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1.
Poult Sci ; 102(10): 102993, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37611453

ABSTRACT

Heavy selection for growth in turkeys has led to a decay in leg soundness and walking ability. In this study, different models and traits were used to investigate the genetic relationships between body weight (BW) and walking ability (WA) in a turkey population. The data consisted of BW and WA traits collected on 276,059 male birds. Body weight was measured at 12 and 20 wk and WA at 20 wk of age. For WA, birds were scored based on a 1 (bad) to 6 (good) grading system. Due to the small number of records with scores 5 and 6, birds with WA scores of 4, 5, and 6 were grouped together resulting in only 4 classes. Additionally, a binary classification of WA (scores 1 and 2 = Similarly, an estimate of the genetic correlation between WA and BW at 20 wk was -0.45, indicating a more pronounced class 1; scores 3, 4, 5, and 6 = class 2) was evaluated. The inheritability estimates of WA ranged between 0.25 and 0.27 depending on the number of classes. The Heritability of BW at 12 and 20 wk was 0.44 and 0.51, respectively. The genetic correlation between WA and BW at 12 wk was around -0.35, indicating that heavy birds tend to have poor WA. antagonistic relationship between BW and WA. The genetic correlation between BW at 12 and 20 wk was positive and high (0.80). The residual correlation between WA and BW at 12 and 20 wk of age was -0.07 and -0.02, respectively. The residual correlation between body weight traits was 0.57. Similar results were observed when a binary classification was adopted for WA. The probability of an individual with a given genetic merit expressing a certain class of WA was determined for different fixed effect designations. Predictive probabilities clearly showed that birds when hatched in the winter would have a small chance to exhibit good WA phenotypes.


Subject(s)
Chickens , Turkeys , Male , Animals , Turkeys/physiology , Body Weight/genetics , Linear Models , Walking
2.
Platelets ; 34(1): 2206916, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37143347

ABSTRACT

Cryopreservation significantly alters the phenotype of platelets; generating distinct subpopulations, which may influence the formation of platelet leukocyte aggregates (PLA). PLAs are immunomodulatory and have been associated with transfusion-associated adverse events. As such, the aim of this study was to examine the effect of cryopreservation on the ability of platelets to form PLAs, using a monocyte-like cell line (THP-1). Platelets were tested pre-freeze, post-thaw and following stimulation with TRAP-6 or A23187, both alone and following co-culture with THP-1 cells for 1 and 24 hours (n = 6). Platelet subpopulations and platelet-THP-1 cell aggregates were analyzed using multi-color imaging flow cytometry using Apotracker Green (ApoT), CD42b, CD62P, CD61, and CD45. Cryopreservation resulted in the generation of activated (ApoT-/CD42b+/CD62P+), procoagulant (ApoT+/CD42b+/CD62P+) and a novel (ApoT+/CD42b+/CD62P-) platelet subpopulation. Co-incubation of cryopreserved platelets with THP-1 cells increased PLA formation compared to pre-freeze but not TRAP-6 or A23187 stimulated platelets. P-selectin on the surface membrane was correlated with increased PLA formation. Our findings demonstrate that cryopreservation increases the interaction between platelets and THP-1 cells, largely due to an increase in procoagulant platelets. Further investigation is required to determine the immunological consequences of this interaction.


What do we know? Cryopreserved platelets are an alternative to overcome issues with the short shelf-life of room-temperature stored plateletsAfter thawing, cryopreserved platelets exhibit changes in cell structure and receptor abundanceActivated platelets can attach to leukocytes, forming platelet-leukocyte aggregates and altering their immune functionPlatelet-leukocyte aggregates can increase inflammation, which is associated with adverse events after transfusion, which can negatively affect patient outcomesWhat did we discover? Cryopreservation results in a heterogenous mix of platelet subpopulationsCryopreserved platelets display increased adherence to a monocyte-like cell line (THP-1 cells). Platelet-THP-1 aggregate formation was linked to expression of CD62P on the surface of the plateletsThe increase in cryopreserved platelet-THP-1 cell aggregates was largely due to an increase in procoagulant plateletsWhat is the impact? Our data demonstrate that cryopreservation increases platelet interaction with a monocyte-like cell lineThis may mediate immune responses and/or circulation time of transfused platelets.


Subject(s)
Blood Platelets , Monocytes , Calcimycin/metabolism , Calcimycin/pharmacology , Blood Platelets/metabolism , Monocytes/metabolism , Phenotype , Cryopreservation/methods , Polyesters/metabolism , P-Selectin/metabolism , Platelet Activation
3.
J Hand Ther ; 36(4): 956-961, 2023.
Article in English | MEDLINE | ID: mdl-36914492

ABSTRACT

INTRODUCTION: This study aimed to identify the relationship between age, body mass index (BMI), weight, height, and wrist circumference and median nerve cross-sectional area (CSA). The study also aimed to examine the difference between CSA in individuals reporting a high amount (>4 hours per day) of electronic device use compared to those reporting a low amount (≤4 hours per day). MATERIALS/METHODS: One hundred twelve healthy individuals volunteered to participate in the study. Anthropometric, demographic, and self-reported electronic device usage data were collected. A transverse image of the median nerve was captured using ultrasonography from the dominant wrist at the carpal tunnel inlet . A Spearman's rho correlation coefficient was used to examine correlations between participant characteristics (age, BMI, weight, height, and wrist circumference) and CSA. Separate Mann-Whitney U tests were used to examine differences in CSA in those younger and older than age 40, in those with BMI <25 kg/m2 and BMI ≥25 kg/m2, and in high and low-frequency device users. RESULTS: BMI, weight, and wrist circumference showed fair correlations with CSA. There were significant differences in CSA between individuals younger than 40 and those older than 40 and between individuals with BMI <25kg/m2 and those with BMI ≥25kg/m2. There were no statistically significant differences in CSA in the low- and high-use electronic device groups. DISCUSSION: Anthropometric and demographic characteristics including age and BMI or weight should be considered when examining the CSA of the median nerve, especially when determining cut-off points for establishing a diagnosis of carpal tunnel syndrome.


Subject(s)
Carpal Tunnel Syndrome , Median Nerve , Humans , Adult , Median Nerve/diagnostic imaging , Cross-Sectional Studies , Wrist , Carpal Tunnel Syndrome/diagnosis , Wrist Joint
4.
Animals (Basel) ; 13(1)2023 Jan 02.
Article in English | MEDLINE | ID: mdl-36611782

ABSTRACT

Fifteen hundred 12−15-month-old tropically adapted heifers inadvertently grazed a paddock which had a refuse dump in it containing burnt out vehicle batteries. The cattle grazed this paddock for approximately seven days. Subsequently these cattle were managed as two cohorts (cull and potential replacement breeding animals). Deaths commenced in the cull heifer group approximately 18 days after initial exposure to the refuse dump during relocation to a feedlot. Mortalities continued for 12 days, with other heifers showing clinical signs of marked central nervous system dysfunction requiring euthanasia. Necropsy of several clinically affected cattle plus blood sampling for lead analysis confirmed a diagnosis of lead intoxication. The crude mortality rate in the cull heifers was 6.6% (n = 685). Following confirmation of the diagnosis most of the potential replacement heifers (second cohort) were also relocated to the feedlot. The estimated crude mortality rate in this cohort was 5.8% (n = 815). All possible lead intoxication deaths occurred within 34 days of initial exposure, and apparently after day 16 at the feedlot no further heifers showed any clinical signs which could be attributed to lead intoxication. Longitudinal monitoring of blood lead concentrations was used to identify cattle suitable for slaughter. Overall, 70% of heifers initially blood sampled (n = 1408) had no detectable lead in their blood, however 16% had markedly elevated blood lead concentrations (> 0.7µmol/L) which persisted, and 2% had above the maximum normal threshold 1.5 years later. These latter cattle were subsequently euthanized, and necropsy revealed that visible pieces of lead were still present in the reticulum of several animals. At no time did any of these heifers with persistently high blood lead concentrations show clinical signs of lead intoxication.

5.
Vox Sang ; 117(8): 1006-1015, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35579630

ABSTRACT

BACKGROUND AND OBJECTIVES: Cold-stored platelets are currently under clinical evaluation and have been approved for limited clinical use in the United States. Most studies have focused on the haemostatic functionality of cold-stored platelets; however, limited information is available examining changes to their immune function. MATERIALS AND METHODS: Two buffy-coat-derived platelet components were combined and split into two treatment arms: room temperature (RT)-stored (20-24°C) or refrigerated (cold-stored, 2-6°C). The concentration of select soluble factors was measured in the supernatant using commercial ELISA kits. The abundance of surface receptors associated with immunological function was assessed by flow cytometry. Platelet aggregation was assessed in response to Escherichia coli and Staphylococcus aureus, in the presence and absence of RGDS (blocks active conformation of integrin α2 ß3 ). RESULTS: Cold-stored platelet components contained a lower supernatant concentration of C3a, RANTES and PF4. The abundance of surface-bound P-selectin and integrin α2 ß3 in the activated conformation increased during cold storage. In comparison, the abundance of CD86, CD44, ICAM-2, CD40, TLR1, TLR2, TLR4, TLR3, TLR7 and TLR9 was lower on the surface membrane of cold-stored platelets compared to RT-stored components. Cold-stored platelets exhibited an increased responsiveness to E. coli- and S. aureus-induced aggregation compared to RT-stored platelets. Inhibition of the active conformation of integrin α2 ß3 using RGDS reduced the potentiation of bacterial-induced aggregation in cold-stored platelets. CONCLUSION: Our data highlight that cold storage changes the in vitro immune characteristics of platelets, including their sensitivity to bacterial-induced aggregation. Changes in these immune characteristics may have clinical implications post transfusion.


Subject(s)
Blood Platelets , Blood Preservation , Bacteria , Cold Temperature , Escherichia coli , Humans , Integrins , Platelet Aggregation , Staphylococcus aureus
6.
Vox Sang ; 117(5): 671-677, 2022 May.
Article in English | MEDLINE | ID: mdl-35023205

ABSTRACT

BACKGROUND AND OBJECTIVES: In many countries, whole blood (WB) donations with collection times between 12 and 15 min are not allowed to be used for platelet concentrates (PC). Since the development of guidelines, many process-related changes have been introduced. We aimed to determine the effect of WB with long collection times on PC quality. MATERIALS AND METHODS: Five participating centres tested buffy coat (BC)-derived PC in platelet additive solution type E prepared from only WB collections lasting <12 min (control) versus similar PC including one BC from a collection lasting >12 min (study group, n = 8). One centre produced platelet-rich plasma (PRP)-derived PC from single donations (<10 or >12 min). All PC were stored at 22 ± 2°C and sampled on Days 1, 6 and 8 post-collection for in vitro quality determination. RESULTS: Average collection time was significantly longer in the study group compared to controls (8.9 ± 2.6 vs. 7.3 ± 1.3 min, p < 0.001). There were no differences in volume, platelet concentration, basal CD62P expression, soluble-CD62P and CCL5 levels, or nucleotide content between the groups. Stimulation with TRAP-6 resulted in comparable levels of cell surface CD62P. On Day 8, all PC fulfilled requirements for pH. The findings from single PRP-derived PC centre were similar. CONCLUSION: PC with one BC and single PRP derived from collections lasting >12 min had equivalent in vitro quality to controls during storage. This study provides evidence that 12-15 min donations should not be excluded for PC preparation and justifies to readdress the guidelines to <15 min instead of <12 min of collection in line with current practice in some countries.


Subject(s)
Blood Donors , Platelet-Rich Plasma , Blood Platelets , Blood Preservation , Humans
7.
Transfusion ; 61(12): 3432-3442, 2021 12.
Article in English | MEDLINE | ID: mdl-34636427

ABSTRACT

BACKGROUND: Cryopreserved platelets are under clinical evaluation as they offer improvements in shelf-life and potentially hemostatic effectiveness. However, the effect of cryopreservation on characteristics related to the immune function of platelets has not been examined. STUDY DESIGN AND METHODS: Buffy coat derived platelets were cryopreserved at -80°C using 5%-6% dimethylsulfoxide (DMSO, n = 8). Paired testing was conducted pre-freeze (PF), post-thaw (PT0), and after 24 h of post-thaw storage at room temperature (PT24). The concentration of biological response modifiers (BRMs) in the supernatant was measured using commercial ELISAs and surface receptor abundance was assessed by flow cytometry. RESULTS: Cryopreservation resulted in increased RANTES, PF4, and C3a but decreased IL-1ß, OX40L, IL-13, IL-27, CD40L, and C5a concentrations in the supernatant, compared to PF samples. C4a, endocan, and HMGB1 concentrations were similar between the PF and PT0 groups. The abundance of surface-expressed P-selectin, siglec-7, TLR3, TLR7, and TLR9 was increased PT0; while CD40, CLEC2, ICAM-2, and MHC-I were decreased, compared to PF. The surface abundance of CD40L, B7-2, DC-SIGN, HCAM, TLR1, TLR2, TLR4, and TLR6 was unchanged by cryopreservation. Following 24 h of post-thaw storage, all immune associated receptors and TLRs increased to levels higher than observed on PF and PT0 platelets. CONCLUSION: Cryopreservation alters the immune phenotype of platelets. Understanding the clinical implications of the observed changes in BRM release and receptor abundance are essential, as they may influence the likelihood of adverse events.


Subject(s)
Blood Platelets , CD40 Ligand , Blood Preservation/methods , Cryopreservation/methods , Dimethyl Sulfoxide , Hemostasis , Humans
8.
Poult Sci ; 100(11): 101366, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34525446

ABSTRACT

The detrimental effects of increased homozygosity due to inbreeding have prompted the development of methods to reduce inbreeding. The detection of runs of homozygosity (ROH), or contiguous stretches of homozygous marker genotypes, can be used to describe and quantify the level of inbreeding in an individual. The estimation of inbreeding coefficients can be calculated based on pedigree information, ROH, or the genomic relationship matrix. The aim of this study was to detect and describe ROH in the turkey genome and compare estimates of pedigree-based inbreeding coefficients (FPED) with genomic-based inbreeding coefficients estimated from ROH (FROH) and the genomic relationship matrix (FGRM). A total of 2,616,890 pedigree records were available. Of these records, 6,371 genotyped animals from three purebred turkey (Meleagris gallopavo) lines between 2013 and 2019 were available, and these were obtained using a dense single nucleotide polymorphism array (56,452 SNPs). The overall mean length of detected ROH was 2.87 ± 0.29 Mb with a mean number of 84.87 ± 8.79 ROH per animal. Short ROH with lengths of 1 to 2 Mb long were the most abundant throughout the genome. Mean ROH coverage differed greatly between chromosomes and lines. Considering inbreeding coefficient means across all lines, genomic derived inbreeding coefficients (FROH = 0.27; FGRM = 0.32) were higher than coefficients estimated from pedigree records (FPED = 0.14). Correlations between FROH and FPED, FROH and FGRM, and FPED and FGRM ranged between 0.19 to 0.31, 0.68 to 0.73, and 0.17 to 0.30, respectively. Additionally, correlations between FROH from different lengths and FPED substantially increased with ROH length from -0.06 to 0.33. Results of the current research, including the distribution of ROH throughout the genome and ROH-derived inbreeding estimates, can provide a more comprehensive description of inbreeding in the turkey genome. This knowledge can be used to evaluate genetic diversity, a requirement for genetic improvement, and develop methods to minimize inbreeding in turkey breeding programs.


Subject(s)
Inbreeding , Animals , Genome , Genotype , Homozygote , Polymorphism, Single Nucleotide , Turkeys
9.
Transfusion ; 61(11): 3075-3080, 2021 11.
Article in English | MEDLINE | ID: mdl-34482545

ABSTRACT

BACKGROUND: Blood components are irradiated to inactivate lymphocytes in an effort to prevent transfusion-associated graft versus host disease. Although gamma irradiators are commonly used, they are subjected to rigorous health, safety, and compliance regulations, compared with X-irradiators which have the advantage of only emitting radiation while the machine is switched on. While the effects of gamma irradiation on platelet components are well known, there is little or no data comparing the effects of X- and gamma-irradiation on the quality of these components. Therefore, this study examined the in vitro quality of platelet components (pooled and apheresis) following X- or gamma-irradiation. STUDY DESIGN AND METHODS: Whole-blood-derived (pooled) and apheresis platelet components in platelet additive solution (n = 20 pairs for each type) were irradiated (X vs. gamma). In vitro platelet quality was tested prior to irradiation (day 1) and subsequently on days 2, 5, and 7. Non-irradiated components were tested on day 5 in parallel as reference controls. Metabolic parameters, surface expression of glycoproteins and activation markers (CD62P and annexin-V binding), and agonist-induced aggregation were measured. RESULTS: All components met Council of Europe specifications. There were no statistical differences in any in vitro quality measurements between X- and gamma-irradiated pooled or apheresis platelet components. CONCLUSION: X- and gamma-irradiation have similar effects on the in vitro quality of stored blood components, indicating that either technology represents a suitable option for irradiation of platelet components.


Subject(s)
Blood Component Removal , Blood Platelets , Blood Preservation , Europe , Gamma Rays , Humans
10.
Transfusion ; 61 Suppl 1: S58-S67, 2021 07.
Article in English | MEDLINE | ID: mdl-34269458

ABSTRACT

BACKGROUND: Refrigeration, or cold-storage, of platelets may be beneficial to extend the limited shelf-life of conventionally stored platelets and support transfusion protocols in rural and military areas. The aim of this study was to compare the morphologic, metabolic, and functional aspects of apheresis platelets stored at room-temperature (RT) or cold conditions, in either plasma or supplemented with platelet additive solution (PAS). STUDY DESIGN AND METHODS: Double-dose apheresis platelets were collected in either 100% plasma or 40% plasma/60% PAS-E using the Trima apheresis platform. One component from each group was either stored at RT (20-24°C) or refrigerated (2-6°C). Platelets were tested over a 21-day period. RESULTS: The platelet concentration decreased by approximately 30% in all groups during 21 days of storage (p > .05). Cold-storage reduced glycolytic metabolism, and the pH was maintained above the minimum specification (>6.4) for 21 days only when platelets were stored in PAS. The surface phenotype and the composition of the supernatant were differentially affected by temperature and storage solution. Functional responses (aggregation, agonist-induced receptor activation, clotting time) were improved during cold-storage, and the influence of residual plasma was assay dependent. CONCLUSION: In vitro platelet quality is differentially affected by storage time, temperature, and solution. Cold-storage, particularly in PAS, better maintains key metabolic, phenotypic, and functional parameters during prolonged storage.


Subject(s)
Blood Platelets/cytology , Blood Preservation/methods , Blood Platelets/metabolism , Cold Temperature , Humans , Platelet Function Tests , Plateletpheresis , Refrigeration
11.
Article in English | MEDLINE | ID: mdl-33807306

ABSTRACT

Supported wellbeing centres were set up in UK hospital trusts as an early intervention aimed at mitigating the psychological impact of COVID-19 on healthcare workers. These provided high quality rest spaces with peer-to-peer psychological support provided by National Health Service (NHS) staff volunteers called 'wellbeing buddies', trained in psychological first aid. The aim of the study was to explore the views of centre visitors and operational staff towards this COVID-19 workforce wellbeing provision. Qualitative semi-structured interviews were undertaken with twenty-four (20F, 4M) employees from an acute hospital trust in the UK. Interviews were digitally recorded and transcribed, data were handled and analysed using thematic analysis. Interviews generated 3 over-arching themes, and 13 sub-themes covering 'exposure and job roles', 'emotional impacts of COVID-19 and 'the wellbeing centres'. Supported wellbeing centres were viewed as critical for the wellbeing of hospital employees during the first surge of COVID-19 in the UK. Wellbeing initiatives require managerial advocacy and must be inclusive. Job-related barriers to work breaks and accessing staff wellbeing provisions should be addressed. High quality rest spaces and access to peer-to-peer support are seen to benefit individuals, teams, organisations and care quality. Training NHS staff in psychological first aid is a useful approach to supporting the wellbeing of the NHS workforce during and beyond the COVID-19 pandemic.


Subject(s)
COVID-19 , Pandemics , First Aid , Humans , SARS-CoV-2 , State Medicine
12.
Vox Sang ; 116(5): 477-488, 2021 May.
Article in English | MEDLINE | ID: mdl-33326606

ABSTRACT

Platelets are now acknowledged as key regulators of the immune system, as they are capable of mediating inflammation, leucocyte recruitment and activation. This activity is facilitated through platelet activation, which induces significant changes in the surface receptor profile and triggers the release of a range of soluble biological response modifiers (BRMs). In the field of transfusion medicine, the immune function of platelets has gained considerable attention as this may be linked to the development of adverse transfusion reactions. Further, component manufacturing and storage methodologies may impact the immunoregulatory role of platelets, and an understanding of this impact is crucial and should be considered alongside their haemostatic characteristics. This review highlights the key interactions between platelets and traditional immune modulators. Further, the potential impact of current and novel component storage methodologies, such as refrigeration and cryopreservation, on this functional capacity is examined, highlighting why further knowledge in this area would be of benefit.


Subject(s)
Blood Platelets/immunology , Blood Safety/methods , Blood Platelets/cytology , Blood Safety/standards , Cryopreservation/methods , Cryopreservation/standards , Humans , Platelet Activation
13.
Article in English | MEDLINE | ID: mdl-33333913

ABSTRACT

Supported Wellbeing Centres have been set up in UK hospital trusts in an effort to mitigate the psychological impact of COVID-19 on healthcare workers, although the extent to which these are utilised and the barriers and facilitators to access are not known. The aim of the study was to determine facility usage and gather insight into employee wellbeing and the views of employees towards this provision. The study included (i) 17-week service use monitoring, (ii) employee online survey with measures of wellbeing, job stressfulness, presenteeism, turnover intentions, job satisfaction, and work engagement, as well as barriers and facilitators to accessing the Wellbeing Centres. Over 17 weeks, 14,934 facility visits were recorded across two sites (peak attendance in single week n = 2605). Facilities were highly valued, but the service model was resource intensive with 134 wellbeing buddies supporting the centres in pairs. 819 hospital employees completed an online survey (88% female; 37.7% working in COVID-19 high risk areas; 52.4% frontline workers; 55.2% had accessed a wellbeing centre). There was moderate-to-high job stress (62.9%), low wellbeing (26.1%), presenteeism (68%), and intentions to leave (31.6%). Wellbeing was higher in those that accessed a wellbeing centre. Work engagement and job satisfaction were high. Healthcare organisations are urged to mobilise access to high-quality rest spaces and psychological first aid, but this should be localised and diversified. Strategies to address presenteeism and staff retention should be prioritised, and the high dedication of healthcare workers should be recognised.


Subject(s)
COVID-19 , Pandemics , Personnel, Hospital/psychology , Adolescent , Adult , Female , Hospitals , Humans , Job Satisfaction , Male , Middle Aged , United Kingdom , Work Engagement , Young Adult
15.
Faraday Discuss ; 222(0): 405-423, 2020 Jun 19.
Article in English | MEDLINE | ID: mdl-32115600

ABSTRACT

Silicon photosensitisation via energy transfer from molecular dye layers is a promising area of research for excitonic silicon photovoltaics. We present the synthesis and photophysical characterisation of vinyl and allyl terminated Si(111) surfaces decorated with perylene molecules. The functionalised silicon surfaces together with Langmuir-Blodgett (LB) films based on perylene derivatives were studied using a wide range of steady-state and time resolved spectroscopic techniques. Fluorescence lifetime quenching experiments performed on the perylene modified monolayers revealed energy transfer efficiencies to silicon of up to 90 per cent. We present a simple model to account for the near field interaction of a dipole emitter with the silicon surface and distinguish between the 'true' FRET region (<5 nm) and a different process, photon tunnelling, occurring for distances between 10-50 nm. The requirements for a future ultra-thin crystalline solar cell paradigm include efficient surface passivation and keeping a close distance between the emitter dipole and the surface. These are discussed in the context of existing limitations and questions raised about the finer details of the emitter-silicon interaction.

16.
J Clin Immunol ; 40(2): 299-309, 2020 02.
Article in English | MEDLINE | ID: mdl-31865525

ABSTRACT

Variants in MAGT1 have been identified as the cause of an immune deficiency termed X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection and neoplasia (XMEN) disease. Here, we describe 2 cases of XMEN disease due to novel mutations in MAGT1, one of whom presented with classical features of XMEN disease and another who presented with a novel phenotype including probable CNS vasculitis, HHV-8 negative multicentric Castelman disease and severe molluscum contagiosum, thus highlighting the clinical diversity that may be seen in this condition. Peripheral blood immunophenotyping of these 2 patients, together with an additional 4 XMEN patients, revealed reduced NKG2D expression, impaired CD28 expression on CD8+ T cells, CD4+ T cell lymphopenia, an inverted CD4:CD8 ratio and decreased memory B cells. In addition, we showed for the first time alterations to the CD8+ T cell memory compartment, reduced CD56hi NK cells, MAIT and iNKT cells, as well as compromised differentiation of naïve CD4+ T cells into IL-21-producing Tfh-type cells in vitro. Both patients were treated with supplemental magnesium with limited benefit. However, one patient has undergone allogeneic haematopoietic stem cell transplant, with full donor chimerism and immune reconstitution. These results expand our understanding of the clinical and immunological phenotype in XMEN disease, adding to the current literature, which we further discuss here.


Subject(s)
Cation Transport Proteins/genetics , Epstein-Barr Virus Infections/genetics , Herpesvirus 4, Human/physiology , Leukocytes, Mononuclear/immunology , Neoplasms/genetics , X-Linked Combined Immunodeficiency Diseases/genetics , Adult , Cell Differentiation , Child , Chimerism , Epstein-Barr Virus Infections/immunology , Hematopoietic Stem Cell Transplantation , Humans , Immunologic Memory , Immunophenotyping , Lymphopenia , Magnesium/metabolism , Male , NK Cell Lectin-Like Receptor Subfamily K/metabolism , Neoplasms/immunology , X-Linked Combined Immunodeficiency Diseases/immunology
17.
Transfusion ; 60(3): 454-459, 2020 03.
Article in English | MEDLINE | ID: mdl-31782799

ABSTRACT

BACKGROUND AND OBJECTIVES: Cryopreservation provides an option for long-term storage of platelet concentrates. While platelets are usually frozen as soon as practical after collection (within 2 days), the ability to freeze units at a later stage of the shelf life may improve inventory management. As such, the aim of this study was to determine the impact of freezing platelets approaching expiry (Day 5/6). MATERIALS AND METHODS: Two ABO-matched buffy coat-derived platelets (30% plasma/70% platelet additive solution) were pooled and split to produce matched pairs (n = 8 pairs). Platelets were frozen on Day 1 after collection (cryopreserved platelets [CPPs]) or Day 5 or 6 (expired-CPPs) at -80°C with 5% to 6% dimethyl sulfoxide. In vitro platelet quality was tested before freezing and after thawing and reconstitution in plasma. RESULTS: The majority of prefreeze parameters were equivalent for all platelet units (Day 1 vs. Day 5 or 6). Expired-CPPs had a higher mean postthaw platelet recovery (82 ± 4%) compared to CPPs (75 ± 4%; p = 0.0021). Cryopreservation resulted in a loss of surface glycoproteins (glycoprotein (GP) Ibα, GPIIb, GPVI), an increase in activation markers (phosphatidylserine and P-selectin) and microparticle release, compared to unfrozen platelets. However, the cryopreservation-induced changes were equivalent in CPPs and expired-CPPs. Functionality was measured by thromboelastography and was similar between expired-CPPs (R-time: 5.3 ± 0.3) and CPPs (R-time: 5.4 ± 0.5; p = 0.7094). CONCLUSION: The phenotype and functional profile of platelets frozen at expiry were similar to platelets frozen 1 day following collection. These data suggest that expired platelets may represent a suitable starting material for cryopreservation.


Subject(s)
Blood Platelets/cytology , Freezing , Blood Buffy Coat/cytology , Cryopreservation/methods , Humans
18.
Forensic Sci Int ; 301: 278-283, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31200260

ABSTRACT

Stabbings have been reported as the most frequent violent crime in countries where there is a severe restriction on obtaining firearms, such as the United Kingdom. Knives, scissors, and screwdrivers, as studied in this research, are among the most commonly encountered weapons involving stabbing events. When any of these implements are used in a stabbing, there is potential for the garment(s) worn by the victim to be damaged. In such an instance, there is an opportunity for fibres to be transferred to the weapon used, thus providing forensic evidence of proof of transfer from the victim's clothing to the weapon. This can offer valuable information in establishing what weapon was used to harm the victim through linking fibres from the victim's garment(s) to a weapon recovered from a suspect. This research simulates vertical stabbings - performed by a human participant - in to a polystyrene block supporting the clothing (essentially acting as the victim's torso), to reflect an authentic scenario. The aforementioned weapons were used along with 3 varieties of garments (cotton, polyester and a linen/viscose mix) offering different characteristics of shedability and structure for the simulated stabbings. Low power microscopy was utilised to view the transferred fibres. The amount of fibres transferred on to the implement were recorded for each repeat. 2279 individual fibres were found over 10 repeats from the knife in relation to the linen/viscose garment. This was the highest amount of transference found with the lowest number attributed to the screwdriver-polyester relationship, providing 320 recorded fibres over 10 repeats. The findings of this study suggest that the number of fibres transferred is not only related to the shedability of the garment but also the surface area characteristics of the receiving weapon and the ability for the garment to tear.

19.
Health Place ; 52: 221-230, 2018 07.
Article in English | MEDLINE | ID: mdl-30015179

ABSTRACT

The health implications of urban development, particularly in rapidly changing, low-income urban neighborhoods, are poorly understood. We describe the Healthy Neighborhoods Study (HNS), a Participatory Action Research study examining the relationship between neighborhood change and population health in nine Massachusetts neighborhoods. Baseline data from the HNS survey show that social factors, specifically income insecurity, food insecurity, social support, experiencing discrimination, expecting to move, connectedness to the neighborhood, and local housing construction that participants believed would improve their lives, identified by a network of 45 Resident Researchers exhibited robust associations with self-rated and mental health. Resident-derived insights into relationships between neighborhoods and health may provide a powerful mechanism for residents to drive change in their communities.


Subject(s)
Health Status , Poverty/statistics & numerical data , Residence Characteristics/statistics & numerical data , Social Change , Urban Renewal , Adolescent , Adult , Black or African American , Aged , Aged, 80 and over , Boston , Community-Based Participatory Research , Community-Institutional Relations , Female , Food Supply , Hispanic or Latino , Humans , Linear Models , Male , Mental Health , Middle Aged , Program Development , Self Report , Social Support , Urban Population , Young Adult
20.
Transfusion ; 58(4): 927-937, 2018 04.
Article in English | MEDLINE | ID: mdl-29330877

ABSTRACT

BACKGROUND: Alternatives to room temperature storage of platelets (PLTs) are of interest to support blood banking logistics. The aim of this study was to compare the presence of biologic response modifiers (BRMs) in PLT concentrates stored under conventional room temperature conditions with refrigerated or cryopreserved PLTs. STUDY DESIGN AND METHODS: A three-arm pool-and-split study was carried out using buffy coat-derived PLTs stored in 30% plasma/70% SSP+. The three matched treatment arms were as follows: room temperature (20-24°C), cold (2-6°C), and cryopreserved (-80°C with DMSO). Liquid-stored PLTs were tested over a 21-day period, while cryopreserved PLTs were tested immediately after thawing and reconstitution in 30% plasma/70% SSP+ and after storage at room temperature. RESULTS: Coagulation factor activity was comparable between room temperature and cold PLTs, with the exception of protein S, while cryopreserved PLTs had reduced Factor (F)V and FVIII activity. Cold-stored PLTs retained α-granule proteins better than room temperature or cryopreserved PLTs. Cryopreservation resulted in 10-fold higher microparticle generation than cold-stored PLTs, but both groups contained significantly more microparticles than those stored at room temperature. The supernatant from both cold and cryopreserved PLTs initiated faster clot formation and thrombin generation than room temperature PLTs. CONCLUSION: Cold storage and cryopreservation alter the composition of the soluble fraction of stored PLTs. These differences in coagulation proteins, cytokines, and microparticles likely influence both the hemostatic capacity of the components and the auxiliary functions.


Subject(s)
Blood Platelets/chemistry , Blood Preservation/methods , Cryopreservation/methods , Immunologic Factors/blood , Temperature , Blood Coagulation Factors/analysis , Blood Platelets/metabolism , Cell-Derived Microparticles , Centrifugation , Cytokines/blood , Cytoplasmic Granules/metabolism , Humans , Intercellular Signaling Peptides and Proteins/blood , Platelet Activation , Refrigeration , Serotonin/blood , Thrombelastography , Thrombin/biosynthesis
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