Genome-resolved metagenomics reveals diverse taxa and metabolic complexity in Antarctic lake microbial structures.

Lake Untersee, a lake in Antarctica that is perennially covered with ice, is home to unique microbial structures that are not lithified. We have evaluated the structure of the community and its metabolic potential across the pigmented upper layers and the sediment-enriched deeper layers in these pinnacle and cone-shaped microbial structures using metagenomics. These microbial structures are inhabited by distinct communities. The upper layers of the cone-shaped structures have a higher abundance of the cyanobacterial MAG Microcoleus, while the pinnacle-shaped structures have a higher abundance of Elainellacea MAG. This suggests that cyanobacteria influence the morphologies of the mats. We identified stark contrasts in the composition of the community and its metabolic potential between the upper and lower layers of the mat. The upper layers of the mat, which receive light, have an increased abundance of photosynthetic pathways. In contrast, the lower layer has an increased abundance of heterotrophic pathways. Our results also showed that Lake Untersee is the first Antarctic lake with a substantial presence of ammonia-oxidizing Nitrospiracea and amoA genes. The genomic capacity for recycling biological molecules was prevalent across metagenome-assembled genomes (MAGs) that cover 19 phyla. This highlights the importance of nutrient scavenging in ultra-oligotrophic environments. Overall, our study provides new insights into the formation of microbial structures and the potential metabolic complexity of Antarctic laminated microbial mats. These mats are important environments for biodiversity that drives biogeochemical cycling in polar deserts.

Fluorine Rich Borate Salt Anion Based Electrolyte for High Voltage Sodium Metal Battery Development.

This study demonstrates the enhanced performance in high-voltage sodium full cells using a novel electrolyte composition featuring a highly fluorinated borate ester anion (1 M Na[B(hfip)4].3DME) in a binary carbonate mixture (EC:EMC), compared to a conventional electrolyte (1 M Na[PF6] EC:EMC). The prolonged cycling performance of sodium metal battery employing high voltage cathodes (NVPF@C@CNT and NFMO) is attributed to uniform and dense sodium deposition along with the formation of fluorine and boron-rich solid electrolyte interphase (SEI) on the sodium metal anode. Simultaneously, a robust cathode electrolyte interphase (CEI) is formed on the cathode side due to the improved electrochemical stability window and superior aluminum passivation of the novel electrolyte. The CEIs on high-voltage cathodes are discovered to be abundant in C-F, B-O, and B-F components, which contributes to long-term cycling stability by effectively suppressing undesirable side reactions and mitigating electrolyte decomposition. The participation of DME in the primary solvation shell coupled with the comparatively weaker interaction between Na+ and [B(hfip)4]- in the secondary solvation shell, provides additional confirmation of labile desolvation. This, in turn, supports the active participation of the anion in the formation of fluorine and boron-rich interphases on both the anode and cathode.

Evolutionary History Mediates Population Response to Rapid Environmental Change through Within-Generational and Transgenerational Plasticity.

AbstractRapid environmental change is affecting many organisms; some are coping well, but many species are in decline. A key mechanism for facilitating success following environmental change is phenotypic plasticity. Organisms use cues to respond phenotypically to environmental conditions; many incorporate recent information (within-generation plasticity) and information from previous generations (transgenerational plasticity). We extend an existing evolutionary model where organisms utilize within-generational plasticity, transgenerational plasticity, and bet hedging to include changes in environmental regime. We show how when rapid evolution of plasticity is not possible, the effect of environmental change (altering the environment mean, variance, or autocorrelation or cue reliability) on population growth rate depends on the population's evolutionary history and past evolutionary responses to historical environmental conditions. We then evaluate the predictions that populations adapted to highly variable environments or with greater within-generational plasticity are more likely to successfully respond to environmental change. We identify when these predictions fail and show that environmental change is most detrimental when previously reliable cues become unreliable. When multiple cues become unreliable, environmental change can cause deleterious effects regardless of the population's evolutionary history. Overall, this work provides a general framework for understanding the role of plasticity in population responses to rapid environmental change.

Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity.

Patients with asthma, a major public health problem, are at high risk for serious disease from influenza virus infection, but the pathogenic mechanisms by which influenza A causes airway disease and asthma are not fully known. We show here in a mouse model that influenza infection acutely induced airway hyper-reactivity (AHR), a cardinal feature of asthma, independently of T helper type 2 (T(H)2) cells and adaptive immunity. Instead, influenza infection induced AHR through a previously unknown pathway that required the interleukin 13 (IL-13)-IL-33 axis and cells of the non-T cell, non-B cell innate lymphoid type called 'natural helper cells'. Infection with influenza A virus, which activates the NLRP3 inflammasome, resulted in much more production of IL-33 by alveolar macrophages, which in turn activated natural helper cells producing substantial IL-13.

Synthesis of Poly(allyl glycidyl ether)-Derived Polyampholytes and Their Application to the Cryopreservation of Living Cells.

Through the postpolymerization modification of poly(allyl glycidyl ether) (PAGE), a functionalizable polyether with a poly(ethylene oxide) backbone, we engineered a new class of highly tunable polyampholyte materials. These polyampholytes can be synthesized to have several useful properties, including low cytotoxicity and pH-responsive coacervate formation. In this study, we used PAGE-based polyampholytes (PAGE-PAs) for the cryopreservation of mammalian cell suspensions. Typically, dimethyl sulfoxide (DMSO) is the cryoprotectant used for preserving mammalian cells, but DMSO suffers from key drawbacks including toxicity and difficult post-thaw removal that motivates the development of new materials and methods. Toxicity and post-thaw survival were dependent on PAGE-PA composition with the highest immediate post-thaw survival for normal human dermal fibroblasts occurring for the least toxic PAGE-PA at a cation/anion ratio of 35:65. With low toxicity, the PAGE-PA concentration could be increased in order to increase immediate post-thaw survival of the immortalized mouse embryonic fibroblasts (NIH/3T3). While immediate post-thaw viability was achieved using only the PAGE-PAs, long-term cell survival was low, highlighting the challenges involved with the design of cryoprotective polyampholytes. An environment utilizing both PAGE-PAs and DMSO in a cryoprotective solution offered promising post-thaw viabilities exceeding 70%, with long-term metabolic activities comparable to unfrozen cells.

Fluoroborate ionic liquids as sodium battery electrolytes.

High-voltage sodium batteries are an appealing solution for economical energy storage applications. Currently available electrolyte materials have seen limited success in such applications therefore the identification of high-performing and safer alternatives is urgently required. Herein we synthesise six novel ionic liquids derived from two fluoroborate anions which have shown great promise in recent battery literature. This study reports for the first time the electrochemically applicable room-temperature ionic liquid (RTIL) N-ethyl-N,N,N-tris(2-(2-methoxyethoxy)ethyl)ammonium (tetrakis)hexafluoroisopropoxy borate ([N2(2O2O1)3][B(hfip)4]). The RTIL shows promising physical properties with a very low glass-transition at -73 °C and low viscosity. The RTIL exhibits an electrochemical window of 5.3 V on a glassy carbon substrate which enables high stability electrochemical cycling of sodium in a 3-electrode system. Of particular note is the strong passivation behaviour of [N2(2O2O1)3][B(hfip)4] on aluminium current-collector foil at potentials as high as 7 V (vs. Na+/Na) which is further improved with the addition of 50 mol% Na[FSI]. This study shows [B(hfip)4]- ionic liquids have the desired physical and electrochemical properties for high-voltage sodium electrolytes.

The many paths to asthma: phenotype shaped by innate and adaptive immunity.

Asthma is a very complex and heterogeneous disease that is characterized by airway inflammation and airway hyper-reactivity (AHR). The pathogenesis of asthma is associated with environmental factors, many cell types, and several molecular and cellular pathways. These include allergic, non-allergic and intrinsic pathways, which involve many cell types and cytokines. Animal models of asthma have helped to clarify some of the underlying mechanisms of asthma, demonstrating the importance of T helper type 2 (T(H)2)-driven allergic responses, as well as of the non-allergic and intrinsic pathways, and contributing to understanding of the heterogeneity of asthma. Further study of these many pathways to asthma will greatly increase understanding of the distinct asthma phenotypes, and such studies may lead to new therapies for this important public health problem.

Pregnancy outcomes in the omalizumab pregnancy registry and a disease-matched comparator cohort.

BACKGROUND: The Observational Study of the Use and Safety of Xolair (omalizumab) during Pregnancy (EXPECT) pregnancy registry was a prospective observational study established in 2006 to evaluate perinatal outcomes in pregnant women exposed to omalizumab and their infants. OBJECTIVE: This analysis compares EXPECT outcomes with those from a disease-matched population of pregnant women not treated with omalizumab. Data from a substudy of platelet counts among newborns are also presented. METHODS: The EXPECT study enrolled 250 women with asthma exposed to omalizumab during pregnancy. The disease-matched external comparator cohort of women with moderate-to-severe asthma (n = 1153), termed the Quebec External Comparator Cohort (QECC), was created by using data from health care databases in Quebec, Canada. Outcome estimates were age adjusted based on the maternal age distribution of the EXPECT study. RESULTS: Among singleton infants in the EXPECT study, the prevalence of major congenital anomalies was 8.1%, which was similar to the 8.9% seen in the QECC. In the EXPECT study 99.1% of pregnancies resulted in live births, which was similar to 99.3% in the QECC. Premature birth was identified in 15.0% of EXPECT infants and 11.3% in the QECC. Small for gestational age was identified in 9.7% of EXPECT infants and 15.8% in the QECC. CONCLUSION: There was no evidence of an increased risk of major congenital anomalies among pregnant women exposed to omalizumab compared with a disease-matched unexposed cohort. Given the observational nature of this registry, however, an absence of increased risk with omalizumab cannot be definitively established.

Mechanism of Polymer-Mediated Cryopreservation Using Poly(methyl glycidyl sulfoxide).

Under the right conditions, some biological systems can maintain high viability after being frozen and thawed, but many others (e.g., organs and many mammalian cells) cannot. To increase the rates of post-thaw viability and widen the library of living cells and tissues that can be stored frozen, an improved understanding of the mode of action of polymeric cryoprotectants is required. Here, we present a polymeric cryoprotectant, poly(methyl glycidyl sulfoxide) (PMGS), that achieved higher post-thaw viability for fibroblast cells than its small-molecule analogue dimethyl sulfoxide. By limiting the amount of water that freezes and facilitating cellular dehydration after ice nucleation, PMGS mitigates the mechanical and osmotic stresses that the freezing of water imparts on cells and facilitates higher-temperature vitrification of the remaining unfrozen volume. The development of PMGS advances a fundamental physical understanding of polymer-mediated cryopreservation, which enables new material design for long-term preservation of complex cellular networks and tissue.

Noradrenergic uptake in the liver on 123 I-mIBG imaging: Influence of heart failure and diabetes.

BACKGROUND AND AIM: Imaging noradrenergic uptake in the liver with norepinephrine analog 123 I-meta-iodobenzylguanidine (mIBG) was explored in normal controls and patients with heart failure (HF). METHODS: A total of 961 HF (343 with diabetes mellitus [DM]) and 94 control subjects underwent anterior planar mIBG images including upper abdomen at 15 min (early) and 3 h 50 min (late) post-injection. Decay-corrected liver activity normalized to injected activity and body surface area (counts/pixel [cpp]/MBq/m2 ) was compared in three groups: HF with DM; HF without DM; and controls. Associations with plasma norepinephrine, liver function tests, and level of cardiac innervation were explored. RESULTS: In controls, liver mIBG activity decreased over time (early: 2.78 vs late: 2.43 cpp/MBq/m2 , P < 0.0001); in HF subjects, activity increased during this interval (HF without DM: 2.85 vs 2.93 [P = 0.005]; HF with DM: 2.37 vs 2.43 [P = 0.054]). Early liver activity was lower in HF with DM subjects than in the other groups (P < 0.001); late liver activity was higher in HF without DM than in the other two groups (P < 0.01). Subjects with elevated plasma norepinephrine (> 520 pg/mL) or ≥ 1 abnormal liver function test had lower early and late liver activity. In subjects with preserved cardiac mIBG uptake, HF subjects had higher and control subjects lower liver activity than comparable subjects with decreased cardiac innervation. CONCLUSIONS: In HF subjects, liver mIBG activity increased over time, reversing the normal washout pattern, suggesting a compensatory change in sympathetic nerve function. DM, abnormal liver function tests, and decreased cardiac innervation were associated with decreased liver mIBG uptake in HF.

Blockade of RGMb inhibits allergen-induced airways disease.

BACKGROUND: Allergic asthma causes morbidity in many subjects, and novel precision-directed treatments would be valuable. OBJECTIVE: We sought to examine the role of a novel innate molecule, repulsive guidance molecule b (RGMb), in murine models of allergic asthma. METHODS: In models of allergic asthma using ovalbumin or cockroach allergen, mice were treated with anti-RGMb or control mAb and examined for airway inflammation and airway hyperreactivity (AHR), a cardinal feature of asthma. The mechanisms by which RGMb causes airways disease were also examined. RESULTS: We found that blockade of RGMb by treatment with anti-RGMb mAb effectively blocked the development of airway inflammation and AHR. Importantly, blockade of RGMb completely blocked the development of airway inflammation and AHR, even if treatment occurred only during the challenge (effector) phase. IL-25 played an important role in these models of asthma because IL-25 receptor-deficient mice did not develop disease after sensitization and challenge with allergen. RGMb was expressed primarily by innate cells in the lungs, including bronchial epithelial cells (known producers of IL-25), activated eosinophils, and interstitial macrophages, which in the inflamed lung expressed the IL-25 receptor and produced IL-5 and IL-13. We also found that neogenin, the canonical receptor for RGMb, was expressed by interstitial macrophages and bronchial epithelial cells in the inflamed lung, suggesting that an innate RGMb-neogenin axis might modulate allergic asthma. CONCLUSIONS: These results demonstrate an important role for a novel innate pathway in regulating type 2 inflammation in patients with allergic asthma involving RGMb and RGMb-expressing cells, such as interstitial macrophages and bronchial epithelial cells. Moreover, targeting this previously unappreciated innate pathway might provide an important treatment option for allergic asthma.

A natural killer T-cell subset that protects against airway hyperreactivity.

BACKGROUND: Infection of suckling mice with influenza virus expands a CD4-CD8- double-negative (DN) natural killer T (NKT) cell subpopulation that protects the mice as adults against allergen-induced airway hyperreactivity (AHR). However, this NKT cell subset has not been characterized, and the underlying mechanisms of protection remain unknown. OBJECTIVE: We characterized this specific NKT cell subpopulation that developed during influenza infection in neonatal mice and that suppressed the subsequent development of AHR. METHODS: A cell-surface marker was identified by comparing the mRNA expression profile of wild-type CD4+ NKT cells with that of suppressive Vα14 DN NKT cells. The marker-enriched NKT cell subset was then analyzed for its cytokine profile and its suppressive in vitro and in vivo abilities. RESULTS: We showed that DN NKT cells with high CD38 expression produced IFN-γ, but not IL-17, IL-4, or IL-13, and inhibited development of AHR through contact-dependent suppression of helper CD4 T-cell proliferation. The NKT subset expanded in the lungs of neonatal mice after infection with influenza and also after treatment of neonatal mice with Nu-α-GalCer, which effectively increased DN CD38hi NKT cell numbers. CONCLUSION: These results suggest that early/neonatal exposure to infection or antigen challenge affects subsequent lung immunity by altering the cellular composition of cells in the lung and that some subsets of NKT cells suppress AHR. These results provide a possible mechanism by which prior infections can protect against the development of allergic asthma and might be further explored as a protective measure for young children.

The effects of exogenous xylanase supplementation on the in vivo generation of xylooligosaccharides and monosaccharides in broilers fed a wheat-based diet.

1. This study quantified xylanase-induced changes in soluble monosaccharides, xylooligosaccharides (XOS) and volatile fatty acid (VFA) contents of the different sections of the gastrointestinal tract (GIT) and whether these were related to altered bird performance. 2. An in vitro digestion of the wheat-based diet was carried out with the xylanase (Econase XT at 16,000BXU/kg diet) to compare the in vitro and in vivo generation of these XOS and monosaccharides. For the in vivo study, 80 male Ross 508 b roiler chicks were split into two groups fed a wheat-based diet with or without Econase XT (16,000BXU/kg diet) for 21 days. 3. There were no effects of Econase XT inclusion on growth performance characteristics, likely a result of the high-quality wheat diet, the corresponding high performance of the control group (FCR average of 1.45 in controls) and the relatively young age of the birds (from four to 26 days of age). 4. Econase XT supplementation increased the xylotetraose (X4) content in the colon (P = 0.046, enzyme x GIT section interaction) and the xylose contents in the colon and caeca (P < 0.001, enzyme x GIT section interaction). 5. The trend for increased acetate production in the caeca of Econase XT treated birds (P = 0.062) suggested that the XOS generated were subsequently fermented in the caeca, potentially impacting upon the types of microbiota present. 6. The present study suggested that wheat arabinoxylan degradation was enhanced by xylanase supplementation, which may have increased the production of beneficial volatile fatty acids (VFA) in the caeca, and thereby potentially modulated the caecal microbiome, but without affecting bird performance at this early age.

Acute kidney injury in patients undergoing endovascular therapy for critical limb ischemia.

BACKGROUND: Similar to coronary angiography and interventions, patients undergoing percutaneous treatment of lower extremity peripheral arterial disease are also at risk of acute kidney injury (AKI). The incidence, risk factors associations, need for dialysis and inhospital mortality related to AKI in patients with critical limb ischemia (CLI) following endovascular therapy is poorly defined. OBJECTIVES: The purpose of this study was to analyze data from the National Inpatient Sample (NIS) to determine the aforementioned outcomes in patients with CLI. METHODS: Using the full NIS admission dataset from 2003 through 2012, ICD-9 codes relevant to comorbid conditions, procedure codes, composite codes for AKI, and inhospital mortality were analyzed using multivariate models. RESULTS: A total of 273,624 patients were included with a mean age of 70.0 ± 27.4 years, 46.0% were female, 57.2% had diabetes, 43.4% had coronary artery disease (CAD), and 29.2% had chronic kidney disease (CKD). The overall rate of AKI was 10.4%, and there was a temporal rise over the analysis period in AKI incidence (p < .001). Age, diabetes, CKD, and heart failure were all associated with AKI (p < .0001). The inhospital mortality rate in the patients with AKI declined over time but was higher than in patients without AKI (6.0% vs. 1.4%), p < .0001. The mortality rate was substantially higher in patients with AKI requiring dialysis as compared to AKI not requiring dialysis (13.4% vs. 5.6%), p < .0001. CONCLUSIONS: AKI is associated with age, CKD, and heart failure. The incidence of AKI following endovascular therapy for CLI is rising and independently associated with inhospital mortality.

Total elbow arthroplasty in haemophilia.

INTRODUCTION: Advanced haemophilic arthropathy of the elbow can be a devastating manifestation of severe haemophilia with significant implications for activities of daily living. AIM: To summarize the currently available data on total elbow arthroplasty (TEA) for haemophilic arthropathy of the elbow, to draw comparisons to TEA for other indications, and to outline some considerations regarding TEA in this unique population. METHODS: A narrative review of the literature has been performed. RESULTS: The scant data regarding outcomes of TEA for haemophilic arthropathy are limited to small case series and case reports. A review of the available literature shows that, while pain relief and patient satisfaction are promising, variable outcomes with significant complications and infection rates may discourage routine use of TEA for haemophilic arthropathy of the elbow. CONCLUSION: While patients with severe haemophilic arthropathy of the elbow are likely to make gains in terms of pain control and range of motion following TEA, there are insufficient data to routinely recommend its use. Complication and infection rates are concerning, and the lack of survival analysis data makes it difficult to quantify the benefit to the patient in light of the risks and resources involved in the procedure.

Extrathymically generated regulatory T cells control mucosal TH2 inflammation.

A balance between pro- and anti-inflammatory mechanisms at mucosal interfaces, which are sites of constitutive exposure to microbes and non-microbial foreign substances, allows for efficient protection against pathogens yet prevents adverse inflammatory responses associated with allergy, asthma and intestinal inflammation. Regulatory T (T(reg)) cells prevent systemic and tissue-specific autoimmunity and inflammatory lesions at mucosal interfaces. These cells are generated in the thymus (tT(reg) cells) and in the periphery (induced (i)T(reg) cells), and their dual origin implies a division of labour between tT(reg) and iT(reg) cells in immune homeostasis. Here we show that a highly selective blockage in differentiation of iT(reg) cells in mice did not lead to unprovoked multi-organ autoimmunity, exacerbation of induced tissue-specific autoimmune pathology, or increased pro-inflammatory responses of T helper 1 (T(H)1) and T(H)17 cells. However, mice deficient in iT(reg) cells spontaneously developed pronounced T(H)2-type pathologies at mucosal sites--in the gastrointestinal tract and lungs--with hallmarks of allergic inflammation and asthma. Furthermore, iT(reg)-cell deficiency altered gut microbial communities. These results suggest that whereas T(reg) cells generated in the thymus appear sufficient for control of systemic and tissue-specific autoimmunity, extrathymic differentiation of T(reg) cells affects commensal microbiota composition and serves a distinct, essential function in restraint of allergic-type inflammation at mucosal interfaces.

Thermal niche evolution of functional traits in a tropical marine phototroph.

Land-based plants and ocean-dwelling microbial phototrophs known as phytoplankton, are together responsible for almost all global primary production. Habitat warming associated with anthropogenic climate change has detrimentally impacted marine primary production, with the effects observed on regional and global scales. In contrast to slower-growing higher plants, there is considerable potential for phytoplankton to evolve rapidly with changing environmental conditions. The energetic constraints associated with adaptation in phytoplankton are not yet understood, but are central to forecasting how global biogeochemical cycles respond to contemporary ocean change. Here, we demonstrate a number of potential trade-offs associated with high-temperature adaptation in a tropical microbial eukaryote, Amphidinium massartii (dinoflagellate). Most notably, the population became high-temperature specialized (higher fitness within a narrower thermal envelope and higher thermal optimum), and had a greater nutrient requirement for carbon, nitrogen and phosphorus. Evidently, the energetic constraints associated with living at elevated temperature alter competiveness along other environmental gradients. While high-temperature adaptation led to an irreversible change in biochemical composition (i.e., an increase in fatty acid saturation), the mechanisms underpinning thermal evolution in phytoplankton remain unclear, and will be crucial to understanding whether the trade-offs observed here are species-specific or are representative of the evolutionary constraints in all phytoplankton.

Acute lion's mane jellyfish, Cyanea capillata (Cnideria: Scyphozoa), exposure to Atlantic salmon (Salmo salar L.).

Jellyfish-induced gill pathology relies upon occasional diagnostic observations yet the extent and impact of jellyfish blooms on aquaculture may be significant. Idiopathic gill lesions are often observed in apparently healthy fish. This study exposed Atlantic salmon (Salmo salar L.) smolts to macerated Cyanea capillata at 2.5 and 5 g/L for 2 hr under controlled laboratory conditions. Blood chemistry and gill histopathology were examined over a subsequent 4-week period. Fish showed an acute response to the presence of jellyfish, including characteristic external "whiplash" discoloration of the skin and acute increases in blood electrolytes and CO2 concentration; however, these were resolved within 4 days after exposure. Histopathologically, gills showed first an acute oedema with epithelial separation followed by focal haemorrhage and thrombus formation, and then progressive inflammatory epithelial hyperplasia that progressively resolved over the 4 weeks post-exposure. Results were consistent with the envenomation of gills with cytotoxic neurotoxins and haemolysins known to be produced by C. capillata. This study suggests that many focal hyperplastic lesions on gills, especially those involving focal thrombi, may be the result of jellyfish stings. Thus, the presence of jellyfish and their impact may be severe and understated in terms of marine fish aquaculture and fish welfare.

Omalizumab facilitates rapid oral desensitization for peanut allergy.

BACKGROUND: Peanut oral immunotherapy is a promising approach to peanut allergy, but reactions are frequent, and some patients cannot be desensitized. The anti-IgE medication omalizumab (Xolair; Genentech, South San Francisco, Calif) might allow more rapid peanut updosing and decrease reactions. OBJECTIVE: We sought to evaluate whether omalizumab facilitated rapid peanut desensitization in highly allergic patients. METHODS: Thirty-seven subjects were randomized to omalizumab (n = 29) or placebo (n = 8). After 12 weeks of treatment, subjects underwent a rapid 1-day desensitization of up to 250 mg of peanut protein, followed by weekly increases up to 2000 mg. Omalizumab was then discontinued, and subjects continued on 2000 mg of peanut protein. Subjects underwent an open challenge to 4000 mg of peanut protein 12 weeks after stopping study drug. If tolerated, subjects continued on 4000 mg of peanut protein daily. RESULTS: The median peanut dose tolerated on the initial desensitization day was 250 mg for omalizumab-treated subjects versus 22.5 mg for placebo-treated subject. Subsequently, 23 (79%) of 29 subjects randomized to omalizumab tolerated 2000 mg of peanut protein 6 weeks after stopping omalizumab versus 1 (12%) of 8 receiving placebo (P < .01). Twenty-three subjects receiving omalizumab versus 1 subject receiving placebo passed the 4000-mg food challenge. Overall reaction rates were not significantly lower in omalizumab-treated versus placebo-treated subjects (odds ratio, 0.57; P = .15), although omalizumab-treated subjects were exposed to much higher peanut doses. CONCLUSION: Omalizumab allows subjects with peanut allergy to be rapidly desensitized over as little as 8 weeks of peanut oral immunotherapy. In the majority of subjects, this desensitization is sustained after omalizumab is discontinued. Additional studies will help clarify which patients would benefit most from this approach.