Male Donors Research Articles

Donor age contributes more to the rheological properties of stored red blood cells than donor sex and biological age distribution

Variation in the quality of stored red cell concentrates (RCCs) has been linked to the biological age distribution of red blood cell (RBCs) subpopulations within blood products. Teen male RCCs contain higher proportions of biologically old RBC subpopulations, with poorer quality. This study sought to assess the contribution of donor sex and age on the deformability characteristics of different ages of RBC subpopulations in stored RCCs. On days 5, 14, 21, and 42 of hypothermic storage, RCCs from healthy teen male, senior male, teen female and senior female donors were biologically age profiled. The deformability of the resulting young (Y-RBCs) and old (O-RBCs) RBC subpopulations in addition to unseparated RBCs was assessed using ektacytometry. Over storage, donor age influenced the rheological profile of RBC subpopulations, with teen male RCCs having the largest reduction in Ohyper (the osmolality in the hypertonic region corresponding to 50% of the EImax). The strongest correlations between Ohyper and MCHC (R2 > 0.5) were witnessed with O-RBCs from senior donors, and to a lesser extent with teen males. O-RBCs from teens, particularly males, had higher elongation indices both under isotonic conditions and in the presence of an increasing osmotic gradient. Consistent across RBCs regardless of their biological age, teen samples were discovered to be more rigid (higher KEI). The donor-to-donor variation in age distribution of RBC subpopulations and its downstream effect on deformability serves as further evidence that factors beyond chronological aging could potentially impact the quality of red cell concentrates and variations in transfusion outcomes.

Factors Associated with Increased Risk of Contamination in Bone Marrow Transplants.

Hematopoietic cell transplantation (HCT) remains the definitive therapeutic modality for numerous malignant and non-malignant hematologic disorders. Conventional bone marrow remains a viable donor source for HCT. However, microbial contamination of bone marrow harvests may present a risk to immunocompromised recipients. This analysis sought to identify clinical factors associated with bone marrow contamination. We analyzed a single institution experience comprising 667 unique bone marrow harvests collected between 1999 and 2021. We trended the yearly microbial contamination rate over this time span. Harvest type (autologous vs allogenic), donor age, donor sex, physician experience, total nucleated cell (TNC) count, volume collected, and TNC concentration were included in a univariate (UV) and multivariate (MV) logistic model to assess which factors were associated with contamination. Males comprised 55.8% of the donor population and the median age of the cohort was 35 [IQR: 27-45]. There were 19 autologous, 151 related allogenic, and 497 unrelated allogenic transplants in this cohort. 87 of the 667 (13.0%) harvests were contaminated and essentially all contaminants were common skin flora. The yearly contamination rates displayed substantial variability, ranging from 0% to 42.9%, with no discernible trend. Harvest type did not exhibit a significant association with contamination risk. However, male donor sex was found to be significantly associated with a higher contamination rate (18%) compared to female sex (6.8%, p < 0.001). In both UV and MV logistic models, male sex emerged as the sole factor linked to contamination risk (OR: 2.90, 95% CI: 1.65 - 5.35). This analysis represents the largest single center investigation of bone marrow harvest microbial contamination rates. Notably, it is the first to establish an association between contamination and male donor sex. We propose that this association may be attributed to differences in skin flora composition or innate immune function between sexes, general hygiene practices or possibly the result of the frequent clipping of body hair in males prior to the harvest procedure. Further research is warranted to explore the underlying mechanisms and clinical implications of this novel finding.

Sequential Irradiation Does Not Improve Fatigue Crack Propagation Resistance of Human Cortical Bone at 15 kGy

Sequential irradiation has been advocated for mitigating the reduction in fatigue properties of tendon compared to a single dose. However, to our knowledge, its capability of mitigating fatigue losses in bone is unknown. Recently, we reported that sequential irradiation did not mitigate losses in high-cycle S-N fatigue life of cortical bone at 15 kGy; however, it is unclear if sequential irradiation provides a benefit to fatigue crack propagation resistance. Our previous study also showed that radiation-induced collagen chain fragmentation and crosslinking increased from 0 to 15 kGy, suggesting that both likely contribute to the reduction in high-cycle S-N fatigue life within this dose range. Our objectives were: 1) to evaluate the fatigue crack propagation resistance of cortical bone and the effect of radiation on fracture plane damage zone thickness (DZT) at the crack tip in the dose range of 0 to 15 kGy, and 2) to evaluate whether sequential irradiation at 15 kGy mitigates the loss of fatigue crack propagation resistance of cortical bone compared to a single irradiation dose. Compact tension specimens from four male donor femoral pairs (ages 21-61 years old) were divided into 5 treatment groups (0 kGy, 5 kGy, 10 kGy, 15 kGy, and a 15 kGy sequential irradiation dose of 5 kGy sequentially irradiated with 10 kGy) and subjected to fatigue crack propagation testing (n=3-4 specimens per group) where fatigue crack growth rate da/dN and cyclic stress intensity factor ΔK were determined. Following testing, specimens were bulk stained in basic fuchsin, embedded in poly(methylmethacrylate), sectioned, and mounted on acrylic slides to evaluate fracture plane DZT at known crack lengths. Sections were then imaged with a fluorescence microscope, and fracture plane DZT was measured using ImageJ (n=3-4 specimens per group) and analyzed as a function of ΔK. We observed a decrease in fatigue crack propagation resistance at 15 kGy compared to doses of 10 kGy or lower (p≤0.013). Fracture plane DZT decreased overall with increasing radiation dose from 0 to 15 kGy. Sequential irradiation offered no improvement in fatigue crack propagation resistance (p=0.98). Radiation-induced collagen chain fragmentation and crosslinking in this dose range likely contribute to a decrease in energy dissipation capability with increasing radiation dose. Other alternative radiation sterilization methods besides sequential irradiation may be warranted to mitigate radiation-induced tissue damage and extend the functional lifetime of structural cortical bone allografts.

Afterload mismatch is associated with gender mismatch and negatively affect long-term outcome after heart transplant

Abstract Background Cardiac physiology changes after heart transplant (HT), resulting in a restrictive physiology with an increase in both arterial elastance (Ea) and ventricular elastance (Ees). This leads to a higher susceptibility to develop afterload mismatch, although the early identification of this phenomenon has not yet been explored. The aim of this study is to identify the presence of afterload mismatch after HT, its determinants, and its impact on cardiac mortality. Methods We conducted an observational, single-centre study based on the historical cohort of patients who underwent HT from 1985 to 2015 at our institution. We included patients who had survived the first year after HT with left ventricular ejection fraction (LVEF) ≥ 50%, International Society of Heart and Lung Transplantation (ISHLT) cardiac allograft vasculopathy of grade 0-1, and ISHLT acute cellular rejection of grade 0-1R at 1 year after HT. Ea and Ees were calculated using a non-invasive method based on blood pressure and end-systolic volume and end-diastolic volume measured at transthoracic echocardiography. Patients were grouped in 3 categories according to the presence of increased afterload and afterload mismatch as follows: low afterload (LA - Ea lower the median), matched high afterload (MHA - Ea higher of equal than the median, Ees higher or equal than the median), afterload mismatch (AM - Ea higher or equal than the median, Ees lower than the median). The impact of AM on long-term outcome, defined as cardiac mortality, was investigated, as well as predictors of AM. Results The study cohort consisted of 345 HT patients. The median of Ea and Ees were 4.0mmHg/mL and 6.75mmHg/mL, respectively. 49 patients (13%) developed AM, while LA and MHA groups accounted for 49% and 36% of the cohort, respectively. Patients with AM were mostly male (91%), with ischemic heart disease (45%) and a higher percentage of left ventricular assisted device prior to HT (8%). LVEF was lower in AM (57% vs 63% and 64% for LA and MHA respectively, p &amp;lt; 0.0001), while stroke volume was lower than LA and similar to MHA (27ml vs 35mL and 26mL for LA and MHA respectively, p = 0.0001). Predictors of AM were male recipient from male donor (Mr/Md) (β 015, p = 0.0067) and Mr from female donor (Mr/Fd) (β 0.6, p = 0.0078). After a median of 11.3-year follow-up, 59 (17%) HT recipients died. Cardiac mortality was higher in AM than in the other groups (AM median survival 17.2y vs 27.8y and 24.1y for LA and MHA respectively, log-rank p = 0.005). After adjusting for confounding variables, AM was a predictor of cardiac mortality (HR: 2.26; 95%CI 1.18 – 4.35), such as Mr/Fd (HR 2.94; 95%CI 1.18 – 4.35, p = 0.0358). Conclusion AM, in the context of a normal LVEF, is associated with male donor and sex mismatch, and negatively affects long-term outcome after HT.KM curvesCox proportional hazard model

NMR Insights into Lipoprotein Particles: analyzing correlations with traditional lipid measurements

Abstract Introduction Lipid metabolism plays a crucial role in various physiological processes. Lipid molecules are transported by lipoproteins, and the intricate involvement of lipoproteins in cardiovascular disease (CVD) is well-established, given their diverse size, density, and lipid composition. The emergence of Nuclear Magnetic Resonance (NMR) spectroscopy, a high-resolution analytical technique, promotes the assessment of lipoprotein particle numbers and sizes. Studies suggest that the measurement of total low-density lipoprotein particle numbers (LDL-P), small LDL-P (SLDL-P), and total high-density lipoprotein particle numbers (HDL-P) provides better evaluation of risk of CVD than enzymatic-based measurements of LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C). Our study examined the correlation between NMR-derived lipoprotein profiles and traditional cholesterol measurements in control and patient populations. Methods Fasting serum samples were collected from healthy male and female donors (n=148), ages 21-64 years. The analysis also included the results from &amp;gt;20,000 patients’ samples submitted to our laboratory for NMR lipid testing. We assessed LDL-P, SLDL-P, HDL-P, large HDL (LHDL-P), and HDL size (HDL-S) by NMR. In addition, total cholesterol (TC) and HDL-C were measured using traditional automated enzymatic assays (Roche Diagnostics); LDL-C was calculated. Statistical analyses, including Spearman correlation, were performed using GraphPad Prism software. Spearman coefficient (r) ≥0.75 indicated a strong correlation, r &amp;lt;0.5 indicated a weak correlation. Results HDL-C only moderately correlated with total HDL-P in samples collected from controls (rcontrols=0.52) and patients (rpatients=0.68), while showing better correlation with LHDL-P (rcontrols=0.90, rpatients=0.89). Traditional LDL-C strongly correlated with total LDL-P (rcontrols=0.76, rpatients=0.81), but showed only weak correlation with SLDL-P (rcontrols=0.42, rpatients=0.28), which is considered more atherogenic and predictive of CVD risk than LDL-C or total LDL-P. Interestingly, among various lipoprotein parameters, SLDL-P correlated the strongest with HDL-S in both study populations (rcontrols=-0.87, rpatients=-0.84). Samples with higher number of SLDL-P also had smaller size of HDL-P, although the number of total HDL-P did not differ between high vs low SLDL-P samples. In contrast, only moderate negative correlation was observed between SLDL-P and traditional HDL-C (rcontrols=-0.74, rpatients=-0.68), suggesting that the size of HDL particles might add value in evaluating CVD risk. Conclusion The NMR technology has advantage over traditional measurements in stratifying an individual’s lipoprotein milieu. It provides insights into the number of small LDL particles and size of HDL particles, which are not included in standard lipid testing and may allow for more individualized patient care. Incorporation of lipoprotein size and particle number in clinical guidelines may help physicians with assessment CVD risk and treatment monitoring.

Association of regular plasmapheresis donation with serum protein and electrolyte levels: a multicentre cross-sectional study in China

BackgroundChina’s plasmapheresis donation policy differs from that of Western countries. The association between regular plasmapheresis donation and donor health in China is still unknown.ObjectivesTo investigate the association of regular plasmapheresis...

Integrated multimodal cell atlas of Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of dementia in older adults. Although AD progression is characterized by stereotyped accumulation of proteinopathies, the affected cellular populations remain understudied. Here we use multiomics, spatial genomics and reference atlases from the BRAIN Initiative to study middle temporal gyrus cell types in 84 donors with varying AD pathologies. This cohort includes 33 male donors and 51 female donors, with an average age at time of death of 88 years. We used quantitative neuropathology to place donors along a disease pseudoprogression score. Pseudoprogression analysis revealed two disease phases: an early phase with a slow increase in pathology, presence of inflammatory microglia, reactive astrocytes, loss of somatostatin+ inhibitory neurons, and a remyelination response by oligodendrocyte precursor cells; and a later phase with exponential increase in pathology, loss of excitatory neurons and Pvalb+ and Vip+ inhibitory neuron subtypes. These findings were replicated in other major AD studies.

Prevalence, incidence, and residual risk for human immunodeficiency virus among blood donors from 2003 to 2022 in Guangzhou, China.

China's significant population affected by HIV poses a substantial threat to blood transfusion safety. Despite advancements in blood testing techniques, a residual risk of HIV transmission persists. Accurately assessing HIV epidemic and the residual risk is vital for monitoring blood supply safety and evaluating the effectiveness of new screening tests. We conducted a retrospective analysis of HIV detection results among voluntary blood donors from 2003 to 2022. The study included data on HIV-confirmed positive donors, HIV prevalence, infection risk factors, and an incidence-window period mathematical model to estimate the residual risk of HIV. Between 2003 and 2022, HIV prevalence among blood donors in Guangzhou showed a peak-shaped trend, initially increasing before declining. The overall HIV prevalence was 18.9 infections per 100,000 donations. Male donors had a significantly higher prevalence compared with female donors. Donors aged 26-35 years had the highest prevalence. Ethnic minority donors had a higher prevalence compared with Han donors. Repeat donors had a lower prevalence compared with first-time donors. Donors from other provinces had a higher prevalence compared with local donors. During the period of 2003 to 2022, the residual risk of HIV in Guangzhou steadily decreased, reaching a notable 1 in 526,316 donations in the past two years. The HIV epidemic among blood donors in Guangzhou remains severe, but the residual risk of HIV is decreasing. Novel detection methods have proven advantageous in reducing this residual risk. Implementing additional effective measures is imperative to ensure blood safety and curb the spread of HIV.

Novel machine learning technique further clarifies unrelated donor selection to optimize transplantation outcomes

AbstractWe investigated the impact of donor characteristics on outcomes in allogeneic hematopoietic cell transplantation (HCT) recipients using a novel machine learning approach, the Nonparametric Failure Time Bayesian Additive Regression Trees (NFT BART). NFT BART models were trained on data from 10 016 patients who underwent a first HLA-A, B, C, and DRB1 matched unrelated donor HCT between 2016 and 2019, reported to the Center for International Blood and Marrow Transplant Research, then validated on an independent cohort of 1802 patients. The NFT BART models were adjusted based on recipient, disease, and transplant variables. We defined a clinically meaningful impact on overall survival (OS) or event-free survival (EFS; survival without relapse, graft failure, or moderate to severe chronic graft-versus-host disease) as >1% difference in predicted outcome at 3 years. Characteristics with <1% impact (within a zone of indifference) were not considered to be clinically relevant. Donor cytomegalovirus, parity, HLA-DQB1, and HLA-DPB1 T-cell epitope matching fell within the zone of indifference. The only significant donor factor that associated with OS was age, in which, compared with 18-year-old donors, donors aged ≥31 years old were associated with lower OS. Both donor age (≤32 years) and use of a male donor, regardless of recipient sex, improved EFS. We, therefore, recommend selecting the earliest available donor within the 18 to 30 years age range for HCT to optimize OS. If several donors in the 18 to 30 years age range are available, a male donor may be chosen to optimize EFS.

The Korean Organ Transplant Registry (KOTRY): Third Official Adult Heart Transplant Report.

The Korean Organ Transplant Registry (KOTRY) provided data for this third official report on adult heart transplantation (HT), including information from 709 recipients. Data from HTs performed at seven major centers in Korea between March 2014 and December 2020 were analyzed, focusing on immunosuppression, acute rejection, cardiac allograft vasculopathy (CAV), post-transplant survival, and mechanical circulatory support (MCS) usage. The median ages of the recipients and donors were 56.0 and 43.0 years, respectively. Cardiomyopathy and ischemic heart disease were the most common preceding conditions for HT. A significant portion of patients underwent HT at waiting list status 1 and 0. In the multivariate analysis, a predicted heart mass mismatch was associated with a higher risk of 1-year mortality. Patients over 70 years old had a significantly increased risk of 6-year mortality. The risk of CAV was higher for male donors and donors older than 45 years. Acute rejection was more likely in patients with panel reactive antibody levels above 80%, while statin use was associated with a reduced risk. The employment of left ventricular assist device as a bridge to transplantation increased from 2.17% to 22.4%. Pre-transplant extra-corporeal membrane oxygenation was associated with worse post-transplant survival. In this third KOTRY report, we analyzed changes in the characteristics of adult HT recipients and donors and their impact on post-transplant outcomes. The most notable discovery was the increased use of MCS before HT and their impact on post-transplant outcomes.

A-114 Protective effect of leukocytes in preventing Cold Induced Hyperkalemia

Abstract Background Cellular components, especially PRBC units stored in blood banks show progressively increasing extracellular potassium because ATP dependent Na+/ K+ATPase that pumps potassium into cells is slowed at cold but K+ leak continues. The extracellular potassium levels in these units may go well above the range of linearity of some electrolyte analyzers and may need dilution to measure accurately. We wanted to see effect of Leukocytes on this progressive cold-storage hyperkalemia. Buffy-Coat, the leukocyte rich layer of spun whole blood, a discard product of blood banks using buffy-coat-method for components, was used as the source of leukocytes. Methods Buffy-Coat-bags (from Terumo Quadruple-bag-set, in CPD) were separated from 32 donations from male donors (with IRB, consent). Eight ABO,Rh compatible pools of four buffy each, were prepared and divided into 2 groups of four pools each:Leukoreduced pools (LR group): Each pool leukoreduced by a clinical-grade commercial Leukofilter (Mitra).Non-leukoreduced pools (NLR group) rich in leukocytes. Potassium/VBG on Cobas B221(Roche), and CBC were done on days 0, 3, 7 on each pool stored at 4oC. Results Potassium was significantly lower in NLR than LR pools on days 3 &amp; 7, and potassium had significant negative correlation with WBC count. Multiple-linear-regression and analysis of additional control experiments consistently showed that independent of days of storage, pH, and Hct, WBC-Count had significant negative correlation with Potassium. Conclusions Preanalytic artefacts like “seasonal-pseudohypokalemia” and pseudohypokalemia in a subset of AMLs (opposite of pseudohyperkalemia in fragile hyperleukocytosis) suggest that leukocytes may be capable of reducing extracellular potassium. Our in-vitro closed-system controlled experiments show that leukocyte-rich/Non-Leuko-Reduced (NLR) pools were relatively protected from hyperkaleimia than filtered leukocyte-poor/Leuko-Reduced (LR) buffy pools, and potassium has significant negative correlation with leukocyte count independent of storage-time, pH &amp; Hct. Though considered otherwise bad/aggravator for “PRBC-storage-lesion”, leukocytes may help abate progressive cold-storage-hyperkalemia.

Sex-biased human thymic architecture guides Tcell development through spatially defined niches.

Within the thymus, regulation of the cellular crosstalk directing Tcell development depends on spatial interactions within specialized niches. To create a spatially defined map of tissue niches guiding humanpostnatal Tcell development, we employed the multidimensional imaging platform co-detection by indexing (CODEX) as well as cellular indexing of transcriptomes and epitopes sequencing (CITE-seq) and assay for transposase accessible chromatin sequencing (ATAC-seq). We generated age-matched 4- to 5-month-old human postnatal thymus datasets for male and female donors, identifying significant sex differences in both Tcell and thymus biology. We demonstrate a possible role for JAG ligands in directing thymic-like dendritic cell development, identify important functions of a population ofextracellular matrix (ECM)- fibroblasts, and characterize the medullary niches surrounding Hassall's corpuscles. Together, these data represent an age-matched spatial multiomic resource to investigate how sex-based differences in thymus regulation and Tcell development arise, providing an essential resource to understand the mechanisms underlying immune function and dysfunction in males and females.

Effect and Influencing Factors of Peripheral Blood Hematopoietic Stem Cells Collection from Unrelated Donors

To analyze the effect of peripheral blood hematopoietic stem cells (PBSC) collection from unrelated donors and its influencing factors. A retrospective analysis was conducted on the mobilization and collection of PBSC from 113 unrelated donors at Yueyang Central Hospital from January 2021 to December 2023. 113 donors were successfully mobilized. The average count of PBSC mononuclear cells (MNC) and CD34+ cells were (12.40±7.41)×108/kg and (10.64±8.07)×106/kg, respectively. Univariate analysis showed that the PBSC CD34+ cells ratio of male donors was significantly higher than that in female donors (P =0.015). The peripheral blood (PB) white blood cell (WBC) count before collection was positively correlated with the PBSC nucleated cells count (r =0.388), and the donor's body weight, the PB CD34+ cell ratio before collection were positively correlated with the PBSC CD34+ cell ratio (r =0.259, r =0.780). The daily dose of rhG-CSF was negatively correlated with the PBSC CD34+ cell ratio (r =-0.285). Both rhG-CSF agents achieved successful mobilization. Multivariate analysis showed that PB WBC count before collection was a factor affecting the count of PBSC nucleated cells (P <0.001), while the PB CD34+cell ratio before collection was a factor affecting the PBSC CD34+ cell ratio (P <0.001). The mobilization and collection of PBSC from unrelated donors are good, and the PB WBC count and CD34+ cell ratio before collection are reliable indicators for predicting the collection effect.

Inflammatory pain resolution by mouse serum-derived small extracellular vesicles

Current treatments for chronic pain have limited efficacy and significant side effects, warranting research on alternative strategies for pain management. One approach involves using small extracellular vesicles (sEVs), or exosomes, to transport beneficial biomolecular cargo to aid pain resolution. Exosomes are 30–150 nm sEVs that can be beneficial or harmful depending on their source and cargo composition. We report a comprehensive multi-modal analysis of different aspects of sEV characterization, miRNAs, and protein markers across sEV sources. To investigate the short- and long-term effects of mouse serum-derived sEVs in pain modulation, sEVs from naïve control or spared nerve injury (SNI) model male donor mice were injected intrathecally into naïve male recipient mice. These sEVs transiently increased basal mechanical thresholds, an effect mediated by opioid signaling as this outcome was blocked by naltrexone. Mass spectrometry of sEVs detected endogenous opioid peptide leu-enkephalin. sEVs from naïve female mice have higher levels of leu-enkephalin compared to male, matching the analgesic onset of leu-enkephalin in male recipient mice. In investigating the long-term effect of sEVs, we observed that a single prophylactic intrathecal injection of sEVs two weeks prior to induction of the pain model in recipient mice accelerated recovery from inflammatory pain after complete Freund’s adjuvant (CFA) injection. Our exploratory studies examining immune cell populations in spinal cord and dorsal root ganglion using ChipCytometry suggested alterations in immune cell populations 14 days post-CFA. Flow cytometry confirmed increases in CD206+ macrophages in the spinal cord in sEV-treated mice. Collectively, these studies demonstrate multiple mechanisms by which sEVs can attenuate pain.

Prevalence of Transfusion-Transmissible Infections Among Voluntary Blood Donors in a Tertiary Care Hospital.

Background Transfusion-transmissible infections (TTIs) pose a significant risk to blood transfusion safety, especially in low-resource settings. TTIs include infections such as HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, and malaria. Over four years, this study assesses the seroprevalence of TTIs among voluntary blood donors at a tertiary care center. Materials and methods This retrospective observational study was conducted at the blood bank of a tertiary care center from June 2019 to December 2022. A total of 4639 voluntary blood donors were screened for TTIs, including HIV, HBV, HCV, syphilis, and malaria, using third-generation enzyme-linked immunosorbent assay (ELISA) kits and rapid diagnostic tests. The data were analyzed to evaluate the seroprevalence of each infection and its trends over the study period. Results The overall prevalence of TTIs among the 4639 donors was 68 (1.46%). The highest seroprevalence was observed for HBV, with 33 (0.71%), followed by syphilis with 22 (0.47%), HIV with nine (0.19%), and HCV with four (0.08%). No cases of malaria were detected. The prevalence of TTIs was highest in 2021, with the seroprevalence of HBV peaking at 15 (1.14%). Male donors accounted for 4412 (98%) of all donations, and the prevalence of TTIs was significantly higher among males than females. Conclusion The study highlights the importance of continuous surveillance and screening for TTIs among blood donors to ensure transfusion safety. The higher seroprevalence of HBV underscores the need for effective vaccination programs, and the disparity in gender distribution calls for strategies to encourage female blood donations. TTIs remain a public health concern, necessitating improved donor screening and public awareness.

Trends of Transfusion Transmissible Infections among Predominantly Male Blood Donors in Rawalpindi: A Five-Year Retrospective Study

Background: Blood transfusion carry an inherent risk of transfusion transmissible infections (TTIs). Monitoring trends and prevalence of TTIs may reveal crucial information regarding safety of blood supply and donor recruitment strategies. Objective: To evaluate the critical indicators of blood safety including seroprevalence and temporal trends of hepatitis B virus, hepatitis C virus, human immunodeficiency virus and syphilis among blood donors in Rawalpindi. Methods: The study was conducted in Armed Forces Institute of Transfusion. The data of 2,78,774 blood donors from 2016-2020 was retrospectively analyzed. Donors’ demographics, type of donation, donation frequency and serological results of TTIs were retrieved and analyzed. Results: Of the 2,78,774 blood donations, 3.6% (n=10,091) blood donors were positive for one or more TTIs. Among these, the most prevalent was HCV (1.5%) and the least prevalent was HIV (0.08%). The seroprevalence of TTIs illustrated a declining trend from 4.2 to 3.4% over the period under study. Regarding trend of each TTI with respect to year, HBV, HCV and HIV depicted fluctuating trend while decreasing trend was observed for syphilis from 2016-2020. Conclusion: The seroprevalence of four major TTIs was evaluated between the year 2016 and 2020. A decreasing trend in the seroprevalence from 4.2 % to 3.6 % was observed over a five-year period. The HCV remained highest throughout the period whereas a gradual increase in HIV and a decrease in syphilis was observed.

Heterogeneity of synaptic NMDA receptor responses within individual lamina I pain-processing neurons across sex in rats and humans.

Excitatory glutamatergic NMDA receptors (NMDARs) are key regulators of spinal pain processing, and yet the biophysical properties of NMDARs in dorsal horn nociceptive neurons remain poorly understood. Despite the clinical implications, it is unknown whether the molecular and functional properties of synaptic NMDAR responses are conserved between males and females or translate from rodents to humans. To address these translational gaps, we systematically compared individual and averaged excitatory synaptic responses from lamina I pain-processing neurons of adult Sprague-Dawley rats and human organ donors, including both sexes. By combining patch-clamp recordings of outward miniature excitatory postsynaptic currents with non-biased data analyses, we uncovered a wide range of decay constants of excitatory synaptic events within individual lamina I neurons. Decay constants of synaptic responses were distributed in a continuum from 1-20ms to greater than 1000ms, suggesting that individual lamina I neurons contain AMPA receptor (AMPAR)-only as well as GluN2A-, GluN2B- and GluN2D-NMDAR-dominated synaptic events. This intraneuronal heterogeneity in AMPAR- and NMDAR-mediated decay kinetics was observed across sex and species. However, we discovered an increased relative contribution of GluN2A-dominated NMDAR responses at human lamina I synapses compared with rodent synapses, suggesting a species difference relevant to NMDAR subunit-targeting therapeutic approaches. The conserved heterogeneity in decay rates of excitatory synaptic events within individual lamina I pain-processing neurons may enable synapse-specific forms of plasticity and sensory integration within dorsal horn nociceptive networks. KEY POINTS: Synaptic NMDA receptors (NMDARs) in spinal dorsal horn nociceptive neurons are key regulators of pain processing, but it is unknown whether their functional properties are conserved between males and females or translate from rodents to humans. In this study, we compared individual excitatory synaptic responses from lamina I pain-processing neurons of male and female adult Sprague-Dawley rats and human organ donors. Individual lamina I neurons from male and female rats and humans contain AMPA receptor-only as well as GluN2A, GluN2B- and GluN2D-NMDAR-dominated synaptic events. This may enable synapse-specific forms of plasticity and sensory integration within dorsal horn nociceptive networks. Human lamina I synapses have an increased relative contribution of GluN2A-dominated NMDAR responses compared with rodent synapses. These results uncover a species difference relevant to NMDAR subunit-targeting therapeutic approaches.

Exercise activates AMPK in mouse and human pancreatic islets to decrease senescence.

Beta (β)-cell senescence contributes to type 2 diabetes mellitus (T2DM). While exercise is vital for T2DM management and significantly affects cellular ageing markers, its effect on β-cell senescence remains unexplored. Here, we show that short-term endurance exercise training (treadmill running, 1 h per day for 10 days) in two male and female mouse models of insulin resistance decreases β-cell senescence. In vivo and in vitro experiments revealed that this effect is mediated, at least in part, by training-induced increases in serum glucagon, leading to activation of 5'-AMP-activated protein kinase (AMPK) signalling in β-cells. AMPK activation resulted in the nuclear translocation of NRF2 and decreased expression of senescence markers and effectors. Remarkably, human islets from male and female donors with T2DM treated with serum collected after a 10-week endurance exercise training programme showed a significant decrease in the levels of senescence markers. These findings indicate that exercise training decreases senescence in pancreatic islets, offering promising therapeutic implications for T2DM.

The influence of lumbar vertebra and cage related factors on cage-endplate contact after lumbar interbody fusion: An in-vitro experimental study

Lumbar interbody fusion (LIF) using interbody cages is an established treatment for lumbar degenerative disc disease, but fusion results are known to be affected by risk factors such as bone mineral density (BMD), endplate geometry and cage position. At present, direct measurement of endplate-cage contact variables that affect LIF have not been fully identified. The aim of this study was to use cadaveric experiments to investigate the dependency between BMD, endplate geometry, cage parameters like type, orientation, position, and contact variables like stress and area. One vertebral body specimen from each of the five lumbar positions was harvested from five male donors. The lower half of each vertebra was potted and placed in a material testing machine (Instron 8874). A spinal cage was clamped to the machine then lowered to bring it into contact against the superior endplate. A lockable ball-joint was used to rotate the cage such that its inferior surface was congruent with the local endplate surface. A pressure sensor (Tekscan) was placed between the cage and endplate to record contact area and the peak and average contact pressures. Axial compression of 400 N was performed for five positions using a straight cage, and in one anterior position using a curved cage. The linear mixed model was utilised to perform data analyses for experimental results with statistical significance set at p < 0.05. The results indicated two trends toward significance for contact area, one for volumetric BMD (vBMD) of the vertebra (p = 0.081), and another for predicted contact area (p = 0.057). Peak contact pressure correlated significantly with vBMD (p = 0.041), and there was a trend between average contact pressure and lateral position of cage (p = 0.051). In addition, predicted contact area correlated significantly with cage orientation (p < 0.001). These results indicated that high vBMD of vertebra and a medially positioned cage led to higher contact pressures. Logically, low vBMD of vertebra and transverse cage orientation increased the contact area between the cage and endplate. In conclusion, the study identified significant influence of vBMD of vertebra, cage position and orientation on cage-endplate contact which may help to inform cage selection and design for LIF.

Abstract C150: Evaluating breast cancer risk by race and ethnicity using the Tyrer Cuzick and Gail models in the Komen Tissue Bank cohort

Abstract Introduction: Breast cancer is the second leading cause of cancer death in women after lung cancer in the United States. While early detection is critical to reducing morbidity and mortality, predication of individualized risk is important in prevention and could also reduce unnecessary costs related to screening. The Susan G. Komen Tissue Bank (KTB) at Indiana University is the only tissue bank in the world that provides breast tissue specimens donated by healthy individuals to further to breast cancer research; however, as donors are volunteers, it is not clear how representative they are with respect to breast cancer risk compared to the general population. Methods: In this study, we calculated Breast Cancer Risk Assessment scores using Tyrer Cuzick (TCZ) and the Breast Cancer Risk Assessment Tool (The Gail Model, GM) in the KTB cohort by race and ethnicity. Recruited between 2007 and 2023, the participants completed a questionnaire encompassing their demographics, personal health and reproductive history, family history, and modifiable risk factors like smoking and alcohol use. In both models, participants with a lifetime risk of breast cancer of more than 15% were classified as having higher than average risk, while those with a risk of less than 15% were classified as having an average risk. Data analysis was performed using SAS v.9.4 software. Statistical significance was determined by p-values &amp;lt;0.05. Results: Out of 5118 participants, 206 with prior breast cancer and 37 male donors were excluded, resulting in a final sample of 4875 participants (aged 18–90) for analysis. The cohort was predominantly non-Hispanic white (NHW, 69.73%), followed by non-Hispanic black (NHB, 16.7%), Hispanic (8. 6%), and Asian individuals (3.3%), with 1.8% reporting multiracial or other race. The GM consistently categorized fewer women as having higher than average risk compared to the TZM. Across both TCZ and GM, the percentages of individuals classified as higher than average risk was greatest for NHW women, with 29.2% being categorized as higher than average risk in the TCZ, compared to 21.0% in the GM. The greatest discordance between the models was seen in NHB women, with the TCZ estimating 25.2% were at greater than average risk, and the GM only reporting 3.7% to be at greater than average risk. Overall, risk assessment scores varied across racial and ethnic groups (p- value&amp;lt;0.001). Factors driving these differences will be presented in additional analyses. Conclusion: There are known limitations in breast cancer risk assessment models by race and ethnicity that were confirmed in the women who comprise the KTB cohort. Donors to the KTB are generally representative of the US population with respect to breast cancer risk. As the KTB cohort continues to grow and mature, it can be utilized to assess breast cancer risk models for various racial and ethnic groups to assist in the identification of high-risk individuals that may benefit from prevention strategies and targeted screening. Citation Format: Vidya Patil, Michele L. Cote, Jenny Cui. Evaluating breast cancer risk by race and ethnicity using the Tyrer Cuzick and Gail models in the Komen Tissue Bank cohort [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C150.