Optimization of the diagnosis and characterization of gibberellin-regulated protein sensitization: An Italian cohort study.

BACKGROUND: Pru p 7 was the first gibberellin-regulated protein (GRP) to be identified as a food allergen as the basis of a pollen food allergy syndrome. OBJECTIVE: To clinically and biologically characterize a group of patients with suspected allergy to Pru p 7 to optimize the diagnostic workup of GRP sensitization. METHODS: Allergy to Pru p 7 was suspected in the presence of a systemic allergic reaction to plant food, positive skin prick test results for cypress pollen and lipid-transfer protein-enriched peach extract, and absence of Pru p 3-specific immunoglobulin E. Controls were patients with food allergies, patients sensitized to Pru p 3, and patients with cypress allergy without food allergy. Diagnostic workup included skin tests, basophil activation test, Western blot, and single and multiplex assays. RESULTS: In total, 23 patients and 14 controls were enrolled. The most implicated food was peach (91.3%). Approximately 70% of patients reacted to multiple foods. Mueller 4 reactions were 8.7%. In 26.1% of cases, a cofactor triggered the reaction. The basophil activation test results were positive for rPru p 7 in 87% of the patients. Specific immunoglobulin E to Pru p 7 was detected in 95.7% by singleplex and in 73.9% by multiplex assays in patients with suspected allergies; 73.9% of them also reacted to cypress pollen GRP (Cup s 7) in Western blot analysis. CONCLUSION: Patients with Pru p 7-Cup s 7 allergy in our cohort confirm a mild-to-severe clinical syndrome characterized by pollen and food allergy. The diagnosis may benefit from the proposed selection criteria that can be used as preliminary steps to further characterize the cross-reactive GRP sensitization.

Predictors of poor outcome in tocilizumab treated patients with Sars-CoV-2 related severe respiratory failure: A multicentre real world study.

INTRODUCTION: Despite Tocilizumab is now recognized as a concrete therapeutic option in patients with severe SARS-CoV-2 related respiratory failure, literature lacks about factors influencing the response to it in this context. Therefore, the aim of our study was to provide evidence about predictors of poor outcome in Tocilizumab treated patients in the real-world practice. MATERIALS AND METHODS: We retrospectively analyzed clinical, laboratory and chest computer tomography (CCT) data of patients firstly admitted in non Intensive Care Units (ICU) and suffering from severe respiratory failure, who were treated with the IL-6 antagonist Tocilizumab. We compared patients who died and/or required admission to ICU with oro-tracheal intubation (OTI) with those who did not. RESULTS: Two hundreds and eighty-seven patients (29.9% females) with mean age ± SD 64.1 ± 12.6 years were the study population. In-hospital mortality was 18.8%, while the composite endpoint in-hospital mortality and/or ICU admission with OTI occurred in 23.7%. At univariate analysis, patients who died and/or were admitted to ICU with OTI were significantly older and co-morbid, had significantly higher values of creatinine, C-reactive protein (CRP) and procalcitonin and lower lymphocytes count, PaO2/FiO2 ratio (P/F) and room air pulsossimetry oxygen saturation (RAO2S) at hospital admission. Computed tomography ground glass opacities (CT-GGO) involving the pulmonary surface ≥ 50% were found in 55.4% of patients who died and/or were admitted to ICU with OTI and in 21.5% of patients who did not (p=0.0001). At multivariate analysis, age ≥ 65 years (OR 17.3, 95% CI: 3.7-81.0), procalcitonin ≥ 0.14 (OR 9.9, 95%CI: 1.7-56.1), RAO2S ≤ 90% (OR 4.6, 95%CI: 1.2-17.0) and CCT-GGO involvement ≥ 50% (OR 5.1, 95%CI: 1.2-21.0) were independent risk factors associated with death and/or ICU admission with OTI. CONCLUSION: Tocilizumab has shown to improve outcome in patients with severe respiratory failure associated to SARS-CoV-2 related pneumonia. In our multicentre study focusing on Tocilizumab treated severe COVID-19 patients, age ≥ 65 years, procalcitonin ≥ 0.14 ng/mL, RAO2S ≤ 90% and CCT-GGO involvement ≥ 50% were independent factors associated with poor outcome.

Oral CorticoSteroid sparing with biologics in severe asthma: A remark of the Severe Asthma Network in Italy (SANI).

According to the data derived from several national and international registries, including SANI (Severe Asthma Network Italy), and considering the strong impact that frequent or regular use of oral corticosteroid has on quality of life (QoL) of severe asthmatics, as well as on the costs for managing corticosteroid-related diseases, oral corticosteroid sparing up to withdrawal should be considered a primary outcome in the management of severe asthma. New biologics have clearly demonstrated that this effect is possible, with concomitant reduction in the rate of exacerbations and in symptom control. Then, there is no reason for using so frequently oral corticosteroid before having explored all alternatives currently available for a large part of severe asthmatics.

Frequency-Domain Quantum Interference with Correlated Photons from an Integrated Microresonator.

Frequency encoding of quantum information together with fiber and integrated photonic technologies can significantly reduce the complexity and resource requirements for realizing all-photonic quantum networks. The key challenge for such frequency domain processing of single photons is to realize coherent and selective interactions between quantum optical fields of different frequencies over a range of bandwidths. Here, we report frequency-domain Hong-Ou-Mandel interference with spectrally distinct photons generated from a chip-based microresonator. We use four-wave mixing to implement an active "frequency beam splitter" and achieve interference visibilities of 0.95±0.02. Our work establishes four-wave mixing as a tool for selective high-fidelity two-photon operations in the frequency domain which, combined with integrated single-photon sources, provides a building block for frequency-multiplexed photonic quantum networks.

Strong Nonlinear Coupling in a Si_{3}N_{4} Ring Resonator.

We demonstrate that nondegenerate four-wave mixing in a Si_{3}N_{4} microring resonator can result in a nonlinear coupling rate between two optical fields exceeding their energy dissipation rate in the resonator, corresponding to strong nonlinear coupling. We demonstrate that this leads to a Rabi-like splitting, for which we provide a theoretical description in agreement with our experimental results. This yields new insight into the dynamics of nonlinear optical interactions in microresonators and access to novel phenomena.

All-optically tunable buffer for single photons.

We demonstrate a photon buffer for quantum communication systems via a quantum frequency conversion-dispersion technique based on Bragg scattering four-wave mixing. The all-fiber setup is capable of imparting all-optical and continuously tunable delays onto single photons with minimal photon noise and absorption. Tunable delays up to 23 times the photon duration are demonstrated with on/off efficiencies as high as 55%.

Frequency multiplexing for quasi-deterministic heralded single-photon sources.

Parametric single-photon sources are well suited for large-scale quantum networks due to their potential for photonic integration. Active multiplexing of photons can overcome the intrinsically probabilistic nature of these sources, resulting in near-deterministic operation. However, previous implementations using spatial and temporal multiplexing scale unfavorably due to rapidly increasing switching losses. Here, we break this limitation via frequency multiplexing in which switching losses remain fixed irrespective of the number of multiplexed modes. We use low-noise optical frequency conversion for efficient frequency switching and demonstrate multiplexing of three modes. We achieve a generation rate of 4.6 × 104 photons per second with an ultra-low g(2)(0) = 0.07 indicating high single-photon purity. Our scalable, all-fiber multiplexing system has a total loss of just 1.3 dB, such that the 4.8 dB multiplexing enhancement markedly overcomes switching loss. Our approach offers a promising path to creating a deterministic photon source on an integrated chip-based platform.

Ramsey Interference with Single Photons.

Interferometry using discrete energy levels of nuclear, atomic, or molecular systems is the foundation for a wide range of physical phenomena and enables powerful techniques such as nuclear magnetic resonance, electron spin resonance, Ramsey-based spectroscopy, and laser or maser technology. It also plays a unique role in quantum information processing as qubits may be implemented as energy superposition states of simple quantum systems. Here, we demonstrate quantum interference involving energy states of single quanta of light. In full analogy to the energy levels of atoms or nuclear spins, we implement a Ramsey interferometer with single photons. We experimentally generate energy superposition states of a single photon and manipulate them with unitary transformations to realize arbitrary projective measurements. Our approach opens the path for frequency-encoded photonic qubits in quantum information processing and quantum communication.

Dual-pumped degenerate Kerr oscillator in a silicon nitride microresonator.

We demonstrate a degenerate parametric oscillator in a silicon nitride microresonator. We use two frequency-detuned pump waves to perform parametric four-wave mixing and operate in the normal group-velocity dispersion regime to produce signal and idler fields that are frequency degenerate. Our theoretical modeling shows that this regime enables generation of bimodal phase states, analogous to the χ(2)-based degenerate OPO. Our system offers potential for realization of CMOS-chip-based coherent optical computing and an all-optical quantum random number generator.

Tunable frequency combs based on dual microring resonators.

In order to achieve efficient parametric frequency comb generation in microresonators, external control of coupling between the cavity and the bus waveguide is necessary. However, for passive monolithically integrated structures, the coupling gap is fixed and cannot be externally controlled, making tuning the coupling inherently challenging. We design a dual-cavity coupled microresonator structure in which tuning one ring resonance frequency induces a change in the overall cavity coupling condition. We demonstrate wide extinction tunability with high efficiency by engineering the ring coupling conditions. Additionally, we note a distinct dispersion tunability resulting from coupling two cavities of slightly different path lengths, and present a new method of modal dispersion engineering. Our fabricated devices consist of two coupled high quality factor silicon nitride microresonators, where the extinction ratio of the resonances can be controlled using integrated microheaters. Using this extinction tunability, we optimize comb generation efficiency as well as provide tunability for avoiding higher-order mode-crossings, known for degrading comb generation. The device is able to provide a 110-fold improvement in the comb generation efficiency. Finally, we demonstrate open eye diagrams using low-noise phase-locked comb lines as a wavelength-division multiplexing channel.