Publications by authors named "Munasinghe J"
Head and neck paragangliomas (HNPGLs) are typically slow-growing, hormonally inactive tumors of parasympathetic paraganglia. Inactivation of prolyl-hydroxylase domain-containing 2 protein causing indirect gain-of-function of hypoxia-inducible factor-2α (HIF-2α), encoded by EPAS1, was recently shown to cause carotid body hyperplasia. We previously described a syndrome with multiple sympathetic paragangliomas caused by direct gain-of-function variants in EPAS1 (Pacak-Zhuang syndrome, PZS) and developed a corresponding mouse model.
View Article and Find Full Text PDFIntroduction: In USA, six million individuals with Sub-Saharan ancestry carry two high-risk variants, which increase the risk for kidney diseases. Whether APOL1 high-risk variants are independent risk factors for cardiovascular diseases is unclear and requires further investigation.
Methods: We characterized a mouse model to investigate the role of APOL1 in dyslipidemia and cardiovascular diseases.
In 2022-2023, a global outbreak of Mpox was reported especially in nonendemic countries. We report the first laboratory-confirmed neonatal case of Mpox infection complicated by bronchopneumonia in Sri Lanka.
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- * Researchers created a mouse model using CRISPR/Cas9 to study the disease, which mimics characteristics seen in human patients, such as specific gait abnormalities and a reduction in motor skills over time.
- * The Glb1 mice also display progressive brain atrophy and increased levels of a pentasaccharide biomarker, supporting their relevance for developing new treatments for GM1 gangliosidosis, particularly the less severe type II variant.
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- Disrupted sleep and excessive daytime sleepiness are common symptoms in brain tumor patients, especially after they undergo radiotherapy, with unclear biological causes.
- Researchers developed a mouse model to study how cranial radiation causes sleep disturbances that mimic human conditions, revealing varying levels of DNA damage across different brain areas.
- Preliminary findings suggest that certain brain regions related to cognitive functions and sleep regulation are particularly sensitive to radiation, which could inform better treatment strategies for patients.
Article Synopsis
- Researchers have discovered a previously unknown transtentorial venous system (TTVS) that connects venous drainage in the human brain, challenging earlier beliefs that this part was mainly avascular.
- The study used mice as a model to investigate the TTVS and found that it is present in adult mice and can be traced back to an embryonic stage where it aids in draining the choroid plexus.
- The findings suggest that the TTVS is conserved between humans and mice, making mice a suitable model for further research into the development and implications of this venous system in brain physiology.
Article Synopsis
- The inner ear, located within the petrous bone of the skull, plays a critical role in transmitting sound and balance signals to the brain through cranial nerves, developing from neural crest during early growth stages.
- While the anatomy of the inner ear in mice has been well-studied only up to day 6 after birth, both mice and humans continue to develop their inner ear and skull base into early adulthood.
- Traditional methods for studying the inner ear structure have limitations, particularly as the bone hardens after birth, but modern imaging techniques like high-resolution Micro-CT and MRI now enable detailed 3D visualization of this complex anatomy, resulting in the creation of a new atlas for the murine inner ear.
Age plays a critical role in disease development and tolerance to cancer treatment, often leading to an increased risk of developing negative symptoms including sleep disturbances. Circadian rhythms and sleep become disrupted as organisms age. In this study, we explored the behavioral alterations in sleep, circadian rhythms, and masking using a novel video system and interrogate the long-term impact of age-based changes in the non-image forming visual pathway on brain anatomy.
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- * Researchers conducted tests using a mouse model with the EPAS1A529V mutation to examine vascular malformations through various imaging techniques and histological analyses.
- * Results indicated that patients and mutant mice exhibited a range of vascular malformations, with the patient vessels showing a higher presence of mutations compared to normal tissue, establishing vascular malformation as a new clinical characteristic of EPAS1 gain-of-function syndrome.
Purpose: Abrupt halt of service provision due to pandemic state of COVID-19, significantly affected care of patients with chronic diseases like epilepsy; its impact being greater on caregivers of vulnerable groups such as children with epilepsy. We performed this study to describe difficulties posed by the lockdown to caregivers of children with epilepsy in a low-middle income country and describe their responses and self-management strategies to overcome difficulties and prepare for a recurrence.
Method: A cross-sectional all-island survey was carried out at paediatric neurology centers in Sri Lanka.
Article Synopsis
- Preclinical models are crucial for studying the immune response to gliomas, and this study focused on comparing fluorescently transfected GL261 murine glioma cells with non-fluorescent versions.
- The research involved implanting mice with different GL261 cell types and assessing their survival rates and immune responses through cytokine profiling.
- Results showed that mice with non-fluorescent GL261 cells had shorter median survival compared to those with fluorescent GL261-Luc2 cells, which also exhibited increased inflammatory cytokines, indicating a stronger anti-tumor immune response.
Article Synopsis
- Tumor heterogeneity impacts how well cancer treatments work, making it essential to predict therapy responses early for better cancer management.
- A new hybrid nanovesicle using activatable inflammation magnetic resonance imaging (aiMRI) has been developed to assess how well tumors respond to radiotherapy.
- The research showed strong correlations between imaging results and immune responses as well as tumor growth inhibition, suggesting aiMRI could be a valuable tool for predicting treatment outcomes in cancer radiotherapy and improving precision medicine strategies.
Article Synopsis
- The study aimed to explore how a specific mutation in the HIF-2α protein affects brain and spine development in patients with gain-of-function syndrome, which is linked to conditions like paragangliomas and polycythemia.
- Eight patients were evaluated, revealing that all had malformations in the posterior fossa, mostly Chiari malformations, while many also experienced spinal dysraphism and vertebral segmentation issues.
- Findings from transgenic mouse models mirrored human symptoms, showcasing similar spinal malformations and suggesting that the mutation leads to incomplete mesenchymal transition, potentially affecting normal development.
Article Synopsis
- Early detection of aggressive brain tumors, particularly IDH-mutant gliomas, is challenging due to limitations in traditional imaging techniques, making it difficult to understand their progression mechanisms.
- Researchers used various model systems of IDH1 mutant gliomas to study their metabolomic, transcriptomic, and epigenomic profiles, aiming to link metabolism with tumor behavior.
- The study found that more aggressive glioma models show loss of DNA methylation in glycolytic enzyme promoters, increased glycolytic activity, and this high glycolytic phenotype is linked with poorer patient outcomes, suggesting lactate levels could be an early biomarker for tumor aggressiveness.
Article Synopsis
- Metabolic variations within and among tumors significantly influence cancer treatment outcomes, but non-invasive methods to assess these differences are limited.
- The study focuses on pancreatic ductal adenocarcinoma, showing that tumors with the same genetic makeup can be differentiated by their rates of 13C labeled glucose metabolism using advanced imaging techniques.
- This imaging approach reveals unique metabolic profiles and regions of lactate production in tumors, highlighting tumor heterogeneity that conventional methods like FDG-PET may fail to detect.
Article Synopsis
- MRI diagnosis can be improved by using contrast agents to enhance signal contrast, but traditional methods still face challenges with sensitivity.
- Researchers developed a new T- T dual-modal MRI contrast agent using an albumin-binding molecule and manganese ion, significantly improving imaging at high magnetic fields.
- This dual-modal approach enhances signal-to-noise and contrast-to-noise ratios in imaging, reducing false positives and artifacts, and may revolutionize MRI diagnostics in precision medicine.
Article Synopsis
- * C magnetic resonance spectroscopy (MRS) offers potential advantages for detecting metabolism changes but struggles with low sensitivity, mainly used in single voxel measurements, unless enhanced by complex methods like dDNP.
- * A new method using MRI chemical shift imaging (CSI) with advanced post-processing via tensor decomposition significantly boosts signal-to-noise ratio, allowing effective imaging of glucose metabolism and the Warburg effect without needing hyperpolarization, achieving great spatial and temporal resolution.
Article Synopsis
- Epilepsy, deafness, and other disorders linked to TBC1D24 mutations are not fully understood, prompting researchers to create a mouse model with a specific mutant gene variant associated with early infantile epileptic encephalopathy (EIEE).
- The engineered mice exhibit normal hearing but develop spontaneous seizures around postnatal day 15, mimicking the human condition, which corresponds with a change in how the TBC1D24 protein is made during development.
- The study highlights the important role of TBC1D24 in neuronal function and opens the door for testing new medications to treat seizure disorders linked to TBC1D24 mutations.
Article Synopsis
- Cerebral malaria (CM) is the deadliest complication of infection in African children, with a high fatality rate of 15 to 25%, and currently has no additional treatments beyond antimalarial drugs.
- Previous studies showed that the glutamine antagonist DON could save mice from experimental CM even after severe brain damage occurred.
- Recent research using MR imaging demonstrated that a new DON prodrug, JHU-083, can reverse critical brain injury markers in infected mice, suggesting it might be an effective adjunctive therapy for treating CM in children and adults.
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- Cancer is a major global health issue, and new therapies are needed to improve treatment options; ferroptosis therapy (FT) is proposed as a promising approach.
- Researchers developed Fenton-reaction-acceleratable magnetic nanoparticles (FeGd-HN@Pt@LF/RGD2) that can effectively deliver essential reactants directly to brain tumors, enabling enhanced FT by crossing the blood-brain barrier and targeting cancer cells.
- The nanoparticles release key components that promote the Fenton reaction, generating reactive oxygen species that kill cancer cells, while also allowing for real-time monitoring of tumor response through intrinsic MRI capabilities.
Background: Dengue fever is a mosquito-borne viral disease with a very high incidence in Southeast Asia. Most patients with dengue fever recover following a self-limiting febrile illness, while a small proportion may progress to develop severe disease with complications such as acute liver failure, acute kidney injury, and multiorgan failure. Secondary bacterial infections and thrombotic events are very rare.
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- Hypoxic zones in tumors make them resistant to radiation therapy, but drugs that improve oxygen levels, like SQAP, can enhance treatment effectiveness.
- The study used various imaging techniques to show how SQAP affects oxygen levels and blood flow in tumors before radiation.
- Results indicated that SQAP improves tumor oxygenation and blood perfusion, leading to better responses to radiation therapy and potentially delaying tumor growth.
Importance: Poorly controlled hypertension is a leading global public health problem requiring new treatment strategies.
Objective: To assess whether a low-dose triple combination antihypertensive medication would achieve better blood pressure (BP) control vs usual care.
Design, Setting, And Participants: Randomized, open-label trial of a low-dose triple BP therapy vs usual care for adults with hypertension (systolic BP >140 mm Hg and/or diastolic BP >90 mm Hg; or in patients with diabetes or chronic kidney disease: >130 mm Hg and/or >80 mm Hg) requiring initiation (untreated patients) or escalation (patients receiving monotherapy) of antihypertensive therapy.
Article Synopsis
- The study investigated how local oxygen levels relate to energy metabolism in tumors using advanced imaging techniques like electron paramagnetic resonance imaging (EPRI) and magnetic resonance imaging (MRI) with hyperpolarized [1-C] pyruvate.
- It compared two types of tumors (SCCVII and HT29) in mice, finding that the SCCVII tumor had a larger hypoxic area and a higher rate of converting pyruvate to lactate, especially after radiation treatment.
- The combination of EPRI and C-MRI effectively highlighted metabolic changes in tumors, particularly in hypoxic regions following radiation therapy, indicating potential for better understanding tumor behavior and treatment responses.