Abstract Aims Long-term, placebo-controlled cholesterol-lowering trials have demonstrated legacy effects (clinical benefits that persist or emerge after trial end). It is unknown whether legacy effects follow a short period of very low low-density lipoprotein cholesterol (LDL-C) levels achieved with statin plus proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. Methods and results In 18 924 patients with recent acute coronary syndrome, the ODYSSEY OUTCOMES trial compared the PCSK9 inhibitor alirocumab with placebo, each added to high-intensity or maximum-tolerated statin therapy. Patients with two consecutive LDL-C levels <0.39 mmol/L (15 mg/dL) on alirocumab had blinded placebo substitution for the remainder of the trial with continued statin treatment. In post hoc analyses, major adverse cardiovascular events (MACE) in these patients were compared to MACE in propensity score–matched patients from the placebo group with similar baseline characteristics and study medication adherence. In the alirocumab group, 730 patients had blinded placebo substitution at a median of 8.3 months from randomization, after a median of 6.0 months with LDL-C <0.39 mmol/L. They were matched to 1460 placebo patients. Both groups had lower baseline LDL-C and lipoprotein(a) and better study medication adherence than those of the overall cohort. Over a median follow-up of 2.8 years, MACE occurred in 47 (6.4%) alirocumab patients with limited-duration, very low achieved LDL-C vs. 122 (8.4%) matched placebo patients (treatment hazard ratio 0.72; 95% confidence interval 0.51, 0.997; P = 0.047). Conclusion A short period of LDL-C levels <0.39 mmol/L achieved with statin and alirocumab, followed by statin monotherapy, was associated with a lower risk of MACE than statin monotherapy throughout the observation period. Clinical benefit persisted for several years. Trial registration ClinicalTrials.gov NCT01663402

Introduction: Since 1956 karyotype analysis becomes an essential part of routine medical diagnostics, and helped medical professionals investigate the origin of genetic abnormalities in many constitutional and cancer diseases. Karyotyping also provided more information in the monitoring of fertility problems. An inversion does not usually have a phenotypic effect, especially if it involves a heterochromatin area, such as 9qh. Chromosome 9 polymorphism, with breakpoints p11q13/p12q13, can be the cause of variant abnormal clinical conditions such as congenital abnormalities, hematological diseasesand also could have a connection with pregnancy loss and fertility failure. Methods: A retrospective study was conducted on 1784 cytogenetics examination results from peripheral blood samples in the period from January, 2012 to December, 2022. The patients, carriers inv(9) in their karyotype were highlighted for detailed analysis. Results: Among the 1784 patients, constitutional pericentric inversion inv(9)(p11q13) was found in 13 females (0,72%), while it was seen in 17 cases of males (0.95%). The total average amount of inv (9) in this study is 1.68%. The inv(9) population consists of 60% cases with infertility problems, 6,66% females who had spontaneous abortus and 33,33% were patientsreferred to our laboratory for other reasons. Conclusion: In this research, the prevalence of inv (9) in the population of patients of Northeast Bosnia and Herzegovina who had the reproductive failure is shown. We believe that these results will help in finding the key to the truth about the association of this chromosome polymorphism with some pathological conditions such as fertility problems.

The COVID-19 pandemic led to an increase in healthcare waste (HCW). HCW management treatment needs to be re-taken into focus to deal with this challenge. In practice, there are several treatments of HCW with their advantages and disadvantages. This study is conducted to select the appropriate treatment for HCW in the Brčko District of Bosnia and Herzegovina. Six HCW management treatments are analyzed and observed through twelve criteria. Ten-level linguistic values were used to bring this evaluation closer to human thinking. A fuzzy rough approach is used to solve the problem of inaccuracy in determining these values. The OPA method from the Bonferroni operator is used to determine the weights of the criteria. The results of the application of this method showed that the criterion Environmental Impact (C4) received the highest weight, while the criterion Automation Level (C8) received the lowest value. The ranking of HCW management treatments was performed using MARCOS methods based on the Aczel–Alsina function. The results of this analysis showed that the best-ranked HCW management treatment is microwave (A6) while landfill treatment (A5) is ranked worst. This study has provided a new approach based on fuzzy rough numbers where the Bonferroni function is used to determine the lower and upper limits, while the application of the Aczel–Alsina function reduced the influence of decision-makers on the final decision because this function stabilizes the decision-making process.

Purpose. To select recommendations on the use of physical culture means for students of future teachers, it is necessary to identify their functional features and genetically determined properties of the nervous system. Purpose: to reveal the relationship between the performance of the nervous system, orthostatic test and professional specialization of students of pedagogical universities. Material and methods. Students from 9 different faculties of Ukraine's leading pedagogical institute took part in the study. The total number of subjects was 841 people. Soon the reactions were determined by the program "Psychodiagnostics". Orthostatic reactions were determined by the results of heart rate in the supine position and in the standing position. An analysis of variance (ANOVA) was performed using Duncan's method to determine the influence of teaching faculty on test performance. A correlation analysis of testing indicators and ranks of faculties was carried out using the Tau-b Kendall method. Results. Students of all experimental faculties were divided into 4 groups according to the number of errors in the choice reaction test based on the results of variance analysis (Duncan method). Faculties were divided into ranks from the first to the fourth. A significant negative correlation of the rank of the faculty according to the indicator of the strength and speed of nervous processes with the heart rate in the standing position (p<0.05) and the difference between the heart rate in the standing and lying positions (p<0.01) was revealed. Conclusions. Physical exercises should be applied according to the professional characteristics and personal inclinations of the students, who were divided into 4 groups according to the indicators of reaction speed and orthostatic test. For students of the faculties of primary education and preschool education (1st group), we recommend using mobile and sports games. For students of humanities and natural sciences faculties (2nd group), any physical exercises that require an average manifestation of all physical qualities are suitable: dances, gymnastics, sports games, martial arts. Students of the Faculty of Arts (3rd group) are suitable for physical exercises that require high concentration of attention for a long time, for example, cyclical exercises. We recommend that students of the Faculty of Physical Education and Sports (4th group) continue to improve in their chosen sport, while also studying other sports.

Copper (II) complexes with commercial antibiotics, amoxicillin (AMX), azithromycin (AZT) and ciprofloxacin (CFL) were synthesized and isolated as solids. Structures of the isolated products were determined by FTIR spectroscopy. Antibacterial activities were determined on reference bacterial strains from the ATCC collection by diffusion technique. The results show that AMX and CFL coordinate Cu (II) ion as bidentate O-donor ligand. AZT coordinates metal center as bidentate NO-donor ligand. A difference in the morphology of antibiotic crystals and the synthesized complexes was found. Complex of Cu (AMX)2 show complete absence of antibacterial activity, while the other com-plexes show the same or even lower activity than the parent ligands.  

Background Computational signal preprocessing is a prerequisite for developing data-driven predictive models for clinical decision support. Thus, identifying the best practices that adhere to clinical principles is critical to ensure transparency and reproducibility to drive clinical adoption. It further fosters reproducible, ethical, and reliable conduct of studies. This procedure is also crucial for setting up a software quality management system to ensure regulatory compliance in developing software as a medical device aimed at early preclinical detection of clinical deterioration. Objective This scoping review focuses on the neonatal intensive care unit setting and summarizes the state-of-the-art computational methods used for preprocessing neonatal clinical physiological signals; these signals are used for the development of machine learning models to predict the risk of adverse outcomes. Methods Five databases (PubMed, Web of Science, Scopus, IEEE, and ACM Digital Library) were searched using a combination of keywords and MeSH (Medical Subject Headings) terms. A total of 3585 papers from 2013 to January 2023 were identified based on the defined search terms and inclusion criteria. After removing duplicates, 2994 (83.51%) papers were screened by title and abstract, and 81 (0.03%) were selected for full-text review. Of these, 52 (64%) were eligible for inclusion in the detailed analysis. Results Of the 52 articles reviewed, 24 (46%) studies focused on diagnostic models, while the remainder (n=28, 54%) focused on prognostic models. The analysis conducted in these studies involved various physiological signals, with electrocardiograms being the most prevalent. Different programming languages were used, with MATLAB and Python being notable. The monitoring and capturing of physiological data used diverse systems, impacting data quality and introducing study heterogeneity. Outcomes of interest included sepsis, apnea, bradycardia, mortality, necrotizing enterocolitis, and hypoxic-ischemic encephalopathy, with some studies analyzing combinations of adverse outcomes. We found a partial or complete lack of transparency in reporting the setting and the methods used for signal preprocessing. This includes reporting methods to handle missing data, segment size for considered analysis, and details regarding the modification of the state-of-the-art methods for physiological signal processing to align with the clinical principles for neonates. Only 7 (13%) of the 52 reviewed studies reported all the recommended preprocessing steps, which could have impacts on the downstream analysis. Conclusions The review found heterogeneity in the techniques used and inconsistent reporting of parameters and procedures used for preprocessing neonatal physiological signals, which is necessary to confirm adherence to clinical and software quality management system practices, usefulness, and choice of best practices. Enhancing transparency in reporting and standardizing procedures will boost study interpretation and reproducibility and expedite clinical adoption, instilling confidence in the research findings and streamlining the translation of research outcomes into clinical practice, ultimately contributing to the advancement of neonatal care and patient outcomes.

Recent studies have shown that people who are immunocompromised may inadvertently play a role in spurring the mutations of the virus that create new variants. This is because some immunocompromised individuals remain at risk of getting COVID-19 despite vaccination, experience more severe disease, are susceptible to being chronically infected and remain contagious for longer if they become infected and considering that immunocompromised individuals represent approximately 2% of the overall population, this aspect should be carefully considered. So far, some autoimmune rheumatic disease (ARD) patients with COVID-19 have been treated with antiviral therapies or anti-SARS-CoV-2 antibody products. However, there is no homogeneous approach to these treatment strategies. This issue was addressed within the European Reference Network (ERN) on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ReCONNET) in a discussion among experts and patient's representatives in the context of the rare and complex connective tissue diseases (rCTDs) covered by the Network. ERN ReCONNET is one of the 24 ERNs launched by the European Commission in 2017 with the aim of tackling low prevalence and rare diseases that require highly specialised treatment and promoting concentration of knowledge and resources through virtual networks involving healthcare providers (HCPs) across the European Union (EU). Considering the urgent need to provide guidance not only to the rCTDs community, but also to the whole ARDs community, a multidisciplinary Task Force, including expert clinicians and European Patient Advocacy Group (ePAG) Advocates, was created in the framework of ERN ReCONNET with the aim of developing overarching principles (OP) and points-to-consider (PtC) on a homogenous approach to treat immunocompromised patients with ARDs (with a particular focus on CTDs) affected by COVID-19 using antiviral therapies and anti-SARS-CoV-2 antibody products. The present work reports the final OP and PtC agreed by the Task Force.

Devido à falha dos protocolos de biossegurança nas cooperativas de reciclagem, os separadores de resíduos se expõem a agentes biológicos, como vírus, fungos e bactérias, tornando-se mais susceptíveis a infecções por estes agentes. Este estudo objetivou estudar o risco biológico ao qual estão expostos os cooperados na atividade de triagem/separação dos resíduos recicláveis, avaliando o uso de equipamentos de proteção individual e a ocorrência de acidentes e da prática da higienização das mãos. Para isso, realizou-se um estudo descritivo quantitativo no Estado de Alagoas, nas Cooperativas de Reciclagem de Resíduos COOPREL e COOPLUM. A ocorrência de microrganismos, provenientes do manuseio dos resíduos foi investigada através da coleta de material das mãos dos cooperados, com auxílio de swab, antes e após do processo de higienização habitual, seguida da orientada. O material coletado foi transportado e analisado quanto à presença de bactérias aeróbias e anaeróbias, bolores e leveduras. Após o cultivo e análise microbiológica, verificou-se a presença de microrganismos da família Enterobacreriaceae, bolores e leveduras. Entretanto, a coleta realizada após a higienização orientada houve significativa redução do número de bactérias em 88%; em relação à amostra inicial da coleta antes ou depois da higienizaçao habitual. Referente à presença de bolores e leveduras observou-se uma redução de 37,50%. Logo, este estudo identificou que 54% dos cooperados sofreram acidentes com material perfurocortante nos últimos doze meses, e identificou bactérias da família Enterobacteriaceae nas mãos dos cooperados (56,41%), refletindo além do risco biológico, a exacerbação do risco social representado pelas precárias condições de trabalho.

Syneresis represents the appearance of separation of whey on the surface of the product and is considered an important parameter of the quality of fermented dairy products. For the production of the fermented milk drink, kombucha was used as a non-traditional starter. Two sweeteners were used, honey and sucrose.The aim of the work was to examine the influence of starter and sweetener on changes in the subsequent acidity and intensity of syneresis of the samples during storage. The results were compared with a control sample obtained by inoculation with a conventional starter culture. During storage, there was a drop in pH value and an increase in titratableacidity, as a resultof the constant metabolic activity of the microflora and the production of lactic acid in the produced samples. Honey, as a sweetener, had an effect on the lower pH value of the fermented milk drink samples. The analysis of variance showed a statistically significant difference in the titratable acidity results and the intensity of syneresis of the samples during storage.Samples that were produced with kombucha as a starter showed better structure stability during storage and better quality. During storage, sample kb4 showed the best structural stability and the lowest intensity of syneresis. KEYWORDS:stinging nettle extract;bioactive components;extraction;antioxidant