Arthrofibrosis After Total Knee Arthroplasty: A Critical Analysis Review.

¼ Arthrofibrosis after total knee arthroplasty (TKA) is the new formation of excessive scar tissue that results in limited ROM, pain, and functional deficits.¼ The diagnosis of arthrofibrosis is based on the patient's history, clinical examination, absence of alternative diagnoses from diagnostic testing, and operative findings. Imaging is helpful in ruling out specific causes of stiffness after TKA. A biopsy is not indicated, and no biomarkers of arthrofibrosis exist.¼ Arthrofibrosis pathophysiology is multifactorial and related to aberrant activation and proliferation of myofibroblasts that primarily deposit type I collagen in response to a proinflammatory environment. Transforming growth factor-beta signaling is the best established pathway involved in arthrofibrosis after TKA.¼ Management includes both nonoperative and operative modalities. Physical therapy is most used while revision arthroplasty is typically reserved as a last resort. Additional investigation into specific pathophysiologic mechanisms can better inform targeted therapeutics.

Outcomes of a Multicenter 10-Year Review of Postinjection Endophthalmitis and Associated Systemic Medical Comorbidities.

Purpose: To investigate whether any systemic medical conditions may be associated with a higher risk for developing postinjection endophthalmitis. Methods: This case-control study is a retrospective review within the Emory Eye Center from 2009 to 2019 and The Cleveland Clinic Foundation from 2012 to 2019. Each case was matched in a 1:4 case-to-control ratio. The associations between medical comorbidities and endophthalmitis were explored using multivariable logistic regression models on the combined sample. Results: Sixty-six individuals were diagnosed with injection-associated endophthalmitis. Systemic immunocompromised status was found to be a risk factor associated with developing endophthalmitis with an adjusted odds ratio (aOR) of 3.17 (P = .009). Other conditions with increased risk approaching statistical significance included a history of pulmonary disease (aOR, 1.74; P = .08) and a history of smoking (aOR, 1.72; P = .06). Conclusions: This is the first report to our knowledge demonstrating that immunocompromised status is associated with an increased risk for developing postinjection endophthalmitis. While this study may be limited due to its retrospective nature, the result may nevertheless serve as a guidance for risk counseling. Future analysis using a large-scale database will be needed.

Management of a Massive Solitary Femoral Condyle Bone Cyst at the Site of Knee Osteoarthritis with a Synthetic Bone Graft and Primary Robotic-assisted Cementless Total Knee Arthroplasty: A Case Report.

Introduction: Subarticular cystic lesions, also known as geodes, present a challenge in the management of patients undergoing primary total knee arthroplasty (TKA). Although multiple treatment options are available for addressing these lesions, uncertainty persists regarding the optimal approach. Case Report: A 58-year-old man with a history of rheumatoid arthritis presented with several years of left knee pain. Evaluation showed severe left knee degenerative osteoarthritis complicated by the presence of a large lateral femoral condyle cyst. After failing conservative management, a robotic-assisted cementless cruciate-retaining TKA was indicated. The large bone cyst was managed with augmentation using synthetic bone grafting. 1 year postoperatively, he showed excellent clinical outcomes and radiographic evidence of osteointegration. Conclusion: This case highlights the value of robotic-assisted technology to plan and execute bone grafting of a large femoral cystic lesion while performing TKA with primary components. A computed tomography-imaged robotic TKA offers the potential benefit of screening bone cysts and thus planning a surgical approach in which bone preservation can be maximized.

Revision Total Hip Arthroplasty Using a Tibial Cone and Impaction Grafting for Severe Femoral Bone Loss: A Case Report.

CASE: An 84-year-old woman presented 6 years after revision total hip arthroplasty (rTHA) with worsening hip pain and a Paprosky classification IIIB femoral defect. rTHA was performed using a proximal femur replacement. Given her osteoporosis and poor bone stock, a tibial cone and impaction grafting (IG) were used for megaprosthesis fixation. At the 33-month follow-up, the patient was pain-free and radiographs demonstrated a well-fixed implant. CONCLUSION: In the setting of massive defects of poor-quality bone, novel use of a tibial cone and IG can be implemented to achieve implant fixation and maximize patient outcomes.

Robotic-Assisted Patellofemoral Arthroplasties Following Failed Treatment for Trochlear Dysplasia and Patellar Instability: A Case Report.

Introduction: Indications for patellofemoral arthroplasty (PFA) remain under debate, with many surgeons favoring total knee arthroplasty (TKA) even in patients with limited degeneration in the tibiofemoral compartments. Case Report: A 30-year-old man with a history of bilateral patellar instability treated in youth with multiple surgeries presented with 8+ months of recurrent bilateral knee pain. Evaluation showed bilateral severe patellofemoral arthritis with preserved medial and lateral compartments. Bilateral sequential robotic-assisted PFAs (RA-PFA) were offered as a precise approach to reconstructing patellofemoral biomechanics while minimizing bone resection to avoid compromising potential future TKA. Four months after his latest surgery, he returned to a physically demanding job, and he remains active and pain free at 1 year postoperatively. Conclusion: RA-PFA can provide less invasive, accurate, and individualized treatment for younger patients with severe disease without compromising future conversion to TKA.

Vitreoretinal lymphoma with central nervous system involvement in a patient with sarcoidosis: a case report.

PURPOSE: To describe a case of primary vitreoretinal lymphoma with central nervous system involvement in a patient with sarcoidosis. METHODS: Single, retrospective chart review. PATIENT: A 59-year-old male with sarcoidosis. RESULTS: The patient presented with a 3-year history of bilateral panuveitis thought secondary to his sarcoidosis diagnosed 11 years prior. Shortly before presentation, the patient demonstrated recurrent uveitis with a lack of response to aggressive immunosuppression therapy. At presentation, ocular exam showed significant anterior and posterior inflammation. Fluorescein angiography demonstrated hyperfluorescence of the optic nerve with late and small vessel leakage in the right eye. The patient also described a two-month history of memory and word-finding deficits. An inflammatory and infectious disease work-up was unremarkable. A brain MRI showed multiple enhancing periventricular lesions with vasogenic edema, while a lumbar puncture was negative for malignant cells. A diagnostic pars plana vitrectomy confirmed a diagnosis of large B-cell lymphoma. CONCLUSION: Sarcoidosis and vitreoretinal lymphoma are known masqueraders. Recurrent inflammation typical of sarcoid uveitis may mask a more sinister diagnosis such as vitreoretinal lymphoma. Furthermore, sarcoid uveitis treatment with corticosteroids may transiently improve symptoms but further delay a timely diagnosis of primary vitreoretinal lymphoma.

Robotic assisted transabdominal preperitoneal approach for repair of Morgagni hernia in elderly female.

Morgagni hernia's are relatively rare congenital diaphragmatic hernias that are typically described in pediatric populations. It is rare for patients to present with symptoms related to this defect in adulthood. Several techniques have been successfully utilized. This case report offers the successful utilization of the robotic assisted transabdominal preperitoneal approach (r-TAPP) for primary repair of a symptomatic Morgagni hernia in a high risk patient. To date, there are few publications describing the r-TAPP technique for Morgagni hernia repair, and no publications were found in the context described in our case. From this, we are able to provide increasing evidence of the efficacy and deployment of r-TAPP in age variable presentation of this pathology.

Lifestyle of health workers from pediatric units during the pandemic: a cross-sectional study / Estilo de vida de profissionais de saúde pediátricos na pandemia: estudo transversal

ABSTRACT This study aimed to assess the lifestyle of health workers in pediatric units of Bahia, Brazil, by comparing the total and domain scores of the Fantastic Lifestyle Questionnaire (FLQ) according to sex, age group, and employment profile. This cross-sectional study included 407 health workers from four pediatric health units in Bahia. The FLQ and a sociodemographic questionnaire were answered via Google Forms during the COVID-19 pandemic. Men scored significantly lower than women in the 'tobacco and toxics' (p = 0.046) and 'alcohol' (p < 0.001) domains but higher in the 'sleep, seat belt, stress, and safe sex' domain (p = 0.01). Younger health workers (18 to 34 years old) scored significantly higher than older workers (35 to 64 years old) in the 'tobacco and toxics' domain (p = 0.03). Direct healthcare workers (e.g., nurses and doctors) scored significantly higher than indirect healthcare workers (e.g., administrators) in the 'tobacco and toxics' domain (p = 0.04). Despite the COVID-19 pandemic, the lifestyle of most workers was classified as very good (56.02%). Our findings indicate changes in the lifestyle of health workers, especially concerning the use of tobacco, alcohol, and conditions related to sleep, stress, safe sex, and traffic safety behaviors. Future studies are recommended to understand better the determinants and conditioning factors of tobacco use by health workers and design targeted public health initiatives.

RESUMO O objetivo deste estudo foi avaliar o estilo de vida dos profissionais de saúde de unidades pediátricas da Bahia, Brasil, comparando o escore total e o escore de cada domínio do Questionário de Estilo de Vida Fantástico com sexo, faixa etária e perfil profissional. Participaram 407 profissionais de saúde de quatro unidades de saúde pediátricas, neste estudo transversal. O questionário Fantástico e um questionário sociodemográfico foram respondidos por meio de formulário do Google durante a pandemia de COVID-19. Os homens obtiveram significativamente pontuações mais baixas que as mulheres nos domínios 'tabaco e tóxicos' (p=0,046) e 'álcool' (p<0,001), e mais altas no domínio 'sono, cinto de segurança, estresse e sexo seguro' (p=0,01). Os profissionais de saúde mais jovens (18 a 34 anos) alcançaram pontuações significativamente superiores aos mais velhos (35 a 64 anos) no domínio 'tabaco e tóxicos' (p=0,03). Os profissionais de saúde de assistência direta (por exemplo, enfermeiros e médicos) obtiveram pontuações superiores aos profissionais de assistência indireta (por exemplo, administradores) no domínio 'tabaco e tóxicos' (p = 0,04). Apesar da pandemia de COVID-19, o estilo de vida da maioria dos trabalhadores foi classificado como muito bom (56,02%). Nossos achados alertam para mudanças no estilo de vida dos profissionais, principalmente quanto ao uso de tabaco, álcool, condições relacionadas ao sono, estresse, sexo seguro e comportamentos de segurança no trânsito. Estudos futuros são recomendados para entender melhor os determinantes e condicionantes do uso do tabaco pelos profissionais de saúde, permitindo o direcionamento de ações no contexto da saúde pública.

Vaccine-induced immune thrombotic thrombocytopenia after COVID-19 vaccination: Description of a series of 39 cases in Brazil.

OBJECTIVE: Describe a case series of vaccine-induced immune thrombotic thrombocytopenia (VITT) after COVID-19 vaccination in Brazil that included ChAdOx1 nCoV-19, Ad26.COV2.S and BNT162b2 vaccines, describing their clinical and laboratory characteristics. METHODOLOGY: Descriptive case series study using Bio-Manguinhos/Fiocruz/AstraZeneca Brazil and National Immunization Program/Ministry of Health (NIP/MoH) data on COVID-19 AEFI surveillance. We obtained patient-level data from pharmacovigilance for AEFI surveillance and used both the NIP/MoH and Bio-Manguinhos/Fiocruz pharmacovigilance databases to create the study database. Thirty-nine cases of suspect VITT were included, 36 after ChAdOx1 nCoV-19, one after BNT162b2 and two after Ad26.COV2.S vaccine. All cases were based on meeting the Brighton Collaboration criteria for VITT. The primary outcomes were clinical and laboratory features, site of thrombosis, and anti-PF4 ELISA, when available. RESULTS: Thirty-nine cases met the criteria, 38 of which were classified as level 1 and one as level 3 according to Brighton Collaboration. Most cases had the central nervous system (CNS) as the main site of thrombosis (21/39) and happened after the vaccine first dose (34/39). The median age of the cases was 41 years old (23 to 86 yo). Most of the cases (61.5%) occurred in women. The median interval between vaccination and onset of symptoms was 8 days (0-37 days). The platelet count and D-dimer count had median values of 34,000/µL and 19,235 µg FEU/L, respectively. The ELISA anti-PF4 antibody was positive in 18 samples. The overall mortality rate was 51% and was higher in cases of CNS thrombosis with intracerebral bleeding. CONCLUSION: Our case series shows that Brazilian VITT cases have similar clinical and laboratory profiles as demonstrated in the literature. Brazil has administered more than 300 million doses of COVID-19 vaccines (more than 110 million from ChAdOx1 nCoV-19). VITT seems to be a very rare but serious adverse event following COVID-19 immunization, especially adenoviral vector immunization.

Patient-Reported Complications after Intravitreal Injection and Their Predictive Factors.

PURPOSE: The intravitreal injection (IVI) of pharmacologic agents is the most commonly performed ocular procedure and is associated with a host of complications. Most IVI-related complications data are derived from randomized controlled clinical trials, which report a high adverse event rate. The nature of these protocol-driven trials limit their applicability to the diverse circumstances seen in routine clinical practice. The goal of this study was to determine the prevalence of patient-reported IVI-related complications, their risk factors, and the manner in which patients sought treatment at a tertiary eye care center. DESIGN: Retrospective, institutional review board-approved study. PARTICIPANTS: Forty-four thousand seven hundred thirty-four injections in 5318 unique patients at the Cleveland Clinic Cole Eye Institute from 2012 through 2016. METHODS: Intravitreal injection. MAIN OUTCOME MEASURES: Complication occurrence within 15 days of injection. RESULTS: From 2012 through 2016, a total of 44734 injections were performed in 5318 unique patients. Overall, complication rates were low, representing 1.9% of all injections, with 1031 unique complications in 685 patients (12.9%). The most common minor complications, or those not requiring intervention, were irritation (n = 312) and subconjunctival hemorrhage (n = 284). The most common serious complications, or those requiring intervention, were corneal abrasion (n = 46) and iritis (n = 31). Most complications (66%) were managed adequately by a telephone or Epic (Epic Systems Corp., Verona, WI) electronic message encounter only. Importantly, no injection protocol parameter, such as type of anesthesia, preparation, or post-injection medication, increased the risk of a complication. However, a patient's gender, age, number of previous injections, and provider strongly influenced the risk of patient-reported complications. CONCLUSIONS: Overall, complication rates seen in routine clinical practice were low compared with clinical trial reporting. Providers should feel confident in the safety and administration of IVI during times when follow-up office visits and resources may be limited. When performing an IVI, factors such as a patient's gender, age, number of previous injections, and provider must be taken into account to ensure the best possible outcomes.

Unmasking of infectious retinitis and intraocular lymphoma in patients after uneventful dropless cataract surgery.

In this case series, 3 unique cases of severe immune-mediated pathologies (primary ocular lymphoma, toxoplasmosis chorioretinitis, and syphilitic retinitis) after dropless cataract surgery with intraocular steroid injection are reported. Patient immune status and subsequent local immunosuppression after dropless cataract surgery played roles in the worsening of these pathologies. This report demonstrates the need for vigilance when administering immunosuppressive agents locally during cataract surgery.

Hickam's Dictum: Pseudoxanthoma elasticum and Usher syndrome in a single patient.

BACKGROUND: To report the case of a patient with two distinct genetic systemic diseases - pseudoxanthoma elasticum (PXE) and Usher syndrome - confirmed by genetic testing. MATERIALS AND METHODS: Single Retrospective Case Report. RESULTS: A 36-year-old woman presented with acute central vision loss of the left eye (OS). Fundus exam revealed choroidal neovascularization OS in the setting of angioid streaks secondary to an underlying diagnosis of PXE. Unexpectedly, she also exhibited peripheral bony spicules with significant visual field constriction. Physical exam revealed skin papules on her neck and hearing loss. The presence of angioid streaks and skin findings was compatible with PXE; the etiology of her pigmentary retinopathy and hearing loss was elucidated using genetic testing. The patient was found to be compound heterozygous for pathogenic variants in both the ABCC6 and USH2A genes, confirming the diagnosis of two rare disorders in a single patient. CONCLUSIONS: PXE and Usher syndrome are rare systemic disorders that cause distinctive retinal abnormalities. This report highlights the importance of genetic testing in diagnosing uncommon hereditary retinal disorders and outlines the progression of disease over 6 years.

Initial development of biosimilar immune checkpoint blockers using HEK293 cells.

Antibodies that block interaction of immune checkpoint receptors with its ligands have revolutionized the treatment of several cancers. Despite the success of this approach, the high cost has been restricted the use of this class of drugs. In this context, the development of biosimilar can be an important strategy for reducing prices and expanding access after patent has been dropped. Here, we evaluated the use of HEK293 cells for transient expression of an immune checkpoint-blocking antibody as a first step for biosimilar development. Antibody light and heavy chain genes were cloned into pCI-neo vector and transiently expressed in HEK293 cells. The culture supernatant was then subjected to protein A affinity chromatography, which allowed to obtain the antibody with high homogeneity. For physicochemical comparability, biosimilar antibody and reference drug were analyzed by SDS-PAGE, isoelectric focusing, circular dichroism and fluorescence spectroscopy. The results indicated that the both antibodies have a high degree of structural similarity. Lastly, the biosimilar antibody binding capacity to target receptor was shown to be similar to reference product in ELISA and flow cytometry assays. These data demonstrate that the HEK293 system can be used as an important tool for candidate selection and early development of biosimilar antibodies.

Preparing a Single Cell Suspension from Zebrafish Retinal Tissue for Flow Cytometric Cell Sorting of Müller Glia.

Preparation of a single cell suspension from solid tissue is vital for a successful flow cytometry experiment. We report a detailed and reproducible method to produce a quality cell suspension from the zebrafish retina. Zebrafish retinas, especially their Müller glia cells, are of particular interest for their inherent regenerative capacity, making them a useful model for regenerative medicine and cell therapy research. Here, we detail a papain-based dissociation that is gentle enough to keep cells intact, but strong enough to disrupt cell-cell and cell-matrix interactions to yield a cell suspension that produces clean and reliable flow cytometric cell sorting results. This procedure consistently results in over 90% viability and three populations of cells based on GFP expression. The dissociation procedure described herein has been optimized for the collection of Müller glia from Tg(apoe:gfp) zebrafish retinas; however, the overall process may be applicable to other cell types in the fish retina, additional flow cytometric techniques, or preparing cell suspensions from similar tissues. © 2019 International Society for Advancement of Cytometry.

Sample seal-and-drop device and methodology for high temperature oxide melt solution calorimetric measurements of PuO2.

Thermodynamic properties of refractory materials, such as standard enthalpy of formation, heat content, and enthalpy of reaction, can be measured by high temperature calorimetry. In such experiments, a small sample pellet is dropped from room temperature into a calorimeter operating at high temperature (often 700 °C) with or without a molten salt solvent present in an inert crucible in the calorimeter chamber. However, for hazardous (radioactive, toxic, etc.) and/or air-sensitive (hygroscopic, sensitive to oxygen, pyrophoric, etc.) samples, it is necessary to utilize a sealed device to encapsulate and isolate the samples, crucibles, and solvent under a controlled atmosphere in order to prevent the materials from reactions and/or protect the personnel from hazardous exposure during the calorimetric experiments. We have developed a sample seal-and-drop device (calorimetric dropper) that can be readily installed onto the dropping tube of a calorimeter such as the Setaram AlexSYS Calvet-type high temperature calorimeter to fulfill two functions: (i) load hazardous or air-sensitive samples in an air-tight, sealed container and (ii) drop the samples into the calorimeter chamber using an "off-then-on" mechanism. As a case study, we used the calorimetric dropper for measurements of the enthalpy of drop solution of PuO2 in molten sodium molybdate (3Na2O·4MoO3) solvent at 700 °C. The obtained enthalpy of -52.21 ± 3.68 kJ/mol is consistent with the energetic systematics of other actinide oxides (UO2, ThO2, and NpO2). This capability has thus laid the foundation for thermodynamic studies of other Pu-bearing phases in the future.

Heterogeneity of cultured melanocyte elongation and proliferation factor in bilateral diffuse uveal melanocytic proliferation.

A patient with bilateral diffuse uveal melanocytic proliferation (BDUMP) associated with endometrial cancer was treated with plasmapheresis, but failed therapy with progressive serous retinal detachment. We collected plasma before and after plasmapheresis therapy. Our goal was to determine if the cultured melanocyte elongation and proliferation (CMEP) factor and hepatocyte growth factor (HGF) was present in the IgG enriched fraction and understand why our patient failed plasmapheresis therapy. Melanocytes were cultured for 3-5 days in the presence of control medium, unfractionated pre-plasmapheresis BDUMP medium, IgG enriched or IgG depleted BDUMP medium, or unfractionated post-plasmapheresis BDUMP medium. Subretinal fluid was collected from patients with BDUMP and control retinal detachments and analyzed by electropheresis with immunoblotting. Medium with unfractionated BDUMP plasma stimulated melanocyte growth 1.4-1.5 fold compared to control medium on days 3-5 (p < 0.001 for all). Both IgG enriched and IgG depleted BDUMP medium mildly increased melanocyte growth 1.3 fold (p < 0.05 for enriched, p < 0.01 for depleted) compared to control. In comparison, unfractionated BDUMP medium caused a 1.7-fold increase in melanocyte growth, which was significantly more than the enriched (p < 0.01) and depleted (p < 0.05) fractions. Pre-plasmapheresis and post-plasmapheresis unfractionated BDUMP medium equally stimulated melanocyte growth 1.7-fold (p < 0.05) compared to control. HGF was present in IgG depleted, pre-plasmapheresis, and post-plasmapheresis samples, but absent in the IgG enriched fraction. There was no enrichment of IgG in the subretinal fluid from eyes with BDUMP. In conclusion, CMEP factor is not concentrated in the IgG enriched plasma fraction in our patient who failed plasmapheresis therapy. HGF levels have no correlation with melanocyte growth. Because plasmapheresis preferentially removes immunoglobulins from the plasma, our patient responded poorly to plasmapheresis treatment with worsening retinal detachment.

Animal models of radiation retinopathy - From teletherapy to brachytherapy.

Radiation retinopathy is a serious vision-impairing complication of radiation therapy used to treat ocular tumors. Characterized by retinal vasculopathy and subsequent retinal damage, the first sign of radiation retinopathy is the preferential loss of vascular endothelial cells. Ensuing ischemia leads to retinal degradation and late stage neovascularization. Despite the established disease progression, the pathophysiology and cellular mechanisms contributing to radiation retinopathy remain unclear. Clinical experience and basic research for other retinal vasculopathies, such as diabetic retinopathy and retinopathy of prematurity, can inform our understanding of radiation retinopathy; however, the literature investigating the fundamental mechanisms in radiation retinopathy is limited. Treatment trials have shown modest success but, ultimately, fail to address the cellular events that initiate radiation retinopathy. Animal models of radiation retinopathy could provide means to identify effective therapies. Here, we review the literature for all animal models of radiation retinopathy, summarize anatomical highlights pertaining to animal models, identify additional physiological factors to consider when investigating radiation retinopathy, and explore the use of clinically relevant tests for studying in vivo models of radiation retinopathy. We encourage further investigation into the mechanistic characterization of radiation retinopathy in the hope of discovering novel treatments.

Anticoagulation in a patient with antiphospholipid syndrome and a mechanical heart valve: a case study.

: A case report of a patient with antiphospholipid syndrome (APS) with positive lupus anticoagulant and a mechanical mitral valve replacement (MVR) who presented with a thrombosis and difficult-to-control INRs. Current literature on anticoagulation options for patients who present with these conditions as well as alternate laboratory assays are reviewed. APS can present a unique complexity and challenge to appropriate anticoagulation on warfarin. Although there are emerging data regarding the use of novel oral anticoagulants to treat this condition, they do not justify their use in a patient with APS and an MVR because of a current lack of evidence. CFX testing may be used to calibrate INRs when there is a concern for false readings because of lupus anticoagulant interaction with INR assays.

ROCK inhibitor primes human induced pluripotent stem cells to selectively differentiate towards mesendodermal lineage via epithelial-mesenchymal transition-like modulation.

Robust control of human induced pluripotent stem cell (hIPSC) differentiation is essential to realize its patient-tailored therapeutic potential. Here, we demonstrate a novel application of Y-27632, a small molecule Rho-associated protein kinase (ROCK) inhibitor, to significantly influence the differentiation of hIPSCs in a lineage-specific manner. The application of Y-27632 to hIPSCs resulted in a decrease in actin bundling and disruption of colony formation in a concentration and time-dependent manner. Such changes in cell and colony morphology were associated with decreased expression of E-cadherin, a cell-cell junctional protein, proportional to the increased exposure to Y-27632. Interestingly, gene and protein expression of pluripotency markers such as NANOG and OCT4 were not downregulated by an exposure to Y-27632 up to 36h. Simultaneously, epithelial-to-mesenchymal (EMT) transition markers were upregulated with an exposure to Y-27632. These EMT-like changes in the cells with longer exposure to Y-27632 resulted in a significant increase in the subsequent differentiation efficiency towards mesendodermal lineage. In contrast, an inhibitory effect was observed when cells were subjected to ectodermal differentiation after prolonged exposure to Y-27632. Collectively, these results present a novel method for priming hIPSCs to modulate their differentiation potential with a simple application of Y-27632.