Background: Central nervous system (CNS) injury following brain-directed radiotherapy remains a major challenge. Proton radiotherapy (PRT) minimizes radiation to healthy brain, potentially limiting sequelae. We characterized CNS radiotoxicity, including radiation-induced leukoencephalopathy (RIL), brain tissue necrosis (TN), and cerebral microbleeds (CMB), in glioma patients treated with PRT or photons (XRT).
View Article and Find Full Text PDFThe composition and function of the gut microbiota are intimately tied to nutrient acquisition strategies and metabolism, with significant implications for host health. Both dietary and host-intrinsic factors influence community structure and the basic modes of bacterial energy metabolism. The intestinal tract is rich in carbon and nitrogen sources; however, limited access to oxygen restricts energy-generating reactions to fermentation.
View Article and Find Full Text PDFUnlabelled: Enteric pathogens such as serovar Typhimurium experience spatial and temporal changes to the metabolic landscape throughout infection. Host reactive oxygen and nitrogen species non-enzymatically convert monosaccharides to alpha hydroxy acids, including L-tartrate. utilizes L-tartrate early during infection to support fumarate respiration, while L-tartrate utilization ceases at later time points due to the increased availability of exogenous electron acceptors such as tetrathionate, nitrate, and oxygen.
View Article and Find Full Text PDFObjective: In the current era of the World Health Organization's Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders 2022-2031 (IGAP), precise and updated estimates of epilepsy burden are vital in formulating policies to improve the care of persons with epilepsy, especially in Asian countries with significant treatment gap. Hence, we aimed to consolidate the available data and quantify epilepsy prevalence and incidence estimates in Asian countries.
Methods: We systematically searched PubMed, Embase, Ovid, and Scopus databases from inception until March 2023 for studies reporting epilepsy prevalence and incidence in Asian countries.
Neurological conditions are the leading cause of death and disability combined. This public health crisis has become a global priority with the introduction of WHO's Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders 2022-2031 (IGAP). 18 months after this plan was adopted, global neurology stakeholders, including representatives of the OneNeurology Partnership (a consortium uniting global neurology organisations), take stock and advocate for urgent acceleration of IGAP implementation.
View Article and Find Full Text PDFEnteric pathogens such as serovar Typhimurium experience spatial and temporal changes to the metabolic landscape throughout infection. Host reactive oxygen and nitrogen species non-enzymatically convert monosaccharides to alpha hydroxy acids, including L-tartrate. utilizes L-tartrate early during infection to support fumarate respiration, while L-tartrate utilization ceases at later time points due to the increased availability of exogenous electron acceptors such as tetrathionate, nitrate, and oxygen.
View Article and Find Full Text PDFNeurological conditions are the leading cause of disability and mortality combined, demanding innovative, scalable, and sustainable solutions. Brain health has become a global priority with adoption of the World Health Organization's Intersectoral Global Action Plan in 2022. Simultaneously, rapid advancements in artificial intelligence (AI) are revolutionizing neurological research and practice.
View Article and Find Full Text PDFAcute gastrointestinal infection with intracellular pathogens like Salmonella Typhimurium triggers the release of the proinflammatory cytokine interleukin 1β (IL-1β). However, the role of IL-1β in intestinal defense against Salmonella remains unclear. Here, we show that IL-1β production is detrimental during Salmonella infection.
View Article and Find Full Text PDFLouis Pasteur's experiments on tartaric acid laid the foundation for our understanding of molecular chirality, but major questions remain. By comparing the optical activity of naturally-occurring tartaric acid with chemically-synthesized paratartaric acid, Pasteur realized that naturally-occurring tartaric acid contained only L-tartaric acid while paratartaric acid consisted of a racemic mixture of D- and L-tartaric acid. Curiously, D-tartaric acid has no known natural source, yet several gut bacteria specifically degrade D-tartaric acid.
View Article and Find Full Text PDFPurpose: The intracranial benefit of offering dual immune-checkpoint inhibition (D-ICPI) with ipilimumab and nivolumab to patients with melanoma or non-small cell lung cancer (NSCLC) receiving stereotactic radiosurgery (SRS) for brain metastases (BMs) is unknown. We hypothesized that D-ICPI improves local control compared with SRS alone.
Methods And Materials: Patients with melanoma or NSCLC treated with SRS from 2014 to 2022 were evaluated.
Background: Radiation-induced damage (RID) after radiotherapy (RT) of primary brain tumors and metastases can be challenging to clinico-radiographically distinguish from tumor progression. RID includes pseudoprogression and radiation necrosis; the latter being irreversible and often associated with severe symptoms. While histopathology constitutes the diagnostic gold standard, biopsy-controlled clinical studies investigating RID remain limited.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2023
The gut microbiota plays a role in many human diseases, but high-throughput sequence analysis does not provide a straightforward path for defining healthy microbial communities. Therefore, understanding mechanisms that drive compositional changes during disease (gut dysbiosis) continues to be a central goal in microbiome research. Insights from the microbial pathogenesis field show that an ecological cause for gut dysbiosis is an increased availability of host-derived respiratory electron acceptors, which are dominant drivers of microbial community composition.
View Article and Find Full Text PDFCurr Treat Options Oncol
November 2023
Central nervous system (CNS) radiotoxicity remains a challenge in neuro-oncology. Dose distribution advantages of protons over photons have prompted increased use of brain-directed proton therapy. While well-recognized among pediatric populations, the benefit of proton therapy among adults with CNS malignancies remains controversial.
View Article and Find Full Text PDFObjectives: The folate antagonist high-dose methotrexate (HD-MTX) is integral to induction chemotherapy for primary CNS lymphoma (PCNSL); however, it can be associated with leukoencephalopathy. Methylenetetrahydrofolate reductase (MTHFR) is involved in intracellular folate depletion. We assessed whether polymorphisms affect the risk of leukoencephalopathy.
View Article and Find Full Text PDFserovar Typhimurium induces intestinal inflammation to create a niche that fosters the outgrowth of the pathogen over the gut microbiota. Under inflammatory conditions, utilizes terminal electron acceptors generated as byproducts of intestinal inflammation to generate cellular energy through respiration. However, the electron donating reactions in these electron transport chains are poorly understood.
View Article and Find Full Text PDFNeuro Oncol
December 2023
Radiation necrosis, also known as treatment-induced necrosis, has emerged as an important adverse effect following stereotactic radiotherapy (SRS) for brain metastases. The improved survival of patients with brain metastases and increased use of combined systemic therapy and SRS have contributed to a growing incidence of necrosis. The cyclic GMP-AMP (cGAMP) synthase (cGAS) and stimulator of interferon genes (STING) pathway (cGAS-STING) represents a key biological mechanism linking radiation-induced DNA damage to pro-inflammatory effects and innate immunity.
View Article and Find Full Text PDFChicks are ideal to follow the development of the intestinal microbiota and to understand how a pathogen perturbs this developing population. Taxonomic/metagenomic analyses captured the development of the chick microbiota in unperturbed chicks and in chicks infected with Salmonella enterica serotype Typhimurium (STm) during development. Taxonomic analysis suggests that colonization by the chicken microbiota takes place in several waves.
View Article and Find Full Text PDFBackground: Intestinal inflammation disrupts the microbiota composition leading to an expansion of Enterobacteriaceae family members (dysbiosis). Associated with this shift in microbiota composition is a profound change in the metabolic landscape of the intestine. It is unclear how changes in metabolite availability during gut inflammation impact microbial and host physiology.
View Article and Find Full Text PDFHematol Oncol Clin North Am
February 2022
Cancer treatment related injury to the central nervous system (CNS) is well-recognized in the setting of brain-directed radiation therapies and conventional and novel systemic anticancer therapies. Late-delayed treatment-induced CNS complications frequently result in permanent neurologic disability. Therapeutic options are supportive with limited clinical benefit, whereby alteration or discontinuation of the overall antineoplastic treatment plan is frequently necessary to prevent further neurologic injury.
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