorded. Ease of use, degree of clinician input, program stability, and tract output type were also assessed. Results: 13 patients (31±;19 yrs; 6F) were included. Mean workflow duration was significantly longer for MP (22:51 min) versus SV (7:35 min) (p<0.0001). Successful WMT reconstruction occurred in 9/13 (69.2%) with MP, versus 5/13 (38.5%) for SV. MP was rated to have superior usability, stability and required less clinician input but technical parameters (e.g. FA) or export object type was inflexible. Conclusions: Synaptive’s MP permitted more robust WMT reconstruction with enhanced usability and stability but with significantly longer workflow.

Background: Surgical access to the clival region is challenging, but advanced endoscopic endonasal approaches (EEA) provide a minimally invasive corridor. This study aimed to review the clinical outcomes of patients who underwent EEA for skull base lesions involving the clivus and to analyze prognostic factors. Methods: A retrospective review was conducted of patients who underwent EEA for resection of clival lesions between October 2001 and October 2023. Data on demographics, approach type, reconstruction technique, tumor pathology and outcomes were collected. Results: Forty-six patients underwent transclival EEA. The majority had ASA scores II and III (71.7%), with clival chordomas being the most common pathology (37%). Cranial nerve impairment was present in 65% of patients, and 80% showed improvement post-surgery. The mean procedure duration was 308 minutes, with a mean blood loss of 424 mL. A lumbar drain was used in 10.9%, and 76.1% received a pedicled nasoseptal flap for reconstruction. Complete tumor resection was achieved in 74% of malignant cases. Postoperative CSF leaks occurred in 4.3%, and the mean length of stay was 12.2 days. Higher readmission rates were associated with ASA IV classification (p=0.006). Conclusions: EEA to the clival region is safe and effective, with low perioperative complications and high rates of postoperative improvement.

The Indian Pulsar Timing Array (InPTA) employs unique features of the upgraded Giant Metrewave Radio Telescope (uGMRT) to monitor dozens of the International Pulsar Timing Array (IPTA) millisecond pulsars (MSPs), simultaneously in the 300–500 MHz and the 1260–1460 MHz bands. This dual-band approach ensures that any frequency-dependent delays are accurately characterised, significantly improving the timing precision for pulsar observations, which is crucial for pulsar timing arrays. We present details of InPTA’s second data release that involves 7 yr of data on 27 IPTA MSPs. This includes sub-banded times of arrival (ToAs), dispersion measures (DM), and initial timing ephemerides for our MSPs. A part of this dataset, originally released in InPTA’s first data release, is being incorporated into IPTA’s third data release, which is expected to detect and characterise nanohertz gravitational waves (GWs) in the coming years. The entire dataset is reprocessed in this second data release providing some of the highest precision DM estimates so far and interesting solar wind-related DM variations in some pulsars. This is likely to characterise the noise introduced by the dynamic inter-stellar ionised medium much better than the previous release thereby increasing sensitivity to any future GW search.

Background: We previously developed a DNA methylation-based risk predictor for meningioma, which has been used locally in a prospective fashion. As a follow-up, we validate this model using a large prospective cohort and introduce a streamlined next-generation model compatible with newer methylation arrays. Methods: The performance of our next-generation predictor was compared with our original model and standard-of-care 2021 WHO grade using time-dependent receiver operating characteristic curves. A nomogram was generated by incorporating our methylation predictor with WHO grade and extent of resection. Results: A total of 1347 meningioma cases were utilized in the study, including 469 prospective cases from 3 institutions and a retrospective cohort of 100 WHO grade 2 cases for model validation. Both the original and next-generation models significantly outperformed 2021 WHO grade in predicting postoperative recurrence. Dichotomizing into grade-specific risk subgroups was predictive of outcome within both WHO grades 1 and 2 tumours (log-rank p<0.05). Multivariable Cox regression demonstrated benefit of adjuvant radiotherapy in high-risk cases specifically, reinforcing its informative role in clinical decision making. Conclusions: This next-generation DNA methylation-based meningioma outcome predictor significantly outperforms 2021 WHO grading in predicting time to recurrence. This will help improve prognostication and inform patient selection for RT.

Background: Neurofibromatosis 1 (NF1) is a multisystem neurocutaneous disorder. Treatment involves multiple specialists. There are currently no multidisciplinary clinics for adults with NF1 in BC, which impacts communication between subspecialties. We sought perspectives of patients and providers to identify the impact of and solutions to gaps in care. Methods: Focus groups with patients (2 groups; 9 patients) and physicians (10) who see people with NF1 were conducted. Thematic content analysis was applied to the data to derive major themes. Concurrently, quarterly NF multidisciplinary rounds were initiated to enhance coordination of care. Results: Major themes emerged around the need for increased coordination and communication amongst providers. Specifically, physicians identified working in “siloed care structures”, and patients and providers identified lack of awareness of expertise and barriers to accessing care. Conclusions: Focus groups enable inclusion of patient and provider perspectives in developing solutions to gaps in care. The importance of supporting interdisciplinary communication in caring for NF1 patients was confirmed in focus groups. To date, we have held multidisciplinary NF rounds, with 12 cases discussed. Disciplines represented include neurology, pediatrics, radiology, neuro-ophthalmology, neuro-otology, pathology, orthopedic plastic and neurosurgery, medical and radiation oncology, and the hereditary cancer program. Telehealth format enables participation from distributed centres across BC.

The current study characterized voice onset time (VOT) and vowel onset fundamental frequency (F0) in the production of three Vietnamese alveolar stops (i.e. /t̪ʰ/, /t/, and /d/) by monolingual Vietnamese children and adults. Eighty Vietnamese children aged 3–7 years and 16 adults aged 22–44 years participated in this study. Unlike speakers of other languages with a three-way voicing contrast, Vietnamese children were able to produce distinct categories for the three Vietnamese stop categories by 3 years of age. However, differences in vowel onset F0 among the three voicing categories were not significant in any age group. These findings enhance our understanding of how Vietnamese children acquire three-way voicing contrast in stop production and offer broader insights into stop consonant acquisition across languages.

Background: Generalized myasthenia gravis (gMG) is a rare, chronic, autoimmune disease characterized by muscle weakness and fatigue. This study aims to describe the natural history, disease burden and treatment patterns of gMG patients in Canada. Methods: Data was analyzed from the Adelphi MG II DSP™, a gMG patient-level cross-sectional database, collected through surveys between February-June 2024. Neurologists provided sociodemographic, symptomatology, and treatments data. Results: Fifteen neurologists provided data for 46 gMG patients. The cohort’s mean (SD) age was 58.1 (14.7) years, 52.2% male, 82.6% White/Caucasian and 89.1% were anti-AChR Ab positive. Mean time since diagnosis was 3.4 (3.1) years, 22% reported a change in employment status due to gMG. Most had public insurance (68.9%). Disease severity was mostly MGFA class II (78.2%) patients. Common symptoms included eyelid ptosis (76.1%), dysarthria (50.0%), and dyspnea (54.3%) – mean MG-ADL was 5.6 (5.1). During their disease course, 34.9% experienced ≥1 myasthenic crisis, while 25.6% reported symptom exacerbation. At time of survey, patients had used 1.8 (0.9) lines of maintenance treatment. Most prescribed treatments (alone or in combinations) were pyridostigmine (95.6%), corticosteroids (48.9%), non-steroidal immunosuppressants (42.2%), Immunoglobulins (31.1%), and biologics (22.2%). Conclusions: gMG patients continue to experience symptoms burden and crisis/exacerbations. These findings highlight an unmet need for new, safe and effective therapeutics that are publicly covered to manage gMG-related clinical manifestations.

In March 1645, a large number of Potiguara people from various regions of north-eastern Brazil gathered in the aldeamento (Indigenous settlements under colonial control or supervision) of Tapesserica on Itamaracá. The primary objectives of the assembly included the establishment of Indigenous câmaras (municipal councils) and deliberations on the law of native freedom. Notably, in this period, some Indigenous people in Brazil were still held as slaves in territories under Dutch jurisdiction. The Tapesserica Assembly produced a remonstrance (‘remonstrantie’), which was delivered to the Dutch government in Recife by the Potiguara. This article scrutinises the Potiguara Assembly, the earliest recorded Indigenous assembly in Brazil, and reconstructs its connections to Indigenous political culture predating the European arrival in Brazil. It explores the Indigenous perspective on the Dutch–Portuguese wars and demonstrates the role of the Potiguara as historical agents, navigating the complexities of conflict and decision-making processes that ultimately shaped their destiny.

Background: Presence of right-to-left shunt has been proposed as a mechanism of paradoxical embolism in patients with active cancer. Our study thus aims to investigate the role of shunting in stroke occurrence among cancer patients. Methods: This is a retrospective study with our population consisting of patients presenting to the Ottawa Hospital with ischemic stroke between January 01, 2020, and December 31, 2022. Presence of right-to-left shunting is identified in patients with and without cancer diagnosis within one year of ischemic stroke. The prevalence of shunt is assessed using 95% confidence intervals (CI). Results: Among654 patients, 495 (37% female, median age 53 years) were included in the study, in which 47 (9.5%) had active cancer, with 12 patients (25.5%, 95% CI 14 - 40) diagnosed with a shunt. In contrast, among 448 patients (90.5%) without active cancer, 133 patients (30%, 95% CI 25 - 34) were found to have a shunt. Conclusions: The prevalence of right-to-left shunting tends to be lower in patients with ischemic stroke and active cancer diagnosis. Our results are similar to a recent study indicating a higher rate of shunt among patients without cancer. Our finding does not support the hypothesis that cancer-associated stroke is related to right-to-left shunting.

Background: Absence epilepsy is a common epilepsy syndrome in children. This can have a negative impact on the cognitive abilities of preschool and school-age children. The objective was to study in the Guinean context, the epidemiological, clinical, electrophysiological, therapeutic and evolutionary aspects of this syndrome. Methods: The study included all children diagnosed with absence epilepsy based on evidence obtained from history, clinical, and electroencephalogram. Results: The cohort was made up of 41 girls and 28 boys with a sex ratio (F/M) equal to 1.46. The mean age was 8 ± 2 years with extremes of 2 and 14 years. The simple absences were observed in 42.02% of cases. The components : tonic was associated in 11.59%, clonic in 10.14%, atonic in 13.04%, automatisms in 15.94% and vegetative in 7.25%. EEG was typical in 75.36%. As monotherapy, sodium valproate was used in 92.75% and ethosuximide in 2.9%. The evolution was marked by a remission of seizures in 85.51%. During follow-up, the appearance of tonic-clonic convulsions was noted in 4.3%, myoclonus in 2.9%, a combination of myoclonus and tonic-clonic convulsions noted in 4.3%. Conclusions: Effective and efficient collaboration between stakeholders is essential for the best overall management of this syndrome with serious cognitive repercussions in children.

Background: Body image research in young people with physical disabilities like cerebral palsy (CP) has received very little attention. The goal of this pilot study is to ask youth with CP (of all levels of disability) directly about body image to learn their perspective. Methods: Our study includes quantitative data of quality-of-life measures, along with qualitative interview data summarized via thematic analysis. Our data is augmented with input from siblings (without CP) of our primary participants to represent a control group in the same family unit. Results: Twelve youths with CP (7 male, 5 female) participated in the study. Withe the higher score representing more positive the body image, scores averaged 17.93/25 (SD 4.73) for those with CP, 18.62/25 (SD 5.45) for those without CP. There were higher scores for males and those ≤13yo compared to 14-18yo. Interview thematic analysis uncovers themes of functional capability, the wish to reduce burden on family, pride in the CP identity, and mixed desirability of media representation. Conclusions: There is greater difference between age groups and genders than there is between those with CP and not. Interviews with participants revealed the important recurring theme of functional capacity connected to positive self-image, which may be considered justification for interventions.