Long-term programme of biophysical monitoring of the personnel involved in the construction of the new safe confinement

The international Shelter Implementation Plan (SIP) foresees a step-by-step transformation of the Chornobyl site into the safe condition. The New Safe Confinement (NSC), is an unprecedented 108-meter tall structure over the destroyed Unit 4 of the Chernobyl Nuclear Power Plant, and is a central element of SIP. Many workers involved in SIP may have a direct contact with fragments of the irradiated fuel, fuel-containing aerosols, and other contaminated material at the Chornobyl industrial site. Isotopes of plutonium, americium, strontium, and cesium are dominating in internal exposure of SIP workers. The safety of workers is a high priority of SIP. Starting from 2004 the Ukrainian Radiation Protection Institute (RPI) is performing a large-scale Internal Dosimetry Program as an integral part of SIP. Pu contents in fecal and urine samples and the whole-body counters‟ (WBC) data and are the main source of the quantitative data used for the dose assessment. The RPI radiochemical laboratories in Kyiv and at the Chornobyl site employed the standard radiochemical technique and equipped with ninety six alpha-spectrometers. The range of WBCs includes the scanning low-background WBC, four Canberra FastScan WBCs, and four chair-type WBCs. The car-borne WBC is located in Kiev and reserved for the emergency purposes. As on September 2017 the Internal Dosimetry Program has covered more than 17 000 workers, which undergone 1 230 000 measurements of ¹³⁷Cs on WBCs, 87 000 measurements of ²³⁹⁺²⁴⁰Pu contents in fecal samples and 4 400 measurements of ²³⁹⁺²⁴⁰Pu contents in urine samples. Such a large-scale programme ensured a reliable monitoring of intakes of the insoluble radioactive material.У міжнародному Плані здійснення заходів (ПЗЗ) передбачається поетапне перетворення чорнобильського майданчика у безпечний стан. Новий безпечний конфайнмент є безпрецедентною структурою заввишки 108 м над зруйнованим 4-м блоком ЧАЕС, він є центральним елементом ПЗЗ. Багато працівників, залучених у ПЗЗ, можуть мати прямий контакт із фрагментами опроміненого палива, паливовмісними аерозолями та іншими забрудненими матеріалами на промисловому майданчику в Чорнобилі. Ізотопи плутонію, америцію, стронцію і цезію домінують у внутрішньому опроміненні працівників ПЗЗ. Безпека працівників має високий пріоритет у ПЗЗ. Починаючи з 2004 р., Науково-дослідний інститут радіаційного захисту АТН України (ІРЗ) здійснює великомасштабну програму дозиметрії внутрішнього опромінення як невід‟ємну частину ПЗЗ. Дані вмісту плутонію у пробах калу і сечі та лічильників випромінювань людини (ЛВЛ) і основним джерелом кількісних даних, що використовуються для оцінки дози. Радіохімічні лабораторії ІРЗ у Києві і на майданчику в Чорнобилі використовували стандартну радіохімічну методику, вони оснащені 96 альфа-спектрометрами. Номенклатура ЛВЛ включає в себе скануючий низькофоновий ЛВЛ, чотири ЛВЛ Canberra FastScan і чотири ЛВЛ типу “крісло”. Мобільний ЛВЛ розташований у Києві і зарезервований для надзвичайних цілей. Станом на вересень 2017 р. рамками програми дозиметрії внутрішнього опромінення було охоплено понад 17 000 працівників, які пройшли 1 230 000 вимірювань ¹³⁷Cs на ЛВЛ, 87 000 вимірювань вмісту ²³⁹⁺²⁴⁰Pu у пробах калу і 4 400 вимірювань вмісту ²³⁹⁺²⁴⁰Pu у пробах сечі. Така великомасштабна програма забезпечила надійний контроль надходжень нерозчинного радіоактивного матеріалу.В международном Плане осуществления мероприятий (ПОМ) предусматривается поэтапное преобразование чернобыльской площадки в безопасное состояние. Новый безопасный конфайнмент – это беспрецедентная структура высотой 108 м над разрушенным 4-м блоком ЧАЭС, он является центральным элементом ПОМ. Многие работники, вовлеченные в ПОМ, могут иметь прямой контакт с фрагментами облученного топлива, топливосодержащими аэрозолями и другими загрязненными материалами на промышленной площадке в Чернобыле. Изотопы плутония, америция, стронция и цезия доминируют во внутреннем облучении работников ПОМ. Безопасность работников имеет высокий приоритет в ПОМ. Начиная с 2004 г., Научно-исследовательский институт радиационной защиты АТН Украины (ИРЗ) осуществляет крупномасштабную программу дозиметрии внутреннего облучения как неотъемлемую часть ПОМ. Данные содержания плутония в пробах кала и мочи, а также счетчиков излучений человека (СИЧ) являются основным источником количественных данных, используемых для оценки дозы. Радиохимические лаборатории ИРЗ в Киеве и на площадке в Чернобыле использовали стандартную радиохимическую методику, они оснащены 96 альфа-спектрометрами. Номенклатура СИЧ включает в себя сканирующий низкофоновый СИЧ, четыре СИЧ Canberra FastScan и четыре СИЧ типа “кресло”. Мобильный СИЧ расположен в Киеве и зарезервирован для чрезвычайных целей. По состоянию на сентябрь 2017 г. в рамках программы дозиметрии внутреннего облучения было охвачено более 17 000 работников, которые прошли 1 230 000 измерений ¹³⁷Cs на СИЧ, 87 000 измерений содержания ²³⁹⁺²⁴⁰Pu в пробах кала и 4 400 измерений содержания ²³⁹⁺²⁴⁰Pu в пробах мочи. Такая крупномасштабная программа обеспечила надежный контроль поступлений нерастворимого радиоактивного материала

Gold(III) Complexes Activity Against Multidrug-Resistant Bacteria Of Veterinary Significance

The emergence and spread of multidrug-resistant bacteria are a global concern. The lack of new antibiotics in the pipeline points to the need for developing new strategies. In this sense, gold(III) complexes (G3Cs) could be a promising alternative due to their recently described antibacterial activity. The aim of this study was to evaluate the antimicrobial activity of G3Cs alone and in combination with colistin against pathogenic bacteria from veterinary sources. Minimal inhibitory concentration (MIC) values were determined by broth microdilution and compared with clinically relevant antibiotics. Antibiofilm activity was determined by crystal violet staining. Combinations of selected G3Cs with colistin and cytotoxicity in commercial human cell lines were evaluated. Four and seven G3Cs showed antibacterial effect against Gram-negative and Gram-positive strains, respectively, with this activity being higher among Gram-positive strains. The G3Cs showed antibiofilm activity against Gram-negative species at concentrations similar or one to four folds higher than the corresponding MICs. Combination of G3Cs with colistin showed a potential synergistic antibacterial effect reducing concentrations and toxicity of both agents. The antimicrobial and antibiofilm activity, the synergistic effect when combined with colistin and the in vitro toxicity suggest that G3Cs would provide a new therapeutic alternative against multidrug-resistant bacteria from veterinary origin

In vitro and in vivo Virulence Potential of the Emergent Species of the Acinetobacter baumannii (Ab) Group

The increased use of molecular identification methods and mass spectrometry has revealed that Acinetobacter spp. of the A. baumannii (Ab) group other than A. baumannii are increasingly being recovered from human samples and may pose a health challenge if neglected. In this study 76 isolates of 5 species within the Ab group (A. baumannii n = 16, A. lactucae n = 12, A. nosocomialis n = 16, A. pittii n = 20, and A. seifertii n = 12), were compared in terms of antimicrobial susceptibility, carriage of intrinsic resistance genes, biofilm formation, and the ability to kill Caenorhabditis elegans in an infection assay. In agreement with previous studies, antimicrobial resistance was common among A. baumannii while all other species were generally more susceptible. Carriage of genes encoding different efflux pumps was frequent in all species and the presence of intrinsic class D β-lactamases was reported in A. baumannii, A. lactucae (heterotypic synonym of A. dijkshoorniae) and A. pittii but not in A. nosocomialis and A. seifertii. A. baumannii and A. nosocomialis presented weaker pathogenicity in our in vitro and in vivo models than A. seifertii, A. pittii and, especially, A. lactucae. Isolates from the former species showed decreased biofilm formation and required a longer time to kill C. elegans nematodes. These results suggest relevant differences in terms of antibiotic susceptibility patterns among the members of the Ab group as well as highlight a higher pathogenicity potential for the emerging species of the group in this particular model. Nevertheless, the impact of such potential in the human host still remains to be determined

Novel gold(III)-dithiocarbamate complex targeting bacterial thioredoxin reductase: antimicrobial activity, synergy, toxicity, and mechanistic insights

IntroductionAntimicrobial resistance is a pressing global concern that has led to the search for new antibacterial agents with novel targets or non-traditional approaches. Recently, organogold compounds have emerged as a promising class of antibacterial agents. In this study, we present and characterize a (C^S)-cyclometallated Au(III) dithiocarbamate complex as a potential drug candidate.Methods and resultsThe Au(III) complex was found to be stable in the presence of effective biological reductants, and showed potent antibacterial and antibiofilm activity against a wide range of multidrug-resistant strains, particularly gram-positive strains, and gram-negative strains when used in combination with a permeabilizing antibiotic. No resistant mutants were detected after exposing bacterial cultures to strong selective pressure, indicating that the complex may have a low propensity for resistance development. Mechanistic studies indicate that the Au(III) complex exerts its antibacterial activity through a multimodal mechanism of action. Ultrastructural membrane damage and rapid bacterial uptake suggest direct interactions with the bacterial membrane, while transcriptomic analysis identified altered pathways related to energy metabolism and membrane stability including enzymes of the TCA cycle and fatty acid biosynthesis. Enzymatic studies further revealed a strong reversible inhibition of the bacterial thioredoxin reductase. Importantly, the Au(III) complex demonstrated low cytotoxicity at therapeutic concentrations in mammalian cell lines, and showed no acute in vivo toxicity in mice at the doses tested, with no signs of organ toxicity.DiscussionOverall, these findings highlight the potential of the Au(III)-dithiocarbamate scaffold as a basis for developing novel antimicrobial agents, given its potent antibacterial activity, synergy, redox stability, inability to produce resistant mutants, low toxicity to mammalian cells both in vitro and in vivo, and non-conventional mechanism of action

The SARS-Unique Domain (SUD) of SARS Coronavirus Contains Two Macrodomains That Bind G-Quadruplexes

Since the outbreak of severe acute respiratory syndrome (SARS) in 2003, the three-dimensional structures of several of the replicase/transcriptase components of SARS coronavirus (SARS-CoV), the non-structural proteins (Nsps), have been determined. However, within the large Nsp3 (1922 amino-acid residues), the structure and function of the so-called SARS-unique domain (SUD) have remained elusive. SUD occurs only in SARS-CoV and the highly related viruses found in certain bats, but is absent from all other coronaviruses. Therefore, it has been speculated that it may be involved in the extreme pathogenicity of SARS-CoV, compared to other coronaviruses, most of which cause only mild infections in humans. In order to help elucidate the function of the SUD, we have determined crystal structures of fragment 389–652 (“SUDcore”) of Nsp3, which comprises 264 of the 338 residues of the domain. Both the monoclinic and triclinic crystal forms (2.2 and 2.8 Å resolution, respectively) revealed that SUDcore forms a homodimer. Each monomer consists of two subdomains, SUD-N and SUD-M, with a macrodomain fold similar to the SARS-CoV X-domain. However, in contrast to the latter, SUD fails to bind ADP-ribose, as determined by zone-interference gel electrophoresis. Instead, the entire SUDcore as well as its individual subdomains interact with oligonucleotides known to form G-quadruplexes. This includes oligodeoxy- as well as oligoribonucleotides. Mutations of selected lysine residues on the surface of the SUD-N subdomain lead to reduction of G-quadruplex binding, whereas mutations in the SUD-M subdomain abolish it. As there is no evidence for Nsp3 entering the nucleus of the host cell, the SARS-CoV genomic RNA or host-cell mRNA containing long G-stretches may be targets of SUD. The SARS-CoV genome is devoid of G-stretches longer than 5–6 nucleotides, but more extended G-stretches are found in the 3′-nontranslated regions of mRNAs coding for certain host-cell proteins involved in apoptosis or signal transduction, and have been shown to bind to SUD in vitro. Therefore, SUD may be involved in controlling the host cell's response to the viral infection. Possible interference with poly(ADP-ribose) polymerase-like domains is also discussed

Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study

Background Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours.Methods In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186.Findings Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78 center dot 6%] female patients and 4922 [21 center dot 4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1 center dot 4 [IQR 0 center dot 6-3 center dot 4]) compared with the prepandemic phase (2 center dot 0 [0 center dot 9-3 center dot 7]; p<0 center dot 0001) and pandemic decrease phase (2 center dot 3 [1 center dot 0-5 center dot 0]; p<0 center dot 0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69 center dot 0%] of 3704 vs 1515 [71 center dot 5%] of 2119; OR 1 center dot 1 [95% CI 1 center dot 0-1 center dot 3]; p=0 center dot 042), lymph node metastases (343 [9 center dot 3%] vs 264 [12 center dot 5%]; OR 1 center dot 4 [1 center dot 2-1 center dot 7]; p=0 center dot 0001), and tumours at high risk of structural disease recurrence (203 [5 center dot 7%] of 3584 vs 155 [7 center dot 7%] of 2006; OR 1 center dot 4 [1 center dot 1-1 center dot 7]; p=0 center dot 0039).Interpretation Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation.Funding None.Copyright (c) 2023 Published by Elsevier Ltd. All rights reserved

Learning a lesson from a famous puppet player Susumu Tange : A good practice of "Practical training of child-care skills" in Kyoto Women's college

textabstractCoronaviruses can cause respiratory and enteric disease in a wide variety of human and animal hosts. The 2003 outbreak of severe acute respiratory syndrome (SARS) first demonstrated the potentially lethal consequences of zoonotic coronavirus infections in humans. In 2012, a similar previously unknown coronavirus emerged, Middle East respiratory syndrome coronavirus (MERS-CoV), thus far causing over 650 laboratory-confirmed infections, with an unexplained steep rise in the number of cases being recorded over recent months. The human MERS fatality rate of∼30% is alarmingly high, even though many deaths were associated with underlying medical conditions. Registered therapeutics for the treatment of coronavirus infections are not available. Moreover, the pace of drug development and registration for human use is generally incompatible with strategies to combat emerging infectious diseases. Therefore, we have screened a library of 348 FDA-approved drugs for anti-MERS-CoV activity in cell culture. If such compounds proved sufficiently potent, their efficacy might be directly assessed in MERS patients. We identified four compounds (chloroquine, chlorpromazine, loperamide, and lopinavir) inhibiting MERS-CoV replication in the lowmicromolar range (50% effective concentrations [EC50s], 3 to 8 μM). Moreover, these compounds also inhibit the replication of SARS coronavirus and human coronavirus 229E. Although their protective activity (alone or in combination) remains to be assessed in animal models, our findings may offer a starting point for treatment of patients infected with zoonotic coronaviruses like MERS-CoV. Although they may not necessarily reduce viral replication to very low levels, a moderate viral load reduction may create a window during which to mount a protective immune response. Copyrigh

Migration-related detention centers : The challenges of an ecological perspective with a focus on justice

Background: In recent years, border control and migration-related detention have become increasingly widespread practices affecting the lives of undocumented migrants, their families, and communities at large. In spite of the concern within academia, few studies have directly witnessed the life and experiences of people confined to migration-related detention centers. In the medical and psychological fields, a considerable body of research has demonstrated the pathogenic nature of detention in terms of mental health, showing an association between length of detention and severity of distress. Nevertheless, it was limited to the assessment of individuals’ clinical consequences, mainly focusing on asylum seekers. There currently exists a need to adopt an ecological perspective from which to study detained migrants’ experiences as context-dependent, and influenced by power inequalities. This paper addresses this gap. Discussion: Drawing upon advances in community psychology, we illustrate an ecological framework for the study of migration-related detention contexts, and their effects on the lives of detained migrants and all people exposed to them. Making use of existing literature, Kelly’s four principles (interdependence, cycling of resources, adaptation, succession) are analyzed at multiple ecological levels (personal, interpersonal, organizational, communal), highlighting implications for future research in this field. A focus on justice, as a key-dimension of analysis, is also discussed. Wellbeing is acknowledged as a multilevel, dynamic, and value-dependent phenomenon. Summary: In presenting this alternative framework, the potential for studying migration-related detention through an ecological lens is highlighted, pointing the way for future fields of study. We argue that ecological multilevel analyses, conceptualized in terms of interdependent systems and with a focus on justice, can enhance the comprehension of the dynamics at play in migration-related detention centers, providing an effective tool to address the multi-level challenges of doing research within them. Furthermore, they can contribute to the development of policies and practices concerned with health, equality, and human rights of all people exposed to migration-related detention. Consistent with these assumptions, empirical studies adopting such a framework are strongly encouraged. These studies should use mixed and multi-method culturally situated designs, based on the development of collaborative and empowering relationships with participants. Ethnographic approaches are recommended.Fundação para a Ciência e Tecnologia (FCT

SUPPORT SYSTEM FOR THE DOSIMETRIC INTERPRETATION OF THE INTERNAL EXPOSURE

Paper describes the computer system, which was developed for the purposes of the retrospective dosimetry of internal exposure by specialists of the Radiation Protection Institute of Academy of Technological Sciences of Ukraine. The system gives tools for analysis and interpretation of biophysical measurements, for reconstruction of intakes and related doses of the internal exposure. The main aim of the system is retrospective estimation of the doses of internal exposure from single acute or multiple intakes of radionuclides on the base of the bioassay and whole body counter measurements