Commensal E. coli limits Salmonella gut invasion during inflammation by producing toxin-bound siderophores in a tonB-dependent manner.

The gastrointestinal tract is densely colonized by a polymicrobial community known as the microbiota which serves as primary line of defence against pathogen invasion. The microbiota can limit gut-luminal pathogen growth at different stages of infection. This can be traced to specific commensal strains exhibiting direct or indirect protective functions. Although these mechanisms hold the potential to develop new approaches to combat enteric pathogens, they remain far from being completely described. In this study, we investigated how a mouse commensal Escherichia coli can outcompete Salmonella enterica serovar Typhimurium (S. Tm). Using a salmonellosis mouse model, we found that the commensal E. coli 8178 strain relies on a trojan horse trap strategy to limit S. Tm expansion in the inflamed gut. Combining mutants and reporter tools, we demonstrated that inflammation triggers the expression of the E. coli 8178 antimicrobial microcin H47 toxin which, when fused to salmochelin siderophores, can specifically alter S. Tm growth. This protective function was compromised upon disruption of the E. coli 8178 tonB-dependent catecholate siderophore uptake system, highlighting a previously unappreciated crosstalk between iron intake and microcin H47 activity. By identifying the genetic determinants mediating S. Tm competition, our work not only provides a better mechanistic understanding of the protective function displayed by members of the gut microbiota but also further expands the general contribution of microcins in bacterial antagonistic relationships. Ultimately, such insights can open new avenues for developing microbiota-based approaches to better control intestinal infections.

In Patients With Inflammatory Bowel Disease, Racial Disparities Exist in Burden of Vaccine-preventable Disease Hospitalizations and Outcomes.

OBJECTIVE: Patients with inflammatory bowel disease (IBD) are at increased risk of vaccine-preventable diseases (VPDs). Despite the increasing prevalence of IBD in non-white populations, little is known regarding racial disparities in VPD burden. METHODS: Retrospectively analyzing the 2016 to 2020 National Inpatient Sample, we identified adults with IBD hospitalized for a principal diagnosis of VPD. The primary outcome investigated was hospitalization for VPD stratified by patient-reported race. Secondary outcomes were in-hospital morbidity, mortality, length of stay, and health care utilization. Multivariable regression analysis was performed to adjust for patient and hospital characteristics. RESULTS: The search identified 554,114 hospitalizations for VPD, including 4170 hospitalizations in patients with IBD. Patients with IBD had significantly greater odds of hospitalization from herpes zoster virus (adjusted odds ratio [aOR]: 1.73) and varicella zoster virus (aOR: 2.31). Comparing white and non-white patients with IBD, significant racial disparities were noted. Non-white patients were at greater odds of hospitalization from influenza (aOR: 1.74), herpes zoster virus (aOR: 1.77), and varicella zoster virus (aOR: 1.62). In-hospital morbidity was greater in non-white patients, including greater odds of requiring intensive care unit stay (aOR: 1.18). Morbidity was elevated in African Americans, with greater odds of acute kidney injury (aOR: 1.25), venous thromboembolism (aOR: 1.17), respiratory failure (aOR: 1.16), and intensive care unit stay (aOR: 1.18). No differences were found in mortality, length of stay, and health care utilization. CONCLUSIONS: Significant racial disparities in VPD hospitalization and in-hospital morbidity were found among adults with IBD in the United States. With the increasing prevalence of IBD in non-white populations, targeted efforts are needed to improve health equity.

Assessment of Gait Patterns during Crutch Assisted Gait through Spatial and Temporal Analysis.

The use of crutches is a common method of assisting people during recovery from musculoskeletal injuries in the lower limbs. There are several different ways to walk with crutches depending on the patient's needs. The structure of crutch gaits or crutch gait patterns varies based on the delay between the aid and foot placement, the number of concurrent points of contact, and laterality. In a rehabilitation process, the prescribed pattern may differ according to the injury, the treatment and the individual's condition. Clinicians may improve diagnosis, assessment, training, and treatment by monitoring and analyzing gait patterns. This study aimed to assess and characterize four crutch walking patterns using spatial and temporal parameters obtained from the instrumented crutches. For this purpose, 27 healthy users performed four different gait patterns over multiple trials. Each trial was recorded using a portable system integrated into the crutches, which measured force, position, and acceleration. Based on the data angle, an algorithm was developed to segment the trials into gait cycles and identify gait phases. The next step was to determine the most appropriate metrics to describe each gait pattern. Several metrics were used to analyze the collected data, including force, acceleration, angle, and stride time. Among 27 participants, significant differences were found between crutch gait patterns. Through the use of these spatial and temporal parameters, promising results were obtained for monitoring assisted gait with crutches. Furthermore, the results demonstrated the possibility of using instrumented crutches as a clinical tool.

Incidence, Burden, and Predictors of Readmission for Acute Alcoholic Pancreatitis: A National Analysis over 11 Months.

BACKGROUND/OBJECTIVES: Data regarding incidence, health-care burden, and predictors for readmission in patients with acute alcoholic pancreatitis (AAP) is scarce. We aim to identify incidence, health-care burden, and predictors of readmission over an 11-month period. METHODS: Retrospective cohort study using the 2016 National Readmission Database of adult patients admitted with a principal diagnosis of AAP in January and 11-month readmission follow up for all-cause readmission. Incidence of all-cause readmission, mortality rate, morbidity, length of stay (LOS), total hospitalization charges and costs were evaluated. Independent risk factors for all-cause readmission were identified using a Cox multivariate logistic regression analysis. RESULTS: A total of 6633 patients were included in the study. The mean age was 45.7 years and 28.9% of patients were female. 73.1% of patients had a modified BISAP score of 0. The 11-month readmission rate was 43.1%. The main cause of readmission was another episode of AAP. The mortality rate of readmission was 0.5% and the mortality rate during the index admission (IA) was 1.1% (P = 0.03). The mean LOS, total hospitalization charges and costs for readmission were 4.5 days, $34,307 and $8958, respectively. Independent predictors of readmission were Charlson Comorbidity Index score of ≥ 3, associated chronic alcoholic pancreatitis, and chronic pancreatitis (CP) from other causes. CONCLUSION: Among patients admitted with AAP, the 11-month readmission rate was 43.1%. Over one-third of readmissions were due to another episode of AAP. Readmission associated with significant resource utilization. Special attention should be placed in patients with underlying CP due to the increased risk of readmission.

Morphological Electrical and Hardness Characterization of Carbon Nanotube-Reinforced Thermoplastic Polyurethane (TPU) Nanocomposite Plates.

The impacts on the morphological, electrical and hardness properties of thermoplastic polyurethane (TPU) plates using multi-walled carbon nanotubes (MWCNTs) as reinforcing fillers have been investigated, using MWCNT loadings between 1 and 7 wt%. Plates of the TPU/MWCNT nanocomposites were fabricated by compression molding from extruded pellets. An X-ray diffraction analysis showed that the incorporation of MWCNTs into the TPU polymer matrix increases the ordered range of the soft and hard segments. SEM images revealed that the fabrication route used here helped to obtain TPU/MWCNT nanocomposites with a uniform dispersion of the nanotubes inside the TPU matrix and promoted the creation of a conductive network that favors the electronic conduction of the composite. The potential of the impedance spectroscopy technique has been used to determine that the TPU/MWCNT plates exhibited two conduction mechanisms, percolation and tunneling conduction of electrons, and their conductivity values increase as the MWCNT loading increases. Finally, although the fabrication route induced a hardness reduction with respect to the pure TPU, the addition of MWCNT increased the Shore A hardness behavior of the TPU plates.

Characterization of 58 STRs and 94 SNPs with the ForenSeq™ DNA signature prep kit in Mexican-Mestizos from the Monterrey city (Northeast, Mexico).

BACKGROUND: STR allele frequency databases from populations are necessary to take full advantage of the increased power of discrimination offered by massively parallel sequencing (MPS) platforms. MATERIAL AND METHODS: For this reason, we sequenced 58 STRs (aSTRs, X-STRs, and Y-STRs) and 94 identity informative SNPs (iiSNPs) on 105 Mestizo (admixed) individuals from Monterrey City (Northeast, Mexico), with the Primer Set-A of the ForenSeq™ DNA Signature Prep Kit. RESULTS: Most of the STR markers were in Hardy Weinberg equilibrium, with a few exceptions. We found 346 different length-based alleles for these 58 STRs; nevertheless, they became 528 alleles when the sequence was assessed. The combined power of discrimination from autosomal STRs (aSTRs) was -virtually- 100% in both length and sequence-based alleles, while the power of exclusion was 99.9999999976065 and 99.9999999999494%, respectively. Haplotypes based on X-STRs and Y-STRs showed 100% of discriminatory capacity. CONCLUSIONS: These results provide -for the first time- forensic genomic population data from Mexico necessary for interpretation in kinship and criminal analyses.

Heat-health action planning in the WHO European Region: Status and policy implications.

Adverse health effects from extreme heat remain a major risk, especially in a changing climate. Several European countries have implemented heat health action plans (HHAPs) to prevent ill health and excess mortality from heat. This paper assesses the state of implementation of HHAPs in the WHO European Region and discusses barriers and successes since the early 2000s. The results are based on a web-based survey among 53 member states on the current national and federal HHAPs in place. Guided by the eight core elements of HHAPs as outlined by the WHO Regional Office for Europe guidance from 2008, we analyzed which elements were fully or partially implemented and which areas of improvement countries identified. HHAP adaptations to account for COVID-19 were sought via literature search and expert consultations. 27 member states provided information, of which 17 countries reported having a HHAP. Five out of eight core elements, namely agreement on a lead body, accurate and timely alert systems, heat-related health information plans, strategies to reduce health exposure, and care for vulnerable groups, were at least partially implemented in all 17 plans. Alert systems were implemented most often at 94%. The least often implemented items were real-time surveillance, long-term urban planning, and preparedness of health and social systems. Five countries had published COVID-19 guidance online. Our findings suggest a progressive improvement in the development and rollout of HHAPs overall and awareness of vulnerable population groups in WHO/Europe, while integration of HHAPs into long-term climate change and health planning remains a challenge.

Thirty-Day Readmission After Bariatric Surgery: Causes, Effects on Outcomes, and Predictors.

BACKGROUND: Bariatric surgery (BSx) is one of the most common surgical procedures in North America. Readmissions may be associated with a high burden to the healthcare system. METHODS: Retrospective study of the 2016 National Readmission Database of adult patients readmitted within 30 days after an index admission for BSx. Outcomes were: 30-day readmission rate, mortality, healthcare-related utilization resources, and independent predictors of readmission. Comparison groups were index admission, readmitted, and non-readmitted patients. RESULTS: A total of 161,141 patients underwent BSx. The 30-day readmission rate was 3.3%. Main causes for readmission were dehydration, acute kidney injury, venous thromboembolism events, and sepsis. Readmitted patients were more likely to develop shock (0.5% vs. 0.1%; P < 0.01) with no differences in mechanical ventilation (1.9% vs. 2.0%; P = 0.83) during index admission compared to non-readmitted patients. Readmission was associated with higher in-hospital mortality rate (1.5% vs. 0.1%; P < 0.01) and prolonged length of stay (4.6 vs. 2.4 days; P < 0.01). The total in-hospital economic burden of readmission was $234 million in total charges and $58.7 million in total costs. Independent predictors of readmission were: Charlson comorbidity index of ≥ 3, longer length of stay, admission to larger bed size hospitals, discharge to nursing home, and acute kidney injury. Medicaid, private insurance, BMI of 30-39 kg/m2, and 40-44 kg/m2 were associated with lower odds for readmission. CONCLUSION: Readmissions after BSx are associated with higher in-hospital mortality rate and pose a high healthcare burden. We identified risk factors that can be targeted to decrease readmissions after BSx, healthcare burden, and patient morbidity and mortality.

A high-density EEG investigation into the neurocognitive mechanisms underlying differences between personality profiles in social information processing.

This study investigated whether differences between personality styles in the processing of social stimuli reflect variability in underlying general-purpose or social-specific neurocognitive mechanisms. Sixty-five individuals classified previously into two distinct personality profiles underwent high-density electroencephalography whilst performing tasks that tap into both aspects of cognitive processing - namely, two distinct facets of general-purpose response inhibition (interference resolution and action withholding) during social information processing. To determine the stage of processing at which personality differences manifest, we assessed event-related components associated with the early visual discrimination of social stimuli (N170, N190) and later more general conflict-related processes (N2, P3). Although a performance index of interference resolution was comparable between the personality profiles, differences were detected in action withholding. Specifically, individuals expressing a wider repertoire of personality styles and more adaptive emotion regulation performed significantly better at withholding inappropriate actions to neutral faces presented in emotional contexts compared with those exhibiting stronger preferences for fewer and less adaptive personality styles and more ruminative affective tendencies. At the neurophysiological level, however, difference between the profiles was observed in brain responses elicited to the same stimuli within the N170. These results indicate that neural processes related to early visual discrimination might contribute to differences in the suppression of inappropriate responses towards social stimuli in populations with different personality dispositions.

Imitation or Polarity Correspondence? Behavioural and Neurophysiological Evidence for the Confounding Influence of Orthogonal Spatial Compatibility on Measures of Automatic Imitation.

During social interactions, humans tend to imitate one another involuntarily. To investigate the neurocognitive mechanisms driving this tendency, researchers often employ stimulus-response compatibility (SRC) tasks to assess the influence that action observation has on action execution. This is referred to as automatic imitation (AI). The stimuli used frequently in SRC procedures to elicit AI often confound action-related with other nonsocial influences on behaviour; however, in response to the rotated hand-action stimuli employed increasingly, AI partly reflects unspecific up-right/down-left biases in stimulus-response mapping. Despite an emerging awareness of this confounding orthogonal spatial-compatibility effect, psychological and neuroscientific research into social behaviour continues to employ these stimuli to investigate AI. To increase recognition of this methodological issue, the present study measured the systematic influence of orthogonal spatial effects on behavioural and neurophysiological measures of AI acquired with rotated hand-action stimuli in SRC tasks. In Experiment 1, behavioural data from a large sample revealed that complex orthogonal spatial effects exert an influence on AI over and above any topographical similarity between observed and executed actions. Experiment 2 reproduced this finding in a more systematic, within-subject design, and high-density electroencephalography revealed that electrocortical expressions of AI elicited also are modulated by orthogonal spatial compatibility. Finally, source localisations identified a collection of cortical areas sensitive to this spatial confound, including nodes of the multiple-demand and semantic-control networks. These results indicate that AI measured on SRC procedures with the rotated hand stimuli used commonly might reflect neurocognitive mechanisms associated with spatial associations rather than imitative tendencies.

Thirty-Day Readmission Among Patients with Alcoholic Acute Pancreatitis.

BACKGROUND/OBJECTIVES: Alcoholic acute pancreatitis (AAP) comprises the second most common cause of acute pancreatitis in the USA, and there is lack of data regarding 30-day specific readmission causes and predictors. We aim to identify 30-day readmission rate, causes, and predictors of readmission. METHODS: Retrospective analysis of the 2016 National Readmission Database of adult patients readmitted within 30 days after an index admission for AAP. RESULTS: Totally, 76,609 AAP patients were discharged from the hospital in 2016. The 30-day readmission rate was 12%. The main cause of readmission was another episode of AAP. Readmission was not associated with higher mortality (1.3% vs. 1.2%; P = 0.21) or prolonged length of stay (5.2 vs. 5.0 days; P = 0.06). The total health care economic burden was $354 million in charges and $90 million in costs. Independent predictors of readmission were having Medicaid insurance, a Charlson comorbidity index score ≥ 3, use of total parenteral nutrition, opioid abuse disorder, prior pancreatic cyst, chronic alcoholic pancreatitis, and other chronic pancreatitis. Obesity was associated with lower odds of readmission. CONCLUSION: Readmission rate for AAP is high and its primary cause are recurrent episodes of AAP. Alcohol and substance abuse pose a high burden on our health care system. Public health strategies should be targeted to provide alcohol abuse disorder rehabilitation and cessation resources to alleviate the burden on readmission, the health care system and to improve patient outcomes.

Nutritional and Functional Evaluation of Inula crithmoides and Mesembryanthemum nodiflorum Grown in Different Salinities for Human Consumption.

The nutritional composition and productivity of halophytes is strongly related to the biotic/abiotic stress to which these extremophile salt tolerant plants are subjected during their cultivation cycle. In this study, two commercial halophyte species (Inula crithmoides and Mesembryanthemum nodiflorum) were cultivated at six levels of salinity using a soilless cultivation system. In this way, it was possible to understand the response mechanisms of these halophytes to salt stress. The relative productivity decreased from the salinities of 110 and 200 mmol L-1 upwards for I. crithmoides and M. nodiflorum, respectively. Nonetheless, the nutritional profile for human consumption remained balanced. In general, I. crithmoides vitamin (B1 and B6) contents were significantly higher than those of M. nodiflorum. For both species, ß-carotene and lutein were induced by salinity, possibly as a response to oxidative stress. Phenolic compounds were more abundant in plants cultivated at lower salinities, while the antioxidant activity increased as a response to salt stress. Sensory characteristics were evaluated by a panel of culinary chefs showing a preference for plants grown at the salt concentration of 350 mmol L-1. In summary, salinity stress was effective in boosting important nutritional components in these species, and the soilless system promotes the sustainable and safe production of halophyte plants for human consumption.

Analysis of venous thromboembolism in neurosurgical patients undergoing standard versus routine ultrasonography.

Routine screening of high-risk asymptomatic trauma or surgical patients for venous thromboembolism (VTE) is controversial. Studies suggest against screening while others recognize that some patients at high risk may benefit. The purpose of this pilot study is to evaluate the benefit of routine screening using doppler ultrasonography for the early detection of deep venous thrombosis (DVT) in post-operative neurosurgical patients. This was a quasi-experimental study at a major academic tertiary care medical center. A total of 157 adults underwent cranial or spinal surgical interventions from March through August 2017 and received either standard screening (n = 104) versus routine ultrasonography screening (n = 53). There was no significant difference in incidence of DVT between the two groups: 11 (11%) in the standard screening group versus 5 (9%) in the routine screening group, p = 0.823. Upper and lower extremity ultrasonography was performed in 43 (41%) of the standard screening group versus 53 (100%) in the routine screening group, p < 0.001. DVT was identified in nearly one of every 6 ultrasonography screenings in the standard screening group versus 27 ultrasonography screenings required to identify one DVT in the routine screening group. There were the same number of screenings for upper extremity ultrasonography, but they did not yield or detect DVT; instead only superficial, untreatable, DVTs were reported. Total cost to diagnose one DVT, including screening and labor, averaged $13,664 in the standard group versus $56,525 in the routine group. Routine screening in neurosurgical patients who received VTE prophylaxis was not associated with lower incidence of VTE and mortality attributed to PE. Thus, routine screening may not be cost effective to prevent complications from DVT incidence.

Safety and Effectiveness of Factor VIII Inhibitor Bypassing Activity (FEIBA) and Fresh Frozen Plasma in Oral Anticoagulant-Associated Intracranial Hemorrhage: A Retrospective Analysis.

BACKGROUND: Oral anticoagulant (OAT)-associated intracranial hemorrhage (ICH) is a life-threatening emergency for which prothrombin complex concentrates (PCC) are considered first-line reversal agents. The only approved PCC in the USA for warfarin-associated ICH is non-activated PCC. Little data are available regarding the safety and effectiveness of factor VIII inhibitor bypassing activity (FEIBA) which is an activated prothrombin complex concentrate (aPCC). The aim of this analysis was to assess the safety and effectiveness of FEIBA compared to fresh frozen plasma (FFP) for reversal of OAT-associated ICH. METHODS: Data were retrospectively collected to compare coagulation markers and in-hospital clinical outcomes in patients who received aPCC with or without FFP versus FFP alone for the reversal of OAT-associated ICH. RESULTS: Eighty-four patients met inclusion criteria; 50 patients received FFP alone, and 34 patients received FEIBA (mean dose 20 U/kg) with or without FFP for OAT-associated ICH. The proportion of diagnosed thrombotic events during hospitalization was similar in both groups (8% in the FFP group vs. 12% in the FEIBA group; P = 0.56). Median time to INR < 1.5 was achieved faster in the FEIBA group versus the FFP group (0.5 h [IQR 0.5-1.] vs. 10 h [IQR 5-16.3], respectively; P < 0.001) reflecting a trend toward shorter median time to neurosurgical intervention. Hematoma expansion, length of stay, and all-cause mortality were similar between both groups. CONCLUSIONS: Administration of FEIBA does not appear to increase the risk of thrombotic events compared with FFP. FEIBA administration resulted in faster INR reversal with a trend toward shorter time to neurosurgical intervention. However, there was no difference in hematoma expansion, mortality or length of stay.

Exogenous Vasopressin-Induced Hyponatremia in Patients With Vasodilatory Shock: Two Case Reports and Literature Review.

Vasopressin has gained wide support as an adjunct vasopressor in patients with septic shock. This agent exerts its vasoconstriction effects through smooth muscle V1 receptors and also has antidiuretic activity via renal V2 receptors. This interaction with the renal V2 receptors results in the integration of aquaporin 2 channels in the apical membrane of the renal collecting duct leading to free water reabsorption. Thus, water intoxication with subsequent hyponatremia, although rare, is a potentially serious side effect of exogenous vasopressin administration. We present 2 patients who developed hyponatremia within hours of initiation of vasopressin infusion. Extensive diuresis followed its discontinuation with subsequent normalization of serum sodium. One of the patients required the use of hypertonic saline for more rapid normalization of serum sodium due to concerns for potential seizure activity. A review of the literature relevant to the incidence of vasopressin-induced hyponatremia is provided as well as discussion on additional factors relevant to septic shock that should be considered when determining the relative risk of hyponatremia in patients receiving vasopressin.

Comparative Efficacy of Pyrethroid-Based Paints against Turkestan Cockroaches.

The Turkestan cockroach, Periplaneta lateralis (Walker), is an invasive urban pest prevalent in dry areas of the southwestern United States. Treatment with liquid spray formulations containing insecticides is the most conventional method to decrease Turkestan cockroach population abundance around buildings. Intensive application of insecticide treatments near natural environments has prompted concerns regarding the impacts on non-target aquatic and terrestrial ecosystems. Technologies embedding insecticides in a paint matrix have successfully been used for the long-term reduction in disease-vector populations in tropical areas. Here, we evaluated the potential effectiveness of three pyrethroid-based paints against Turkestan cockroach nymphs on common surfaces inhabited by this species. Turkestan cockroaches continuously exposed for 1 h to 1-month aged alphacypermethrin and deltamethrin paints applied to concrete, metal, or PVC caused moderate to high mortality. Evaluations using choice boxes indicated that deltamethrin and transfluthrin paints had combined lethal and repellent effects on cockroaches. Alphacypermethrin also caused repellency and killed cockroaches rapidly. We discuss the implications of these findings on cockroach control practices.

Insights into the Bioactive Composition, Antioxidant Properties and In Vitro Cell Effects of Disphyma crassifolium.

Disphyma crassifolium, commonly known as sea fingers, is a halophyte plant recently introduced in gourmet cuisine. The present study aims to extract the bioactive compounds of D. crassifolium using ultrasound-assisted extraction and employing green solvents (water and ethanol). The antioxidant/antiradical activities, scavenging capacity against reactive species, phenolic profile, and intestinal effects were evaluated. The highest total phenolic (53.13 mg of gallic acid equivalent (GAE)/g on dry weight (dw)) and flavonoid contents (18.98 mg of catechin equivalent (CE)/g dw) as well as antioxidant (149.69 µmol of ferrous sulphate equivalent (FSE)/g dw) and antiradical capacities (9.37 mg of ascorbic acid equivalent (AAE)/g dw) were achieved for the alcoholic extract. Moreover, the alcoholic extract exhibited an efficient uptake of HOCl (IC50 = 1.97 µg/mL) and ROO• (0.34 µmol of Trolox equivalent (TE)/mg dw). A total of 34 phenolic compounds were identified in the extracts, with flavonols (isorhamnetin-3-O-rutinoside, quercetin-3-O-galactoside, and myricetin), flavanols (catechin), and phenolic acids (gallic and ellagic acids) being the principal classes. The intestinal cell viability assays attested that the alcoholic extract presented the lowest IC50 values (289.82 and 35.77 µg/mL for HT29-MTX and Caco-2), showing probable anticancer activity. These results emphasize the potential of D. crassifolium as a nutraceutical ingredient.

Endogenous Nodal switches Wnt interpretation from posteriorization to germ layer differentiation in geometrically constrained human pluripotent cells.

The Wnt pathway is essential for inducing the primitive streak, the precursor of the mesendoderm, as well as setting anterior-posterior coordinates. How Wnt coordinates these diverse activities remains incompletely understood. Here, we show that in Wnt-treated human pluripotent cells, endogenous Nodal signaling is a crucial switch between posteriorizing and primitive streak-including activities. While treatment with Wnt posteriorizes cells in standard culture, in micropatterned colonies, higher levels of endogenously induced Nodal signaling combine with exogenous Wnt to drive endoderm differentiation. Inhibition of Nodal signaling restores dose-dependent posteriorization by Wnt. In the absence of Nodal inhibition, micropatterned colonies undergo spontaneous, elaborate morphogenesis concomitant with endoderm differentiation even in the absence of added extracellular matrix proteins like Matrigel. Our study shows how Wnt and Nodal combinatorially coordinate germ layer differentiation with AP patterning and establishes a system to study a natural self-organizing morphogenetic event in in vitro culture.