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Optimization and comparison of [18F]FET synthesis on two distinct automated radiochemistry systems
No full textO-(2-[18F]Fluoroethyl)- L -tyrosine ([18F]FET) is a promising amino acid PET tracer for assessment of malignant brain tumors. Herein, we report optimized production of [18F]FET for clinical use on two commercial radiochemistry systems: Sofie ELIXYS and GE FASTlab 2. While the Sofie ELIXYS procedure requires high performance liquid chromatography (HPLC) purification, the GE FASTlab 2 method uses solid-phase extraction (SPE) purification. In both cases, [18F]FET met release specifications for clinical investigation laid out in the United States Pharmacopeia (USP) and/or European Pharmacopeia (Ph. Eur.). The radiochemical yield of [18F]FET was 35-55% and 30-55% decay corrected to start of synthesis (SOS) for Sofie ELIXYS and GE FASTlab 2, respectively. The overall synthesis time was 75-85 and 70-80 min from SOS for Sofie ELIXYS and GE FASTlab 2, respectively. The radiochemical purity was > 99%, and the molar activity (Am) was 340-464 GBq/µmol at end of synthesis (EOS)
Correlation of Airway POCUS Measures with Screening and Severity Evaluation Tools in Obstructive Sleep Apnea: An Exploratory Study
Get PDFBackground: Obstructive Sleep Apnea (OSA) is a common occurrence in the perioperative patient population but is often undiagnosed. Point-of-Care Ultrasound (POCUS) has emerged as a promising tool for perioperative assessment; however, its effectiveness in detecting the presence or severity of OSA needs to be evaluated. Objective: We assessed the ability of airway POCUS as a screening and severity evaluation tool for OSA by examining its correlation with STOP-BANG scores and the Apnea-Hypopnea Index (AHI). Design: Cross-sectional observational study. Setting: A single-center study in a tertiary care hospital between June 2020 to May 2021. Patients: Adult patients aged 18-65 with prior Polysomnography (PSG) for OSA workup were screened. Interventions: The participants completed the STOP-BANG questionnaire and subsequently underwent POCUS examinations, either pre- or post-surgery. Ten different POCUS views previously used for evaluating OSA were acquired in a predefined sequence, with subsequent measurements of airway parameters. Outcome measures: Generalized linear modeling was used to explore and assess the relationships between the measured parameters, STOP-BANG, and AHI scores (modeled continuously and categorized into risk levels of STOP-BANG and AHI). Results: A total of 260 patients were screened, of which 142 were enrolled and 127 completed the scanning studies. The median AHI was 16.71, while the STOP-BANG scores were mostly between 5 and 6, indicating a moderate-to-high OSA risk in the study population. Notably, only neck circumference was significantly associated with AHI severity (p = 0.012), whereas none of the other POCUS measures were. Among the POCUS measures, significant associations with STOP-BANG scores were observed for the Tongue Cross-Sectional Area (T-CSA) (p = 0.002), Retro-Palatal Diameter (RPD) (p = 0.034), Distance Between Lingual Arteries (DLA) (p = 0.034), and Geniohyoid Muscle Thickness (GMT) (p = 0.040). Conclusions: Neck circumference is a more reliable predictor of OSA severity (AHI) compared to other POCUS measurements. Many of the POCUS measures had a good correlation with the STOP-BANG scores, highlighting the utility of POCUS as a screening tool for OSA rather than as a severity evaluation tool
Retinal vascular biomarkers in mild cognitive impairment and Alzheimer's disease: a comprehensive review and meta‐analysis
Get PDFRetinal vasculature could be a novel, non-invasive, and inexpensive biomarker for Alzheimer's disease (AD) -related neuropathology. In this comprehensive review and meta-analysis from studies that assessed retinal vasculature using optical coherence tomography angiography in AD dementia, we calculated the pooled standardized mean differences (SMDs) in vascular density (VD)-whole, VD-parafoveal, vessel length density (VLD) and foveal avascular zone (FAZ) between AD and cognitively normal (CN), and between mild cognitive impairment (MCI) and CN. Thirty-six studies were included in the meta-analysis. The pooled SMD between AD and CN in VD-whole, VD-parafoveal, VLD, and FAZ was -0.69 (p < 0.01), -0.38 (p = 0.01), -0.59 (p < 0.01), and 0.33 (p = 0.06), respectively, and between MCI and CN in VD-whole, VD-parafoveal, VLD, and FAZ was -0.36 (p = 0.03), -0.17 (p = 0.44), -0.34 (p = 0.03), and 0.31 (p = 0.07), respectively. We identified a significant reduction in retinal vasculature in AD and MCI compared to CN.
Highlights: We performed a meta-analysis of 36 studies using optical coherence tomography angiography to assess the retinal vasculature.These included 4129 participants, of which 1175 had Alzheimer's disease (AD), 1004 had mild cognitive impairment, and 1926 were cognitively normal.We identified a significant reduction in retinal vasculature in AD and mild cognitive impairment compared to cognitively normal.Retinal perfusion measured using optical coherence tomography angiography could be used as a potential biomarker for AD dementia
Detection of Insensitive Munitions Using Blow Flies as Environmental Sampling Devices
Get PDFIndiana University-Purdue University Indianapolis (IUPUI)Insensitive munitions are high explosives that are less shock sensitive than historical high explosives. Munitions compounds 2,4-dinitroanisole, nitrotriazolone, and nitroguanidine commonly comprise the explosives. As the demand for insensitive munitions has increased, contamination from manufacturing sites and training ranges has also increased. Munitions compounds can seep out of soil into waterways, potentially impacting the environment and contaminating food and water supplies. Therefore, determining the presence of these compounds in the environment is important. Direct sampling by collecting soil and water samples can be difficult due to the need to collect samples over wide areas, sometimes in dangerous, remote, or access restricted areas.
In this project, blow flies were used as environmental sampling tools to determine the presence of insensitive munitions in soil. In all fly experiments, blow flies were exposed to an insensitive munitions water-soil mixture. Three types of experiments were conducted: pooling multiple flies during extraction, feeding flies a protein-rich food source prior to munitions, and determining the persistence of munitions in blow flies after a one-time exposure. The amount of munitions present in flies was detected via high performance liquid chromatography-mass spectrometry.
Reverse-phase and hydrophilic interaction liquid chromatography (HILIC) methods were developed to detect insensitive munitions. The reverse-phase method detected munitions in soil and blow flies immediately after exposure. However, ion suppression of compounds nitrotriazolone and nitroguanidine by glucose metabolites in aged flies limited the ability for detection with this method. A comparison of single blow fly and multi-blow fly extracts was done. Multi-fly extracts had increased signal to noise ratios, indicating method sensitivity improvement.
The development of a HILIC method improved retention of the analytes impacted by ion suppression in reverse-phase liquid chromatography. However, separation of 2,4-dinitroanisole and its primary transformation product 2,4-dinitrophenol was not seen with this method. The HILIC method was used to determine persistence of IM in blow flies after controlled exposures to spiked soil. Blow flies were sampled at 0-, 1-, 3-, and 5-days post exposure at varying temperatures. 2,4-dinitroanisole/2,4-dinitrophenol was detected in flies one day post-exposure. Nitrotriazolone was detected in flies 3- days post feed. Nitroguanidine was detected 5 days post-exposure.
This proof-of-concept project proved the ability to detect insensitive munitions in blow flies. Future directions of blow fly analysis include sampling blow flies baited from real-world contamination sites and development of a QuEChERS technique for improved detection from fly matrices
Development and Application of In Vivo Protein Labeling Methods in Caenorhabditis Elegans
Get PDFIUIThe existence and preservation of life relies on the concerted orchestra of numerous biological processes of which proteins are the primary workhorse. In the highly complex intracellular environment, proteins must be synthesized, properly folded, carry out their specific functions, and be efficiently degraded when no longer required. Over time, we have learned even the most minute mutation in protein can have profound impacts on health and disease. Thus, developing methods to dissect protein dynamics and function are critical to understand the basic molecular processes that govern life. Protein pulse-chase is a versatile tool that can be used to study protein dynamics in cells and multicellular organisms. Original protein pulse-chase methods involved global, non-specific labeling of the entire proteome. While informative, spatial expression and dynamics across tissues are lost. The development of self-labeling enzyme tags such as HaloTag enable protein-specific pulse-chase. Pulse-chase experiments using these tags have been performed in various biological systems. However, their broader application is limited by significant technical and economic challenges. This work outlines the development and application of a HaloTag fluorescent pulse-chase method in the model organism, Caenorhabditis elegans. Strains expressing intestine-specific HaloTag histone reporter proteins were generated and could be efficiently pulse-labeled by soaking animals in the presence of HaloTag fluorescent ligand. Stability of labeled histone reporter protein could be feasibly monitored over time using confocal microscopy and was dependent on the animals’ nutritional state. HaloTag fluorescent labeling was further applied to investigate and characterize aberrant extranuclear divisions in the anterior intestine of C. elegans driven by the exogenous expression of a histone H3.3 protein. Collectively, this work serves as entrée to illustrate the potential of in vivo labeling methodologies in C. elegans. Technical advancements made in C. elegans will serve as a stepping-stone to address a variety of questions in metazoan biology. From pulse-labeling to detection, the method is highly adaptable to cater investigation into a wide variety of biological processes in vivo
Sex and Genetic Differences in Behavioral Engagement of Crossed High Alcohol‐Preferring and Low Alcohol‐Preferring Mice
Get PDFExcessive levels of alcohol consumption play a major role in numerous alcohol-related harms, including a heightened risk of developing problematic drinking behaviors. Those who develop alcohol use disorder (AUD) often struggle with persistent difficulties in controlling their drinking, experience withdrawal symptoms, and engage in risky behaviors that pose danger to themselves and others. Advances in treating AUD may be supported by identifying specific cognitive and emotional factors that drive excessive alcohol consumption. Recognizing reliable behavioral biomarkers is instrumental in assessing the risk of developing alcohol problems and preventative care strategies. This study investigates innate behavioral differences associated with genetic predisposition for alcohol use by comparing crossed high alcohol-preferring (cHAP) and low alcohol-preferring (LAP) mice. Since there have been links between heightened impulsivity and excessive alcohol use, we hypothesized that cHAP mice would exhibit higher levels of impulsivity compared to LAPs. No significant differences were found in impulsivity between the mouse lines or sexes. cHAPs adapted to shorter stimulus durations (SDs), whereas LAPs showed a marked decline in correct responses and an increase in omission rates as task difficulty increased. Significant sex differences within the cHAP line were found, with females demonstrating higher accuracy, lower correct latency, and increased perseveration. This behavior points to potential sex-specific neural activation in cognitive processing areas. Future studies should explore salient brain regions to understand their roles in behavioral regulation and sex-specific responses to challenges. This study provides a foundation for exploring the interaction of genetic predisposition, sex differences, and neural mechanisms in alcohol preference and behavior
Assessing the nutrient intake and diet quality of adults wearing dentures using the healthy eating index
No full textBackground: Diet quality might be impacted among individuals after receiving their dentures. This study assessed nutrient intake and diet quality among adults wearing maxillary and/or mandibular complete dentures using 24-hour dietary recalls and compared with the dietary reference intakes recommended for healthy individuals.
Methods: An observational clinical study was conducted with adult participants aged ≥ 50 years wearing maxillary and/or mandibular complete denture/s. They completed two 24-hour dietary recalls, first at an in-person visit and the second within seven days via phone using the Automated Self-Administered (ASA24®) 24-hour web-based platform. Diet quality for each participant was measured as Healthy Eating Index (HEI) scores ranging from 0 to 100 based on 13 food components. HEI is classified as (1) "poor" ( 80) diet quality. Descriptive statistics included participant characteristics, nutrient intake, and diet quality. The Macro and micronutrient intakes of the study participants were compared with the estimated average requirements and adequate intake values. Multivariable regression methods determined the association between the diet quality and participant characteristics. Furthermore, Spearman Correlation was used to estimate the associations between diet quality, macro, and micronutrient intake.
Results: A total of 93 participants participated in the study. 57% were female, 50% were black, 54% wore maxillary and mandibular dentures, 43% received dentures between 50 and 59 years, and 51% wore dentures for more than 10 years. The average HEI score was 54 (sd = 11.9), with a need for diet improvement among 59% of the participants. None of the participants had a good diet quality. More than 90% of the participants consumed dietary fiber, vitamin D, vitamin E, and choline below nutrient recommendations. Study participants with poor diet quality had significantly lower daily intake of fiber, magnesium, potassium, and vitamins A, D, C, B-6, and K (p < 0.05).
Conclusion: The diet of the denture-wearing study participants was inadequate. Routine monitoring of the quality of dietary intake of individuals wearing dentures must be incorporated into a dental clinician's workflow. Further studies must be conducted to evaluate the diet quality of individuals undergoing prosthodontic treatment plans. Based on evidence-based research findings, interdisciplinary care approaches to promote continuity of care among denture wearers need to be established
The Patatin-Like Phospholipase Domain-Containing 3 148M Variant Exacerbates Alcohol-Induced Liver Injury and Tumorigenesis in Mice
No full textPatatin-like phospholipase domain-containing 3 (PNPLA3) protein 148M variant is strongly associated with cirrhosis and hepatocellular carcinoma (HCC); however, the underlying mechanisms remain elusive. This study aimed to elucidate the role of the PNPLA3148M variant in alcohol-related HCC development. Control and humanized PNPLA3148M transgenic mice were fed with an ethanol-containing diet for 12 weeks. The animals were examined for liver tumors. After the alcohol feeding, the PNPLA3148M mice had twofold higher liver cancer incidence rates and larger tumor sizes than those in the control mice. Cancer stem cell markers in the PNPLA3148M mouse livers were elevated relative to those in the control mouse livers. Alcohol detoxification was impaired in the PNPLA3148M mouse livers. Hepatic oxidative stress and DNA damage were elevated in the PNPLA3148M mice. Wnt/β-catenin and Yes-associated protein (YAP) and WW domain-containing transcription regulator 1 (TAZ) were activated in the PNPLA3148M mouse livers. The data suggest that the PNPLA3148M variant has a strong interaction with alcohol in HCC development through attenuation of alcohol detoxification and promotion of oncogenic pathways. Targeting the PNPLA3148M variant might be useful for the prevention or treatment of alcohol-associated HCC in patients carrying this variant
Defining Keypoints to Align H&E Images and Xenium DAPI-Stained Images Automatically
No full text10X Xenium is an in situ spatial transcriptomics platform that enables single-cell and subcellular-level gene expression analysis. In Xenium data analysis, defining matched keypoints to align H&E and spatial transcriptomic images is critical for cross-referencing sequencing and histology. Currently, it is labor-intensive for domain experts to manually place keypoints to perform image registration in the Xenium Explorer software. We present Xenium-Align, a keypoint identification method that automatically generates keypoint files for image registration in Xenium Explorer. We validated our proposed method on 14 human kidney samples and one human skin Xenium sample representing healthy and diseased states, with expert manually marked results. These results show that Xenium-Align could generate accurate keypoints for automatically implementing image alignment in the Xenium Explorer software for spatial transcriptomics studies. Our future research aims to optimize the method's runtime efficiency and usability for image alignment applications
Machine reading and recovery of colors for hemoglobin-related bioassays and bioimaging
No full textDespite advances in machine learning and computer vision for biomedical imaging, machine reading and learning of colors remain underexplored. Color consistency in computer vision, color constancy in human perception, and color accuracy in biomedical imaging are intertwined, complicating digital color-based diagnostics. Existing color reference charts and correction algorithms are inadequate for mobile health (mHealth) and telemedicine in digital health applications where detecting subtle color changes is critical. We present a machine reading and learning platform for color recognition and quantification to extract diagnostic information from colors. A unique combination of spectroscopic gamut determination, reference color optimization, nonsubjective quantification metrics, and neural network-based color recovery retrieves absolute colors of biological tissue. Studies on inflammation bioimaging of photocarcinogenesis and mHealth blood hemoglobin assessment demonstrate accuracy and precision in color recovery across diverse acquisition scenarios. The reported framework overcomes limitations of conventional colorimetric detection, enabling machine-compatible color-based bioassays and bioimaging, advancing digital diagnostics