Porous Polymer Structures with Tunable Mechanical Properties Using a Water Emulsion Ink.

Recently, the manufacturing of porous polydimethylsiloxane (PDMS) with engineered porosity has gained considerable interest due to its tunable material properties and diverse applications. An innovative approach to control the porosity of PDMS is to use transient liquid phase water to improve its mechanical properties, which has been explored in this work. Adjusting the ratios of deionized water to the PDMS precursor during blending and subsequent curing processes allows for controlled porosity, yielding water emulsion foam with tailored properties. The PDMS-to-water weight ratios were engineered ranging from 100:0 to 10:90, with the 65:35 specimen exhibiting the best mechanical properties with a Young's Modulus of 1.17 MPa, energy absorption of 0.33 MPa, and compressive strength of 3.50 MPa. This led to a porous sample exhibiting a 31.46% increase in the modulus of elasticity over a bulk PDMS sample. Dowsil SE 1700 was then added, improving the storage capabilities of the precursor. The optimal storage temperature was probed, with -60 °C resulting in great pore stability throughout a three-week duration. The possibility of using these water emulsion foams for paste extrusion additive manufacturing (AM) was also analyzed by implementing a rheological modifier, fumed silica. Fumed silica's impact on viscosity was examined, revealing that 9 wt% of silica demonstrates optimal rheological behaviors for AM, bearing a viscosity of 10,290 Pa·s while demonstrating shear-thinning and thixotropic behavior. This study suggests that water can be used as pore-formers for PDMS in conjunction with AM to produce engineered materials and structures for aerospace, medical, and defense industries as sensors, microfluidic devices, and lightweight structures.

New insights into the role of VKORC1 polymorphisms for optimal warfarin dose selection in Caribbean Hispanic patients through an external validation of a population PK/PD model.

Warfarin, an oral anticoagulant, has been used for decades to prevent thromboembolic events. The complex interplay between CYP2C9 and VKORC1 genotypes on warfarin PK and PD properties is not fully understood in special sub-groups of patients. This study aimed to externally validate a population pharmacokinetic/pharmacodynamic (PK/PD) model for the effect of warfarin on international normalized ratio (INR) and to evaluate optimal dosing strategies based on the selected covariates in Caribbean Hispanic patients. INR, and CYP2C9 and VKORC1 genotypes from 138 patients were used to develop a population PK/PD model in NONMEM. The structural definition of a previously published PD model for INR was implemented. A numerical evaluation of the parameter-covariate relationship was performed. Simulations were conducted to determine optimal dosing strategies for each genotype combinations, focusing on achieving therapeutic INR levels. Findings revealed elevated IC50 for G/G, G/A, and A/A VKORC1 haplotypes (11.76, 10.49, and 9.22 mg/L, respectively), in this population compared to previous reports. The model-guided dosing analysis recommended daily warfarin doses of 3-5 mg for most genotypes to maintain desired INR levels, although subjects with combination of CYP2C9 and VKORC1 genotypes * 2/* 2-, * 2/* 3- and * 2/* 5-A/A would require only 1 mg daily. This research underscores the potential of population PK/PD modeling to inform personalized warfarin dosing in populations typically underrepresented in clinical studies, potentially leading to improved treatment outcomes and patient safety. By integrating genetic factors and clinical data, this approach could pave the way for more effective and tailored anticoagulation therapy in diverse patient groups.

Differential effects of early life adversity on male and female rhesus macaque lifespan.

Early life adversity predicts shorter adult lifespan in several animal taxa. Yet, work on long-lived primate populations suggests the evolution of mechanisms that contribute to resiliency and long lives despite early life insults. Here, we tested associations between individual and cumulative early life adversity and lifespan on rhesus macaques at the Cayo Santiago Biological Field Station using 50 years of demographic data. We performed sex-specific survival analyses at different life stages to contrast short-term effects of adversity (i.e., infant survival) with long-term effects (i.e., adult survival). Female infants showed vulnerability to multiple adversities at birth, but affected females who survived to adulthood experienced a reduced risk later in life. In contrast, male infants showed vulnerability to a lower number of adversities at birth, but those who survived to adulthood were negatively affected by both early life individual and cumulative adversity. Our study shows profound immediate effects of insults  on female infant cohorts and suggests that affected female adults are more robust. In contrast, adult males who experienced harsh conditions early in life showed an increased mortality risk at older ages as expected from hypotheses within the life course perspective. Our analysis suggests sex-specific selection pressures on life histories and highlights the need for studies addressing the effects of early life adversity across multiple life stages.

Unknown QRS Morphology Change at Peak Exercise: To Stop or to Continue?

Electrocardiogram changes during stress tests are well standardized and understood. We present and explain a reversible QRS morphology change at peak exercise previously unreported. (Level of Difficulty: Intermediate.).

Burnout Among Service Providers for People Living with HIV: Factors Related to Coping and Resilience.

Individuals who provide services for people living with HIV (PLWH) face numerous work-related challenges, including psychosocial and structural factors affecting the quality of care that they provide. Little is known about the factors that relate to burnout among service providers for PLWH. The current study seeks to examine the factors associated with burnout and the role of resilience and coping in the context of burnout. Via convenience sampling, data was collected from 28 professionals (e.g., peer counselors, HIV testers, case managers/case workers, group facilitators, or social workers) serving PLWH in the USA. Participants completed quantitative measures on sociodemographics, organizational factors, discrimination, trauma, depression, and burnout. A sub-sample of 19 participants provided in-depth qualitative data via semi-structured interviews on burnout, coping, and resilience as a buffer against the effects of burnout. Thematic content analysis revealed themes on the factors related to burnout (e.g., discrimination, limited financial and housing resources, and COVID-19), rejuvenating factors, coping with burnout, and intervention strategies. Additionally, Pearson's product moment correlations revealed significant associations between mental health variables such as depressive and posttraumatic stress disorder symptomology with (a) discrimination and microaggressions and (b) burnout. The current study highlights challenges to providing HIV care, including structural barriers and discrimination that are doubly impactful to the professionals in this sample who share identities with the PLWH whom they serve. These findings may inform the development of an intervention targeting burnout among individuals providing services to PLWH and motivate change to remove structural barriers and improve quality of care for PLWH.

Gynecologic Conditions in a Cohort with Inflammatory Bowel Disease: A Descriptive Analysis.

OBJECTIVE: Past studies have demonstrated that women with inflammatory bowel disease (IBD) have a higher risk of gynecological conditions than do women without it. We aimed to characterize the gynecological histories of Hispanic Women living in Puerto Rico with IBD. METHODS: We identified women, aged 21 to 55 years, with a confirmed IBD diagnosis and receiving follow-up care from the University of Puerto Rico IBD clinics from 2017 through 2020. A questionnaire was administered to acquire sociodemographics, family history, past medical history, IBD diagnosis, and gynecologic aspects. RESULTS: One hundred eighty-six women were recruited. Fifty-three (28%) patients had ulcerative colitis, while 133 (72%) had Crohn's disease. Fifty-six percent of all the participants had a chronic illness in addition to than their IBD. Seventy-four out of 186 patients reported having had at least 1 late period within the last 12 months. Fifty-three (28%) described their period patterns as irregular. Thirty-nine (21%) of the patients reported having been vaccinated against human papillomavirus (HPV), and 8 (4%) had been infected by it. Nine out of 186 (5%) patients reported suffering from infertility. CONCLUSION: The results showed that our Hispanic patients (living in Puerto Rico) had a prevalence of irregular menstrual cycles that was similar to that observed in other populations. On the other hand, the presence of HPV, infertility, and cervical cancer were lower and the frequency of Papanicolaou smears performed higher than what has been seen in the continental United States, suggesting that this topic should be investigated in future studies.

Features and Long-Term Outcomes of Stage IV Melanoma Patients Achieving Complete Response Under Anti-PD-1-Based Immunotherapy.

BACKGROUND: Immune checkpoint inhibition (ICI) has changed the melanoma treatment spectrum. Few studies have examined the characteristics and long-term outcomes of patients achieving complete response (CR) under ICI. MATERIALS AND METHODS: We evaluated patients with unresectable stage IV melanoma treated with first-line ICI. The characteristics of those achieving CR were compared with those not achieving CR. Progression-free survival (PFS) and overall survival (OS) were assessed. Late-onset toxicities, response to second-line treatment, the prognostic value of clinicopathologic features, and blood markers were examined. RESULTS: A total of 265 patients were included; 41 (15.5%) achieved CR, while 224 (84.5%) had progressive disease, stable disease, or partial response. At the therapy start, those who had CR were more likely to be older than 65 years of age (p = 0.013), have a platelet-to-lymphocyte ratio below 213 (p = 0.036), and have lower lactate dehydrogenase levels (p = 0.008) than those not achieving a CR. For those who discontinued therapy after CR, the median follow-up time after CR was 56 months (interquartile range [IQR] 52-58) and the median time from CR to therapy end was 10 months (IQR 1-17). Five-year PFS after CR was 79% and 5-year OS was 83%. Most complete responders had a normalization of S100 at the time of CR (p < 0.001). In simple Cox regression analysis, age below 77 years at CR (p = 0.04) was associated with better prognosis after CR. Eight patients received second-line ICI; disease control was seen in 63%. Late immune-related toxicities occurred in 25% of patients, most being cutaneous immune-related toxicities. CONCLUSIONS: Response, according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, is, until now, the most important prognostic factor, and CR is a valid surrogate marker for long-term survival in patients treated with ICI. Our results highlight the importance of investigating the optimal therapy duration in complete responders.

Rhesus macaques compensate for reproductive delay following ecological adversity early in life.

Adversity early in life can shape the reproductive potential of individuals through negative effects on health and life span. However, long-lived populations with multiple reproductive events may present alternative life history strategies to optimize reproductive schedules and compensate for shorter life spans. Here, we quantify the effects of major hurricanes and density dependence as sources of early-life ecological adversity on Cayo Santiago rhesus macaque female reproduction and decompose their effects onto the mean age-specific fertility, reproductive pace, and lifetime reproductive success (LRS). Females experiencing major hurricanes exhibit a delayed reproductive debut but maintain the pace of reproduction past debut and show a higher mean fertility during prime reproductive ages, relative to unaffected females. Increasing density at birth is associated to a decrease in mean fertility and reproductive pace, but such association is absent at intermediate densities. When combined, our study reveals that hurricanes early in life predict a delay-overshoot pattern in mean age-specific fertility that supports the maintenance of LRS. In contrast to predictive adaptive response models of accelerated reproduction, this long-lived population presents a novel reproductive strategy where females who experience major natural disasters early in life ultimately overcome their initial reproductive penalty with no major negative fitness outcomes. Density presents a more complex relation with reproduction that suggests females experiencing a population regulated at intermediate densities early in life will escape density dependence and show optimized reproductive schedules. Our results support hypotheses about life history trade-offs in which adversity-affected females ensure their future reproductive potential by allocating more energy to growth or maintenance processes at younger adult ages.

N-Terminal Targeting of Regulator of G Protein Signaling Protein 2 for F-Box Only Protein 44-Mediated Proteasomal Degradation.

Regulator of G protein signaling (RGS) proteins are negative modulators of G protein signaling that have emerged as promising drug targets to improve specificity and reduce side effects of G protein-coupled receptor-related therapies. Several small molecule RGS protein inhibitors have been identified; however, enhancing RGS protein function is often more clinically desirable but presents a challenge. Low protein levels of RGS2 are associated with various pathologies, including hypertension and heart failure. For this reason, RGS2 is a prominent example wherein enhancing its function would be beneficial. RGS2 is rapidly ubiquitinated and proteasomally degraded, providing a point of intervention for small molecule RGS2-stabilizing compounds. We previously identified a novel cullin-RING E3 ligase utilizing F-box only protein 44 (FBXO44) as the substrate recognition component. Here, we demonstrate that RGS2 associates with FBXO44 through a stretch of residues in its N terminus. RGS2 contains four methionine residues close to the N terminus that can act as alternative translation initiation sites. The shorter translation initiation variants display reduced ubiquitination and proteasomal degradation as a result of lost association with FBXO44. In addition, we show that phosphorylation of Ser3 may be an additional mechanism to protect RGS2 from FBXO44-mediated proteasomal degradation. These findings contribute to elucidating mechanisms regulating steady state levels of RGS2 protein and will inform future studies to develop small molecule RGS2 stabilizers. These would serve as novel leads in pathologies associated with low RGS2 protein levels, such as hypertension, heart failure, and anxiety. SIGNIFICANCE STATEMENT: E3 ligases provide a novel point of intervention for therapeutic development, but progress is hindered by the lack of available information about specific E3-substrate pairs. Here, we provide molecular detail on the recognition of regulator of G protein signaling protein 2 (RGS2) by its E3 ligase, increasing the potential for rational design of small molecule RGS2 protein stabilizers. These would be clinically useful in pathologies associated with low RGS2 protein levels, such as hypertension, heart failure, and anxiety.

Genotype-driven pharmacokinetic simulations of warfarin levels in Puerto Ricans.

Objectives The inter-individual variability of warfarin dosing has been linked to genetic polymorphisms. This study was aimed at performing genotype-driven pharmacokinetic (PK) simulations to predict warfarin levels in Puerto Ricans. Methods Analysis of each individual dataset was performed by one-compartmental modeling using WinNonlin®v6.4. The k e of warfarin given a cytochrome P450 2C9 (CYP2C9) genotype ranged from 0.0189 to 0.0075 h-1. K a and V d parameters were taken from literature. Data from 128 subjects were divided into two groups (i.e., wild-types and carriers) and statistical analyses of PK parameters were performed by unpaired t-tests. Results In the carrier group (n=64), 53 subjects were single-carriers and 11 double-carriers (i.e., *2/*2, *2/*3, *2/*5, *3/*5, and *3/*8). The mean peak concentration (Cmax) was higher for wild-type (0.36±0.12 vs. 0.32±0.14 mg/L). Likewise, the average clearance (CL) parameter was faster among non-carriers (0.22±0.03 vs. 0.17±0.05 L/h; p=0.0001), with also lower area under the curve (AUC) when compared to carriers (20.43±6.97 vs. 24.78±11.26 h mg/L; p=0.025). Statistical analysis revealed a significant difference between groups with regard to AUC and CL, but not for Cmax. This can be explained by the variation of k e across different genotypes. Conclusions The results provided useful information for warfarin dosing predictions that take into consideration important individual PK and genotyping data.

Painful Sleep: Insomnia in Patients with Chronic Pain Syndrome and its Consequences.

Insomnia is a chronic condition that occurs a minimum of three times per week over a period of three or more subsequent months. There are multiple causes of insomnia, and even though it is considered a symptom, it can be associated with chronic illnesses. Chronic pain syndrome, which is defined as pain that persists for a period longer than 3 months, is one of several etiologies of insomnia. The prevalence of insomnia among chronic pain patients is greater in comparison with the general population (percentage or ratio). Chronic pain is common in patients with rheumatoid arthritis, spinal pain (such as chronic back pain) and fibromyalgia. The prevalence of in-somnia is also higher in cancer patients when compared to the general population. When the clinical history indicates a straightforward diagnosis of chronic pain syndrome, patients will complain of insomnia as part of their symptomatology. It is imperative to manage their underlying illness to alleviate their sleep disorder. Various medications may be used to relieve and even improve pain symptoms. Other than pharmacological interventions, non-pharmacological alternatives such as yoga, meditation, acupuncture, and psychotherapy can help improve the quality of life of these patients. The purpose of this article is to review the diagnosis and management of insomnia in chronic pain syndrome and its impact on the quality of life.

Genotype-driven pharmacokinetic simulations of warfarin levels in Puerto Ricans.

OBJECTIVES: The inter-individual variability of warfarin dosing has been linked to genetic polymorphisms. This study was aimed at performing genotype-driven pharmacokinetic (PK) simulations to predict warfarin levels in Puerto Ricans. METHODS: Analysis of each individual dataset was performed by one-compartmental modeling using WinNonlin®v6.4. The ke of warfarin given a cytochrome P450 2C9 (CYP2C9) genotype ranged from 0.0189 to 0.0075 h-1. Ka and Vd parameters were taken from literature. Data from 128 subjects were divided into two groups (i.e., wild-types and carriers) and statistical analyses of PK parameters were performed by unpaired t-tests. RESULTS: In the carrier group (n=64), 53 subjects were single-carriers and 11 double-carriers (i.e., *2/*2, *2/*3, *2/*5, *3/*5, and *3/*8). The mean peak concentration (Cmax) was higher for wild-type (0.36±0.12 vs. 0.32±0.14 mg/L). Likewise, the average clearance (CL) parameter was faster among non-carriers (0.22±0.03 vs. 0.17±0.05 L/h; p=0.0001), with also lower area under the curve (AUC) when compared to carriers (20.43±6.97 vs. 24.78±11.26 h mg/L; p=0.025). Statistical analysis revealed a significant difference between groups with regard to AUC and CL, but not for Cmax. This can be explained by the variation of ke across different genotypes. CONCLUSIONS: The results provided useful information for warfarin dosing predictions that take into consideration important individual PK and genotyping data.

The Cowpox Controversy: Memory and the Politics of Public Health in Cuba.

Vaccination played an important role in the formation of a national consciousness in Cuba, and vaccination's earliest promoters dominate nationalist narratives of medical achievement on the island. This article investigates the intense hostility exhibited by the creole medical elite toward a pivotal figure in the history of smallpox vaccination in Cuba, Spanish physician Dr. Vicente Ferrer (1823-83), the first in the Americas to mass produce smallpox vaccine using calf vaccinifiers. I argue that anger and mistrust of both Ferrer and his innovatory vaccine production technology originated in the relationship between medical politics and cultural identity in late nineteenth-century Cuba. By the late nineteenth century, smallpox vaccination was linked to glorified memories of a Cuban creole-led vaccination program and a disinterested medical profession. Both Ferrer and his private institution for the mass production of "cowpox" became associated with destructive changes in public health, challenging cultural narratives and regional power structures.

Optical imaging for breast cancer prescreening.

Breast cancer prescreening is carried out prior to the gold standard screening using X-ray mammography and/or ultrasound. Prescreening is typically carried out using clinical breast examination (CBE) or self-breast examinations (SBEs). Since CBE and SBE have high false-positive rates, there is a need for a low-cost, noninvasive, non-radiative, and portable imaging modality that can be used as a prescreening tool to complement CBE/SBE. This review focuses on the various hand-held optical imaging devices that have been developed and applied toward early-stage breast cancer detection or as a prescreening tool via phantom, in vivo, and breast cancer imaging studies. Apart from the various optical devices developed by different research groups, a wide-field fiber-free near-infrared optical scanner has been developed for transillumination-based breast imaging in our Optical Imaging Laboratory. Preliminary in vivo studies on normal breast tissues, with absorption-contrasted targets placed in the intramammary fold, detected targets as deep as 8.8 cm. Future work involves in vivo imaging studies on breast cancer subjects and comparison with the gold standard X-ray mammography approach.

The non-surgical management of a patient with Kostmann syndrome-associated periodontitis: a case report.

Kostmann syndrome is a rare, congenital immunological disorder caused by a mutation of the hematopoietic cell-specific LYN substrate 1-associated protein X1. These patients pose a unique challenge to the dental practitioner due to the severe oral infections that are often seen in this population. The patient described in this report is a 16-year-old female with Kostmann syndrome-associated periodontitis. The treatment consisted of scaling and root planing performed in conjunction with subgingival irrigation with povidone-iodine solution. This report details how Kostmann syndrome-associated periodontitis can be successfully treated and maintained long-term, using non-surgical treatment modalities and local antimicrobial therapy.

Dampened neural activity and abolition of epileptic-like activity in cortical slices by active ingredients of spices.

Active ingredients of spices (AIS) modulate neural response in the peripheral nervous system, mainly through interaction with TRP channel/receptors. The present study explores how different AIS modulate neural response in layer 5 pyramidal neurons of S1 neocortex. The AIS tested are agonists of TRPV1/3, TRPM8 or TRPA1. Our results demonstrate that capsaicin, eugenol, menthol, icilin and cinnamaldehyde, but not AITC dampen the generation of APs in a voltage- and time-dependent manner. This effect was further tested for the TRPM8 ligands in the presence of a TRPM8 blocker (BCTC) and on TRPM8 KO mice. The observable effect was still present. Finally, the influence of the selected AIS was tested on in vitro gabazine-induced seizures. Results coincide with the above observations: except for cinnamaldehyde, the same AIS were able to reduce the number, duration of the AP bursts and increase the concentration of gabazine needed to elicit them. In conclusion, our data suggests that some of these AIS can modulate glutamatergic neurons in the brain through a TRP-independent pathway, regardless of whether the neurons are stimulated intracellularly or by hyperactive microcircuitry.

Extracellular matrix domain formation as an indicator of chondrocyte dedifferentiation and hypertrophy.

Cartilage injury represents one of the most significant clinical conditions. Implantation of expanded autologous chondrocytes from noninjured compartments of the joint is a typical strategy for repairing cartilage. However, two-dimensional culture causes dedifferentiation of chondrocytes, making them functionally inferior for cartilage repair. We hypothesized that functional exclusion of dedifferentiated chondrocytes can be achieved by the selective mapping of collagen molecules deposited by chondrogenic cells in a three-dimensional environment. Freshly isolated and in vitro expanded human fetal or adult articular chondrocytes were cultured in a thermoreversible hydrogel at density of 1 × 10(7) cells/mL for 24 h. Chondrocytes were released from the gel, stained with antibodies against collagen type 2 (COL II) or COL I or COL X and sorted by fluorescence activated cell sorting. Imaging flow cytometry, immunohistochemistry, quantitative polymerase chain reaction, and glycosaminoglycan (GAG) assays were performed to evaluate the differences between COL II domain forming and COL II domain-negative cells. Freshly dissected periarticular chondrocytes robustly formed domains that consisted of the extracellular matrix surrounding cells in the hydrogel as a capsule clearly detectable by imaging flow cytometry (ImageStream) and confocal microscopy. These domains were almost exclusively formed by COL II. In contrast to that, a significant percentage of freshly isolated growth plate pre-hypertrophic and hyperdrophic chondrocytes deposited matrix domains positive for COL II, COL I, and COL X. The proportion of the cells producing COL II domains decreased with the increased passage of in vitro expanded periarticular fetal or adult articular chondrocytes. Sorted COL II domain forming cells deposited much higher levels of COL II and GAGs in pellet assays than COL II domain-negative cells. COL II domain forming cells expressed chondrogenic genes at higher levels than negative cells. We report a novel method that allows separation of functionally active chondrogenic cells, which deposit high levels of COL II from functionally inferior dedifferentiated cells or hypertrophic chondrocytes producing COL X. This approach may significantly improve current strategies used for cartilage repair.

Crestal approach for maxillary sinus augmentation in patients with ≤ 4 mm of residual alveolar bone.

PURPOSE: Less morbidity is the major advantage to a one-stage crestal approach to maxillary sinus elevation. However, the ability to ensure high primary implant stability in a severely atrophied ridge is of chief concern. The purpose of this study is to measure and compare the success rate of implants placed at the time of crestal approach sinus lift in patients with ≤ 4 mm of residual alveolar bone (RAB) and >4 mm of RAB. MATERIALS AND METHODS: In this three-site multicenter study, one hundred two patients, 53 males and 49 females, (23-89 years old; mean = 56.2) were evaluated. Three experienced surgeons (>15 years) performed the crestal approach sinus lift microsurgeries with simultaneous implant placement. At baseline and at the follow-up appointments, calibrated examiners measured radiographic interproximal bone level using ImageJ for Windows after calibration of the radiographs. References for the bone level measurements were the platform, first and second threads of the implants. Statistical analyses, using STATA version 12, stratified patients according to RAB height (group 1: RAB of ≤ 4 mm; n = 35 and group 2: RAB > 4 mm; n = 67), age, gender, and treatment center. RESULTS: The success rate was 100% for group 1 and 98.51% for group 2 at 6 to 100 months postprosthetic loading (mean = 29.7 months). The peri-implant bone loss averaged 0.55 mm (interquartile range [IQR] = 0.5 [0-1]) in group 1 and 0.07 mm (IQR = 0 [0-0]) in group 2. There was no statistically significant difference between the two groups. Clinical outcomes were independent of age, gender, and treatment center. CONCLUSIONS: The RAB height did not increase crestal bone loss or reduce the success rate of the implants and associated prostheses. The crestal approach should be considered a viable technique for use in patients with residual bone height of ≤ 4 mm and merits further evaluation.

Human developmental chondrogenesis as a basis for engineering chondrocytes from pluripotent stem cells.

Joint injury and osteoarthritis affect millions of people worldwide, but attempts to generate articular cartilage using adult stem/progenitor cells have been unsuccessful. We hypothesized that recapitulation of the human developmental chondrogenic program using pluripotent stem cells (PSCs) may represent a superior approach for cartilage restoration. Using laser-capture microdissection followed by microarray analysis, we first defined a surface phenotype (CD166(low/neg)CD146(low/neg)CD73(+)CD44(low)BMPR1B(+)) distinguishing the earliest cartilage committed cells (prechondrocytes) at 5-6 weeks of development. Functional studies confirmed these cells are chondrocyte progenitors. From 12 weeks, only the superficial layers of articular cartilage were enriched in cells with this progenitor phenotype. Isolation of cells with a similar immunophenotype from differentiating human PSCs revealed a population of CD166(low/neg)BMPR1B(+) putative cartilage-committed progenitors. Taken as a whole, these data define a developmental approach for the generation of highly purified functional human chondrocytes from PSCs that could enable substantial progress in cartilage tissue engineering.