Maternal psychological risk and the neural correlates of infant face processing: A latent profile analysis.

Maternal psychological factors, including anxiety, depression, and substance use, may negatively affect parenting. Previous works with mothers have often assessed each of these factors in isolation despite their frequent co-occurrence. Psychological factors have also been associated with neural processing of facial stimuli, specifically the amplitude (i.e., size) and latency (i.e., timing) of the face-specific N170 event-related potential. In the current study, 106 mothers completed measures assessing maternal psychological factors-anxiety, depression, and substance use. A latent profile analysis was used to identify profiles of psychological factors and assess profile associations with the N170 elicited by infant faces and with parental reflective functioning (PRF) as a measure related to caregiving. Two profiles (termed high and low psychological risk) were identified, with the higher risk profile associated with delayed N170 latency responses to infant faces. An exploratory analysis evidenced an indirect effect between the higher psychological risk profile and lower PRF through delayed N170 latency responses to infant faces. Taken together, maternal psychological risk across multiple indicators may together shape neural processing of infant faces, which may have downstream consequences for caregiving.

Racial disparities in EEG research and their implications for our understanding of the maternal brain.

Racial disparities in maternal health are alarming and persistent. Use of electroencephalography (EEG) and event-related potentials (ERPs) to understand the maternal brain can improve our knowledge of maternal health by providing insight into mechanisms underlying maternal well-being, including implications for child development. However, systematic racial bias exists in EEG methodology-particularly for Black individuals-and in psychological and health research broadly. This paper discusses these biases in the context of EEG/ERP research on the maternal brain. First, we assess the racial/ethnic diversity of existing ERP studies of maternal neural responding to infant/child emotional expressions, using papers from a recent meta-analysis, finding that the majority of mothers represented in this research are of White/European ancestry and that the racially and ethnically diverse samples that are present are limited in terms of geography. Therefore, our current knowledge base in this area may be biased and not generalizable across racially diverse mothers. We outline factors underlying this problem, beginning with the racial bias in EEG equipment that systematically excludes individuals of African descent, and also considering factors specific to research with mothers. Finally, we highlight recent innovations to EEG hardware to better accommodate diverse hairstyles and textures, and other important steps to increase racial and ethnic representativeness in EEG/ERP research with mothers. We urge EEG/ERP researchers who study the maternal brain-including our own research group-to take action to increase racial diversity so that this research area can confidently inform understanding of maternal health and contribute to minimizing maternal health disparities.

Gender-Based Microaggressions in Surgery: A Scoping Review of the Global Literature.

BACKGROUND: In addition to systemic gender disparities, women in surgery encounter interpersonal microaggressions. The objective of this study is to describe the most common forms of microaggressions reported by women in surgery. METHODS: We conducted a scoping review using PubMed/MEDLINE, Ovid, and Web of Science to describe the international, indexed English-language literature on gender-based microaggressions experienced by female surgeons, surgical trainees, and medical students in surgery. After screening by title, abstract, and full-text, 37 articles were retained for data extraction and analysis. Microaggressions were analyzed using the Sexist Microaggression Experience and Stress Scale (MESS) framework and stratified by country of origin. RESULTS: Gender-based microaggression publications most commonly originated from the United States (n = 27 articles), Canada (n = 3), and India (n = 2). Gender-based microaggressions were classified into environmental invalidations (n = 20), being treated like a second-class citizen (n = 18), assumptions of traditional gender roles (n = 12), sexual objectification (n = 11), assumptions of inferiority (n = 10), being forced to leave gender at the door (n = 8), and experiencing sexist language (n = 6). Additionally, attendings were more frequently reported to experience microaggressions than surgical trainees and medical students, but more articles reported data on attendings (n = 16) than surgical trainees (n = 10) or students (n = 4). CONCLUSION: While recent advancements have opened the field of surgery to women, there is still a lack of female representation, and persistent microaggressions may perpetuate this gender disparity. Addressing microaggressions against female surgeons is essential to achieving gender equity in surgical practice.

Development of MacroPics: A novel food picture set to dissociate the effects of carbohydrate and fat on eating behaviors.

Emerging evidence suggests that fat and carbohydrate interact to potentiate the reward value of food (DiFeliceantonio et al., 2018). The primary goal of the current study was to develop a novel picture set to facilitate research into the effects of macronutrient composition on food choice and eating behavior. Toward this aim, we developed "MacroPics." In Experiment 1, we photographed 120-kcal portions of 60 snack foods falling into one of the three macronutrient categories: (1) mostly carbohydrate, (2) mostly fat, or (3) a combination of fat and carbohydrate. Sixty-one participants rated the images for liking, familiarity, frequency of consumption, healthiness, estimated energy content (in kcal), and expected satiation. A subset of these images consisting of 36 items was then selected in an iterative process to minimize differences in ratings between the macronutrient categories while simultaneously ensuring similar within-category variability on a number of food characteristics (e.g., energy density, portion size, retail price) and visual properties (e.g., color, complexity, visual area). In Experiment 2, an independent sample of 67 participants rated the pictures of the final 36-item MacroPics. Both experiments reveal similar participant ratings across categories for item liking, familiarity, frequency, healthiness, and estimated energy content. Protein content was higher in the fat compared to the carbohydrate and combination categories, leading to higher ratings of estimated satiety and energy density for fatty foods. Item and macronutrient category characteristics of the final MacroPics set are reported.

C-Terminal Tail Polyglycylation and Polyglutamylation Alter Microtubule Mechanical Properties.

Microtubules are biopolymers that perform diverse cellular functions. Microtubule behavior regulation occurs in part through post-translational modification of both the α- and ß-subunits of tubulin. One class of modifications is the heterogeneous addition of glycine and/or glutamate residues to the disordered C-terminal tails (CTTs) of tubulin. Because of their prevalence in stable, high-stress cellular structures such as cilia, we sought to determine if these modifications alter microtubules' intrinsic stiffness. Here, we describe the purification and characterization of differentially modified pools of tubulin from Tetrahymena thermophila. We found that post-translational modifications do affect microtubule stiffness but do not affect the number of protofilaments incorporated into microtubules. We measured the spin dynamics of nuclei in the CTT backbone by NMR spectroscopy to explore the mechanism of this change. Our results show that the α-tubulin CTT does not protrude out from the microtubule surface, as is commonly depicted in models, but instead interacts with the dimer's surface. This suggests that the interactions of the α-tubulin CTT with the tubulin body contributes to the stiffness of the assembled microtubule, thus providing insight into the mechanism by which polyglycylation and polyglutamylation can alter microtubule mechanical properties.

No evidence for an association between obesity and milkshake liking.

BACKGROUND: Prevailing models of obesity posit that hedonic signals override homeostatic mechanisms to promote overeating in today's food environment. What researchers mean by "hedonic" varies considerably, but most frequently refers to an aggregate of appetitive events including incentive salience, motivation, reinforcement, and perceived pleasantness. Here we define hedonic as orosensory pleasure experienced during eating and set out to test whether there is a relationship between adiposity and the perceived pleasure of a palatable and energy-dense milkshake. METHODS: The perceived liking, wanting, and intensity of two palatable and energy-dense milkshakes were assessed using the Labeled Hedonic Scale (1), visual analog scale (VAS), and Generalized Labeled Magnitude Scale (2) in 110 individuals ranging in body mass index (BMI) from 19.3 to 52.1 kg/m2. Waist circumference, waist-hip ratio, and percent body fat were also measured. Importantly, unlike the majority of prior studies, we attempted to standardize internal state by instructing participants to arrive to the laboratory neither hungry nor full and at least 1-h fasted. Data were analyzed with general linear and linear mixed effects models (GLMs). Hunger ratings were also examined prior to hedonic measurement and included as covariates in our analyses. RESULTS: We identified a significant association between ratings of hunger and milkshake liking and wanting. By contrast, we found no evidence for a relationship between any measure of adiposity and ratings of milkshake liking, wanting, or intensity. CONCLUSIONS: We conclude that adiposity is not associated with the pleasure experienced during consumption of our energy-dense and palatable milkshakes. Our results provide further evidence against the hypothesis that heightened hedonic signals drive weight gain.

In-Cell NMR within Budding Yeast Reveals Cytoplasmic Masking of Hydrophobic Residues of FG Repeats.

In-cell NMR spectroscopy is a powerful tool to determine the properties of proteins and nucleic acids within living cells. In-cell NMR can give site-specific measurements of interactions, modifications, and dynamics as well as their modulation by the cellular environment. In-cell NMR requires selective incorporation of heavy isotopes into a protein of interest, either through the introduction of exogenously produced protein to a cell's interior or the selective overexpression of a protein. We developed conditions to allow the use of Saccharomyces cerevisiae, which was chosen because of its genetic tractability, as a eukaryotic expression system for in-cell NMR. We demonstrate this technique using a fragment of S. cerevisiae Nsp1, an FG Nup. FG Nups are intrinsically disordered proteins containing phenylalanine (F)-glycine (G) repeats and form the selective barrier within the nuclear pore complex. Yeast FG Nups have previously been shown to be maintained in a highly dynamic state within living bacteria as measured by in-cell NMR. Interactions thought to stabilize this dynamic state are also present in the protein's native organism, although site specificity of interaction is different between the two cytosols.

Identification of a novel link between adiposity and visuospatial perception.

OBJECTIVE: Recent work has reported a negative association between BMI and performance on the Penn Line Orientation Task. To determine the reliability of this effect, a comprehensive assessment of visual function in individuals with healthy weight (HW) and those with overweight/obesity (OW/OB) was performed. METHODS: Visual acuity/contrast, Penn Line Orientation Task, and higher-order visuospatial function were measured in 80 (40 with HW, 40 with OW/OB) case-control study participants. Adiposity, fasting glucose, hemoglobin A1c, diet, physical activity, and heart rate variability were also assessed. A subgroup of 22 participants plus 5 additional participants (n = 27) underwent functional magnetic resonance imaging scanning. RESULTS: Compared with those with HW, individuals with OW/OB performed worse on tasks requiring judgments of line orientation. This effect was mediated by body fat percentage and was unrelated to other measures. Functional magnetic resonance imaging revealed a negative association between BMI and response in the primary visual cortex (V1) during line orientation judgment. Performance was unrelated to V1 response but positively correlated with response in a network of regions, including the lateral occipital cortex, when BMI was accounted for in the model. CONCLUSIONS: These results demonstrate a selective deficit in line orientation perception associated with adiposity and blunted activation in the V1 that cannot be attributed to visual acuity and does not generalize to other visuospatial tasks.

Brain Health Indicators Following Acute Neuro-Exergaming: Biomarker and Cognition in Mild Cognitive Impairment (MCI) after Pedal-n-Play (iPACES).

Facing an unrelenting rise in dementia cases worldwide, researchers are exploring non-pharmacological ways to ameliorate cognitive decline in later life. Twenty older adults completed assessments before and after a single bout of interactive physical and cognitive exercise, by playing a neuro-exergame that required pedaling and steering to control progress in a tablet-based video game tailored to impact executive function (the interactive Physical and Cognitive Exercise System; iPACES v2). This study explored the cognitive and biomarker outcomes for participants with mild cognitive impairment (MCI) and normative older adults after 20 min of pedal-to-play exercise. Neuropsychological and salivary assessments were performed pre- and post-exercise to assess the impact. Repeated-measures ANOVAs revealed significant interaction effects, with MCI participants experiencing greater changes in executive function and alpha-amylase levels than normative older adults; within-group changes were also significant. This study provides further data regarding cognitive effects and potential mechanisms of action for exercise as an intervention for MCI.

Evaluation of Closed-system Transfer Devices in Reducing Potential Risk for Surface Contamination Following Simulated Hazardous-drug Preparation and Compounding.

Closed-system transfer devices mitigate occupational exposure risks associated with hazardous-drug handling. This study was conducted in a controlled laboratory to evaluate the effectiveness of a needle-free and a needle-based closed-system transfer device in minimizing surface contamination during simulated compounding, preparation, and administration. A needle-based and a needle-free closed-system transfer device underwent three trials per system. Each trial included reconstituting cyclophosphamide in a vial, withdrawing cyclophosphamide from the vial, and pushing cyclophosphamide into an intravenous bag. After every trial, wipe samples were collected from five sources: biological safety cabinet workbench (left and right sides), biological safety cabinet grill, biological safety cabinet airfoil, and technicians' gloves. Wipe samples were then analyzed using high-performance liquid chromatography with dual-mass spectrometry to measure cyclophosphamide concentrations. Surface contamination levels from 30 post-trial tests (15 per device) are reported, representing five different surface wipe samples from three trials for each device. Pre-trial samples of precleaned vials and work surfaces were obtained to ensure no cyclophosphamide contamination. Field blank samples were analyzed for quality-control purposes. Post-trial wipe sample analyses following each of the three needle- free trials did not detect cyclophosphamide on the biological safety cabinet workbench (both left/right), biological safety cabinet grill, biological safety cabinet airfoil, or the technician's gloves. For the needle-based closed-system transfer device, the wipe sample analyses after the first trial showed no contamination; however, cyclophosphamide was detected on the right biological safety cabinet workbench at concentrations of 0.223 ng/cm2 and 0.021 ng/cm2, respectively, following the second and third trials. No cyclophosphamide was found on the technician's gloves after any of the three needle- based closed-system transfer device trials. Based on surface contamination analyses, this study verified the ability of a needle-free closed-system transfer device in preventing the escape of cyclophosphamide during simulated compounding and preparation. Needle-free closed-system transfer devices warrant consideration for the handling of hazardous drugs.

Evaluation of Closed-system Transfer Devices in Reducing Potential Risk for Surface Contamination Following Simulated Hazardous-drug Preparation and Compounding.

Closed-system transfer devices mitigate occupational exposure risks associated with hazardous-drug handling. This study was conducted in a controlled laboratory to evaluate the effectiveness of a needle-free and a needle-based closed-system transfer device in minimizing surface contamination during simulated compounding, preparation, and administration. A needle-based and a needle-free closed-system transfer device underwent three trials per system. Each trial included reconstituting cyclophosphamide in a vial, withdrawing cyclophosphamide from the vial, and pushing cyclophosphamide into an intravenous bag. After every trial, wipe samples were collected from five sources: biological safety cabinet workbench (left and right sides), biological safety cabinet grill, biological safety cabinet airfoil, and technicians' gloves. Wipe samples were then analyzed using high-performance liquid chromatography with dual-mass spectrometry to measure cyclophosphamide concentrations. Surface contamination levels from 30 post-trial tests (15 per device) are reported, representing five different surface wipe samples from three trials for each device. Pre-trial samples of precleaned vials and work surfaces were obtained to ensure no cyclophosphamide contamination. Field blank samples were analyzed for quality-control purposes. Post-trial wipe sample analyses following each of the three needle- free trials did not detect cyclophosphamide on the biological safety cabinet workbench (both left/right), biological safety cabinet grill, biological safety cabinet airfoil, or the technician's gloves. For the needle-based closed-system transfer device, the wipe sample analyses after the first trial showed no contamination; however, cyclophosphamide was detected on the right biological safety cabinet workbench at concentrations of 0.223 ng/cm2 and 0.021 ng/cm2, respectively, following the second and third trials. No cyclophosphamide was found on the technician's gloves after any of the three needle- based closed-system transfer device trials. Based on surface contamination analyses, this study verified the ability of a needle-free closed-system transfer device in preventing the escape of cyclophosphamide during simulated compounding and preparation. Needle-free closed-system transfer devices warrant consideration for the handling of hazardous drugs.

Fat and Carbohydrate Interact to Potentiate Food Reward in Healthy Weight but Not in Overweight or Obesity.

Prior work suggests that actual, but not estimated, energy density drives the reinforcing value of food and that energy from fat and carbohydrate can interact to potentiate reward. Here we sought to replicate these findings in an American sample and to determine if the effects are influenced by body mass index (BMI). Thirty participants with healthy weight (HW; BMI 21.92 ± 1.77; M ± SD) and 30 participants with overweight/obesity (OW/OB; BMI 29.42 ± 4.44) rated pictures of common American snacks in 120-kcal portions for liking, familiarity, frequency of consumption, expected satiety, healthiness, energy content, energy density, and price. Participants then completed an auction task where they bid for the opportunity to consume each food. Snacks contained either primarily carbohydrate, primarily fat, or roughly equal portions of fat and carbohydrate (combo). Replicating prior work, we found that participants with HW bid the most for combo foods in linear mixed model analyses. This effect was not observed among individuals with OW/OB. Additionally, in contrast with previous reports, our linear regression analyses revealed a negative relationship between the actual energy density of the snacks and bid amount that was mediated by food price. Our findings support altered macronutrient reinforcement in obesity and highlight potential influences of the food environment on the regulation of food reward.

Screening for Alzheimer's Disease Using Saliva: A New Approach Based on Machine Learning and Raman Hyperspectroscopy.

BACKGROUND: Alzheimer's disease and related dementias (ADRDs) are being diagnosed at epidemic rates, with incidence to triple from 35 to 115 million cases worldwide. Most ADRDs are characterized by progressive neurodegeneration, and Alzheimer's disease (AD) is the sixth leading cause of death in the United States. The ideal moment for diagnosing ADRDs is during the earliest stages of its progression; however, current diagnostic methods are inefficient, expensive, and unsuccessful at making diagnoses during the earliest stages of the disease. OBJECTIVE: The aim of this project was to utilize Raman hyperspectroscopy in combination with machine learning to develop a novel method for the diagnosis of AD based on the analysis of saliva. METHODS: Raman hyperspectroscopy was used to analyze saliva samples collected from normative, AD, and mild cognitive impairment (MCI) individuals. Genetic Algorithm and Artificial Neural Networks machine learning techniques were applied to the spectral dataset to build a diagnostic algorithm. RESULTS: Internal cross-validation showed 99% accuracy for differentiating the three classes; blind external validation was conducted using an independent dataset to further verify the results, achieving 100% accuracy. CONCLUSION: Raman hyperspectroscopic analysis of saliva has a remarkable potential for use as a non-invasive, efficient, and accurate method for diagnosing AD.

The interactive Physical and Cognitive Exercise System (iPACES™): effects of a 3-month in-home pilot clinical trial for mild cognitive impairment and caregivers.

BACKGROUND: Alzheimer's and related dementias are on the rise, and older adults and their families are seeking accessible and effective ways to stave off or ameliorate mild cognitive impairment (MCI). AIM: This pilot clinical trial (ClinicalTrials.gov Identifier: 03069391) examined neuropsychological and neurobiological outcomes of interactive physical and mental exercise. PARTICIPANTS AND METHODS: Older adults (MCI and caregivers) were enrolled in a 3-month, in-home trial of a portable neuro-exergame (the interactive Physical and Cognitive Exercise System [iPACES™]), in which they pedaled and steered along a virtual bike path to complete a list of errands (Memory Lane™). Neuropsychological function and salivary biomarkers were measured at pre-, mid-, and posttrial. Ten older adults complied with the recommended use of iPACES (complete dose; ≥2×/wk, 67% of the 15 who also had pre- and postevaluation data). Statistical analyses compared change over time and also change among those with a complete dose vs inadequate dose. Correlations between change in neuropsychological and biomarker measures were also examined. RESULTS: Executive function and verbal memory increased after 3 months (p = 0.01; no significant change was found with an inadequate dose). Change in salivary biomarkers was moderately associated with increasing cognition (cortisol, r = 0.68; IGF-1, r = 0.37). CONCLUSION: Further research is needed, but these pilot data provide preliminary indications to suggest neuro-exergaming can impact cognitive function, perhaps via neurobiological mechanisms, and as such may provide an effective and practical way to promote healthy aging.

The Enhanced Interactive Physical and Cognitive Exercise System (iPACESTM v2.0): Pilot Clinical Trial of an In-Home iPad-Based Neuro-Exergame for Mild Cognitive Impairment (MCI).

Given increasing longevity worldwide, older adults and caregivers are seeking ways to curb cognitive decline especially for those with mild cognitive impairment (MCI, now mild neurocognitive disorder, mNCD, Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-V). This quasi-experimental, within-subjects pilot clinical trial was designed to replicate and extend the study of cognitive benefits for MCI by improving upon our prior interactive Physical and Cognitive Exercise Study (iPACESTM v1.0) by increasing the usability of the neuro-exergame and exploring possible underlying neurobiological mechanisms. Older adults were enrolled in a three-month, in-home trial of a portable neuro-exergame (iPACES™ v2.0) where participants pedaled and steered along a virtual bike path (Memory Lane™). Neuropsychological function was assessed at baseline after component familiarization intervals (e.g., two weeks of exercise-only, game-only, etc.) and after three months of interactive neuro-exergame intervention. Fourteen participants were enrolled in the study and seven completed the final evaluation. Intent-to-treat analyses were conducted with imputed missing data (total n = 14). Significant improvement in executive function (Stroop) was found (d = 0.68, p = 0.02) only. Changes in salivary biomarkers (cortisol and insulin-like growth factor 1; IGF-1) were significantly associated with improved cognition. Further research is needed, but pilot data suggest that a portable in-home neuro-exergame may be an additional, practical tool to fight back against cognitive decline and dementia.

Flexible and Stable Value Coding Areas in Caudate Head and Tail Receive Anatomically Distinct Cortical and Subcortical Inputs.

Anatomically distinct areas within the basal ganglia encode flexible- and stable-value memories for visual objects (Hikosaka et al., 2014), but an important question remains: do they receive inputs from the same or different brain areas or neurons? To answer this question, we first located flexible and stable value-coding areas in the caudate head (CDh) and caudate tail (CDt) of two rhesus macaque monkeys, and then injected different retrograde tracers into these areas of each monkey. We found that CDh and CDt received different inputs from several cortical and subcortical areas including temporal cortex, prefrontal cortex, cingulate cortex, amygdala, claustrum and thalamus. Superior temporal cortex and inferior temporal cortex projected to both CDh and CDt, with more CDt-projecting than CDh-projecting neurons. In superior temporal cortex and dorsal inferior temporal cortex, layers 3 and 5 projected to CDh while layers 3 and 6 projected to CDt. Prefrontal and cingulate cortex projected mostly to CDh bilaterally, less to CDt unilaterally. A cluster of neurons in the basolateral amygdala projected to CDt. Rostral-dorsal claustrum projected to CDh while caudal-ventral claustrum projected to CDt. Within the thalamus, different nuclei projected to either CDh or CDt. The medial centromedian nucleus and lateral parafascicular nucleus projected to CDt while the medial parafascicular nucleus projected to CDh. The inferior pulvinar and lateral dorsal nuclei projected to CDt. The ventral anterior and medial dorsal nuclei projected to CDh. We found little evidence of neurons projecting to both CDh and CDt across the brain. These data suggest that CDh and CDt can control separate functions using anatomically separate circuits. Understanding the roles of these striatal projections will be important for understanding how value memories are created and stored.

Molecular Determinants of Tubulin's C-Terminal Tail Conformational Ensemble.

Tubulin is important for a wide variety of cellular processes including cell division, ciliogenesis, and intracellular trafficking. To perform these diverse functions, tubulin is regulated by post-translational modifications (PTM), primarily at the C-terminal tails of both the α- and ß-tubulin heterodimer subunits. The tubulin C-terminal tails are disordered segments that are predicted to extend from the ordered tubulin body and may regulate both intrinsic properties of microtubules and the binding of microtubule associated proteins (MAP). It is not understood how either interactions with the ordered tubulin body or PTM affect tubulin's C-terminal tails. To probe these questions, we developed a method to isotopically label tubulin for C-terminal tail structural studies by NMR. The conformational changes of the tubulin tails as a result of both proximity to the ordered tubulin body and modification by mono- and polyglycine PTM were determined. The C-terminal tails of the tubulin dimer are fully disordered and, in contrast with prior simulation predictions, exhibit a propensity for ß-sheet conformations. The C-terminal tails display significant chemical shift differences as compared to isolated peptides of the same sequence, indicating that the tubulin C-terminal tails interact with the ordered tubulin body. Although mono- and polyglycylation affect the chemical shift of adjacent residues, the conformation of the C-terminal tail appears insensitive to the length of polyglycine chains. Our studies provide important insights into how the essential disordered domains of tubulin function.

Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors.

IMPORTANCE: Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional thyroid cancer. OBJECTIVE: To evaluate clinical outcomes, refine diagnostic criteria, and develop a nomenclature that appropriately reflects the biological and clinical characteristics of EFVPTC. DESIGN, SETTING, AND PARTICIPANTS: International, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC, including 109 patients with noninvasive EFVPTC observed for 10 to 26 years and 101 patients with invasive EFVPTC observed for 1 to 18 years. Review of digitized histologic slides collected at 13 sites in 5 countries by 24 thyroid pathologists from 7 countries. A series of teleconferences and a face-to-face conference were used to establish consensus diagnostic criteria and develop new nomenclature. MAIN OUTCOMES AND MEASURES: Frequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence, in patients with noninvasive and invasive EFVPTC diagnosed on the basis of a set of reproducible histopathologic criteria. RESULTS: Consensus diagnostic criteria for EFVPTC were developed by 24 thyroid pathologists. All of the 109 patients with noninvasive EFVPTC (67 treated with only lobectomy, none received radioactive iodine ablation) were alive with no evidence of disease at final follow-up (median [range], 13 [10-26] years). An adverse event was seen in 12 of 101 (12%) of the cases of invasive EFVPTC, including 5 patients developing distant metastases, 2 of whom died of disease. Based on the outcome information for noninvasive EFVPTC, the name "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) was adopted. A simplified diagnostic nuclear scoring scheme was developed and validated, yielding a sensitivity of 98.6% (95% CI, 96.3%-99.4%), specificity of 90.1% (95% CI, 86.0%-93.1%), and overall classification accuracy of 94.3% (95% CI, 92.1%-96.0%) for NIFTP. CONCLUSIONS AND RELEVANCE: Thyroid tumors currently diagnosed as noninvasive EFVPTC have a very low risk of adverse outcome and should be termed NIFTP. This reclassification will affect a large population of patients worldwide and result in a significant reduction in psychological and clinical consequences associated with the diagnosis of cancer.