Autoimmune diseases and immune-checkpoint inhibitors for cancer therapy: review of the literature and personalized risk-based prevention strategy.

Patients with cancer and with preexisting active autoimmune diseases (ADs) have been excluded from immunotherapy clinical trials because of concerns for high susceptibility to the development of severe adverse events resulting from exacerbation of their preexisting ADs. However, a growing body of evidence indicates that immune-checkpoint inhibitors (ICIs) may be safe and effective in this patient population. However, baseline corticosteroids and other nonselective immunosuppressants appear to negatively impact drug efficacy, whereas retrospective and case report data suggest that use of specific immunosuppressants may not have the same consequences. Therefore, we propose here a two-step strategy. First, to lower the risk of compromising ICI efficacy before their initiation, nonselective immunosuppressants could be replaced by specific selective immunosuppressant drugs following a short rotation phase. Subsequently, combining ICI with the selective immunosuppressant could prevent exacerbation of the AD. For the most common active ADs encountered in the context of cancer, we propose specific algorithms to optimize ICI therapy. These preventive strategies go beyond current practices and recommendations, and should be practiced in ICI-specialized clinics, as these require multidisciplinary teams with extensive knowledge in the field of clinical immunology and oncology. In addition, we challenge the exclusion from ICI therapy for patients with cancer and active ADs and propose the implementation of an international registry to study such novel strategies in a prospective fashion.

Root and canal morphology of maxillary premolar teeth in an Egyptian subpopulation using two classification systems: a cone beam computed tomography study.

AIM: To investigate the number of roots and root canal configurations using two coding systems and the root canal diverging and merging levels in extracted maxillary premolars in an Egyptian subpopulation using cone beam computed tomography (CBCT). METHODOLOGY: A total of 700 maxillary premolars were examined using CBCT in an Egyptian subpopulation. The number of roots was identified, and root canal configurations were classified according to Vertucci's classification and a new system for classifying root and canal morphology. In addition, the position where roots bifurcated and the levels where canals merged or diverged were identified. Fisher's exact test and independent t-test were used for statistical analysis, and the level of significance was set at 0.05 (P = 0.05). RESULTS: More than half of maxillary first premolars were double-rooted, and the majority of maxillary second premolars were single-rooted (P < 0.001). Most of the double-rooted samples had bifurcations in the middle of the root. According to the Vertucci classification, canal configuration type IV was the most common in both first and second maxillary premolars. According to the new system, the code 2 FP B1 P1 was the most common for maxillary first premolars, whilst 2 SP B1 P1 , 1 SP2 and 1 SP2-1 codes were the most common for maxillary second premolars. The three-canalled morphology in double- and three-rooted maxillary premolars had considerable variations. Root canal merging and diverging levels were comparable in both tooth types. CONCLUSION: Maxillary premolars in this Egyptian subpopulation had a wide range of root and canal anatomical variations. Clinicians should be aware of where canals merge and diverge to facilitate the treatment of all canals. The new system for classifying canal morphology describes the root and canal configurations in a more accurate and practical manner compared to the Vertucci classification.

Estimation of alpha exposure on CR-39 detector using a UV-VIS spectrophotometer.

This work is dedicated to study the possibility of using UV-VIS spectrophotometer, a non-invasive technique with a versatile applications that is being used to determine the optical properties of matter, to estimate the CR-39 exposure to alpha particles. CR-39 detectors were exposed to alpha particles from two different alpha sources: 241Am and radon gas. Tracks densities on CR-39 were determined using the traditional counting method by an optical microscope. The transmittances of CR-39 detectors were measured using UV-VIS spectroscopy in the range of 400-1000 nm, and results were correlated with measured tracks densities. The comparison showed that this method is effective in estimating exposure of CR-39 to alpha particles, and that its efficiency has increased by increasing the etching time of the detectors.

Unveiling Disparities: Exploring Differential Attainment in Postgraduate Training Within Clinical Oncology.

AIMS: Differential attainment (DA) in post graduate medical training is a recognised challenge and refers to unexplained variation across groups when split by several protected characteristics. The Royal College of Radiology is committed to fostering diversity, inclusivity, and equality with the goal of narrowing existing gaps and improving training outcomes. MATERIALS AND METHODS: This was a mixed methods study aiming to understand the causes of DA with view to helping the RCR develop strategies to address this. A cross-sectional survey was completed by 140 clinical oncology trainees in September 2022. Trainees and trainers (17 and 6 respectively) from across England, Scotland, Wales and Northern Ireland, took part in focus group and interviews from August to December 2022. Quantitative and qualitative data merged and interpreted. RESULT: Results showed international medical graduates and trainees from ethnic minority backgrounds were more likely to encounter challenges. The qualitative findings were used to identify three themes through which these problems could be framed. The trainee as a "space invader," the hidden curriculum of clinical oncology training and the process of navigating and tacking the training journey. CONCLUSION: Differential attainment is the product of a complex interplay between the trainee, trainer, and the training environment. Therefore, interventions must be tailored to different people and contexts. At a national level, the RCR can adopt general policies to promote this such as mentorship programmes, protected time for supervision and cultural competency training. Efficacy of proposed interventions for trial and their impact on DA should be evaluated to drive evidence-based changes.

Infective endocarditis surgery timing.

BACKGROUND: The optimum timing of surgical intervention in complicated left-sided infective endocarditis is not well established. Guidelines from various professional societies are not consistent regarding this. Data concerning this remains limited with conflicting results. METHODS: The national inpatient database (NIS) was used to identify patients hospitalized from the year 2016 to 2020 for infective endocarditis and who underwent surgical intervention for complicated left-sided endocarditis. Primary and secondary outcomes were analyzed in patients who had surgical intervention within 7 days (early surgery group) and after 7 days (late surgery group) of the index hospitalization. RESULTS: Primary outcome [composite of all-cause death, acute cerebrovascular accident (CVA), peripheral septic emboli, intracranial or intraspinal abscess, and cardiac arrest] was better in the early surgery group compared to the late surgery group 32.6 % vs 45.1 % [adjusted Odds ratio (aOR) = 0.59, 95 % Confidence interval (CI) = 0.52-0.67, P value â‰ª 0.001]. This was mainly due to better incidence of acute CVA (15.7 %vs 24 %, aOR = 0.59, CI = 0.50-0.69, P value â‰ª 0.001), peripheral septic emboli (18.5 % vs 27.3 %, aOR = 0.60, CI = 0.52-0.70, P value â‰ª 0.001) and intracranial/intraspinal abscess (1.2 % vs 4.74 %, aOR = 0.24, CI = 0.14-0.38, P value â‰ª 0.001). There is no difference in the incidence of all-cause in-hospital death (7.57 % vs 7.75 % aOR = 0.97, CI = 0.77-1.23, P value = 0.82) or cardiac arrest (3.4 % vs 3.54 %, aOR = 0.96, CI = 0.68-1.35, P value = 0.80). CONCLUSION: Surgical intervention within 7 days of index hospitalization is associated with a better incidence of acute CVA, peripheral septic emboli, and intracranial or intraspinal abscess but not with a better incidence of all-cause in-hospital death.

Plant-derived single domain COVID-19 antibodies.

Data show a decrease in the risk of hospitalization and death from COVID-19. To date, global vaccinations for SARS-CoV-2 protections are underway, but additional treatments are urgently needed to prevent and cure infection among naïve and even vaccinated people. Neutralizing monoclonal antibodies are very promising for prophylaxis and therapy of SARS-CoV-2 infections. However, traditional large-scale methods of producing such antibodies are slow, extremely expensive and possess a high risk of contamination with viruses, prions, oncogenic DNA and other pollutants. The present study is aimed at developing an approach of producing monoclonal antibodies (mAbs) against SARS-CoV-2 spike (S) protein in plant systems which offers unique advantages, such as the lack of human and animal pathogens or bacterial toxins, relatively low-cost manufacturing, and ease of production scale-up. We selected a single N-terminal domain functional camelid-derived heavy (H)-chain antibody fragments (VHH, AKA nanobodies) targeted to receptor binding domain of SARS-CoV-2 spike protein and developed methods of their rapid production using transgenic plants and plant cell suspensions. Isolated and purified plant-derived VHH antibodies were compared with mAbs produced in traditional mammalian and bacterial expression systems. It was found that plant generated VHH using the proposed methods of transformation and purification possess the ability to bind to SARS-CoV-2 spike protein comparable to that of monoclonal antibodies derived from bacterial and mammalian cell cultures. The results of the present studies confirm the visibility of producing monoclonal single-chain antibodies with a high ability to bind the targeted COVID-19 spike protein in plant systems within a relatively shorter time span and at a lower cost when compared with traditional methods. Moreover, similar plant biotechnology approaches can be used for producing monoclonal neutralizing antibodies against other types of viruses.

TAVR vs balloon aortic valvotomy for severe aortic stenosis and cardiogenic shock: An insight from the National Inpatient Sample database.

BACKGROUND: Severe Aortic stenosis (AS) complicated by cardiogenic shock (CS) represents a grave clinical condition with limited treatment options. Evidence from small observation studies favors that Transcatheter Aortic Valve Replacement (TAVR) might be a feasible option in these patients in contrast to emergent Balloon Aortic Valvuloplasty (BAV) which is associated with very high short and long-term mortality. METHODS: 11,405 hospitalizations with severe AS complicated by CS between 2016 and 2020 were identified using the National Inpatient Sample (NIS) Database, and patients were then stratified according to whether they received TAVR or BAV. Propensity-score matching was used to account for differences in the baseline characteristics. Primary and secondary outcomes were then compared between 3485 hospitalizations in direct TAVR group and with 3485 matched hospitalizations in the BAV group. The primary outcome was a composite of all-cause in-hospital death, acute cerebrovascular accident (CVA), and myocardial infarction (MI). Secondary outcomes and safety outcomes were also compared between the two groups. RESULTS: TAVR was associated with fewer primary outcomes events as compared to BAV {36.8 % vs 56.8 %, aOR (95%CI) = 0.38(0.30-0.47)}, due to fewer all-cause in-hospital deaths {17.8 % vs 38.9 %, aOR (95%CI) =0.34 (0.26-0.43)} and MI {12.3 % vs 32.4 %, aOR (95%CI) = 0.29 (0.22-0.39)}. TAVR was associated with higher rates of acute CVA {6.17 % vs 3.44 %, aOR (95%CI) = 1.84 (1.08-3.21)} and pacemaker implantation post procedure {11.9 % vs 6.03 %, aOR (95%CI) = 2.10 (1.41-3.18)}. CONCLUSION: Direct TAVR in shock and severe Aortic stenosis is a better strategy than rescue Balloon aortic valvotomy.

ESTIMATION OF SCATTERED NEUTRONS CONTRIBUTION IN A NEUTRON CALIBRATION BUNKER USING A MONTE CARLO SIMULATION.

The contribution of scattered neutrons is inevitable in neutron calibration facilities. This contribution complicates the measurements of neutron radiation, therefore, it should be estimated to correct the response of neutron probe instruments. In the present work, Monte Carlo simulation was performed for a neutron calibration bunker using the MCNP-4C code. This simulation aimed to calculate the contribution ratio of scattered neutrons to the neutron field. To simulate the neutron field, 241Am-Be neutron source defined in the ISO 8529-1 was used. The results of the simulation reported in this work were found to be consistent with those found experimentally in previous work. Additionally, the distribution of both the ambient dose equivalent rate and the contribution ratio of scattered neutrons in the bunker were mapped using this simulation.

Early Neonatal Death Possibly From a Rare Congenital Coronary Artery Anomaly.

We report a term female newborn who presented with bradycardia and weak respiratory efforts immediately after birth. Mother had an uneventful pregnancy and the infant was delivered by cesarean section secondary to arrest of labor. The infant did not respond to the neonatal resuscitation and was declared dead 32 minutes after birth. Autopsy findings include left coronary artery (LCA) ostium stenosis and moderate-to-severe chorioamnionitis on placental examination. An autopsy did not find any anatomic or histologic abnormalities in other organ systems that could be attributed to the cause of early neonatal death. To the best of our knowledge, ours is the third case reported in the literature on LCA ostium stenosis presenting immediately after delivery. Unfortunately, all the infants had a fatal outcome. Our case report emphasizes the importance of a meticulous autopsy examination, considering coronary artery anomalies, in case of early neonatal deaths.

Pediatric Cardiac Arrest Outcomes in the United States: A Nationwide Database Cohort Study.

Background Knowledge about the causes and outcomes of pediatric cardiac arrest in the emergency department is limited. The aim of our study was to evaluate the characteristics and outcomes of pediatric cardiac arrest in the emergency department (EDCA) and inpatient (IPCA) settings in the United States using a large database designed to provide nationwide estimates. Methods We performed a retrospective cohort study using the Nationwide Emergency Department Sample (NEDS), a database that includes both ED and inpatient encounters. The NEDS was analyzed for episodes of cardiac arrest between 2016-2018 in patients aged ≤18 years. Patients with cardiac arrest were identified using the International Classification of Diseases, 10th revision codes. Results A total of 15,348 pediatric cardiac arrest events with cardiopulmonary resuscitation were recorded, of which 13,239 had EDCA and 2,109 had IPCA. A lower survival rate of 19% was observed for EDCA compared to 40.4% for IPCA. While more than half of the EDCA events had no associated diagnoses, trauma (15.6%), respiratory failure (5%), asphyxiation (2.7%), acidosis (2.4%), and ventricular arrhythmia (1.4%) were associated with the remaining events. In comparison, the most frequently associated diagnoses for IPCA were respiratory failure (75.8%), acidosis (43.9%), acute kidney injury (27.2%), trauma (27.1%), and sepsis (22.5%).  Conclusions Survival rates for EDCA were less than half of that for IPCA. The low survival rates along with the distinctive characteristics of EDCA events suggest the need for further research in this area to identify remediable factors and improve survival.

Gadolinium-labeled affibody-XTEN recombinant vector for detection of HER2+ lesions of ovarian cancer lung metastasis using quantitative MRI.

Ovarian cancer has the highest mortality rate among all gynecologic malignancies. HER2+ ovarian cancer is a subtype that is aggressive and associated with metastasis to distant sites such as the lungs. Therefore, accurate biological characterization of metastatic lesions is vital as it helps physicians select the most effective treatment strategy. Functional imaging of ovarian cancer with PET/CT is routinely used in the clinic to detect metastatic disease and evaluate treatment response. However, this imaging method does not provide information regarding the presence or absence of cancer-specific cell surface biomarkers such as HER2. As a result, this method does not help physicians decide whether to choose immunotherapy to treat metastasis. To differentiate the HER2+ from HER2¯ lesions in ovarian cancer lung metastasis, AbX50C4:Gd vector composed of a HER2 targeting affibody and XTEN peptide was genetically engineered. It was then labeled with gadolinium (Gd) via a stable linker. The vector was characterized physicochemically and biologically to determine its purity, molecular weight, hydrodynamic size and surface charge, stability in serum, endotoxin levels, relaxivity and ability to target the HER2 antigen. Then, SCID mice were implanted with SKOV-3 (HER2+) and OVASC-1 (HER2¯) tumors in the lungs and injected with the Gd-labeled HER2 targeted AbX50C4:Gd vector. The mice were imaged using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), followed by R1-mapping and quantitative analysis of the images. Our data demonstrate that the developed HER2-targeted vector can differentiate HER2+ lung metastasis from HER2¯ lesions using DCE-MRI. The developed vector could potentially be used in conjunction with other imaging modalities to prescreen patients and identify candidates for immunotherapy while triaging those who may not be considered responsive.

Late-onset and long-lasting immune-related adverse events from immune checkpoint-inhibitors: An overlooked aspect in immunotherapy.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy but frequently cause immune-related adverse events (irAEs). Description of late-onset and duration of irAEs in the literature is often incomplete. METHODS: To investigate reporting and incidence of late-onset and long-lasting irAEs, we reviewed all registration trials leading to ICI's approval by the US FDA and/or EMA up to December 2019. We analysed real-world data from all lung cancer (LC) and melanoma (Mel) patients treated with approved ICIs at the University Hospital of Lausanne (CHUV) from 2011 to 2019. To account for the immortal time bias, we used a time-dependent analysis to assess the potential association between irAEs and overall survival (OS). RESULTS: Duration of irAEs and proportion of patients with ongoing toxicities at data cut-off were not specified in 56/62 (90%) publications of ICIs registration trials. In our real-world analysis, including 437 patients (217 LC, 220 Mel), 229 (52.4%) experienced at least one grade ≥2 toxicity, for a total of 318 reported irAEs, of which 112 (35.2%) were long-lasting (≥6 months) and about 40% were ongoing at a median follow-up of 369 days [194-695] or patient death. The cumulative probability of irAE onset from treatment initiation was 42.8%, 51.0% and 57.3% at 6, 12 and 24 months, respectively. The rate of ongoing toxicity from the time of first toxicity onset was 42.8%, 38.4% and 35.7% at 6, 12 and 24 months. Time-dependent analysis showed no significant association between the incidence of irAEs and OS in both cohorts (log Rank p = 0.67 and 0.19 for LC and Mel, respectively). CONCLUSIONS: Late-onset and long-lasting irAEs are underreported but common events during ICIs therapy. Time-dependent survival analysis is advocated to assess their impact on OS. Real-world evidence is warranted to fully capture and characterise late-onset and long-lasting irAEs in order to implement appropriate strategies for patient surveillance and follow-up.

Can the Pediatric Early Warning Score (PEWS) Predict Hospital Length of Stay?

BACKGROUND: Limited studies have evaluated the utility of scoring systems in the pediatric emergency department (PED) and no studies have evaluated their ability to predict hospital length of stay (LOS) and the usage of Observation units (OUs). OBJECTIVE: To evaluate the utility of the Pediatric Early Warning Score (PEWS) in predicting LOS in pediatric patients and thus anticipate admission to an OU versus the pediatric ward. METHODS: A retrospective study of pediatric inpatients (0 to 18 years) at an inner-city community hospital between January 2014 and December 2014. Patients with psychiatric illness, non-medical reasons for hospital stay, and those not discharged to 'home' were excluded. Demographic data, PEWS in the ED, and LOS for each patient were recorded and analyzed. RESULTS: A total of 719 patients were analyzed. PEWS range was 0 to 8. The mean LOS was 56.8 hours for patients with PEWS 0-1 compared to 62.7 hours for patients with PEWS ≥2 (p=0.02). There was a significant difference in PEWS for LOS ≤24 and ≤36 hours in comparison to those with LOS >24 hours and >36 hours, respectively (p<0.001). Overall, the PEWS correlated with LOS (r=0.11, p=0.002). Age correlated inversely with LOS (r=-0.16, p<0.001), without correlation to PEWS (r=-0.002, p= 0.96). CONCLUSIONS:  PEWS correlated weakly with LOS. A statistically significant lower PEWS was observed for patients who had short stays (both ≤24 and ≤36 hours) in comparison to those requiring longer inpatient care. Therefore, the PEWS is a useful tool to predict LOS and aid ED physicians to determine disposition, although further prospective studies in centers with OUs would better characterize its ability to suggest admission to an OU compared to the wards.

Viruses Causing Aseptic Meningitis: A Tertiary Medical Center Experience With a Multiplex PCR Assay.

Background: Central nervous system (CNS) infection is associated with high rates of morbidity and mortality, and despite advancements in molecular testing, aseptic meningitis remains challenging to diagnose. Aseptic meningitis cases are often underreported worldwide, which impacts the quality of patient care. Therefore, we aimed to assess the results of BioFire® FilmArray® meningitis/encephalitis (ME) PCR panel, clinical characteristics, and etiologies of aseptic meningitis patients. Methods: From January 2018 to January 2020, all pediatric and adult patients in a large tertiary medical center who underwent lumbar puncture and cerebrospinal fluid (CSF) testing by a ME multiplex PCR panel and who fit the aseptic meningitis definition were retrospectively reviewed. Results: Data were reviewed from 1,607 patients; 240 met the inclusion criteria (54.6% males; 68.8% <4 years of age). The rate of detected viral causes of aseptic meningitis was 40.4%; therefore, 59.6% of the patients remained with unidentified etiology. Among the identified viral meningitis, enterovirus and human herpesvirus 6 (HHV-6) were the most common (25 and 7.9%, respectively). The median length of hospital stay was 6 days, and it was longer in patients with unidentifiable aseptic meningitis (p < 0.0001). Conclusion: Aseptic meningitis is common among suspected meningitis patients, but most cases remained of unknown etiology. The most common identified viruses were enterovirus followed by HHV-6, and there is predominance in males and the pediatric age group. These results highlight that further research is needed to identify other etiologies and possible additional viral pathogens for aseptic meningitis in the current diagnostic methods.

Bioengineered adipose-derived stem cells for targeted enzyme-prodrug therapy of ovarian cancer intraperitoneal metastasis.

The objective of this study was to develop a stem cell-based system for targeted suicide gene therapy of recurrent, metastatic, and unresectable ovarian cancer. Malignant cells were obtained from the ascites of a patient with advanced recurrent epithelial ovarian cancer (named OVASC-1). Cancer cells were characterized to determine the percentages of drug-resistant ALDH+ cells, MDR-1/ABCG2 overexpressing cells, and cancer stem-like cells. The sensitivity and resistance of the OVASC-1 cells and spheroids to the metabolites of three different enzyme/prodrug systems were assessed, and the most effective one was selected. Adipose-derived stem cells (ASCs) were genetically engineered to express recombinant secretory human carboxylesterase-2 and nanoluciferase genes for simultaneous disease therapy and quantitative imaging. Bioluminescent imaging, magnetic resonance imaging and immuno/histochemistry results show that the engineered ASCs actively targeted and localized at both tumor stroma and necrotic regions. This created the unique opportunity to deliver drugs to not only tumor supporting cells in the stroma, but also to cancer stem-like cells in necrotic/hypoxic regions. The statistical analysis of intraperitoneal OVASC-1 tumor burden and survival rates in mice shows that the administration of the bioengineered ASCs in combination with irinotecan prodrug in the designed sequence and timeline eradicated all intraperitoneal tumors and provided survival benefits. In contrast, treatment of the drug-resistant OVASC-1 tumors with cisplatin/paclitaxel (standard-of-care) did not have any statistically significant benefit. The histopathology and hematology results do not show any toxicity to major peritoneal organs. Our toxicity data in combination with efficacy outcomes delineate a nonsurgical and targeted stem cell-based approach to overcoming drug resistance in recurrent metastatic ovarian cancer.

A novel chemotherapeutic protocol for peritoneal metastasis and inhibition of relapse in drug resistant ovarian cancer.

The majority of ovarian cancer patients are diagnosed in late stages of the disease, in which the tumor cells have leaked into the peritoneum and are present as tumorspheres. These tumorspheres are rich in cancer stem-like cells (CSCs), which are resistant to therapy and are a major source of relapse. The purpose of this research was to identify a safe therapeutic approach that could eradicate the peritoneal CSC-rich tumorspheres and inhibit relapse. Highly metastatic ascitic cells (OVASC-1) that are resistant to standard-of-care chemotherapy due to upregulation of MDR1 gene were obtained from a patient with ovarian carcinoma and recurrent disease. CSC-rich tumorspheres were generated, characterized, and treated with different chemotherapeutics. The most effective drug combination that could eradicate tumorspheres at nanomolar levels despite upregulation of MDR1 gene was identified. Luciferase-expressing OVASC-1 cells were implanted in the peritoneum of nude mice and treated with the identified drug combination. The progression of disease, response to therapy and recurrence were studied by quantitative imaging. Toxicity to abdominal tissues was studied by histopathology. Mice implanted with intraperitoneal (IP) OVASC-1 xenografts showed limited response to combination therapy with cisplatin/paclitaxel at the maximum tolerated dose. Despite overexpression of MDR1 on OVASC-1 cells, mice treated with our combination IP low-dose MMAE and SN-38 chemotherapy showed complete response without relapse. No signs of toxicity to abdominal tissues were observed. While MMAE and SN-38 are not administered as free drugs due to their high potency and potential for systemic toxicity, our low-dose localized therapy approach effectively restricted the cytotoxic effects to the tumor cells in the peritoneum. Consequently, maximum efficacy with minimal adverse effects was achieved. These remarkable results with IP low-dose combination chemotherapy encourage investigation into its potential clinical application as either first-line therapy or in cases of acquired resistance to cisplatin and paclitaxel.

Combined effect of retinoic acid and calcium on the in vitro differentiation of human adipose-derived stem cells to adipocytes.

CONTEXT: It has been shown that adipogenesis can be modulated by factors such as all-trans retinoic acid (ATRA) and calcium. OBJECTIVE: To determine, the combined effect of ATRA and calcium on the differentiation of human adipose-derived stem cells (hADSCs). METHODS: Mesenchymal stem cells (MSCs) were differentiated into the adipocytes by 0.5 and 1 µM of ATRA and 5 and 10 mM calcium separately or in combination. After MTS assay the differentiation of MSCs to adipocyte was evaluated, Oil Red O staining, GLUT4 concentration and gene expression of PPARG2, adiponectin, and GLUT4 were measured by Real-Time PCR. RESULTS: Except 10 mM calcium treated group, other groups and more significantly combination treatments could reduce all adipocyte markers compared to the control. CONCLUSION: These results suggest that ATRA and calcium together have significant inhibitory effect on adipogenesis that can be helpful for finding new mechanisms to prevent or control the adipogenesis.