Six-month therapy of CGRP monoclonal antibodies in real-world clinical practice: an interim analysis of efficacy and safety data

Introduction. Migraine is one of the most common disabling neurological disorders. Recently developed monoclonal antibodies to calcitonin gene-related peptide (CGRP) or its receptor are the first targeted medication for preventive therapy of both episodic and chronic migraine. They have been thoroughly investigated in clinical trials; however, there is little data from real-world clinical practice available to date. The aim of this study is to assess the efficacy and safety of 6 months of treatment with erenumab in real-world clinical practice and investigate the effect of the drug on the patients’ sensitivity to medicines for migraine headaches relief and patient satisfaction after treatment.Materials and methods. Our observational cohort prospective study included patients in our Headache Clinic prescribed monoclonal antibodies blocking the  CGRP-receptor  – erenumab. During the  investigation, we evaluated the  previous preventive therapy and its efficacy, the number of days with migraine per month, adverse events occurring during the erenumab treatment, depression and anxiety (HADS), migraine disability (MIDAS), the presence of allodynia (ACS-12) and improved response to acute therapy after treatment. A total of 42 patients participated in the study: 6 men, 36 women, the average age was 43.9 ± 12.2. Of them, 38 patients (90%) had chronic migraine. Thirty-two patients (76%) had previously been prescribed preventive therapy, which proved ineffective, and 10 patients (24%) had not once received any type of migraine prevention.Results. Among our patients, we identified 11 patients with resistant migraine and one patient with refractory migraine. During the study, two patients dropped out due to adverse events (constipation). Thirty patients continued the administration of erenumab 70 mg for at least six months. The average number of migraine days per month before treatment was 22.8, and after six months of treatment, it dropped to 7.3. Twenty-nine patients (72.5%) also noted that the response to acute headache treatment improved after the therapy.Conclusion. The results of our study are consistent with the international experience of using erenumab and confirm its effectiveness for migraine preventive therapy, including difficult-to-treat migraine cases. However, further studies with more participants and evaluation of predictors of successful monoclonal antibody therapy are still needed

Overview of mathematical approaches used to model bacterial chemotaxis II: bacterial populations

We review the application of mathematical modeling to understanding the behavior of populations of chemotactic bacteria. The application of continuum mathematical models, in particular generalized Keller–Segel models, is discussed along with attempts to incorporate the microscale (individual) behavior on the macroscale, modeling the interaction between different species of bacteria, the interaction of bacteria with their environment, and methods used to obtain experimentally verified parameter values. We allude briefly to the role of modeling pattern formation in understanding collective behavior within bacterial populations. Various aspects of each model are discussed and areas for possible future research are postulated

Model-Based Deconvolution of Cell Cycle Time-Series Data Reveals Gene Expression Details at High Resolution

In both prokaryotic and eukaryotic cells, gene expression is regulated across the cell cycle to ensure “just-in-time” assembly of select cellular structures and molecular machines. However, present in all time-series gene expression measurements is variability that arises from both systematic error in the cell synchrony process and variance in the timing of cell division at the level of the single cell. Thus, gene or protein expression data collected from a population of synchronized cells is an inaccurate measure of what occurs in the average single-cell across a cell cycle. Here, we present a general computational method to extract “single-cell”-like information from population-level time-series expression data. This method removes the effects of 1) variance in growth rate and 2) variance in the physiological and developmental state of the cell. Moreover, this method represents an advance in the deconvolution of molecular expression data in its flexibility, minimal assumptions, and the use of a cross-validation analysis to determine the appropriate level of regularization. Applying our deconvolution algorithm to cell cycle gene expression data from the dimorphic bacterium Caulobacter crescentus, we recovered critical features of cell cycle regulation in essential genes, including ctrA and ftsZ, that were obscured in population-based measurements. In doing so, we highlight the problem with using population data alone to decipher cellular regulatory mechanisms and demonstrate how our deconvolution algorithm can be applied to produce a more realistic picture of temporal regulation in a cell

Adjusting Phenotypes by Noise Control

Genetically identical cells can show phenotypic variability. This is often caused by stochastic events that originate from randomness in biochemical processes involving in gene expression and other extrinsic cellular processes. From an engineering perspective, there have been efforts focused on theory and experiments to control noise levels by perturbing and replacing gene network components. However, systematic methods for noise control are lacking mainly due to the intractable mathematical structure of noise propagation through reaction networks. Here, we provide a numerical analysis method by quantifying the parametric sensitivity of noise characteristics at the level of the linear noise approximation. Our analysis is readily applicable to various types of noise control and to different types of system; for example, we can orthogonally control the mean and noise levels and can control system dynamics such as noisy oscillations. As an illustration we applied our method to HIV and yeast gene expression systems and metabolic networks. The oscillatory signal control was applied to p53 oscillations from DNA damage. Furthermore, we showed that the efficiency of orthogonal control can be enhanced by applying extrinsic noise and feedback. Our noise control analysis can be applied to any stochastic model belonging to continuous time Markovian systems such as biological and chemical reaction systems, and even computer and social networks. We anticipate the proposed analysis to be a useful tool for designing and controlling synthetic gene networks

Cellular anatomy of the mouse primary motor cortex.

An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted1. Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based anatomical description of one exemplar brain structure, the mouse primary motor cortex, upper limb area (MOp-ul). Using genetic and viral labelling, barcoded anatomy resolved by sequencing, single-neuron reconstruction, whole-brain imaging and cloud-based neuroinformatics tools, we delineated the MOp-ul in 3D and refined its sublaminar organization. We defined around two dozen projection neuron types in the MOp-ul and derived an input-output wiring diagram, which will facilitate future analyses of motor control circuitry across molecular, cellular and system levels. This work provides a roadmap towards a comprehensive cellular-resolution description of mammalian brain architecture

Dabigatran experience in primary and secondary prevention of cardioembolic stroke

The review of novel oral anticoagulants (dabigatran, rivaroxaban and apixaban) in stroke prevention and also own data of administration of dabigatran in primary and secondary prevention of ischemic stroke in 45 patients with cerebrovascular diseases are presented. Most patients received dabigatran 14 days after the first stroke associated with nonvalvular atrial fibrillation. In other cases dabigatran was used for primary prevention of stroke in patients with chronic forms of cerebrovascular diseases and nonvalvular atrial fibrillation. Dabigatran shows good tolerability and efficacy. Recurrent strokes were diagnosed in 2 patients. The reasons for these events were arterial hypertension in one case and symptomatic atherosclerotic plaque in the other case

ENDOVASCULAR METHODS FOR CLOSURE OF THE LEFT ATRIAL APPENDAGE IN PATIENTS WITH NONVALVULAR ATRIAL FIBRILLATION FOR STROKE PREVENTION

The paper presents an update on endovascular methods for closure of the left atrial appendage in order to prevent thromboembolic events in patients with nonvalvular atrial fibrillation. It analyzes the results of occlusion devices as an alternative to longterm anticoagulant therapy from the standpoint of evidencebased medicine, advantages, and features of design and implantation of occlusion devices, such as Watchman, Amplatzer, WaveCrest, and Lariat system. Literature searching was carried out using the databases PubMed and Scopus

Hepatic Epithelioid Hemangioendothelioma

The paper gives a clinical example of diagnosing hepatic epithelioid hemangioendothelioma. With allowance made for that the tumor occurs rarely (less than 1% of cases of all vascular tumors), the authors provide the clinical example to demonstrate the capabilities of imaging techniques, by applying an integrated approach

ACTH-PRODUCING PERIPHERAL PULMONARY CARCINOID

The paper describes a clinical example of the topical diagnosis of adrenocorticotropic hormone (ACTH)-producing typical peripheral pulmonary carcinoid. The first stage in its diagnosis was to rule out the production of ACTH by the pituitary gland. The paper presents information on the most common localization of functioning neuroendocrine tumors, as well as a diagnostic algorithm to search for an ectopic focus of the ACTH-secreting tumor that causes hypercorticism. Taking into account that bronchopulmonary neuroendocrine tumors with ectopic hormone production occur rarely (5%), a clinical example is given to demonstrate the capabilities of imaging techniques and standards for their implementation using an integrated approach

The evaluation of immunological state of patient with stage II-III non-small cell cancer of the lung treated by immunomodulator galavit

The article presents the results of a clinicoimmunological examination of 61 patients with stage II-III non-small cell cancer of the lung. It has been shown that in the presence of immunomodulating therapy all links of the immunity are being recovered