736 research outputs found
Post transplant lymphoproliferative disorder
Introduction: Post-transplant lymphoproliferative disorder (PTLD) is a recognized complication exclusive to solid organ transplant recipients and carries a high mortality.
Methods: We retrospectively reviewed records of all renal transplant recipients under follow up at our institution over the last seven years (2005-2011). We reviewed the patient characteristics, immunosuppression regimen and risk factors for the development of PTLD and its outcomes in our transplant cohort.
Results: Four out of 63 patients were diagnosed with PTLD. PTLD was incidentally diagnosed on a transplant biopsy that was performed for an unexplained rise in serum creatinine in three patients. The fourth patient presented with left submandibular lymphadenopathy. Majority presented within 18 months of renal transplantation. After the diagnosis of PTLD on graft biopsy, all patients were fully investigated and two patients had systemic involvement. In the
patients with systemic involvement, reduction of immunosuppression and anti B cell therapy with Rituximab was used with good success. The patient with submandibular lymphadenopathy received chemotherapy in addition to reduction of immunosuppression. Three PTLD cases were polyclonal and diagnosed early whereas the fourth case was monoclonal.
Conclusion: PTLD can sometimes be incidentally diagnosed on an allograft biopsy performed for rejection. The incidence of PTLD in our centre is higher than reports from other centres but our outcome is good if recognised and treated early
Evaluating cardiovascular risk in chronic kidney disease patients: a biomarker approach
Cardiovascular disease (CVD) is a major cause of morbidity and mortality in chronic kidney disease (CKD) patients. This study aimed to determine the roles of CVD biomarkers in CKD patients. This was a case-control study which recruited consecutive patients with stage 2-4 CKD patients with and without CVD. Serum levels of highly-sensitive C reactive protein (hs-CRP), cystatin C (CysC), asymmetrical dimetylarginine (ADMA) and symmetrical dimethylarginine (SDMA) were measured. Sixty two stage 2-4 CKD patients with a mean age of 60.3 Β± 10.4 years were recruited. Twenty three (37.1%) of them had CVD. Those CKD patients with CVD were older (64.1Β±8.0 vs 58.1Β± 1.1, p0.05). There were no differences in their mean serum levels of hs-CRP, CysC, ADMA and SDMA. Risk factors including age, diabetes mellitus, hypertension and renal functions were still the most important CVD risk factors in CKD patients
Multi-lepton signals from the top-prime quark at the LHC
We analyze the collider signatures of models with a vector-like top-prime
quark and a massive color-octet boson. The top-prime quark mixes with the top
quark in the Standard Model, leading to richer final states than ones that are
investigated by experimental collaborations. We discuss the multi-lepton final
states, and show that they can provide increased sensitivity to models with a
top-prime quark and gluon-prime. Searches for new physics in high multiplicity
events are an important component of the LHC program and complementary to
analyses that have been performed.Comment: 7 pages, 4 figures, 2 table
A Novel Strategy to Screen Bacillus Calmette-GuΓ©rin Protein Antigen Recognized by Ξ³Ξ΄ TCR
BACKGROUND: Phosphoantigen was originally identified as the main Ξ³Ξ΄ TCR-recognized antigen that could activate Ξ³Ξ΄ T cells to promote immune protection against mycobacterial infection. However, new evidence shows that the Ξ³Ξ΄ T cells activated by phosphoantigen can only provide partial immune protection against mycobacterial infection. In contrast, whole lysates of Mycobacterium could activate immune protection more potently, implying that other Ξ³Ξ΄ TCR-recognized antigens that elicit protective immune responses. To date, only a few distinct mycobacterial antigens recognized by the Ξ³Ξ΄ TCR have been characterized. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we established a new approach to screen epitopes or protein antigens recognized by the Ξ³Ξ΄ TCR using Bacillus Calmette-GuΓ©rin- (BCG-) specific Ξ³ TCR transfected cells as probes to pan a 12-mer random-peptide phage-displayed library. Through binding assays and functional analysis, we identified a peptide (BP3) that not only binds to the BCG-specific Ξ³Ξ΄ TCR but also effectively activates Ξ³Ξ΄ T cells isolated from human subjects inoculated with BCG. Importantly, the Ξ³Ξ΄ T cells activated by peptide BP3 had a cytotoxic effect on THP-1 cells infected with BCG. Moreover, the oxidative stress response regulatory protein (OXYS), a BCG protein that matches perfectly with peptide BP3 according to bioinformatics analysis, was confirmed as a ligand for the Ξ³Ξ΄ TCR and was found to activate Ξ³Ξ΄ T cells from human subjects inoculated with BCG. CONCLUSIONS/SIGNIFICANCE: In conclusion, our study provides a novel strategy to identify epitopes or protein antigens for the Ξ³Ξ΄ TCR, and provides a potential means to screen mycobacterial vaccines or candidates for adjuvant
Intramuscular midazolam, olanzapine, or haloperidol for the management of acute agitation: A multi-centre, double-blind, randomised clinical trial
Β© 2021 The Authors Background: The safety and effectiveness of intramuscular olanzapine or haloperidol compared to midazolam as the initial pharmacological treatment for acute agitation in emergency departments (EDs) has not been evaluated. Methods: A pragmatic, randomised, double-blind, active-controlled trial was conducted from December 2014 to September 2019, in six Hong Kong EDs. Patients (aged 18β75 years) with undifferentiated acute agitation requiring parenteral sedation were randomised to 5 mg intramuscular midazolam (n = 56), olanzapine (n = 54), or haloperidol (n = 57). Primary outcomes were time to adequate sedation and proportion of patients who achieved adequate sedation at each follow-up interval. Sedation levels were measured on a 6-level validated scale (ClinicalTrials.gov Identifier: NCT02380118). Findings: Of 206 patients randomised, 167 (mean age, 42 years; 98 [58Β·7%] male) were analysed. Median time to sedation for IM midazolam, olanzapine, and haloperidol was 8Β·5 (IQR 8Β·0), 11Β·5 (IQR 30Β·0), and 23Β·0 (IQR 21Β·0) min, respectively. At 60 min, similar proportions of patients were adequately sedated (98%, 87%, and 97%). There were statistically significant differences for time to sedation with midazolam compared to olanzapine (p = 0Β·03) and haloperidol (p = 0Β·002). Adverse event rates were similar across the three arms. Dystonia (n = 1) and cardiac arrest (n = 1) were reported in the haloperidol group. Interpretation: Midazolam resulted in faster sedation in patients with undifferentiated agitation in the emergency setting compared to olanzapine and haloperidol. Midazolam and olanzapine are preferred over haloperidol's slower time to sedation and potential for cardiovascular and extrapyramidal side effects. Funding: Research Grants Council, Hong Kong
Chalcogenide Glass-on-Graphene Photonics
Two-dimensional (2-D) materials are of tremendous interest to integrated
photonics given their singular optical characteristics spanning light emission,
modulation, saturable absorption, and nonlinear optics. To harness their
optical properties, these atomically thin materials are usually attached onto
prefabricated devices via a transfer process. In this paper, we present a new
route for 2-D material integration with planar photonics. Central to this
approach is the use of chalcogenide glass, a multifunctional material which can
be directly deposited and patterned on a wide variety of 2-D materials and can
simultaneously function as the light guiding medium, a gate dielectric, and a
passivation layer for 2-D materials. Besides claiming improved fabrication
yield and throughput compared to the traditional transfer process, our
technique also enables unconventional multilayer device geometries optimally
designed for enhancing light-matter interactions in the 2-D layers.
Capitalizing on this facile integration method, we demonstrate a series of
high-performance glass-on-graphene devices including ultra-broadband on-chip
polarizers, energy-efficient thermo-optic switches, as well as graphene-based
mid-infrared (mid-IR) waveguide-integrated photodetectors and modulators
BCAA catabolism in brown fat controls energy homeostasis through SLC25A44.
Branched-chain amino acid (BCAA; valine, leucine and isoleucine) supplementation is often beneficial to energy expenditure; however, increased circulating levels of BCAA are linked to obesity and diabetes. The mechanisms of this paradox remain unclear. Here we report that, on cold exposure, brown adipose tissue (BAT) actively utilizes BCAA in the mitochondria for thermogenesis and promotes systemic BCAA clearance in mice and humans. In turn, a BAT-specific defect in BCAA catabolism attenuates systemic BCAA clearance, BAT fuel oxidation and thermogenesis, leading to diet-induced obesity and glucose intolerance. Mechanistically, active BCAA catabolism in BAT is mediated by SLC25A44, which transports BCAAs into mitochondria. Our results suggest that BAT serves as a key metabolic filter that controls BCAA clearance via SLC25A44, thereby contributing to the improvement of metabolic health
A Decline in p38 MAPK Signaling Underlies Immunosenescence in Caenorhabditis elegans
The decline in immune function with aging, known as immunosenescence, has been implicated in evolutionarily diverse species, but the underlying molecular mechanisms are not understood. During aging in Caenorhabditis elegans, intestinal tissue deterioration and the increased intestinal proliferation of bacteria are observed, but how innate immunity changes during C. elegans aging has not been defined. Here we show that C. elegans exhibits increased susceptibility to bacterial infection with age, and we establish that aging is associated with a decline in the activity of the conserved PMK-1 p38 mitogen-activated protein kinase pathway, which regulates innate immunity in C. elegans. Our data define the phenomenon of innate immunosenescence in C. elegans in terms of the age-dependent dynamics of the PMK-1 innate immune signaling pathway, and they suggest that a cycle of intestinal tissue aging, immunosenescence, and bacterial proliferation leads to death in aging C. elegans
Syntheses and Fundamental Properties of Fe-rich Metastable Phase Alloys with Saturation Magnetization Exceeding 1.9 T
Visualization of Allostery in P-Selectin Lectin Domain Using MD Simulations
Allostery of P-selectin lectin (Lec) domain followed by an epithelial growth factor (EGF)-like domain is essential for its biological functionality, but the underlying pathways have not been well understood. Here the molecular dynamics simulations were performed on the crystallized structures to visualize the dynamic conformational change for state 1 (S1) or state 2 (S2) Lec domain with respective bent (B) or extended (E) EGF orientation. Simulations illustrated that both S1 and S2 conformations were unable to switch from one to another directly. Instead, a novel S1' conformation was observed from S1 when crystallized B-S1 or reconstructed βE-S1β structure was employed, which was superposed well with that of equilibrated S1 Lec domain alone. It was also indicated that the corresponding allosteric pathway from S1 to S1' conformation started with the separation between residues Q30 and K67 and terminated with the release of residue N87 from residue C109. These results provided an insight into understanding the structural transition and the structure-function relationship of P-selectin allostery
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