Female Donors Research Articles

Regular high-frequency whole blood donation and risk of cardiovascular disease in middle-aged and older blood donors in Australia.

Previous mixed findings on the associations between whole blood (WB) donation and risk of cardiovascular diseases (CVD) may in part reflect inadequate adjustment for the "healthy donor effect" (HDE). We used the Sax Institute's 45 and Up Study linked with blood donation history and other health-related databases to examine the association between regular, high-frequency WB donation and the risk of CVD. To mitigate the impact of HDE, we used a "5-years qualification period," in which donors must donate at least 1 WB donation in the 1st and 5th year of "qualification period." We then compared the risk of CVD in the years following the "qualification period" between the regular high-frequency WB donors (≥2 WB donation in each qualification year) and others using Cox proportional-hazards models. Analyses were adjusted for potential confounders, such as sociodemographic, lifestyle, and health-related variables, and results are reported separately for male and female donors. A total of 2736 male and 2917 female donors were included in the analyses. The median years of follow-up per donor was 5.84 years (Q1-Q3, 5.47-6.23). The rate of CVD hospitalization was 11.20 and 4.50 per 1000 person-years for males and females, respectively. In fully adjusted models, the risk (hazard ratio) of CVD in regular high-frequency donors compared to other donors was 0.93 (95% Confidence Interval (CI), 0.68-1.29) for males and 0.79 (95% CI, 0.49-1.28) for females. We did not observe a statistically significant reduction of CVD risk in regular, high-frequency WB donors when adjusted for potential confounders.

Effect of Donor Sex on Recipient Mortality in Transfusion

BackgroundConflicting observational evidence exists regarding the association between the sex of red-cell donors and mortality among transfusion recipients. Evidence to inform transfusion practice and policy is limited.MethodsIn this multicenter, double-blind trial, we randomly assigned patients undergoing red-cell transfusion to receive units of red cells from either male donors or female donors. Patients maintained their trial-group assignment throughout the trial period, including during subsequent inpatient and outpatient encounters. Randomization was conducted in a 60:40 ratio (male donor group to female donor group) to match the historical allocation of red-cell units from the blood supplier. The primary outcome was survival, with the male donor group as the reference group.ResultsA total of 8719 patients underwent randomization before undergoing transfusion; 5190 patients were assigned to the male donor group, and 3529 to the female donor group. At baseline, the mean (±SD) age of the enrolled patients was 66.8±16.4 years. The setting of the first transfusion was as an inpatient in 6969 patients (79.9%), of whom 2942 (42.2%) had been admitted under a surgical service. The baseline hemoglobin level before transfusion was 79.5±19.7 g per liter, and patients received a mean of 5.4±10.5 units of red cells in the female donor group and 5.1±8.9 units in the male donor group (difference, 0.3 units; 95% confidence interval [CI], −0.1 to 0.7). Over the duration of the trial, 1141 patients in the female donor group and 1712 patients in the male donor group died. In the primary analysis of overall survival, the adjusted hazard ratio for death was 0.98 (95% CI, 0.91 to 1.06).ConclusionsThis trial showed no significant difference in survival between a transfusion strategy involving red-cell units from female donors and a strategy involving red-cell units from male donors. (Funded by the Canadian Institutes of Health Research; iTADS ClinicalTrials.gov number, NCT03344887.)

Unexpectedly high mutation rate of cyp11b1 compared to cyp21a2 in randomly-selected turkish women: a large screening study.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders resulting from enzyme deficiencies associated with steroidogenesis. The clinical presentation of non-classic CAH (NCAH) in females is often indistinguishable from other hyperandrogenic disorders like polycystic ovary syndrome (PCOS). The data on the prevalence of NCAH in unselected women in the literature is scanty. The research aimed to evaluate the prevalence of NCAH, carrier frequencies, and the correlation between clinical symptoms and genotype in Turkish women. The study group comprised two hundred and seventy randomly-selected unrelated asymptomatic women of reproductive age (18-45). Subjects were recruited from female blood donors. All volunteers underwent clinical examination and hormone measurements. The protein-encoding exons and exon-intron boundaries of the CYP21A2, CYP11B1, HSD3β2 and CYP21A2 promoter were sequenced by direct DNA sequencing. After genotyping, seven (2.2%) individuals were diagnosed with NCAH. The heterozygous carrier frequencies of CYP21A2, CYP21A2 promoter, CYP11B1, and HSD3β2 genes with 34, 34, 41, and 1 pathologic mutation were determined at 12.6%, 12.6%, 15.2%, and 0.37% of volunteers, respectively. Gene-conversion (GC) frequencies between CYP21A2/CYP21A1P and CYP11B1/CYP11B2 were determined as 10.4% and 14.8%, respectively. Despite GC-derived higher mutation frequency determined in the CYP11B1 gene, the reason for the low frequency of NCAH due to 11OHD compared to 21OHD might be that gene-conversion arises with active CYP11B2 rather than an inactive pseudogene. HSD3β1 exhibits high homology with HSD3β2 located on the same chromosome; remarkably, it demonstrates low heterozygosity and no GC, most probably the outcome of a tissue-specific expression pattern.

Sphingosine 1-phosphate has a negative effect on RBC storage quality.

Blood storage promotes the rapid depletion of red blood cell (RBC) high-energy adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (DPG), which are critical regulators of erythrocyte physiology and function, as well as oxygen kinetics and posttransfusion survival. Sphingosine-1-phosphate (S1P) promotes fluxes through glycolysis. We hypothesized that S1P supplementation to stored RBC units would improve energy metabolism and posttransfusion recovery. We quantified S1P in 1929 samples (n= 643, storage days 10, 23, and 42) from the REDS RBC Omics study. We then supplemented human and murine RBCs from good storer (C57BL6/J) and poor storer strains (FVB) with S1P (1, 5, and 10 μM) before measurements of metabolism and posttransfusion recovery. Similar experiments were repeated for mice with genetic ablation of the S1P biosynthetic pathway (sphingosine kinase 1 [Sphk1] knockout [KO]). Sample analyses included metabolomics at steady state, tracing experiments with 1,2,3-13C3-glucose, proteomics, and analysis of end-of-storage posttransfusion recovery, under normoxic and hypoxic storage conditions. Storage promoted decreases in S1P levels, which were the highest in units donated by female or older donors. Supplementation of S1P to human and murine RBCs boosted the steady-state levels of glycolytic metabolites and glycolytic fluxes, ie the generation of ATP and DPG, at the expense of the pentose phosphate pathway. Lower posttransfusion recovery was observed upon S1P supplementation. All these phenomena were reversed in Sphk1 KO mice or with hypoxic storage. S1P is a positive regulator of energy metabolism and a negative regulator of antioxidant metabolism in stored RBCs, resulting in lower posttransfusion recoveries in murine models.

Transfusion-Related Acute Lung Injury (TRALI): A Narrative Literature Review

Transfusion-related acute lung injury (TRALI) is defined as the onset of respiratory distress in a patient after receiving a blood component transfusion. So far, TRALI is considered a rare complication in the field of blood transfusion. However, in the last decade, there has been a shift in perspective. Currently, the US Food and Drug Administration recognizes the syndrome as the leading cause of transfusion-related death. This literature review aims to describe TRALI and its prevention strategies. Understanding the pathogenesis of TRALI drives prevention strategies from a blood bank perspective. A major breakthrough in efforts to reduce the incidence of TRALI was excluding female donors from the high plasma volume product, which resulted in an approximately two-thirds reduction in incidence. However, this strategy has not completely eliminated complications of transfusion. In recent years, research has identified patient-associated risk factors for the development of TRALI and empowered clinicians to take an individualized approach to patients requiring transfusion.

INSTRUMENTATION INACCURACIES STRONGLY INFLUENCE THE BIOMECHANICAL AND COMPUTATIONAL FAILURE RISK OF FRACTURE FIXATIONS

Despite past advances of implant technologies, complication rates of fixations remain high at challenging sites such as the proximal humerus [1]. These may not only be owed to the implant itself but also to dissatisfactory surgical execution of fracture reduction and implant positioning. Therefore, the aim of this study was to quantify the instrumentation accuracy of a highly standardised and guided procedure and its influence on the biomechanical outcome and predicted failure risk.Preoperative planning of osteotomies creating an unstable 3-part fracture and fixation with a locking plate was performed based on CT scans of eight pairs of low-density proximal humerus samples from elderly female donors (85.2±5.4 years). 3D-printed subject-specific guides were used to osteotomise and instrument the samples according to the pre-OP plan. Instrumentation accuracies in terms of screw lengths and orientations were evaluated by comparing post-OP CT scans with the pre-OP plan. The fixation constructs were biomechanically tested until cyclic cut-out failure [2]. Failure risks of the planned and the post-OP configurations were predicted using a validated sample-specific finite element (FE) simulation approach [2] and correlated with the experimental outcomes.Small deviations were found for the instrumented screw trajectories compared to the planned configuration in the proximal-distal (0.3±1.3º) and anterior-posterior directions (-1.7±1.8º), and for screw tip to joint distances (-0.3±1.1 mm). Significantly higher failure risk was predicted for the post-OP compared to the planned configurations (p<0.01) via FE. When incorporating the instrumentation inaccuracies, the biomechanical results could be predicted well with FE (R2=0.70).Despite the high instrumentation accuracy achieved using sophisticated subject-specific 3D-printed guides, even minor deviations from the pre-OP plan significantly increased the FE-predicted risk of failure. This underlines the importance of intraoperative guiding technology [3] in tandem with careful pre-OP planning to assist surgeons to achieve optimal outcomes.AcknowledgementsThis study was performed with the assistance of the AO Foundation via the AOTRAUMA Network.

Identification, forensic evidences and effect of the most used lip cosmetics on the human STR profiling at Kingdom of Saudi Arabia

This study aimed to identify the DNA STR profiles that were obtained from the lips with various lip cosmetics involved in lip pencil, lipsticks and lip gloss for a brand – Makeup Forever and lip balms (Labello brand) – have been popularly used by Saudi women at KSA. The study was involved 35 unrelated participants (healthy female donors) aged between 26 and 32. The swabbing of lip cosmetics was done prior to using them as negative control samples, other sterilized swabs were collected from the used lip cosmetics which contained the lip cells for each participant as a study sample. Moreover, the buccal swabs were firmly collected from the cleaned oral cavities for the same donors as reference samples. The air-drying of the collected swabs was done for ten minutes at room temperature and then stored them at − 20 °C before the DNA analysis. The 7500 Real-Time PCR (qRT-PCR) was quantified the extracted DNA. The amplification of 16 STR loci was done using the AmpFlSTR® Identifiler® PCR amplification kit using the Thermocycler ABI 9700 to amplify the extracted DNA. The Applied Bio-systems 3130™ Genetic Analyzer with Gene Mapper® ID-X Software v3.5 was used to analyze the PCR products. The data for quantifying DNA recorded significant decrease in the concentrations of DNA samples ranged from 0.15 to 0.55 ng/µL in comparison to the reference samples, while DNA was not detected in all the negative control samples. Some STR loci showed considerably high inhibition and low heterozygosity loss in the study samples compared to the reference and negative samples. The possibility of extracting DNA samples from lip cosmetics were used in the present study could be useful and successful in some cases due to the effect of the chemical compositions such as heavy pigments, organic components, and aromatic wax on the STR profiles in the lip cosmetics, especially in the lipsticks, lip glosses and lip pencils.

Duplicated Inferior Vena Cava in a 69-Year-Old White Female Donor

While relatively uncommon, a duplication of the inferior vena cava is moderately well-discussed in the literature. This anatomical variation was noted in a 69-year-old white female donor. This variation is typically asymptomatic; however, it can be associated with complications, such as confusion with a mediastinal mass, increased risk for thromboembolism, and hemorrhage during surgery. It is also associated with a handful of comorbidities, including, but not limited to, congenital renal anomalies such as horseshoe kidney or fused crossed kidney. Research supports that the variation of a duplicated IVC (DIVC) can be due to a failure of the left supracardinal vein to regress during embryonic development.

Abstract 1933: Transcriptomic profiling of Hispanic colorectal cancer disparities

Abstract Colorectal cancer (CRC) was reported as the third most diagnosed cancer worldwide with approximately 1.93 million new cases reported in 2020. Within the U.S., the incidence and death rates differ by ethnicity. Among Hispanics, CRC accounted for 12% and 8% of all estimated new cases of cancer and 11% and 9% of all cancer deaths in men and women, respectively, in 2018. Though CRC is preventable, and the overall survival rate is approximately 90% when detected at early stages, only about 39% of CRC patients are diagnosed in the early stages, mostly because screening rates in the US are low, especially among Hispanics. Access to health care for Hispanics is limited when compared to non-Hispanic Whites (NHWs); as a result, they tend to present with later-stage CRC, which likely accounts for their inferior survival after CRC. Essential to improving treatment, prognosis, and detection strategies is the identification and validation of new ethnicity-specific transcriptomic profiles. Here, we have conducted RNA sequencing from Hispanic and NHW CRC (n=10 each) and normal adjacent tissues (NATs; n=3 each), to identify the differentially expressed genes (DEGs) in these two populations. The Illumina sequencing reads were mapped against the reference human genome, and the read counts were normalized using the median of ratios method using DESeq2 software. The transcriptomic analysis revealed that as compared to the respective NATs, 7222 and 7873 genes were observed to be differentially expressed in NHW and Hispanic CRC tissues. Among these, 213 and 363 genes were unique to the NHW and Hispanic CRC cohorts, respectively. Within the Hispanic cohort, gender-based analyses revealed that 504 and 266 genes were differentially expressed in the female and male donors (n=5 each), respectively, as compared to the NHW counterparts. Further, 271 and 475 genes were found to be differentially expressed in early (stage I/II; n=5) and late (stage III/IV; n=3) stages of Hispanic CRC tissues, respectively, as compared to the NHW counterparts. Pathway enrichment analysis of the unique DEGs from the Hispanic and NHW cohorts was conducted using Ingenuity Pathway Analysis software. The genes involved in cysteine biosynthesis, ferroptosis, and GABA receptor signaling pathways were seen to be enriched in the NHW cohort, whereas the genes involved in glucocorticoid receptor (GR) signaling, bile, and androgen biosynthesis pathways were enriched in the Hispanic cohort. Previous studies have implicated, GR signaling to promote tumor heterogeneity and invasion in CRC via CDK1, or bile acids to regulate numerous genes including p53, CDK1, cyclooxygenase 2, IL8, and various miRNAs leading to CRC metastasis. As each pathway likely regulates specific cellular behaviors, the DEGs identified from this study will constitute potential ethnicity-specific biomarkers or attractive targets for the development of novel therapeutic interventions. Citation Format: Soumya Nair, Aditi Kulkarni, Sourav Roy. Transcriptomic profiling of Hispanic colorectal cancer disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1933.

Abstract 2140: DNA damage response in circulating tumor cells shows predictive value for metastatic breast cancer patients receiving CDK4/6 inhibitors

Abstract Background: Resistance to CDK4/6 inhibitors (CDK4/6i), like Palbociclib and Ribociclib, plus endocrine therapy (TX) is an omnipresent topic for metastatic (M), hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) patients (pts). Circulating tumor cells (CTCs) represent the oncogenic heterogeneity in real time. Here, we aim to identify markers of resistance to CDK4/6i by mRNA profiling of CTCs. Methods: Blood of 90 HR+/HER2-MBC pts drawn before CDK4/6i plus endocrine TX (baseline: n=57 pts first line; n=33 second or more line pts), 19 HR+/HER2-MBC pts receiving endocrine monoTX (control group) and matched samples of 78/62 of these 109 pts after six months of TX/at progression (PD) were analyzed. Isolation of CTCs was conducted using the AdnaTest EMT2/StemCell Select. Expression profiling was conducted with preamplified cDNA utilizing QuantiNova LNA Probe assays targeting 25 genes. qPCR data were normalized to CD45 and data of 20 healthy female donors. Consumables: QIAGEN, Germany. Only results with Benjamini Hochberg corrected p<0.05 in univariate Cox regression and multivariate Cox regression with non-adjusted p<0.05 are demonstrated. Results: At baseline, in pts treated with CDK4/6i in the first line, CETN2 (HR 3.6)/MLH3 (HR 4)/E2F1 (HR 5.3) overexpression signals in CTCs correlated significantly with shorter progression-free survival (PFS) and shorter overall survival [(baseline to death, OS) (HR 8.3/HR 4.9/HR 3.8)], whereas ESR1 signals correlated with a shorter OS (HR 4.4). After six months of TX, in CDK4/6i treated pts, CXCR4 and CETN2 signals correlated with a shorter PFS and the signal dynamics from baseline to six months of CXCR4, CETN2 and PCNA also correlated with a shorter PFS. At PD, STAT1 signals were identified as potential Ribociclib specific resistance markers and Hippo pathway inhibition as a potential new approach for postCDK4/6i TX, because TEAD2 and WWTR1 correlated with shorter remaining time to death. Conclusion: We identified overexpression of transcripts involved in DNA damage response mechanisms (CETN2, MLH3 and/or PCNA) at baseline to have predictive and/or prognostic value in first line CDK4/6i treated pts while signal dynamics of CETN2 and PCNA to six months of TX could serve as monitoring marker in these pts. Currently, further longitudinal blood sampling over the course of treatment is underway to give a deeper insight in resistance development under CDK4/6i treatment. Citation Format: Corinna Keup, Charlotte Gruber, Stefanos Ioannis Moukas, Mitra Tewes, Hans-Christian Kolberg, Rainer Kimmig, Sabine Kasimir-Bauer. DNA damage response in circulating tumor cells shows predictive value for metastatic breast cancer patients receiving CDK4/6 inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2140.

(519) Oversized Donors for Patients with Pulmonary Hypertension Awaiting Heart Transplant: Busting the Myth of Using Female Donors

(519) Oversized Donors for Patients with Pulmonary Hypertension Awaiting Heart Transplant: Busting the Myth of Using Female Donors

MP60-14 A CELLULAR ATLAS OF THE NORMAL ADULT HUMAN FEMALE URETHRA

You have accessJournal of UrologyCME1 Apr 2023MP60-14 A CELLULAR ATLAS OF THE NORMAL ADULT HUMAN FEMALE URETHRA John Lafin, Alicia Malewska, Philippe Zimmern, Maude Carmel, Gary Lemack, Douglas Strand, and Ramy Goueli John LafinJohn Lafin More articles by this author , Alicia MalewskaAlicia Malewska More articles by this author , Philippe ZimmernPhilippe Zimmern More articles by this author , Maude CarmelMaude Carmel More articles by this author , Gary LemackGary Lemack More articles by this author , Douglas StrandDouglas Strand More articles by this author , and Ramy GoueliRamy Goueli More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003318.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urinary voiding dysfunction is highly prevalent in aging women. A deeper understanding of the cellular composition of female urethra in the non-diseased state could provide insights into the etiology of dysfunction. Single cell RNA sequencing was performed on female urethra to generate a cellular atlas. METHODS: Urethra from female organ donors aged 18-45 (N=4) was collected fresh from surgery and enzymatically digested into a single cell suspension. Single cell RNA sequencing was performed using 10x Genomics V3 chemistry. Data were analyzed in Seurat for cell type annotation. Immunohistochemical validation of cell types was performed on FFPE sections using differentially expressed genes from clustered data. RESULTS: The female proximal urethral lumen is lined with a stratified urothelium composed of KRT5+/KRT14- basal cells with KRT13+ hillock epithelia and KRT4+ luminal epithelia. Ducts emerging from dorsal urethra (Skene's glands) contain basal and club cells similar to prostatic urethra. The urethral lumen is surrounded by two discrete layers of fibroblasts (peri-urethral and interstitial) and circumferential smooth muscle and skeletal muscle. CONCLUSIONS: The identification of 1) specialized fibroblasts surrounding the urethra, and 2) club cells in dorsal ducts could yield new insight into the regulation of infection, inflammation and obstruction, which are the putative etiologies of most urethral dysfunction. Source of Funding: DK115477, DK104310, DK129994 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e848 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information John Lafin More articles by this author Alicia Malewska More articles by this author Philippe Zimmern More articles by this author Maude Carmel More articles by this author Gary Lemack More articles by this author Douglas Strand More articles by this author Ramy Goueli More articles by this author Expand All Advertisement PDF downloadLoading ...

Successful Bridging to Allogeneic Hematopoietic Stem Cell Transplantation by Azacitidine and Venetoclax in a Case of Acute Myeloid Leukemia With t(3;3)(q21.3;q26.2) Developed Early After Orthotopic Heart Transplantation

A 48-year-old male patient developed acute myeloid leukemia (AML) with t(3;3)(q21.3;q26.2) chromosomal mutation 8 months after orthotopic heart transplantation from a human leukocyte antigen-unmatched brain-dead donor for cardiac sarcoidosis. He had sequelae of stroke and chronic renal failure at the time of AML diagnosis. He received 3 cycles of azacitidine and venetoclax induction therapy and achieved complete hematological remission with incomplete count recovery without causing severe complications, including infection. He sequentially underwent allogeneic peripheral blood stem cell transplantation from a HLA-8/8 matched, ABO-blood matched, unrelated female donor and successfully achieved donor cell engraftment. His transplanted heart was viable, and the coronary vessels were not damaged even after allogeneic peripheral blood stem cell transplantation. Although AML relapsed afterward, azacytidine/venetoclax was a tolerable bridging therapy even for early-onset AML after heart transplantation.

Prope tolerance after pediatric liver transplantation: Experience at Shiraz Organ Transplant Center

BackgroundChildren receive transplants at a younger age, and the period of immunosuppression therapy may extend over decades. However, immunosuppression seems to be responsible for long-term mortality and morbidity. Pediatric liver transplant recipients can benefit from achieving immune tolerance and the opportunity of freedom from lifelong immunosuppression. This study aimed to investigate the frequency of prope tolerance among pediatric liver transplant recipients and the characteristics of these patients. MethodsIn this retrospective cohort study of pediatric liver transplant recipients, the medical records of transplant recipients treated at Shiraz Organ Transplant Center between 1994 and 2017 were reviewed. Prope tolerance was defined as normal laboratory values and stable clinical status on low-dose monotherapy. Children treated with low-dose monotherapy were categorized as the prope tolerant group. We compared the characteristics of prope tolerant recipients on low-dose monotherapy with patients on standard immunosuppression, i.e. full-dose tacrolimus plus steroids and mycophenolate mofetil. The data were analyzed with the t-test, chi-squared test, and a Cox proportional hazard model at a 5% significance level in SPSS software version 16. ResultsA total of 585 children with a mean age of 8.32 ± 5.23 years were enrolled. 341 patients were categorized as prope tolerant and 244 comprised the full immunosuppression regimen group. Mean age at transplantation and rejection frequency were lower in the prope tolerant group (p < 0.001, p < 0.001). Based on the underlying diseases, metabolic/genetic, biliary tract, and cryptogenic liver diseases were significantly more prevalent in the prope tolerant group (p < 0.001). However, autoimmune liver disease was found to be more prevalent in the full immunosuppression regimen group. Also, those who received living organs (p = 0.001) and recipients of organs from female donors had a greater likelihood of achieving prope tolerant. According to the multiple Cox regression results, age at transplantation (p = 0.022), rejection frequency (p < 0.001), and autoimmune liver diseases (p = 0.028) had a prognostic effect on prope tolerance. ConclusionFactors as underlying disease, age at transplantation, and rejection frequency were factors that were predictive of prope tolerance in this sample of children. However, the risk of rejection should be considered during the tapering period.

A novel approach toward the generation of oocytes by direct diploid cell haploidization

Oocyte-mediated somatic cell haploidization is a process in which a diploid cell halves its chromosomal content by segregating its homologue within the ooplasm. Replacing the donor oocyte nucleus with a patient's female diploid somatic nucleus can generate patient-genotyped oocytes. Insemination of these resulting constructs enables their activation and induces a reductive meiotic division, haploidizing the diploid female donor cell that can subsequently support syngamy with the male genome and create a zygote. So far, experimental data for this method have been limited and have not consistently proven the generation of chromosomally normal embryos. Overall, we achieved reconstruction of murine oocytes with a micromanipulation survival rate of 56.5%, and a correct haploidization and fertilization rate of 31.2%, resulting in a 12.7% blastocyst rate. Time-lapse analysis revealed that reconstructed embryos underwent a timely polar body extrusion and pronuclear appearance followed by a satisfactory embryonic cleavage, comparable with the control. Whole genome sequencing of the analyzed embryos indicated that 27.3% (6/22) were properly diploid. Our findings suggest that diploid cell haploidization may be a feasible technique for creating functional gametes in mammals.

Sex disparity in dialysis and kidney transplantation over 20 years in Korea.

Sex disparity is prevalent in organ transplantations worldwide. This study aimed to understand sex disparities in dialysis and kidney transplantation in Korea over the last 20 years. Data for incident dialysis, waiting list registration, and donors and recipients were retrospectively collected between January 2000 and December 2020 from the Korean Society of Nephrology end-stage renal disease registry and the database of the Korean Network for Organ Sharing. Data regarding the proportion of females for dialysis, waiting list, and kidney transplantation donors or recipients were analyzed using linear regression analysis. The average proportion of females on dialysis over the past 20 years was 40.5%. The proportion of females on dialysis was 42.8% in 2000, and decreased to 38.2% in 2020, showing a decreasing trend. The average proportion of women on the waiting list was 38.4%, which was lower than that for dialysis. The average proportion of female recipients in living donor kidney transplantation and female living donors were 40.1% and 53.2%, respectively. The overall proportion of female donors in living donor kidney transplantation showed an increasing trend. However, there was no change in the proportion of female recipients in living donor kidney transplantation. Sex disparities in organ transplantation exist, including an increasing trend of female donors in living donor kidney transplantation. Further studies are needed to identify the biological and socioeconomic factors involved to resolve these disparities.

Exposure to oxLDL impairs TGF-β activity in human tendon cells

BackgroundPrevious studies have shown that patients with hypercholesterolemia experience elevated levels of oxidized LDL (oxLDL), a molecule which triggers inflammation and collagenase activity. In this study we discovered novel mechanistic effects of oxLDL on tendon cells and the mediators regulating matrix remodeling by analyzing the expression and activity of related proteins and enzymes. These effects may contribute to tendon damage in patients with high cholesterol.MethodsIsolated human tendon cells (male and female donors age 28 ± 1.4 age 37 ± 5.7, respectively) were incubated in the presence or absence of oxLDL. The influence of oxLDL on the expression level of key mRNA and proteins was examined using real time quantitative PCR, ELISA and Western blots. The activities of enzymes relevant to collagen synthesis and breakdown (lysyl oxidase and matrix metalloproteinases) were quantified using fluorometry. Finally, the isolated human tendon cells in a 3D construct were exposed to combinations of oxLDL and TGF-β to examine their interacting effects on collagen matrix remodeling.ResultsThe one-way ANOVA of gene expression indicates that key mRNAs including TGFB, COL1A1, DCN, and LOX were significantly reduced in human tendon cells by oxLDL while MMPs were increased. The oxLDL reduced the activity of LOX at 50 µg/ml, whereas conversely MMP activities were induced at 25 µg/ml (P ≤ 0.01). COL1A1 synthesis and TGF-β secretion were also inhibited (P ≤ 0.05). Adding recombinant TGF-β reversed the effects of oxLDL on the expression of collagens and LOX. OxLDL also impaired collagen matrix remodeling (P ≤ 0.01), and adding TGF-β restored the native phenotype.ConclusionExposure to oxLDL in patients with hypercholesterolemia may adversely affect the mechanical and structural properties of tendon tissue through a direct action of oxLDL on tendon cells, including impairment of TGF-β expression. This impairment leads to disturbed matrix remodeling and synthesis, thereby potentially leading to increased risk of acute or chronic tendon injury. Our discovery may provide an opportunity for developing effective treatments for tendon injury in hypercholesterolemia patients by targeting the TGF-β pathway.

PATTERNS OF SEROPREVALENCE FOR TRANSFUSION-TRANSMISSIBLE INFECTIONS AMONG BLOOD DONORS IN A BLOOD CENTRE OF NORTHEAST INDIA

Introduction: Transfusion– Transmissible Infections (TTIs) are the infections resulting from the introduction of a pathogen into a person through blood transfusion. In an attempt to mitigate the inherent risk of TTIs, the demographic information of blood donors including knowledge on local prevalence of infections and its pattern in the donor population is important for formulating recruitment strategies and planning other precautionary measures. Materials &amp; Methods: This cross-sectional study was conducted in the Blood Centre, Jawaharlal Nehru Institute of Medical Sciences, Imphal between January 2019 and December 2022. All donated blood units were tested for the mandatory TTI markers for HIV 1 &amp; 2, Hepatitis B, Hepatitis C, Syphilis and Malarial parasite. The prevalence and patterns of seropositivity for TTIs were studied based on the donor demographic characteristics such as donation type, gender and age group. Results: The overall seroprevalence among blood donors (n=31,563) was 1.79%. The seroprevalence was lower among voluntary donors (1.08%) than the replacement donors (2.10%). Seropositivities among female and male donors were 0.79% and 1.93% respectively. The lowest TTI seropositivity was seen among female voluntary donors (0.59%) and highest among male replacement donors (2.24%). The seroprevalence for specic TTI markers among the blood donors were 0.15% for HIV; 0.57% for HBV; 0.93% for HCV; 0.14% for Syphilis and no donor was found positive for Malaria. The frequency of TTI seropositivity was increased with increase in the age groups of donors in both sexes. There were 9 (0.029%) donors who had co-infection of TTIs. The patterns of TTI markers for co-infections were HCV+HIV=3; HCV+HBV=3; HCV+Syphilis=2 and HIV+ Syphilis=1. Conclusion: The measures to provide safe blood may include collection of blood from the targeted low risk donor population, using more sensitive testing methods, implementing pathogen reduction technologies and other public health measures.

Impact of Universal Donor History Questionnaire in Pre-Donation Deferrals a Tertiary Care Hospital Experience

Objective: The purpose of this research was to better understand the factors that lead to pre-donation deferral at a tertiary care hospital's Blood bank. Understanding the factors that lead donors to decline can inform more effective selection criteria. Study Design: Cross-sectional/Descriptive study Place and Duration: Diagnostic and research laboratory Liaquat university of Medical and Health Sciences Jamshoro Hyderabad. January 2022-December 2022 Methods: This study comprised of 2200 donors at blood bank of LUMHS. The UDHQ included 25 questions to assess donors' backgrounds in regards to things like injections, medicines, time since last donation, tattoos, general health, dental work, sexual relationships, malaria/T.B., surgery, jaundice, vaccination, positive viral markers, etc. Haemoglobin (Hemacue 50/Diaspect Hb with daily quality control), Heart rate/rhythm, Blood pressure, Body temperature, Weight/Height, and Jaundice were all part of the physical exam. Results: There were majority 1578 (71.7%) males and 622 (28.3%) female donors among all cases. Donors mean age was 26.12±9.88 years and mean weight was 61.3±8.49 kg. 1435 (65.2%) cases were from urban areas. Among all, 1650 (75%) donors were accepted and 550 (25%) donors were deferral. Most common cause of deferral was low hemoglobin followed by anemia, HCV, HBV, inappropriate pulse rate, low BP, jaundice, active infection, malaria, syphilis, allergy, aspirin intake, drugs, last donation, skin/eye colour and sexual relationship. There were 1870 (85%) cases of replacement donors among all cases. Conclusion: The selection of healthy blood and the reduction of donor injury will be made possible by a thorough pre-donation screening interview and physical examination. Our setup has a somewhat higher blood donor deferral rate because to stringent donor sector requirements and extra attention paid to donor selection processes. The increased replacement donor deferral rate is a result of refusals for past injection history and poor hemoglobin levels. Keywords: Donors, Deferrals, Hemoglobin, Infection, HCV

A variability in response of osteoclasts to zoledronic acid is mediated by smoking-associated modification in the DNA methylome

BackgroundClinical trials have shown zoledronic acid as a potent bisphosphonate in preventing bone loss, but with varying potency between patients. Human osteoclasts ex vivo reportedly displayed a variable sensitivity to zoledronic acid > 200-fold, determined by the half-maximal inhibitory concentration (IC50), with cigarette smoking as one of the reported contributors to this variation. To reveal the molecular basis of the smoking-mediated variation on treatment sensitivity, we performed a DNA methylome profiling on whole blood cells from 34 healthy female blood donors. Multiple regression models were fitted to associate DNA methylation with ex vivo determined IC50 values, smoking, and their interaction adjusting for age and cell compositions.ResultsWe identified 59 CpGs displaying genome-wide significance (p < 1e−08) with a false discovery rate (FDR) < 0.05 for the smoking-dependent association with IC50. Among them, 3 CpGs have p < 1e−08 and FDR < 2e−03. By comparing with genome-wide association studies, 15 significant CpGs were locally enriched (within < 50,000 bp) by SNPs associated with bone and body size measures. Furthermore, through a replication analysis using data from a published multi-omics association study on bone mineral density (BMD), we could validate that 29 out of the 59 CpGs were in close vicinity of genomic sites significantly associated with BMD. Gene Ontology (GO) analysis on genes linked to the 59 CpGs displaying smoking-dependent association with IC50, detected 18 significant GO terms including cation:cation antiporter activity, extracellular matrix conferring tensile strength, ligand–gated ion channel activity, etc.ConclusionsOur results suggest that smoking mediates individual sensitivity to zoledronic acid treatment through epigenetic regulation. Our novel findings could have important clinical implications since DNA methylation analysis may enable personalized zoledronic acid treatment.