Re-examine the transfusion transmitted risk of SARS-CoV-2 virus during a major COVID-19 outbreak in 2022.

INTRODUCTION: Although no case of COVID-19 transmission through transfusion has been reported, blood transfusion service (BTS) continues to implement pre-donation and post-donation measures to minimise the risk. In year 2022, when local healthcare system was badly impacted by a major outbreak, it opened an opportunity to re-examine the viraemia risk in these asymptomatic donors. MATERIALS AND METHODS: Records were retrieved from blood donors who reported COVID-19 after donation and follow-up was also made for recipients who received their blood. Blood samples at donation were tested for SARS-CoV-2 viraemia by single-tube nested real-time RT-PCR assay designed to detect most SARS-CoV-2 variants including the prevailing delta and omicron variants. RESULTS: From 1 January to 15 August 2022, the city with 7.4 M inhabitants recorded 1 187 844 COVID-19 positive cases and 125 936 successful blood donations were received. 781 donors reported to the BTS after donation with 701 being COVID-19 related (including close contact and symptoms respiratory tract infection). 525 COVID-19 were positive at the time of call back or follow-up. Of the 701 donations, they were processed into 1480 components with 1073 discarded upon donors' call back. For remaining 407 components, no recipient was found to have adverse event or COVID-19 positive. 510 samples from the above 525 COVID-19 positive donors were available and all tested negative for SARS-CoV-2 RNA. DISCUSSION: With the negative SARS-CoV-2 RNA in blood donation samples and follow up data in transfusion recipients, the risk of transfusion transmitted COVID-19 appears negligible. However, current measures remains important in securing blood safety with ongoing surveillance of their effectiveness.

Thermal plasticity due to parental and early-life environments in the jacky dragon (Amphibolurus muricatus).

Developmental plasticity creates marked variation in individual phenotypes when the environment is patchy, such as when the thermal environment varies. Plasticity may occur in response to the environment experienced during an individual's lifetime or to the environment experienced by parents (transgenerational plasticity), and may be adaptive if it enhances fitness. In particular, plasticity in thermal traits, such as preferred temperatures and thermal limits, may improve performance and fitness based on temperatures in the local environment. This study examined the influence of parental and offspring thermal environments (duration of access to a basking lamp) on offspring thermal traits (preferred temperatures and panting threshold) in jacky dragons (Agamidae: Amphibolurus muricatus). Long-bask parental environments led, indirectly, to higher preferred temperatures of offspring due to increased offspring body mass compared to offspring of short-bask parents. The increase in median temperature preference was associated with a higher voluntary minimum body temperature and a narrower preference range, suggesting tradeoffs in thermal behavior and a matching of offspring preferences to the parental environment. Parental thermal treatment did not influence offspring panting threshold. Instead, the panting threshold tended to be higher in offspring that were reared in the long-bask treatment compared to those in the short-bask treatment, suggesting longer basking environments increased thermal tolerance. Parental and offspring thermal environment did not exhibit any interactive effect on thermal traits. The results indicate that thermal environments experienced by lizards can have both transgenerational and within-generation impacts on thermal traits, thus influencing how populations respond to fluctuating or changing climates.

Subcellular localization of EEN/endophilin A2, a fusion partner gene in leukaemia.

EEN (extra eleven nineteen), also known as EA2 (endophilin A2), a fusion partner of the MLL (mixed-lineage leukaemia) gene in human acute leukaemia, is a member of the endophilin A family, involved in the formation of endocytic vesicles. We present evidence to show that EEN/EA2 is localized predominantly in nuclei of various cell lines of haemopoietic, fibroblast and epithelial origin, in contrast with its reported cytoplasmic localization in neurons and osteoclasts, and that EEN/EA2 exhibits nucleocytoplasmic shuttling. During the cell cycle, EEN/EA2 shows dynamic localization: it is perichromosomal in prometaphase, co-localizes with the bipolar spindle in metaphase and anaphase and redistributes to the midzone and midbody in telophase. This pattern of distribution coincides with changes in protein levels of EEN/EA2, with the highest levels being observed in G2/M-phase. Our results suggest that distinct subcellular localization of the endophilin A family members probably underpins their diverse cellular functions and indicates a role for EEN/EA2 in the cell cycle.

Vitamin B12 deficiency--need for a new guideline.

OBJECTIVES: Many patients with vitamin B12 deficiency do not have anemia or macrocytosis, but the prevalence of B12 deficiency in patients without macrocytosis is not known. METHODS: We investigated the prevalence of B12 deficiency among patients with normocytosis and microcytosis and recommended a screening strategy. All patients (n = 3714) with serum B12 measured at the Prince of Wales Hospital in 1996 were reviewed. The prevalence of serum B12 less than 140 pmol/L was determined for the following patient subgroups: younger than 70 y, older than 70 y, anemic, non-anemic, macrocytic, normocytic, microcytic, documented iron deficiency, and documented thalassemia. RESULTS: The prevalence of B12 deficiency (<140 pmol/L) ranged from 4.8% to 9.8% among the different subgroups. CONCLUSIONS: Whatever screening criteria were used, a significant number of B12-deficient patients will be missed. Therefore, there may be a case for universal vitamin B12 screening.

Differential impacts of coping strategies on trati the mental health of Chinese nurses in hospitals in Hong Kong.

This study examined the types of coping strategies used by hospital nurses in Hong Kong. The impacts of these coping strategies on the mental health of nurses were also investigated. Results showed that coping strategies were both situation-specific and culture-specific, with direct action coping, acceptance and positive thinking used more frequently than avoidance and alcohol. It was found that more than one-third of the nurses were considered to be at risk of developing poor mental health, and the most frequent symptomatic complaints included anxieties and feelings of inadequacy in handling daily activities. Nurses who were mentally healthy used more direct action coping and positive thinking, and fewer avoidance strategies and drinking than did nurses who were at risk of developing poor mental health. Contrary to our hypothesis, nurses who adopted more acceptance strategies had poorer mental health. Implications of the study are discussed.

Expression and protein-binding studies of the EEN gene family, new interacting partners for dynamin, synaptojanin and huntingtin proteins.

EEN, identified initially as a fusion partner to the mixed-lineage leukaemia gene in human leukaemia, and its related members, EEN-B1 and EEN-B2, have recently been shown to interact with two endocytic molecules, dynamin and synaptojanin, as well as with the huntingtin protein. In the present study, we show that the expression of the EEN gene-family members is differentially regulated. Multiple-spliced variants were identified for EEN-B2. In the brain, EEN-B1 and EEN-B2 mRNA are preferentially expressed in the cerebellar Purkinje and granule cells, dentate gyrus cells, hippocampal pyramidal neurons and cerebral granule cells. The expression patterns of EEN-B1 and EEN-B2 mRNA in the brain overlap with those of dynamin-I/III, synaptojanin-I and huntingtin, whereas the ubiquitous expression of EEN is consistent with that of dynamin-II. In testes, members of the EEN family are co-expressed with testis-type dynamin and huntingtin in Sertoli cells and germ cells respectively. Our results on the overlapping expression patterns are consistent with the proposed interaction of EEN family members with dynamin, synaptojanin and huntingtin protein in vivo. Although all three EEN family members bind to dynamin and synaptojanin, EEN-B1 has the highest affinity for binding, followed by EEN and EEN-B2. We also demonstrate that amphiphysin, a major synaptojanin-binding protein in brain, can compete with the EEN family for binding to synaptojanin and dynamin. We propose that recruitment of the EEN family by dynamin/synaptojanin to clathrin-coated pits can be regulated by amphiphysin.

The interaction between EEN and Abi-1, two MLL fusion partners, and synaptojanin and dynamin: implications for leukaemogenesis.

The mixed lineage leukaemia gene, MLL (also called HRX, ALL-1) in acute leukaemia is fused to at least 16 identified partner genes that display diverse structural and biochemical properties. Using GST pull down and the yeast two hybrid system, we show that two different MLL fusion partners with SH3 domains, EEN and Abi-1, interact with dynamin and synaptojanin, both of which are involved in endocytosis. Synaptojanin, a member of the inositol phosphatase family that has recently been shown to regulate cell proliferation and survival, is also known to bind to Eps15, the mouse homologue of AF1p, another fusion partner of MLL. Expression studies show that synaptojanin is strongly expressed in bone marrow and immature leukaemic cell lines, very weakly in peripheral blood leukocytes and absent in Raji, a mature B cell line. We found that the SH3 domains of EEN and Abi-1 interact with different proline-rich domains of synaptojanin while the EH domains of Eps15 interact with the NPF motifs of synaptojanin. In vitro competitive binding assays demonstrate that EEN displays stronger binding affinity than Abi-1 and may compete with it for synaptojanin. These findings suggest a potential link between MLL fusion-mediated leukaemogenesis and the inositol-signalling pathway.

The impact of differential binding of wild-type RARalpha, PML-, PLZF- and NPM-RARalpha fusion proteins towards transcriptional co-activator, RIP-140, on retinoic acid responses in acute promyelocytic leukemia.

Retinoic acid receptor (RA) heterodimer (RAR/RXR) activities have been shown to be repressed by transcriptional co-repressor, SMRT/N-CoR, in the absence of the ligand while upon all-trans retionic acid (ATRA) treatment, SMRT/N-CoR is dissociated from RARalpha leading to gene expression by the recruitment of transcriptional co-activators to the transcriptional complex. The difference in response to ATRA therapy between acute promyelocytic leukemia (APL) patients with PML-RARalpha fusion and PLZF-RARalpha fusion has recently been found to be partially due to the strong association of the transcriptional co-repressor, SMRT/N-CoR, with PLZF domain. We demonstrate that SMRT association, as with PML-RARalpha, can be released from NPM-RARalpha at pharmacological concentration of ATRA (10-6 M). Moreover, we show for the first time that the interaction between the transcriptional co-activator, RIP-140, and PML-, PLZF- or NPM-RARalpha fusion proteins can be positively stimulated by ATRA although they are less sensitive as compared with the wild-type RARalpha. Our results suggest that the dissociation of transcriptional co-repressors, SMRT/N-CoR, and recruitment of co-activators, eg RIP-140, to APL-associated fusion proteins constitute a common molecular mechanism in APL and underlie the responsiveness of the disease to RA therapy. Leukemia (2000) 14, 77-83.

Complex variant 15;17 translocations in acute promyelocytic leukemia. A case report and review of three-way translocations.

Complex variant 15;17 translocations are increasingly recognized in acute promyelocytic leukemia (APL). We report a novel three-way translocation in APL involving chromosomes 15, 17, and X in the form of t(X;17;15)(q13;q12;q21). Southern blot analysis showed retinoic acid receptor alpha (RARA) gene rearrangement at intron 2. Clinical and morphologic findings are typical of APL, and a complete remission was attained with a course of conventional chemotherapy. A review of three-way complex variants of 15;17 translocation in the literature reveals 21 published cases in addition to ours. PML/RARA fusion was observed in all 8 cases in which molecular genetic analysis had been performed. More cases need to be analyzed to determine if clustering to particular chromosomal bands occurs in variant translocations, and whether APL cases harboring complex 15;17 variants differ clinically from those with classical 15;17 translocation.

Coexpression of the lysyl oxidase-like gene (LOXL) and the gene encoding type III procollagen in induced liver fibrosis.

We have isolated a mouse lysyl oxidase-like (LOXL) cDNA from a mouse embryo cDNA library and used this cDNA to measure changes in steady state levels of LOXL mRNA during the development of carbon tetrachloride-induced liver fibrosis in adult mice. These results revealed the coincident appearance of increased steady state levels of LOXL mRNA and type III procollagen mRNA early in the development of liver fibrosis. In contrast, steady state levels of lysyl oxidase mRNA increased throughout the onset of hepatic fibrosis and appeared in parallel with the increased steady state levels of pro-alphaI (I) collagen mRNA. These findings suggest that the LOXL protein (possibly an isoform of lysyl oxidase) is involved in the development of lysine-derived cross-links in collagenous substrates. Moreover, the substrate specificity of the LOXL protein may be different to that of lysyl oxidase and this difference may be collagen-type specific.

MLL self fusion mediated by Alu repeat homologous recombination and prognosis of AML-M4/M5 subtypes.

Fifty-six patients with de novo acute myeloid leukemia M4/M5 subtypes were studied for rearrangements of the mixed lineage leukemia gene, MLL (also called HRX, Htrx-1, or ALL-1). Ten patients (18%) showed rearrangements of the MLL gene, 9 in a major breakpoint cluster region within a centromeric 8.3-kb BamHI fragment, whereas rearrangement in one patient was the result of a direct tandem duplication of exons 2-6 of MLL. Analysis of sequences at the duplication junction revealed that the points of MLL fusion within introns 6 and 1 both lie within Alu elements. This suggests the involvement of Alu repeat mediated homologous recombination in MLL self fusion. For the 10 rearranged samples, cytogenetics analysis revealed a normal karyotype in 3, and 3 had abnormalities other than 11q23. Survival analysis of patients revealed no difference between those with rearrangement of MLL and those showing the germ-line configuration.

Comparison of the HbH inclusion test and a PCR test in routine screening for alpha thalassaemia in Hong Kong.

AIM: To compare the haemoglobin (Hb) H inclusion test with a polymerase chain reaction (PCR) test in routine screening for alpha thalassaemia. METHODS: Ninety nine peripheral blood samples from Chinese patients with mean corpuscular volume below 80 fl were screened for alpha thalassaemia using the HbH inclusion test and by PCR utilising primers bridging the common deletion breakpoint of the South East Asian (--SEA/) deletion. RESULTS: The HbH inclusion test was positive in 78 (79%) patients, 73 (93.7%) of whom carried the (--SEA/) deletion on analysis of their DNA by PCR, as did one patient with a negative HbH inclusion test. CONCLUSIONS: These results suggest that in areas with a high prevalence of the (--SEA/) deletion, such as Hong Kong, the HbH inclusion test can be replaced by PCR as the investigation of choice in screening for alpha thalassaemia.

Effects of follicle-stimulating hormone on inhibin release by different testicular compartments in the adult ram.

The aim of this study was to determine the bidirectional release of immunoreactive inhibin-alpha (irINH-alpha) by different testicular compartments in the adult ram and to assess the effects of FSH on the distribution of inhibin in the testis. Immunoreactive INH-alpha was measured by RIA in fluid samples collected concurrently from the three testicular compartments--the seminiferous tubules, the interstitium, and the vascular system--through catheters inserted surgically into the rete testis, testicular lymphatic duct system, and spermatic veins, respectively. Overall, the concentration of irINH-alpha in rete testis fluid was 25 times the level in testicular lymph and over 500 times the concentration in peripheral blood. The pattern of irINH-alpha concentration in rete testis fluid was inversely related to that in testicular lymph, but i.v. administration of FSH had a decoupling effect on this relationship by depressing inhibin concentration in testicular lymph without affecting inhibin levels in rete testis fluid. Nevertheless, increased flow of testicular lymph more than compensated for the transient fall in irINH-alpha concentration so that, overall, the total output of inhibin via the testicular lymphatic duct system (and the vascular system) increased significantly. No persistent or significant changes were observed in the flow rate of rete testis fluid or concentration of irINH-alpha in the fluid after administration of FSH. The time frame for the response of the testis to FSH is indicative of the involvement of a mediator. Electrophoretic analysis of serially collected testicular lymph samples consistently revealed an FSH-induced release of a series of proteins in the M(r) range of 30,000-32,000.(ABSTRACT TRUNCATED AT 250 WORDS)