Improvement Of Clinical Protocols Research Articles

Cesarean section rate: navigating the gap between WHO recommended range and current obstetrical challenges

The cesarean section (CS) rate is very heterogeneous all over the world, reflecting the differences in the access to healthcare services. In higher-income countries, changes observed in the obstetrical population brought to an increased rate of cesarean section for maternal request. Besides, clinicians are facing an increasing number of induction of labor, with the consequent risk of CS if the management is inappropriate. Analyzing the rate of primary CS, the interpretation of intrapartum CTG and a tailored management of labor are also red flags that must be considered. In this optic, the implementation of obstetrics training and simulation programs and the improvement of clinical protocols with the latest evidence can lead to the reduction of unnecessary CS.

РЕЗУЛЬТАТ ПЯТИЛЕТНЕГО НАБЛЮДЕНИЯ ЗА СОСТОЯНИЕМ КОСТНОЙ ТКАНИ В ОБЛАСТИ РАЗРАБОТАННОГО БИО-ИМПЛАНТАТА НА ОСНОВЕ ДИОКСИДА ЦИРКОНИЯ (КЛИНИЧЕСКИЙ СЛУЧАЙ)

The subject of the study is the prospects for the introduction of an endossal all-ceramic screw single-stage immediate implant in the clinical practice.
 The objectives. The aim is to conduct a comparative analysis of the state of bone tissue according to CT data and long-term clinical use of the developed zirconium dioxide bio-implant in comparison with a titanium implant with SLA-coating.
 Methodology. The paper presents 5-year clinical results of monitoring the state of bone tissue in the area of the developed bio-implant and titanium implant installed under the same clinical conditions in one patient.
 Results. The development of new biocompatible materials and the improvement of technologies for obtaining surfaces with a given micro-roughness, new technologies for applying bio-coatings to the surface of a dental implant made of zirconium dioxide and the improvement of clinical protocols have made it possible to use such zirconium dioxide implants as a reliable alternative to their titanium counterparts.
 The 5-year clinical results of the patient's treatment with the use of patented bio-implants based on zirconium dioxide in comparison with implants based on titanium alloys are presented. 
 The new all-ceramic implant developed by the author of the study (RF Patent for Invention No. 2651052; Eurasian Patent No. 035482) is distinguished by its design and the method of treating the surface of the exclusively threaded part of the implant with calcium hydroxyapatite.
 The possibility of using the developed implant will meet the needs of patients in minimally invasive implantation procedure, ensuring its cost-effectiveness in relation to analog imported dental implant systems. In addition, due to specialized surface treatment, the developed implant does not require the use of bone-substituting drugs, and the presence of a bio-coating allows to expand the use in groups of patients with somatic pathologies.
 Conclusions. The performed study shows that the developed system of all-ceramic immediate implants has reliable long-term clinical results, as well as preserves and maintains the volume and density of bone tissue in comparison with titanium systems. This clinical observation allows us to recommend the use of the developed bio-implant in clinical dentistry.

Adherence to screening and management guidelines of maternal Group B Streptococcus colonization in pregnancy.

AimsTo investigate Group B Streptococcus (GBS) colonization in pregnancy; adherence to antenatal GBS screening and adherence to the intrapartum antibiotics protocol within two models of care (midwifery and non‐midwifery led).DesignThis retrospective quantitative study has employed a descriptive design using administrative health data.MethodsData from five maternity hospitals in metropolitan and regional Western Australia that included 22,417 pregnant women who gave birth between 2015 and 2019 were examined, applying descriptive statistics using secondary data analysis.ResultsThe study revealed an overall GBS colonization rate of 21.7% with similar rates in the different cohorts. A lower adherence to screening was found in the midwifery led model of care (MMC, 68.76%, n = 7232) when compared with the non‐midwifery led model of care (NMMC, 90.49%, n = 10,767). Over the 5 years, screening rates trended down in the MMC with stable numbers in the counterpart. Adherence in relation to intrapartum antibiotic prophylaxis revealed discrepant findings between the study groups.ConclusionAdherence to screening and management guidelines of maternal GBS colonization in pregnancy is lower within the MMC when compared with the NMMC.ImpactThis is the first cohort study to describe the adherence to the recommended Western Australian GBS screening guidelines in the two different models of care. Findings may assist in the guidance and improvement of clinical protocols as well as the planning of clinical care in relation to GBS screening to reduce the risk of neonatal GBS infection.

Research progress of signal transduction pathways associated with glucocorticoid resistance in acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the common malignant tumor. Despite the great improvements in clinical protocols, some patients relapse or suffer from failure of treatment. Glucocorticoid is the core drug in the treatment of ALL. However, the resistance of glucocorticoid in ALL is a common problem in clinical treatment and the main cause of failure of treatment. Mechanism of glucocorticoid resistance is very complex. The expression of drug resistance proteins and the production of drug resistance in tumor cells are regulated by multiple signal transduction pathways, which mainly include MAKP, PI3K/AKT/mTOR, JAK/STAT, Wnt/β-catenin signal transduction pathway. In this paper, the recent progresses of glucocorticoid resistance related signal transduction pathway in ALL was reviewed. Key words: Leukemia, lymphoid; Precursor cell lymphoblastic leukemia-lymphoma; Signal transduction; Glucocorticoid; Drug resistance

Adoptive Transfer of T-Cell-Receptor Engineered Human T Cells Specifically Reduces Viral Titers in HLA-Transgenic NSG Mice Infected with a Humanized Cytomegalovirus

Reactivation of latent human cytomegalovirus (HCMV) infection is a frequent complication in patients after allogeneic hematopoietic stem cell transplantation (HSCT). Preclinical research in murine models as well as clinical phase I/II trials have shown that the adoptive transfer of virus-specific CD8+ T cells is a therapeutic option for preventing HCMV disease. However, the feasibility of HCMV-specific immunotherapy is currently limited in clinical routine due to technical restrictions. It has also limitations, if the donor is HCMV-seronegative or carries only low numbers of HCMV-specific memory T cells. In this situation, grafting non-reactive T cells by virus-antigen specific T-cell receptors (TCR) may be an alternative means to transfer HCMV-specific T-cell function into HSCT recipients. Nevertheless, improvement of clinical protocols is needed before HCMV-specific cell therapy can be implemented in general clinical practice.Here we describe a novel preclinical mouse model that will help to evaluate new HCMV-immunotherapy options. Due to the strict species specificity of CMV, we constructed a recombinant murine CMV (mCMV) coding for the HLA-A2 restricted pp65495-503 (NLV) peptide epitope of HCMV. This peptide is expressed with flanking amino acids within the mCMV-IE2-protein in the context of experimental infection with mCMV-IE2/NLV. The NLV peptide was found to be presented by infected murine fibroblasts from NOD/SCID/IL-2Rγc-/--HLA-A2-transgenic (NSG-A2) mice as shown by T cell specific recognition in ELISPOT and cytotoxicity assays. Interestingly, this presentation proved to be susceptible to the inhibitory function of mCMV immune evasion proteins. NSG-A2 mice were then used to evaluate antiviral control by HCMV-NLV-specific TCR (TCRNLV)-engineered human T cells. After infection with mCMV-IE2-NLV, the NSG-A2 mice showed high viral titers in liver, spleen, lungs, and salivary glands as well as a dramatic virus-induced morbidity and mortality. In contrast, after intravenous injection of TCRNLV-transduced human CD4+/CD8+ T cells, viral infection was reduced in all tested organs, and mice showed improved survival. These findings suggest that the NLV peptide is processed and presented by stromal and parenchymal cells of the NSG-A2 mice and promise validity of the model for preclinical evaluation of adoptive transfer protocols, for instance cell therapy with TCR-engineered T cells alone or in combination with therapeutic vaccination. DisclosuresNo relevant conflicts of interest to declare.

347. Long-Term Gene Expression and Phenotypic Correction of FANCC Deficient Lymphoblastoid Cells Using the Sleeping Beauty Transposon System

We are moving forward with development of our proprietary Sleeping Beauty Transposon (SBT) system for the treatment of Fanconi anemia (FA) via ex vivo electroporation of hematopoietic stem cells. FA is an inherited recessive disorder caused by deficiency in one of a number of genes whose products form a complex involved in DNA repair. The primary hematological hallmarks of the disease are aplastic anemia, bone marrow failure, and increased susceptibility to leukemias thought to be caused by defective cellular mechanisms for DNA repair. Allogeneic bone marrow transplantation is currently the only curative treatment for these aspects of the disease and despite improvements in clinical protocols over the years difficulties with allotransplants for FA still persist. The primary goal of this study is to evaluate the potential of SBT vectors carrying the FANCC gene to effectaffect transposition and establish long-term expression in FANCC-deficient cell populations after introduction by electroporation. Additionally, we show that integration of FANCC transposons can correct the sensitivity of lymphoblastoid cell lines (LCL) derived from FANCC patients to DNA damaging agents such as mytomycin C. We constructed a transposon containing a PGK promoter to regulate transcription of the normal human FANCC cDNA sequence. The vector containing the transposon also includes a ubiquitin promoter regulating expression of the SB transposase gene, encoded outside of the transposon. The SBT-FANCC vector was introduced via electroporation into FANCC deficient and normal control LCLs. Long-term maintenance of FANCC complementation in the FANCC-deficient cells was observed as a sustained reduction in sensitivity to mitomycin C similar to normal controls. In addition, the isolation and molecular characterization of clonal populations of these FANCC-complemented cells demonstrated FANCC transposon integration into the genome by SB mediated transposition. Preliminary results using SBT vectors in K562 cells suggest that a transposase provided on a separate plasmid may increase the efficiency of transposition. As a result, studies are also underway to characterize the efficacy of the SBT-FANCC vector described above compared to a similar vector in which the transposase is supplied either by a separate plasmid or by a SB-encoding mRNA. These studies demonstrate molecular feasibility of the SB transposon system in combination with electroporation-based cell loading technology for genetic therapy of Fanconi anemia.