Setting thresholds for potentially toxic chemicals migrating from medical devices

Summary Introduction. As part of ensuring the safety of medical devices, the formation of a list of priority substances that are part of medical devices and pose an increased danger, is a necessary step that precedes the procedure for establishing permissible levels of toxic components from medical devices entering the human body during their use. The aim of the study is to analyze the components of medical devices and data on the toxicity of potentially hazardous substances, followed by the formation of a list of substances hazardous to health. Materials and methods. Analytical studies were carried out on the formation of a list of priority substances that are part of medical devices, as well as on the properties of these components hazardous to health. Results. For the first time, a toxicological dossier of chemicals was formed taking into account the available information on the quantitative characteristics of carcinogenic and non-carcinogenic risks, a list of substances was developed to establish acceptable levels of entry into the human body when using medical devices. Conclusion. The toxicological dossiers formed within the framework of these studies on the list of substances dangerous to health, in the future, will allow to scientifically substantiate the choice of relevant toxicity indicators and uncertainty factors to establish acceptable levels of intake into the human body when using medical devices

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Population genetic structure and mating system in the hybrid zone between Pinus sibirica Du Tour and P. pumila (Pall.) Regel at the Eastern Baikal Lake shore

<span style="font-family: Arial,Helvetica,sans-serif; font-size: small;">Genetic structure of sympatric Pinus sibirica Du Tour and P. pumila (Pall.) Regel populations and putative interspecific hybrids between them was analyzed in the Baikal Lake region (Barguzin Biosphere Natural Reserve, Davsha River basin) by means of 31 allozyme loci controlling 18 enzyme systems. Several alleles at loci Adh-1, Fest-2, Lap-3, Pgi-1, Sod-3 and Skdh-1 were diagnostic for P. sibirica, while alleles typical for P. pumila were detected at loci Gdh, Got-3, Lap-3, Mdh-2, Mdh-4, Pepca, Pgi-1, Pgd-2, Pgd-3, Pgm-1 and Pgm-2. All hybrids were heterozygous for the diagnostic Skdh-2 locus. Classification into hybrids and parental species using PCA analysis of multilocus allozyme genotypes had good correspondence with diagnoses made by morphological and anatomical analyses. Approximately 27% of embryos in P. pumila seeds had P. sibirica paternal contribution, and 8% of haplotypes in effective pollen pool combined alleles typical for P. pumila and P. sibirica, and therefore were classified as pollinated by the hybrids. About 83% of embryos in seeds from the hybrids most likely originated from fertilization by P. sibirica pollen, 14% from P. pumila and 3% from hybrid trees. This result favours the view that hybrids make both male and female contributions to the reproductive output of the population and confirm the presence of backcrosses and F2 hybrids.</span

Start of reproduction and allozyme heterozygosity in Pinus sibirica under different techniques of artificial forest stand establishment

<p>Siberian stone pine (Pinus sibirica Du Tour) is one of the main forest-forming tree species in boreal forests of Eurasia. Large edible<br />seeds of this species have an important resource value because of their high nutritious properties. Development of approaches to<br />establishment of early cone producing Siberian stone pine stands including utilization of corresponding genetic background is one of the priorities of forest resource management. The goal of our study was to evaluate the effect of stand density on the differentiation of trees by<br />the age of first reproduction and the relationship of allozyme heterozygosity and morphological traits variability in Siberian stone pine.<br />Morphological and allozyme variability in artificial Pinus sibirica stands with high and low density was investigated. In the high-density<br />stand the distance between trees was 0.7 and 3 meters (4080 trees per ha) while in the lowdensity stand it was 8 and 8 meters (144 trees<br />per ha). Age of formation of first male and female cones was evaluated by retrospective method based on analysis of tracks of cones on<br />a shoot bark. Tree height, diameter and number of male, female and vegetative shoots in a crown of model trees were measured.<br />Genotypes of the trees were determined by 29 isozyme loci coding for 16 enzymes (ADH, FDH, FEST, GDH, GOT, IDH, LAP, MDH, MNR, PEPCA, 6-PGD, PGI, PGM, SDH, SKDH, SOD). In the low-density stand, the portion of generative trees was higher and differentiation of trees by age of reproduction starting was lower in spite of the smaller age of trees as compared to the high-density stand. In<br />both samples, the age of formation of first generative organs was related negatively with stem height, stem diameter and number of<br />female shoots. In the high-density stand, positive relation of age of first reproduction with total number of shoots and number of<br />male shoots was found. In both samples nonreproductive trees were less heterozygous at isozyme loci as compared to trees starting cone<br />production. Allozyme heterozygosity correlated positively with the age of first cone production in the high-density stand only. We<br />conclude that the degree of competition between trees due to different stand density determined age and timing of first reproduction<br />and development of tree crowns. The relationship of allozyme heterozygosity and the age of first reproduction was expressed more in the high-density stand of Siberian stone pine.</p

Эффективность и безопасность опиоидной терапии хронического болевого синдрома у пациентов с раком поджелудочной железы: клинико-патогенетические особенности

Aim. To study the influence of clinical and pathogenetic factors in patients with pancreatic cancer on the efficacy and safety of analgesic therapy of chronic pain syndrome. Materials and methods. Clinical features of formation of chronic pain syndrome predetermining the efficacy and safety of analgesic therapy were studied in 82 patients with pancreatic cancer. Results. The efficacy and safety of opioids in the comparison groups of morphine sulfate, fentanyl TTC and oxycodone / naloxone in patients with pancreatic cancer was shown.Цель. Изучить влияние клинико - патогенетических факторов у пациентов с раком поджелудочной железы на эффективность и безопасность анальгетической терапии хронического болевого синдрома. Материалы и методы. У 82 пациентов с раком поджелудочной железы изучены клинические особенности формирования хронического болевого синдрома, предопределяющие эффективность и безопасность анальгетической терапии. Результаты. Показана эффективность и безопасность опиоидов в группах сравнения морфина сульфата, фентанила ТТС и оксикодона / налоксона у пациентов с раком поджелудочной железы