Hepatitis E virus in rabbits, Virginia, USA Cossaboom, Caitlin M; Córdoba, Laura; Dryman, Barbara A ...
Emerging infectious diseases,
11/2011, Letnik:
17, Številka:
11
Journal Article
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We identified hepatitis E virus (HEV) in rabbits in Virginia, USA. HEV RNA was detected in 14 (16%) of 85 serum samples and 13 (15%) of 85 fecal samples. Antibodies against HEV were detected in 31 ...(36%) of 85 serum samples. Sequence analyses showed that HEV from rabbits is closely related to genotype 3.
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Endothelial cells (EC) are able to actively control vascular permeability, coagulation, blood pressure and angiogenesis. Most recently, a role for endothelial cells in the immune ...response has been described. Therefore, the endothelium has a dual role controlling homeostasis but also being the first line for host defence and tissue damage repair thanks to its ability to mount an inflammatory response. Endothelial cells have been shown to express pattern-recognition receptors (PRR) including Toll-like receptors (TLR) that are activated in response to stimuli within the bloodstream including pathogens and damage signals. TLRs are strategic mediators of the immune response in endothelial cells but they also regulate the angiogenic process critical for tissue repair. Nevertheless, endothelial activation and angiogenesis can contribute to some pathologies. Thus, inappropriate endothelial activation, also known as endothelial dysfunction, through TLRs contributes to tissue damage during autoimmune and inflammatory diseases such as atherosclerosis, hypertension, ischemia and diabetes associated cardiovascular diseases. Also TLR induced angiogenesis is required for the growth of some tumors, atherosclerosis and rheumatoid arthritis, among others. In this review we discuss the importance of various TLRs in modulating the activation of endothelial cells and their importance in immunity to infection and vascular disease as well as their potential as therapeutic targets.
Despite the impressive results of autologous CAR-T cell therapy in refractory B lymphoproliferative diseases, CAR-NK immunotherapy emerges as a safer, faster, and cost-effective approach with no ...signs of severe toxicities as described for CAR-T cells. Permanently scrutinized for its efficacy, recent promising data in CAR-NK clinical trials point out the achievement of deep, high-quality responses, thus confirming its potential clinical use. Although CAR-NK cell therapy is not significantly affected by the loss or downregulation of its CAR tumor target, as in the case of CAR-T cell, a plethora of common additional tumor intrinsic or extrinsic mechanisms that could also disable NK cell function have been described. Therefore, considering lessons learned from CAR-T cell therapy, the emergence of CAR-NK cell therapy resistance can also be envisioned. In this review we highlight the processes that could be involved in its development, focusing on cytokine addiction and potential fratricide during manufacturing, poor tumor trafficking, exhaustion within the tumor microenvironment (TME), and NK cell short
in vivo
persistence on account of the limited expansion, replicative senescence, and rejection by patient’s immune system after lymphodepletion recovery. Finally, we outline new actively explored alternatives to overcome these resistance mechanisms, with a special emphasis on CRISPR/Cas9 mediated genetic engineering approaches, a promising platform to optimize CAR-NK cell function to eradicate refractory cancers.
CAR-T-cell therapy against MM currently shows promising results, but usually with serious toxicities. CAR-NK cells may exert less toxicity when redirected against resistant myeloma cells. CARs can be ...designed through the use of receptors, such as NKG2D, which recognizes a wide range of ligands to provide broad target specificity. Here, we test this approach by analyzing the antitumor activity of activated and expanded NK cells (NKAE) and CD45RA
T cells from MM patients that were engineered to express an NKG2D-based CAR. NKAE cells were cultured with irradiated Clone9.mbIL21 cells. Then, cells were transduced with an NKG2D-4-1BB-CD3z-CAR. CAR-NKAE cells exhibited no evidence of genetic abnormalities. Although memory T cells were more stably transduced, CAR-NKAE cells exhibited greater in vitro cytotoxicity against MM cells, while showing minimal activity against healthy cells. In vivo, CAR-NKAE cells mediated highly efficient abrogation of MM growth, and 25% of the treated mice remained disease free. Overall, these results demonstrate that it is feasible to modify autologous NKAE cells from MM patients to safely express a NKG2D-CAR. Additionally, autologous CAR-NKAE cells display enhanced antimyeloma activity demonstrating that they could be an effective strategy against MM supporting the development of NKG2D-CAR-NK-cell therapy for MM.
In the recent decades, zinc (Zn) and its alloys have been drawing attention as promising candidates for bioresorbable cardiovascular stents due to its degradation rate more suitable than magnesium ...(Mg) and iron (Fe) alloys. However, its mechanical properties need to be improved in order to meet the criteria for vascular stents. This work investigates the mechanical properties, biodegradability and biocompatibility of Zn-Mg and Zn-Cu alloys in order to determine a proper alloy composition for optimal stent performance. Nanoindentation measurements are performed to characterize the mechanical properties at the nanoscale as a function of the Zn microstructure variations induced by alloying. The biodegradation mechanisms are discussed and correlated to microstructure, mechanical performance and bacterial/cell response. Addition of Mg or Cu alloying elements refined the microstructure of Zn and enhanced yield strength (YS) and ultimate tensile strength (UTS) proportional to the volume fraction of secondary phases. Zn-1Mg showed the higher YS and UTS and better performance in terms of degradation stability in Hanks’ solution. Zn-Cu alloys presented an antibacterial effect for S. aureus controlled by diffusion mechanisms and by contact. Biocompatibility was dependent on the degradation rate and the nature of the corrosion products.
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ZnO nanoparticles (NPs) are arising as promising novel antibiotics toward device-related infections. The surface functionalization of Zn, a novel resorbable biomaterial, with ZnO NPs could present an ...effective solution to overcome such a threat. In this sense, the antibacterial and antibiofilm activity of nano- and microsized ZnO coatings was studied against clinically relevant bacteria, methicillin resistant Staphylococcus aureus (MRSA). The bacterial viability of planktonic and biofilm cells together with the corresponding biofilm structures revealed that only the nanosized ZnO coating had an antibiofilm effect. To elucidate this effect, a novel approach was taken: preconditioning of bacteria with this ZnO coating followed by exposure to subinhibitory concentrations of antibiotics with well-known modes of actions. This approached revealed (i) a decreased biofilm formation in combination with gentamycin, targeting protein synthesis, and (ii) an increased biofilm formation in the presence of rifampicin and vancomycin, acting on RNA and cell wall biosynthesis, respectively. The increased bacteria resistance to these two antibiotics gave new insights into the antibiofilm effect of this nanosized ZnO coating. The synergistic effect observed for gentamycin opened new perspectives for the design of effective solutions against implant-related infections. During the in vitro degradation of this nanosized ZnO-coated Zn, a specific corrosion product, hopeite Zn3(PO4)2, was depicted. Interestingly, the increased deposition of hopeite-derived compounds on MRSA cells surface seemed to be related to unhealthy and dead bacterial cells. This observation suggested that hopeite may well play a key role in this antibiofilm activity. The results obtained herein shed light on the possible antibacterial effect of a nanosized ZnO coating, and strengthened its antimicrobial (antibacterial and antifungal) potential, therefore providing a potentially effective material to overcome the growing trend of implant-related infections.
Synopsis
The uterine tourniquet is a temporary intervention that facilitates the application of other procedures for definitive control of postpartum hemorrhage.
Postpartum bleeding visual underestimation: A persistent problem Zea‐Prado, Francisco; Espino‐Y‐Sosa, J. Salvador; Sarria‐Ortiz, Daniela ...
International journal of gynecology and obstetrics,
February 2024, 2024-Feb, 2024-02-00, 20240201, Letnik:
164, Številka:
2
Journal Article
Recenzirano
Synopsis
Postpartum bleeding volume calculated by the visual method is lower than the bleeding volume that is objectively quantified.
Abstract Objective To evaluate the utility of low‐cost simulation models to teach surgical techniques for placenta accreta spectrum (PAS), included in a multimodal education workshop for PAS. Methods ...This was an observational, survey‐based study. Participants were surveyed before and after the use of low‐fidelity mannequins to simulate two surgical techniques for PAS (one‐step conservative surgery OSCS and modified subtotal hysterectomy MSTH), within a multimodal educational workshop. The workshops included pre‐course preparation, didactics, simulated practice of the techniques using low‐cost models, and viewing live surgery. Results Six OSCS/MSTH training workshops occurred across six countries and a total of 270 participants were surveyed. The responses of 127 certified obstetricians and gynecologists (OB–GYNs) were analyzed. Participants expressed favorable impressions of all components of the simulated session. Perceived anatomical simulator fidelity, scenario realism, educational component effectiveness, and self‐assessed performance improvement received ratings of 4–5 (positive end of the Likert scale) from over 90% of respondents. When asked about simulation's role in technique comprehension, comfort level in technique performance, and likelihood of recommending this workshop to others, more than 75% of participants rated these aspects with a score of 4–5 (positively) on the five‐point scale. Conclusion Low‐cost simulation, within a multimodal education strategy, is a well‐accepted intervention for teaching surgical techniques for PAS.
Synopsis Six global OSCS/MSTH workshops engaged 270 participants, earning over 90% approval for simulator fidelity, scenario realism, education, and performance improvement. Over 75% recommending the workshop.
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