Number Of Donors Research Articles

Estimating the hydrophobicity extent of molecular fragments using reversed-phase liquid chromatography.

A fast HPLC method was developed to study the hydrophobicity extent of pharmaceutically relevant molecular fragments. By this strategy, the reduced amount of sample available for physico-chemical evaluations in early-phase drug discovery programs does not represent a limiting factor. The sixteen acid fragments investigated were previously synthesized also determining potentiometrically their experimental log D values. For four fragments it was not possible to determine such property since their values were outside of the instrumental working range (2<pKa <12). An RP-HPLC method was therefore optimized. For each scrutinized method, some derived chromatographic indices were calculated, and Pearson's correlation coefficient (r) allowed to select the so-called "φ0 index" as the best correlating with the log D. The was fixed at 3.5 and a modification of some variables [organic modifier (methanol vs. ACN), stationary phase (octyl vs. octadecyl), presence/absence of the additives n-octanol, n-butylamine, and n-octylamine], allowed to select the best correlation conditions, producing a r=0.94 (p<0.001). Importantly, the φ0 index enabled the estimation of log D values for four fragments which were unattainable by potentiometric titration. Moreover, a series of molecular descriptors were calculated to identify the chemical characteristics of the fragments explaining the obtained φ0 . The number of hydrogen bond donors and the index of cohesive interaction correlated with the experimental data.

TARGETING CANCER STEM CELLS WITH A CDK2 INHIBITOR IN GLIOBLASTOMA

Abstract Glioblastoma (GB) is the most common and aggressive adult brain tumor with no cure. Brain tumor stem cells (BTSCs) are a rare population of self-renewing multipotent stem cells in GB that contribute to tumorigenesis, therapeutic resistance, and tumour recurrence. Here, we report a CDK2 inhibitor that suppresses BTSCs via OSM/OSMR/STAT3 signalling pathway. To begin with, we performed high throughput screening (HTS) of ~8400 compounds including FDA-approved drugs in patient derived human BTSCs that naturally harbour EGFRvIII mutation and elevated STAT3 phosphorylation, in search of compounds that can suppress EGFRvIII/OSMR/STAT3 oncogenic pathway. The screen led to the identification of a panel of CDK inhibitors that possessed important characteristics including a) ability to cross the blood-brain barrier with mall molecular weights of 277-566 kDa, b) low Topological Polar Surface Area (TPSA) of 76-115 A°, c) a low number of Hydrogen Bond Donors (HBDs) (1-4), and d) cLogP values ranging from 2-4. Following counter screens, we focused on a CDK2 inhibitor that significantly and most efficiently reduced OSM/OSMR signalling and STAT3 activation. Importantly, we found that the compound inhibited the self-renewal and growth of BTSCs in EGFRvIII subtype of BTSCs. This research has led to future investigation on in vivo assessment of this CDK2 inhibitor in combination with ionizing radiation and chemotherapy in preclinical models of GB.

Immunogenetic characteristics of hematopoietic stem cell donors representing the most numerous ethnic groups in Russia

Development of criteria for the optimal donor selection based on the analysis of the allo-HSCT results, high-resolution HLA typing for the donor and recipient resulted in decreased incidence of immunological complications, primarily an acute «graft-versus-host reaction». However, due to the pronounced allelic polymorphism of the main histocompatibility complex (MHC) genes, the search for an optimal donor is ineffective in a number of patients. To increase the chances of selecting a donor for patients with rare HLA genotypes, the hematopoietic stem cell donor registries recruit the persons of various nationalities. An increased number of donors from different ethnic groups provide a broader immunogenetic diversity of the donor cohort. Currently, the registry of hematopoietic stem cell donors at the Russian Research Institute of Hematology and Transfusiology includes representatives of 49 nationalities, most of which, are considered themselves Russians. The third largest ethnic group in the registry comprises Tatars. The purpose of this study is a comparative analysis of immunogenetic characteristics of potential hematopoietic stem cells donors in the registry, who have self-identified as Russians and Tatars. As a result of the study, we have not found significant differences in frequencies of HLA allelic groups in the compared cohorts, a trend for higher frequency of the HLA-B*27 group was noted in Tatars. However, significant differences have been revealed for the distribution of HLA haplotypes in Russians and Tatars. The most common HLA haplotype among Tatars was A*02-B*44-DRB1*07, being much less common in Russians (4.61% vs 0.55%, p = 0.002). HLA haplotype A*03-B*13-DRB1*07, belonging to the ten most common among Tatars, was significantly less frequently detected in Russians (1.62% vs 0.08%, p = 0.026). HLA haplotype A*03-B*08-DRB1*03 was also significantly more common in Tatars compared to Russians (1.42% vs 0.06%, p = 0.026). HLA haplotypes A*02-B*18-DRB1*11, A*02-B*15-DRB1*04, A*02-B*15-DRB1*13, presented in Russians at a frequency of &gt; 1%, were not determined among the tested Tatars. HLA haplotypes A*31-B*58-DRB1*04, A*24-B*44-DRB1*01, presented in Tatars at a frequency of &gt; 1%, were not detectable in Russians. The results of our study indicate a need for recruiting more representatives of the Tatar ethnicity to the registry, thus increasing immunogenetic diversity of the donor pool and resulting into increased chances of compatible unrelated donor selection for the patients with HLA haplotypes, which are now underrepresented in our registry.

Blood Service in a Region of China's Qinghai-Tibetan Plateau.

Objectives: The purpose of this paper is to describe blood services in the Aba Tibetan and Qiang Regions, (hereinafter referred to as Aba Prefecture), a region of China's Qinghai-Tibetan Plateau, the third largest area of Tibet and the main inhabited area of the Qiang people. Design: We present a comprehensive investigation into blood donations, donors, screening and supply in the 13 counties of Aba Prefecture based on data from 2013 to 2018. Geography and population were also used to analyze the differences in blood services among different regions. Participants: The number of blood donors totaled 19,047. Results: Over the past 6 years, blood donations have increased by 29 and clinical blood usage by 45%. The blood donation rate was 3.4‱ and per capita blood use was 1.04 mL, both of which were significantly lower than the national average, and blood donation decreased with altitude. It should be noted that the donation rate of the Tibetan and Qiang peoples is much lower than that of the Han population. Moreover, the rejection rate of blood in laboratory testing was found to be higher than the national average, especially in counties located at higher altitudes. Conclusions: Blood donations and usage increased every year in Aba Prefecture, but blood shortage is still an important issue. In addition, the prevalence of transfusion-transmitted diseases is relatively high, which may be linked to lower-education and unfavorable geographical and medical conditions.

Old Age and Frailty in Deceased Organ Transplantation and Allocation-A Plea for Geriatric Assessment and Prehabilitation.

Due to demographic ageing and medical progress, the number and proportion of older organ donors and recipients is increasing. At the same time, the medical and ethical significance of ageing and old age for organ transplantation needs clarification. Advanced age is associated with the frailty syndrome that has a negative impact on the success of organ transplantation. However, there is emerging evidence that frailty can be modified by suitable prehabilitation measures. Against this backdrop, we argue that decision making about access to the transplant waiting list and the allocation of donor organs should integrate geriatric expertise in order to assess and manage frailty and impairments in functional capacity. Prehabilitation should be implemented as a new strategy for pre-operative conditioning of older risk patients' functional capacity. From an ethical point of view, advanced chronological age per se should not preclude the indication for organ transplantation and the allocation of donor organs.

A Three-Dimensional UCAV Path Planning Approach Based on Immune Plasma Algorithm

Path planning of an unmanned aerial vehicle (UAV) or its variant supported with weapon systems, also called unmanned combat aerial vehicle (UCAV), is one of the most crucial steps for the autonomous flight and requires compelling decisions being made by considering the existence of the enemy defence, obstacles, and battery or fuel capacity of the vehicle optimally before starting the flight. Immune plasma algorithm (IP algorithm or IPA), inspired by the convalescent plasma treatment which is a medical method being popularized again with the rise of new coronavirus or COVID-19, has been introduced recently as a new optimization technique and the promising performance of the mentioned algorithm validated through a set of numerical and engineering problems. In this study, the IP algorithm was specialized as a three-dimensional UCAV path planner for the first time. Its performance was investigated particularly by using three different battlefield environments and assigning various constants to the population size. Moreover, the effect of two IPA-specific control parameters that are responsible for determining the number of donors and number of receivers on the qualities of the calculated paths were analyzed in detail. The results obtained by the IPA were compared with the results of other three-dimensional path planners guiding optimization algorithms such as simulated annealing (SA), gray wolf optimizer (GWO) and symbiotic organism search (SOS). Experimental studies showed that the main idea lying behind the usage of qualified solutions as donors and transferring information directly from them to the receivers representing the poor solutions of the problem gives a positive contribution to the exploitation-dominant operations of IPA and fully complies with the challenging requirements of the path planning problem. Especially in the battlefields for which an optimal or near optimal path contains complex maneuvers, the advantages from the subtly balanced operational steps of the IPA become more apparent by setting the number of donors and receivers appropriately and IPA is found to be more stable and successful compared to the other tested algorithms.

The Impact of Ex Situ Heart Perfusion in Pediatric Transplantation: An Analysis of the OPTN Database.

Ex situ heart perfusion (ESHP) has increased the pool of donors in adults. However, this is not true in pediatrics due to lack of devices. Therefore, we sought to understand organ refusal in pediatrics and estimate donor heart usage with ESHP. Donor hearts offered to pediatrics were identified from the Organ Procurement and Transplantation Network Database (2000-2019). A linear regression model was built to predict average travel speed, and the extended maximum permitted distance with ESHP was calculated. This extended distance was compared with the policy for maximum travel distance. There were 33,708 donor offers (n = 10,807 hearts) to pediatric programs [24.1% (n = 2,604) transplanted]. Six percent of the offers (n = 1,832) (n = 771 hearts) were turned down due to distance, with 676 of the hearts never transplanted. Based on the modeling and using an ESHP time of 5.5 hours, 84% (n = 570/676) of hearts turned down due to distance could be utilized by pediatric programs. This proportion increased to 100% with 10 hours of support time. By addressing prolonged ischemic time due to distance, ESHP has the potential to increase the number of donors utilized in pediatric candidates. Although no device exists for pediatrics, this analysis lends support to the importance of developing this technology.

Protein–Protein Interfaces as Druggable Targets: A Common Motif of the Pyridoxal-5′-Phosphate-Dependent Enzymes to Receive the Coenzyme from Its Producers

Pyridoxal-5′-phosphate (PLP), a phosphorylated form of vitamin B6, acts as a coenzyme for numerous reactions, including those changed in cancer and/or associated with the disease prognosis. Since highly reactive PLP can modify cellular proteins, it is hypothesized to be directly transferred from its donors to acceptors. Our goal is to validate the hypothesis by finding common motif(s) in the multitude of PLP-dependent enzymes for binding the limited number of PLP donors, namely pyridoxal kinase (PdxK), pyridox(am)in-5′-phosphate oxidase (PNPO), and PLP-binding protein (PLPBP). Experimentally confirmed interactions between the PLP donors and acceptors reveal that PdxK and PNPO interact with the most abundant PLP acceptors belonging to structural folds I and II, while PLPBP – with those belonging to folds III and V. Aligning sequences and 3D structures of the identified interactors of PdxK and PNPO, we have identified a common motif in the PLP-dependent enzymes of folds I and II. The motif extends from the enzyme surface to the neighborhood of the PLP binding site, represented by an exposed alfa-helix, a partially buried beta-strand, and residual loops. Pathogenicity of mutations in the human PLP-dependent enzymes within or in the vicinity of the motif, but outside of the active sites, supports functional significance of the motif that may provide an interface for the direct transfer of PLP from the sites of its synthesis to those of coenzyme binding. The enzyme-specific amino acid residues of the common motif may be useful to develop selective inhibitors blocking PLP delivery to the PLP-dependent enzymes critical for proliferation of malignant cells.

Insights into Chemical Structure-Based Modeling for New Sweetener Discovery.

The search for novel, natural, high-sweetness, low-calorie sweeteners remains open and challenging. In the present study, the structure-based machine learning modeling and sweetness recognition mechanism were investigated to assist this process. It was found that whether or not a compound was sweet was closely related to molecular connectivity and composition (the number of hydrogen bond acceptors and donors), tpsaEfficiency, structural complexity, and shape (nAtomP and Fsp3). While the relative sweetness of sweet compounds was more determined by the molecular properties (tpsaEfficiency and Log P), structural complexity and composition (nAtomP and ATSm 1). The built machine learning models exhibited very good performance for classifying the sweet/non-sweet compounds and predicting the relative sweetness of the compounds. Moreover, a specific binding pocket was found for sweet compounds, and the sweet compounds mainly interacted with the VFT domain of the T1R2-T1R3 through hydrogen bonds. In addition, the results indicated that among the sweet compounds, those that were sweeter bound to the VFT domain stronger than those that had low sweetness. This study provides very useful information for developing new sweeteners.

Seroprevalence of human herpesvirus type 8 (HHV-8) in blood donors at Laquintinie Hospital of Douala (LHD), Cameroon

Background: The Human Herpesvirus type 8 (HHV-8), also called Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic virus. Its prevalence is high in many sub-Saharan African countries and some Asian areas. HHV-8 is transmitted through saliva and is acquired in early childhood. HHV-8 can also be transmitted sexually and by organ transplant or blood transfusion. Cameroon is an endemic area. That is why, for improving transfusion safety purpose, we assessed the HHV-8 infection rate in blood donors since the risk of transmission by blood transfusion was shown. Material and methods: Blood samples were collected from blood donors at Laquintinie Hospital of Douala (Cameroon) blood bank for 5 months. Participants were from different ages. Collected samples were tested for detection of antibodies against HHV-8 using enzyme-linked immunosorbent assay (ELISA). Data analysis was perform and P-value of 0.05 was statistical significance threshold. Results: Our result showed 2.2 % (2/91) seroprevalence rate of HHV-8 in blood donors. The two positive results were single and male-gendered. These observations were not statistically significant (P=0.6959 and P=0.851 respectively). Males were the most represented of our participants (92.31%). The mean age of our subject was 29±7 years. None of the studied population were at risk of HHV-8 infection. However, young adults aged between 18 to 28 years (54.94%) were the most represented. No evident association with socio-demographic data such as age, sex, level of education, and marital status was observed. Though, the high the educational level was the fewer we had volunteers for blood donation. Also, the number of blood donors decreased in an age-depending manner. Conclusion: Thus in our study, the HHV-8 infection rate was low in blood donors. Even though the potential risk of transmission might be low, we should consider HHV-8 infection check in some special cases such as immunodeficiency.

Evaluation of hemoglobin concentration, red blood cell indices and microscopic examination of red blood cell in Sudanese blood donors in Gezira state (Sudan) - 2023

Objective: To detect hemoglobin level and Red blood cell indices in apparently healthy Sudanese male, to establish safety for both donor and recipient. To perform hemoglobin estimation and Red blood cell indices for blood donors using automated machine (Blood cell counter). Material and Methods: Venous blood samples were taken from 200 apparently healthy males donors and Hemoglobin level was measured using an automated cell counter (Sysmex KN21), accompanied by peripheral blood films were assessed to detect any abnormalities. Results: The study revealed that the mean hemoglobin values were 14.5 g/dl ±1.2076, with minimum count (10.1 g/dl) and maximum count 17.8 g/dl. Hemoglobin less than 12.5 g/dl was obtained in 30 donors (6%) and they were reported as fit for blood donation using copper sulphate for hemoglobin estimation. Those 30 donors actually they are not fit for blood donation because their hemoglobin concentration must be more than 12.5 g/dl. Conclusion: The study revealed that a significant number of anemic donors were not detected by estimation of Hb by copper sulphate method.

Bronchial Stenosis After Lung Transplantation From cDCD Donors Using Simultaneous Abdominal Normothermic Regional Perfusion: A Single-center Experience.

Controlled donation after circulatory death (cDCD) has increased the number of lung donors significantly. The use of abdominal normothermic regional perfusion (A-NRP) during organ procurement is a common practice in some centers due to its benefits on abdominal grafts. This study aimed to assess whether the use of A-NRP in cDCD increases the frequency of bronchial stenosis in lung transplant (LT) recipients. A single-center, retrospective study including all LTs was performed between January 1, 2015, and August 30, 2022. Airway stenosis was defined as a stricture that leads to clinical/functional worsening requiring the use of invasive monitoring and therapeutic procedures. A total of 308 LT recipients were included in the study. Seventy-six LT recipients (24.7%) received lungs from cDCD donors using A-NRP during organ procurement. Forty-seven LT recipients (15.3%) developed airway stenosis, with no differences between lung recipients with grafts from cDCD (17.2%) and donation after brain death donors (13.3%; P = 0.278). A total of 48.9% of recipients showed signs of acute airway ischemia on control bronchoscopy at 2 to 3 wk posttransplant. Acute ischemia was an independent risk factor for airway stenosis development (odds ratio = 2.523 [1.311-4.855], P = 0.006). The median number of bronchoscopies per patient was 5 (2-9), and 25% of patients needed >8 dilatations. Twenty-three patients underwent endobronchial stenting (50.0%) and each patient needed a median of 1 (1-2) stent. Incidence of airway stenosis is not increased in LT recipients with grafts obtained from cDCD donors using A-NRP.

Establishing the Role of Iridoids as Potential Kirsten Rat Sarcoma Viral Oncogene Homolog G12C Inhibitors Using Molecular Docking; Molecular Docking Simulation; Molecular Mechanics Poisson-Boltzmann Surface Area; Frontier Molecular Orbital Theory; Molecular Electrostatic Potential; and Absorption, Distribution, Metabolism, Excretion, and Toxicity Analysis.

The RAS gene family is one of the most frequently mutated oncogenes in human cancers. In KRAS, mutations of G12D and G12C are common. Here, 52 iridoids were selected and docked against 8AFB (KRAS G12C receptor) using Sotorasib as the standard. As per the docking interaction data, 6-O-trans-p-coumaroyl-8-O-acetylshanzhiside methyl ester (dock score: -9.9 kcal/mol), 6'-O-trans-para-coumaroyl geniposidic acid (dock score: -9.6 kcal/mol), 6-O-trans-cinnamoyl-secologanoside (dock score: -9.5 kcal/mol), Loganic acid 6'-O-beta-d-glucoside (dock score: -9.5 kcal/mol), 10-O-succinoylgeniposide (dock score: -9.4), Loganic acid (dock score: -9.4 kcal/mol), and Amphicoside (dock score: -9.2 kcal/mol) showed higher dock scores than standard Sotorasib (dock score: -9.1 kcal/mol). These common amino acid residues between iridoids and complexed ligands confirmed that all the iridoids perfectly docked within the receptor's active site. The 100 ns MD simulation data showed that RMSD, RMSF, radius of gyration, and SASA values were within range, with greater numbers of hydrogen bond donors and acceptors. MM/PBSA analysis showed maximum binding energy values of -7309 kJ/mol for 6-O-trans-p-coumaroyl-8-O-acetylshanzhiside methyl ester. FMO analysis showed that 6-O-trans-p-coumaroyl-8-O-acetylshanzhiside methyl ester was the most likely chemically reactive molecule. MEP analysis data highlighted the possible electrophilic and nucleophilic attack regions of the best-docked iridoids. Of all the best-docked iridoids, Loganic acid passed Lipinski, Pfizer, and GSK filters with a similar toxicity profile to Sotorasib. Thus, if we consider these iridoids to be KRAS G12C inhibitors, they will be a boon to mankind.

Changing the method of consent to increase the numbers of cadaveric donors in Saudi Arabia: the autonomy paradox

Background: In Saudi Arabia, the gap between the demand and availability of organs persists, with a total of 13,731 patients who remain on the waiting list in 2019. Family refusal is a major obstacle limiting donation since their consent must be obtained prior to the retrieval of organs. The cause of family refusal is mainly due to the unknown wishes of their loved one to become a donor. This analysis aimed to compare three systems of obtaining consent in terms of effectiveness, respect for personal autonomy, and the cultural role of families in Saudi Arabia to ensure feasibility and effectiveness in increasing the number of donors. Policy alternatives and implications: The consent systems include opt-in (explicit consent), opt-out (presumed consent), and mandated choice systems. The mandated choice policy might be the optimal solution to investigate since it could balance the respect for individual autonomy and the cultural role of families in Saudi Arabia. Conclusions and recommendations: Mandated choice could be an option that ensures the respect of personal autonomy while influencing the next of kin's decision to donate the organs. Nevertheless, more research should be conducted to support adopting this policy in the Saudi context. Additionally, a recommendation to decision makers is to utilize the Tawakkalna app to send alerts to the next of kin when a user registers as a donor with the user's consent.

P-606 Does trigger timing make a difference in oocyte donation?

Abstract Study question Is there optimal trigger timing in controlled ovarian stimulation (COS) for egg donors for better clinical outcome? Summary answer Different trigger timings may not affect oocyte maturity rate. 35 hour’s trigger may create optional timing for embryology to complete fertilization into a natural concept. What is known already Trigger exposure time is still a debatable clinical issue. Ovulation is triggered by administration of hCG or GnRH agonist, with retrieval taking place between 35th and 38th hour post triggering. There was a tendency to decrease post maturity risk for MII oocytes also early triggering will create optional timing for embryology laboratory for denudation, oocyte vitrification and fertilization process under oocyte cytoplasmic maturity (38 hours post trigger) and natural concept fertilization (till 40 hours post trigger) for better clinical outcome. Study design, size, duration This single center retrospective study included oocyte donors (n = 1289) with different timing of eggs retrieving. They were divided into two groups: group A, with exposure of the medicine trigger for 35 h and group B with timing which was 36 h before egg retrieval. We evaluated the concordance between the follicle-to-oocyte index (FOI), antral follicle count (AFC), number of MII oocytes, maturation rate (MR), utilization rate (UR) and the timing of triggering. Participants/materials, setting, methods The number of donors was 784 and 505 in A and B groups respectively. The mean age of the patients in this study was (SD) 26,2 (3,2) and 26,7 (3,3) years. Cycle characteristics were compared. Data was assessed using the Shapiro-Wilk test for the normality of the distribution of the variables. The association between COS cycle parameters and the differences in COS output was assessed by T-Student (parametric) or U-Mann-Whitney (non-parametric). Main results and the role of chance Donors in groups A and B had a similar mean number of oocytes retrieved (33,50±14,12 vs 30,44±13,00), in groups A and B respectively. The same tendency with no statistical difference was mentioned for values number of MII oocytes (SD): 25,16 (11,73) and 20,50 (10,19), for MR - 81% vs 80% and for AFC: 33,50 (14,18) and 30,44 (13,00) in groups A and B, respectively. Unexpectedly, values for UR and FOI (SD) were statistically significant different (p = &amp;lt;0.05): 94,1% (17,2) vs 89,1% (20,2) and 92,51 (11,43) vs 83,43 (15,63), accordingly, in group A and B respectively. Group A donor oocytes vitrified on 38 hours post trigger and fertilized on 40 hours from sibling oocytes. Group B donor oocytes vitrified on 39 hours and fertilized on 42 hours from sibling oocytes. Values for oocyte survival rate post warming were statistically non-significant different (p &amp;gt; 0.05): 96,64% (10,95) vs 95,08% (10,03). Cleavage arrest rate were statistically significant different; 8,01% vs 28,06% and used blastocysts rate were statistically significant different; 54,67% (5,02) vs 42,36% (4,08). Values for fertilization were statistically non-significant different; (p &amp;gt; 0.05): 98,64% (12,24) vs 97,08% (11.96) and used blastocysts rate were statistically significant different; 67,22% (6,18) vs 51,88%. (5,07) Limitations, reasons for caution This study is limited by its retrospective nature and the established strict time parameters of the study can be considered a limitation. Wider implications of the findings As we can see, the issue of the optimal period for oocyte retrieval after the administration of human chorionic gonadotropin should be considered very individually and in further studies it is possible to take into account wider time intervals in the design of trials. Trial registration number not applicable

P-430 Characterization of secondary follicles from cultured cryopreserved-thawed human ovarian cortical tissue

Abstract Study question Can we obtain secondary follicles from cultured cryopreserved-thawed human cortical tissue? Summary answer We obtained a comparable percentage of secondary follicles after culture of cryopreserved-thawed human cortical tissue to that reported after culture of fresh human cortical tissue. What is known already The complete in vitro maturation of oocytes starting from primary oocytes (present in unilaminar follicles) until mature MII oocytes has been achieved previously by two different multi-step culture protocols. These protocols were applied to culture fresh ovarian cortical tissue from adult cisgender donors. However, the efficiency of these two protocols for growing unilaminar follicles to secondary follicles starting from cryopreserved cortical tissue from cisgender patients has not been investigated. As the ovarian tissue available for fertility preservation is cryopreserved, it is important to understand the potential of cryopreserved unilaminar follicles to mature in vitro. Study design, size, duration Cryopreserved ovarian cortical tissue from 4 cisgender adult donors was used for in vitro culture. According to the existing culture protocols, cortical ovarian tissue was cultured either for 8 days using the first step medium (Telfer’s medium) reported by M.McLaughlin 2018 (doi: 10.1093/molehr/gay002) or for 7 and 21 days using the first step medium (Xu’s medium) reported by Xu 2021 (doi: 10.1093/humrep/deab003). Participants/materials, setting, methods Ovarian cortical tissue obtained from adult cisgender donors undergoing oophorectomy for fertility preservation purposes was cryopreserved before chemotherapy. The cryopreserved ovarian cortical tissue was thawed and cut into small pieces. Several pieces were fixed immediately (day 0), the others were either cultured in Telfer’s medium or Xu’s medium. After culture, follicle survival, growth and morphology were assessed by histology and immunofluorescence. Main results and the role of chance We performed quantification of the different follicular stages (primordial, primary, secondary and atretic) after culture and observed that the percentage of secondary follicles increased independently of the culture media used. However, the ovarian cortical tissue cultured using Telfer’s protocol resulted in a higher percentage of secondary follicles and lower percentage of atretic follicles compared to that using Xu’s protocol. After culture, the ovarian cortical tissue was further immunostained for TUNEL, PCNA, COLLIV, STAR, AMH and KRT19. We observed that secondary follicles present in ovarian cortical tissue cultured in Telfer’s medium showed more proliferative (PCNA+) FOXL2+ granulosa cells and less apoptotic (TUNEL+) stromal cells. By contrast, ovarian cortical tissue cultured in Xu’s medium showed less proliferative (PCNA+) FOXL2+ granulosa cells and more apoptotic (TUNEL+) stromal cells. Moreover, the expression of AMH was high in granulosa cells of secondary follicles present in ovarian cortical tissue cultured in Telfer’s medium and low in Xu’s medium. Finally, in both Telfer’s and Xu’s medium cultures the expression of KRT19 was low in granulosa cells of secondary follicles present in ovarian cortical tissue. Limitations, reasons for caution The number of donors was limited and the study lacked fresh ovarian cortical tissue as control. Only the first step in Telfers’ and Xu’s protocol was performed, hence further culture is required to determine whether complete maturation of oocytes in vitro is possible starting from cryopreserved human cortical tissue. Wider implications of the findings Our study showed evidence of follicular growth in cryopreserved-thawed human ovarian cortical tissue after a period of in vitro culture. This is an important first step to achieve in vitro maturation of oocytes from cryopreserved-thawed human ovarian cortical tissue that could be used for clinical applications. Trial registration number NOT APPLICABLE

P-458 Egg donation in the Czech Republic: Responsibility of ART clinics in the provision of information to potential egg donors

Abstract Study question Do ART clinics’ websites provide sufficient information for potential egg donors regarding all aspects related to donation? Summary answer There is an imbalance of information provided online by ART clinics. The benefits exceed the potential side effects and risks associated with donation. What is known already There is high demand for egg donors in the Czech Republic due to the extreme interest of international couples in ART procedures, e.g. because of the affordability of the treatment, the lack of a waiting list or the extended age limit for recipients up to 49 years. Thus, for a population of approximately 10.5 million, there are more than 40 clinics specializing in reproductive medicine in the country. Study design, size, duration In this research, all information available on ART clinics’ websites for egg donors was analyzed. Each clinic has a different advertising and marketing strategy, and in this work, we will compare the information provided by public and private clinics regarding the egg donation process. Five themes have emerged for the analysis: 1. General information 2. Legislation, 3. Benefits, 4. Risks, 5. Advertisement. The duration of this research was 4 months. Participants/materials, setting, methods A quantitative-qualitative analysis of recruitment strategies of IVF centers in the Czech Republic (29 unique clinic websites, 12 of which were specifically designed for marketing purposes) based on 16 criteria reflecting different donor needs. Main results and the role of chance In the case of donor recruitment, there are registered websites with predominantly suggestive slogans, emotive photos, and only positive stories of donors highlighting psychological, health, or financial benefits. The exact amount of remuneration (20.000 - 33.000 CZK) was specified by 89.7 % of clinics. The lower and upper limit are not regulated by law in the Czech Republic. ART clinics set the limit themselves to attract more donors by offering higher financial compensation and other benefits. This causes a huge imbalance between bigger and smaller ART clinics causing donor recruitment to become the focus of marketing strategies. The potential risks associated with donation were found in only 51,7 % of clinics’ websites. Not only is this an important question of legal noncompliance, but the misinformation may also cause disappointment and feelings of betrayal among donors. It may also result in the emergence of anti-campaigns, impacting the number of donors and devaluing donation in general. Therefore, there is a need to find a compromise between marketing strategies and providing a complete, transparent, and truly informative picture for potential donors in advance of the donation program. Limitations, reasons for caution We analyzed all ART providers that presented their facility online, focussing on both private and public providers. Public providers had very little information available about ART treatments in general let alone donor programs, so minimal information was available. Wider implications of the findings We believe that it's crucial to inform all donors not only about benefits associated with donation but also of potential risks, so they can make an informed decision about donation and also about their reproductive health and future parenthood. Trial registration number TL05000144

Characteristics and mechanism of Glutathione in inhibiting coal spontaneous combustion

Inhibitors play an important role in preventing and controlling coal spontaneous combustion (CSC). In this study, the inhibitory effects of antioxidant-reduced glutathione (G-SH) on CSC were examined. Thermogravimetric-differential scanning calorimetry (TG-DSC), cross-point temperature (CPT), and oxidation product tests were used to examine the effect of G-SH on the tendency of CSC and compare the discrepancy in the inhibition effect of G-SH and the halogen inhibitor. The changes in the free radical type, concentration, and surface functional groups in coal before and after the addition of G-SH were analyzed using electron spin resonance spectroscopy (ESR) and Fourier transform infrared spectroscopy (FT-IR). Six common active radical models were constructed, and the thermodynamic parameters of the reaction were calculated using density functional theory (DFT). The results revealed that G-SH inhibits the spontaneous combustion of coal. The inhibitory effect of G-SH was significantly stronger than that of the halogen salt inhibitors CaCl2 and MgCl2, and the higher the concentration of G-SH, the stronger is the inhibitory effect. The characteristic temperature points in the thermogravimetric experiment of coal samples with G-SH shifted to a higher temperature zone, and the CO concentration and oxygen consumption were lower than those of raw coal. After G-SH treatment, the type and relative concentration of free radicals in coal were lower than those in raw coal, the content of aliphatic hydrocarbon functional groups and oxygen-containing functional groups decreased, and the content of sulfur-containing functional groups increased. According to the calculation of Gibbs free energy and reaction enthalpy, G-SH can effectively neutralize the active free radicals in the process of coal oxidation, and the reaction activity with the free radicals in the process of coal oxidation is ·OOH > ·OH > ·CH3 > RO· > R· > ROO·. According to the experimental results, it is inferred that G-SH continuously supplies a large number of hydrogen donors (·H) for the reaction during the oxidation process and simultaneously neutralizes carbon free radicals and carbon oxygen free radicals, thereby reducing the concentration and reactivity of free radicals in the whole chain reaction process and blocking the occurrence of coal-oxygen composite reaction.

Избирательный скрининг на наличие антител к ядерному антигену вируса гепатита В у доноров в Хабаровске

The article analyzes the results of selective screening for the presence of antibodies to the core antigen of the hepatitis B virus in donors in Khabarovsk for the period 2021–2022 in accordance with the order of the Ministry of Health of the Russian Federation No. 1166n dated October 28, 2020. Hepatitis B virus core antigen was detected in 35 donors, which accounted for 14.5% of the number of studies and 0.07% of the total number of donors for 2021–2022. Investigation of blood samples of donors for the presence of antibodies to the core antigen of the hepatitis B virus makes it possible to identify infected HBsAg-negative donors and provides additional viral safety of blood transfusions

HLA Linked Regional Differences in Donor Selection: A 9-Year Study of the Swiss Registry

Introduction: The large HLA diversity in worldwide populations is a major challenge for matched unrelated haematopoietic stem cell (HSC) donor searches. The impact of regional diversity on the effective HSC donor selection has not been documented so far for national registries. Methods: The aim of the study was to analyse the 532 consecutive work-up (WU) requests received by Swiss Blood Stem Cells (SBSC), over a 9-year period (2011–2019) with respect to criteria including the geographical origin of the donors as derived from the postal codes, countries requesting SBSC donors, HLA-matching parameters, and patients’ HLA haplotype frequencies. Results: Highly matched donors (10/10) represented 73.5% of the WU, whereas 8–9/10 mismatched donors accounted for 24.0%. The remaining donors were 7–8/8 matched (1.7%) or had an unknown matching grade (0.8%). Among the 10/10 matched patient/donor pairs with full HLA-DPB1 typing information, the rate of 11–12/12 matched donors was 73.3%. Of the 532 WU requests, 47.6% were for patients of the four neighbouring countries and for national patients. The ratio of WU requests was directly proportional to the total number of donors registered in each region (Pearson’s r = 0.977). However, for two regions (lemanic and north-eastern areas of Switzerland (CH)), the proportion of selected donors was slightly above the min-max ratio of registered donors throughout the study period. The number of WU requests differed between countries when considering donors from the northern and southern parts of the country delineated by the alpine barrier. Conclusion: This study shows the value of the SBSC registry for both national and international patients. Two countries (USA and Germany) which operate the two worldwide largest registries (>19 million donors) requested 30% of SBSC registered donors, while the Swiss transplant centres accounted for 13% of the WU requests. When considering the geographic origin of SBSC donors, we observe a correlation of WU requests with the total number of registered donors in each subregion. This finding thus supports recruitment efforts throughout all regions. Interestingly, donors from three regions (lemanic area, Zurich and Ticino) are slightly over-represented, which is possibly related to higher HLA haplotypic diversity. A focus on planning recruitment in these regions might contribute to more successful donor searches.