Background: Consensus is lacking on best practices regarding treatment of elevated intracranial pressure. One method is placement of an external ventricular drain to divert cerebrospinal fluid via continuous or intermittent drainage.
Objective: To explore the time required for fluid to finish draining at various pressure gradients under high- and low-compliance conditions.
Lung cancer is the leading cause of all cancer-related deaths in the United States and remains a global health challenge. While targeted therapy has revolutionized the treatment landscape of nonsmall cell lung cancer, many patients lack actionable mutations. Immunotherapy, particularly immune checkpoint inhibitors (ICIs), have significantly impacted outcomes in lung cancer in the last decade.
View Article and Find Full Text PDFIntrauterine inflammation is a significant cause of early preterm birth and fetal injury. There is a lack of effective interventions for intrauterine inflammation. This study aimed to determine whether direct fetal treatment with IL-1 receptor antagonists (IL-1RA), specifically anakinra (competitive IL-1RA) or rytvela (allosteric IL-1RA), could reduce intrauterine inflammation caused by intraamniotic injection of E.
View Article and Find Full Text PDFObjectives: Demonstrate a methodology for improving discoverability of rare disease datasets by enriching source data with biological associations.
Materials And Methods: We developed an extension of the Biolink semantic model to incorporate patient data and generated a knowledge graph (KG) comprising patient data and associations between biological entities in an existing KG, leveraging existing mappings and mapping standards.
Results: The enriched model of patient data can support a search application that is aware of biological associations and provides a semantic search interface to discover and summarize patient datasets within the broader biological context.
Anecdotal reports and preliminary clinical trials suggest that the psychoactive alkaloid ibogaine and its active metabolite noribogaine have powerful anti-addictive properties, producing long-lasting therapeutic effects across a range of substance use disorders and co-occurring neuropsychiatric diseases such as depression and post-traumatic stress disorder. Here we report a gram-scale, seven-step synthesis of ibogaine from pyridine. Key features of this strategy enabled the synthesis of three additional iboga alkaloids, as well as an enantioselective total synthesis of (+)-ibogaine and the construction of four analogues.
View Article and Find Full Text PDFProtein language models (PLMs) have recently demonstrated potential to supplant classical protein database search methods based on sequence alignment, but are slower than common alignment-based tools and appear to be prone to a high rate of false labeling. Here, we present NEAR, a method based on neural representation learning that is designed to improve both speed and accuracy of search for likely homologs in a large protein sequence database. NEAR's ResNet embedding model is trained using contrastive learning guided by trusted sequence alignments.
View Article and Find Full Text PDFBACKGROUND: Changes in pupil reactivity secondary to cerebral mass effect are traditionally linked to compression of the oculomotor nerve by the uncus or by horizontal midbrain displacement. The neurological pupil index (NPi) is a metric to assess the pupillary light reflex. This study explores the relationship of midline shift, cisternal, and sulcal effacement or ventricular compression in patients with a new finding of abnormal pupillary light reflex.
View Article and Find Full Text PDFBACKGROUND: Status epilepticus is an emergency, and applying electroencephalography (EEG) monitoring is an important part of diagnosing and treating seizure. The use of rapidly applied limited array continuous EEG (rapid EEG) has become technologically feasible in recent years. Nurse-led protocols using rapid EEG as a point-of-care monitor are increasingly being adopted.
View Article and Find Full Text PDFVector-borne pathogens, which are transmitted by blood-feeding arthropods to animals and people, are common in tropical regions where, combined with economic factors, can cause significant public health burden. A community-level study was undertaken in southwestern Guatemala to assess the presence of vector-borne pathogens in blood samples from humans (n = 98), their animals (n = 90), and ectoparasites (n = 83) over a period of 2 weeks. Human capillary blood was collected from participant's index finger, and animal venous blood (chickens, pigs, dogs, and cats) was collected from the jugular or cephalic veins at the enrollment period of a concurrent study.
View Article and Find Full Text PDFBlood pressure (BP) is a dynamic measure that is frequently discussed in static terms. There exist many limitations in current documentation systems whereby documented BP values may not be reflective of the dynamic variability of BP. This study used an observational, prospective, non-randomized study design to examine the variability in BP response during intravenous vasoactive medication administration in an intensive care unit setting.
View Article and Find Full Text PDFAgouti-related peptide (AgRP) is a well-established potent orexigenic peptide primarily expressed in hypothalamic neurons. Nevertheless, the expression and functional significance of extrahypothalamic AgRP remain poorly understood. In this study, utilizing histological and molecular biology techniques, we have identified a significant expression of Agrp mRNA and AgRP peptide production in glomus type I cells within the mouse carotid body (CB).
View Article and Find Full Text PDFObjective: Several groups of neurons in the NTS suppress food intake, including Prlh-expressing neurons (NTS cells). Not only does the artificial activation of NTS cells decrease feeding, but also the expression of Prlh (which encodes the neuropeptide PrRP) and neurotransmission by NTS neurons contributes to the restraint of food intake and body weight, especially in animals fed a high fat diet (HFD). We set out to determine roles for putative PrRP receptors in the response to NTS PrRP and exogenous PrRP-related peptides.
View Article and Find Full Text PDFNumerous preclinical studies have demonstrated that psychedelics promote the growth of cortical neurons in the prefrontal cortex. However, measuring psychedelic-induced structural plasticity in humans has remained a challenge. New advances in positron emission tomography imaging could facilitate the measurement of synaptic proteins in humans following psychedelic administration.
View Article and Find Full Text PDFBackground: There are limited objective methods when it comes to identifying and diagnosing concussion. Pupil assessment is performed routinely as a standard-of-care following traumatic brain injury (TBI). Unlike the highly subjective and limited reliability of pupil assessment using penlights and flashlights, Quantitative pupillometry (QP) is an established, valid, and reliable method of pupillary assessment.
View Article and Find Full Text PDFBackground: There is practice heterogeneity in the use, type, and duration of prophylactic antiseizure medications (ASM) in patients hospitalized with acute nontraumatic intracerebral hemorrhage (ICH).
Methods: We conducted a systematic review and meta-analysis assessing ASM primary prophylaxis in adults hospitalized with acute nontraumatic ICH. The following population, intervention, comparison, and outcome (PICO) questions were assessed: (1) Should ASM versus no ASM be used in patients with acute ICH with no history of clinical or electrographic seizures? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT/fPHT) be preferentially used? and (3) If an ASM is used, should a long (> 7 days) versus short (≤ 7 days) duration of prophylaxis be used? The main outcomes assessed were early seizure (≤ 14 days), late seizures (> 14 days), adverse events, mortality, and functional and cognitive outcomes.
Background: Clostridium thermocellum is a promising candidate for production of cellulosic biofuels, however, its final product titer is too low for commercial application, and this may be due to thermodynamic limitations in glycolysis. Previous studies in this organism have revealed a metabolic bottleneck at the phosphofructokinase (PFK) reaction in glycolysis. In the wild-type organism, this reaction uses pyrophosphate (PP) as an energy cofactor, which is thermodynamically less favorable compared to reactions that use ATP as a cofactor.
View Article and Find Full Text PDFTransient exposure to ketamine can trigger lasting changes in behavior and mood. We found that brief ketamine exposure causes long-term suppression of futility-induced passivity in larval zebrafish, reversing the "giving-up" response that normally occurs when swimming fails to cause forward movement. Whole-brain imaging revealed that ketamine hyperactivates the norepinephrine-astroglia circuit responsible for passivity.
View Article and Find Full Text PDF: Handheld quantitative pupilometers (QPs) measure each phase of the pupillary light reflex (PLR) and provide a summary score based on these values. One phase of the PLR is the period of time from the onset of light exposure to the maximum constriction of the pupil, also known as time to maximum constriction (tMC). Although tMC has been found to vary significantly among patients with neurological injury, there are no studies reporting tMC in healthy controls.
View Article and Find Full Text PDFBACKGROUND: Certified stroke treatment centers are classified based on their available resources to treat stroke including an Acute Stroke Ready Hospital (ASRH), a primary stroke center (PSC), a Thrombectomy-Capable Stroke Center (TCSC), and comprehensive stroke centers (CSCs). These hospitals all provide varying levels of care with CSCs being the most able to treat all types and complexities of stroke. This undergraduate nursing-led study explored the public's preference for treatment at different certified stroke treatment centers.
View Article and Find Full Text PDF