DigitalCommons@KCU (Kansas City Univ.)
Not a member yet
2803 research outputs found
Sort by
Reanimation After Hemorrhagic Shock Using Intra-arterially Infused Phospholipid Nanoparticles
No full textIntroduction: On the battlefield, 91% of potentially survivable mortality is due to blood loss leading to clinical death (CD) before transport to a medical facility. Therefore, we developed a rat model of CD due to severe rapid blood loss. In prior experiments, we found that intraarterial (IA) infusion was superior to intravenous (IV) in restoring cardiac contraction and respiration. Blood cannot be available to the battlefield. There is a need for an effective reanimation fluid. Therefore, we investigated the use of VBI-1, which is a phospholipid nanoparticle emulsion (particle diameter is 17 nm) that absorbs nitric oxide (NO). NO is produced early during hemorrhagic shock and induces hypotension. These findings have led us to hypothesize that the IA infusion of VBI-1 will be superior to other fluids in increasing mean arterial blood pressure (MAP). Methods: Six female and 6 male rats were subjected to reanimation with either shed blood or VBI-1. Under isoflurane anesthesia, both femoral arteries were canulated. CD was induced by withdrawing blood until respiration ceased. This occurred after withdrawing 40 to 45% of the blood at a rate of 1.5 mL/min. Immediately following CD, shed blood or VBI-I was infused IA in an equivalent volume to the blood loss at a rate of 10 mL/min. MAP was continuously measured for 12 hours post infusion. Data are mean ± SE. Results: In preliminary experiments, VBI-1 was superior to blood, Ringer’s lactate, and VBI-S, another phospholipid particle formulation (diameter is 250 nm), in elevating MAP at 4 hours after CD. Therefore, we decided to directly compare blood and VBI-1 to extend reanimation to 12 hours. MAP ± SE prior to blood withdrawal for blood was 79.9 ± 4.9 and VBI-1 was 80.1 ± 2.7. At CD, MAP for blood was 10.6 ± 1.5 and VBI-1 was 8.8 ± 1.9. MAP 12 hours post-blood infusion was 65.4 ± 13.0, whereas post-VBI-1 infusion was 53.4 ± 8.6 mmHg. 2-way ANOVA showed no significant difference between shed blood and VBI-1 infusion (p = 0.2120). Conclusions: After CD, IA infusion of VBI-1 increased MAP to a level that was equivalent to blood and spontaneous respiration returned. No adverse effects of VBI-1 were observed. Future research should establish the effects of VBI-1 on different organ systems
Phospholipid Nanoparticles Increase P/F Ratio in Septic Shock
No full textIntroduction: Acute respiratory and cardiac failure commonly occur in septic shock patients and may contribute to higher in-hospital mortality. The current protocol for treating septic shock has continued controversy with the use of vasopressors to elevate the mean arterial pressure (MAP) between 60 to 65 mmHg. Hypotension that is minimally responsive to vasopressors occurs in septic shock primarily because of the overproduction of nitric oxide (NO). VBI-S is a phospholipid nanoparticle emulsion that exhibits concentration-dependent absorption and release of NO. We hypothesized that because of this property, infusion of VBI-S would result in the reversal of the patient’s hypotensive state. In our phase IIa clinical trial, VBI-S was administered to severely ill septic patients in whom fluids had failed to increase their MAP greater than or equal to 65 mm Hg. In addition to measuring the changes in MAP, we measured the ratio of arterial pO2 over the fraction of inspired oxygen (P/F). Methods: This was an open-label phase IIa study of 20 patients aged 18 years and above. Hypotensive septic shock patients in whom fluids had failed to elevate MAP above 65 mmHg received VBI-S infusion. VBI-S was infused as a volume sufficient to increase MAP by 10 mmHg or more. A mean of 560.96 ± 83.24 cc was given within 24 hours. The P/F ratio was measured in 17 patients and were analyzed at 24 hours and 48 hours post VBI-S infusion. Data are mean ± SE. Results: The enrolled patients (N = 20) had a sequential organ failure assessment (SOFA) score of 14.0 indicating severe sepsis. All patients were on 1-4 vasopressors. Within a mean of 90 minutes after VBI-S infusion, the MAP increased from 64.50 ± 0.96 to 77.50 ± 1.06 mmHg (p \u3c 0.0001). Patients (N=17) also had an increased P/F from 2.0 ± 0.20 to 2.6 ± 0.20 (p = 0.0024) within 24 hours post-VBI-S infusion and to 2.5 ± 0.22 (p = 0.0210) within 48 hours post-VBI-S infusion. Conclusions: Intravenous infusion of VBI-S increased both the MAP and P/F ratio in septic shock patients. No adverse effects of VBI-S were observed. Future research should establish the biochemical effects of VBI-S in other medical conditions mediated by NO overproduction resulting in decreased MAP and P/F
Spatial Metabolomics Highlights Metabolic Reprogramming in Acute Myeloid Leukemia Mice Through Creatine Pathway
Get PDFAcute myeloid leukemia (AML) is recognized as an aggressive cancer that is characterized by significant metabolic reprogramming. Here, we applied spatial metabolomics to achieve high-throughput, in situ identification of metabolites within the liver metastases of AML mice. Alterations at metabolite and protein levels were further mapped out and validated by integrating untargeted metabolomics and proteomics. This study showed a downregulation in arginine\u27s contribution to polyamine biosynthesis and urea cycle, coupled with an upregulation of the creatine metabolism. The upregulation of creatine synthetases Gatm and Gamt, as well as the creatine transporter Slc6a8, resulted in a marked accumulation of creatine within tumor foci. This process further enhances oxidative phosphorylation and glycolysis of leukemia cells, thereby boosting ATP production to foster proliferation and infiltration. Importantly, we discovered that inhibiting Slc6a8 can counter these detrimental effects, offering a new strategy for treating AML by targeting metabolic pathways
Morphological Variation of the Soleus Muscle: Determining General Patterns and Characteristics of the Connective Tissue Architecture
Get PDFBackground
The tendons within the soleus muscle are commonly utilized to delineate location of injury for soleus muscle strains. Strains within the soleus frequently involve the myotendinous (MTJ) or myofascial (MFJ) junctions, although spatial relationship between these tendinous structures are not well understood. This study aimed to structurally identify the MTJs and MFJs within the soleus as a starting point to understanding the distribution of connective tissue for further anatomical classification.
Methods
Forty (n = 40) soleus muscles, representing left and right sides from twenty (n = 20) formalin-embalmed cadavers (average age 78 years old; 10 males, 10 females) were dissected in-situ to analyze the distribution and orientation of the MTJs and MFJs within classified morphological variants. Muscles were cut in cross-section at three measured locations, proximal, middle, and distal, which allowed for analyzation of tendons through the course of the muscle. Additionally, anterior surfaces of morphological variants were visualized and reconstructed in three dimensions using a handheld blue light 3D scanner.
Results
The study revealed five morphological variants. Bipennate-Midline (n = 25), Bipennate-Medial Deviation (n = 6), Bipennate-Lateral Deviation (n = 3), Unipennate (n = 3), and Hypopennate (n = 3). Muscles included an anterior aponeurosis that was split into medial and lateral components, with each side made up of interconnections between the MTJ and MJF. The average width of the medial aponeurosis was greatest in the middle location, while the average lateral aponeurotic width decreased from proximal to distal. Regression analysis at the middle location revealed that 65 % of the change in width of the medial aponeuroses is due to the width of the medial MFJ.
Conclusions
Proximal-to-distal interconnections between the lateral and medial anterior aponeuroses and their corresponding MTJs and MFJs likely play a role in soleus injury patterns, especially in morphological variants. Awareness of anatomical variations in the location and orientation of these tendinous relationships is crucial for understanding lesions on diagnostic imaging
Machine Learning with Multiple Modalities of Brain Magnetic Resonance Imaging Data to Identify the Presence of Bipolar Disorder
No full textBackground: Bipolar disorder (BD) is a chronic psychiatric mood disorder that is solely diagnosed based on clinical symptoms. These symptoms often overlap with other psychiatric disorders. Efforts to use machine learning (ML) to create predictive models for BD based on data from brain imaging are expanding but have often been limited using only a single modality and the exclusion of the cerebellum, which may be relevant in BD.
Methods: In this study, we sought to improve ML classification of BD by combining information from structural, functional, and diffusion-weighted imaging. Participants (108 BD I, 78 control) with BD type I and matched controls were recruited into an imaging study. This dataset was randomly divided into training and testing sets. For each of the three modalities, a separate ML model was selected, trained, and then used to generate a prediction of the class of each test subject. Majority voting was used to combine results from the three models to make a final prediction of whether a subject had BD. An independent replication sample was used to evaluate the ability of the ML classification to generalize to data collected at other sites.
Results: Combining the three machine learning models through majority voting resulted in an accuracy of 89.5 % for classification of the test subjects as being in the BD or control group. Bootstrapping resulted in a 95 % confidence interval of 78.9 %-97.4 % for test accuracy. Performance was reduced when only using 2 of the 3 modalities. Analysis of feature importance revealed that the cerebellum and nodes of the emotional control network were among the most important regions for classification. The machine learning model performed at chance on the independent replication sample.
Conclusion: BD I could be identified with high accuracy in our relatively small sample by combining structural, functional, and diffusion-weighted imaging data within a single site but not generalize well to an independent replication sample. Future studies using harmonized imaging protocols may facilitate generalization of ML models
Extensively Hydrolyzed Formula and Infant Colic Symptoms: Secondary Analysis of a Prospective Cohort Study
No full textCow\u27s milk protein allergy (CMPA) affects 2% to 3% of infants and is managed with hypoallergenic formulas. The 2022 recalls of infant formulas due to factors including contamination led to specialty formula shortages, highlighting CMPA management challenges. Understanding health care providers\u27 (HCPs) decision-making in transitioning to alternative formulas during shortages is crucial. Limited attention has been given to how pediatric physicians make these choices. This study utilized US HCPs\u27 de-identified survey data to assess driving factors when switching extensively hydrolyzed formulas during shortages. A total of 104 eligible HCPs participated, including general pediatrics, pediatric allergy/immunology, and pediatric gastroenterology specialists. Safety, tolerability, and efficacy were identified as top factors for switching formulas. Formula 1 was considered well-tolerated, patient-accepted, and safe by all HCPs. Most expressed strong belief in Formula 1\u27s safety and effectiveness. Findings inform CMPA management during shortages, offering guidance to HCPs for suitable formula selection and enhanced infant care
My One Wild and Precious Life - The Purpose of Medical Care
No full text“My One Wild and Precious Life - The Purpose of Medical Care”, contains reflections of a medical student as a naive little boy, inspired by his late grandfather, pinning to becoming a physician, who later struggles to find purpose in the unidealistic world of the current healthcare system. But, through his exposure to “Pallium India”, a non-profit palliative care organization in Kerala, India, healthcare once more gains meaning and signifies the importance of love and care amidst a patient\u27s journey through pain and suffering