Treatment of atopic dermatitis with upadacitinib: adcare single center experience.

Introduction: The role of upadacitinib in the management of moderate to severe atopic dermatitis seems promising, but more data on its efficacy and safety are needed. This study endeavors to assess the practical impact and safety of upadacitinib in patients with moderate to severe atopic dermatitis. The study aims to evaluate the efficacy and safety of upadacitinib in the treatment of moderate to severe atopic dermatitis, focusing on analyzing patient responses to the treatment.

[Efficacy of dupilumab in real practice in the treatment of severe forms of asthma and atopic dermatitis (comparative retrospective study)].

Background: Dupilumab, a fully human monoclonal antibody directed against the common α-subunit of interleukin (IL)-4 receptors and blocking signaling from both IL-4 and IL-13, may be recommended for the treatment of moderate to severe atopic dermatitis (AD) and bronchial asthma (BA).

Aim: To perform a comparative assessment of the effectiveness of maintenance therapy with dupilumab in patients with severe BA as the main indication for genetically engineered biological drugs and in patients with severe asthma with concomitant severe AD as the indication for targeted therapy.

Materials And Methods: A 6-month retrospective comparative study was performed at the specialized reference center for allergology and immunology.

[Pre-exposure prophylaxis of new COVID-19 coronavirus infection with tixagevimab/cilgavimab in adult Moscow patients with primary immunodeficiencies].

Background: Primary immunodeficiencies (PIDs), now known as inborn errors of immunity, are a group of inherited diseases caused by defects in the genes that control the immune response. Patients with PIDs have risks of developing a severe course and/or death in COVID-19. Passive immunization with long-acting monoclonal antibodies (MABs) to SARS-CoV-2 should be considered as pre-exposure prophylaxis in patients with PIDs.

Etiopathogenetic substantiation of surgical treatment of neurogenic pain syndromes.

The purpose of the study was to improve classification of neurogenic (neuropathic) pain syndromes. This will make it possible to define the indications for appropriate analgesic surgery for each type of drug-resistant neurogenic pain syndrome. Incorrect management of neurogenic pain syndromes is usually associated with underestimation of pathogenetic prerequisites for its occurrence.

[Analysis of predictors of response to anti-IgE therapy in patients with severe atopic bronchial asthma in real clinical practice].

Introduction: Guidelines on Biological Therapy for Bronchial Asthma of the European Academy of Allergy and Clinical Immunology (EAACI) identified a number of controversial issues for additional outcome analysis using randomized clinical trials and data from routine clinical practice. In particular, there is unmet need to clarify algorithms for prescribing biologicals using predictors of response and its timing, taking into account risk factors and multimorbidity. Omalizumab is a recombinant humanized monoclonal anti-IgE antibody of IgG1 class used for the treatment of severe refractory atopic bronchial asthma (BA) and a variety of IgE-mediated diseases.

SARS-CoV-2 evolution in a patient with secondary B-cell immunodeficiency: A clinical case.

The article highlights the course of long-term SARS-CoV-2 infection in a patient with a secondary immunodeficiency developed with B-cell-depleting therapy of the underlying disease. Analysis of the intrapatient virus evolution revealed an inpatient S:G75A mutation that alters the 72GTNGTKR78 motif of the S-protein, with a possible role in binding to alternative cellular receptors. Therapy with a ready-made COVID-19-globulin preparation (native human immunoglobulin G (IgG) derived from the plasma of convalescent COVID-19-patients) resulted in rapid improvement of the patient's condition, fast, and stable elimination of the virus, and passive immunization of the patient for at least 30 days.

Photoassisted access to complex polyheterocycles containing a β-lactam moiety.

Intramolecular cycloadditions of aza-o-xylylenes generated via excited state intramolecular proton transfer (ESIPT) to furanacetic acid-based unsaturated pendants was shown to overcome the unfavorable energetics of the azetidinone ring formation, offering rapid access to β-lactams as primary photoproducts. These 2,3- and 3,4-dihydrofuran-containing reactive intermediates are suitable for a broad spectrum of postphotochemical transformations yielding complex polyheterocyclic molecular architectures possessing the β-lactam moiety.

Photoinduced "Double Click" Cascade Offers Access to Complex Polyheterocycles from Readily Available Isatin-Based Photoprecursors.

The cascade photoassisted synthetic strategy for accessing complex N,O-polyheterocycles of unprecedented molecular architecture is developed. It is based on intramolecular cycloadditions of aza-o-xylylenes formed in situ via excited-state intramolecular proton transfer (ESIPT) of o-acylanilides. The photoprecursors are synthesized via a two-step one-pot method from readily available starting materials.

Photoassisted Synthesis of Complex Molecular Architectures: Dearomatization of Benzenoid Arenes with Aza-o-xylylenes via an Unprecedented [2+4] Reaction Topology.

A new method was developed for the photoinduced dearomatization of arenes through an intramolecular cycloaddition with aza-o-xylylenes generated by excited-state intramolecular proton transfer (ESIPT) in the readily available photoprecursors. The [2+4] topology of this cycloaddition is unprecedented for photo-dearomatizations of benzenoid aromatic carbocycles. It provides rapid access to novel heterocycles, cyclohexadieno-oxazolidino-quinolinols, as valuable synthons for a broad range of post-photochemical transformations.

Oxazolines as Dual-Function Traceless Chromophores and Chiral Auxiliaries: Enantioselective Photoassisted Synthesis of Polyheterocyclic Ketones.

2-(o-Amidophenyl)oxa- and -thiazolines undergo excited-state intramolecular proton transfer (ESIPT), generating aza-o-xylylenes capable of intramolecular [4+2] and [4+4] cycloadditions with tethered unsaturated pendants. Facile hydrolysis of the primary photoproducts, spiro-oxazolidines and thiazolidines, under mild conditions unmasks a phenone functionality. Variations in linkers allow for access to diverse core scaffolds in the primary photoproducts, rendering the approach compatible with the philosophy of diversity-oriented synthesis.

Relativistic Force Field: Parametrization of (13)C-(1)H Nuclear Spin-Spin Coupling Constants.

Previously, we reported a reliable DU8 method for natural bond orbital (NBO)-aided parametric scaling of Fermi contacts to achieve fast and accurate prediction of proton-proton spin-spin coupling constants (SSCC) in (1)H NMR. As sophisticated NMR experiments for precise measurements of carbon-proton SSCCs are becoming more user-friendly and broadly utilized by the organic chemistry community to guide and inform the process of structure determination of complex organic compounds, we have now developed a fast and accurate method for computing (13)C-(1)H SSCCs. Fermi contacts computed with the DU8 basis set are scaled using selected NBO parameters in conjunction with empirical scaling coefficients.

Conformationally Constrained Penta(hetero)cyclic Molecular Architectures via Photoassisted Diversity-Oriented Synthesis.

Intramolecular cycloadditions of photogenerated azaxylylenes provide access to unprecedented polyheterocyclic scaffolds, suitable for subsequent postphotochemical modifications to further grow molecular complexity. Here we explore approaches to rapid "assembly" of novel photoprecursors with nitrogen/oxygen-rich tethers capable of producing potential pharmacophores and also compatible with subsequent 1,3-dipolar cycloadditions to furnish pentacyclic heterocycles with new structural cores, minimal number of rotatable bonds, and a high content of sp hybridized carbons. The modular "assembly" of the photoprecursors and potential variety of postphotochemical modifications of primary photoproducts provide framework for combinatorial implementation of this synthetic strategy.

Amino Azaxylylenes Photogenerated from o-Amido Imines: Photoassisted Access to Complex Spiro-Poly-Heterocycles.

Upon irradiation, cyclic imines containing o-amido groups are shown to produce reactive intermediates, amino azaxylylenes, which undergo intramolecular cycloadditions to tethered unsaturated pendants to yield complex N,O-heterocycles having an additional spiro-connected nitrogen heterocyclic moiety. Modular assembly of the photoprecursors allows expeditious increase of the complexity of the target poly-heterocyclic scaffolds with a minimal number of experimentally simple reaction steps. The photocyclization and subsequent postphotochemical transformations are accompanied by an increase of Lovering's fsp3 factor, thus producing unprecedented three-dimensional molecular architectures, and offering extended sampling of chemical space.

Minimalist Relativistic Force Field: Prediction of Proton-Proton Coupling Constants in (1)H NMR Spectra Is Perfected with NBO Hybridization Parameters.

We previously developed a reliable method for multiparametric scaling of Fermi contacts to achieve fast and accurate prediction of proton-proton spin-spin coupling constants (SSCC) in (1)H NMR. We now report that utilization of NBO hybridization coefficients for carbon atoms in the involved C-H bonds allows for a significant simplification of this parametric scheme, requiring only four general types of SSCCs: geminal, vicinal, 1,3-, and long-range constants. The method is optimized for inexpensive B3LYP/6-31G(d) molecular geometries.

Photoinduced Cycloadditions in the Diversity-Oriented Synthesis Toolbox: Increasing Complexity with Straightforward Postphotochemical Modifications.

Rapid growth of complexity and unprecedented molecular architectures are realized via the excited-state intramolecular proton transfer (ESIPT) in -acylamidobenzaldehydes and ketones followed by [4+2] or [4+4] cycloadditions with subsequent postphotochemical modifications. The approach is congruent with Diversity-Oriented Synthesis: photoprecursors are synthesized in a modular fashion allowing for up to four diversity inputs. The complexity of the primary photoproducts is further enhanced using straightforward and high-yielding postphotochemical modification steps such as reactions with nitrile oxides, nitrones, Povarov reaction, and oxa-Diels-Alder reaction.

Photoassisted diversity-oriented synthesis: accessing 2,6-epoxyazocane (oxamorphan) cores.

The modular synthesis of photoprecursors and their photoinduced cyclization into substituted 1-benzazocanes of two distinct topologies is described. The key step producing an extended polyheterocyclic system involves the photogeneration of azaxylylenes and their subsequent intramolecular cycloaddition with furan-containing pendants tethered either via the aniline nitrogen or through the carbonyl group containing arm. The primary photoproducts-secondary or tertiary anilines which are not acylated at the nitrogen atom-undergo facile acid-catalyzed or spontaneous ring-opening-ring-closing rearrangement to yield fused polyheterocyclic structures possessing a 2,6-epoxyazocane (or oxamorphan) core.

Photoactive Spatial Proximity Probes for Binding Pairs with Epigenetic Marks.

A new strategy for encoding polypeptide libraries with photolabile tags is developed. The photoassisted assay, based on conditional release of encoding tags only from bound pairs, can differentiate between peptides which have minor differences in a form of post-translational modifications with epigenetic marks. The encoding strategy is fully compatible with automated peptide synthesis.

Relativistic force field: parametric computations of proton-proton coupling constants in (1)H NMR spectra.

Spin-spin coupling constants in (1)H NMR carry a wealth of structural information and offer a powerful tool for deciphering molecular structures. However, accurate ab initio or DFT calculations of spin-spin coupling constants have been very challenging and expensive. Scaling of (easy) Fermi contacts, fc, especially in the context of recent findings by Bally and Rablen (Bally, T.

Intramolecular photoassisted cycloadditions of azaxylylenes and postphotochemical capstone modifications via Suzuki coupling provide access to complex polyheterocyclic biaryls.

Modular preassembly of azaxylylene photoprecursors, halogen-substituted in the aromatic ring, their intramolecular [4 + 4] or [4 + 2] cycloadditions to tethered unsaturated pendants, and subsequent postphotochemical capstone modification of the primary photoproducts via Suzuki coupling provides rapid access to diverse biaryls of unprecedented topology. This synthetic sequence allows for rapid growth of molecular complexity and is well aligned with methodology of Diversity-Oriented Synthesis.

Photoassisted synthesis of enantiopure alkaloid mimics possessing unprecedented polyheterocyclic cores.

Enantiopure alkaloid mimics are synthesized via high yielding intramolecular cycloadditions of photogenerated azaxylylenes tethered to pyrroles, with further growth of molecular complexity via post-photochemical transformations of primary photoproducts. This expeditious access to structurally unprecedented polyheterocyclic cores is being developed in the context of diversity-oriented synthesis, as the modular design allows for rapid "pre-assembly" of diverse photoprecursors from simple building blocks/diversity inputs.

Photoassisted access to enantiopure conformationally locked ribofuranosylamines spiro-linked to oxazolidino-diketopiperazines.

N-Furoylated L-threonine-, serine-, or cysteine-based aminoacetals are coupled with o-aminoketones or aldehydes to offer rapid access to diverse enantiopure polyheterocycles possessing conformationally locked aminoglycoside-containing molecular scaffolds. The key step involves photogeneration of azaxylylenes which undergo [4 + 4] or [4 + 2] cycloadditions to the tethered furoyl pendants.

[Hypoglycemic activity of bicyclic diterpenoids of the clerodane series as compared to adebit and maninil].

Biocyclic diterpenoids--salvin, salvicin and salvifolin, administered per os to rats at a dose of 50 mg/kg show marked hypoglycemic activity in intact animals as well as in animals with experimental hyperglycemia developing against a background of GTT (3000 mg/kg intraperitoneally) or alloxan (150 mg/kg subcutaneously). They are superior to adebit but inferior to maninil. Prophylactic and therapeutic administration of these compounds ensure the preservation of islet beta-cells in animals with alloxan diabetes.