An integrated analysis of bile acid metabolism in humans with severe obesity.

BACKGROUND AND AIMS: Bile acids (BA) are vital regulators of metabolism. BAs are AQ6 secreted in the small intestine, reabsorbed, and transported back to the liver, where they can modulate metabolic functions. There is a paucity of data regarding the portal BA composition in humans. This study aimed to address this knowledge gap by investigating portal BA composition and the relation with peripheral and fecal BA dynamics in conjunction with the gut microbiome. APPROACH AND RESULTS: Thirty-three individuals from the BARIA cohort were included. Portal plasma, peripheral plasma, and feces were collected. BA and C4 levels were measured employing mass spectrometry. FGF19 was measured using ELISA. Gut microbiota composition was determined through metagenomics analysis on stool samples. Considerable diversity in the portal BA composition was observed. The majority (n = 26) of individuals had a 9-fold higher portal than peripheral BA concentration. In contrast, 8 individuals showed lower portal BA concentration compared with peripheral and had higher levels of unconjugated and secondary BA in this compartment, suggesting more distal origin. The altered portal BA profile was associated with altered gut microbiota composition. In particular, taxa within Bacteroides were reduced in abundance in the feces of these individuals. CONCLUSIONS: Characterization of the portal BA composition in relation to peripheral and fecal BA increased insight into the dynamics of BA metabolism in individuals with obesity. Peripheral BA composition was much more diverse due to microbial metabolism. About 24% of the portal samples was surprisingly low in total BA; the underlying mechanism requires further exploration.

The Impact of an Accelerated Diagnostic Protocol Using Conventional Troponin I for Patients With Cardiac Chest Pain in the Emergency Department.

Background: This study strove to assess the impact of the implementation of an accelerated diagnostic protocol (ADP), using shortened serial-testing intervals and a conventional troponin I (c-TnI) test, on emergency department (ED) length of stay (LOS). Methods: This retrospective cohort study included adults (aged ≥ 18 years) presenting to a Canadian ED with a primary complaint of cardiac chest pain between January 14, 2017 and January 15, 2019. For non-high-risk patients, the troponin delta timing decreased from 6 hours to 3 hours, and a different conventional troponin I level cut-point was implemented on January 15, 2018. The primary outcome was ED LOS. Secondary outcomes included disposition status, consultation proportions, and major adverse cardiac events within 30 days. Results: A total of 3133 patient interactions were included. Although the overall decrease in median ED LOS was not significant (P = 0.074), a significant reduction occurred in ED LOS (-33 minutes; 95% confidence interval: -53.6 to -12.4 minutes) among patients who were discharged in the post-ADP group. Consultations were unchanged between groups (36.1% before vs 33.8% after; P = 0.17). The major adverse cardiac events outcomes were unchanged across cohorts (15.9% vs 15.3%; P = 0.62). Conclusions: The implementation of an ADP, with a conventional troponin I test, for cardiac chest pain in a Canadian ED was not associated with a significant reduction of LOS for all patients; however, a significant reduction occurred for patients who were discharged, and the strategy appears safe.

Contexte: Cette étude visait à évaluer les répercussions de la mise en œuvre d'un protocole de diagnostic accéléré avec intervalles plus courts entre les épreuves séquentielles et dosage classique de la troponine I sur la durée du séjour à l'urgence. Méthodologie: Cette étude de cohortes rétrospective a été menée chez des adultes (âgés de 18 ans ou plus) qui se sont présentés à l'urgence d'un hôpital canadien principalement pour une douleur thoracique cardiaque entre le 14 janvier 2017 et le 15 janvier 2019. Chez les patients qui n'étaient pas exposés à un risque élevé, l'intervalle de dosage de la troponine (delta) est passé de 6 heures à 3 heures, et une nouvelle valeur seuil a été utilisée pour le dosage classique de la troponine I à compter du 15 janvier 2018. Le critère d'évaluation principal était la durée du séjour à l'urgence. Les critères d'évaluation secondaires comprenaient le statut au moment de la sortie, les proportions de consultation et les événements cardiovasculaires indésirables majeurs dans les 30 jours. Résultats: Au total, 3 133 interactions avec des patients ont été incluses. Bien que la diminution globale de la durée médiane du séjour à l'urgence n'ait pas été significative (p = 0,074), une réduction significative du séjour à l'urgence (-33 minutes; intervalle de confiance à 95 % : -53,6 à -12,4 minutes) a été observée chez les patients ayant reçu leur congé appartenant au groupe dans lequel le protocole de diagnostic accéléré a été mis en œuvre. Les consultations étaient inchangées entre les groupes (36,1 % avant vs 33,8 % après; p = 0,17). Les résultats relatifs aux événements cardiovasculaires indésirables majeurs sont demeurés inchangés dans les cohortes (15,9 % vs 15,3 %; p = 0,62). Conclusions: La mise en œuvre d'un protocole de diagnostic accéléré, avec un dosage classique de la troponine I, en cas de douleur thoracique d'origine cardiaque, à l'urgence d'un établissement canadien ne s'est pas traduite par une réduction significative du séjour à l'urgence chez tous les patients. Une réduction significative a néanmoins été observée chez les patients qui ont reçu leur congé, et la stratégie s'est avérée sûre.

Assessing spectral effectiveness in color fundus photography for deep learning classification of retinopathy of prematurity.

Significance: Retinopathy of prematurity (ROP) poses a significant global threat to childhood vision, necessitating effective screening strategies. This study addresses the impact of color channels in fundus imaging on ROP diagnosis, emphasizing the efficacy and safety of utilizing longer wavelengths, such as red or green for enhanced depth information and improved diagnostic capabilities. Aim: This study aims to assess the spectral effectiveness in color fundus photography for the deep learning classification of ROP. Approach: A convolutional neural network end-to-end classifier was utilized for deep learning classification of normal, stage 1, stage 2, and stage 3 ROP fundus images. The classification performances with individual-color-channel inputs, i.e., red, green, and blue, and multi-color-channel fusion architectures, including early-fusion, intermediate-fusion, and late-fusion, were quantitatively compared. Results: For individual-color-channel inputs, similar performance was observed for green channel (88.00% accuracy, 76.00% sensitivity, and 92.00% specificity) and red channel (87.25% accuracy, 74.50% sensitivity, and 91.50% specificity), which is substantially outperforming the blue channel (78.25% accuracy, 56.50% sensitivity, and 85.50% specificity). For multi-color-channel fusion options, the early-fusion and intermediate-fusion architecture showed almost the same performance when compared to the green/red channel input, and they outperformed the late-fusion architecture. Conclusions: This study reveals that the classification of ROP stages can be effectively achieved using either the green or red image alone. This finding enables the exclusion of blue images, acknowledged for their increased susceptibility to light toxicity.

Glycodeoxycholic acid inhibits primary bile acid synthesis with minor effects on glucose- and lipid homeostasis in humans.

BACKGROUND: Bile acids play vital roles in control of lipid-, glucose-, and energy metabolism by activating Takeda G protein-coupled receptor 5 (TGR5) and Farnesoid X receptor (FXR), the latter promoting production of the endocrine-acting fibroblast growth factor 19 (FGF19). Short-term administration of single bile acids has been reported to enhance plasma levels of GLP-1 and to enhance energy expenditure. However, prolonged bile acid supplementation, e.g. of chenodeoxycholic acid (CDCA) for gallstone dissolution, has been reported to have adverse effects. STUDY DESIGN: In this proof-of-concept study, we assessed the safety and metabolic effects of oral glycine-conjugated deoxycholic acid (GDCA) administration at 10 mg/kg/day using regular and slow-release capsules (mimicking physiological bile acid release) over 30 days in two groups of each 10 healthy lean men respectively. MAIN FINDINGS: GDCA increased postprandial total bile acid and FGF19 concentrations while suppressing those of the primary bile acids CDCA and cholic acid. Plasma levels of 7α-hydroxy-4-cholesten-3-one were reduced, indicating repressed hepatic bile acid synthesis. There were minimal effects on indices of lipid-, glucose-, and energy metabolism. No serious adverse events were reported during GDCA administration in either capsule types, although 50% of participants showed mild increases in plasma levels of liver transaminases and 80% (regular capsules) and 50% (slow-release capsules) of participants experienced gastrointestinal adverse events. CONCLUSION: GDCA administration leads to elevated FGF19 levels and effectively inhibits primary bile acid synthesis, supporting therapy compliance and its effectiveness. However, effects on lipid, glucose- and energy metabolism were minimal, indicating that expanding the pool of this relatively hydrophobic bile acid does not impact energy metabolism in healthy subjects.

Differential artery-vein analysis improves the OCTA classification of diabetic retinopathy.

This study investigates the impact of differential artery-vein (AV) analysis in optical coherence tomography angiography (OCTA) on machine learning classification of diabetic retinopathy (DR). Leveraging deep learning for arterial-venous area (AVA) segmentation, six quantitative features, including perfusion intensity density (PID), blood vessel density (BVD), vessel area flux (VAF), blood vessel caliber (BVC), blood vessel tortuosity (BVT), and vessel perimeter index (VPI) features, were derived from OCTA images before and after AV differentiation. A support vector machine (SVM) classifier was utilized to assess both binary and multiclass classifications of control, diabetic patients without DR (NoDR), mild DR, moderate DR, and severe DR groups. Initially, one-region features, i.e., quantitative features extracted from the entire OCTA, were evaluated for DR classification. Differential AV analysis improved classification accuracies from 78.86% to 87.63% and from 79.62% to 85.66% for binary and multiclass classifications, respectively. Additionally, three-region features derived from the entire image, parafovea, and perifovea, were incorporated for DR classification. Differential AV analysis further enhanced classification accuracies from 84.43% to 93.33% and from 83.40% to 89.25% for binary and multiclass classifications, respectively. These findings highlight the potential of differential AV analysis in augmenting disease diagnosis and treatment assessment using OCTA.

Novel Proteome Targets Marking Insulin Resistance in Metabolic Syndrome.

CONTEXT/OBJECTIVE: In order to better understand which metabolic differences are related to insulin resistance in metabolic syndrome (MetSyn), we used hyperinsulinemic-euglycemic (HE) clamps in individuals with MetSyn and related peripheral insulin resistance to circulating biomarkers. DESIGN/METHODS: In this cross-sectional study, HE-clamps were performed in treatment-naive men (n = 97) with MetSyn. Subjects were defined as insulin-resistant based on the rate of disappearance (Rd). Machine learning models and conventional statistics were used to identify biomarkers of insulin resistance. Findings were replicated in a cohort with n = 282 obese men and women with (n = 156) and without (n = 126) MetSyn. In addition to this, the relation between biomarkers and adipose tissue was assessed by nuclear magnetic resonance imaging. RESULTS: Peripheral insulin resistance is marked by changes in proteins related to inflammatory processes such as IL-1 and TNF-receptor and superfamily members. These proteins can distinguish between insulin-resistant and insulin-sensitive individuals (AUC = 0.72 ± 0.10) with MetSyn. These proteins were also associated with IFG, liver fat (rho 0.36, p = 1.79 × 10-9) and visceral adipose tissue (rho = 0.35, p = 6.80 × 10-9). Interestingly, these proteins had the strongest association in the MetSyn subgroup compared to individuals without MetSyn. CONCLUSIONS: MetSyn associated with insulin resistance is characterized by protein changes related to body fat content, insulin signaling and pro-inflammatory processes. These findings provide novel targets for intervention studies and should be the focus of future in vitro and in vivo studies.

Socioeconomic Influence on Surgical Management and Outcomes in Patients with Craniosynostosis - A Systematic Review.

OBJECTIVE: Disparities in insurance and socioeconomic status (SES) may impact surgical management and subsequent postoperative outcomes for patients with craniosynostosis. This systematic review summarizes the evidence on possible differences in surgical care, including procedure type, age at surgery, and differences in surgical outcomes such as complications, length of hospital stay, and child development based on SES. DESIGN: The databases Scopus, PubMed, and CINAHL were searched between May and July 2022. Following PICO criteria, studies included focused on patients diagnosed with craniosynostosis; corrective surgery for craniosynostosis; comparison of insurance, income, or zip code; and surgical management of postoperative outcomes. RESULTS: The initial search yielded 724 articles. After three stages of screening, 13 studies were included. Assessed outcomes included: type of procedure (6 articles), age at time of surgery (3 articles), post-operative complications (3 articles), referral delay (2 articles), length of stay (2 articles), hospital costs (2 articles), and child development (1 article). Of the studies with significant results, insurance type was the main SES variable of comparison. While some findings were mixed, these studies indicated that patients with public medical insurance were more likely to experience a delay in referral, undergo an open rather than minimally-invasive procedure, and have more complications, longer hospitalization, and higher medical charges. CONCLUSIONS: This study demonstrated that SES may be associated with several differences in the management of patients with craniosynostosis. Further investigation into the impact of SES on the management of patients with craniosynostosis is warranted to identify possible interventions that may improve overall care.

Comparison of Speech Outcomes Between Speech Therapy Only and Double-Opposing Z-Plasty Combined With Speech Therapy in Patients With Submucous Cleft Palate.

The purpose of this study was to compare speech outcomes in patients with submucous cleft palate (SMCP) between speech therapy alone and double-opposing Z-plasty (DOZ) combined with speech therapy. The subjects were 67 patients with SMCP (overt type, 45 males, 22 females), who were divided into the observation group (n=18), the speech therapy group (n=24; duration, 17.8 mo), and the DOZ and speech therapy (DOZ-speech therapy) group (n=25; median age at DOZ, 5.3 years, duration, 18.6 mo). The median age at initial and final speech assessments were 3 and 5 years. After age, sex, syndromic status, duration of speech therapy, surgery timing, and speech outcomes were investigated, statistical analysis was performed. After tailored interventions, both isolated and non-isolated SMCP patients experienced significant improvements in speech outcomes, including nasal emission, hypernasality, compensatory articulation, and unintelligible speech. Since comparable improvements were observed, there were no significant differences in the final assessments regardless of initial speech issues between the speech therapy group and the DOZ-speech therapy group (all P>0.05). In the DOZ-speech therapy group, the rate of achieving "socially acceptable" speech was 92.3% in isolated cases and 90% in non-isolated cases. Multivariate analysis revealed that DOZ showed a tendency to reduce hypernasality, compensatory articulation, and "unintelligible" speech; syndromic or developmental conditions influenced outcomes in nasal emission and hypernasality; and initial hypernasality and compensatory articulation were correlated with outcomes. Therefore, DOZ surgery could be recommended to resolve hypernasality and compensatory articulation in SMCP patients before speech issues worsen.

Impact of upper airway obstruction management in Robin Sequence on need for myringotomy tubes.

OBJECTIVE: Investigate an association between upper airway obstruction (UAO) management in Robin Sequence (RS) and need for bilateral myringotomy and tubes (BMT). METHODS: Retrospective chart review of RS patients treated at a tertiary free-standing pediatric hospital from 1995 to 2020 was performed. Patients were grouped based on airway management: conservative, tracheostomy, tongue-lip adhesion (TLA), and mandibular distraction osteogenesis (MDO). Demographic data, cleft palate (CP) association, numbers of BMT and ear infections, and audiogram data including tympanograms were collected. One-way ANOVA and Chi-square/Fisher's exact tests were used to compare continuous and categorical data, respectively. Multivariable regression analysis was used to compare BMT rates between treatment groups. RESULTS: One hundred forty-eight patients were included, 70.3 % of which had CP. Most patients (67.6 %) had at least one BMT; 29.1 % required two or more BMT. The rate of BMT was higher in patients with CP compared to those with intact palates (p = 0.003; 95 % CI 1.30-3.57) and those treated with tracheostomy (p = 0.043; 95 % CI 1.01, 2.27). Surgically managed patients were more likely to have hearing loss (67.5 % vs. 35.3 %, p = 0.017) and ear infections (42.1 % vs. 20.0 %, p = 0.014) pre-compared to post-procedure for airway management. CONCLUSION: Most RS patients require at least 1 set of BMT. Those with CP and/or treated with tracheostomy had a higher likelihood of needing BMT. Rate of hearing loss and ear infection was higher in surgically managed RS patients. Patients with RS and overt CP require a statistically higher number of BMTs compared to those with either submucous cleft palate or intact palate.

Plasticity of Gene Expression and Thermal Tolerance: Implications for Climate Change Vulnerability in a Tropical Forest Lizard.

AbstractTropical ectotherms are thought to be especially vulnerable to climate change because they have evolved in temporally stable thermal environments and therefore have decreased tolerance for thermal variability. Thus, they are expected to have narrow thermal tolerance ranges, live close to their upper thermal tolerance limits, and have decreased thermal acclimation capacity. Although models often predict that tropical forest ectotherms are especially vulnerable to rapid environmental shifts, these models rarely include the potential for plasticity of relevant traits. We measured phenotypic plasticity of thermal tolerance and thermal preference as well as multitissue transcriptome plasticity in response to warmer temperatures in a species that previous work has suggested is highly vulnerable to climate warming, the Panamanian slender anole lizard (Anolis apletophallus). We found that many genes, including heat shock proteins, were differentially expressed across tissues in response to short-term warming. Under long-term warming, the voluntary thermal maxima of lizards also increased, although thermal preference exhibited only limited plasticity. Using these data, we modeled changes in the activity time of slender anoles through the end of the century under climate change and found that plasticity should delay declines in activity time by at least two decades. Our results suggest that slender anoles, and possibly other tropical ectotherms, can alter the expression of genes and phenotypes when responding to shifting environmental temperatures and that plasticity should be considered when predicting the future of organisms under a changing climate.

A Retrospective Review of Patient-reported Outcomes after Postaxial Polydactyly Ligation and Surgical Excision.

Background: Interventions for type B postaxial polydactyly include suture ligation and surgical excision, yet there is a paucity of literature comparing the outcomes of these procedures. This study sought to compare patient-reported long-term outcomes of postaxial digit excision. Methods: A six-question survey was distributed from January 2021 to March 2022 to patients who underwent treatment for type B postaxial polydactyly at a single pediatric institution from 2010 to 2016. Patients were queried about the incidence of pain sensitivity, keloid healing, and/or persistent presence of bump ("nubbin") at the treatment site. Results: A total of 158 responses accounting for 258 digits were attained for a 53% response rate. The majority of digits (67.4%, n = 174) were surgically excised. Median age at procedure was 49 days: 13.0 days for ligation, 63.0 days for surgical excision. Median age at survey was 8 [IQR 5.4-10.2] years. Short-term (<30 days after procedure) complications rate was 1.6%. The rate of a raised or sensitive scar was 39.5% (ligation 51.5% versus surgery 35.4%, P < 0.05). The likelihood of postoperative sensitivity (P = 0.80) was similar among groups. However, the odds of a residual bump or raised scar at the surgical site was significantly higher in the ligation group (P = 0.001). These findings remained significant in the adjusted analysis. Conclusion: This study suggests that suture ligation can be used in select cases without increasing the prevalence of long-term pain or sensitivity, albeit with greater risk of a bump or raised scar at the excision site compared with surgical excision.

Colour fusion effect on deep learning classification of uveal melanoma.

BACKGROUND: Reliable differentiation of uveal melanoma and choroidal nevi is crucial to guide appropriate treatment, preventing unnecessary procedures for benign lesions and ensuring timely treatment for potentially malignant cases. The purpose of this study is to validate deep learning classification of uveal melanoma and choroidal nevi, and to evaluate the effect of colour fusion options on the classification performance. METHODS: A total of 798 ultra-widefield retinal images of 438 patients were included in this retrospective study, comprising 157 patients diagnosed with UM and 281 patients diagnosed with choroidal naevus. Colour fusion options, including early fusion, intermediate fusion and late fusion, were tested for deep learning image classification with a convolutional neural network (CNN). F1-score, accuracy and the area under the curve (AUC) of a receiver operating characteristic (ROC) were used to evaluate the classification performance. RESULTS: Colour fusion options were observed to affect the deep learning performance significantly. For single-colour learning, the red colour image was observed to have superior performance compared to green and blue channels. For multi-colour learning, the intermediate fusion is better than early and late fusion options. CONCLUSION: Deep learning is a promising approach for automated classification of uveal melanoma and choroidal nevi. Colour fusion options can significantly affect the classification performance.

Metabolic causes of liver disease among adults living with HIV from low- and middle-income countries: a cross-sectional study.

INTRODUCTION: Liver disease is a leading cause of morbidity and mortality among persons living with HIV (PLHIV). While chronic viral hepatitis has been extensively studied in low- and middle-income countries (LMICs), there is limited information about the burden of metabolic disorders on liver disease in PLHIV. METHODS: We conducted a cross-sectional analysis of baseline data collected between October 2020 and July 2022 from the IeDEA-Sentinel Research Network, a prospective cohort enrolling PLHIV ≥40 years on antiretroviral treatment (ART) for ≥6 months from eight clinics in Asia, Americas, and central, East, southern and West Africa. Clinical assessments, laboratory testing on fasting blood samples and liver stiffness measurement (LSM)/controlled attenuation parameter (CAP) by vibration-controlled transient elastography were performed. Multivariable logistic regression models assessed factors associated with liver fibrosis (LSM ≥7.1 kPa) and steatosis (CAP ≥248 dB/m). Population attributable fraction (PAF) of each variable associated with significant liver fibrosis was estimated using Levin's formula. RESULTS: Overall, 2120 PLHIV (56% female, median age 50 [interquartile range: 45-56] years) were included. The prevalence of obesity was 19%, 12% had type 2 diabetes mellitus (T2DM), 29% had hypertension and 53% had dyslipidaemia. The overall prevalence of liver fibrosis and steatosis was 7.6% (95% confidence interval [CI] 6.1-8.4) and 28.4% (95% CI 26.5-30.7), respectively, with regional variability. Male sex at birth (odds ratio [OR] 1.62, CI 1.10-2.40), overweight/obesity (OR = 2.50, 95% CI 1.69-3.75), T2DM (OR 2.26, 95% CI 1.46-3.47) and prolonged exposure to didanosine (OR 3.13, 95% CI 1.46-6.49) were associated with liver fibrosis. Overweight/obesity and T2DM accounted for 42% and 11% of the PAF for liver fibrosis, while HBsAg and anti-HCV accounted for 3% and 1%, respectively. Factors associated with steatosis included overweight/obesity (OR 4.25, 95% CI 3.29-5.51), T2DM (OR 2.06, 95% CI 1.47-2.88), prolonged exposure to stavudine (OR 1.69, 95% CI 1.27-2.26) and dyslipidaemia (OR 1.68, 95% CI 1.31-2.16). CONCLUSIONS: Metabolic disorders were significant risk factors for liver disease among PLHIV in LMICs. Early recognition of metabolic disorders risk factors might be helpful to guide clinical and lifestyle interventions. Further prospective studies are needed to determine the causative natures of these findings.

Linkage Mapping and Genome-Wide Association Study Identified Two Peanut Late Leaf Spot Resistance Loci, PLLSR-1 and PLLSR-2, Using Nested Association Mapping.

Identification of candidate genes and molecular markers for late leaf spot (LLS) disease resistance in peanut (Arachis hypogaea) has been a focus of molecular breeding for the U.S. industry-funded peanut genome project. Efforts have been hindered by limited mapping resolution due to low levels of genetic recombination and marker density available in traditional biparental mapping populations. To address this, a multi-parental nested association mapping population has been genotyped with the peanut 58K single-nucleotide polymorphism (SNP) array and phenotyped for LLS severity in the field for 3 years. Joint linkage-based quantitative trait locus (QTL) mapping identified nine QTLs for LLS resistance with significant phenotypic variance explained up to 47.7%. A genome-wide association study identified 13 SNPs consistently associated with LLS resistance. Two genomic regions harboring the consistent QTLs and SNPs were identified from 1,336 to 1,520 kb (184 kb) on chromosome B02 and from 1,026.9 to 1,793.2 kb (767 kb) on chromosome B03, designated as peanut LLS resistance loci, PLLSR-1 and PLLSR-2, respectively. PLLSR-1 contains 10 nucleotide-binding site leucine-rich repeat disease resistance genes. A nucleotide-binding site leucine-rich repeat disease resistance gene, Arahy.VKVT6A, was also identified on homoeologous chromosome A02. PLLSR-2 contains five significant SNPs associated with five different genes encoding callose synthase, pollen defective in guidance protein, pentatricopeptide repeat, acyl-activating enzyme, and C2 GRAM domains-containing protein. This study highlights the power of multi-parent populations such as nested association mapping for genetic mapping and marker-trait association studies in peanuts. Validation of these two LLS resistance loci will be needed for marker-assisted breeding.

New solutions to old problems: A practical approach to identify samples with intravenous fluid contamination in clinical laboratories.

OBJECTIVES: Contamination with intravenous (IV) fluids is a common cause of specimen rejection or erroneous results in hospitalized patients. Identification of contaminated samples can be difficult. Common measures such as failed delta checks may not be adequately sensitive nor specific. This study aimed to determine detection criteria using commonly ordered tests to identify IV fluid contamination and validate the use of these criteria. METHODS: Confirmed contaminated and non-contaminated samples were used to identify patterns in laboratory results to develop criteria to detect IV fluid contamination. The proposed criteria were implemented at a tertiary care hospital laboratory to assess performance prospectively for 6 months, and applied to retrospective chemistry results from 3 hospitals and 1 community lab to determine feasibility and flagging rates. The algorithm was also tested at an external institution for transferability. RESULTS: The proposed algorithm had a positive predictive value of 92 %, negative predictive value of 91 % and overall agreement of 92 % when two or more criteria are met (n = 214). The flagging rates were 0.03 % to 0.07 % for hospital and 0.003 % for community laboratories. CONCLUSIONS: The proposed algorithm identified true contamination with low false flagging rates in tertiary care urban hospital laboratories. Retrospective and prospective analysis suggest the algorithm is suitable for implementation in clinical laboratories to identify samples with possible IV fluid contamination for further investigation.

Multispectral Fundus Photography of Choroidal Nevi With Trans-Palpebral Illumination.

Purpose: The purpose of this study was to investigate the spectral characteristics of choroidal nevi and assess the feasibility of quantifying the basal diameter of choroidal nevi using multispectral fundus images captured with trans-palpebral illumination. Methods: The study used a widefield fundus camera with multispectral (625 nm, 780 nm, 850 nm, and 970 nm) trans-palpebral illumination to examine eight subjects diagnosed with choroidal nevi. Geometric features of nevi, including border clarity, overlying drusen, and lesion basal diameter, were characterized. Clinical imagers, including scanning laser ophthalmoscopy (SLO), autofluorescence (AF), and optical coherence tomography (OCT), were utilized for comparative assessment. Results: Fundus images depicted nevi as dark regions with high contrast against the background. Near-infrared (NIR) fundus images provided enhanced visibility of lesion borders compared to visible fundus images and SLO images. Lesion-background contrast measurements revealed 635 nm SLO at 11% and 625 nm fundus at 42%. Significantly enhanced contrasts were observed in NIR fundus images at 780 nm (73%), 850 nm (63%), and 970 nm (67%). For quantifying the diameter of nevi, NIR fundus images at 780 nm and 850 nm yielded a deviation of less than 10% when compared to OCT measurements. Conclusions: NIR fundus photography with trans-palpebral illumination enhances nevi visibility and boundary definition compared to SLO. Agreement in diameter measurements with OCT validates the accuracy and reliability of this method for choroidal nevi assessment. Translational Relevance: Multispectral fundus imaging with trans-palpebral illumination improves choroidal nevi visibility and accurately measures basal diameter, promising to enhance clinical practices in screening, diagnosis, and monitoring of choroidal nevi.

Quantifying the effect of nutritional interventions on metabolic resilience using personalized computational models.

The manifestation of metabolic deteriorations that accompany overweight and obesity can differ greatly between individuals, giving rise to a highly heterogeneous population. This inter-individual variation can impede both the provision and assessment of nutritional interventions as multiple aspects of metabolic health should be considered at once. Here, we apply the Mixed Meal Model, a physiology-based computational model, to characterize an individual's metabolic health in silico. A population of 342 personalized models were generated using data for individuals with overweight and obesity from three independent intervention studies, demonstrating a strong relationship between the model-derived metric of insulin resistance (ρ = 0.67, p < 0.05) and the gold-standard hyperinsulinemic-euglycemic clamp. The model is also shown to quantify liver fat accumulation and ß-cell functionality. Moreover, we show that personalized Mixed Meal Models can be used to evaluate the impact of a dietary intervention on multiple aspects of metabolic health at the individual level.

Multispectral Fundus Photography of Choroidal Nevi with Trans-Palpebral Illumination.

Purpose: To investigate the spectral characteristics of choroidal nevi and assess the feasibility of quantifying the basal diameter of choroidal nevi using multispectral fundus images captured with trans-palpebral illumination. Methods: The study employed a widefield fundus camera with multispectral (625 nm, 780 nm, 850 nm, and 970 nm) trans-palpebral illumination. Geometric features of choroidal nevi, including border clarity, overlying drusen, and lesion basal diameter, were characterized. Clinical imagers, including scanning laser ophthalmoscopy (SLO), autofluorescence (AF), and optical coherence tomography (OCT), were utilized for comparative assessment. Results: Fundus images captured with trans-palpebral illumination depicted nevi as dark regions with high contrast against the background. Near-infrared (NIR) fundus images provided enhanced visibility of lesion borders compared to visible light fundus images and SLO images. Lesion-background contrast measurements revealed 635 nm SLO at 11% and 625 nm fundus at 42%. Significantly enhanced contrasts were observed in NIR fundus images at 780 nm (73%), 850 nm (63%), and 970 nm (67%). For quantifying the basal diameter of nevi, NIR fundus images at 780 nm and 850 nm yielded a deviation of less than 10% when compared to OCT B-scan measurements. Conclusion: NIR fundus photography with trans-palpebral illumination enhances nevi visibility and boundary definition compared to SLO. Agreement in basal diameter measurements with OCT validates the accuracy and reliability of this method for choroidal nevi assessment.