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Ceramic lattices hold great potential for bone scaffolds to facilitate bone regeneration and integration of native tissue with medical implants. While there have been several studies on additive manufacturing of ceramics and their osseointegrative and osteoconductive properties, there is a lack of a comprehensive examination of their mechanical behavior. Therefore, the aim of this study was to assess the mechanical properties of different additively manufactured ceramic lattice structures under different loading conditions and their overall ability to mimic bone tissue properties. Eleven different lattice structures were designed and manufactured with a porosity of 80% using two materials, hydroxyapatite (HAp) and zirconium dioxide (ZrO 2 ). Six cell-based lattices with cubic and hexagonal base, as well as five Voronoi-based lattices were considered in this study. The samples were manufactured using lithography-based ceramic additive manufacturing and post-processed thermally prior to mechanical testing. Cell-based lattices with cubic and hexagonal base, as well as Voronoi-based lattices were considered in this study. The lattices were tested under four loading conditions: compression, four-point bending, shear and tension. The manufacturing process of the different ceramics leads to different deviations of the lattice geometry, hence, the elastic properties of one structure cannot be directly inferred from one material to another. ZrO 2 lattices prove to be stiffer than HAp lattices of the same designed structure. The Young's modulus for compression of ZrO 2 lattices ranges from 2 to 30GPa depending on the used lattice design and for HAp 200MPa to 3.8GPa. The expected stability, the load where 63.2% of the samples are expected to be destroyed, of the lattices ranges from 81 to 553MPa and for HAp 6 to 42MPa. For the first time, a comprehensive overview of the mechanical properties of various additively manufactured ceramic lattice structures is provided. This is intended to serve as a reference for designers who would like to expand the design capabilities of ceramic implants that will lead to an advancement in their performance and ability to mimic human bone tissue., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Nucleic acid testing (NAT) for HIV, HBV and HCV shortens the time between infection and detection by available testing. A group of experts was selected to develop recommendations for the use of NAT in the HIV/HBV/HCV screening of potential organ donors. The rapid turnaround times needed for donor testing and the risk of death while awaiting transplantation make organ donor screening different from screening blood-or tissue donors. In donors with no identified risk factors, there is insufficient evidence to recommend routine NAT, as the benefits of NAT may not outweigh the disadvantages of NAT especially when false-positive results can lead to loss of donor organs. For donors with identified behavioral risk factors, NAT should be considered to reduce the risk of transmission and increase organ utilization. Informed consent balancing the risks of donor-derived infection against the risk of remaining on the waiting list should be obtained at the time of candidate listing and again at the time of organ offer. In conclusion, there is insufficient evidence to recommend universal prospective screening of organ donors for HIV, HCV and HBV using current NAT platforms. Further study of viral screening modalities may reduce disease transmission risk without excessive donor loss.

Background: Our laboratory previously reported that leukemia patients who developed > or = 10% gammadelta+ T cells during the first six months after receiving an anti-TCRalphabeta T-cell-depleted (TCD) graft from a partially mismatched related donor (PMRD) had a disease-free survival (DFS) advantage. These gammadelta+ T cells were V81+CD3+CD4-CD8-CD69+HLADR+ and are cytotoxic to K562 cells., Methods: In order to determine whether the anti-alphabeta TCD regimen was associated with these findings, we compared the reconstitution of gammadelta+ T cells from patients who received TCD PMRD grafts using the anti-TCRc4 MAb TIOB9-1A31 (previously reported) with similar patients who received grafts using the anti-CD3 MAb OKT3., Results: Increased cytotoxic Vdelta1+ T cells were seen in 10 of 43 T10B9 TCD patients compared to 7 of 100 in the OKT3 TCD group (23% versus 7%, p = 0.010). T10B9 patients with increased gammadelta+ T cells also exhibited a higher range of increased gammadelta+ T cells and the length of time the gammadelta+ T cells remained high was longer when compared to OKT3 patients. Patients with increased gammadelta+ T cells whose grafts were T-cell depleted with T10B9 showed a significant decrease in relapse (p = 0.038). Similar rates and reduction in relapse were seen in OKT3 TCD patients, although significance was not reached due to the small number of patients with increased gammadelta+ T cells. Estimated 3 year disease-free survival was significantly improved in T10B9 patients with increased gammadelta+ T cells (0.79 versus 0.31, p = 0.009), a trend also seen in OKT3 patients (p = 0.091)., Discussion: These observations indicate that Vdelta1+CD4-CD8-cytotoxic T cells are associated with lower relapse rates and improved survival, and thus may have a role in a graft-versus-leukemia effect.

Most patients requiring allogeneic bone marrow transplant (allo-BMT) do not have an HLA-matched sibling donor. A phenotypically matched unrelated donor graft has been made available for approximately 50% of Caucasians and less than 10% of ethnic and racial minorities in need. However, almost all patients have a readily available partially mismatched related donor (PMRD). We summarize our experience with 72 patients who ranged from 1 to 50 years of age (median, 16 years) and who were recipients of a PMRD allo-BMT from haploidentical family members following conditioning therapy using total body irradiation (TBI) and multiagent, high-dose chemotherapy. T-cell depletion and post-BMT immunosuppression were combined for graft-versus-host disease (GVHD) prophylaxis. The probability of engraftment was 0.88 at 32 days. Six of 10 patients who failed to engraft achieved engraftment after secondary transplant. Grade II to IV acute GVHD was seen in 9 of 58 (16%) evaluable patients; extensive chronic GVHD was seen in 4 of 48 (8%) evaluable patients. There was a statistically significant difference in 2-year survival probability between low-risk and high-risk patients (0.55 v 0.27, P = .048). Prognostic factors that affected outcomes in multivariate analysis were (1) a lower TBI dose and 3-antigen rejection mismatch decreased stable engraftment (P = .005 and P = .002, respectively); (2) a higher T-cell dose increased acute GVHD (P = .058); (3) a higher TBI dose increased chronic GVHD (P = .016); and (4) a high-risk disease category increased treatment failure from relapse or death (P = .037). A PMRD transplant can be performed with acceptable rates of graft failure and GVHD. Using sequential immunomodulation, the disease status at the time of transplant is the only prognostic factor significantly associated with long-term successful outcome after PMRD allo-BMT. When allogeneic rather than autologous BMT is indicated, progression in disease status before transplant can be avoided using a PMRD with equal inclusion of all ethnic or racial groups.

The macrophage colony-stimulating factor receptor and several other hematopoietic growth factor receptors induce the tyrosine phosphorylation of a 145- to 150-kD protein in murine cells. We have previously cloned a cDNA for the murine 150-kD protein, SHIP, and found that it encodes a unique signaling intermediate that binds the SHC PTB domain through at least one tyrosine phosphorylated (NPXY) site in the carboxyl-terminal region. SHIP also contains several potential SH3 domain-binding sites, an SH2 domain for binding other tyrosine phosphorylated proteins, and an enzymatic activity that removes the phosphate from the 5 position of phosphatidylinositol 3,4,5-phosphate or from inositol 1,3,4,5-phosphate. SHIP has a negative effect on cell growth and therefore loss or modification may have profound effects on hematopoietic cell development. In this study, we have cloned a cDNA for human SHIP and examined mRNA and protein expression of SHIP and related species in bone marrow and blood cells. Flow cytometry indicates that at least 74% of immature CD34+ cells express SHIP cross-reacting protein species, whereas within the more mature population of CD33+ cells, only 10% of cells have similar expression. The majority of T cells react positively with the anti-SHIP antibodies, but significantly fewer B cells are positive. Immunoblotting detects up to seven different cross-reacting SHIP species, with peripheral blood mononuclear cells exhibiting primarily a 100-kD protein and a CD34+ acute myeloblastic leukemia expressing mainly 130-kD and 145-kD forms of SHIP. Overall, these results indicate that there is an enormous diversity in the size of SHIP or SHIP-related mRNA and protein species. Furthermore, the expression of these protein species changes according to both the developmental stage and differentiated lineage of the mature blood cell.

Purpose: To investigate an association of the severity of the human immunodeficiency virus (HIV) disease with decreased tear production in a controlled setting., Patients and Methods: Seventy-two patients (144 eyes) and 30 age- and sex-matched control subjects (60 eyes) were studied prospectively. Tear production was measured using the Schirmer I test (measured in millimeters after 5 minutes). Patients were classified into three clinical groups: asymptomatic HIV infection, lymphadenopathy syndrome (LAS) or acquired immune deficiency syndrome (AIDS)-related complex (ARC), and AIDS. Additionally, patients were classified according to the CD4+ lymphocyte count., Results: Tear production (mean +/- standard deviation) did not differ (P = 0.32) among eyes of patients with asymptomatic HIV infection (17.1 +/- 10.8; n = 14), LAS or ARC (18.3 +/- 10.3; n = 70), and AIDS (20.7 +/- 10.3; n = 60). In addition, mean tear production was not decreased significantly when comparing each clinical group with the control subjects (17.8 +/- 4.4). However, the relative frequency of eyes with significantly decreased tear production (< 9 mm) was 23.6% in all 144 eyes. In addition, the relative frequency of significantly decreased tear production did not differ (P = 0.52) between eyes of patients with asymptomatic HIV infection (35.7%), LAS or ARC (21.4%), and AIDS (24.1%). In addition, the relative frequency of significantly decreased tear production did not differ (P = 0.30) between eyes of patients with a CD4+ count of more than 400 cells/microliters (23.1%; n = 26), 400 to 200 cells/microliters (31.3%; n = 48), 200 to 50 cells/microliters (14.3%; n = 42), and less than 50 cells/microliters (21.4%; n = 28)., Conclusion: The authors data show that decreased tear production occurs in approximately 20% to 25% of patients with HIV infection. This increased frequency of decreased tear production is not associated with the CD4+ count, or related to the severity of HIV disease, respectively. The possibility of an autoimmune-like pathogenesis of abnormalities of tear production in patients with HIV infection should be studied intensively.

The gene locus nuo of the proton-translocating NADH: ubiquinone oxidoreductase in Escherichia coli was identified by means of a DNA probe made by the polymerase chain reaction. The primers used for the reaction were derived from consensus sequences of the NAD(H)-binding subunit of mitochondrial NADH: ubiquinone oxidoreductase and the NAD(+)-reducing hydrogenase of Alcaligenes eutrophus. The nuo locus lies between minutes 49.2 and 49.6 on the E. coli chromosome and contains a cluster of 14 genes. They are bordered upstream by a sequence resembling sigma 70-dependent promoters and downstream by a sequence resembling rho-independent terminators. All 14 proteins derived from the nuo-genes are related to subunits of mitochondrial NADH: ubiquinone oxidoreductase, among which all subunits presumed to bind the substrates and to harbour the redox groups are found, as well as all seven mitochondrially encoded subunits. The E. coli enzyme seems to represent the minimal form of a proton-translocating NADH: ubiquinone oxidoreductase. The gene order in the nuo locus is conserved in comparison with other bacterial genomes and the chloroplast genome of higher plants. To some extent, the gene order correlates with the topological arrangement of the encoded subunits. The conception of modular evolution of NADH: ubiquinone oxidoreductase is further supported by the arrangement of the nuo-genes.