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How air masses transform during meridional transport into and out of the Arctic is not well represented by numerical models. The airborne field campaign HALO-(𝒜𝒞)3 applied the High Altitude and Long-range Research Aircraft (HALO) within the framework of the collaborative research project on Arctic amplification (𝒜𝒞)3 to address this question by providing a comprehensive observational basis. The campaign took place from 7 March to 12 April 2022 in the North Atlantic sector of the Arctic, a main gateway of atmospheric transport into and out of the Arctic. Here, we investigate to which degree the meteorological and sea ice conditions during the campaign align with the long-term climatology (1979–2022). For this purpose, we use the European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis v5 (ERA5), satellite data, and measurements at Ny-Ålesund, including atmospheric soundings. The observations and reanalysis data revealed two distinct periods with different weather conditions during HALO-(𝒜𝒞)3: the campaign started with a warm period (11–20 March 2022) where strong southerly winds prevailed that caused poleward transport of warm and moist air masses, so-called moist and warm air intrusions (WAIs). Two WAI events were identified as atmospheric rivers (ARs), which are narrow bands of strong moisture transport. These warm and moist air masses caused the highest measured 2 m temperatures (5.5 °C) and daily precipitation rates (42 mm d−1) at Ny-Ålesund for March since the beginning of the record (1993). Over the sea ice northwest of Svalbard, ERA5 indicated record-breaking rainfall. After the passage of a strong cyclone on 21 March 2022, a cold period followed. Northerly winds advected cold air into the Fram Strait, causing marine cold air outbreaks (MCAOs) until the end of the campaign. This second phase included one of the longest MCAO events found in the ERA5 record (19 d). On average, the entire campaign period was warmer than the climatological mean due to the strong influence of the ARs. In the Fram Strait, the sea ice concentration was well within the climatological variability over the entire campaign duration. However, during the warm period, a large polynya opened northeast of Svalbard, untypical for this season. Compared to previous airborne field campaigns focusing on the evolution of (mixed-phase) clouds, a larger variety of MCAO conditions was observed during HALO-(𝒜𝒞)3. In summary, air mass transport into and out of the Arctic was more pronounced than usual, providing exciting prospects for studying air mass transformation using HALO-(𝒜𝒞)3.

In this study, we analyse the contribution of atmospheric rivers (ARs), cyclones, and fronts to the total precipitation in the Arctic. We focus on two distinct periods of different weather conditions from two airborne campaigns: ACLOUD (Arctic Cloud Observations Using airborne measurements during polar day; May/June 2017) and AFLUX (Aircraft campaign Arctic Boundary Layer Fluxes; March/April 2019). Both campaigns covered the northern North Atlantic sector, the area in the Arctic that is affected by the highest precipitation rates. Using ERA5 reanalysis, we identify pronounced regional anomalies with enhanced precipitation rates compared to the climatology during ACLOUD due to these weather systems, whereas during AFLUX enhanced precipitation rates occur over most of the area. We have established a new methodology that allows us to analyse the contribution of ARs, cyclones, and fronts to precipitation rates based on ERA5 reanalysis and different detection algorithms. Here, we distinguish whether these systems occur co-located or separately. The contributions differ between the two periods. During ACLOUD (early summer), the precipitation rates are mainly associated with AR- (40 %) and front-related (55 %) components, especially if they are connected, while cyclone-related components (22 %) play a minor role. However, during AFLUX (early spring) the precipitation is mainly associated with cyclone-related components (62 %). For both campaign periods, snow is the dominant form of precipitation, and the small rain occurrence is almost all associated with ARs. About one-third of the precipitation can not be attributed to one of the weather systems, the so-called residual. While the residual can be found more frequently as convective than as large-scale precipitation, the rare occasion of convective precipitation (roughly 20 %) can not completely explain the residual. The fraction of precipitation classified as residual is reduced significantly when a precipitation threshold is applied that is often used to eliminate “artificial” precipitation. However, a threshold of 0.1 mm h−1 reduces the total accumulated precipitation by a factor of 2 (ACLOUD) and 3 (AFLUX), especially affecting light precipitation over the Arctic Ocean. We also show the dependence of the results on the choice of the detection algorithm serving as a first estimate of the uncertainty. In the future, we aim to apply the methodology to the full ERA5 record to investigate whether the differences found between the campaign periods are typical for the different seasons in which they were performed and whether any trends in precipitation associated with these weather systems can be identified.

In this study, we investigate how the regional climate model HIRHAM5 reproduces the spatial and temporal distribution of Arctic snowfall when compared to CloudSat satellite observations during the examined period of 2007–2010. For this purpose, both approaches, i.e., the assessments of the surface snowfall rate (observation-to-model) and the radar reflectivity factor profiles (model-to-observation), are carried out considering spatial and temporal sampling differences. The HIRHAM5 model, which is constrained in its synoptic representation by nudging to ERA-Interim, represents the snowfall in the Arctic region well in comparison to CloudSat products. The spatial distribution of the snowfall patterns is similar in both identifying the southeastern coast of Greenland and the North Atlantic corridor as regions gaining more than twice as much snowfall as the Arctic average, defined here for latitudes between 66 and 81∘ N. Excellent agreement (difference less than 1 %) in the Arctic-averaged annual snowfall rate between HIRHAM5 and CloudSat is found, whereas ERA-Interim reanalysis shows an underestimation of 45 % and significant deficits in the representation of the snowfall rate distribution. From the spatial analysis, it can be seen that the largest differences in the mean annual snowfall rates are an overestimation near the coastlines of Greenland and other regions with large orographic variations as well as an underestimation in the northern North Atlantic Ocean. To a large extent, the differences can be explained by clutter contamination, blind zone or higher resolution of CloudSat measurements, but clearly HIRHAM5 overestimates the orographic-driven precipitation. The underestimation of HIRHAM5 within the North Atlantic corridor south of Svalbard is likely connected to a poor description of the marine cold air outbreaks which could be identified by separating snowfall into different circulation weather type regimes. By simulating the radar reflectivity factor profiles from HIRHAM5 utilizing the Passive and Active Microwave TRAnsfer (PAMTRA) forward-modeling operator, the contribution of individual hydrometeor types can be assessed. Looking at a latitude band at 72–73∘ N, snow can be identified as the hydrometeor type dominating radar reflectivity factor values across all seasons. The largest differences between the observed and simulated reflectivity factor values are related to the contribution of cloud ice particles, which is underestimated in the model, most likely due to the small sizes of the particles. The model-to-observation approach offers a promising diagnostic when improving cloud schemes, as illustrated by comparison of different schemes available for HIRHAM5.

The Arctic is warming faster than the global average and any other region of a similar size. One important factor in this is the poleward atmospheric transport of heat and moisture, which contributes directly to the surface and air warming. In this case study, the atmospheric circulation and spatio-temporal structure of a moisture intrusion event is assessed, which occurred from 5 to 7 June 2017 over the Nordic seas during an intensive measurement campaign over Svalbard. This analysis focuses on high-spatial-resolution simulations with the ICON (ICOsahedral Non-hydrostatic) model which is put in context with coarser-resolution runs as well the ERA5 reanalysis. A variety of observations including passive microwave satellite measurements is used for evaluation. The global operational ICON forecasts from the Deutscher Wetterdienst (DWD) at 13 km horizontal resolution are used to drive high-resolution Limited-Area Mode (LAM) ICON simulations over the Arctic with 6 and 3 km horizontal resolutions. The results show the skilful capacity of the ICON-LAM model to represent the observed spatio-temporal structure of the selected moisture intrusion event and its signature in the temperature, humidity and wind profiles, and surface radiation. In several aspects, the high-resolution simulations offer a higher accuracy than the global simulations and the ERA5 reanalysis when evaluated against observations. One feature where the high-resolution simulations demonstrated an advanced skill is the representation of the changing vertical structure of specific humidity and wind associated with the moisture intrusion passing Ny-Ålesund (western Svalbard); the humidity increase at 1–2 km height topped by a dry layer and the development of a low-level wind jet are best represented by the 3 km simulation. The study also demonstrates that such moisture intrusions can have a strong impact on the radiative and turbulent heat fluxes at the surface. A drastic decrease in downward shortwave radiation by ca. 500 W m−2 as well as an increase in downward longwave radiation by ca. 100 W m−2 within 3 h have been determined. These results highlight the importance of both moisture and clouds associated with this event for the surface energy budget.

The Southern Ocean is a critical component of Earth's climate system, but its remoteness makes it challenging to develop a holistic understanding of its processes from the small scale to the large scale. As a result, our knowledge of this vast region remains largely incomplete. The Antarctic Circumnavigation Expedition (ACE, austral summer 2016/2017) surveyed a large number of variables describing the state of the ocean and the atmosphere, the freshwater cycle, atmospheric chemistry, and ocean biogeochemistry and microbiology. This circumpolar cruise included visits to 12 remote islands, the marginal ice zone, and the Antarctic coast. Here, we use 111 of the observed variables to study the latitudinal gradients, seasonality, shorter-term variations, geographic setting of environmental processes, and interactions between them over the duration of 90 d. To reduce the dimensionality and complexity of the dataset and make the relations between variables interpretable we applied an unsupervised machine learning method, the sparse principal component analysis (sPCA), which describes environmental processes through 14 latent variables. To derive a robust statistical perspective on these processes and to estimate the uncertainty in the sPCA decomposition, we have developed a bootstrap approach. Our results provide a proof of concept that sPCA with uncertainty analysis is able to identify temporal patterns from diurnal to seasonal cycles, as well as geographical gradients and “hotspots” of interaction between environmental compartments. While confirming many well known processes, our analysis provides novel insights into the Southern Ocean water cycle (freshwater fluxes), trace gases (interplay between seasonality, sources, and sinks), and microbial communities (nutrient limitation and island mass effects at the largest scale ever reported). More specifically, we identify the important role of the oceanic circulations, frontal zones, and islands in shaping the nutrient availability that controls biological community composition and productivity; the fact that sea ice controls sea water salinity, dampens the wave field, and is associated with increased phytoplankton growth and net community productivity possibly due to iron fertilisation and reduced light limitation; and the clear regional patterns of aerosol characteristics that have emerged, stressing the role of the sea state, atmospheric chemical processing, and source processes near hotspots for the availability of cloud condensation nuclei and hence cloud formation. A set of key variables and their combinations, such as the difference between the air and sea surface temperature, atmospheric pressure, sea surface height, geostrophic currents, upper-ocean layer light intensity, surface wind speed and relative humidity played an important role in our analysis, highlighting the necessity for Earth system models to represent them adequately. In conclusion, our study highlights the use of sPCA to identify key ocean–atmosphere interactions across physical, chemical, and biological processes and their associated spatio-temporal scales. It thereby fills an important gap between simple correlation analyses and complex Earth system models. The sPCA processing code is available as open-access from the following link: https://renkulab.io/gitlab/ACE-ASAID/spca-decomposition (last access: 29 March 2021). As we show here, it can be used for an exploration of environmental data that is less prone to cognitive biases (and confirmation biases in particular) compared to traditional regression analysis that might be affected by the underlying research question.

Water vapor is an important component in the water and energy cycle of the Arctic. Especially in light of Arctic amplification, changes in water vapor are of high interest but are difficult to observe due to the data sparsity of the region. The ACLOUD/PASCAL campaigns performed in May/June 2017 in the Arctic North Atlantic sector offers the opportunity to investigate the quality of various satellite and reanalysis products. Compared to reference measurements at R/V Polarstern frozen into the ice (around 82∘ N, 10∘ E) and at Ny-Ålesund, the integrated water vapor (IWV) from Infrared Atmospheric Sounding Interferometer (IASI) L2PPFv6 shows the best performance among all satellite products. Using all radiosonde stations within the region indicates some differences that might relate to different radiosonde types used. Atmospheric river events can cause rapid IWV changes by more than a factor of 2 in the Arctic. Despite the relatively dense sampling by polar-orbiting satellites, daily means can deviate by up to 50 % due to strong spatio-temporal IWV variability. For monthly mean values, this weather-induced variability cancels out, but systematic differences dominate, which particularly appear over different surface types, e.g., ocean and sea ice. In the data-sparse central Arctic north of 84∘ N, strong differences of 30 % in IWV monthly means between satellite products occur in the month of June, which likely result from the difficulties in considering the complex and changing surface characteristics of the melting ice within the retrieval algorithms. There is hope that the detailed surface characterization performed as part of the recently finished Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) will foster the improvement of future retrieval algorithms.

Investigating precipitation phase transitions is crucial for improving our understanding of precipitation formation processes and impacts, particularly in Polar Regions. This study uses observational data and numerical modelling to investigate precipitation phase transitions in the western and northern Antarctic Peninsula (AP) during austral summer. The analysis is based on the ERA5 reanalysis product, dynamically downscaled using the Polar-WRF (Polar Weather Research and Forecasting) model, evaluated using regular meteorological observations and additional measurements made during the Year of Polar Prediction special observing period. We analyse three cases of extra-tropical cyclones bringing precipitation with phase transitions, observed at the Chilean station Professor Julio Escudero (King George Island, north of the AP) and the Ukrainian Antarctic Akademik Vernadsky station (western side of the AP) during the first week of December 2018. We use observed and modelled near-surface air temperature and pressure, precipitation amount and type, and vertical temperature profiles. Our results show that precipitation type (snow or rain) is well-represented by ERA5 and Polar-WRF, but both overestimate the total amount of precipitation. The ERA5 daily variability and vertical air temperature profile are close to the observed, while Polar-WRF underestimates temperature in the lower troposphere. However, ERA5 underestimates the temperature inversion, which is present during the atmospheric river event, while Polar-WRF represents that inversion well. The average weekly temperature, simulated with Polar-WRF, is lower compared to ERA5. The Polar-WRF fraction of snow in the total precipitation amount is higher than for ERA5; nevertheless, Polar-WRF represents the precipitation phase transition better than ERA5 during the event, associated with an atmospheric river. These case studies demonstrated a relationship between specific synoptic conditions and precipitation phase transitions at the AP, evaluated the ability of the state-of-the-art reanalysis and regional climate model to represent these events, and demonstrated the added value of combined analysis of observations from the western and northern AP, particularly for characterizing precipitation during synoptic events affecting the entire AP.

Meridional atmospheric transport is an important process in the climate system and has implications for the availability of heat and moisture at high latitudes. Near-surface cold and warm temperature advection over the ocean in the context of extratropical cyclones additionally leads to important air–sea exchange. In this paper, we investigate the impact of these air–sea fluxes on the stable water isotope (SWI) composition of water vapour in the Southern Ocean's atmospheric boundary layer. SWIs serve as a tool to trace phase change processes involved in the atmospheric water cycle and, thus, provide important insight into moist atmospheric processes associated with extratropical cyclones. Here we combine a 3-month ship-based SWI measurement data set around Antarctica with a series of regional high-resolution numerical model simulations from the isotope-enabled numerical weather prediction model COSMOiso. We objectively identify atmospheric cold and warm temperature advection associated with the cold and warm sector of extratropical cyclones, respectively, based on the air–sea temperature difference applied to the measurement and the simulation data sets. A Lagrangian composite analysis of temperature advection based on the COSMOiso simulation data is compiled to identify the main processes affecting the observed variability of the isotopic signal in marine boundary layer water vapour in the region from 35 to 70∘ S. This analysis shows that the cold and warm sectors of extratropical cyclones are associated with contrasting SWI signals. Specifically, the measurements show that the median values of δ18O and δ2H in the atmospheric water vapour are 3.8 ‰ and 27.9 ‰ higher during warm than during cold advection. The median value of the second-order isotope variable deuterium excess d, which can be used as a measure of non-equilibrium processes during phase changes, is 6.4 ‰ lower during warm than during cold advection. These characteristic isotope signals during cold and warm advection reflect the opposite air–sea fluxes associated with these large-scale transport events. The trajectory-based analysis reveals that the SWI signals in the cold sector are mainly shaped by ocean evaporation. In the warm sector, the air masses experience a net loss of moisture due to dew deposition as they are advected over the relatively colder ocean, which leads to the observed low d. We show that additionally the formation of clouds and precipitation in moist adiabatically ascending warm air parcels can decrease d in boundary layer water vapour. These findings illustrate the highly variable isotopic composition in water vapour due to contrasting air–sea interactions during cold and warm advection, respectively, induced by the circulation associated with extratropical cyclones. SWIs can thus potentially be useful as tracers for meridional air advection and other characteristics associated with the dynamics of the storm tracks over interannual timescales.

The Atmospheric River Tracking Method Intercomparison Project (ARTMIP) is an international collaborative effort to understand and quantify the uncertainties in atmospheric river (AR) science based on detection algorithm alone. Currently, there are many AR identification and tracking algorithms in the literature with a wide range of techniques and conclusions. ARTMIP strives to provide the community with information on different methodologies and provide guidance on the most appropriate algorithm for a given science question or region of interest. All ARTMIP participants will implement their detection algorithms on a specified common dataset for a defined period of time. The project is divided into two phases: Tier 1 will utilize the Modern-Era Retrospective analysis for Research and Applications, version 2 (MERRA-2) reanalysis from January 1980 to June 2017 and will be used as a baseline for all subsequent comparisons. Participation in Tier 1 is required. Tier 2 will be optional and include sensitivity studies designed around specific science questions, such as reanalysis uncertainty and climate change. High-resolution reanalysis and/or model output will be used wherever possible. Proposed metrics include AR frequency, duration, intensity, and precipitation attributable to ARs. Here, we present the ARTMIP experimental design, timeline, project requirements, and a brief description of the variety of methodologies in the current literature. We also present results from our 1-month proof-of-concept trial run designed to illustrate the utility and feasibility of the ARTMIP project.

Scientist relevance. Antibacterials can have nephrotoxic effects because medicinal products of this class are primarily excreted by the kidneys.Aim. The study aimed to analyse literature data on the mechanisms, risk factors and specific features of toxic nephropathy development during antibiotic therapy.Discussion. The article considers mechanisms of development of acute interstitial nephritis, acute tubular necrosis, crystal deposits in the tubules, proximal or distal tubulopathy with electrolyte abnormalities during the use of antibiotics. Nephrotoxicity was shown to be most often associated with the use of aminoglycosides, beta-lactams, and vancomycin. The authors analysed the dependence of nephrotoxicity on antibacterial agent lipophilicity and drug–drug interactions. The main risk factors for developing nephropathy are older age; male sex; black race; hypovolaemia; arterial hypotension; angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, non-steroidal anti-inflammatory drugs or their combinations; and individual genetic characteristics. Nephrotoxicity is associated with genetic characteristics of the systems responsible for metabolism and excretion of antibacterial products: cytochrome P450 isoenzymes, P-glycoprotein, multidrug resistance protein (MRP), multidrug and toxin extrusion (MATE), breast cancer resistance protein (BCRP), and organic anion transporters. Severe generalised infections change pharmacokinetic parameters of antibacterial products. This should be taken into account when prescribing the hydrophilic antibiotics that are excreted by tubular secretion and reabsorbed in the renal tubules.Conclusions. The study demonstrated the effectiveness of the method comprising a combination of dose adjustment based on therapeutic drug monitoring results and renal function monitoring for improving the safety of antibiotic therapy.

Nonsteroidal anti-inflammatory drugs, including acetylsalicylic acid, can have a dose-dependent nephrotoxic effect. The study of the pharmacokinetics of acetylsalicylic acid products will contribute to timely detection and correction of side effects caused by this medicinal product.The aim of the study was to evaluate potential nephrotoxic effects following a single oral administration of 75 mg of acetylsalicylic acid, based on the analysis of the pharmacokinetic parameters.Materials and methods: the study involved 24 healthy volunteers who received 75 mg of acetylsalicylic acid (tablets) once orally. The measurement of the active metabolite of acetylsalicylic acid—salicylic acid—in blood plasma was performed by HPLC/MS using an Agilent 1200 liquid chromatography system coupled to an Agilent 6140 tandem mass spectrometer. Agilent Eclipse XDB-C18 column (4.6 mm×150 mm; 5.0 μm) was used for chromatographic separation. The test procedure used in the study was validated. The results obtained were used to calculate the pharmacokinetic parameters: Cmax (maximum concentration), Tmax (time to maximum concentration), T1/2 (half-life of the drug), AUC0-t (area under the pharmacokinetic curve from 0 to the last time point of the curve), AUC0-∞ (total area under the pharmacokinetic curve from 0 to ∞), MRT (mean residence time of the drug in the blood), Kel (elimination rate constant), Cl/F (total clearance), Vd/F (apparent volume of distribution). The Statistics (22.0.0.0) software was used for statistical processing of the results.Results: T1/2 of salicylic acid in blood plasma was determined to be 1.6 ± 0.5 h, Cmax was 4523.0 ± 725.0 ng/mL, and Tmax was 0.98 ± 0.4 h. AUC0–t was equal to 16183.0 ± 3823.0 ng×h/m, Vd/F was 12.0 ± 3.1 L/kg, and MRT was 2.9 ± 0.6 h.Conclusions: the analysis of the pharmacokinetic parameters demonstrated a high absorption rate, intensive distribution, and moderate elimination rate of salicylic acid (the main metabolite of acetylsalicylic acid), indicating a low risk of nephrotoxic effects associated with the studied dose of the drug.

Widespread use of cephalosporin antibiotics in clinical practice calls for greater attention to the risk of adverse drug reactions. Information on serious or unexpected adverse events reported during post-marketing experience is submitted to national and international pharmacovigilance databases. Analysis of these reports helps to identify new adverse drug reactions.The aim of the study was to analyse the safety profile of cephalosporin antibiotics based on spontaneous reports in the international VigiBase database.Materials and methods: the analysis of the adverse reaction profile of cephalosporin antibiotics was based on MedDRA system organ classes and included spontaneous reports submitted to VigiBase from the moment of its creation until August 2020.Results: the authors identified the most clinically significant adverse reactions for different cephalosporin generations. They compared and analysed information on adverse events in VigiBase and in patient information leaflets of medicinal products authorised in the Russian Federation. It was demonstrated that some serious events described in VigiBase spontaneous reports for V-generation cephalosporins are not included in the “Side effects” section of the patient information leaflets. According to VigiBase, the use of ceftaroline was associated with the development of generalised exfoliative dermatitis, Stevens–Johnson syndrome, tubulointerstitial nephritis, while the use of ceftolozane was associated with acute kidney injury, renal insufficiency, sepsis, pneumonia, and respiratory insufficiency.Conclusion: reporting of unexpected and serious adverse drug reactions to cephalosporin antibiotics is an important task of healthcare practitioners. Availability of information on class-specific and generation-specific serious adverse reactions will help predict and prevent their development.

Current guidelines for the management of patients with dyslipidemia define low-density lipoprotein cholesterol (LDL-C) as the primary target in addressing lipid-lowering therapy. The target level of LDL-C in real clinical practice is achieved in no more than a third of patients who have undergone a coronary event and receive high-intensity lipid-lowering therapy. Achieving the goals of lipid-lowering therapy in a significant proportion of patients with atherosclerotic cardiovascular diseases (ACVD) is impossible with the use of even high doses of statins, which requires its enhancement by other drugs. The article considers the place of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in the prevention of cardiovascular diseases in patients with ACVD in accordance with the latest Russian and international guidelines. A modern decision-making algorithm for the initiation of PCSK9 inhibitors therapy in patients with ACVD is presented. The authors provide a clear understanding about the patient populations that will benefit most from the taking of PCSK9 inhibitors. Particular attention is paid to Guidelines for the management of dyslipidemias developed by European Society of Cardiology and European Atherosclerosis Society in 2019. The issues of patients provision with PCSK9 inhibitors with reference to Russian conditions are described in details in accordance with the requirements for territorial programs of state guarantees. Further improvement in the provision of PCSK9 inhibitors to patients with indications for this therapy is necessary, considering the potential of these drugs in reducing cardiovascular morbidity and mortality in patients with ACVD.

Modern tactics of treatment of arterial hypertension (AH) involves the use of both monotherapy and combination therapy. Monotherapy is recommended primarily for low-risk patients with systolic blood pressure (BP)< 150 mm Hg. Monotherapy should also be preferred in very high risk patients with high normal BP and frail elderly patients. However, combination therapy is recommended for most hypertensive patients as initial therapy. Starting combination therapy is more effective in lowering BP than monotherapy. Even at low doses, it is usually more effective than maximum dose monotherapy. The most commonly prescribed combinations today contain a renin-angiotensin system blocker (angiotensin converting enzyme inhibitors or angiotensin II receptor blocker) with a calcium antagonist or diuretic. The combination of lisinopril with amlodipine not only proved its high efficiency in various international and Russian studies, but also turned out to be pharmacoeconomically more profitable. Fixed combinations of lisinopril and amlodipine are the optimal choice in the treatment of hypertensive patients, due to all the advantages of both components: higher efficacy and safety rates compared to monotherapy and better patient adherence to treatment.

AIMS: Investigation of spontaneous and induced secretion of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and the anti-inflammatory chemokine C-C Motif Chemokine Ligand 18 (CCL18) by monocytes isolated from blood of patients with long-term type 2 diabetes mellitus (T2DM), both with or without foot ulcers and the effect of the course use of the combined metabolic drug Kokarnit as part of complex therapy on the dynamics of the severity of symptoms of DSPN and the cytokine phenotype in patients with long-term non-healing ulcers of the lower extremities MATERIALS AND METHODS: 121 patients with T2DM, 79 without diabetic foot syndrome (DFS) and 42 patients with DFS were included. CD14+ monocytes were isolated from patients’ blood and stimulated by interferon-γ (IFN-γ) and interleukine-4 (IL-4) for induction of pro- and anti-inflammatory monocyte activation, respectively. The concentrations of TNF-α and CCL18 in the culture medium were measured using ELISA on day 1 and day 6 after cell stimulation in all patients before taking the combined metabolic drug Kokarnit. Then they were randomly allocated either to the control group (57 people), to whom Kokarnit was added to standard treatment, or to the comparison group. After a 9-day course of application of Kokarnit, the dynamics of indicators was evaluated on a TSS scale. Assessment of cytokine status was carried out in 18 people with long-term non-healing ulcerative defects of the lower extremities, on the first and ninth day of treatment. RESULTS: A correlation was found between HbA1c and levels of stimulated secretion of TNFα (r=0.726, p=0.027), CCL18 (r=-0.949, p=0.051) in patients with DSPN. In all patients with different duration of VDS, an increase in secretion of TNF-α and CCL18 was observed (p

The article highlights modern concepts of inflammatory diseases in adults and children in terms of genetic possibilities for diagnosing Crohn's disease and ulcerative colitis. It names the main candidate genes, which, in the presence of their specific polymorphisms, indicate the occurrence of a high risk of inflammatory bowel disease. The principles of modern therapy, the possibilities of pharma-cogenetic testing in predicting the effectiveness or risks of reducing the safety of drug therapy are described. The article focuses on modern trends and perspectives in ulcerative colitis and Crohn's disease treatment.

This article looks into interchangeability and therapeutic equivalence of innovator and generic anticonvulsants — the first-generation and new antiepileptic drugs (AEDs). The results of a number of clinical trials assessing therapeutic equivalence of generic AEDs support the opinion that these medicines could only be substituted provided an ultra-cautious approach is used, even if the case involves only one International Nonproprietary Name, including, but not limited to different dosage forms of one and the same product. The aim of the study was to analyse factors leading to incorrect assessment of therapeutic equivalence of new and generic anticonvulsant drugs, and to improve methodological approaches to conducting clinical trials of these products. The paper cites data from Russian and foreign sources which state that the substitution of AEDs in some patients in full remission may result in adverse reactions or relapse of seizures. The analysis of the experience of scientific, expert, and regulatory institutions made it possible to develop a course of actions to be used when substituting AEDs and conducting clinical trials that assess therapeutic equivalence of new and generic anticonvulsants. The proposed methodology will help minimise potential health risks brought about by various factors that result in incorrect assessment of AEDs therapeutic equivalence and interchangeability.

The article presents a review of modern regulatory and legal framework and draft regulatory documents on circulation of interchangeable drugs with regard to standard instructions for medical use. The analysis included more than 70 documents. There are two slightly different notions in this field: a generic drug and an interchangeable drug. A generic drug is not necessarily an interchangeable drug. The interchangeability of a drug is determined during pre-marketing evaluation. Some differences concerning normative requirements to the content of standard instructions for interchangeable drugs have been observed when comparing the regulatory framework of Russia, CIS countries and the EU. It is necessary to look not only at bioequivalence as an equivalent of interchangeability, but also take into account characteristics of excipients, and therapeutic equivalence based on preclinical and clinical trial results. The analysis of differences in regulatory documents can form the basis for further harmonization of requirements to instructions for medical use of interchangeable drugs.

The Atmospheric River (AR) Tracking Method Intercomparison Project (ARTMIP) is a community effort to systematically assess how the uncertainties from AR detectors (ARDTs) impact our scientific understanding of ARs. This study describes the ARTMIP Tier 2 experimental design and initial results using the Coupled Model Intercomparison Project (CMIP) Phases 5 and 6 multi-model ensembles. We show that AR statistics from a given ARDT in CMIP5/6 historical simulations compare remarkably well with the MERRA-2 reanalysis. In CMIP5/6 future simulations, most ARDTs project a global increase in AR frequency, counts, and sizes, especially along the western coastlines of the Pacific and Atlantic oceans. We find that the choice of ARDT is the dominant contributor to the uncertainty in projected AR frequency when compared with model choice. These results imply that new projects investigating future changes in ARs should explicitly consider ARDT uncertainty as a core part of the experimental design., (© 2021. Battelle Memorial Institute. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: The US National Institutes of Health (NIH) and Centers for Medicare and Medicaid Services (CMS) sponsored a randomized clinical trial comparing six versus three times per week in-center hemodialysis (the Frequent Hemodialysis Network [FHN] Daily Trial), to test the effects of frequent hemodialysis on an array of intermediate outcomes. Herein we report challenges to enrollment and randomization into the trial., Methods: Screening and enrollment was tracked at all participating dialysis clinics and specific reasons for dropout after baseline assessment were recorded for all enrolled subjects. Reasons for consent refusal were recorded in a subset of (10 out of 65) sites., Results: The trial screened 6276 hemodialysis patients on three times weekly hemodialysis in 65 hemodialysis clinics, 3481 (55%) were considered eligible for enrollment, and 3124 (90%) were approached for consent; 378 (12%) consented and 245 were randomized (65% of those enrolled). Prospective subjects chose not to participate primarily because of the anticipated time required for three extra treatments per week and the difficulties in following the protocol., Conclusions: Recruitment into the FHN Daily Trial proved challenging but the goal of 250 randomized subjects was almost met.