Introduction
The impact of blood storage on red blood cell (RBC) alloimmunization remains controversial, with some studies suggesting enhancement of RBC‐induced alloantibody production and others ...failing to observe any impact of storage on alloantibody formation. Since evaluation of storage on RBC alloimmunization in patients has examined antibody formation against a broad range of alloantigens, it remains possible that different clinical outcomes reflect a variable impact of storage on alloimmunization to specific antigens.
Methods
RBCs expressing two distinct model antigens, HEL‐OVA‐Duffy (HOD) and KEL, separately or together (HOD × KEL), were stored for 0, 8, or 14 days, followed by detection of antigen levels prior to transfusion. Transfused donor RBC survival was assessed within 24 h of transfusion, while IgM and IgG antibody production were assessed 5 and 14 days after transfusion.
Results
Stored HOD or KEL RBCs retained similar HEL or KEL antigen levels, respectively, as fresh RBCs, but did exhibit enhanced RBC clearance with increased storage age. Storage enhanced IgG antibody formation against HOD, while the oppositive outcome occurred following transfusion of stored KEL RBCs. The distinct impact of storage on HOD or KEL alloimmunization did not appear to reflect intrinsic differences between HOD or KEL RBCs, as transfusion of stored HOD × KEL RBCs resulted in increased IgG anti‐HOD antibody development and reduced IgG anti‐KEL antibody formation.
Conclusions
These data demonstrate a dichotomous impact of storage on immunization to distinct RBC antigens, offering a possible explanation for inconsistent clinical experience and the need for additional studies on the relationship between RBC storage and alloimmunization.
Glycosaminoglycans (GAGs) such as chondroitin sulfate (CS) are the chief natural polysaccharides which reside in biological tissues mainly in extracellular matrix. These CS along with adhesion ...molecules and growth factors are involved in central nervous system (CNS) development, cell progression and pathogenesis. The chondroitin lyases are the enzyme that degrade and alter the CS chains and hence modify various signalling pathways involving CS chains. These CS lyases are substrate specific, can precisely manipulate the CS polysaccharides and have various biotechnological, medical and therapeutic applications. These enzymes can be used to produce the unsaturated oligosaccharides, which have immune-modulatory, anti-inflammatory and neuroprotective properties. This review focuses on the major breakthrough of the chondroitin sulfate degrading enzymes, their structures and functioning mechanism. This also provides comprehensive information regarding production, purification, characterization of CS lyases and their major applications, both established as well as emerging ones such as neural development.
•Probiotics offer health benefits by modulating the microbial community and enhancing host immunity.•Probiotics interfere with local and systemic immune reactions and thus improve barrier function of ...the intestinal mucosa.•Confer immuno-regulatory, anti-angiogenic, anti-allergic, anti-asthmatic, anti-colitis and anti-dermatitic activities.•Nutritional interventions with probiotics can impact health in a positive way.•Above statements have been discussed across models by literature search.
Immunity is the ability of the body to counteract pathogenic invasions. Dearth of it compromises health and survival, rendering its retention and escalation to be of paramount importance. In this regard, probiotics, the live microorganisms that offer health benefits by modulating gut microbiota and reinforcing host immunity, have proven to be very crucial. Probiotics along with their effector molecules have been demonstrated to confer immuno-regulatory, anti-angiogenesis, anti-allergic, anti-colitis and anti-dermatitic activities, among others. Interaction between probiotics and immune cells are vital for mucosal tissue homeostasis and innate immunity. Ample evidences have accumulated in recent times, supporting these findings. The major in vitro, in vivo and clinical trial findings have been summarized here. How nutritional interventions with probiotics can bolster innate immunity is the focal point of discussion. The immunological mechanisms of probiotic action in mucosal architecture restoration and pathogen elimination have been explained. Augmentation of probiotics by pairing with prebiotics has been briefly analyzed. The revolutionizing power of personalized probiotics in healthcare has been furnished in a nutshell. Probiotics have already been established as important components of functional foods. This review provides the immunomodulatory aspect of probiotics in appreciating their potentials, and discerning deficiencies.
Eichhornia crassipes
or water hyacinth is a free-floating plant, growing plentifully in the tropical water bodies. This invasive weed poses multiple hazards ranging from ecological and economical to ...social. It tends to endanger biodiversity, cause eutrophication, shelter pests, clog fresh waterways, affect agriculture and aquaculture, hamper shipping and recreational activities. Existing control methods have been insufficient to contain its aggressive propagation. Recently, it has been envisaged that successful utilization of this weed can solve the associated problems associated with them. It is being speculated that the huge biomass can be used in waste water treatment, heavy metal and dye remediation, as substrate for bioethanol and biogas production, electricity generation, industrial uses, human food and antioxidants, medicines, feed, agriculture and sustainable development. Towards this quest many approaches have been undertaken and partial success is achieved. If harnessed properly, this weed-based green technology can solve many of the issues our society faces now. In this context, the papers published in recent years have been reviewed, with the objective of creating public awareness and bolstering management and utilization of this cumbersome invasive weed.
Anti-CD19 chimeric antigen receptor T (CAR-T) cells have demonstrated activity against relapsed/refractory lymphomas. Cytokine release syndrome (CRS) and immune effector cell - associated ...neurotoxicity syndrome (ICANS) are well-known complications. Tocilizumab, a monoclonal antibody targeting the interleukin-6 (IL-6) receptor was administered 1 hour prior to infusion of anti-CD19 CAR-T cells with CD3ζ/4-1BB costimulatory signaling used to treat non-Hodgkin lymphoma patients. Relapsed/refractory lymphoma patients treated with anti-CD19 CAR-T cells were included in this analysis. Cytokine plasma levels were measured by electrochemiluminescence before lymphodepleting chemotherapy, prior to infusion and then on days 2, 4,6, and 14 days after treatment. Twenty patients were treated. Cell products included locally manufactured anti-CD19 CAR-T (n=18) and tisagenlecleucel (n=2). There were no adverse events attributed to tocilizumab. Ten patients had grade 1-2 CRS at a median of 4 (range 3-7) days. There were no cases of grade ≥3 CRS. Five patients had ICANS, grade 1 (n=4) and grade 4 (n=1). Laboratory studies obtained prior to lymphodepleting chemotherapy were comparable between patients with and without CRS, except for interleukin (IL)-15 plasma concentrations. patients with CRS had higher post-infusion ferritin and C reactive protein, with more marked increases in inflammatory cytokines, including IL-6, IL-15, IFN-γ, fractalkine and MCP-1. Fifteen patients (75%) achieved CR and 2 (10%), PR. One-year OS and PFS estimates were 83% and 73%. Prophylactic tocilizumab was associated with low CRS incidence and severity. There were no adverse events associated with tocilizumab, no increase in frequency or severity of ICANS and excellent disease control and overall survival.
To understand the effects of nutrition security and social determinants of health (SDOHs) on pressure injury (PI) progression through a scoping review and retrospective review of patients reporting ...to New England's largest healthcare system.
Authors performed a scoping review for full-text, original articles reporting outcomes data specific to PIs in patients with socially informed nutrition insecurity. Investigators also performed a retrospective review of all patients from 2012 to 2021 to search for patients with PI documentation and International Classification of Diseases, Tenth Revision Z codes related to the SDOHs.
A full-text review of 2,323 articles from 1965 to 2020 failed to locate any eligible studies. Investigators identified 1,044 patients who met the inclusion criteria; 50.7% were men, 74.3% were White, and 13.3% had evidence of detrimental SDOHs. The average PI duration was 12.13 days (interquartile range, 6 days). Multivariate regression analysis revealed that PI duration was longer in men, Black patients, and patients with evidence of detrimental SDOHs compared with their converse counterparts (P < .0001). The presence of detrimental SDOHs independently predicted an increased duration of disease by 13.07 days (95% CI, 8.99-17.15; t = 6.29, P < .0001).
A patient's SDOH history has a significant and considerably stronger correlation with disease progression than predictors that are traditionally studied such as sex, race, or body mass index. These findings are novel, as highlighted by the absence of data uncovered in the literature. These data carry relevance for plastic surgeons wishing to prevent early recurrence following operative closure of PI-related wounds.
Red blood cell (RBC) alloimmunization can make it difficult to procure compatible RBCs for future transfusion, directly leading to increased morbidity and mortality in transfusion-dependent patients. ...However, the factors that regulate RBC alloimmunization remain incompletely understood. As complement has been shown to serve as a key adjuvant in the development of antibody (Ab) responses against microbes, we examined the impact of complement on RBC alloimmunization. In contrast to the impact of complement component 3 (C3) in the development of an immune response following microbial exposure, transfusion of C3 knockout (C3 KO) recipients with RBCs expressing KEL (KEL RBCs) actually resulted in an enhanced anti-KEL Ab response. The impact of C3 appeared to be specific to KEL, as transfusion of RBCs bearing another model antigen, the chimeric HOD antigen (hen egg lysozyme, ovalbumin and Duffy), into C3 KO recipients failed to result in a similar increase in Ab formation. KEL RBCs experienced enhanced C3 deposition and loss of detectable target antigen over time when compared to HOD RBCs, suggesting that C3 may inhibit Ab formation by impacting the accessibility of the target KEL antigen. Loss of detectable KEL on the RBC surface did not reflect antigen masking by C3, but instead appeared to result from actual removal of the KEL antigen, as western blot analysis demonstrated complete loss of detectable KEL protein. Consistent with this, exposure of wild-type B6 or C3 KO recipients to KEL RBCs with reduced levels of detectable KEL antigen resulted in a significantly reduced anti-KEL Ab response. These results suggest that C3 possesses a unique ability to actually suppress Ab formation following transfusion by reducing the availability of the target antigen on the RBC surface.
Fungal keratitis is a serious ocular infection that is considered to be rare among contact lens wearers. The recent Fusarium keratitis outbreak raised questions regarding the background rate of ...Fusarium-related keratitis and other fungal keratitis in this population.
Retrospective, multicenter case series.
Six hundred ninety-five cases of fungal keratitis cases who presented to 1 of 10 tertiary medical centers from 2001 to 2007.
Ten tertiary care centers in the United States performed a retrospective review of culture-positive fungal keratitis cases at their centers between January 2001 and December 2007. Cases were identified using microbiology, pathology, and/or confocal microscopy records. Information was collected on contact lens status, method of diagnosis, and organism(s) identified. The quarterly number of cases by contact lens status was calculated and Poisson regression was used to evaluate presence of trends. The Johns Hopkins Medicine Institutional Review Board (IRB) and the IRBs at each participating center approved the research.
Quarterly number of fungal keratitis cases and fungal species.
We identified 695 fungal keratitis cases; 283 involved the use of contact lenses. The quarterly number of Fusarium cases increased among contact lens wearers (CLWs) during the period that ReNu with MoistureLoc (Bausch & Lomb, Rochester, NY) was on the market, but returned to prior levels after withdrawal of the product from the market. The quarterly frequency of other filamentous fungi cases showed a statistically significant increase among CLWs comparing October 2004 through June 2006 with July 2006 through December 2007 with January 2001 through September 2004 (P < 0.0001).
The quarterly number of Fusarium fungal keratitis cases among CLWs returned to pre-Renu with Moistureloc levels after removal of the product from the market. However, the number of other filamentous fungal keratitis cases, although small, seems to have increased among refractive CLWs. Reasons for these apparent increases are unclear.
Functional oligosaccharides have emerged as valuable components of food and dietary supplements. Their resistance to digestion and fermentation by colonic microbes has given them the nutritional ...edge. Apart from implications as dietary fibers, sweeteners, and humectants, they are hailed as prebiotics. Their beneficial effects extend from antioxidant, anti‐inflammatory, immunomodulatory, antiallergic, hypotensive, hyperlipemic, neuroprotective to anticancer. The rising popularity of bioactive oligosaccharides has accelerated the search for their generation from new, sustainable sources. The surfacing crucial role in healthcare and unprecedented demand necessitates deeper investigation. The present review embodies an overview on various aspects of production, properties with emphasis on therapeutic applications of functional oligosaccharides. The biological efficacy and possible mechanisms of action of oligosaccharides have also been discussed.
Abstract Inflammation is a pivotal defense system of body. Unfortunately, when homeostasis falters, the same inflammatory mechanism acts as a double-edged sword, and turns offensive, paving the path ...for a broad array of pathologies. A multi-protein complex termed as inflammasome perceives the PAMPs (pathogen associated molecular patterns) and DAMPs (danger associated molecular patterns), executing immune responses. This activation predominantly encompasses the elaboration of effector cytokines IL-1β, IL-18, and the cysteine proteases (caspase 1 and 11). Extensive study on an inflammasome NLRP3 has revealed its role in the onset and progression of pathogenic, metabolic, autoimmune, neural, and geriatric diseases. In this regard, this inflammasome's immune activation mechanisms and inhibition strategies have been discussed. Through this rigorous literature analysis, the superficial diversity between pathogens/allergens and mutagens, and NLRP3 activity towards them has been emphasized. Though there is a scope for inhibition of aberrant inflammasomes, including that of NLRP3, given their complexity and unpredictability, prevention of their activation by lifestyle correction has been suggested.
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