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Bloqueo Neuromuscular , Fármacos Neuromusculares no Despolarizantes , Rocuronio , Humanos , Rocuronio/administración & dosificación , Fármacos Neuromusculares no Despolarizantes/administración & dosificación , Bloqueo Neuromuscular/métodos , Sugammadex , Relación Dosis-Respuesta a Droga , gamma-Ciclodextrinas/uso terapéuticoRESUMEN
BACKGROUND: Malaria is a mosquito-transmitted disease that kills more than half a million people annually. The lack of effective malaria vaccines and recently increasing malaria cases urge innovative approaches to prevent malaria. Previously, we reported that the extract from the soil-dwelling fungus Purpureocillium lilacinum, a common fungus from the soil, reduced Plasmodium falciparum oocysts in Anopheles gambiae midguts after mosquitoes contacted the treated surface before feeding. METHODS: We used liquid chromatography to fraction fungal crude extract and tract the active fraction using a contact-wise approach and standard membrane feeding assays. The purified small molecules were analyzed using precise mass spectrometry and tandem mass spectrometry. RESULTS: We isolated four active small molecules from P. lilacinum and determined them as leucinostatin A, B, A2, and B2. Pre-exposure of mosquitoes via contact with very low-concentration leucinostatin A significantly reduced the number of oocysts. The half-maximal response or inhibition concentration (EC50) via pre-exposure was 0.7 mg/m2, similar to atovaquone but lower than other known antimalarials. The inhibitory effect of leucinostatin A against P. falciparum during intraerythrocytic development, gametogenesis, sporogonic development, and ookinete formation, with the exception of oocyst development, suggests that leucinostatins play a part during parasite invasion of new cells. CONCLUSIONS: Leucinostatins, secondary metabolites from P. lilacinum disrupt malaria development, particular transmission to mosquitoes by contact. The contact-wise malaria control as a nonconventional approach is highly needed in malaria-endemic areas.
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Anopheles , Plasmodium falciparum , Animales , Anopheles/efectos de los fármacos , Anopheles/parasitología , Anopheles/microbiología , Plasmodium falciparum/efectos de los fármacos , Mosquitos Vectores/efectos de los fármacos , Mosquitos Vectores/parasitología , Mosquitos Vectores/microbiología , Hypocreales/química , Hypocreales/efectos de los fármacos , Antimaláricos/farmacología , Antimaláricos/química , Oocistos/efectos de los fármacos , Malaria Falciparum/transmisión , Malaria Falciparum/prevención & control , Malaria Falciparum/parasitología , Cromatografía Liquida , Femenino , Péptidos Catiónicos AntimicrobianosRESUMEN
BACKGROUND: Injuries to the proximal interphalangeal joint (PIPJ) of the fingers are commonly treated in hand therapy departments. Conservative management for PIPJ volar plate injuries typically involves a dorsal blocking orthosis and flexion exercises. Historically hand therapists have placed the PIPJ in varying degrees of flexion but the optimal angle is unknown. PURPOSE: To compare the outcomes of two treatment groups who received dorsal blocking orthoses: Those who the orthosis was positioned in neutral compared to those in 25-30° of flexion. STUDY DESIGN: Retrospective cohort study. METHOD: Patients treated by the hand therapy service at a major metropolitan hospital network in Melbourne, Australia, for conservative management of a PIPJ volar plate injury over a three-year period were included in our study. Data regarding patient demographics, digits affected and injury type were collected. Outcomes included presence of a fixed flexion deformity (FFD), amount of hand therapy received and total active flexion at the PIPJ. RESULTS: One hundred and eleven participants were included in our study. The mean age was 26 and 59 (53%) were males. Seventy two (64%) participants received a dorsal blocking orthosis positioned in neutral and 39 (35%) were positioned in 25-30° flexion at the PIPJ. Participants whose orthosis was positioned at 25-30° had an average of 24 more minutes in hand therapy (which equates to approximately one appointment) compared to those whose PIPJ was positioned in neutral (p=0.006, d=0.5). Eight percent less participants developed a FFD (p = 0.24) and 13% more participants achieved full flexion (p = 0.06) in the group who received a dorsal blocking orthosis in neutral, however these results were not statistically significant. CONCLUSION: PIPJ volar plate injures treated in an orthosis positioned in neutral required fewer hand therapy appointments. There was no statistically significant difference between groups regarding development of a FFD or full flexion.
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Insect growth-blocking peptides (GBPs) are a family of cytokines found in several insect orders and are known for their roles in regulating development, paralysis, cell proliferation, and immune responses. Despite their diverse functions, the potential of GBPs as biocontrol targets against the pest Spodoptera frugiperda (Lepidoptera: Noctuidae) has not been fully explored. In this study, S. frugiperda GBP (SfGBP) was identified and functionally characterized. SfGBP is synthesized as a 146 amino acid proprotein with a 24 amino acid C-terminal active peptide (Glu123-Gly146). Predominant expression of SfGBP occurs in fourth to sixth instar larvae and in the larval fat body, with significant upregulation in response to pathogens and pathogen-associated molecular patterns. Injection of the synthetic active peptide into larvae induced growth retardation, delayed pupation, and increased survival against Beauveria bassiana infection. Conversely, RNA interference-mediated knockdown of SfGBP resulted in accelerated growth, earlier pupation, and decreased survival against B. bassiana infection. Further analysis revealed that SfGBP promoted SF9 cell proliferation and spreading, enhanced bacteriostatic activity of larval hemolymph, and directly inhibited germination of B. bassiana conidia. In addition, SfGBP enhanced humoral responses, such as upregulation of immunity-related genes and generation of reactive oxygen species, and cellular responses, such as nodulation, phagocytosis, and encapsulation. These results highlight the dual regulatory role of SfGBP in development and immune responses and establish it as a promising biocontrol target for the management of S. frugiperda.
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Proteínas de Insectos , Larva , Spodoptera , Animales , Spodoptera/efectos de los fármacos , Spodoptera/inmunología , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Larva/efectos de los fármacos , Larva/inmunología , Beauveria/fisiología , Secuencia de Aminoácidos , Control Biológico de Vectores/métodosRESUMEN
A well-judged combination of a high axial ligand field and a bridging radical ligand in a dinuclear lanthanide complex provides a single-molecule magnet with a higher effective energy barrier for magnetic relaxation and blocking temperature compared to its non-radical analog due to significant magnetic exchange coupling between radical and Ln(III) ions. In this work, we report two chloranilate (CA) bridged dinuclear dysprosium complexes, [{(bbpen)Dy(µ2-CA)Dy(bbpen)}] (1Dy) and [{(bbpen)Dy(µ2-CAâ¢)Dy(bbpen)}-{CoCp2}+] (2Dy), where 2Dy is the radical bridged Dy-complex obtained via the chemical reduction of bridging CA moiety (H2bbpen = N,N'-bis(2-hydroxybenzyl)-N,N'-bis(2-methylpyridyl)ethylenediamine). The presence of high electronegative phenoxide moiety enhances the axial anisotropy of pseudo-square antiprismatic Dy(III) ions. The diffused spin of radical is efficiently coupled with anisotropic Dy(III) centres and decreases the quantum tunnelling of magnetization (QTM) in the magnetic relaxation process. The magnetic relaxation of 1Dy follows Orbach, Raman, and QTM processes whereas for 2Dy it follows Orbach and Raman Processes. Due to less involvement of the QTM relaxation process, 2Dy shows a higher thermal energy barrier (Ueff = 700 K) and a high blocking temperature (6.7 K), compared to its non-radical analog. Remarkably, the radical coupled 2Dy complex shows the highest energy barrier among the radical bridged Dy(III)-based SMMs to date.
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Background: Transmission-blocking vaccines (TBVs) can effectively prevent the community's spread of malaria by targeting the antigens of mosquito sexual stage parasites. At present, only a few candidate antigens have demonstrated transmission-blocking activity (TBA) potential in P. vivax. Quiescin-sulfhydryl oxidase (QSOX) is a sexual stage protein in the rodent malaria parasite Plasmodium berghei and is associated with a critical role in protein folding by introducing disulfides into unfolded reduced proteins. Here, we reported the immunogenicity and transmission-blocking potency of the PvQSOX in P. vivax. Methods and findings: The full-length recombinant PvQSOX protein (rPvQSOX) was expressed in the Escherichia coli expression system. The anti-rPvQSOX antibodies were generated following immunization with the rPvQSOX in rabbits. A parasite integration of the pvqsox gene into the P. berghei pbqsox gene knockout genome was developed to express full-length PvQSOX protein in P. berghei (Pv-Tr-PbQSOX). In western blot, the anti-rPvQSOX antibodies recognized the native PvQSOX protein expressed in transgenic P. berghei gametocyte and ookinete. In indirect immunofluorescence assays, the fluorescence signal was detected in the sexual stages, including gametocyte, gamete, zygote, and ookinete. Anti-rPvQSOX IgGs obviously inhibited the ookinetes and oocysts development both in vivo and in vitro using transgenic parasites. Direct membrane feeding assays of anti-rPvQSOX antibodies were conducted using four field P. vivax isolates (named isolates #1-4) in Thailand. Oocyst density in mosquitoes was significantly reduced by 32.00, 85.96, 43.52, and 66.03% with rabbit anti-rPvQSOX antibodies, respectively. The anti-rPvQSOX antibodies also showed a modest reduction of infection prevalence by 15, 15, 20, and 22.22%, respectively, as compared to the control, while the effect was insignificant. The variation in the DMFA results may be unrelated to the genetic polymorphisms. Compared to the P.vivax Salvador (Sal) I strain sequences, the pvqsox in isolate #1 showed no amino acid substitution, whereas isolates #2, #3, and #4 all had the M361I substitution. Conclusions: Our results suggest that PvQSOX could serve as a potential P. vivax TBVs candidate, which warrants further evaluation and optimization.
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Anticuerpos Antiprotozoarios , Vacunas contra la Malaria , Malaria Vivax , Plasmodium berghei , Plasmodium vivax , Proteínas Recombinantes , Plasmodium vivax/inmunología , Plasmodium vivax/genética , Plasmodium vivax/enzimología , Animales , Conejos , Vacunas contra la Malaria/inmunología , Anticuerpos Antiprotozoarios/inmunología , Malaria Vivax/prevención & control , Malaria Vivax/transmisión , Malaria Vivax/inmunología , Plasmodium berghei/inmunología , Plasmodium berghei/genética , Plasmodium berghei/enzimología , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Ratones , Escherichia coli/genética , Antígenos de Protozoos/inmunología , Antígenos de Protozoos/genética , Proteínas Protozoarias/inmunología , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Femenino , Humanos , Inmunogenicidad Vacunal , Ratones Endogámicos BALB CRESUMEN
PURPOSE: The aim of this study was to compare the effect of a pressure-controlled strategy allowing non-synchronised unassisted spontaneous ventilation (PC-SV) to a conventional volume assist-control strategy (ACV) on the outcome of patients with acute respiratory distress syndrome (ARDS). METHODS: Open-label randomised clinical trial in 22 intensive care units (ICU) in France. Seven hundred adults with moderate or severe ARDS (PaO2/FiO2 < 200 mmHg) were enrolled from February 2013 to October 2018. Patients were randomly assigned to PC-SV (n = 348) or ACV (n = 352) with similar objectives of tidal volume (6 mL/kg predicted body weight) and positive end-expiratory pressure (PEEP). Paralysis was stopped after 24 h and sedation adapted to favour patients' spontaneous ventilation. The primary endpoint was in-hospital death from any cause at day 60. RESULTS: Hospital mortality [34.6% vs 33.5%, p = 0.77, risk ratio (RR) = 1.03 (95% confidence interval [CI] 0.84-1.27)], 28-day mortality, as well as the number of ventilator-free days and organ failure-free days at day 28 did not differ between PC-SV and ACV groups. Patients in the PC-SV group received significantly less sedation and neuro-muscular blocking agents than in the ACV group. A lower proportion of patients required adjunctive therapy of hypoxemia (including prone positioning) in the PC-SV group than in the ACV group [33.1% vs 41.3%, p = 0.03, RR = 0.80 (95% CI 0.66-0.98)]. The incidences of pneumothorax and refractory hypoxemia did not differ between the groups. CONCLUSIONS: A strategy based on PC-SV mode that favours spontaneous ventilation reduced the need for sedation and adjunctive therapies of hypoxemia but did not significantly reduce mortality compared to ACV with similar tidal volume and PEEP levels.
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The prevalence of asthma, rhinitis, and food allergies has increased dramatically over the last few decades. This increase originally started in western countries, but is now also evident in many other regions of the world. Given the fact that the increase is so quick, the noted increase cannot be linked to a genetic effect, and many environmental factors have been identified that are associated with increased or reduced prevalence of allergies, like changing dietary habits, increased urbanization, pollution, exposure to microorganisms and LPS, and the farming environment and raw milk consumption. Although the key role of allergen-specific IgE in allergies is well known, the role of allergen-specific IgG and IgA antibodies is less well defined. This review will provide an overview of the functions of allergen-specific IgE in allergy, the role of allergen-specific antibodies (IgG (4) and IgA) in allergen immunotherapy (AIT), the possibility to use allergen-specific antibodies for treatment of ongoing allergies, and the potential role of allergen-specific antibodies in tolerance induction to allergens in a preventive setting. In the last, more speculative, section we will present novel hypotheses on the potential role of allergen-specific non-IgE antibodies in allergies by directing antigen presentation, Th2 development, and innate immune training.
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Enterotoxigenic Escherichia coli (ETEC) is the major bacterial cause of diarrheal diseases in pigs, particularly at young ages, resulting in significant costs to swine farming. The pathogenicity of ETEC is largely dependent on the presence of fimbriae and the ability to produce toxins. Fimbriae are responsible for their initial adhesion to the intestinal epithelial cells, leading to the onset of infection. In particular, the F4 type (K88) fimbriae are often attributed to neonatal infections and have also been associated with post-weaning diarrheal infections. This disease is traditionally prevented or treated with antibiotics, but their use is being severely restricted due to the emergence of resistant bacteria and their impact on human health. Emerging approaches such as aptamers that target the F4-type fimbriae and block the initial ETEC adhesion are a promising alternative. The aim of this study is to assess the effectiveness of two aptamers, Apt31 and Apt37, in controlling ETEC infection in the G. mellonella in vivo model. Initially, the dissociation constant (KD) of each aptamer against ETEC was established using real-time quantitative PCR methodology. Subsequently, different concentrations of the aptamers were injected into Galleria mellonella to study their toxicity. Afterwards, the anti-ETEC potential of Apt31 and Apt37 was assessed in the larvae model. The determined KD was 81.79 nM (95% CI: 31.21-199.4 nM) and 50.71 nM (95% CI: 26.52-96.15 nM) for the Apt31 and Apt37, respectively, showing no statistical difference. No toxicity was observed in G. mellonella following injection with both aptamers at any concentration. However, the administration of Apt31 together with ETEC-F4+ in G. mellonella resulted in a significant improvement of approximately 30% in both larvae survival and health index compared to ETEC-F4+ alone. These findings suggest that aptamers have promising inhibitory effect against ETEC infections and pave the way for additional in vivo studies.
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Background Neuromuscular blocking agents are crucial for anesthesia but can cause reversible paralysis, leading to risks like postoperative residual dysfunction. Undetected paralysis in the post-anesthesia care unit (PACU) jeopardizes patient safety by impairing airway function and increasing complications. Effective reversal, assessed clinically or via nerve stimulation, is critical to prevent residual postoperative curarization (RPOC), which is linked to significant morbidity and mortality. Evaluating agents like rocuronium and cisatracurium helps optimize anesthesia outcomes and patient recovery. Methodology The study included 100 American Society of Anaesthesiologists (ASA) I and II patients approved by the Institutional Review Board of Kasturba Medical College, Mangalore, India. Patients were briefed about the study, provided written informed consent, and underwent pre-anesthetic evaluations, including discussions on anesthetic procedures and associated risks. They were instructed to fast overnight after consenting. Results The study compared 100 ASA I and II patients receiving rocuronium or cisatracurium during anesthesia, analyzing age distribution (p=0.429), gender (p=0.839), ASA status (p=0.228), and physical characteristics (height, weight, BMI, p>0.05). Recovery parameters such as hand grip, sustained head lift, and double burst stimulation (DBS) twitch response showed no significant differences between groups (p=0.538 for hand grip and sustained head lift; p=0.220 for DBS. Late recovery rates at 15 minutes were observed with 16% for hand grip, 14% for sustained head lift, and 26% for DBS in the rocuronium group; compared to 14%, 10%, and 16%, respectively, in the cisatracurium group. Conclusion The study found significant postoperative residual curarization in both groups, emphasizing the need for intraoperative and PACU peripheral nerve stimulation for effective assessment. Further research on intraoperative variables could improve understanding of residual paralysis in PACU, guiding better anesthesia management.
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Background: Neuromuscular blocking agents (NMBAs) are primarily used during surgical procedures to facilitate endotracheal intubation and optimize surgical conditions. This study aimed to explore the adverse event signals of NMBAs, providing reference for clinical safety. Methods: This study collected reports of atracurium, cisatracurium, rocuronium, and vecuronium as primary suspect drugs in The US Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the third quarter of 2023. The adverse events (AEs) reported in the study were retrieved based on the Preferred Terms (PTs) of the Medical Dictionary for Regulatory Activities. In addition, we conducted disproportionality analysis on relevant reports using the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method. A positive signal was generated when both algorithms show an association between the target drug and the AE. Results: A total of 11,518 NMBA-related AEs were reported in the FAERS database. The most AEs of rocuronium were collected. NMBA-related AEs involved 27 different system organs (SOCs), all of the four NMBAs had positive signals in "cardiac disorders," "immune system disorders," "respiratory, thoracic and mediastinal disorders" and "vascular disorders." At the PTs level, a total of 523 effective AEs signals were obtained for the four NMBAs. AEs labled in the instructions such as anaphylaxis (include anaphylactic reaction and anaphylactic shock), bronchospasm, respiratory arrest and hypotension were detected positive signals among all NMBAs. In addition, we also found some new AEs, such as ventricular fibrillation for the four NMBAs, hyperglycaemia for atracurium, kounis syndrome and stress cardiomyopathy for rocuronium, hepatocellular injury for cisatracurium, hyperkalaemia for vecuronium. To further investigated the AEs associated with serious clinical outcomes, we found that cardiac arrest and anaphylaxis were the important risk factors for death due to NMBAs. Conclusion: NMBA-related AEs have a significant potential to cause clinically severe consequences. Our study provides valuable references for the safety profile of NMBAs, and considering the limitations of the FAERS database, further clinical data are needed to validate the findings of this study.
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Interleukin-6 (IL-6) is a cytokine that can bind to IL-6 receptor and induce pleiotropic effects. It serves as a critical biomarker, involved in inflammation amplification, tumor progression, and many other disease developments. Nanobodies, featuring small structure and high affinity, are a powerful and versatile tool in medical diagnostics and therapeutics. Here, based on a scaffold optimized for humanization and stability, we developed a synthetic phage display library that rapidly generated high-affinity and humanized nanobodies, negating the need for animal immunization. Using enhanced green fluorescent protein (eGFP) as a benchmark, we demonstrated that the library produced humanized nanobodies with high function and great intracellular stability. The library was then subjected to screening against IL-6. We identified a standout nanobody, NbL3, which exhibited high affinity (22.16 nM) and stability and significantly inhibited IL-6-enhanced migration on the human breast cancer cell MCF-7 at a relatively low concentration. NbL3's strong blocking activity provides a promising therapeutic alternative for the IL-6-targeted intervention strategy, underscoring the broader potential of our synthetic library as a versatile platform for the development of humanized nanobodies against multiple antigens.
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Behavioral skills training (BST) has been used to improve football players' performance in one prior study, but limited data were collected on how the skill generalized from the training environment to the natural environment. The purpose of this study was to further evaluate the effects of BST in enhancing football players' performance while also evaluating the generalization of a skill taught in a training environment (i.e., practice) to the natural environment (i.e., game-simulated scrimmage). This study included five high school offensive line football players and recorded their run-blocking skills in the training context and a game context in baseline and following BST. The results showed that BST improved performance in the training environment, with run-blocking skills slightly generalizing from the training environment to game-simulated scrimmages. When BST was conducted in the natural environment, it further improved the participants' run-blocking skills.
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OBJECTIVE: The Society of Critical Care Medicine released the first guideline for the prevention and -management of pain, agitation, neuromuscular blockade, and delirium in critically ill pediatric patients but offered conditional recommendations for sedation practices and monitoring during neuromuscular blockade. This study aimed to characterize sedation practices, patient awareness, and depth of blockade with neuromuscular blocking agent (NMBA) infusion administration in a single pediatric and cardiac intensive care unit. METHODS: This retrospective chart review of critically ill pediatric patients queried orders for continuous infusion NMBA. Analgosedation agent(s), dose, and dose changes were assessed, along with depth of blockade monitoring via Train of Four (TOF) and awareness via Richmond Agitation and Sedation Scale (RASS). RESULTS: Thirty-one patients were included, of which 27 (87%) had a documented sedation agent infusing at time of NMBA initiation and 17 patients (54%) were receiving analgesia. The most common agents used were rocuronium (n = 28), dexmedetomidine (n = 23), and morphine (n = 14). RASS scores were captured in all patients; however, 9 patients (29%) had recorded positive scores and 1 patient (3%) never achieved negative scores. TOF was only captured for 11 patients (35%), with majority of the scores being 0 or 4. CONCLUSIONS: Majority of the study population did not receive recommended depth of blockade monitoring via TOF. Similarly, RASS scores were not consistent with deep sedation in half of the patients. The common use of dexmedetomidine as a single sedation agent calls into question the appropriateness of current sedation practices during NMBA continuous infusions.
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The performance of a triboelectric nanogenerator (TENG) device depends on the amount of generated surface charges during triboelectrification and the retention of surface charges. Here, we present the fabrication of a double-layer nanocomposite structure for the electronegative layer in a TENG, which resulted in the enhanced generation of surface charges and retention of generated charges. The double-layer structure is a stack of two different nanocomposite layers, in which the top layer is a nanocomposite of PVDF and MXene and the bottom layer is a nanocomposite layer of PDMS and NaNbO3 nanoparticles. The use of the double-layer structure for the electronegative layer enhanced the generated voltage to 150 V and the current to 4.3 µA, resulting in an output power density of 134 µW/cm2, which is â¼5.8 times higher compared to the performance of a TENG with a single PVDF electronegative layer. Through systematic Kelvin probe force microscopy measurements, it is shown that the introduction of a highly electronegative MXene in the PVDF matrix improved the electron affinity of the friction layer, resulting in enhanced charge generation during contact electrification. The introduction of NaNbO3 ferroelectric nanoparticles in the PDMS matrix is shown to result in enhanced internal polarization and increased trap sites, resulting in the retention of generated surface charges for longer durations. The combined effect of the two layers resulted in a substantial improvement in TENG performance. The application of the TENG device in wireless communication for signal transfer is also presented.
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Since reservoirs with permeability less than 10 mD are characterized by high injection difficulty, high-pressure drop loss, and low pore throat mobilization during the water drive process, CO2 is often used for development in actual production to reduce the injection difficulty and carbon emission simultaneously. However, microfractures are usually developed in low-permeability reservoirs, which further reduces the injection difficulty of the driving medium. At the same time, this makes the injected gas flow very fast, while the gas utilization rate is low, resulting in a low degree of recovery. This paper conducted a series of studies on the displacement effect of CO2-soluble foaming systems in low-permeability fractured reservoirs (the permeability of the core matrix is about 0.25 mD). For the two CO2-soluble blowing agents CG-1 and CG-2, the effects of the CO2 phase state, water content, and oil content on static foaming performance were first investigated; then, a more effective blowing agent was preferred for the replacement experiments according to the foaming results; and finally, the effects of the blowing agents on sealing and improving the recovery degree of a fully open fractured core were investigated at different injection rates and concentrations, and the injection parameters were optimized. The results show that CG-1 still has good foaming performance under low water volume and various oil contents and can be used in subsequent fractured core replacement experiments. After selecting the injection rate and concentration, the blowing agent can be used in subsequent fractured cores under injection conditions of 0.6 mL/min and 2.80%. In injection conditions, the foaming agent can achieve an 83.7% blocking rate and improve the extraction degree by 12.02%. The research content of this paper can provide data support for the application effect of a CO2-soluble blowing agent in a fractured core.
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Instead of using the Infection and Treatment Method (ITM)-based vaccine, is it possible to control East Coast Fever (ECF) through blocking Theileria parva transmission in ticks and cattle? This review pursues this question. It's over 100 years since Arnold Theiler (1912) first illustrated the natural ITM as a vaccination approach against ECF-cattle disease. The approach entails infecting cattle with live Theileria sporozoites and co-treatment with long-acting tetracycline. Building on the ITM principle, the "Muguga"-cocktail ECF vaccine was developed in the 1970s and it remains the only commercially available-one. Although the vaccine induces cattle-protection, the vaccination approach still raises several drawbacks. Of those, the most outstanding is the vaccine-safety. This is implied because after ITM vaccination, cattle revert to T. parva pathogen reservoirs, therefore, during blood meal-acquisition, the ticks co-ingest T. parva pathogens. Ultimately, the pathogens are further transmitted transstadial; from larvae to nymph and nymph-adults and later re-transmitted to cattle during blood-meal acquisition. Consequently, the vaccine-constituting T. parva strains are introduced and (re) spread in non-endemic/ endemic areas. Precisely, rather than eradicating the disease, the ITM vaccination-approach promotes ECF endemicity. With advent of novel vaccination approaches toward vector and vector-borne disease control, ECF-control based on ITM of vaccination is considered outdated. The review highlights the need for embracing a holistic integrative vaccination approach entailing blocking Theileria pathogen-development and transmission both in the ticks and cattle, and/or the tick-population.
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Objective: To explore the bacterial blocking effect of oriented multilayer MXene/polyvinyl alcohol (PVA) nanocomposite hydrogels and their effect on the repair of intestinal defects. Methods: MXene/PVA nanocomposite hydrogels were prepared using the traditional freezing method and the bidirectional freezing ice template method. The structures of the different hydrogels were observed using scanning electron microscopy (SEM) and micro-CT reconstruction. The rheological properties of the hydrogels were measured using a dynamic rheometer, and their mechanical properties were assessed using a universal testing machine. The burst pressure of the hydrogels was determined through burst experiments, and bacterial colony growth was observed by the osmosis method to assess the bacteria blocking ability of the hydrogels in vitro. A rat model of cecal perforation was established, and the hydrogels were used for intestinal repair. Gram staining was performed to observe in vivo the bacterial blocking ability of the hydrogels, HE staining was performed to observe the intestinal inflammation, and CD31 and CD68 immunofluorescence staining and proliferating cell nuclear antigen (PCNA) staining were performed to observe the repair effect of the hydrogels on intestinal defects. Results: SEM and micro-CT reconstruction revealed that the hydrogel prepared by the traditional freezing method exhibited a random porous structure, while the hydrogel prepared by the bidirectional freezing method showed an oriented multilayer structure. Rheological and tensile tests indicated that the oriented hydrogel had superior mechanical properties, and the burst pressure of the oriented multilayer hydrogel was as high as 27 kPa, significantly higher than that of the non-oriented hydrogel (P<0.001). Bacterial colony growth was observed by the osmosis method and it was found that, compared with the non-oriented hydrogel, the oriented multilayer hydrogel could effectively prevent the infiltration of Escherichia coli and Staphylococcus aureus in vitro. Gram staining results showed that the oriented multilayer hydrogel could effectively block intestinal bacteria from entering the abdominal cavity in vivo. HE staining results showed that the oriented multilayer hydrogel could effectively reduce intestinal inflammation in vivo. CD31 and CD68 immunofluorescence staining and PCNA staining results showed that the oriented multilayer hydrogel had a repairing effect on intestinal defects in vivo. Conclusion: The oriented multilayer hydrogel prepared by bidirectional freezing effectively prevents bacterial infiltration and reduces intestinal inflammation.
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Hidrogeles , Alcohol Polivinílico , Animales , Alcohol Polivinílico/química , Ratas , Hidrogeles/química , Congelación , Ratas Sprague-Dawley , IntestinosRESUMEN
Background: Corneal inflammatory hem- and lymphangiogenesis significantly increase the risk for immune rejection after subsequent allogeneic corneal transplantation. The purpose of this study was to analyze the impact of temporary selective inhibition of lymphangiogenesis after transplantation on graft survival. Methods: Allogeneic transplantation from C57BL/6 mice to BalbC mice was performed as "high-risk" keratoplasty in a prevascularized corneal host bed (suture-induced inflammatory corneal neovascularization). The treatment group received integrin α5ß1-blocking small molecules (JSM6427) at the time of transplantation and for two weeks afterwards. Control mice received a vehicle solution. Grafts were evaluated weekly for graft rejection using an opacity score. At the end of the follow-up, immunohistochemical staining of corneal wholemounts for lymphatic vessels as well as CD11b+ immune cells was performed. Results: Temporary postoperative inhibition of lymphangiogenesis by JSM6427 improved the corneal graft survival significantly. At the end of the follow-up, no significant reduction in CD11b+ immunoreactive cells within the graft compared to controls was found. Conclusions: The significant improvement of corneal graft survival by the selective, temporary postoperative inhibition of lymphangiogenesis after keratoplasty using integrin antagonists shows the impact of lymphatic vessels in the early postoperative phase. Retarding lymphatic vessel ingrowth into the graft might be sufficient for the shift to immunological tolerance in the postoperative period, even after high-risk keratoplasty.
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The use of neuromuscular blocking agents (NMBA) has grown due to the development of laparoscopic and minimally invasive procedures. Respiratory insufficiency, an elevated risk of aspiration, postoperative pulmonary complications, and subsequent reintubation are among the risks linked to the residual block. The normal clinical practice calls for the pharmacologic "reversal" of these agents with either sugammadex or neostigmine prior to extubation. The administration of neostigmine is linked to a number of potential complications. In response, anaesthesiologists have begun to prescribe sugammadex more frequently for treating residual block and reversing blockade with NMBA. This review article compares and assesses neostigmine and sugammadex thoroughly in order to determine the extent to which they work as agents to reverse neuromuscular blockade. The review's findings highlight sugammadex's considerable advantages - Sugammadex's ability to quickly and reliably achieve desired train-of-four (TOF) ratios - over neostigmine in reversing neuromuscular blockade in a variety of surgical settings. In contrast, neostigmine's limitations regarding efficacy and rate of reversal were consistently noted in all of the reviewed studies, despite the fact that it is still widely used due to its lower cost and extensive clinical experience. Sugammadex is a superior option for reversing neuromuscular blockade, but incorporating it into standard clinical practice necessitates carefully weighing its potential benefits and drawbacks. Sugammadex provides notable benefits over neostigmine in terms of speed, predictability, and safety.