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In this study, the cationic monomer [2-(acryloyloxy)ethyl]trimethylammonium chloride solution (AETAC) and vinyl imidazole (VI) were used with the free radical polymerization technique, which is a simple and rapid synthesis method, to synthesize p(AETAC-co-VI) hydrogels. To increase the density of cationic charge on the hydrogel, it underwent the protonation process with HCl. The obtained p(AETAC-co-VI)/Q hydrogel was modified with Au nanoparticles to increase bactericidal effect to obtain the AuNPs/p(AETAC-co-VI)/Q nanocomposite hydrogel. The morphology and chemical structure of the hydrogels were characterized with SEM and FTIR. Additionally, the swelling capabilities were tested in different pH media. XRD and TEM confirmed the formation of the nanocomposite hydrogel. The antibacterial activity of the hydrogels was tested against E. coli and S. aureus, and controlled release implementations were completed with sodium diclofenac (NaDc) drug. The NaDc drug release profiles of the hydrogels were researched using the Korsmeyer-Peppas model at 37 degrees C in different simulated buffer (pH 6.0, 7.2, and 8.0) solutions. It was found that both the hydrogel and nanocomposite hydrogel followed non-Fickian diffusion mechanisms as free release mechanism. Here, the maximum drug release efficacy was found to be 97%, and drug release was more rapid in basic media when release media were compared. The AuNPs/p(AETAC-co-VI)/Q nanocomposite hydrogels produced in this study with advanced antibacterial features were suitable for recommendation as good carriers for in vitro release of NaDc drugs in areas like the biomedical and pharmaceutical industries.

Objective: Non-Hodgkin's lymphomas (NHLs) are the result of malign proliferation of lymphoid cells. According to the morphological, immunological and genetic characteristics of childhood NHLs, they are classified as Burkitt lymphoma (BL), Lymphoblastic lymphoma (LL), diffuse large B-cell lymphoma (DLBCL) and anaplastic large cell lymphoma (ALCL). Anaplastic large cell lymphoma is a distinct form of non-Hodgkin lymphoma (NHL) which accounts for 15% of all childhood lymphomas. We report a girl presented with a breast mass and diagnosed with systemic ALCL. Case: A 14-year-old girl was referred to our hospital with without a painless mass in the left breast. Physical examination, it was seen two painless mass was found in the left breast. Also, a 2x2 cm, painless lymphadenopathy was found in the left axilla. She had no systemic symptoms In laboratory tests; hemoglobin, white blood cell count, platelet count, liver and kidney function tests, LDH, and uric acid levels were normal. In the imaging and metastasis screenings made to the patient; ultrasound and computed tomography (CT) showed two masses breast region. A large number of lymphadenopathies were detected in the left axillary, which surrounded the paraaortic, the paracaval, and the celiac truncus. She was found to have a hypermetabolic two masses in the breast (SUVmax=33.05) and lymphadenopathies (SUVmax=27.04) in the left axillary, paraaortic, the paracaval, and the celiac truncus on Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) scan. Excisional biopsy of the tumor mass in the breast was done and immunohistochemical analysis showed CD30 and anaplastic lymphoma kinase (ALK) positive ALCL. The patient was diagnosed with stage III anaplastic large cell lymphoma with systemic involvement and she began chemotherapeutic treatment, according to the NHL BFM 1995 protocol. Bone marrow aspirate was normal, and no malignancy was observed in the cerebrospinal fluid. After V-phase, AM block, and BM block treatments evaluation were performed with ¹⁸F-FDG PET/CT according to protocol. In ¹⁸F-FDG PET/CT, it was seen that the lymph nodes in the abdominal and the small mass in the breast were completely retracted, and another lymph nodes had no detected. These results showed that the response to the treatment was complete and the patient's chemotherapy was completed by continuing with the protocol. ¹⁸F-FDG PET/CT taken after the completion of chemotherapy revealed no evidence of mass or lymph node. The patient's controls continue smoothly. Conclusions: Anaplastic large cell lymphoma should also be considered in the differential diagnosis of children presented with a breast mass. Treatment procedures should be planned according to the involvement site and spread of the disease.

In this study, hydroxyethyl starch (HES)-based hydrogels, hydroxyethyl starch/p(sodium acrylate) (HES/p(NaAAc)), hydroxyethyl starch/p(3-(acrylamidopropyl) trimethyl ammonium chloride) (HES/p(APTMACl)) and hydroxyethyl starch/p(acrylamide) (HES/p(AAm)) were synthesized with redox polymerization. The structural, morphological, and water absorption characterization of the synthesized hydrogels was investigated. HES-based hydrogels, containing anionic, cationic and neutral functional groups, were used for adsorption of methyl violet (MV) as a model cationic dye and methyl orange (MO) as a model anionic dye from aqueous media. HES/p(APTMACl) and HES/p(NaAAc) hydrogels had maximum adsorption values for MO and MV dyes of 238.1 mg/g and 185.2 mg/g. The isotherm and kinetic parameters for both dye adsorptions were determined. The adsorption isotherm and kinetic data were compatible with the Langmuir isotherm and pseudo-first-order kinetic models.

This study used biocompatible and biodegradable hydroxyethyl starch (HES), 2-hydroxyethyl methacrylate (HEMA) and N-vinyle-2-pyrrolidone (NVP) monomers for hydrogel synthesis with the aim of use as a drug carrier system. As a result of the synthesis reactions using the redox polymerization technique, hydrogels were produced in both film and cylindrical form. The morphological characterization and structural characterization of hydrogels were performed using scanning electron microscope (SEM) and Fourier transform infrared spectroscopy (FT-IR), respectively. In addition, swelling characterizations of hydrogels to be used for drug release in various media were examined. The release properties of sodium diclofenac (NaDc) and trimethoprim (TMP) loaded into hydrogels produced in order to use as drug carrier material for controlled drug release were examined in media with pH = 1.2 and 7. It was determined that the hydrogels performed controlled release according to the type of drug and the pH values of the medium. Drug release mechanisms deviated from Fickian mode according to determined drug release rate constants, diffusion exponent (n) and regression values at different pH values. In addition, antibacterial properties of drug-loaded hydrogels against B. subtilus, S. aureus and E. coli were investigated.

In this study, N-tert-butylmaleimic acid was designed for the first time and synthesized by reaction of maleic anhydride with tert-butylamine and evaluated as a new functional monomer for preparation of new pH-responsive hydrogels. Its structure was verified with FTIR, 1H and 13C NMR. A new pH- and temperature-responsive hydrogel p(TBMAC-co-NIPAM), based on TBMAC and NIPAM, was successfully prepared via free-radical copolymerization technique in an aqueous solution. The chemical and structural properties of the hydrogels were identified by FTIR and SEM. The swelling properties of these hydrogels were systematically investigated according to various parameters such as time, temperature, pH and salt effects, and the results show that they are strongly influenced by the content of TBMAC and exhibit strong pH, temperature and salinity sensitivity. In addition, swelling kinetics and water diffusion mechanisms in hydrogels were discussed. In addition, in vitro drug release studies were performed in simulated gastric, isotonic serum and intestinal fluid at two different temperatures (23 and 37 °C) by taking R6G as a model drug. Drug loading results were investigated with various isotherm models such as Langmuir, Freundlich, Temkin and Dubinin-Radushkevich. Various kinetic models such as zero-order, first-order, Higuchi model and Korsmeyer-Peppas models were applied to determine the drug release mechanism. The results indicated that drug release involves non-Fickian transport mechanism. These results suggest that this new pH- and thermo-responsive hydrogel may be used to improve sustained release of drugs.

Vogt, Bruno/0000-0002-1548-6387; Dufek, Stephanie/0000-0002-6323-6673; Liu, Lili/0000-0002-2622-9669; Paczek, Leszek/0000-0003-0160-3009; Cui, Zhao/0000-0002-5837-1926; amoroso, antonio/0000-0002-9437-9407; Rosen, Raphael/0000-0003-1025-1965; Loos, Ruth/0000-0002-8532-5087; coenen, marieke/0000-0001-8796-2031; zanoni, francesca/0000-0001-9567-6713; CUCCA, Francesco/0000-0002-7414-1995; Ars, Elisabet/0000-0002-4118-4358; Hamilton, Patrick/0000-0001-6703-3745 WOS:000563559600001 PubMed ID: 32231244 Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 x 10(-12)) and IRF4 (rs9405192, OR = 1.29, P = 1.4 x 10(-14)), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 x 10(-103)) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 x 10(-49)), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 x 10(-93)), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 x 10(-23) and OR = 3.39, P = 5.2 x 10(-82), respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk. National Institute for Diabetes and Digestive Kidney Diseases (NIDDK) [RC2-DK116690, R01-DK105124, R01-DK097053, R01-DK108805]; National Institute on Minority Health and Health Disparities (NIMHD)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Minority Health & Health Disparities (NIMHD) [R01-MD009223]; Charles Woodson Clinical Research Fund; Nephrotic Syndrome Study Network Consortium (NEPTUNE) [U54-DK-083912]; Columbia University, Columbia Glomerular Center; Office of Rare Diseases Research, National Center for Advancing Translational Sciences (NCATS); National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); University of MichiganUniversity of Michigan System; NephCure Kidney International; Halpin Foundation; National Key Research and Development Program of China [2016YFC0904100]; Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81621092]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81870460, 81570598]; Science and Technology Innovation Action Plan of Shanghai Science and Technology Committee [17441902200]; Shanghai Municipal Education Commission, Gaofeng, Clinical Medicine Grant [20152207]; Shanghai Jiao Tong University School of Medicine, Multi-Center Clinical Research Project [DLY201510]; International Cooperation and Exchange Projects of Shanghai Science and Technology Committee [14430721000]; Outstanding Young Scholar Award [81622009]; Shanghai Health and Family Planning Committee Hundred Talents Program [2018BR37]; Seoul National University Hospital Human Biobank, a member of the National Biobank of Korea - Ministry of Health and Welfare, Republic of Korea; MRCMedical Research Council UK (MRC) [MR/J010847/1]; Manchester Academic Health Science Centre [MAHSC 186/200]; Greater Manchester Local Clinical Research Network; Kidneys for Life Charity; David and Elaine Potter Charitable Foundation; St Peter's Trust for Kidney, Bladder and Prostate Research; Kids Kidney Research UKKidney Research UK (KRUK); Kidney Research UKKidney Research UK (KRUK); Italian Ministry of Health grantMinistry of Health, Italy [GR-2011-02350438]; Department of Excellence Grant 2018-2022 - Italian Ministry of Education for the Department of Medical Sciences of the University of Turin; Columbia University; Poznan University of Medical Sciences, Poland; German Ministry of Education and Research (BMBF)Federal Ministry of Education & Research (BMBF) [01ER0804]; KfH Foundation for Preventive Medicine; Bayer Pharma AG; German Research FoundationGerman Research Foundation (DFG) [CRC 1140, KO 3598/3-1, CRC 992]; European Research CouncilEuropean Research Council (ERC) [ERC-2012ADG_2012-0314, 322947]; 7th Framework Programme of the European Community contract [2012-305608]; National Research Agency grant MNaims [ANR-17-CE17-0012-01]; Dutch Kidney Foundation [OW08, KJPB11.021]; National Human Genome Research Institute (NHGRI)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI); NIMHD We are grateful to all study participants across multiple nephrology centres worldwide for their contributions to this work. This work was supported by the following institutions, grants and funding agencies in the US: Columbia University, Columbia Glomerular Center, National Institute for Diabetes and Digestive Kidney Diseases (NIDDK) grants RC2-DK116690 (K.K., M.K.), R01-DK105124 (K.K.), R01-DK097053 (L.H.B., M.K.), R01-DK108805 (M.G.S.), and National Institute on Minority Health and Health Disparities (NIMHD) grant R01-MD009223 (K.K., A.G.G., A.B.). M.G.S. is additionally supported by the Charles Woodson Clinical Research Fund. The Nephrotic Syndrome Study Network Consortium (NEPTUNE), U54-DK-083912, is a part of the National Institutes of Health (NIH) Rare Disease Clinical Research Network (RDCRN), supported through a collaboration between the Office of Rare Diseases Research, National Center for Advancing Translational Sciences (NCATS) and the National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK). Additional funding and/or programmatic support for this project has also been provided by the University of Michigan, the NephCure Kidney International and the Halpin Foundation. The recruitment and analysis of the Chinese cohorts were supported by the National Key Research and Development Program of China (2016YFC0904100), Natural Science Foundation of China to the Innovation Research Group (81621092), National Natural Science Foundation of China (No. 81870460, 81570598), Science and Technology Innovation Action Plan of Shanghai Science and Technology Committee (No.17441902200), Shanghai Municipal Education Commission, Gaofeng, Clinical Medicine Grant (No.20152207), Shanghai Jiao Tong University School of Medicine, Multi-Center Clinical Research Project (No.DLY201510), International Cooperation and Exchange Projects of Shanghai Science and Technology Committee (No.14430721000), the Outstanding Young Scholar Award for Zhao Cui (No.81622009), and Shanghai Health and Family Planning Committee Hundred Talents Program for Jingyuan Xie (No.2018BR37). The recruitment of the Korean cohort was supported by the Seoul National University Hospital Human Biobank, a member of the National Biobank of Korea, financed by the Ministry of Health and Welfare, Republic of Korea. P.B. and P.H. acknowledge financial support from MRC project "Autoimmunity in Membranous Nephropathy", grant MR/J010847/1 which funded the sample collection from MN patients across the UK. P.B., P.H. and S.H. acknowledge support from Manchester Academic Health Science Centre (MAHSC 186/200), the Greater Manchester Local Clinical Research Network and Kidneys for Life Charity for supporting research in MN in Manchester. We are grateful to the MENTOR study (clinical trials no. NCT01180036), for contributing blood samples of trial participants. The UK cohort was supported in part by grants from the David and Elaine Potter Charitable Foundation (to S.H.P. and R.K.), St Peter's Trust for Kidney, Bladder and Prostate Research (to D.B., H.C.S., S.H.P. and R.K.), Kids Kidney Research UK and Kidney Research UK (to D.B. and R.K.). The Italian cohorts were supported by the Italian Ministry of Health grant GR-2011-02350438 (G.Z., S.G.) and the Department of Excellence Grant 2018-2022 funded by the Italian Ministry of Education for the Department of Medical Sciences of the University of Turin (A.A.).; The recruitment of Polish cases was sponsored by the Polish Kidney Genetics Network (POLYGENES), a collaborative effort between Columbia University and Poznan University of Medical Sciences, Poland. The full list of POLYGENES collaborators can be found in the Supplementary Materials. The GCKD (German Chronic Kidney Disease) study was funded by grants from the German Ministry of Education and Research (BMBF, No. 01ER0804) and the KfH Foundation for Preventive Medicine, with genotyping supported by Bayer Pharma AG. The list of GCKD investigators can be found in the Supplementary Materials. The work of M.W. and A.K. was funded by the CRC 1140 Initiative and by KO 3598/3-1 and CRC 992 (A.K.) of the German Research Foundation. The work of E.H. and R.A.K.S. was funded by the CRC 1192 from the German Research Foundation (Projects B1 and C1). P.R. is a recipient of European Research Council ERC-2012ADG_2012-0314 grant 322947, 7th Framework Programme of the European Community contract 2012-305608 (European Consortium for High-Throughput Research in Rare Kidney Diseases), and the National Research Agency grant MNaims (ANR-17-CE17-0012-01). The Dutch studies were supported by grants from the Dutch Kidney Foundation to JMH and JFW (Nierstichting Nederland grant OW08 and grant KJPB11.021). We would like to thank the Population Architecture Using Genomics and Epidemiology (PAGE) consortium, funded by the National Human Genome Research Institute (NHGRI) with co-funding from the NIMHD, for providing population controls for this study. For full acknowledgment of the PAGE consortium, please see Supplementary Materials. The funding sources were not involved in the study design, collection, analysis, and interpretation of data, writing of the report, or in the decision to submit the paper for publication.

BackgroundT cell responses are at the core of checkpoint inhibitor success in treating cancer; however, generating targeted antigen presentation to stimulate T cell responses remains challenging. Here, we take advantage of the natural process of eryptosis by professional antigen presenting cells (APCs) to drive antigen presentation and T cell activation in human and mouse models. Through the delivery of tumor antigen and adjuvant to red blood cells (RBCs) using the Cell Squeeze® platform, we generate activating antigen carriers (AACs) for use in tumor-specific cancer vaccines.MethodsFollowing intravenous AAC administration, we measured clearance kinetics of AACs and characterized the site and cell type of AAC uptake. We investigated upregulation of activation markers on phagocytes that engulf AACs, and the effect of priming and boosting on endogenous T cell responses. To determine the ability of AACs to control implanted tumors, we measured tumor growth rates in mice therapeutically treated with AACs. Tumor growth of AAC-treated mice in combination with a chemotherapy treatment was also assessed. Additionally, the in vitro uptake of adjuvant loaded human AACs and resultant maturation of monocyte-derived dendritic cells (MoDCs) was measured to qualify adjuvant delivery. Peptide antigen delivery to human AACs was measured with flow cytometry and fluorescence microscopy.ResultsSqueezing effectively loads AACs with antigen and adjuvant and leads to exposure of phosphatidylserine on the AAC membrane. When administered into a mouse, mouse AACs were cleared from circulation within one hour and were engulfed by professional phagocytes in both the spleen and liver. In vivo, AACs induced upregulation of maturation markers on endogenous dendritic cells (DCs) and macrophages. Therapeutic AACs administration significantly slowed growth of the HPV-associated tumor, TC-1, and extended survival of treated animals. These anti-tumor responses correlated with >500-fold increase in antigen-specific CD8+ tumor-infiltrating lymphocytes compared to untreated mice. Boosting enhanced endogenous T cell responses and enhanced the efficacy of low dose vaccinations in a tumor model. Combination with early (days 7 and 9) or late (days 17 and 24) treatment with a chemotherapeutic agent cleared tumors in treated animals. In an in vitro human system, the intracellular delivery of peptide antigen and adjuvant to human AACs induced MoDC maturation and stimulated E7-specific CD8+ T cell responses.ConclusionsAACs loaded with antigen and adjuvant can effectively drive antigen presentation and prime a potent anti-tumor response in mice. These preclinical data support the further study of SQZ AACs as an immunotherapy for cancer treatment.Ethics ApprovalAll methods were performed in accordance with the relevant guidelines and regulations. Animal studies were approved by the Institutional Animal Care and Use Committee (IACUC) at SQZ Biotechnologies, using the recommendations from the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and the Office of Laboratory Animal Welfare. All activities were also conducted in accordance with Public Health Service (PHS) Policy on Humane Use and Care of Laboratory Animals.

Disinfection can be accomplished by adding external chemical agents to kill harmful microorganisms or by removing them using membranes. However, most chemicals are toxic for humans and animals if it is consuming above a certain concentration. Likewise, membranes have fouling problems. The aim of this study is to investigate the effect of diode laser, which is an environmentally friendly application, on pathogenic microorganisms such as Escherichia coli (ATCC 10536), Staphylococcus aureus (ATCC 6538) and Candida albicans. To reveal the effect of diode laser on aforementioned, various parameters have been studied on how diode laser type, laser irradiation time, laser power density, laser penetration efficiency, and biofilm inhibition effect on microorganisms. As a result of the study, it was observed that the blue laser was more effective than red and green lasers, and the inhibition rates for 15 min at 0.36 W/cm2 laser power density were 65.9%> 34.52%> 43.63% for S. aureus, E. coli and C. albicans respectively. After 30 min of blue laser irradiation, the microbial growth inhibitions were found as 85.39%, 41.18%, and 54.55% for S. aureus, E. coli and C. albicans, respectively. The highest biofilm inhibition was as 94.61% when S. aureus cells exposed to blue laser irradiation for 60 min. The microbial growth kinetics on three microorganisms were tested by using at 0.54 W/cm2 laser power density for 28 h and there were not observed any microbial development in microbial cultures. Moreover, blue laser irradiation was successfully disinfected wastewater and natural milk at 0.54 W/cm2 laser power density for 30, 60, 120, 180, and 240 min.

Aims: The current study aimed to evaluate the efficacy, side effects of radiotherapy and factors influencing treatment outcome in patients received radiotherapy for cerebral meningiomas. Methods and Material: In the last two decades, a total of 35 patients with cerebral meningioma who received radiotherapy in our clinic were evaluated statistically in terms of survival, toxicity and prognostic factors. The records of patients diagnosed with cerebral meningioma who underwent postoperative radiotherapy were retrospectively analyzed. Statistical analysis used: Statistical comparisons were made using IBM SPSS v24.0. Kaplan-Meier method was used to compare survival times. Results: Five of the patients had grade I meningioma showing recurrence, 18 were grade II meningioma and 12 were grade III meningioma. Patients were treated with 54 or 60 Gy adjuvant radiotherapy with 2 Gy daily fractions according to histopathological grade and operation type. Three and five-year overall survival rates were 56% and 40%, respectively and median overall survival was 36 months. Progression was observed in 15 of the 35 patients included in the study. Three and five-year progression-free survival (PFS) rates of the patients were 56% and 50%, respectively. There was a statistically significant correlation between histopathological grade and overall survival among patients. However; no statistical difference found in overall survival of patients in terms of tumor location, operation type and age. Conclusions: In the treatment of cerebral meningiomas, changes in radiotherapy dose and field designs can be predicted according to the tumor grade and operation type. In addition, it is thought that large scale studies are needed to determine prognostic factors more meticulously.

Recently, Human Immunodeficiency Virus (HIV) infection has become a chronic infection that can be effectively managed by early diagnosis, regular follow-up and antiretroviral therapy. With the newly diagnosed cases each year, a cumulatively increasing number of patients become HIV-infected. HIV infection and AIDS are often diagnosed with comorbidities such as opportunistic infections or malignancies that are caused by immunosuppression. However, in individuals with risky sexual behaviors and / or appropriate clinical findings, despite an irrelevant chief complaint or presentation without AIDS-defining infections, suspicion of HIV infection is very important for the early detection of the disease. In this article, we aimed to present a case of acute HIV infection mimicking acute sinusitis in a 35-year-old male patient.

Acute graft-versus-host disease is a frequent complication associated with allogeneic hematopoietic stem cell transplantation. Patients that become refractory to initial steroid treatment have a poor prognosis. apceth-201 consists of human allogeneic mesenchymal stromal cells, engineered by lentiviral transduction to express the protease inhibitor alpha-1 antitrypsin, to augment the anti-inflammatory potential of the mesenchymal stromal cells. We show that apceth-201 mesenchymal stromal cells efficiently suppress T cell proliferation and polarize macrophages to an anti-inflammatory M2 type, in vitro. To assess the in vivo efficacy of apceth-201, it was tested in two different mouse models of acute graft-versus-host disease. Control animals in a humanized model succumbed quickly to disease, whereas median survival was doubled in apceth-201-treated animals. The product was also tested in a graft-versus-host disease model system that closely mimics haploidentical hematopoietic stem cell transplantation, an approach that is now being evaluated for use in the clinic. Control animals succumbed quickly to disease, whereas treatment with apceth-201 resulted in long-term survival of 57% of the animals. Within 25 days after the second injection, clinical scores returned to baseline in responding animals, indicating complete resolution of graft-versus-host disease. These promising data have led to planning of a phase I study using apceth-201.

Turkish olive cultivar known as “Halhalı” that is locally grown in Mardin (Derik) province, situated in the southeast Anatolia, was used for virgin olive oil (VOO) production. Halhalı olive was processed in the “Mobile Olive Oil Processing Unit” (TEM Oliomio 500-2GV, Italy) designed as the first mobile olive mill in Turkey. Some chemical and physical properties (colour, UV absorbance values, free fatty acid content, peroxide value, phenolic and tocopherol profiles) were determined and monitored during one year of storing in the dark at room temperature once in every three months. Results showed that up to the eighth month of storage, free fatty acid content, peroxide and UV-absorption values (K232 and K232 values) did not exceed the limits reported by International Olive Council (IOC) and olive oils were categorized as Extra Virgin Olive Oil (EVOO). Colour changed from green to yellow and UV absorbance values altered during storage. Total phenol and vitamin E (α- tocopherol) contents decreased by 18% and 16.38%, respectively. Luteolin and apigenin were the most abundant phenolics and their contents decreased up to 22% and 28% during storing, respectively.

Objectives: The aim of this study is to compare the annual SJR and to evaluate the other parameters that show the scientific effect of journals in terms of open access (OA) or subscription access (SA) in the field of obstetrics and gynecology according to the SCImago database. Material and methods: This study was conducted between September-December 2019 at Near East University. The SCImago Journal & Country Rank database was used to collect information about the journals. We evaluated and compared the changes in the one-year SJR (SCImago Journal Rank) and journal impact factor (JIF) of OA and SA journals. Results: Data from 183 scientific journals in the field of obstetrics and gynecology from the period between 1999 and 2018 were evaluated, where 140 of these journals were SA and 43 were OA. The average SJR of OA journals in 1999 was 0.17, while it was 0.38 for SA journals. In 2018, these values were 0.31 and 0.78 for OA and SA journals, respectively. In the comparison of JIF, the average of the OA journals in 1999 was 0.09, while it was 0.66 for SA journals. In 2018, these values were 0.80 and 1.93 for OA and SA journals, respectively. Conclusions: Access to information has become easier due to technological developments and this will continue to affect the access policies of journals. Despite the disadvantages of predator journals, the rise of OA journals in terms of number and quality is likely to continue.

The pandemic of SARS-CoV-2, known as COVID-19, has continued to show its effect all over the world. The clinical course of the disease in solid-organ transplant recipients is a matter of concern. Lung transplant recipients also demonstrate special features because the graft encounters the COVID-19 pathogen directly as a result of inhalation, and the lungs are the most important organs affected by the disease. We shared the development process of acute rejection followed by rapid progression of chronic lung allograft dysfunction after COVID-19 in a recipient who was followed-up in the fifth year after lung transplant.

Background: To investigate the results of internal limiting membrane (ILM) peeling in patients with resistant diabetic macular edema (DME). Methods: In this randomized, controlled and prospective clinical study, the patients with resistant DME due to proliferative diabetic retinopathy were divided into two groups. Both groups underwent 23 gauge pars plana vitrectomy (PPV). Additionally ILM peeling was performed only to the cases in Group 2. During follow-ups, complete ophthalmological examinations, optical coherence tomography and fundus fluorescein angiography were performed. After PPV, intravitreal dexamethasone implant injection was performed for DME treatment when necessary. The patients were followed for 1 year. Results: A total of 40 eyes of 37 patients were included in the study. The average age was 57.5 ± 5.4 and 56.9 ± 5.8 years, and the ratio of male:female was 9:11 and 6:14 in Group 1 and Group 2, respectively (p >0.05). The improvement level in BCVA was more evident especially in the first and third months postoperatively in both groups (p Conclusion:PPV is beneficial in the management of resistant DME, and ILM peeling seems to be useful for macular function and may accelerate improvement in visual acuity.

Background: Seasonal agricultural workers group is one of the most disadvantageous groups of working life in Turkey same as many other countries. We aimed to determine the status of cardiovascular disease risk factors among migrant seasonal agricultural workers (MSAW) and to compare obtained data with local residents. Methods: This study cross-sectional study was conducted among MSAW in Eskisehir, Turkey and closest town residents in 2015 during agricultural season. These 455 MSAW were living in camps composed of 20 or more tents. Local residents sample composed of 532 local residents were reached at their houses by using random sampling method with data acquired from health organization records. Both groups were subjected to same questionnaire. Results: The prevalence of overweight/obesity among MSAW women was 40.5%, hypertension 19.9%, diabetes 4.9% and hypercholesterolemia 6.5%. These prevalences were 68.0%, 38.6%, 13.9% and 20.8% respectively among local residents. The prevalence of smoking risk among local residents was 1.5 times more than MSAW. In addition, the prevalence of overweight/obese risk was 4 times more; hypertension risk 1.8 times more, diabetes risk 3.8 times more and hypercholesterolemia risk 2.7 times more among local residents than MSAW (P

We aimed to explore factors for optimizing antimicrobial treatment in emergency departments. A single-day point prevalence survey was conducted on January 18, 2020, in 53 referral/tertiary hospitals in 22 countries. 1957 (17%) of 11557 patients presenting to EDs had infections. The mean qSOFA score was 0.37 +/- 0.74. Sepsis (qSOFA >= 2) was recorded in 218 (11.1%) patients. The mean qSOFA score was significantly higher in low-middle (1.48 +/- 0.963) compared to upper-middle (0.17 +/- 0.482) and high-income (0.36 +/- 0.714) countries ( P < 0.001). Eight (3.7%) patients with sepsis were treated as outpatients. The most common diagnoses were upper-respiratory (n = 877, 43.3%), lower-respiratory (n = 316, 16.1%), and lower-urinary (n = 201, 10.3%) infections. 1085 (55.4%) patients received antibiotics. The most-commonly used antibiotics were beta-lactam (BL) and BL inhibitors (n = 307, 15.7%), third-generation cephalosporins (n = 251, 12.8%), and quinolones (n = 204, 10.5%). Irrational antibiotic use and inappropriate hospitalization decisions seemed possible. Patients were more septic in countries with limited resources. Hence, a better organizational scheme is required.

International audience; Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects.

Objective The purpose of this study was to examine the diagnostic performance of real-time tissue elastography in detecting lymph node involvement in skin cancers. Methodology We retrospectively analyzed B-mode sonography and real-time elastography (RTE) images of 70 lymph nodes from 34 patients diagnosed with squamous cell carcinoma (SCC) or malignant melanoma (MM). In the B-mode examination, the appearance or loss of the hilar architecture in the lymph node, contour lobulation, and the presence of focal cortical thickening were evaluated. Elastography scores were classified according to the ratio of soft and hard areas across the lymph node on a 4-point scale system. Largely soft lymph nodes were scored as "1" and largely hard lymph nodes were scored as "4". Results When patients with SCC and MM were evaluated together, the sensitivity of elastography was 94%, specificity was 70%, and the accuracy rate was 86% in detecting lymph node involvement. When both tumor groups were evaluated separately, for SCC, the sensitivity of elastography was 90%, specificity was 61%, and the accuracy rate was 80% in detecting lymph node involvement. When the receiver operating characteristic (ROC) curve was taken, the area under the curve (AUC) was 0.78 for SCC. Elastography showed full compliance with pathology in lymph node metastases of MM and the AUC was 1.00. Conclusions Based on our findings, RTE provides important contributions to B-mode ultrasonography (USG) in evaluating lymph node metastases of skin cancers.

Background The presentation of sufficient antigen on major histocompatibility complex class I (MHC-I) is essential to prime CD8+ T cells. Methods To achieve efficient MHC-I presentation, we used microfluidics cell squeezing (Cell Squeeze®) to deliver antigens directly to the cytosol of antigen presenting cells (APCs), bypassing the need for cross-presentation. In addition to facilitating priming by professional APCs, this approach enables lymphocytic subsets within peripheral blood mononuclear cells (PBMCs) to function as unconventional APCs in mouse preclinical models. Results We demonstrated that microfluidic cell squeezing delivers cargo to major cell populations within splenocytes (T cells, B cells, NK cells, and monocytes) and that protein, peptide, or mRNA antigens are rapidly processed and presented. In vivo, squeezed splenocytes directly presented antigen to CD8+ T cells. In the TC-1 tumor model for HPV+ cancers, squeezed splenocytes completely protect mice when administered prophylactically, protecting 15/15 animals from primary challenge and 11/15 animals from tumor re-challenge. Following therapeutic administration, squeezed splenocytes significantly improved median survival time to 56 days from 28 days, as observed with untreated controls. Immunization can also be combined with chemotherapy to further enhance therapeutic efficacy, improving median survival to over 100 days compared to 81 days with SQZ monotherapy or 32 days with chemotherapy alone. When tumor infiltrating lymphocytes (TILs) were analyzed following therapeutic immunization, squeezed splenocyte immunization elicited a significant influx of antigen specific CD8+ T cells: with SQZ treatment, ~87% of tumor-infiltrating CD8 T cells were antigen-specific, as measured by an E7-tetramer stain, while only ~33.6% and ~1.15% of infiltrating CD8 T cells were specific for E7 with subcutaneous peptide vaccination and no treatment, respectively. Conclusions Through the direct cytosolic delivery of antigen, we have engineered unfractionated PBMCs to function as potent APCs. This strategy generates potent antigen-specific CD8+ T cell responses in mouse models. Taken together, these findings support the potential of SQZ-PBMCs as an effective antigen-specific vaccination strategy against cancer. SQZ-PBMC-HPV is currently under clinical evaluation for HPV16+ tumor indications. Ethics Approval All methods were performed in accordance with relevant guidelines and regulations; Animal studies were approved by the Institutional Animal Care and Use Committee (IACUC) at SQZ Biotechnologies, using the recommendations from the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and the Office of Laboratory Animal Welfare. All activities were also conducted in accordance with Public Health Service (PHS) Policy on Humane Use and Care of Laboratory Animals.

Metabolic syndrome is a fatal endocrinopathy, which is progressed towards pandemic, and characterized by insulin resistance, abdominal obesity, dyslipidemia, diabetes mellitus, hypertension and coronary artery disease (CAD). In the present study, it is aimed to investigate the histomorphological and histochemical changes caused by the metabolic syndrome in rat kidneys. For this purpose, the material was divided into two groups: 10 rats in the control group and 15 rats in the experimental group. During 16 weeks, while tap water was given to control group rats, water including 20% fructose solution was given to experimental group rats as drinking water. At the end of the study, Crossman's triple staining method was performed to determine the histological appearance and histomorphological changes in the sections taken from the kidneys. Periodic Acid Schiff Reagent (PAS) staining method was performed for histochemical analysis. The results of the study showed that the tubulus proximalis diameter, tubulus proximalis glycogen density, and glomerular mesangial matrix density increased, corpusculum renis diameter, width of cavum glomeruli and ascending limb of Henle’s loop diameter decreased. In conclusion, it is demonstrated that metabolic syndrome may adversely affect kidney histology and cause renal damage. Metabolik sendrom pandemiye doğru ilerleyen, insülin direnci, abdominal obezite, dislipidemi, diabetes mellitus, hipertansiyon ve koroner arter hastalığı (KAH) ile karakterize ölümcül bir endokrinopatidir. Sunulan çalışamada metabolik sendromun rat böbreklerinde oluşturduğu histomorfolojik ve histokimyasal değişimlerin araştırılması amaçlanmıştır. Bu amaçla materyal kontrol grubunda 10, metabolik sendrom grubunda 15 rat içerecek şekilde iki gruba ayrıldı. Kontrol grubundaki ratlara 16 hafta süresince çeşme suyu verilirken, metabolik sendrom grubundaki ratlara içme suyu olarak % 20 fruktoz çözeltisi verildi. Deneme sürecinin sonunda böbreklerden alınan kesitlerde histolojik görünümü ve histomorfolojik değişimleri belirlemek amacıyla Crossman’s üçlü boyama metodu, histokimyasal analiz amacıyla Periyodik Asit Schiff Reagent (PAS) boyama metodu uygulandı. Elde edilen veriler tubulus proksimalis çapı ve glikojen yoğunluğu ile glomerular mezangial matriks yoğunluğunun arttığını, korpuskulum renis çapı, Bowman aralığı genişliği ve çıkan henle çapının azaldığını göstermiştir. Sonuç olarak, metabolik sendromun böbrek histolojisini olumsuz yönde etkileyerek renal hasara sebep olabileceği ortaya konmuştur.

Toxic epidermal necrolysis (TEN) is a severe autoimmune idiosyncratic reaction, which is mostly caused by drugs, involves for more than 30% of the body surface and affects the entire mucosa, and is characterized by extensive epidermal loss. The worldwide incidence of TEN is estimated to be 0.4-1.3 million. The mortality rate of TEN is between 30-50%, and primary death cause is septicemia and multiple organ failure. The Scorten Mortality Scoring is widely used in assay of mortality and morbidity and gives substantially correct results. Since lesions are similar with burns and the possibility of sepsis in TEN, their follow-up in the burn intensive care unit (BICU) is widely accepted. In this case report, a 30-year-old male patient who developed TEN on the third day of cefuroxime axetil oral use due to upper respiratory tract infection was presented in the BICU follow-up, in company with the literature data.

It is very challenging to treat raw pistachio processing wastewater (PPW) by one step process due to its high chemical oxygen demand (COD) and total phenols (TP). In this study, electrochemical (EC) process and anaerobic digestion are combined to improve treatment efficiency. Central composite design (CCD) was used in EC experimental design with three factors at three levels of the independent variables. Impact of current density (50─100 A/m2), electrode distance (2─6 cm), and reaction time (60─300 min) on the removal of COD and TP were systematically investigated. A maximum removal efficiency of 43.7 and 56.4% of COD and TP, respectively, was obtained with the current density of 100 A/m2, electrode distance of 6 cm, and reaction time of 293 min. Specific energy consumption (SEC) was measured as 7.80 kWh/kgCOD for the same experimental conditions. In order to achieve further treatment, a batch anaerobic reactor was combined with EC process to produce biogas. COD and TP removal efficiency were measured in the anaerobic reactors at appropriate time intervals (0, 10, 25, 30, 40, and 50th d) and biochemical methane potential (BMP) tests lasted up to 50 d. BMP enhancement of raw PPW was found as 35.7 and 16.5% for electrocoagulated PPW under maximum COD and TP removal efficiency condition (100 A/m2 current density, 6 cm electrode distance, and 293 min reaction time) and under cost driven approach condition (53 A/m2 current density, 2 cm electrode distance, and 182 min reaction time) compared to raw PPW. The results showed that pre-treated PPW with EC process had the highest COD and TP removal efficiencies and enhanced the biochemical methane production, by decreasing the concentration of total phenols in the PPW. Energy balance revealed that EC under cost driven approach condition combined with anaerobic digestion can be used as an energy positive process for the treatment of PPW.

Purpose: In this study, we aimed to explain the role of oxidative stress in women with overactive bladder (OAB) by investigating the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, and malondialdehyde (MDA), an indicator of lipid peroxidation. Materials and Methods: A total of 90 women were included in the study: 45 female patients diagnosed with OAB at Hopa State Hospital Urology Polyclinic and 45 healthy women without any metabolic or neurologic disease. Levels of MDA and 8-OHdG were measured in 24-hour urine samples for all subjects. Results: Urinary levels of MDA and 8-OHdG were significantly higher in the OAB group than in the control group (p

In this study, we synthesized a novel phosphazene compound hexakis[4-(acrylamido)phenoxy]cyclotriphosphazene (HAAP) as crosslinker. The structure of compound was identified using spectroscopic techniques. Then, HAAP was used as crosslinker for the synthesis of thermo and pH responsive p(NIPAM-co-VI) hydrogels. The structure and swelling behavior of hydrogel was investigated. Then, HAAP-crosslinked p(NIPAM-co-VI) hydrogels were used for in vitro release of Rhodamine 6G as drug release matrix. Additionally, HAAP-crosslinked p(NIPAM-co-VI) hydrogels were used as support material for the preparation of cobalt metal catalysts. The prepared HAAP-crosslinked p(NIPAM-co-VI)-Co composite catalyst was used as catalyst for the reduction reaction of 4-nitrophenol.

In this study, p([2-(acryloyloxy)ethyl]trimethylammonium chloride-co-1-vinyl-2-pyrrolidinone) (p(AETAC-co-NVP) hydrogels containing positive charge in the structure were synthesized for the removal of anionic dyes from the aqueous media. The swelling behaviors affecting the adsorption properties of hydrogels structurally characterized by FTIR, SEM and EDX/mapping analysis were investigated. The effects of pH, dye concentration, adsorbent amount, dissolved anions and temperature on the adsorption of methyl orange (MO) and alizarin red S (AR) from aqueous media using p(AETAC-co-NVP) hydrogels were investigated. Using data obtained in adsorption studies, the Langmuir, Freundlich, Temkin and Dubinin-Radushkevich isotherms and pseudo-first order (PFO), pseudo-second order (PSO), intra-particular diffusion, and Elovich kinetic model analyses were performed. The results showed that the p(AETAC-co-NVP) hydrogel was a good adsorbent for MO and AR anionic dyes and the adsorption process for both dyes complied with the Freundlich isotherm and PSO kinetic model. This situation indicates that the dominant mechanism for the adsorption of MO and AR dyes by the p(AETAC-co-NVP) hydrogel is strong electrostatic interactions and occurs as multilayered adsorption, not only on a planar region. Additionally, to the maximum adsorption values using p(AETAC-co-NVP) hydrogel for MO and AR dyes were reached at pH values of 7.0 and 5.0, respectively. According to all these findings, it can be said that the p(AETAC-co-NVP) hydrogel containing positivelly charged groups is a super adsorbent for adsorption of anionic dyes.

The combinations of treatment processes are one of the hot topics in environmental engineering. Especially, the highly-polluted wastewater can be treated effectively using combined processes. The objective of the present study was to investigate the treatment performance of brewery wastewater using electrocoagulation (EC), ultrasonication (US), and sono-electrocoagulation (SEC) processes. A cross-flow membrane system was integrated to succeed continuous treatment. The effect of electrode combination (Fe and Al), current density (50–100 A/m2), pH (5.0–9.0), and operating time (0–60 min) on the treatment of wastewater were investigated to obtain maximum treatment efficiency. The maximum removal efficiencies of color and chemical oxygen demand (COD) were obtained as 99.2 and 60.5%, respectively, at the electrode combination of Al/Al, current density of 100 A/m2, pH 7.0, and reaction time of 60 min. In order to improve treatment quality, a cross-flow membrane process was integrated to the sono-electrocoagulation process. Nanofiltration (NF) and reverse osmosis (RO) membranes were tested. The combined sono-assisted electrocoagulation and membrane system supplied 100% color and 90.8% COD removal efficiency when supported with RO membrane. The results indicated that the proposed integrated process supplied higher pollutant removal compared to the alone electrocoagulation and sonication process. Operating cost of the combined process was calculated as 1.83 $/m3. Moreover, the genotoxic effect of brewery wastewater was also assessed by comet assay before and after treatment. This process can be used to treat a different kind of wastewater as an efficient technique.

Atypical hemolytic uremic syndrome and C3 glomerulopathy (dense deposit disease and C3 glomerulonephritis) are characterized as inappropriate activation of the alternative complement pathway. Genetic mutations affecting the alternative complement pathway regulating proteins (complement factor H, I, membrane cofactor protein and complement factor H-related proteins) and triggers (such as infection, surgery, pregnancy and autoimmune disease flares) result in the clinical manifestation of these diseases. A decade ago, prognosis of these disease states was quite poor, with most patients developing end-stage renal disease. Furthermore, renal transplantation in these conditions was associated with poor outcomes due to graft loss to recurrent disease. Recent advances in targeted complement inhibitor therapy resulted in significant improvement in disease remission, renal recovery, health-related quality of life and allograft survival.

In patients with a solitary kidney; residual renal volume is an important prognostic factor for kidney survival. At present, the impact of renal cysts on solitary kidney survival is not clear. The aim of this study is to examine the association of cysts on progression of renal failure in patients with a solitary kidney. METHODS This study included sixtyfive solitary kidney patients. The remaining kidneys after indication nephrectomy (IN) were evaluated with urinary system ultrasound. The primary outcome of the study is the progression of kidney failure during follow-up which was defined as: 25% decrease in glomerular filtration rate (GFR) and / or the need for renal replacement therapy (RRT). RESULTS The mean age of the patients was 55 ± 14 years and mean follow-up was 53 ± 27 months. Renal cysts were present in 30.7% of patients. 33.8 percent of patients had kidney disease progression and 10.7 % required RRT. Those with progressive disease were older (61 ± 13, 52 ± 14; P = 0.011), had lower baseline GFR (30 ± 11, 39 ± 18; P = 0.035), higher proteiuria (2.84 ± 0.58, 2.47 ± 0.57; P = 0.031) and frequently harboring cysts in the solitary kidney (52.3%, 20.4%; P = 0.006). Progression to kidney failure and RRT requirement in cases with or without renal cysts was (60% vs. 22%; P = 0.004) and (20% vs. 6.6%; P = 0.123), respectively. Acquired cysts in solitary kidney was independently associated with progression to kidney failure and RRT respectively (Exp(B) 3.173; P = 0.01 and Exp(B) 12.35; P = 0.04). CONCLUSION Simple renal cysts in solitary kidney patients with impaired renal function is associated with poor renal outcome. Large-scale studies are needed to clarify this issue.

Regulatory T cells maintain immunological tolerance and dampen inflammatory responses. Administering regulatory T cells can prevent the immune-mediated tissue destruction of graft-versus-host disease, which frequently accompanies hematopoietic stem cell transfer. Neutralizing the T cell-specific kinase, protein kinase C theta, which promotes T cell effector functions and represses regulatory T cell differentiation, augments regulatory T cell immunosuppression and stability. We used a synthetic, cell-penetrating peptide mimic to deliver antibodies recognizing protein kinase C theta into primary human CD4 T cells. When differentiated ex vivo into induced regulatory T cells, treated cells expressed elevated levels of the regulatory T cell transcriptional regulator forkhead box P3, the surface-bound immune checkpoint receptor programmed death receptor-1, and pro-inflammatory interferon gamma, previously ascribed to a specific population of stable, highly suppressive human induced regulatory T cells. The in vitro suppressive capacity of these induced regulatory T cells was 10-fold greater than that of T cells differentiated without antibody delivery. When administered at the time of graft-versus-host disease induction, using a humanized mouse model, antibody-treated regulatory T cells were superior to non-treated T cells in attenuating lethal outcomes. This antibody delivery approach may overcome obstacles currently encountered using patient-derived regulatory T cells as a cell-based therapy for immune modulation.

Introduction: This Experts' opinion provides an updated scientific support to gynecologists, obstetricians, endocrinologists, nutritionists, neurologists and general practitioners on the use of Inositols in the therapy of Polycystic Ovary Syndrome (PCOS) and non-insulin dependent (type 2) diabetes mellitus (NIDDM). Areas covered: This paper summarizes the physiology of Myo-Inositol (MI) and D-Chiro-Inositol (DCI), two important molecules present in human organisms, and their therapeutic role, also for treating infertility. Some deep differences between the physiological functions of MI and DCI, as well as their safety and intestinal absorption are discussed. Updates include new evidence on the efficacy exerted in PCOS by the 40:1 MI/DCI ratio, and the innovative approach based on alpha-lactalbumin to overcome the decreased therapeutic efficacy of Inositols in some patients. Expert opinion: The evidence suggests that MI, alone or with DCI in the 40:1 ratio, offers a promising treatment for PCOS and NIDDM. However, additional studies need to evaluate some still unresolved issues, such as the best MI/DCI ratio for treating NIDDM, the potential cost-effectiveness of reduced gonadotropins administration in IVF due to MI treatment, or the benefit of MI supplementation in ovulation induction with clomiphene citrate in PCOS patients.

INTRODUCTION: Obstetric history and maternal body composition and lifestyle may be associated with serious complications both for the mother, such as gestational diabetes mellitus (GDM), and for the fetus, including congenital malformations such as neural tube defects (NTDs). AREAS COVERED: In view of the recent knowledge, changes of nutritional and physical activity habits ameliorate glycemic control during pregnancy and in turn improve maternal and neonatal health outcomes. Recently, a series of small clinical and experimental studies indicated that supplementation with inositols, a family of insulin sensitizers, was associated with beneficial impact for both GDM and NTDs. EXPERT OPINION: Herein, we discuss the most significant scientific evidence supporting myo-inositol administration as a prophylaxis for the above-mentioned conditions.

Objectives: The aim is to compare the hormonal status and anti-mullerian hormone (AMH) levels of patients who have different polycystic ovary syndrome (PCOS) phenotypes, polycystic ovarian morphology (PCOM) and healthy women. Material and methods: A total of 350 PCOS women, 71 women with PCOM and 79 healthy women with normal ovarian morphology (NOM) were observed. PCOS patients were divided into groups according to the phenotypes. Phenotype A- characterized by anovulation, hyperandrogenism and PCOM; phenotype B- defined as anovulation, hyperandrogenism; Phenotype C- identified as hyperandrogenism and PCOM; Phenotype D- outlined as anovulation and PCOM. AMH levels were compared for each group. Results: Among 350 PCOS patients the highest number belonged to phenotype A (n = 117, 33.4%). The rest were distrubuted as follows: phenotype B (n = 89, 25.4%), phenotype C (n = 72, 20.6%), phenotype D (n = 72, 20.6%). Phenotype A (9.17 ± 4.56) had the highest mean AMH levels in our study. Comparison of AMH levels showed a statistically significant difference between phenotypes A and D. There was a statistically significant difference on comparison of AMH between NOM, PCOM and all PCOS phenotypes. Conclusions: Phenotype A is the most serious form of PCOS and these patients has all three features which are hyperandrogenism, anovulation and ultrasound findings of polycystic ovary (PCO). AMH reflects the severity of PCOS and patients with Phenotype A have higher AMH levels.

Objectives: The objective of the current research is to compare hormonal, metabolic and ovarian stromal blood flow outcomes in smoking versus non-smoking polycystic ovary syndrome (PCOS) patients. Material and methods: 79 PCOS women (Group 1) and 79 healthy subjects (Group 2) were recruited. Both groups were subdivided according to their smoking habits. Ovarian stromal blood flow was assessed with pulsatility and resistance index for both ovaries and compared among smoking women. Results: The smokers in the PCOS group had statistically significant higher levels of pulsatility and resistance index in both ovaries compared to nonsmoker PCOS patients (p < 0.001). Comparison of ovarian stromal blood flow indexes shows that pulsatility and resistance index for both ovaries is statistically significantly high in smoking healthy patients compared to the nonsmoking group (p < 0.001). There is a positive correlation between smoking and free androgen index (r = 0.866, p < 0.001) for PCOS patients and healthy women. Conclusions: Smoking reduces ovarian blood flow in PCOS patients and healthy subjects. Smoke components effect the vascular structure and form endothelial injuries that may reduce ovarian tissue perfusion. In this study, the positive correlation between smoking and free androgen index shows that the main effect of smoking on ovarian blood flow may be through androgen metabolism.

It is well known that myo-inositol (MI) and D-chiro-inositol (DCI) are insulin-sensitizing agents, and MI is of proven utility in polycystic ovary syndrome (PCOS). In addition, MI plays a pivotal role in the physiology of reproduction, and has beneficial effects on the development of oocytes, spermatozoa, and embryos. By contrast, DCI has little effect on spermatozoa, but high concentrations in the ovary can negatively affect the quality of oocytes and the blastocyst. Overall, the evidence in the literature supports the beneficial effects of MI in both female and male reproduction, warranting clinical use of MI in assisted reproductive treatment (ART).

To evaluate whether 4 gram myoinositol and 400 mcg folic acid(MYO) therapy has any effects on ovarian stromal blood flow by using pulsed and color Doppler at 3 months follow-up period in polycystic ovary syndrome (PCOS). One-hundred eighty patients were designed into six groups; Group 1: PCOS patients that received OCP containing 30 mcg ethinyl estradiol (EE) plus 3 mg drospirenone (DRP); Group 2: PCOS patients that received MYO; Group 3: PCOS patients that received no medication. Group 4: Healthy patients that received OCP; Group 5: Healthy patients that received MYO; Group 6: Healthy patients that received no medication. Resistance index (RI) and pulsatility index (PI) of both ovaries were assessed. There was a significant increase in RI and PI of both ovarian stromal blood flow women with PCOS who received OCP (Group 1, p < .001) and MYO (Group 2, p < .001). The rate of increment in both RI and PI values were similar for OCP users (Group 1) and MYO users(Group2) in PCOS patients. MYO therapy reduced ovarian vascularization in both PCOS and healthy users after 3 months and this decrease is especially noticeable in women with PCOS compared to healthy women. OCP therapy also reduced ovarian vascularization just like MYO therapy.

This paper proposes a method to synthesise controllers for systems with possibly infinite number of states that satisfy a specification given as an LTL ∖ ∘ formula. A common approach to handle this problem is to first compute a finite-state abstraction of the original state space and then synthesise a controller for the abstraction. This paper proposes to use an abstraction method called divergent stutter bisimulation to abstract the state space of the system. As divergent stutter bisimulation factors out stuttering steps, it typically results in a coarser and therefore smaller abstraction, at the expense of not preserving the temporal “next” operator. The paper leverages results about divergent stutter bisimulation from model checking and shows that divergent stutter bisimulation is a sound and complete abstraction method when synthesising controllers subject to specifications in LTL ∖ ∘ .

Antigen-specific CD8+ T cell priming is critical for mounting an effective immune response against altered self or foreign antigens that are found in most tumors and virally infected cells. T cell priming events require antigen presenting cells (APCs) to process and load antigenic peptides onto MHC molecules. One recently established method for providing APCs with foreign antigen is through delivery of mRNA. An advantage of using antigen-encoding mRNA, compared to protein or peptides, is the inherent protein amplification of mRNA translation; a single mRNA can be translated multiple times. In addition, when antigen-encoding mRNA is delivered directly to the cell, the antigens will have the appropriate post-translational modifications, potentially increasing the immunogenicity. Whereas typical mRNA vaccine platforms require modified nucleotides and lipid nanoparticle encapsulation, Cell Squeeze® technology allows for delivery of uncomplexed and unmodified mRNA directly into the cytosol. Here, we use ex vivo microfluidic Cell Squeeze® technology to deliver uncomplexed and unmodified mRNA encoding for disease related antigens into human peripheral blood mononuclear cells (PBMCs) to generate PBMC APCs. We demonstrate that squeezing PBMCs with mRNA results in effective delivery and translation of mRNA in major cell subsets including T cells, B cells, NK cells, and monocytes. Delivery of antigen-encoding mRNA to human PBMCs enables them to function as APCs, capable of presenting antigenic peptides on MHC molecules for activation of antigen-specific T cells. Specifically, we demonstrate squeezing antigen-encoding mRNA (e.g. HPV16 E7) into human PBMCs results in PBMC APCs that can elicit robust in vitro activation of antigen-specific CD8+ T cells. This approach to APC engineering demonstrates Cell Squeeze® technology's potential to leverage the modularity, cost-effectiveness, and streamlined manufacturing of multiple mRNAs to create cellular vaccines for treating various tumor and infectious disease targets. Citation Format: Michael F. Maloney, Emrah Ilker Ozay, Christian Yee, Amy Merino, Paul R. Dunbar, Mubeen Mosaheb, Kelly Volk, Carolyne Smith, Katherine J. Seidl, Howard Bernstein, Scott M. Loughhead. Cell Squeeze® delivery of antigen-encoding mRNA enables human PBMCs to drive antigen-specific CD8+ T cell responses for diverse clinical applications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1523.

Antigen-specific CD8+ T cells are critical effectors of the immune system that help limit persistence of tumors and virally infected cells. During priming, T cells integrate three signals which determine the magnitude and quality of response generated. Signal one is T cell receptor(TCR) and peptide-MHC (pMHC) engagement, which determines the specificity of the response.Signal two is cell surface costimulation by antigen presenting cells (APCs). Signal three is provided through the local cytokine milieu at the time of priming. Here, we use microfluidic CellSqueeze® technology to deliver mRNAs encoding antigen (signal 1), costimulatory molecules(signal 2), and chimeric membrane-tethered cytokines (signal 3) to the cytosol of human peripheral blood mononuclear cells (PBMCs), generating antigen presenting cells (APCs) with multiple enhanced functions. We demonstrate that microfluidic squeezing enables delivery and expression of single or multiple mRNAs encoding signal 1 (various antigens), signal 2 (CD70 orCD86) and/or signal 3 (membrane-tethered form of IL-2) by the major subsets of PBMCs (T cells, B cells, NK cells, and monocytes). While unsqueezed PBMCs showed no to minimal expression of signal 2 and no expression of signal 3 molecules, expression of delivered signal 2and 3 mRNAs in squeezed PBMCs could be observed on the cell surface for several days post squeeze delivery - a timeframe that could potentially support improved T cell priming. When these signal 2/3 molecules were delivered alone or in combination, antigen-specific CD8+ T cell responses could be increased as much as ten-fold compared to delivery of antigen alone.Therefore, microfluidic cell squeezing enables us to efficiently deliver mRNA antigens that have potential to generate multiple immune epitopes in an HLA agnostic manner. Moreover,multiplexing these antigens with signal 2/3 mRNAs enhances the antigen presenting potency ofSQZ APCs inducing stronger antigen-specific CD8+ T cell responses. The potential to deliver numerous materials simultaneously and engineer compound signals via mRNA could allow for applications for HLA-agnostic patient population in oncology and infectious disease areas. Citation Format: Emrah Ilker Ozay, Paul Dunbar, Kelly Volk, Michael F. Maloney, Christian Yee, Mubeen Mosaheb, Christine Trumpfheller, Pablo Umana, Katherine J. Seidl, Howard Bernstein, Scott M. Loughhead. Enhancing potency of antigen presenting cells via signal 2/3 mRNA engineering through Cell Squeeze® technology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1525.