Особенности процессов перекисного окисления липидов и антиоксидантной защиты у больных с сочетанной протозойно-урогенитальной микст-инфекцией при озонотерапии

Изучены состояние и динамика перекисного окисления липидов (ПОЛ) и общей антиоксидантной защиты (ОАОЗ) у 124 пациентов, из которых 99 (79,8 %) страдали сочетанной хронической протозойно−урогенитально−вирусной инфекцией. Определены резервные возможности ОАОЗ при проведении озонотерапии с установленной индивидуальной дозой озона. При включении в комплексное лечение оригинальных методов озонотерапии достигнуты достоверное улучшение и нормализация всех показателей ПОЛ и ОАОЗ, что обеспечивает санацию организма больных от возбудителей инфекции и восстановление физико−химических свойств его клеточных мембран.Досліджено стан і динаміку перекисного окислення ліпідів (ПОЛ) і загального антиоксидантного захисту (ЗАОЗ) у 124 пацієнтів, з яких 99 (79,8 %) хворіли на сполучену хронічну протозойно−урогенітально−вірусну інфекцію. Визначено резервні можливості ЗАОЗ під час проведення озонотерапії з установленою індивідуальною дозою озону. При включенні в комплексне лікування оригінальних методів озонотерапії було досягнуто достовірне поліпшення й нормалізацію всіх показників ПОЛ та ЗАОЗ, що забезпечує санацію організму хворих від збудників штфекції і відновлення фізико−хімічних властивостей його клітинних мембран.The state and dynamics of lipid peroxidation (LP) and general antioxidant protection (GAOP) were investigated in 123 patients, of them 99 (79,8 %) had combined chronic protozoal urogenital viral infection. The reserve capabilities of GAOP were determined at ozone therapy with individually adjusted ozone dose. The use of the original methods of ozone therapy significantly improved and normalized all LP and GAOP parameters, which promoted treatment of the organism from the infection agents and restoration of physicochemical properties of the cellular membranes

On Form Factors in nested Bethe Ansatz systems

We investigate form factors of local operators in the multi-component Quantum Non-linear Schr\"odinger model, a prototype theory solvable by the so-called nested Bethe Ansatz. We determine the analytic properties of the infinite volume form factors using the coordinate Bethe Ansatz solution and we establish a connection with the finite volume matrix elements. In the two-component models we derive a set of recursion relations for the "magnonic form factors", which are the matrix elements on the nested Bethe Ansatz states. In certain simple cases (involving states with only one spin-impurity) we obtain explicit solutions for the recursion relations.Comment: 34 pages, v2 (minor modifications

Reducing errors in health care: cost-effectiveness of multidisciplinary team training in obstetric emergencies (TOSTI study); a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>There are many avoidable deaths in hospitals because the care team is not well attuned. Training in emergency situations is generally followed on an individual basis. In practice, however, hospital patients are treated by a team composed of various disciplines. To prevent communication errors, it is important to focus the training on the team as a whole, rather than on the individual. Team training appears to be important in contributing toward preventing these errors. Obstetrics lends itself to multidisciplinary team training. It is a field in which nurses, midwives, obstetricians and paediatricians work together and where decisions must be made and actions must be carried out under extreme time pressure.</p> <p>It is attractive to belief that multidisciplinary team training will reduce the number of errors in obstetrics. The other side of the medal is that many hospitals are buying expensive patient simulators without proper evaluation of the training method. In the Netherlands many hospitals have 1,000 or less annual deliveries. In our small country it might therefore be more cost-effective to train obstetric teams in medical simulation centres with well trained personnel, high fidelity patient simulators, and well defined training programmes.</p> <p>Methods/design</p> <p>The aim of the present study is to evaluate the cost-effectiveness of multidisciplinary team training in a medical simulation centre in the Netherlands to reduce the number of medical errors in obstetric emergency situations. We plan a multicentre randomised study with the centre as unit of analysis. Obstetric departments will be randomly assigned to receive multidisciplinary team training in a medical simulation centre or to a control arm without any team training.</p> <p>The composite measure of poor perinatal and maternal outcome in the non training group was thought to be 15%, on the basis of data obtained from the National Dutch Perinatal Registry and the guidelines of the Dutch Society of Obstetrics and Gynaecology (NVOG). We anticipated that multidisciplinary team training would reduce this risk to 5%. A sample size of 24 centres with a cluster size of each at least 200 deliveries, each 12 centres per group, was needed for 80% power and a 5% type 1 error probability (two-sided). We assumed an Intraclass Correlation Coefficient (ICC) value of maximum 0.08.</p> <p>The analysis will be performed according to the intention-to-treat principle and stratified for teaching or non-teaching hospitals.</p> <p>Primary outcome is the number of obstetric complications throughout the first year period after the intervention. If multidisciplinary team training appears to be effective a cost-effective analysis will be performed.</p> <p>Discussion</p> <p>If multidisciplinary team training appears to be cost-effective, this training should be implemented in extra training for gynaecologists.</p> <p>Trial Registration</p> <p>The protocol is registered in the clinical trial register number NTR1859</p

Association between COVID-19 lockdown measures and the incidence of iatrogenic versus spontaneous very preterm births in the Netherlands:a retrospective study

Background: The COVID-19 pandemic led to regional or nationwide lockdowns as part of risk mitigation measurements in many countries worldwide. Recent studies suggest an unexpected and unprecedented decrease in preterm births during the initial COVID-19 lockdowns in the first half of 2020. The objective of the current study was to assess the effects of the two months of the initial national COVID-19 lockdown period on the incidence of very and extremely preterm birth in the Netherlands, stratified by either spontaneous or iatrogenic onset of delivery, in both singleton and multiple pregnancies. Methods: Retrospective cohort study using data from all 10 perinatal centers in the Netherlands on very and extremely preterm births during the initial COVID-19 lockdown from March 15 to May 15, 2020. Incidences of very and extremely preterm birth were calculated using an estimate of the total number of births in the Netherlands in this period. As reference, we used data from the corresponding calendar period in 2015–2018 from the national perinatal registry (Perined). We differentiated between spontaneous versus iatrogenic onset of delivery and between singleton versus multiple pregnancies. Results: The incidence of total preterm birth < 32 weeks in singleton pregnancies was 6.1‰ in the study period in 2020 versus 6.5‰ in the corresponding period in 2015–2018. The decrease in preterm births in singletons was solely due to a significant decrease in iatrogenic preterm births, both < 32 weeks (OR 0.71; 95%CI 0.53 to 0.95) and < 28 weeks (OR 0.53; 95%CI 0.29 to 0.97). For multiple pregnancies, an increase in preterm births < 28 weeks was observed (OR 2.43; 95%CI 1.35 to 4.39). Conclusion: This study shows a decrease in iatrogenic preterm births during the initial COVID-19-related lockdown in the Netherlands in singletons. Future studies should focus on the mechanism of action of lockdown measures and reduction of preterm birth and the effects of perinatal outcome

Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome

Transposable elements (TEs) have no longer been totally considered as “junk DNA” for quite a time since the continual discoveries of their multifunctional roles in eukaryote genomes. As one of the most important and abundant TEs that still active in human genome, Alu, a SINE family, has demonstrated its indispensable regulatory functions at sequence level, but its spatial roles are still unclear. Technologies based on 3C(chromosomeconformation capture) have revealed the mysterious three-dimensional structure of chromatin, and make it possible to study the distal chromatin interaction in the genome. To find the role TE playing in distal regulation in human genome, we compiled the new released Hi-C data, TE annotation, histone marker annotations, and the genome-wide methylation data to operate correlation analysis, and found that the density of Alu elements showed a strong positive correlation with the level of chromatin interactions (hESC: r=0.9, P<2.2×1016; IMR90 fibroblasts: r = 0.94, P < 2.2 × 1016) and also have a significant positive correlation withsomeremote functional DNA elements like enhancers and promoters (Enhancer: hESC: r=0.997, P=2.3×10−4; IMR90: r=0.934, P=2×10−2; Promoter: hESC: r = 0.995, P = 3.8 × 10−4; IMR90: r = 0.996, P = 3.2 × 10−4). Further investigation involving GC content and methylation status showed the GC content of Alu covered sequences shared a similar pattern with that of the overall sequence, suggesting that Alu elements also function as the GC nucleotide and CpG site provider. In all, our results suggest that the Alu elements may act as an alternative parameter to evaluate the Hi-C data, which is confirmed by the correlation analysis of Alu elements and histone markers. Moreover, the GC-rich Alu sequence can bring high GC content and methylation flexibility to the regions with more distal chromatin contact, regulating the transcription of tissue-specific genes

Accelerated menopausal changes as human disease model 'FOCUM' for the development of osteoarthritis and other degenerative disorders:protocol for a prospective cohort study

INTRODUCTION: The incidence of degenerative disorders, including osteoarthritis (OA), increases rapidly in women after menopause. However, the influence of the menopause is still insufficiently investigated due to the slowness of menopausal transition. In this study, a novel human model is used in which it is expected that menopausal-related changes will occur faster. This is the Females discontinuing Oral Contraceptives Use at Menopausal age model. The ultimate aim is to link these changes to OA and other degenerative disorders, including cardiovascular diseases, diabetes, osteoporosis and tendinopathies. METHODS AND ANALYSIS: This is a pilot observational prospective cohort study with 2 years of follow-up. Fifty women aged 50–60 who use oral contraceptive (OC) and have the intention to stop are included. Measurements are performed once before stopping OC, and four times thereafter at 6 weeks, 6 months, 1 year and 2 years. At every time point, a questionnaire is filled in and a sample of blood is drawn. At the first and final time points, a physical examination, hand radiographs and a MRI scan of one knee are performed. The primary OA outcome is progression of the MRI Osteoarthritis Knee Score. Secondary OA outcomes are the development of clinical knee and hand OA, development of knee OA according to the MRI definition, and progression of radiographic features for hand OA. Principal component analysis will be used to assess which changes occur after stopping OC. Univariate and multivariate generalised estimating equation models will be used to test for associations between these components and OA. ETHICS AND DISSEMINATION: The study has been approved by the Medical Ethics Committee of the Erasmus MC University Medical Center Rotterdam (MEC-2019-0592). All participants must give informed consent before data collection. Results will be disseminated in national and international journals. TRIAL REGISTRATION NUMBER: NL70796.078.19

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved