Thymol increases primordial follicle activation, protects stromal cells, collagen fibers and down-regulates expression of mRNA for superoxide dismutase 1, catalase and periredoxin 6 in cultured bovine ovarian tissues.

This study aims to investigate the influence of thymol on primordial follicle growth and survival, as well as on collagen fibers and stromal cells density in bovine ovarian tissues cultured in vitro. The activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), the thiol levels and the expression of mRNAs for SOD1, CAT, periredoxin 6 (PRDX6) and GPX1 were also investigated. Ovarian cortical tissues were cultured in α-MEM+ alone or with thymol (400, 800, 1600 or 3200 µg/mL) for six days. Before and after culture, the tissues were processed for histological analysis to evaluate follicular activation, growth, morphology, ovarian stromal cell density and collagen fibers. The levels of mRNA for SOD1, CAT, GPX1 and PRDX6 were evaluated by real-time PCR. The results show that tissues cultured with thymol (400 and 800 µg/mL) had increased percentages of normal follicles, when compared to tissues cultured in other treatments. At concentrations of 400 and 800 µg/mL, thymol maintained the rate of normal follicles similar to the uncultured control. In addition, 400 µg/mL thymol increased follicle activation, collagen fibers and stromal cell density of when compared to tissues cultured in control medium. The presence of 800 µg/mL thymol in culture medium increased CAT activity, while 400 or 800 µg/mL thymol reduced mRNA levels for SOD1, CAT and PRDX6, but did not alter GPX1 expression. In conclusion, 400 µg/mL thymol increases primordial follicle activation, preserves stromal cells, collagen fibers, and down-regulates expression of mRNA for SOD1, CAT and PRDX6 in cultured bovine ovarian tissues.

Conformally invariant free-parafermionic quantum chains with multispin interactions.

We calculate the spectral properties of two related families of non-Hermitian free-particle quantum chains with N-multispin interactions (N=2,3,...). The first family have a Z(N) symmetry and are described by free parafermions. The second have a U(1) symmetry and are generalizations of XX quantum chains described by free fermions. The eigenspectra of both free-particle families are formed by the combination of the same pseudo-energies. The models have a multicritical point with dynamical critical exponent z=1. The finite-size behavior of their eigenspectra, as well as the entanglement properties of their ground-state wave function, indicate the models are conformally invariant. The models with open and periodic boundary conditions show quite distinct physics due to their non-Hermiticity. The models defined with open boundaries have a single conformal invariant phase, while the XX multispin models show multiple phases with distinct conformal central charges in the periodic case.

Classification of Corrosion Severity in SPCC Steels Using Eddy Current Testing and Supervised Machine Learning Models.

Steel Plate Cold-Rolled Commercial (SPCC) steel is known to have long-term durability. However, it still undergoes corrosion when exposed to corrosive environments. This paper proposes an evaluation method for assessing the corrosion level of SPCC steel samples using eddy current testing (ECT), along with two different machine learning approaches. The objective is to classify the corrosion of the samples into two states: a less corroded state (state-1) and a highly corroded state (state-2). Generative and discriminative models were implemented for classification. The generative classifier was based on the Gaussian mixture model (GMM), while the discriminative model was based on the logistic regression model. The features used in the classification models are the peaks of the perturbated magnetic fields at two different frequencies. The performance of the classifiers was evaluated using metrics such as absolute error, accuracy, precision, recall, and F1 score. The results indicate that the GMM model is more conducive to categorizing states with higher levels of corrosion, while the logistic regression model is helpful in estimating states with lower levels of corrosion. Meanwhile, high classification accuracy can be achieved based on both methods using eddy current testing.

Differential atrophy along the longitudinal hippocampal axis in Alzheimer's disease for the Alzheimer's Disease Neuroimaging Initiative.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that primarily affects the hippocampus. Since hippocampal studies have highlighted a differential subregional regulation along its longitudinal axis, a more detailed analysis addressing subregional changes along the longitudinal hippocampal axis has the potential to provide new relevant biomarkers. This study included structural brain MRI data of 583 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cognitively normal (CN) subjects, mild cognitively impaired (MCI) subjects and AD patients were conveniently selected considering the age and sex match between clinical groups. Structural MRI acquisitions were pre-processed and analysed with a new longitudinal axis segmentation method, dividing the hippocampus in three subdivisions (anterior, intermediate, and posterior). When normalizing the volume of hippocampal sub-divisions to total hippocampus, the posterior hippocampus negatively correlates with age only in CN subjects (r = -.31). The longitudinal ratio of hippocampal atrophy (anterior sub-division divided by the posterior one) shows a significant increase with age only in CN (r = .25). Overall, in AD, the posterior hippocampus is predominantly atrophied early on. Consequently, the anterior/posterior hippocampal ratio is an AD differentiating metric at early disease stages with potential for diagnostic and prognostic applications.

Probing the Critical Role of Interfaces for Superior Performance in PbS Quantum Dot/Graphene Nanohybrid Broadband Photodetectors.

Colloidal quantum dots/graphene (QD/Gr) nanohybrids have been studied intensively for photodetection in a broadband spectrum including ultraviolet, visible, near-infrared, and shortwave infrared (UV-vis-NIR-SWIR). Since the optoelectronic process in the QD/Gr nanohybrid relies on the photogenerated charge carrier transfer from QDs to graphene, understanding the role of the QD-QD and QD-Gr interfaces is imperative to the QD/Gr nanohybrid photodetection. Herein, a systematic study is carried out to probe the effect of these interfaces on the noise, photoresponse, and specific detectivity in the UV-vis-NIR-SWIR spectrum. Interestingly, the photoresponse has been found to be negligible without a 3-mercaptopropionic acid (MPA) ligand exchange, moderate with a single ligand exchange after all QD layers are deposited on graphene, and maximum if it is performed after each QD layer deposition up to five layers of total QD thickness of 260-280 nm. Furthermore, exposure of graphene to C-band UV (UVC) for a short period of 4-5 min before QD deposition leads to improved photoresponse via removal of polar molecules at the QD/Gr interface. With the combination of the MPA ligand exchange and UVC exposure, optimal optoelectronic properties can be obtained on the PbS QD/Gr nanohybrids with high specific detectivity up to 2.6 × 1011, 1.5 × 1011, 5 × 1010, and 1.9 × 109 Jones at 400, 550, 1000, and 1700 nm, respectively, making the nanohybrids promising for broadband photodetection.

Psychosis in Alzheimer's disease is associated with specific changes in brain MRI volume, cognition and neuropathology.

Psychosis in Alzheimer's Disease (AD) is prevalent and indicates poor prognosis. However, the neuropathological, cognitive and brain atrophy patterns underlying these symptoms have not been fully elucidated. In this study, we evaluated 178 patients with AD neuropathological change (ADNC) and ante-mortem volumetric brain magnetic resonance imaging (MRI). Presence of psychosis was determined using the Neuropsychiatric Inventory Questionnaire. Clinical Dementia Rating Sum-of-boxes (CDR-SB) was longitudinally compared between groups with a follow-up of 3000 days using mixed-effects multiple linear regression. Neuropsychological tests closest to the time of MRI and brain regional volumes were cross-sectionally compared. Psychosis was associated with lower age of death, higher longitudinal CDR-SB scores, multi-domain cognitive deficits, higher neuritic plaque severity, Braak stage, Lewy Body pathology (LB) and right temporal lobe regional atrophy. Division according to the presence of LB showed differential patterns of AD-typical pathology, cognitive deficits and regional atrophy. In conclusion, psychosis in ADNC with and without LB has clinical value and associates with subgroup patterns of neuropathology, cognition and regional atrophy.

Melatonin improves the viability and ultrastructure of bovine oocyte-granulosa complexes of in vitro cultured early antral follicles.

This study aims to investigate the effects of melatonin on follicular growth, viability and ultrastructure, as well as on the levels of mRNA for antioxidant enzymes, reactive oxygen species (ROS) and meiotic progression in oocytes from in vitro cultured bovine early antral follicles. To this end, isolated early antral follicles (500-600 µm) were cultured in TCM-199+ alone or supplemented with 10-6 , 10-7 or 10-8 M melatonin at 38.5°C with 5% CO2 for 8 days. Follicle diameters were evaluated at days 0, 4 and 8 of culture. At the end of culture, ultrastructure, chromatin configuration, viability (calcein-AM and ethidium homodimer-1 staining), and the levels of ROS and mRNA for catalase (CAT), superoxide dismutase (SOD) and peroxiredoxin 6 (PRDX6) and glutathione peroxidase (GPx) were investigated in oocyte-granulosa cell complexes (OGCs). The results showed that early antral follicles cultured with 10-6 and 10-8 M melatonin had a progressive and significant increase in their diameters throughout the culture period (p < .05). Additionally, oocytes from follicles cultured with 10-7 or 10-8 M melatonin had increased fluorescence for calcein-AM, while those cultured with 10-6 or 10-7 M had reduced fluorescence for ethidium homodimer-1. Different from follicles cultured in other treatments, those cultured with 10-8 M melatonin had well-preserved ultrastructure of oocyte and granulosa cells. Melatonin, however, did not influence the levels of ROS, the mitochondrial activity, oocyte meiotic resumption and expression mRNA for SOD, CAT, GPX1 and PRDX6. In conclusion, the presence of 10-8 M melatonin in culture medium improves viability and preserves the ultrastructure of oocyte and granulosa cells of early antral follicles cultured in vitro.

A Novel Postbiotic Product Based on Weissella cibaria for Enhancing Disease Resistance in Rainbow Trout: Aquaculture Application.

Postbiotics are innovative tools in animal husbandry, providing eco-friendly solutions for disease management within the industry. In this study, a new postbiotic product was evaluated for its impact on the health of rainbow trout (Oncorhynchus mykiss). In vivo studies were conducted to assess the safety of the Weissella cibaria strains used in postbiotic production. Additionally, this study evaluated the impact of diet supplementation with 0.50% postbiotics on growth performance during a 30-day feeding trial; the gut microbial communities, immunomodulation, and protection against Yersinia ruckeri infection were evaluated. The strains did not harm the animals during the 20-day observation period. Furthermore, the effect of postbiotics on growth performance was not significant (p < 0.05). The treated group showed a significant increase in acid-lactic bacteria on the 30th day of the feeding trial, with counts of 3.42 ± 0.21 log CFU/mL. Additionally, there was an up-regulation of the pro-inflammatory cytokine IL-1ß in head kidney samples after 48 h of feed supplementation, whereas cytokines IL-10, IL-8, INF-γ, and TNF-α were down-regulated. The findings indicate that rainbow trout fed with postbiotics saw an improvement in their survival rate against Y. ruckeri, with a 20.66% survival improvement in the treated group. This study proves that incorporating postbiotics from two strains of W. cibaria previously isolated from rainbow trout into the diet of fish has immunomodulatory effects, enhances intestinal microbial composition, and improves fish resistance against Y. ruckeri.

Success-driven opinion formation determines social tensions.

Polarization is common in politics and public opinion. It is believed to be shaped by media as well as ideologies, and often incited by misinformation. However, little is known about the microscopic dynamics behind polarization and the resulting social tensions. By coupling opinion formation with the strategy selection in different social dilemmas, we reveal how success at an individual level transforms to global consensus or lack thereof. When defection carries with it the fear of punishment in the absence of greed, as in the stag-hunt game, opinion fragmentation is the smallest. Conversely, if defection promises a higher payoff and also evokes greed, like in the prisoner's dilemma and snowdrift game, consensus is more difficult to attain. Our research thus challenges the top-down narrative of social tensions, showing they might originate from fundamental principles at individual level, like the desire to prevail in pairwise evolutionary comparisons.

Multicenter Quantification of Radiation Exposure and Associated Risks for Prostatic Artery Embolization in 1476 Patients.

Background Prostatic artery embolization (PAE) is a safe, minimally invasive angiographic procedure that effectively treats benign prostatic hyperplasia; however, PAE-related patient radiation exposure and associated risks are not completely understood. Purpose To quantify radiation dose and assess radiation-related adverse events in patients who underwent PAE at multiple centers. Materials and Methods This retrospective study included patients undergoing PAE for any indication performed by experienced operators at 10 high-volume international centers from January 2014 to May 2021. Patient characteristics, procedural and radiation dose data, and radiation-related adverse events were collected. Procedural radiation effective doses were calculated by multiplying kerma-area product values by an established conversion factor for abdominopelvic fluoroscopy-guided procedures. Relationships between cumulative air kerma (CAK) or effective dose and patient body mass index (BMI), fluoroscopy time, or radiation field area were assessed with linear regression. Differences in radiation dose stemming from radiopaque prostheses or fluoroscopy unit type were assessed using two-sample t tests and Wilcoxon rank sum tests. Results A total of 1476 patients (mean age, 69.9 years ± 9.0 [SD]) were included, of whom 1345 (91.1%) and 131 (8.9%) underwent the procedure with fixed interventional or mobile fluoroscopy units, respectively. Median procedure effective dose was 17.8 mSv for fixed interventional units and 12.3 mSv for mobile units. CAK and effective dose both correlated positively with BMI (R2 = 0.15 and 0.17; P < .001) and fluoroscopy time (R2 = 0.16 and 0.08; P < .001). No radiation-related 90-day adverse events were reported. Patients with radiopaque implants versus those without implants had higher median CAK (1452 mGy [range, 900-2685 mGy] vs 1177 mGy [range, 700-1959 mGy], respectively; P = .01). Median effective dose was lower for mobile than for fixed interventional systems (12.3 mSv [range, 8.5-22.0 mSv] vs 20.4 mSv [range, 13.8-30.6 mSv], respectively; P < .001). Conclusion Patients who underwent PAE performed with fixed interventional or mobile fluoroscopy units were exposed to a median effective radiation dose of 17.8 mSv or 12.3 mSv, respectively. No radiation-related adverse events at 90 days were reported. © RSNA, 2024 See also the editorial by Mahesh in this issue.

Contralateral suppression in adrenal venous sampling predicts clinical and biochemical outcome in primary aldosteronism.

CONTEXT: The role for hormone parameters at adrenal venous sampling (AVS) in predicting clinical and biochemical outcome remains controversial. OBJECTIVE: To investigate the impact of hormone parameters at AVS under cosyntropin stimulation on lateralization and on complete biochemical and clinical outcome. METHODS: We retrospectively evaluated 150 sequential AVS under cosyntropin infusion. Bilateral successful cannulation rate was 83.3% (n = 140), 47.9% bilateral and 52.1% unilateral. The lateralization index (LI), aldosterone/cortisol ratio (A/C) in the dominant adrenal vein (AV), relative aldosterone secretion index (RASI = A/C in AV divided by A/C in inferior vena cava) were assessed. The contralateral suppression (CS) percentage was defined by (1 - nondominant RASI) *100. RESULTS: A nondominant RASI <0.5 (CS >50%) had 86.84% sensitivity and 92.96% specificity to predict contralateral lateralization. An A/C ratio in dominant AV >5.9 (74.67% sensitivity and 80% specificity) and dominant RASI >4.7 (35.21% sensitivity and 88.06% specificity) had a worst performance to predict ipsilateral lateralization. Complete biochemical and clinical cure were significantly more frequent in the patients with CS >50% [98.41% vs. 42.86% (p < 0.001) and 41.94% vs. 0% (p < 0.001)]. CS correlated with high aldosterone at diagnosis (p < 0.001) and low postoperative aldosterone levels at 1 month (p = 0.019). Postoperative biochemical hypoaldosteronism was more frequent in patients with CS >50% (70% vs. 16.67%, p = 0.014). In multivariable analysis, a CS >50% was associated with complete biochemical cure (OR 125, 95%CI 11.904-5,000; p = 0.001) and hypertension remission (OR 12.19, 95%CI 2.074-250; p = 0.023). CONCLUSION: A CS >50% was an independent predictor of complete clinical and biochemical cure. Moreover, it can predict unilateral PA and postoperative biochemical hypoaldosteronism. Our findings underscore the usefulness of CS for clinical decision-making.

Functional EPAS1/HIF2A missense variant is associated with hematocrit in Andean highlanders.

Hypoxia-inducible factor pathway genes are linked to adaptation in both human and nonhuman highland species. EPAS1, a notable target of hypoxia adaptation, is associated with relatively lower hemoglobin concentration in Tibetans. We provide evidence for an association between an adaptive EPAS1 variant (rs570553380) and the same phenotype of relatively low hematocrit in Andean highlanders. This Andean-specific missense variant is present at a modest frequency in Andeans and absent in other human populations and vertebrate species except the coelacanth. CRISPR-base-edited human cells with this variant exhibit shifts in hypoxia-regulated gene expression, while metabolomic analyses reveal both genotype and phenotype associations and validation in a lowland population. Although this genocopy of relatively lower hematocrit in Andean highlanders parallels well-replicated findings in Tibetans, it likely involves distinct pathway responses based on a protein-coding versus noncoding variants, respectively. These findings illuminate how unique variants at EPAS1 contribute to the same phenotype in Tibetans and a subset of Andean highlanders despite distinct evolutionary trajectories.

Evolution of a theory of mind.

Even though the Theory of Mind in upper primates has been under investigation for decades, how it may evolve remains an open problem. We propose here an evolutionary game theoretical model where a finite population of individuals may use reasoning strategies to infer a response to the anticipated behavior of others within the context of a sequential dilemma, i.e., the Centipede Game. We show that strategies with bounded reasoning evolve and flourish under natural selection, provided they are allowed to make reasoning mistakes and a temptation for higher future gains is in place. We further show that non-deterministic reasoning co-evolves with an optimism bias that may lead to the selection of new equilibria, closely associated with average behavior observed in experimental data. This work reveals both a novel perspective on the evolution of bounded rationality and a co-evolutionary link between the evolution of Theory of Mind and the emergence of misbeliefs.

Accelerated Corneal Crosslinking to Arrest Progression of Corneal Ectasia: A Prospective Multicenter Study.

OBJECTIVES: To report the results of epithelium-off accelerated corneal collagen crosslinking (accelerated corneal crosslinking [ACXL]) in patients with progressive keratoconus. METHODS: This prospective, nonrandomized, noncomparative, interventional, multicenter clinical study included all patients who underwent ACXL, either continuous (c-ACXL; 9 mW/cm 2 , 10', 5.4 J/cm 2 ) or pulsed (p-ACXL; 2″ON/1″OFF, 30 mW/cm 2 , 4.5', 5.4 J/cm 2 ) between January 2014 and May 2017. Best-corrected visual acuity, sphere, cylinder, spherical equivalent, and topographical keratometry data were collected preoperatively and at 1, 3, 6, 12, 18, and 24 months postoperatively. RESULTS: Ninety-six eyes of 78 patients were included. The mean age was 20.8±4.4 years (14-33) for c-ACXL and 26.7±7.7 years (12-37) for p-ACXL. The mean best-corrected visual acuity was 0.4±0.4 for c-ACXL and 0.01±0.1 for p-ACXL preoperatively, and 0.3±0.3 ( P =0.0014) and -0.01±0.1 ( P =0.1554), respectively, at the last follow-up. The subjective sphere and spherical equivalent did not show statistically significant differences between the time points ( P >0.05). The subjective cylinder showed significant differences ( P =0.0013 for c-ACXL; P =0.0358 for p-ACXL). Keratometric values (K steep , K flat , and SimK) remained stable, with no statistically significant differences ( P >0.05). No major complications were noted. CONCLUSIONS: Both c-ACXL and p-ACXL are equally safe and effective ACXL protocols in stabilizing the progression of keratoconus and can be considered alternatives to the conventional Dresden protocol.

Corneal Neuropathic Pain: A Patient and Physician Perspective.

Corneal neuropathic pain (CNP) is a debilitating condition characterized by pain in the absence of a noxious stimulus. Symptoms such as ocular stinging, burning, photophobia, irritation, and a deep aching pain can be severe despite a seemingly normal ocular surface on examination. CNP may develop due to either peripheral or central sensitization. Peripheral sensitization develops due to aberrant regeneration of corneal nociceptors and nerve fibers as a result of corneal injury or disease of peripheral corneal nerves. Whereas, central sensitization develops due to upregulation of excitatory neurotransmitters as a result of chronic inflammation, which leads to amplification of neuronal response to stimuli. Unfortunately, due to the disparity in severity of symptomology and the observable signs on examination, patients' symptoms are commonly thought to be "psychological" or "functional", and patients report feeling ignored and neglected. Additionally, diagnosis is often delayed which adversely affects patient outcomes. Research to date has focused on the scientific aspects of corneal neuropathic pain: its pathophysiology, epidemiology, investigations, and management. Research into the patient personal experience and the challenges faced by individual patients and their clinicians is lacking. We present the patient and physician perspective on the journey of both patients in order to provide insights into the challenges faced by patients and physicians in the diagnosis, assessment, and management of corneal neuropathic pain.

Corneal neuropathic pain is a rare disease that causes patients to experience severe eye pain without a painful stimulus. Patients often experience one or more symptoms, such as ocular stinging, burning, irritation, photophobia, and deep aching pains even though ophthalmologists cannot see any abnormality when they examine the eyes. Due to a significant lack of awareness and understanding of the condition, diagnosis is often delayed and patients are left feeling ignored or neglected. Research to date has focused on the scientific aspects of corneal neuropathic pain such as what causes it, the tests doctors use to diagnose it, and the best treatments to manage it. In this article, we present the patient and physician perspective, an understanding of which we believe can improve the care that patients receive and can promote awareness and understanding of the condition, facilitating early diagnosis and treatment.

APOE genotype dictates lipidomic signatures in primary human hepatocytes.

Apolipoprotein E (APOE) genetic variants are most notably known for their divergent impact on the risk of developing Alzheimer's disease. While APOE genotype has been consistently shown to modulate lipid metabolism in a variety of cellular contexts, the effect of APOE alleles on the lipidome in hepatocytes is unknown. In this study, we investigated the contribution of APOE alleles to lipidomic profiles of donor-derived primary human hepatocytes from 77 subjects. Lipidomic data obtained by liquid chromatography-mass spectrometry were analyzed across ε2/ε3, ε3/ε3, and ε3/ε4 genotypes to reveal how APOE modulates lipid relative levels over age and between groups. Hepatic APOE concentration, measured by ELISA, was assessed for correlation with lipid abundance in subjects grouped as per APOE genotype and sex. APOE genotype-specific differential lipidomic signatures associated with age for multiple lipid classes but did not differ between sexes. Compared to ε2/ε3, ε3/ε4 hepatocytes had higher abundance of acylcarnitines (AC) and acylphosphatidylglycerol (AcylPG) as a class, as well as higher medium and long-chain ACs, AcylPG, phosphatidylglycerol (PG), bis(monoacylglycerol)phosphate (BMP), monoacylglycerol (MG) and diacylglycerol (DG) species. The ε3/ε4 hepatocytes also exhibited a higher abundance of medium and long-chain ACs compared to the ε3/ε3 hepatocytes. Only in the ε3/ε4 hepatocytes, APOE concentration was lower and showed a negative correlation with BMP levels, specifically in females. APOE genotype dictates a differential lipidome in primary human hepatocytes. The lipids involved suggest mitochondrial dysfunction with accompanying alterations in neutral lipid storage, reflective of a general disturbance of free fatty acid metabolism in human hepatocytes with the ε4 allele.

Use of a flexible tip bougie (FlexTip) in the management of the first-attempt failure intubation with the C-MAC D-Blade videolaryngoscope in the intensive care unit: A prospective, case series.

We describe a series of 11 cases in which we used the new flexible tip (FlexTip) bougie as a rescue device following first-attempt failure at intubation with the C-MAC D-Blade video laryngoscope in our UCI. We collected data from all intubations performed using the C-MAC D-Blade video laryngoscope over a 16-month period. Ninety six patients were included in the study: 79 (86.8%) were intubated at the first attempt; 11 (12.1%) required 2 attempts; and 1 patient required 3 attempts. The Frova Intubating Introducer was used in 1 of the 12 patients requiring more than 1 intubation attempt, and the FlexTip was used in the remaining 11. This study shows that the new FlexTip bougie is a good rescue device when the first attempt at video laryngoscope intubation fails.

Clinical Outcomes After Endoscopic Management of Low-Risk and High-Risk T1a Esophageal Adenocarcinoma: A Multicenter Study.

INTRODUCTION: Endoscopic eradication therapy (EET) is standard of care for T1a esophageal adenocarcinoma (EAC). However, data on outcomes in high-risk T1a EAC are limited. We assessed and compared outcomes after EET of low-risk and high-risk T1a EAC, including intraluminal EAC recurrence, extraesophageal metastases, and overall survival. METHODS: Patients who underwent EET for T1a EAC at 3 referral Barrett's esophagus endotherapy units between 1996 and 2022 were included. Patients with submucosal invasion, positive deep margins, or metastases at initial diagnosis were excluded. High-risk T1a EAC was defined as T1a EAC with poor differentiation and/or lymphovascular invasion, with low-risk disease being defined without these features. All pathology was systematically assessed by expert gastrointestinal pathologists. Baseline and follow-up endoscopy and pathology data were abstracted. Time-to-event analyses were performed to compare outcomes between groups. RESULTS: One hundred eighty-eight patients with T1a EAC were included (high risk, n = 45; low risk, n = 143) with a median age of 70 years, and 84% were men. Groups were comparable for age, sex, Barrett's esophagus length, lesion size, and EET technique. Rates of delayed extraesophageal metastases (11.1% vs 1.4%) were significantly higher in the high-risk group ( P = 0.02). There was no significant difference in the rates of intraluminal EAC recurrence ( P = 0.79) and overall survival ( P = 0.73) between the 2 groups. DISCUSSION: Patients with high-risk T1a EAC undergoing successful EET had a substantially higher rate of extraesophageal metastases compared with those with low-risk T1a EAC on long-term follow-up. These data should be factored into discussions with patients while selecting treatment approaches. Additional prospective data in this area are critical.

Linking avian malaria parasitemia estimates from quantitative PCR and microscopy reveals new infection patterns in Hawai'i.

Plasmodium parasites infect thousands of species and provide an exceptional system for studying host-pathogen dynamics, especially for multi-host pathogens. However, understanding these interactions requires an accurate assay of infection. Assessing Plasmodium infections using microscopy on blood smears often misses infections with low parasitemias (the fractions of cells infected), and biases in malaria prevalence estimates will differ among hosts that differ in mean parasitemias. We examined Plasmodium relictum infection and parasitemia using both microscopy of blood smears and quantitative polymerase chain reaction (qPCR) on 299 samples from multiple bird species in Hawai'i and fit models to predict parasitemias from qPCR cycle threshold (Ct) values. We used these models to quantify the extent to which microscopy underestimated infection prevalence and to more accurately estimate infection patterns for each species for a large historical study done by microscopy. We found that most qPCR-positive wild-caught birds in Hawaii had low parasitemias (Ct scores ≥35), which were rarely detected by microscopy. The fraction of infections missed by microscopy differed substantially among eight species due to differences in species' parasitemia levels. Infection prevalence was likely 4-5-fold higher than previous microscopy estimates for three introduced species, including Zosterops japonicus, Hawaii's most abundant forest bird, which had low average parasitemias. In contrast, prevalence was likely only 1.5-2.3-fold higher than previous estimates for Himatione sanguinea and Chlorodrepanis virens, two native species with high average parasitemias. Our results indicate that relative patterns of infection among species differ substantially from those observed in previous microscopy studies, and that differences depend on variation in parasitemias among species. Although microscopy of blood smears is useful for estimating the frequency of different Plasmodium stages and host attributes, more sensitive quantitative methods, including qPCR, are needed to accurately estimate and compare infection prevalence among host species.