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Introduction and purpose: Rosacea is a chronic inflammatory dermatosis. It mainly affects the central parts of the face and manifests itself with redness, erythema, telangiectasia, and papulopustular lesions. The aim of the work is to review current rosacea therapy techniques, detailing aesthetic medicine treatments. Material and methods: In order to create the review, the PubMed and Scopus databases were searched in April and May 2024. The searches took place between April 24 and May 15, 2024 and consisted of a critical analysis of the acquired sources of knowledge. State of knowledge: The introduction of lasers to the market has revolutionized the therapy of rosacea and appropriately selected parameters and patient qualification for the treatment ensure therapeutic success. Botulinum toxin is a potent neurotoxin that blocks the release of acetylcholine from the presynaptic vesicle. Appropriate home care is an extremely important factor in maintaining the disease in the remission phase. Conclusion Among the possibilities of aesthetic medicine, rosacea therapy is definitely dominated by laser therapy. There are several lasers available on the market today, the most commonly used of which is IPL. Ablative lasers are used to treat a deformed nose caused by rhinophyma. Botulinum toxin is administered as an intradermal injection, thanks to which it reduces erythema and redness of the skin. After appropriate treatment by a dermatologist and aesthetic medicine doctor, well-selected home care plays a key role in maintaining the disease in the remission phase.

Introduction and Purpose: Multiple sclerosis (MS) is a prevalent autoimmune disease affecting the central nervous system, particularly in young people. Characterized by neurodegenerative and demyelinating processes, MS is influenced by genetic and environmental factors. Research indicates that sufficient levels of vitamin D can reduce the risk of developing MS. Studies show that higher sun exposure and dietary vitamin D intake are associated with a lower incidence of MS. Moreover, vitamin D supplementation may benefit those already diagnosed by alleviating symptoms and improving their quality of life. This review explores the potential benefits of vitamin D and its neuroprotective mechanisms in MS. State of Knowledge: MS research and treatments have focused on immunomodulation, with less emphasis on neuroprotection, including the role of vitamin D. It is well-established that vitamin D has anti-inflammatory effects on the immune system in MS. It influences the proliferation and differentiation of neural stem cells and oligodendrocytes, enhances neurotrophin expression, reduces reactive astrogliosis, decreases oxidative stress, and stabilizes the blood-brain barrier. Research suggests that adequate vitamin D levels and supplementation might improve MS outcomes. Conclusion: New diagnostic tools and therapeutic strategies are urgently needed to address the complex nature of MS, which includes inflammation, neuronal death, demyelination, and oxidative stress. Promoting vitamin D sufficiency and supplementation, alongside developing new neuroprotective agents, remains a valuable approach in combating MS. Understanding the mechanisms of MS and the effects of vitamin D could lead to better management strategies and enhanced quality of life for patients.

Introduction: Chronic Fatigue Syndrome (CFS) is an exhausting continuous medical condition. In most cases it affects patients after a flu-like infection. CFS correlates with alterations in the nervous and immune systems, metabolism, and hormone secretion. Diagnostic process is very challenging due to the absence of a definitive diagnostic test and wide symptomatology. It negatively impacts people's both mental and physical health. Aim of the study: The aim of this literature review is to comprehensively examine current research findings and literature on Chronic Fatigue Syndrome (CFS), understand its etiology, how it affects the body, why it's challenging to diagnose, the various treatments available, new ideas and viewpoints in the field. Describing the State of Knowledge: Despite extensive investigation, the exact etiology of CFS remains unknown. In literature CFS is also often described as Myalgic Encephalomyelitis. In the WHO's most recent classification, the ICD-11, both Chronic Fatigue Syndrome and Myalgic Encephalomyelitis are classified as “other disorders of the nervous system” which indicates the significance of the issue. Conclusions: This literature review underlines the importance of a comprehensive and collaborative approach in addressing the complexities of CFS and improving outcomes for individuals living with this debilitating condition.

Introduction and Purpose: Hydrogen breath tests serve the crucial purpose of evaluating the absorption of nutrients in the small intestine, particularly when carbohydrates are not properly absorbed, leading to bacterial overgrowth. These tests are non-invasive, cost-effective, and widely accessible diagnostic tools used to assess various gastrointestinal disorders. The objective of this review is to evaluate the effectiveness and methodology of Hydrogen breath testing (HBT). State of knowledge: The disposal of hydrogen gas is essential for maintaining efficient microbial fermentation processes in the gut. Hydrogenotrophic microbes, including acetogens, methanogenic archaea, and sulfate-reducing bacteria, are responsible for this process. Hydrogen breath tests, conducted with substrates like glucose and lactulose, aid in diagnosing conditions such as small intestinal bacterial overgrowth (SIBO), lactose and fructose intolerance, and other carbohydrate absorption disorders. These tests generate a large volume of data, which can be analyzed using data mining techniques to uncover new hypotheses. Conclusions: Hydrogen breath tests, using various substrates, are effective in diagnosing gastrointestinal disorders such as SIBO and carbohydrate malabsorption. They offer valuable insights into microbial processes in the gut and can inform individualized treatment strategies. However, careful consideration of contraindications and proper test administration protocols is essential for accurate diagnosis and interpretation of results.

Introduction and purpose: Preeclampsia (PE) is a complication during pregnancy characterized by high blood pressure (≥140/90 mmHg) and signs of organ involvement appearing after 20 weeks’ of gestation. Various factors are known to increase the risk of this condition as well as clinical factors. The pathogenesis of the disease is complex and not fully understood. State of Knowledge: The main roles play two angiogenic factors: soluble fms-like tyrosine kinase 1 (sFlt-1), which is an antiangiogenic protein, and placental growth factor (PlGF), which is a pro-angiogenic protein. Elevated sFlt-1 and reduced PlGF levels in the mother’s blood can predict the future development of preeclampsia during pregnancy. The imbalance between these two angiogenic biomarkers indicates de new-onset preeclampsia, distinct from chronic hypertension. Both MAP and UTA-PI are essential components of first-trimester screening protocols, which, combined with maternal history and other biochemical markers, allow for accurate preeclampsia risk assessment and early intervention to improve maternal and fetal outcomes. Conclusions: Preeclampsia is a major cause of maternal and perinatal morbidity and mortality. The integration of multiple biomarkers, such as PlGF and sFlt-1, along with advanced analytical techniques, enhances early detection and accurate risk stratification, improving maternal and fetal outcomes. Aspirin prophylaxis before 16 weeks’ gestation has been shown to reduce the risk of preeclampsia.

Abstract Background Elder abuse is a worldwide problem with serious consequences for individuals and society. To effectively deal with elder abuse, a timely identification of signals as well as a systematic approach towards (suspected) elder abuse is necessary. This study aimed to develop and test the acceptability and appropriateness of ERASE (EldeR AbuSE) in the emergency department (ED) setting. ERASE is an early warning tool for elder abuse self-administered by the healthcare professional in patients ≥ 70 years. Methods A systematic literature review was previously conducted to identify potential available instruments on elder abuse for use in the ED. Furthermore, a field consultation in Dutch hospitals was performed to identify practice tools and potential questions on the recognition of elder abuse that were available in clinical practice. Based on this input, in three subsequent rounds the ERASE tool was developed. The ERASE tool was tested in a pilot feasibility study in healthcare professionals (n = 28) working in the ED in three Dutch hospitals. A semi-structured online questionnaire was used to determine acceptability and appropriateness of the ERASE tool. Results The systematic literature review revealed seven screening instruments developed for use in the hospital and/or ED setting. In total n = 32 (44%) hospitals responded to the field search. No suitable and validated instruments for the detection of elder abuse in the ED were identified. The ERASE tool was developed, with a gut feeling awareness question, that encompassed all forms of elder abuse as starting question. Subsequently six signalling questions were developed to collect information on observed signs and symptoms of elder abuse and neglect. The pilot study showed that the ERASE tool raised the recognition of healthcare professionals for elder abuse. The tool was evaluated acceptable and appropriate for use in the ED setting. Conclusions ERASE as early warning tool is guided by an initial gut feeling awareness question and six signalling questions. The ERASE tool raised the recognition of healthcare professionals for elder abuse, and was feasible to use in the ED setting. The next step will be to investigate the reliability and validity of the ERASE early warning tool.

Introduction and aim of study: Chronic wounds are increasingly challenging global healthcare. These wounds, which take over 3 months to heal, are complicated by untreated infections and the formation of biofilm, hindering healing and antibiotic effectiveness. To tackle these issues, new treatments like bacteriophage therapy are being explored. Bacteriophages, viruses that target bacteria, offer promise in overcoming antibiotic resistance. However, their use presents challenges that need to be addressed. Material and methods: Our review is based on the analysis of materials collected in Pubmed, Elsevier and other scientific articles using keywords: “chronic wound”, “chronic wounds infection”, “biofilms”, “MDR”, “bacteriophage”, “phage therapy”. Conclusions: The rise of chronic wounds due to resistant infections poses a significant challenge for patients and healthcare systems. Multidrug-resistant bacteria, often forming biofilm, evade current treatments, urging the search for alternatives. Phage therapy, showing efficacy against various stubborn infections, including those from surgery or diabetes, gains attention. Advanced delivery systems enhance targeted treatment, while phage cocktails improve effectiveness, especially against multiple resistant strains. Safety is generally observed, but larger trials are needed. Though not a replacement for antibiotics, phage therapy offers hope, needing robust clinical validation. While challenges exist, its societal, commercial, and economic benefits suggest a promising future beyond clinical use.

Introduction and aim of the study: Ear wax plays many roles in maintaining ear health, such as cleansing, shielding, and lubricating the external auditory canal. Sometimes, when earwax obstruction occurs, for example as a result of improper hygiene procedures (such as using cotton swabs), it can cause a number of disorders ranging from discomfort to even loss of hearing. In such cases, various methods can be used to remove the cerumen impaction. One of these and also the most commonly used, involves the usage of ear drops, which can contain different active substances (water-based compounds, oil-based compounds, a combination of oil and water-based compounds, and non-water, non-oil solutions). The aim of our study is to present current state of knowledge about effectiveness of various types of ear drops in wax cleaning. Material and methods: Our review is based on the analysis of materials collected in Pubmed”, „Google Scholar” and other scientific articles using keywords: „earwax”, cerumen impaction”, „cerumenolytics”, „ear drops”, „cerumen”, „earwax solvents”, „wax solvents”. Conclusions: Despite numerous studies, the Holy Grail has not been found among ear drops. The majority conducted studies did not show that any of the cerumenolitics were superior to the others in a statistically significant way. The only result that was statistically significant was the one showing a higher effectiveness of 2.5% sodium bicarbonate compared to docusate sodium. Further research is needed.

Introduction: Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system, marked by inflammation, demyelination, and neurodegeneration. It severely impacts quality of life with symptoms like spasticity, pain, and cognitive impairment. Conventional treatments often fail, necessitating alternative therapies. Purpose: This review evaluates the efficacy and safety of cannabis extracts in treating MS, enhancing understanding of their benefits and limitations. State of knowledge: Studies suggest that cannabinoids may alleviate MS symptoms, particularly spasticity and pain. Clinical trials have shown significant reductions in muscle stiffness and pain, along with improved sleep quality. Meta-analyses, by Whiting et al. and Cochrane, support these findings but highlight the risk of side effects, which may limit long-term use. Additionally, research on animal models and in vitro studies indicate that cannabinoids may have neuroprotective and immunomodulatory properties, potentially reducing neuroinflammation and demyelination. Conclusion: Cannabinoids exhibit potential as a complementary therapy for managing MS symptoms, especially spasticity and pain. However, evidence is mixed, with some studies showing limited efficacy and considerable risk of side effects. More long-term, high-quality studies are needed to fully understand the therapeutic potential and safety profile of cannabinoids in MS treatment. Despite the challenges, the growing availability and changing legal status of medical cannabis suggest it could be a viable option for some patients, provided its use is carefully monitored and adapted to individual needs.

Introduction and Purpose: Varicose veins in the lower limbs are common, particularly among those with prolonged standing occupations, contributing to chronic venous insufficiency (CVI). CVI affects about 60% of adults, with varicose veins present in 25–33% of women and 10–20% of men, increasing with age. Understanding and addressing this condition is crucial as it impacts daily life and raises the risk of thrombosis. Effective treatments are essential to alleviate these health issues. State of Knowledge: Varicose veins result from a mix of genetic, hemodynamic, and vein wall factors. Family history plays a significant role, increasing susceptibility. Hemodynamic issues include malfunctioning venous valves and elevated venous pressure. Vein wall changes and thrombotic activity also contribute. Symptoms range from cosmetic concerns to pain and complications like venous ulcers. Understanding these factors is key for effective management. Conclusions: Surgical treatments like high ligation and stripping are standard but have drawbacks such as scarring and long recovery. Valvuloplasty addresses deep venous valve issues but is limited. Minimally invasive options, such as endovenous laser therapy and sclerotherapy, offer promising alternatives but with some recurrence risk. Compression therapies, including elastic stockings and pneumatic compression, aid recovery and symptom relief. Elastic bandage therapy is effective but requires precise application to avoid complications. Each method has pros and cons, underscoring the need for tailored treatment approaches.

The authors, in the theoretical part of the paper, define and explain the concept of emotional competence, as well as skills that should be developed and strengthened within the mentioned concept. Also, the importance of emotional competence in exam situations for the academic success of students has been presented, which is supported by the presentation of research related to this topic. The aim of the study was to examine whether students with different academic achievement and from different study programs showed different levels of emotional competence in exam situations. The research was conducted on a sample of 115 students from the Faculty of Philosophy, University of East Sarajevo. The paper presents the results of examining the differences in the development of emotional competence in exam situations in students with different academic achievement and the results of examining the differences in the development of emotional competence in students in exam situations depending on the study program they study. The findings show that there are no differences in the development of emotional competence in exam situations in students with different academic achievement, but there are differences when it comes to the development of emotional competence in exam situations depending on the study program that students' study. This research is a contribution to a better understanding of students' emotional competencies in exam situations and may have practical implications in terms of understanding the importance of improving the emotional sphere in all study programs by expanding study objectives so that they include developing of students' emotional competencies.

120 exposed children/adolescents (75 children and 45 adolescents) from the multi-drug resistant tuberculosis sites underwent the complex clinical radiological and immunological examination.Insignificant functional disorders of cellular response (immunoregulatory processes) caused by the prevalence of suppressor and cytotoxic reactions by 1.3 times and by the prevalence of pro-inflammatory cytokines in the regulatory system (2.0 times above the norm, TNF-α/IL 10.0. р

This research aims to analyze Segmenting, Targeting, and Positioning (STP) strategies to attract the interest of students studying Nahwu at the Nurul Jadid Islamic Boarding School, Probolinggo, East Java, Indonesia. This research uses a qualitative approach with a case study type of research. Researchers conducted observations, in-depth interviews, and documentation to obtain accurate, valid, and accountable data. Data analysis was carried out systemically, starting from data reduction, data presentation, and drawing research conclusions. This research shows that segmenting, targeting, and positioning, mapping, and placing students in learning Nahwu science is very important so that learning can provide comfortable and meaningful conditions for students; this can increase students' interest in studying Nahwu science. This research provides implications regarding the importance of appropriate segmentation, targeting, and positioning in learning Nahwu science so that educational institutions can increase students' interest in learning and involvement in studying Nahwu science more effectively, excitingly, and meaningfully so that learning objectives can be achieved maximally.

Gratitude therapy is a positive psychotherapy approach given to victims of sexual abuse to generate positive thinking by expressing gratitude to the environment, God and other people. This research aims to test gratitude intervention as a religious activity undertaken to reduce negative emotions in victims of sexual abuse. A total of 104 such victims were identified using the snowball sampling method who were divided into an experimental group (N=52) and a control group (N=52). They were diagnosed as having negative emotions based on the child Trauma Questionnaire Shot-Focus (CTQ-SF) and Gratitude Questioner-6 (GQ-6) with triple ANOVA data analysis. The study’s results demonstrate a significant influence of gratitude on negative emotion, with values of F(39,037) = 4.71, p .01, and ηp2 = 0.113. It can increase feelings of gratitude and reduce negative emotions in victims of sexual abuse. Gratitude therapy helps reduce negative emotions and foster positive emotions amongst such victims. The study could be implemented in people who experience negative emotions related to clinical and non-clinical disorders.

Abstract Ischemia/reperfusion injury (IRI) of the heart involves the activation of oxidative and proapoptotic pathways. Simultaneously Klotho protein presents anti-aging, antiapoptotic and antioxidative properties. Therefore, this study aimed to evaluate the effect of Klotho protein on oxidative stress in hearts subjected to IRI. Isolated rat hearts perfused with the Langendorff method were subjected to ischemia, followed by reperfusion, in the presence or absence of recombinant rat Klotho protein. The factors involved in the activation of insulin-like growth factor receptor (IGF1R)/phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) signalling pathway were evaluated. IRI caused activation of the IGF1R (p = 0.0122)/PI3K (p = 0.0022) signalling, as compared to the aerobic control group. Infusion supply of Klotho protein during IRI significantly reduced the level of phospho-IGF1R (p = 0.0436), PI3K (p = 0.0218) and phospho-AKT (p = 0.0020). Transcriptional activity of forkhead box protein O3 (FOXO3) was reduced (p = 0.0207) in hearts subjected to IRI, compared to aerobic control. Administration of Klotho decreased phosphorylation of FOXO3 (p = 0.0355), and enhanced activity of glutathione peroxidase (p = 0.0452) and superoxide dismutase (p = 0.0060) in IRI + Klotho group. The levels of reactive oxygen/nitrogen species (ROS/RNS) (p = 0.0480) and hydrogen peroxide (H2O2) (p = 0.0460), and heart injury (p = 0.0005) were significantly increased in hearts from the IRI group in comparison to the aerobic group. Klotho reduced NADPH oxidase 2 (NOX2) (p = 0.0390), ROS/RNS (p = 0.0435) and H2O2 (p = 0.0392) levels, and heart damage (p = 0.0286) in the hearts subjected to IRI. In conclusion, Klotho contributed to the protection of the heart against IRI and oxidative stress via inhibition of the IGF1R/PI3K/AKT pathway, thus can be recognized as a novel cardiopreventive/cardioprotective agent.

The aim of this study was to identify miRNAs that could potentially influence the activity of SMAD proteins involved in TGFβ signal transduction in five types of breast cancer in Polish women. Patients with five breast cancer subtypes were included in the study: luminal A (n = 130), luminal B HER2− (n = 100), luminal B HER2+ (n = 96), non-luminal HER2+ (n = 36), and TNBC (n = 43). During surgery, tumor tissue was removed along with a margin of healthy tissue (control). Molecular analysis included determination of the expression of genes related to SMAD protein signal transduction using mRNA microarrays and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Protein expression was determined using an enzyme-linked immunosorbent assay (ELISA). The miRNA profiling was performed using miRNA microarrays and the miRDB database. SMAD3 and SMAD5 were overexpressed in all types of breast cancer, which could be related to the reduced expression of miR-145, and the findings for SMAD4 and miR-155 were similar. Additionally, the level of SMAD7 was reduced, which may be due to the low activity of miR-15b and miR21b. This study determined the gene expression profiles involved in SMAD protein signal transduction across five different types of breast cancer and identified the miRNAs potentially regulating their activity. Overexpression of SMAD3, SMAD4, and SMAD5 suggests excessive activation of the TGFβ pathway, potentially promoting tumor growth and development. Concurrently, a significant reduction in SMAD7 expression removes inhibitory control in the TGFβ pathway, a phenomenon that is particularly evident in more aggressive breast cancer types.

Desde la crisis de 2008, las exportaciones de contenido tecnológico de la Argentina pierden mercados. Con menor capacidad de apropiar riqueza a nivel mundial, su economía sufre un achicamiento que deriva en devaluación, inflación, empeoramiento de las condiciones de vida, etc. Proponemos analizar, en términos cuantitativos, la evolución reciente del comercio exterior argentino, atendiendo a la dinámica de exportaciones industriales de relevante contenido tecnológico. Tomamos casos testigos, revisando su evolución, mercados principales y efectos de la expansión china como nuevo proveedor de los socios tradicionales de la Argentina. El objetivo es dilucidar la trayectoria de exportaciones claves en la estructura productiva argentina y pensar, a futuro, un diagnóstico que permita sugerir líneas de acción para relanzar la capacidad exportadora.

Objective: To explore the current state of knowledge and evidence about peer support for various disadvantaged groups; to identify the strengths, weaknesses, opportunities, and threats of peer support to critically reflect on peer support within health and social services. Methods: A rapid scoping review was conducted according to Arksey and O’Malley’s framework, aiming to identify eligible studies in PubMed, APA PsychInfo, Education Resources Information Center, Cochrane Library, Academic Search Premier, ScienceDirect, Directory of Open Access Journals, ResearchGate, WorldCat, and Google Scholar. According to Rodgers’ concept analysis steps and the SWOT model, data was reported using thematic synthesis. Results: Forty-five studies were included, describing a variety of peer support initiatives among groups of young migrants and unsupervised minors, young adults with autism, people with (mental) health problems, foster/shelter families, vulnerable pregnant women, people outside the labour force, older adults, and homeless people. The strength of peer support is its positive effect on the quality of life among vulnerable people. The weakness is represented by peers both being too involved and focused on personal interest or by peers lacking expertise and knowledge. Opportunities for peer support are mutual learning, the anticipated long-term effects, and the potential to facilitate social inclusion. Culture, language barriers, drop-out rates, securing sustainability, and peers’ lack of time and commitment are regarded as threats to peer support. Conclusion: Although peer support offers good outcomes for various groups of vulnerable people, the weaknesses and threats need to be considered to provide and proliferate peer support.

BACKGROUND. The feasibility of combining antimycobacterial therapy (AMBT) with bedaquiline (Bdq) and delamanid (Dlm) with non-specific immunomodulator BI-V in children and adolescents with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/Rif-TBP) needs to be studied. OBJECTIVE. To find out the effectiveness of the use of complex AMBT with Bdq and Dlm with non-specific immunomodulator BI-V in children and adolescents with MDR/Rif-TBP. MATERIALS AND METHODS. Children and adolescents with MDR/Rif-TBP at the initial stage of AMBT were given BI-V (BIVEL, Slovenia) as a non-specific immunomodulator. The patients were divided into two groups: 1st – 20 patients who received Bdq + Dlm + levofloxacin (Lfx) + linezolid (Lzd) + clofazimine (Cfz); 2nd ‒ 28 patients whose complex treatment included BI-V (Вdq + Dlm + Lfx + Lzd + Cfz + BI-V). BI-V was prescribed from the age of 3 years at 5 ml suspension once a day during 24 days RESULTS. The use of BI-V against the background of individualized regimens of AMBT in children and adolescents with MDR/Rif-TBP increased the effectiveness of treatment, contributed to the disappearance of symptoms of intoxication, the resolution of infiltration foci and the healing of decay cavities in system of immune protection, which contributed to the shortening of the inpatient stage of treatment, while maintaining a high therapeutic effectiveness (“cured” ‒ 92.8 %) and the formation of small residual changes in the lungs in the majority (89.3 %). CONCLUSIONS. When using combined complex AMBT with Bdq, Dlm and BI-V, high therapeutic efficiency was observed in most patients (92.8 %).

Background: The rate of in-stent restenosis (ISR) is decreasing; however, it is still a challenge for contemporary invasive cardiologists. Therapeutic methods, including drug-eluting balloons (DEBs), intravascular lithotripsy, excimer laser coronary atherectomy, and imaging-guided percutaneous coronary intervention (PCI) with drug-eluting stents (DES), have been implemented. Patients with diabetes mellitus (DM) are burdened with a higher risk of ISR than the general population. Aims: DM-Dragon is aimed at evaluating the clinical outcomes of ISR treatment with DEBs vs. DES, focusing on patients with co-existing diabetes mellitus. Methods: The DM-Dragon registry is a retrospective study comprising data from nine high-volume PCI centers in Poland. A total of 1117 patients, of whom 473 individuals had DM and were treated with PCI due to ISR, were included. After propensity-score matching (PSM), 198 pairs were created for further analysis. The primary outcome of the study was target lesion revascularization (TLR). Results: In DM patients after PSM, TLR occurred in 21 (10.61%) vs. 20 (10.1%) in non-diabetic patients, p = 0.8690. Rates of target vessel revascularization (TVR), target vessel myocardial infarction, device-oriented composite endpoint (DOCE), and cardiac death did not differ significantly. Among diabetic patients, the risk of all-cause mortality was significantly lower in the DEB group (2.78% vs. 11.11%, HR 3.67 (95% confidence interval, CI) [1.01–13.3), p = 0.0483). Conclusions: PCI with DEBs is almost as effective as DES implantation in DM patients treated for ISR. In DM-Dragon, the rate of all-cause death was significantly lower in patients treated with DEBs. Further large-scale, randomized clinical trials would be needed to support these findings.

CD19-targeted CAR-T cell therapy has revolutionized the treatment of relapsed/refractory (r/r) pre-B acute lymphoblastic leukemia (ALL). However, it can be associated with acute toxicities related to immune activation, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cytokines released from activated immune cells play a key role in their pathophysiology. This study was a prospective analysis of proinflammatory proteins and cytokines in children treated with tisagenlecleucel. Serial measurements of C-reactive protein, fibrinogen, ferritin, IL-6, IL-8, IL-10, IFNγ, and TNFα were taken before treatment and on consecutive days after infusion. The incidence of CRS was 77.8%, and the incidence of ICANS was 11.1%. No CRS of grade ≥ 3 was observed. All complications occurred within 14 days following infusion. Higher biomarker concentrations were found in children with CRS grade ≥ 2. Their levels were correlated with disease burden and CAR-T cell dose. While cytokine release syndrome was common, most cases were mild, primarily due to low disease burden before lymphodepleting chemotherapy (LDC). ICANS occurred less frequently but exhibited various clinical courses. None of the toxicities were fatal. All of the analyzed biomarkers rose within 14 days after CAR-T infusion, with most reaching their maximum around the third day following the procedure.

Background: We aimed to characterize the population of consecutive patients undergoing coronary angiography with simultaneous renal artery angiography and assess prognostic factors at a 10 year follow-up. Methods: The KORONEF study was a prospective, single-center, observational, and descriptive study with 492 patients included. We analyzed several baseline demographics, clinical and periprocedural characteristics, and laboratory data, and we assessed the results of coronary angiography and renal artery angiography. Results: The study population consisted of 37.2% women, and the mean age was 64.4 ± 9.9 years (min. 30 years, max. 89 years). Angiography revealed significant renal artery stenosis (RAS) in 35 (7.1%) patients. Among patients with significant RAS (≥50%), we observed more women (57.1% vs. 35.7%, p = 0.011), and patients were older (69.1 ± 10.4 years vs. 64.0 ± 9.7 years, p = 0.005). In the whole population, all-cause death was reported in 29.9% of patients, myocardial infarction (MI) rate—in 11.8%, and stroke—in 4.9%. In the multivariable analysis, independent predictors of death were age 65–75 years (HR 2.88), age > 75 years (HR 8.07), diabetes (HR 1.59), previous MI (HR 1.64), chronic kidney disease (HR 2.22), unstable angina (HR 0.37), and left ventricular ejection fraction > 60% (HR 0.43). Conclusions: Over a 10 year follow-up, the all-cause death rate was 29.9%, showing no statistically significant differences between patients with and without significant RAS.

We characterized the performance, as well as the safety, of a second-generation thin-strut sirolimus-eluting stent with a biodegradable polymer, Alex Plus (Balton, Poland), implanted in patients with type 2 diabetes (DM) with a 4-year follow-up. We defined the primary endpoint as the 48-month rate of major cardiovascular adverse events (MACE), including cardiac death, myocardial infarction (MI), or target lesion revascularization (TLR). The secondary endpoints were all-cause death, cardiac death, MI, and TLR rates at 12, 24, 36, and 48 months. We enrolled 232 patients in whom 282 stents were implanted, including 97 DM and 135 non-DM patients. The mean age of the DM patients was 69.5 ± 10.1 years and females accounted for 30% of the patients. DM patients had higher rates of arterial hypertension (97% vs. 88%, p = 0.016), dyslipidemia (86% vs. 70%, p = 0.005), prior MI (61% vs. 40%, p = 0.002), prior PCI (65% vs. 50%, p = 0.020), and prior CABG (14% vs. 5.9%, p = 0.029). We recorded statistically significant differences for MACE (HR 1.85, 95% CI 1.01–3.41, p = 0.046), cardiac death (HR 4.46, 95% CI 1.44–13.8, p = 0.010), and MI (HR 3.17, 95% CI 1.10–9.12, p = 0.033), but not for TLR, between DM and non-DM patients in terms of the analyzed endpoints at 4 years. Our study showed that Alex Plus was efficient and safe in a contemporary cohort of real-world DM patients undergoing percutaneous revascularization.

This study aims to identify the speech features employed by male and female influencers while promoting food. This research decided to apply a qualitative method, specifically in the form of a case study. Meanwhile, the researchers chose observation through social media, namely Instagram, as the data collection process. The data analysis consists of three stages, such as reduction, presentation, and conclusion. The researchers found that the female influencers use speech features are intensifier, emphatic stress, tag question, rising intonation, empty adjectives, specialized, hypercorrect grammar, super polite forms, avoidance of strong swear, and one form that belongs to the men known as command and directive. Meanwhile, the speech features employed by the men are command and directive, swearing and taboo words, compliments, and theme, and three forms of speech feature that belong to women, which are intensifier, empty adjective, and emphatic stress. The finding of this study is that both genders are not constantly with their own speech features. Both genders also applied speech features that belong to the opposite gender while doing promotion, although the language features of each gender dominate the respective results. Abstrak Penelitian ini bertujuan mengidentifikasi fitur tuturan yang digunakan oleh influencer pria dan wanita saat melakukan promosi makanan. Penelitian ini menggunakan metode kualitatif, khususnya dalam bentuk studi kasus. Penulis memilih observasi melalui salah satu media sosial, yakni Instagram, pada proses pengumpulan data. Proses analisis data terdiri atas tiga tahap, yaitu reduksi, penyajian, dan penarikan simpulan. Penulis menemukan bahwa para influencer wanita menggunakan fitur ucapan yang intensif, penekanan tegas, tanda pertanyaan, intonasi tinggi, kata sifat kosong, kata khusus, tata bahasa yang berlebihan, bentuk sangat sopan, menghindari umpatan yang kuat, dan satu bentuk milik pria yang dikenal sebagai perintah dan direktif. Sementara itu, ciri-ciri tuturan yang digunakan oleh influencer laki-laki adalah tuturan perintah dan direktif, umpatan dan kata-kata tabu, pujian, dan tema, serta tiga bentuk tuturan yang dimiliki wanita, yaitu intensifier, kata sifat kosong, dan tekanan empatik. Temuan dari penelitian ini adalah bahwa kedua jenis influencer tidak selalu memiliki fitur bicara mereka sendiri. Mereka juga menerapkan fitur bicara milik lawan jenis saat melakukan promosi meskipun hasilnya didominasi oleh ciri fitur bahasa pada masing-masing gender.

[This corrects the article DOI: 10.1371/journal.pone.0262073.].

[This corrects the article DOI: 10.1371/journal.pgph.0001644.].

Precocious puberty is diagnosed when pubertal characteristics appear before the age of 8 years in females. The most common form is gonadotropin-dependent, called axial. The primary method of treatment is administration of gonadotrophin-releasing hormone analogues (GnRHa). The aim of the study was to verify hypothesis that GnRHa therapy in the childhood may be of additive risk factor for polycystic ovary syndrome (PCOS) in adulthood.Material and MethodsThe study group consists of 24 women (median age 22 88 years, median BMI 23.5) treated with GnRHa for central precocious puberty in childhood. The control group includes 40 women (median age 23 years, median BMI 25.6) diagnosed with isolated premature thelarche and not using GnRHa in the childhood. Anthropometric measurements, ultrasound examination of minor pelvis and hormonal profile were performed. PCOS diagnosis was based on Rotterdam criteria.ResultsThe study confirmed a higher prevalence of PCOS in the study group (50%) than in the control group (10%); p=0.0006. Significant, linear correlation between free testosterone levels and ovarian size was found in the study group (R=0.45 p= 0.03).ConclusionsGnRHa therapy during childhood may have a potential influence on incidence of PCOS in the adulthood. Therefore, in this group of patients long-term follow-up focused on screening for PCOS would seem beneficial.

Introduction: Redox imbalance and oxidative stress are involved in the pathogenesis of arrhythmias. They also play a significant role in pathogenesis of heart failure (HF). In patients with HFand implanted cardioverter-defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D), the direct current shocks may be responsible for additional redox disturbances and additionally increase arrhythmia risk. However, the precise role of oxidative stress in potentially fatal arrhythmias and shock induction remains unclear.Methods: 36 patients with diagnosed HF and implanted ICD/CRT-D were included in this study. Patients were qualified to the study group in case of registered ventricular arrhythmia and adequate ICD/CRT-D intervention. The control group consisted of patients without arrhythmia with elective replacement indicator (ERI) status. Activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) in erythrocyte (RBC), SOD, GPx activity and reactive oxygen/nitrogen species (ROS/RNS) concentration in plasma were determined. The values were correlated with glucose, TSH, uric acid, Mg and ion concentrations.Results: In the perishock period, we found a significant decrease in RBC and extracellular (EC) SOD and RBC CAT activity (p = 0.0110, p = 0.0055 and p = 0.0002, respectively). EC GPx activity was also lower (p = 0.0313). In all patients, a decrease in the concentration of all forms of glutathione was observed compared to the ERI group. Important association between ROS/RNS and GSH, Mg, TSH and uric acid was shown. A relationship between the activity of GSH and antioxidant enzymes was found. Furthermore, an association between oxidative stress and ionic imbalance has also been demonstrated. The patients had an unchanged de Haan antioxidant ratio and glutathione redox potential.Conclusion: Here we show significant redox disturbances in patients with HF and ICD/CRT-D interventions. Oxidative stress may be an additional risk factor for the development of arrhythmia in patients with HF. The detailed role of oxidative stress in ventricular arrhythmias requires further research already undertaken by our team.

Introduction. Against the backdrop of multiple and widespread drug resistance of Mycobacterium tuberculosis (MDR-TB), there has been a significant decline in the effectiveness of treatment of tuberculosis (TB) patients in Ukraine and globally. Therefore, in recent years, new antimycobacterial drugs, such as bedaquiline (Bdq), delamanid (Dlm) and pretomanid, have been introduced to improve treatment efficacy in adults, children and adolescents. The purpose - to study the effectiveness of complex treatment with bedaquiline (Bdq) and delamanid (Dlm) in children under 18 years old with multiple and extensively drug-resistant pulmonary TB (MDR/XDR-TB). Materials and methods. To study the clinical efficacy of chemotherapy with Bdq and Dlm, a retrospective cohort analysis of medical records was conducted. The main group consisted of 40 children with MDR/XDR-TB who received comprehensive antimycobacterial therapy with Bdq and Dlm; and the control group consisted of 27 patients who received treatment without Bdq and Dlm. Results. It was found that during the first three months of treatment, there was a decrease in bacilli in all patients treated with Bdq and Dlm and in the group of patients without these new drugs (control), but in the control group, the decrease was significantly slower, p

Abstract Background Per- and polyfluoroalkyl substances (PFAS) are of public health concern, because of their ubiquitous and extremely persistent occurrence, and depending on their structure, their bio-accumulative, mobile and toxic properties. Human health effects associated with exposure to PFAS include adverse effects on the immune system. In 2020, EFSA (the European Food Safety Authority) defined adverse effects on the immune system as the most critical effect for human health risk assessment, based on reduced antibody responses to childhood vaccines and similar effects observed in experimental animal studies. Likewise, the U.S. EPA (Environmental Protection Agency) considers PFAS-induced immunotoxicity, especially in children, as the critical effect for risk assessment. However, the mechanisms by which antibody concentrations are impacted are not completely understood. Furthermore, other targets of the immune system functions have been reported in the literature. Objective The aim of this review is to explore PFAS-associated immune-related effects. This includes, relevant mechanisms that may underlie the observed effects on the immune system, immunosuppression as well as immunoenhancement, such as i) modulation of cell signalling and nuclear receptors, such as NF-κB and PPARs; ii) alteration of calcium signalling and homoeostasis in immune cells; iii) modulation of immune cell populations; iv) oxidative stress and v) impact on fatty acid metabolism & secondary effects on the immune system. Methods A literature research was conducted using three databases (Web of Science, PubMed, and Scopus), which were searched in July 2021 for relevant studies published in the time frame from 2018 to 2021. In total, 487 publications were identified as potentially eligible and following expert-based judgement, articles relevant for mechanisms of PFAS induced immunotoxicity are discussed. Conclusions Taken together, we show that there is substantial evidence from both in vitro and in vivo experimental as well as epidemiological studies, supporting that various PFAS, not only PFOA and PFOS, affect multiple aspects of the immune system. Timing of exposure is critical, because the developing immune system is especially vulnerable to toxic insults, resulting in a higher risk of particularly adverse immune effects but also other organs later in life.

This multicenter, randomized study aimed to compare the sirolimus-eluting BiOSS LIM C dedicated coronary bifurcation stent with second-generation -limus drug-eluting stents (rDESs) in the treatment of non-left main (non-LM) coronary bifurcation. The deployment of a single stent in the main vessel–main branch across a side branch was the default strategy in all patients. The primary endpoint was the rate of major cardiovascular events (cardiac death, myocardial infarction, and target lesion revascularization) at 48 months. We enrolled 230 patients, allocating 116 patients to the BiOSS LIM C group and 114 patients to the rDES group. Most procedures were elective (BiOSS vs. rDES: 48.3% vs. 59.6%, p = 0.09) and performed in bifurcations within the left anterior descending/diagonal branch (BiOSS vs. rDES: 51.7% vs. 61.4%, p = 0.15). At 48 months, there were no statistically significant differences between the BiOSS and rDES groups in terms of major adverse cardiovascular events (MACE), cardiac death, myocardial infarction (MI), or target lesion revascularization (TLR) as follows: MACEs—18.1% vs. 14.9%, HR 1.36, 95% CI 0.62–2.22, and p = 0.33; cardiac death—4.3% vs. 3.5%, HR 1.23, 95% CI 0.33–4.56, and p = 0.75; MI—2.6% vs. 3.5%, HR 0.73, 95% CI 0.17–3.23, and p = 0.68; and TLR—11.2% vs. 7.9%, HR 1.66, 95% CI 0.75–3.71, and p = 0.21. The implantation success rate of the BiOSS LIM C stent was very high, and the cumulative MACE rates were promising. The POLBOS 3 trial sets an important benchmark for treating non-LM coronary bifurcations (ClinicalTrials.gov NCT03548272).

The restoration of blood flow to the ischemic myocardium inflicts ischemia/reperfusion (I/R) heart injury (IRI). The main contributors to IRI are increased oxidative stress and subsequent excessive production of ROS, increased expression of NOS and peroxinitate, activation of MMPs, and enhanced posttranslational modifications of contractile proteins, which make them more susceptible to proteolytic degradation. Since the pathophysiology of IRI is a complex issue, and thus, various therapeutic strategies are required to prevent or reduce IRI and microvascular dysfunction, in the current study we proposed an innovative multi-drug therapy using low concentrations of drugs applied intracoronary to reach microvessels in order to stabilize the pro- and antioxidant balance during a MI in an in vivo pig model. The ability of a mixture of doxycycline (1 μM), ML-7 (0.5 μM), and L-NAME (2 μM) to modulate the pro- and antioxidative balance was tested in the left ventricle tissue and blood samples. Data showed that infusion of a MIX reduced the total oxidative status (TOS), oxidative stress index (OSI), and malondialdehyde (MDA). It also increased the total antioxidant capacity, confirming its antioxidative properties. MIX administration also reduced the activity of MMP-2 and MMP-9, and then decreased the release of MLC1 and BNP-26 into plasma. This study demonstrated that intracoronary administration of low concentrations of doxycycline in combination with ML-7 and L-NAME is incredibly efficient in regulating pro- and antioxidant balance during MI.

Background: In this study, the changes in corneal cap and residual stromal thickness (RST) values during a 180-day observation period after refractive lenticule extraction small incision lenticule extraction (ReLEx SMILE) were assessed. Methods: Fifty patients underwent ReLEx SMILE using the VisuMax 500 femtosecond laser, with corneal imaging conducted pre and post procedure via anterior segment optical coherence tomography (AS-OCT). Cap thickness in the center and 1.5 mm from the center in four meridians was measured at various intervals. Results: The results showed a significant decrease in cap thickness 180 days post procedure compared to earlier intervals (p < 0.05). Similarly, RST decreased gradually and significantly post procedure (p < 0.05). Notably, changes in cap thickness within the central 1.5 mm area were more dynamic than RST changes during the 6-month observation period following SMILE. Conclusions: The corneal cap thickness measured with swept-source AS-OCT within the central 1.5 mm area underwent more dynamic changes than the residual stromal thickness during the 6-month observation following SMILE.

Many studies have proven the involvement of the RhoA/ROCK pathway in autoimmune and cardiovascular diseases and the beneficial effects of its downregulation. Here, we examined whether the effect of simvastatin on experimental autoimmune myocarditis (EAM) may be through targeting the Ras homolog family member A/Rho-associated coiled-coil containing kinases (RhoA/ROCK) pathway and whether previously shown downregulation of metalloproteinase 9 (MMP-9) could be associated with MLC phosphorylation. Two doses of simvastatin were administered to experimental rats with autoimmune myocarditis by gastric gavage for 3 weeks, at the stage of development of the inflammatory process. Immunohistochemical staining for RhoA and ROCK1 was evaluated semi-quantitatively with H-score. The RhoA staining showed no significant differences in expression between the groups, but the ROCK1 expression was significantly upregulated in the hearts of the EAM group and was not downregulated by simvastatin. The Western blotting analysis of the last downstream product of the RhoA/ROCK axis, phosphorylated myosin light chain (phospho-MYL9), revealed that protein content increased in EAM hearts and it was prevented by the highest dose of simvastatin. Our findings suggest that the RhoA/ROCK pathway is upregulated in EAM, and simvastatin in EAM settings inhibits the RhoA/ROCK pathway at the stage of phosphorylation of myosin light chains and provides a new insight into the molecular pathology of autoimmune myocarditis.

Background: The fact that during myocardial ischemia/reperfusion (I/R) injury, myosin light chain 1 (MLC1) and troponin I (TnI) are degraded by matrix metalloproteases activity has already been well established in both in vitro and ex vivo studies. However, I/R injury is a complex issue based on several overlapping mechanisms. Increased activity of myosin light chain kinase and nitric oxide synthase due to oxidative stress leads to post-translational modifications of MLC1, thus leading to the increased degradation of these proteins. Methods: Wistar rats were subjected to left anterior descending coronary artery occlusion. To measure the pharmacological effect of doxycycline, transthoracic echocardiography as well as biochemical tests, concentrations of TnI, LDH, MLC1, MMP-2 and MMP-9 were performed. Gelatinize activity and cytotoxicity level were also assessed; Results: I.p., administration of doxycycline before LAD occlusion surgery increased TnI and LDH content in the heart and decreased cytotoxicity. A reduction of MMP-2 and MMP-9 concentration and MMP-2 activity after administration of Doxy was also observed, as well as improvement in echocardiographic parameters just 7 days after surgery. Conclusions: Inhibition of MMPs by doxycycline, in vivo, may serve as a protective agent in future therapy.

The reasons for unfavorable changes in platelet concentrate (PC) quality during storage are not fully understood yet. We aimed to evaluate whether leukocytes and matrix metalloproteinases (MMPs) lead to a decrease in the quality of PCs and examine whether MMP inhibition will slow down the platelets’ aging. Nine PCs were divided into three parts: (1) leukocyte-depleted (F) PCs, (2) PCs with no additional procedures (NF), and (3) PCs with the addition of an MMP inhibitor—doxycycline (D). Each PC was stored for 144 h, and a sample for testing was separated from each part on the day of preparation and after 24, 48, 72 and 144 h of storage. Blood morphological analysis, platelet aggregation, and the expression of activation markers were evaluated. MMP-2 and MMP-9 concentration, activity, and gene expression were assessed. Platelet aggregation decreased, and platelet activation marker expression increased during the storage. D concentrates showed the lowest level of platelet activation. In turn, leukocyte-depleted PCs showed the highest level of platelet activation in general. MMP-9 platelet activity was higher in leukocyte-containing concentrates at the end of the storage period. We concluded that the filtration process leads to a higher platelet activation level. The presence of doxycycline in PCs reduces the expression of the activation markers as compared to leukocyte-depleted concentrates.

Introdução/Objetivo: A implementação de Programas de Gerenciamento de Antimicrobianos (PGA) tem por objetivo otimizar o uso de antimicrobianos nos serviços de saúde para garantir o efeito farmacoterapêutico máximo, reduzir a ocorrência de eventos adversos, prevenir a disseminação da resistência microbiana e diminuir os custos relacionados à assistência à saúde. O objetivo deste estudo é apresentar os resultados obtidos em um ano de implantação do PGA do Hospital Santa Rita de Cássia (HSRC) em Vitória, ES. Métodos: Foram analisadas diariamente todas as prescrições de antimicrobianos (ATM) entre 01/06/2022 e 30/05/2022. As variáveis analisadas foram espectro de ação, dose, posologia, duração e via de administração, e as intervenções foram realizadas conforme necessidade. Os dados das prescrições foram coletados através do sistema MV módulo PSIH e lançados em planilha Microsoft Office, que também fora alimentada com as intervenções do time operacional, bem como informações referentes a adesão dos médicos assistentes. Nos pacientes convênio, a economia financeira foi calculada a partir de valores de Material e Medicação (MAT/MED) e número de diárias evitadas. Nos pacientes SUS, calculou-se economia relacionada a MAT/MED e giro de leitos. Resultados: Sete mil oitocentos e três (7803) ATM foram avaliados no período. Destes, em 2091 (26,8%) foram realizadas intervenções do time operacional do PGA, e destas, 1514 (19,4%) foram acatadas pelos médicos assistentes. As principais intervenções realizadas foram redução do tempo dos ATM (22,8%), suspensão dos ATM (18,0%) e transição de via endovenosa para via oral (IV > VO) (17,0%). Os motivos de não adesão foram analisados a partir de janeiro de 2023. Das 349 não adesões no período, em 120 (33,2%) o médico não aderiu baseado em gravidade clínica, em 113 (32,4%) o médico assistente discordou da sugestão, e em 116 (34,4%) não houve justificativa do motivo da não adesão. Dos 7803 ATM prescritos no período, 1514 (19,4%) representavam antibioticoterapia perioperatória. O percentual de adequação à prescrição por até 24h subiu de 21,8% em novembro/22 para 72,2% em maio/23. A economia financeira no período foi da ordem de R$ 229.464,98, incluindo intervenções acatadas nos pacientes SUS e Convênio. O giro de leitos no período foi de 346 dias no SUS e 336 dias no Convênio. Conclusão: A implementação do PGA no HSRC gerou redução do tempo de uso de ATM, redução do tempo de internação e considerável economia financeira.

llergic rhinitis (AR) is increasing at an alarming rate in Ukraine. The clinical picture of AR in modern conditions is changing towards more severe and mixed forms. Allergic rhinitis, especially moderate to-severe, has a negative impact on patient quality of life, productivity, direct, and indirect costs. Achieving adequate symptom control is essential for successful AR management, and relies mostly on pharmacotherapy. Most patients use multiple medications to control symptoms faster and better, but symptoms may persist. With the advent of new combination therapies, such as the intranasal formulation of azelastine hydrochloride and fluticasone propionate in a single device (MP-AzeFlu) like Dymista®, most AR symptoms can be treated effectively. MP-AzeFlu acts synergistically and blocks two important pathophysiological pathways involved in the early- and late-phase reactions of the disease, providing rapid relief from all AR-associated symptoms. A total of 13 experts from Ukraine, Germany, and India participated in the development of this consensus statement. The lead author drafted the questions pertaining to diagnosis, management, treatment adherence, and real-life evidence of AR in Ukraine, and was agreed with the co-authors and expert panel. This consensus is obtained through guiding statements and recommendations based on literature evidences (recent research outcomes, randomized, and comparative studies), clinical practices and personal experience of using MP-AzeFlu in AR by allergist/ immunologists/ otolaryngologists from Ukraine. This consensus statement aimed to assist practitioners in selecting the appropriate treatment strategies, facilitate optimum use of MP-AzeFlu and provide symptomatic relief for patients with AR in the in Ukraine