T1 Response Research Articles

Pulmonary Administration of TLR2/6 Agonist after Allergic Sensitization Inhibits Airway Hyper-Responsiveness and Recruits Natural Killer Cells in Lung Parenchyma.

Asthma is a chronic lung disease with persistent airway inflammation, bronchial hyper-reactivity, mucus overproduction, and airway remodeling. Antagonizing T2 responses by triggering the immune system with microbial components such as Toll-like receptors (TLRs) has been suggested as a therapeutic concept for allergic asthma. The aim of this study was to evaluate the effect of a TLR2/6 agonist, FSL-1 (Pam2CGDPKHPKSF), administered by intranasal instillation after an allergic airway reaction was established in the ovalbumin (OVA) mouse model and to analyze the role of natural killer (NK) cells in this effect. We showed that FSL-1 decreased established OVA-induced airway hyper-responsiveness and eosinophilic inflammation but did not reduce the T2 or T17 response. FSL-1 increased the recruitment and activation of NK cells in the lung parenchyma and modified the repartition of NK cell subsets in lung compartments. Finally, the transfer or depletion of NK cells did not modify airway hyper-responsiveness and eosinophilia after OVA and/or FSL-1 treatment. Thus, the administration of FSL-1 reduces airway hyper-responsiveness and bronchoalveolar lavage eosinophilia. However, despite modifications of their functions following OVA sensitization, NK cells play no role in OVA-induced asthma and its inhibition by FSL-1. Therefore, the significance of NK cell functions and localization in the airways remains to be unraveled in asthma.

Molecular Modes Elucidate the Nuclear Magnetic Resonance Relaxation of Viscous Fluids.

The Bloembergen, Purcell, and Pound (BPP) theory of nuclear magnetic resonance (NMR) relaxation in fluids dating back to 1948 continues to be the linchpin in interpreting NMR relaxation data in applications ranging from characterizing fluids in porous media to medical imaging (MRI). The BPP theory is founded on assuming molecules are hard spheres with 1H-1H dipole pairs reorienting randomly; assumptions that are severe in light of modern understanding of liquids. Nevertheless, it is intriguing to this day that the BPP theory was consistent with the original experimental data for glycerol, a hydrogen-bonding molecular fluid for which the hard-sphere-rigid-dipole assumption is inapplicable. To better understand this incongruity, atomistic molecular simulations are used to compute 1H NMR T1 relaxation dispersion (i.e., frequency dependence) in two contrasting cases: glycerol, and a (non hydrogen-bonding) viscosity standard. At high viscosities, simulations predict distinct functional forms of T1 for glycerol compared to the viscosity standard, in agreement with modern measurements, yet both in contrast to BPP theory. The cause of these departures from BPP theory is elucidated, without assuming any relaxation models and without any free parameters, by decomposing the simulated T1 response into dynamic molecular modes for both intramolecular and intermolecular interactions. The decomposition into dynamic molecular modes provides an alternative framework to understand the physics of NMR relaxation for viscous fluids.

Nomenclature of allergic diseases and hypersensitivity reactions: Adapted to modern needs: An EAACI position paper.

The exponential growth of precision diagnostic tools, including omic technologies, molecular diagnostics, sophisticated genetic and epigenetic editing, imaging and nano-technologies and patient access to extensive health care, has resulted in vast amounts of unbiased data enabling in-depth disease characterization. New disease endotypes have been identified for various allergic diseases and triggered the gradual transition from a disease description focused on symptoms to identifying biomarkers and intricate pathogenetic and metabolic pathways. Consequently, the current disease taxonomy has to be revised for better categorization. This European Academy of Allergy and Clinical Immunology Position Paper responds to this challenge and provides a modern nomenclature for allergic diseases, which respects the earlier classifications back to the early 20th century. Hypersensitivity reactions originally described by Gell and Coombs have been extended into nine different types comprising antibody- (I-III), cell-mediated (IVa-c), tissue-driven mechanisms (V-VI) and direct response to chemicals (VII). Types I-III are linked to classical and newly described clinical conditions. Type IVa-c are specified and detailed according to the current understanding of T1, T2 and T3 responses. Types V-VI involve epithelial barrier defects and metabolic-induced immune dysregulation, while direct cellular and inflammatory responses to chemicals are covered in type VII. It is notable that several combinations of mixed types may appear in the clinical setting. The clinical relevance of the current approach for allergy practice will be conferred in another article that will follow this year, aiming at showing the relevance in clinical practice where various endotypes can overlap and evolve over the lifetime.

Experimental investigation of strength repairing effects of chemical grouting on fractured porous sandstone under different temperature conditions

Investigation of the seepage characteristics and the corresponding repairing effects of slurry on fractured rock mass is of great significance to grouting theory and operation parameters designing. Several chemical grouting tests under different temperatures and grouted pressures were conducted and the seepage processes were monitored by the LF-NMR (low field nuclear magnetic resonance) technique. The influence of temperature on the flow properties, grouted volume and permeability of slurry were comprehensively studied through the analysis of the NMR T2 response. The effects of temperature on the mechanical performance of grouted specimens after curing were investigated through the directly shear tests. The results indicated that the temperature has an obvious impact on the seepage characteristics, the higher the temperature, the lower the permeability. The mechanical performance of grouted specimen is closely dependent on the grouting temperature, the inter friction angle φ and the cohesion c exponentially decrease as the temperature increases. A temperature dependent shear strength mechanical model of slurry bonding layer was proposed and verified. The findings of this study are useful for the parameters designing of grouting operation in deep-buried tunnels.

Histopathologic Validation of Stress T1 Mapping in Myocardial Ischemia: Another Step toward Clinical Translation?

Histopathologic Validation of Stress T1 Mapping in Myocardial Ischemia: Another Step toward Clinical Translation?

Reproducibility of the new Leishmania vaccine: Changes in T1, T2 and spleen white pulp responses after re- exposure to live promastigote of Leishmania major

Introduction: Human leishmaniasis is distributed worldwide and is mainly in the tropics and subtropics, with a prevalence of 12 million cases and an approximately incidence of 0.5 million cases of VL and 1.5 million cases of cutaneous leishmaniasis (CL). Leishmania parasites are vector-born protozoan pathogens found in tropical and subtropical regions of both the old and new world. The disease in human can be divided into cutaneous, visceral, and mucosal syndromes. The aim of this study was more experiments over our previous new formulation leishmania major vaccine which had satisfactory experiments results. Method: For detail procedure refers to author’s previous publications. Briefly, hundred and twenty Balb/cmice were randomly divided into four groups as LT, LB, LBT and control groups. LT, LB and LBT injected subcutaneously with the antigen and the same booster doses with two weeks intervals. The expansion rates of the spleen white pulp size was evaluated using a light microscope and the levels of the serum Th1 (IFN- γ, IL-12) and Th2 (IL-4, IL-10) cytokines measured with the ELISA method. Results: Comparing to the LT and LB groups, the LBT group had highest levels of serum IL12, lowest levels of IL10 and highest increase in the spleen white pulp size. Significant correlation was observed between IL12 and IL10 but not IFN gamma or IL4. Conclusion: present study indicated that the LBT group which received crude cocktail leishmania antigen plus alcoholic extract of Teucrium polium and BCG as adjuvant showed satisfactory cytokines profile comparing to groups LT and LB,since highest levels of IL12 and lower levels of IL10 which could help the infected subjects to inhibit or eradication the intracellular leishmania amastigotes, and also was seen highest increase in the spleen white-pulp size which pointed to the synergistic effects of alcoholic extract of T. polium and BCG.

Reproducibility of the new Leishmania vaccine: Changes in T1, T2 and spleen white pulp responses after re- exposure to live promastigote of Leishmania major

Reproducibility of the new Leishmania vaccine: Changes in T1, T2 and spleen white pulp responses after re- exposure to live promastigote of Leishmania major

Early post-bevacizumab change in rCBV from DSC-MRI identifies pseudoresponse in recurrent glioblastoma: Results from ACRIN 6677/RTOG 0625.

Progressive enhancement predicted poor survival in ACRIN 6677/RTOG 0625, a multi-center trial of bevacizumab with irinotecan or temozolomide in recurrent glioblastoma, but pseudoresponse likely limited enhancement-based survival prognostication in T1 non-progressors. We aimed to determine whether early change in cerebral blood volume from baseline (ΔCBV) could further stratify the T1 non-progressors according to overall (OS) and progression-free (PFS) survival. 37/123 enrolled patients had DSC-MRI, including 13, 15, and 8 patients without 2D-T1 progression at 2, 8, and 16 weeks post-treatment initiation, respectively. Mean CBV normalized to white matter (nRCBV) and mean standardized CBV (sRCBV) were extracted from enhancing tumor. ROC curves were derived for ΔCBV using six-month PFS and one-year OS as reference standards. Kaplan-Meier survival estimates and log-rank test compared PFS and OS for both ΔCBV (increase vs. decrease) and T1 response status (stable vs. decreasing enhancement). PFS and OS were significantly worse for increasing CBV at 2 weeks (p=0.003 and p=0.002 for nRCBV, and p=0.03 and p=0.03 for sRCBV, respectively), but not for 2D-T1 patients with stable vs. decreasing enhancement (p=0.44 and p=0.86, respectively). ΔCBV at week 2 was also a good prognostic marker for OS-1 and PFS-6 using ROC analysis. By contrast, 2D-T1 response status at weeks 2, 8, and 16 was not associated with PFS-6. ΔCBV at 16 weeks (p=0.008 for sRCBV) but not 8 weeks (p=0.74 for nRCBV and p=0.56 for sRCBV) was associated with significant difference in median survival, but no difference in survival was observed for 2D-T1 patients with stable vs. decreasing enhancement at 8 weeks (p=0.69) or 16 weeks (p=0.21). At 16 weeks, OS did not differ significantly between 2D-T1 progressors and 2D-T1 non-progressors with increasing CBV (median survival 3.3 months post week 16 scan vs. 9.2 months, respectively; p=0.13), suggesting that 2D-T1 non-progressors with increasing CBV may have a prognosis like that of 2D-T1 progressors. After 2 weeks of anti-angiogenic therapy, ΔCBV in 2D-T1 non-progressors significantly prognosticated PFS and OS, whereas 2D-T1 response status did not, identifying a subpopulation that benefits from bevacizumab. Combining 2D-T1 progression and ΔCBV may yield a response assessment paradigm with 3-tiered OS stratification.

Mixed Wettability Modeling and Nuclear Magnetic Resonance Characterization in Tight Sandstone

Rock wettability significantly impacts fluid distributions in reservoirs and enhanced oil recovery. As the large variety of mixed-wet tight formations becomes increasingly evident, research evaluating wettability has become increasingly important. The nuclear magnetic resonance (NMR) technique is suitable for wettability characterization, but the simplified rock models currently used in NMR studies, that is, entirely water-wet or oil-wet or classified as water- or oil-wet based on pore geometry, may result in inaccurate pore-fluid distributions and wettability estimates. In this paper, a new pore-scale mixed-wet rock model was constructed that considers the contact angle and wetting area. A tight sandstone rock saturated with oil–water is presented as an example to investigate T2 responses and NMR T2-based wettability indices for different wettability features. In the model, a mixed-wet digital rock saturated with oil and water is constructed using the sedimentological process method and the Lattice Boltzmann method. Then, the random walk method is applied to simulate T2 responses in cases with varied wettability properties, such as contact angle, wetting area ratio, and fluid saturation. Finally, the apparent contact angle cosine is used as the wettability indicator for comparison with published NMR T2-based wettability indices. The results showed that the combination of the wetting area ratio (determined by the pore size cutoff), actual contact angle of wetting surfaces, and fluid saturation significantly impacted T2 distributions of fluid-saturated mixed-wet rocks. Simulations and experiments showed that three NMR T2-based wettability indices were inappropriate for wettability assessment in weakly wet or intermediate-wet rocks. This was because those NMR indices are based on wetting areas and do not account for the effect of local contact angles of wetting surfaces. These investigations have provided a theoretical basis for interpreting NMR T2 characterizations in rocks with mixed wettability.

Stress CMR T1-mapping technique for assessment of coronary microvascular dysfunction in a rabbit model of type II diabetes mellitus: Validation against histopathologic changes.

Coronary microvascular dysfunction (CMD) is an early character of type 2 diabetes mellitus (T2DM), and is indicative of adverse events. The present study aimed to validate the performance of the stress T1 mapping technique on cardiac magnetic resonance (CMR) for identifying CMD from a histopathologic perspective and to establish the time course of CMD-related parameters in a rabbit model of T2DM. New Zealand white rabbits (n = 30) were randomly divided into a control (n = 8), T2DM 5-week (n = 6), T2DM 10-week (n = 9), and T2DM 15-week (n = 7) groups. The CMR protocol included rest and adenosine triphosphate (ATP) stress T1-mapping imaging using the 5b(20b)3b-modified look-locker inversion-recovery (MOLLI) schema to quantify stress T1 response (stress ΔT1), and first-pass perfusion CMR to quantify myocardial perfusion reserve index (MPRI). After the CMR imaging, myocardial tissue was subjected to hematoxylin-eosin staining to evaluate pathological changes, Masson trichrome staining to measure collagen volume fraction (CVF), and CD31 staining to measure microvascular density (MVD). The associations between CMR parameters and pathological findings were determined using Pearson correlation analysis. The stress ΔT1 values were 6.21 ± 0.59%, 4.88 ± 0.49%, 3.80 ± 0.40%, and 3.06 ± 0.54% in the control, T2DM 5-week, 10-week, and 15-week groups, respectively (p < 0.001) and were progressively weakened with longer duration of T2DM. Furthermore, a significant correlation was demonstrated between the stress ΔT1 vs. CVF and MVD (r = -0.562 and 0.886, respectively; p < 0.001). The stress T1 response correlated well with the histopathologic measures in T2DM rabbits, indicating that it may serve as a sensitive CMD-related indicator in early T2DM.

Humoral Response after Two Doses of BNT162b2 mRNA Vaccine Has a Role in Predicting Response after Three Doses That Is Related to Plasma HIV Viremia and Nadir CD4+ Cell Count in HIV-Positive Patients.

We investigated the spike IgG levels of HIV+ patients on antiretroviral therapy six months after they received their second dose (T2) and six months after the third dose (T3) of the BNT162b2 mRNA vaccine, as well as the influence of different levels of plasma HIV viremia of overall CD4+ cell count and nadir value on the humoral time course. One hundred eighty-four patients were enrolled. The median age was 55 years, the median CD4+ cell count was 639 cells/mm3 and the median nadir value was 258 cells/mm3. On the basis of all tests performed during the study period, persistently undetectable plasma HIV RNA (PUD) was found in 66 patients, low-level viremia (LLV) in 57 and ongoing viremia (OV) in 61. Serum levels of IgG antibodies against a trimeric S-protein antigen were tested with DiaSorin Liaison SARS-CoV-2 TrimericS IgG and the response was classified as optimal (>75th percentile), intermediate (50th−25th percentile) and low (<25th percentile). The frequencies of the three different patterns of plasma HIV viremia (PUD, LLV and OV) were comparable in patients with low, intermediate and optimal IgG response evaluated at T2, with no difference in overall CD4+ cell count or nadir count. At T3, 92.9% of patients achieved an optimal response: T2 response proved to be the most important factor in predicting T3 optimal response in patients with LLV and OV.A nadir value ≤ 330 cells/mm3 had 100% sensitivity in predicting a non-optimal response. In conclusion, we demonstrated the persistence of anti-spike IgG, with high serum levels occurring in most patients six months after the third dose of the BNT162b2 mRNA vaccine and a predictive role of humoral response at T2 in subjects with detectable plasma HIV viremia. Immunological alterations related to past immunodeficiency may persist despite immune reconstitution, and the nadir value could be a useful tool for elaborating personalized vaccine schedules.

Comprehensive characterization of petrophysical properties in shale by solvent extraction experiments and 2D NMR

Shale oil is one of the important unconventional fossil fuels resources. Understanding the petrophysical properties of shale contributes to the exploration and clean production of shale oil resources. 1H nuclear magnetic resonance (NMR) is a potential technique that can provide for shale petrophysical properties. However, current NMR-based technique for shale petrophysical characterization, due to the complexity of shale, usually requires some auxiliary geochemical experiments. Since a multi-step solvent extraction (MSSE) experiment has a merit in separating hydrocarbons and water in shale, in this work, two-dimensional (2D) NMR measurements combined with MSSE experiments were proposed for the first time to study the petrophysical properties of shale. A mixture of dichloromethane and methanol in a ration of 9:1 was prepared as a solvent for the extraction. Sufficient natural air-drying time allows for the removal of dichloromethane while retaining methanol. The comprehensive experiments show that the signal change induced by residual methanol from T1/T2-T2 map, before and after extraction and natural air-drying, can be used to identify pore-fluid and evaluate the mobility of hydrocarbon. For insight into the essence of experimental phenomena, quasi-1D/2D translational diffusion model were employed to analyze the T1/T2 and T2 responses of pore fluids. Wettability characteristics and detailed hydrocarbon mobility of shale were obtained from the theoretical analyses based on the translational diffusion models and T1/T2-T2 map. Combined the experimental results with the theoretical analysis, a comprehensive interpretation scheme was established for shale based on the T1/T2-T2 map, including fluid identification, wettability evaluation, and hydrocarbon mobility characterization.

Assessment of the New Acceleromyograph TOF 3D Compared with the Established TOF Watch SX: Bland-Altman Analysis of the Precision and Limits of Agreement between Both Devices-A Randomized Clinical Comparison.

The new acceleromyograph TOF 3D was compared with the established TOF Watch SX in patients undergoing elective laparoscopic gynecological surgery. Neuromuscular transmission was assessed by simultaneous recording with both devices. Measurements were performed simultaneously at the left and the right M. adductor pollicis (Group A, 25 patients), or the M. corrugator supercilii (Group CS, 25 patients). The repeatability, time course, and limits of agreement (Bland-Altman) were compared. The primary endpoint was the 90% train-of-four recovery time (TOFR 0.9). Other endpoints included onset time of block, maximum T1 depression, time to 25% T1 recovery, the recovery time course of T1 response, and TOF ratio, respectively. In group CS, the repeatability coefficient of the TOF 3D was lower (4.66 (1.6)) than of the TOF Watch SX (6.02 (1.9); p = 0.026). In group A, the onset of the block was faster when measured by the TOF 3D (98.7 (30) s vs. 112.2 (36) s (mean (SD)); p = 0.032). In group A, time to recovery to a TOFR of 90% was measured earlier by the TOF 3D (bias −0.71 min, limits of agreement from −8.94 to +7.51 min). The TOF 3D provides adequate information with high precision and sensitivity. It is suitable even for measurement sites with small muscle contractions such as the M. corrugator supercilii.

A Bayesian Optimization Approach to the Simultaneous Extraction of Intrinsic Physical Parameters fromT1 andT2 Relaxation Responses

SummaryNuclear magnetic resonance (NMR) relaxation responses in porous media provide a sensitive probe of the microstructure and yet are influenced by a number of factors which are not easily detangled. Low-field T2 transverse relaxation measurements can be carried out quickly and are frequently used as pore size distributions, while adding T1 longitudinal relaxation measurements provides additional insights into surface properties and fluid content. Here we present an inverse solution workflow extracting related intrinsic physical parameters of the system by fitting experiment and numerical simulation(s). An efficient NMR forward solver for the simultaneous calculation of T1 and T2 responses is introduced, which honors existing inequality relationships between T1 and T2 parameters. We propose a Bayesian optimization approach that jointly identifies T1- and T2-related properties satisfying physical constraints by simultaneously fitting T1 and T2 experiments to simulations. This dual-task inverse solution workflow (DT-ISW) identifies the solution by minimizing the sum of the L2 norm of the fitting residuals of both T1 and T2 distributions into a single objective and jointly models the two highly correlated objectives with high efficiency using the vector-valued Gaussian process (GP) kernel for transfer learning. A multimodal search strategy is used to identify nonunique solution sets of the problem. The workflow is demonstrated on Bentheimer sandstone, identifying five intrinsic physical parameters. The performance of the joint DT-ISW (DT-ISW-J) is compared to a sequential DT-ISW (DT-ISW-S) approach as well as an independent single-task ISW (ST-ISW) of the T1 and T2 responses. Both dual-task versions converge more than two times faster than the single-task version. DT-ISW-J equally minimizes the L2 norm of T1 and T2 fitting residuals whereas DT-ISW-S only preferentially minimizes the objective assigned higher importance. A Pareto optimal solution (POS) is provided to allow operators to subjectively balance the preference of T1 and T2 data fits for the slightly conflicting objectives. The ability to extract five intrinsic physical parameters simultaneously provides new techniques for tracking wettability alteration and assessing the influence of clay amount and distribution on petrophysical property estimates.

A phase II study of gemcitabine plus cisplatin chemotherapy in patients with muscle-invasive bladder cancer with bladder preservation for those patients whose tumors harbor deleterious DNA damage response (DDR) gene alterations (Alliance A031701).

TPS4615 Background: While a standard approach to muscle-invasive bladder cancer (MIBC) management involves neoadjuvant cisplatin-based chemotherapy (NAC) followed by radical cystectomy (RC), up to 50% of pts recur with metastatic disease. Moreover, removal of the bladder has a significant impact on pts’ quality of life. Pathologic downstaging to non-muscle-invasive disease (&lt;pT2) or complete response (pT0) at RC is associated with long-term survival benefit. Somatic DDR gene alterations were shown to be enriched in pts who were pT0 at RC following NAC in multiple retrospective analyses. We hypothesize that MIBC pts with somatic loss-of-function alterations within specific DDR genes and clinical responses to NAC can be uniquely managed with a bladder-sparing approach consisting of close cystoscopic and radiographic surveillance, avoiding the toxicities of definitive local therapy. Methods: A031701 is a multicenter phase II trial that will enroll 271 pts with T2-T4aN0/xM0 MIBC diagnosed within 60 days prior to enrollment. Multifocal MIBC, tumors &gt;5 cm by cystoscopic assessment, and Bacillus Calmette-Guérin (BCG)-refractory disease (beyond standard induction and maintenance) are not allowed. Intravesical chemotherapy is allowed. Pts must be eligible for cisplatin chemotherapy. Eligible pts will receive either standard dose or dose dense gemcitabine and cisplatin chemotherapy (investigator’s choice) with simultaneous genetic sequencing of pre-treatment transurethral resection specimens. Pts whose tumors contain deleterious alterations in any 1 of 9 pre-selected DDR genes ( ERCC2, ERCC5, BRCA1, BRCA2, RECQL4, RAD51C, ATM, ATR, and FANCC) and who exhibit &lt;T1 response on clinical restaging are eligible for organ-sparing management. Pts without deleterious DDR gene alterations or with &gt;T1 disease after NAC will undergo RC or chemoradiation therapy (investigator/patient choice). The primary endpoint is 3-year event-free survival in DDR-altered pts who undergo bladder sparing, defined as the proportion of pts without BCG-unresponsive non-muscle invasive recurrences, any &gt;T2 recurrences, or any metastatic recurrences. Secondary endpoints include clinical response rate (&lt;cT1) in patients with deleterious DDR gene alterations following NAC, bladder-intact survival, overall survival, pT0 rate in DDR-altered pts who elect to undergo RC, pT0 rate in pts without DDR gene alterations, 3-year RC rate in pts with DDR gene alterations, and proportion of pts undergoing intravesical management for in-bladder recurrences. The study opened for enrollment in September 2018. Support: U10CA180821, U10CA180882. Clinical trial information: NCT03609216.

Registry analysis of patients with severe allergic asthma and clinically relevant sensitization to fungal allergens treated with genetically engineered biologics

Background. Fungal sensitization (FS) often escapes the attention of clinicians when assessing the spectrum of sensitization in patients with atopic diseases. According to cohort studies is found in 310% of the general population and in 720% of asthmatics; the proportion of patients with severe bronchial asthma (SBA) with HS ranges from 35 to 75%. Fungal conidia have a 1000-fold higher exposure and are among the most important clinically relevant allergens in asthma. Exposure to fungal allergens is capable of generating a sustained T2 response with production of proinflammatory cytokines such as IL-5 and 13, which is indirectly related to the severity of airway eosinophilia. The identification of specific serum IgE is considered the benchmark diagnostic sign of FS, and the encapsulated hydrophobic carrier polymer system is considered preferable to skin prick tests. The process of reclassifying diseases with fungal lung lesions is confusing treatment strategies, leaving the FS problem underestimated. A series of publications have shown that omalizumab and other biologics targeting IL-5 or IL-5 receptor (IL5R) alpha are effective in treating SBA with FS. However, there remains an unmet need in real clinical practice for standardized approaches to genetically engineered biological therapies (BT) for different phenotypes of SBA, especially those associated with impaired microbiological homeostasis and this type of sensitization.&#x0D; Aim. Using retrospective analysis of clinical-dynamic observational data from patients on BT treatment in a real clinical setting to determine phenotypic features of severe allergic bronchial asthma with FS and to perform additional detailed analysis of a cohort of patients on anti-IgE therapy.&#x0D; Materials and methods. A retrospective observational single-center registry study was conducted between June 2017 and August 2021 at the City Reference Center for Allergology and Immunology. The baseline cohort consisted of 198 patients with severe allergic AD who were in the initial phase of BT. Inclusion criteria: age of patients over 18 years; presence of severe allergic bronchial asthma. Complex initial examination of patients included determination of FS by two methods: ImmunoCap ISAC to fungal allergic components alt a1, alt 6 (fungi of genus Alternaria) and asp f1, asp f3, asp f6 (fungi of genus Aspergillus). Specific IgE determinations on fungal panels. Sensitization to fungi was detected in 47 people during allergy examination. The following criteria were considered in evaluation of response to omalizumab: AST score less than 19 and/or difference between initial AST score and this score in dynamics less than 3 points; FEV 1 score less than 80; combination of 2 listed criteria. The minimum period of BT was 16 weeks. Nonparametric methods of descriptive statistics were used: median, interquartile range. Differences were considered significant at p0.05. Data were statistically processed using nonparametric methods in IBM SPSS Statistics V-22 program. MannWhitney U-test and KruskalWallis one-way analysis of variance were used to compare quantitative characteristics. Fisher's 2 test was used to compare qualitative characteristics.&#x0D; Results. Characteristics of the eosinophilic phenotype of SBA combined with FS: middle-aged patients, more often women, with relatively early onset of AD and high baseline eosinophil levels before prescription of biological drug therapy. Concomitant atopic dermatitis and food allergies are additional frequent features of this phenotype. Analysis of the effect of FS on achieving response to omalizumab and further consideration of switching to alternative therapy in SBA and FS patients showed the need to avoid premature revision and perform no earlier than the 10th month of therapy due to delayed response formation. Given the aggressive impact of FS on the barrier functions of the bronchial tree epithelium, it is advisable to test patients for FS at the initial diagnosis of AD. In the presence of atopic dermatitis and/or food allergy as T2 comorbidities in patients with SBA, early testing for FS and increased control of local and systemic inflammation are appropriate, which may improve long-term outcomes and reduce risks of further damage to natural barriers.&#x0D; Conclusion. Further research on various aspects of FS and its role in allergic diseases is extremely relevant in the current context.

Dupilumab: A Review of Present Indications and Off-Label Uses.

Recent advances in our understanding of T2 inflammation have revealed more diseases in which T2 inflammation is involved. Dupilumab is a recently developed monoclonal antibody that blocks signaling of IL-4 and IL-13, both of which are crucial cytokines in the T2 response. New possible indications are increasingly explored and include skin diseases, such as prurigo nodularis, nummular eczema, allergic contact dermatitis, chronic hand eczema, spontaneous chronic urticaria, bullous pemphigoid, alopecia areata, and Netherton syndrome, as well as respiratory diseases, such as allergic bronchopulmonary aspergillosis, chronic eosinophilic pneumonia, and allergic rhinitis. In addition, eosinophilic gastrointestinal disorders, particularly eosinophilic esophagitis, and food allergy, are also research fields of interest. Here, we review published data and clinical trials examining the use of dupilumab in these disorders.

Evaluation of tight waterflooding reservoirs with complex wettability by NMR data: A case study from Chang 6 and 8 members, Ordos Basin, NW China

After long-term water injection, many developed oilfields in the Ordos Basin, China, have entered a period of the high water-cut stage. In waterflooded layers, formation water is a mixture of injected water and primary formation water. The variation of formation water salinity will significantly affect the evaluation of reservoirs using resistivity logging curves while having little effect on the NMR response. It lays a foundation for identifying fluid type and evaluation of waterflooding grade by NMR logging. However, in waterflooding layers with mixed wettability, the NMR T2 responses are still complicated and unclear. In this paper, the tight sandstone samples with different wettability of Chang 6 and Chang 8 members of Triassic Yanchang Formation in the Ordos Basin are used to investigate the NMR experiments under three saturation states: water-saturated state, oil displacing to bound water state (abbreviated as oil flooding) and water flooding to the residual oil state (abbreviated as water flooding). Results show that the distributions of standard T2 spectra, without an external gradient magnetic field, of the water-saturated state in mix-wetted samples is very close to that of after oil flooding. Thus, the standard T2 spectra will be hard to distinguish the oil layer, water layer, and waterflooded layer of mix-wetted reservoirs. The diffusion coefficients of water and oil in pores differ, resulting in different shift T2 spectra results under gradient magnetic field. Therefore, the shift T2 spectra with the external gradient magnetic field and different echo time TEs were calculated and measured. When the echo time TE = 3.6 ms is adopted, the T2 signal of water-saturated tight rock samples will be nearly distributed less than 100 ms with magnetic field gradient G = 18 G/cm, rather the T2 signal greater than 100 ms is the oil signal. This characteristic makes the shift T2 spectra outstanding in the fluid identification of tight reservoirs with complex wettability. Finally, based on this experiment, a residual oil index based on the shift T2 spectrum is constructed to evaluate the flooded grades of tight waterflooding reservoirs. The evaluation results are consistent with the core description and oil test results in the study infilled wells.

Structural and functional state of blood lymphocytes in patients with infectious mononucleosis with different course

The article presents the results of our own studies. The aim was to determine the structural and functional status of blood lymphocytes in patients with acute and prolonged course of infectious mononucleosis (IM) in children. Materials and methods. 102 children were under clinical and laboratory-instrumental supervision, the children were divided into groups: group 1 – 65 children with IM with an acute course of the disease; group 2 – 37 children with a prolonged course of the disease. All children underwent standard clinical laboratory and instrumental laboratory examinations. The diagnosis of IM was confirmed by PCR (detection of EBV DNA in the blood) and ELISA (anti-EBV IgM and IgG). Research results. In the study of the structural state of the cytoplasmic membrane of the lymphocytes in the blood of patients with MI in the onset of the disease, it was found that the average values of penetration rate of the electron paramagnetic resonance of spin probes (PR EPR s. p.) in children of both groups were significantly higher than normal (P &lt; 0.001). There are also differences between groups of patients. In this case, the value of PR EPR s. p. in patients with a prolonged course by 15.8 % exceeded those in patients with acute IM (P &lt; 0.001). According to the rate of microviscosity of the intracellular content (MV IC), its values were reduced compared with the control – by 22.1 % (P &lt; 0.001) in patients with acute course of the disease and by 25.1 % – with a prolonged course of IM). In addition, in patients with a prolonged course of the disease, the values were 9 % lower than in the group with acute infectious mononucleosis. When considering immunological parameters, it was found that the indicators of the T-immune system for patients with a prolonged course of the disease in comparison with the alternative group was characterized by a decrease in the content of CD3 &lt;50 % (respectively in 51.3 % and 26.2 % of patients; P &lt; 0.05); CD4 &lt;31 % (62.1 % and 32.4 %, respectively; P &lt; 0.05) and CD8 &lt;15 % (37.8 % and 10.8 %, respectively; P &lt; 0.01). With regard to the cytokine profile, the level of IL-1 &lt;20.0 pg/ml was determined 3.5 times more often in patients with a prolonged course of the disease compared to the acute course (64.8 % and 18.5 % of patients, respectively); TNFα &lt;20.0 pg/ml 1.9 times more often (48.6 % and 24.6 %, respectively) and a very high (&gt;30.1 pg/ml) level of IL4 in 40.5 % and 20 %). From the B-system of immunity in patients with a prolonged course of IM in comparison with the acute course increased content of CD22 was more often determined, as well as low levels of IgA, IgM &lt;1.1 g/l and IgG &lt;10.0 g/l. Conclusions. According to the results of observations, the pathogenetic role of the violation of the structural organization of blood lymphocytes in the formation of IM is established. It was found that these disorders in the form of increased permeability of their cytoplasmic membrane and reduced viscoelastic properties of their intracellular environment are more pronounced with a prolonged course of the disease, which is a factor in the prolongation of the disease. It is determined that the indicators of cellular and humoral parts of the immune system affect the course of IM. During formation of an acute course of IM in children already in the acute period of a disease activation of both cellular and humoral links of immunity, which is shown in the form of increase in relative content of CD3+, CD4+, CD8+ and CD22+ and levels of immunoglobulins M, A, is noted. For the prolonged course of the disease depression of T-cell immunity in the form of a decrease in the relative content of CD3+, CD4+ and CD8+ lymphocytes and an increase in CD22+, as well as inhibition of antibody genesis are characteristic. It was found that the variant of IM depends on the type of reaction of T-helper clones, namely – in the initial period of manifestation of IM with its acute course there is activation of T1 and T2 helper response, which manifests itself in a significant increase in IL-1, TNFα and moderate IL-4. Prolonged course of the disease is formed against the background of weak activation of pro-inflammatory interleukins (IL-1, TNFα) and significant – anti-inflammatory IL-4.

Acceptability and appropriateness of a clinical pathway for managing anxiety and depression in cancer patients: a mixed methods study of staff perspectives

BackgroundClinical pathways (CPs) can improve health outcomes, but to be sustainable, must be deemed acceptable and appropriate by staff. A CP for screening and management of anxiety and depression in cancer patients (the ADAPT CP) was implemented in 12 Australian oncology services for 12 months, within a cluster randomised controlled trial of core versus enhanced implementation strategies. This paper compares staff-perceived acceptability and appropriateness of the ADAPT CP across study arms.MethodsMulti-disciplinary lead teams at each service tailored, planned, championed and implemented the CP. Staff at participating services, purposively selected for diversity, completed a survey and participated in an interview prior to implementation (T0), and at midpoint (6 months: T1) and end (12 months: T2) of implementation. Interviews were recorded, transcribed and thematically analysed.ResultsSeven metropolitan and 5 regional services participated. Questionnaires were completed by 106, 58 and 57 staff at T0, T1 and T2 respectively. Eighty-eight staff consented to be interviewed at T0, with 89 and 76 at T1 and T2 (response rates 70%, 66% and 57%, respectively). Acceptability/appropriateness, on the quantitative measure, was high at T0 (mean of 31/35) and remained at that level throughout the study, with no differences between staff from core versus enhanced services. Perceived burden was relatively low (mean of 11/20) with no change over time. Lowest scores and greatest variability pertained to perceived impact on workload, time and cost. Four major themes were identified: 1) Mental health is an important issue which ADAPT addresses; 2) ADAPT helps staff deliver best care, and reduces staff stress; 3) ADAPT is fit for purpose, for both cancer care services and patients; 4) ADAPT: a catalyst for change. Opposing viewpoints are outlined.ConclusionsThis study demonstrated high staff-perceived acceptability and appropriateness of the ADAPT CP with regards to its focus, evidence-base, utility to staff and patients, and ability to create change. However, concerns remained regarding burden on staff and time commitment. Strategies from a policy and managerial level will likely be required to overcome the latter issues.Trial registrationThe study was registered prospectively with the ANZCTR on 22/3/2017. Trial ID ACTRN12617000411347. https://www.anzctr.org.au/.