Human Immunoglobulin E monoclonal antibodies (hIgE mAb) are unique tools for investigating IgE responses. Here, the biological activity of hIgE mAb, derived from immortalized B cells harvested from ...the blood of allergic donors, targeting three allergens (Der p 2, Fel d 1 and Ara h 2) was investigated.
Three Der p 2-, three Fel d 1- and five Ara h 2-specific hIgE mAb produced by human B cell hybridomas, were combined in pairs and used to passively sensitize humanized rat basophilic leukemia cells and compared with sensitization using serum pools. Sensitized cells were stimulated with corresponding allergens (recombinant or purified), allergen extracts or structural homologs, having 40-88% sequence similarity, and compared for mediator (β-hexosaminidase) release.
One, two and eight pairs of Der p 2-, Fel d 1- and Ara h 2-specific hIgE mAb, respectively, produced significant mediator release (>50%). A minimum hIgE mAb concentration of 15-30 kU/L and a minimum antigen concentration between 0.01-0.1 µg/mL were sufficient to induce a pronounced mediator release. Individual sensitization with one Ara h 2-specific hIgE mAb was able to induce crosslinking independently of a second specific hIgE mAb. Der p 2- and Ara h 2-specific mAb showed a high allergen specificity when compared to homologs. Mediator release from cells sensitized with hIgE mAb was comparable to serum sensitization.
The biological activity of hIgE mAb reported here provides the foundation for novel methods of standardization and quality control of allergen products and for mechanistic studies of IgE-mediated allergic diseases, using hIgE mAb.
Background. Hemolytic uremic syndrome (HUS) is a life-threatening illness usually caused by infection with Shiga toxin-producing Escherichia coli O157 (STEC O157). We evaluated the age-specific rate ...of HUS and death among persons with STEC O157 infection and the risk factors associated with developing HUS. Methods. STEC O157 infections and HUS cases were reported from 8 sites participating in the Foodborne Diseases Active Surveillance Network during 2000–2006. For each case of STEC O157 infection and HUS, demographic and clinical outcomes were reported. The proportion of STEC O157 infections resulting in HUS was determined. Results. A total of 3464 STEC O157 infections were ascertained; 218 persons (6.3%) developed HUS. The highest proportion of HUS cases (15.3%) occurred among children aged <5 years. Death occurred in 0.6% of all patients with STEC O157 infection and in 4.6% of those with HUS. With or without HUS, persons aged ⩾60 years had the highest rate of death due to STEC O157 infection. Twelve (3.1%) of 390 persons aged ⩾60 years died, including 5 (33.3%) of 15 persons with HUS and 7 (1.9%) of 375 without. Among children aged <5 years, death occurred in 4 (3.0%) of those with HUS and 2 (0.3%) of those without. Conclusions. Young children and females had an increased risk of HUS after STEC O157 infection. With or without HUS, elderly persons had the highest proportion of deaths associated with STEC O157 infection. These data support recommendations for aggressive supportive care of young children and the elderly early during illness due to STEC O157.
Childhood experiences and impressions are important for individuals' health and well‐being—they often set the stage for how people approach relationships across the lifespan and how they make sense ...of their relational worlds. However, impressions of these experiences are likely not static and can change over time, even years after these experiences happened. The current study examined how impressions of parental relationships in childhood changed over time, and predictors of these changes, among middle‐aged and older adults followed over a 4‐year period (N = 2692; Mage = 66.67, SD = 9.15; 64.1% women). Childhood impressions of parental care were mostly stable over time, with 53.5%–65.0% of participants reporting consistent impressions. Becoming divorced/separated as an adult was associated with more negative impressions about relationships with fathers in the past. Having a mother pass away was associated with more positive impressions of mothers' caregiving when participants were children. Higher depressive symptoms at follow‐up were associated with darker perceptions of the past—more negative impressions of mothers and fathers as caregivers. The current study is one of the most comprehensive studies of late‐life changes in childhood impressions to date, suggesting future directions for studying the organization of relational experiences and recollection over time.
Summary
Hepatic veno‐occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a progressive, potentially fatal complication of conditioning for haematopoietic stem cell transplant (HSCT). The ...VOD/SOS pathophysiological cascade involves endothelial‐cell activation and damage, and a prothrombotic‐hypofibrinolytic state. Severe VOD/SOS (typically characterized by multi‐organ dysfunction) may be associated with >80% mortality. Defibrotide is approved for treating severe hepatic VOD/SOS post‐HSCT in the European Union, and for hepatic VOD/SOS with renal or pulmonary dysfunction post‐HSCT in the United States. Previously, defibrotide (25 mg/kg/day in 4 divided doses for a recommended ≥21 days) was available through an expanded‐access treatment protocol for patients with VOD/SOS. Data from this study were examined post‐hoc to determine if the timing of defibrotide initiation post‐VOD/SOS diagnosis affected Day +100 survival post‐HSCT. Among 573 patients, defibrotide was started on the day of VOD/SOS diagnosis in approximately 30%, and within 7 days in >90%. The relationship between Day +100 survival and treatment initiation before/after specific days post‐diagnosis showed superior survival when treatment was initiated closer to VOD/SOS diagnosis with a statistically significant trend over time for better outcomes with earlier treatment initiation (P < 0·001). These results suggest that initiation of defibrotide should not be delayed after diagnosis of VOD/SOS.
Antibodies targeting the Ebola virus surface glycoprotein (EBOV GP) are implicated in protection against lethal disease, but the characteristics of the human antibody response to EBOV GP remain ...poorly understood. We isolated and characterized 349 GP-specific monoclonal antibodies (mAbs) from the peripheral B cells of a convalescent donor who survived the 2014 EBOV Zaire outbreak. Remarkably, 77% of the mAbs neutralize live EBOV, and several mAbs exhibit unprecedented potency. Structures of selected mAbs in complex with GP reveal a site of vulnerability located in the GP stalk region proximal to the viral membrane. Neutralizing antibodies targeting this site show potent therapeutic efficacy against lethal EBOV challenge in mice. The results provide a framework for the design of new EBOV vaccine candidates and immunotherapies.
Solution-processable electronic devices are highly desirable due to their low cost and compatibility with flexible substrates. However, they are often challenging to fabricate due to the hydrophobic ...nature of the surfaces of the constituent layers. Here, we use a protein solution to modify the surface properties and to improve the wettability of the fluoropolymer dielectric Cytop. The engineered hydrophilic surface is successfully incorporated in bottom-gate solution-deposited organic field-effect transistors (OFETs) and hybrid organic–inorganic trihalide perovskite field-effect transistors (HTP-FETs) fabricated on flexible substrates. Our analysis of the density of trapping states at the semiconductor–dielectric interface suggests that the increase in the trap density as a result of the chemical treatment is minimal. As a result, the devices exhibit good charge carrier mobilities, near-zero threshold voltages, and low electrical hysteresis.
MΦs display remarkable plasticity and the ability to activate diverse responses to a host of intracellular and external stimuli. Despite extensive characterization of M1 MΦs and a broad set of M2 ...MΦs, comprehensive characterization of functional phenotype and associated metabotype driving this diverse MΦ activation remains. Herein, an ex vivo model was utilized to produce 6 MΦ functional phenotypes. Isolated CD14
PBMCs were differentiated into resting M0 MΦs, and then polarized into M1 (IFN-γ/LPS), M2a (IL-4/IL-13), M2b (IC/LPS), M2c (IL-10), and M2d (IL-6/LIF) MΦs. The MΦs were profiled using a bioanalyte matrix of 4 cell surface markers, ∼50 secreted proteins, ∼800 expressed myeloid genes, and ∼450 identified metabolites relative to M0 MΦs. Signal protein and expressed gene profiles grouped the MΦs into inflammatory (M1 and M2b) and wound resolution (M2a, M2c, and M2d) phenotypes; however, each had a unique metabolic profile. While both M1 and M2b MΦs shared metabotype profiles consistent with an inflammatory signature; key differences were observed in the TCA cycle, FAO, and OXPHOS. Additionally, M2a, M2c, and M2d MΦs all profiled as tissue repair MΦs; however, metabotype differences were observed in multiple pathways including hexosamine, polyamine, and fatty acid metabolism. These metabolic and other key functional distinctions suggest phagocytic and proliferative functions for M2a MΦs, and angiogenesis and ECM assembly capabilities for M2b, M2c, and M2d MΦs. By integrating metabolomics into a systems analysis of MΦ phenotypes, we provide the most comprehensive map of MΦ diversity to date, along with the global metabolic shifts that correlate to MΦ functional plasticity in these phenotypes.
Research conducted in urban areas has highlighted the impact of housing instability on people who inject drugs (PWID), revealing that it exacerbates vulnerability to drug-related harms and impedes ...syringe service program (SSP) use. However, few studies have explored the effects of houselessness on SSP use among rural PWID. This study examines the relationship between houselessness and SSP utilization among PWID in eight rural areas across 10 states.
PWID were recruited using respondent-driven sampling for a cross-sectional survey that queried self-reported drug use and SSP utilization in the prior 30 days, houselessness in the prior 6 months and sociodemographic characteristics. Using binomial logistic regression, we examined the relationship between experiencing houselessness and any SSP use. To assess the relationship between houselessness and the frequency of SSP use, we conducted multinomial logistic regression analyses among participants reporting any past 30-day SSP use.
Among 2394 rural PWID, 56.5% had experienced houselessness in the prior 6 months, and 43.5% reported past 30-day SSP use. PWID who had experienced houselessness were more likely to report using an SSP compared to their housed counterparts (adjusted odds ratio aOR = 1.24 95% confidence intervals CI 1.01, 1.52). Among those who had used an SSP at least once (n = 972), those who experienced houselessness were just as likely to report SSP use two (aOR = 0.90 95% CI 0.60, 1.36) and three times (aOR = 1.18 95% CI 0.77, 1.98) compared to once. However, they were less likely to visit an SSP four or more times compared to once in the prior 30 days (aOR = 0.59 95% CI 0.40, 0.85).
This study provides evidence that rural PWID who experience houselessness utilize SSPs at similar or higher rates as their housed counterparts. However, housing instability may pose barriers to more frequent SSP use. These findings are significant as people who experience houselessness are at increased risk for drug-related harms and encounter additional challenges when attempting to access SSPs.
n‐Doping electron‐transport layers (ETLs) increases their conductivity and improves electron injection into organic light‐emitting diodes (OLEDs). Because of the low electron affinity and large ...bandgaps of ETLs used in green and blue OLEDs, n‐doping has been notoriously more difficult for these materials. In this work, n‐doping of the polymer poly(9,9‐dioctylfluorene‐2,7‐diyl)‐alt‐(benzo2,1,3thiadiazol‐4,7‐diyl) (F8BT) is demonstrated via solution processing, using the air‐stable n‐dopant (pentamethylcyclopentadienyl)(1,3,5‐trimethylbenzene)ruthenium dimer RuCp*Mes2. Undoped and doped F8BT films are characterized using ultraviolet and inverse photoelectron spectroscopy. The ionization energy and electron affinity of the undoped F8BT are found to be 5.8 and 2.8 eV, respectively. Upon doping F8BT with RuCp*Mes2, the Fermi level shifts to within 0.25 eV of the F8BT lowest unoccupied molecular orbital, which is indicative of n‐doping. Conductivity measurements reveal a four orders of magnitude increase in the conductivity upon doping and irradiation with ultraviolet light. The RuCp*Mes2‐doped F8BT films are incorporated as an ETL into phosphorescent green OLEDs, and the luminance is improved by three orders of magnitude when compared to identical devices with an undoped F8BT ETL.
The n‐dopant RuCp*Mes2 is incorporated into the polymer F8BT via solution processing. Successful n‐doping is verified using photoelectron spectroscopy and conductivity measurements. The doped F8BT film is used as an electron‐transport layer in green organic light‐emitting diodes, allowing good electron injection and high luminance and external quantum efficiency.
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