Search

Abstract A new type of hybrid polymer particles capable of carrying the cytostatic drug doxorubicin and labeled with a gallium compound was prepared. These microparticles consist of a core and a hydrogel shell, which serves as the structural matrix. The shell can be employed to immobilize gallium oxide hydroxide (GaOOH) nanoparticles and the drug, resulting in hybrid beads with sizes of approximately 3.81 ± 0.09 μm. The microparticles exhibit the ability to incorporate a remarkably large amount of doxorubicin, approximately 0.96 mg per 1 mg of the polymeric carrier. Additionally, GaOOH nanoparticles can be deposited within the hydrogel layer at an amount of 0.64 mg per 1 mg of the carrier. These nanoparticles, resembling rice grains with an average size of 593 nm by 155 nm, are located on the surface of the polymer carrier. In vitro studies on breast and colon cancer cell lines revealed a pronounced cytotoxic effect of the hybrid polymer particles loaded with doxorubicin, indicating their potential for cancer therapies. Furthermore, investigations on doping the hybrid particles with the Ga-68 radioisotope demonstrated their potential application in positron emission tomography (PET) imaging. The proposed structures present a promising theranostic platform, where particles could be employed in anticancer therapies while monitoring their accumulation in the body using PET.

Background: Breakthrough neurotechnologies have allowed for new understanding of some brain disorders; however, identification and differential diagnosis of intracranial stenotic and occlusive lesions remains challenging. Magnetic resonance imaging (MRI) with dynamic contrast enhancement (DCE) is a tool that could be used for the quantitative assessment of endothelial permeability and microvascular volume in atherosclerotic plaques (AP). Aim: To assess quantitative parameters of vascular wall abnormalities in AP area and in obviously unchanged wall of intracranial arteries with MRI DCE and high spatial resolution Т1-weighed images before and after contrast injection, with calculation of the wall enhancement index (WEI) by mathematical modelling. Methods: This was a pilot cross-sectional uncontrolled study with consecutive recruitment of 29 patients with atherosclerotic abnormalities of brachiocephalic arteries, including intracranial. The patients’ median age was 66 [57; 72] years; they were mostly men (75.9%, n = 22). For the assessment of any brain abnormalities, MRI (magnetic induction 3 Tesla, Magnetom Prisma, Siemens) was performed in patients with standard sequence (Т2, T2-FLAIR), as well as MRI DCE for the assessment of intracranial arteries, before and after intravenous contrast injection, with high spatial resolution T1-weighed imaging and suppression of the signal from bloodstream and fat, with the calculation of WEI. Results: There were significant differences in WEI in AP and in unchanged wall (0.962 [0.686; 1.387] vs. 0.111 [0.014; 0.206], p 0.001). No significant differences were found between WEI values in internal carotid arteries APs (0.722 [0.573; 1.580]), middle cerebral arteries (0.921 [0.725; 1.183]), and basilar artery (1.343 [1.002; 1.419]) (p = 0.381). We also found significant difference (p = 0.034) in the extravascular extracellular fraction volumes ve (Tofts) in AP located in the basilar artery (0.171 [0.146; 0.325]), internal carotid arteries (0.579 [0.358; 1.000]), and middle cerebral arteries (0.134 [0.101; 0.269]). Conclusion: This is the first description of quantitative parameters characterizing vascular wall abnormalities in intracranial atherosclerosis. Despite its obviously intact state, vascular walls outside the intracranial AP was shown to be abnormal as well.

Abstract In contrast to abiotically formed carbonates, biogenetic carbonates have been observed to be nanocomposite, organo-mineral structures, the basic build-blocks of which are particles of quasi-uniform size (10–100 nm) organized into complex higher-order hierarchical structures, typically with highly controlled crystal-axis alignments. Some of these characteristics serve as criteria for inferring a biological origin and the state of preservation of fossil carbonate materials, and to determine whether the biomineralization process was biologically induced or controlled. Here we show that a calcium storage structure formed by the American lobster, a gastrolith initially consisting of amorphous calcium carbonate (ACC) and amorphous calcium phosphate (ACP), post-mortem can crystallize into (thus secondary) calcite with structural properties strongly influenced by the inherited organic matrix. This secondary calcite meets many structural criteria for biominerals (thus called the biomorphic calcite), but differs in trace element distributions (e.g., P and Mg). Such observations refine the capability to determine whether a fossil carbonates can be attributed to biogenic processes, with implications for the record of life on Earth and other terrestrial planets.

Abstract Mucus stasis is a pathologic hallmark of muco-obstructive diseases, including cystic fibrosis (CF). Mucins, the principal component of mucus, are extensively modified with hydroxyl (O)-linked glycans, which are largely terminated by sialic acid. Sialic acid is a negatively charged monosaccharide and contributes to the biochemical/biophysical properties of mucins. Reports suggest that mucin sialylation may be altered in CF; however, the consequences of reduced sialylation on mucus clearance have not been fully determined. Here, we investigated the consequences of reduced sialylation on the charge state and conformation of the most prominent airway mucin, MUC5B, and defined the functional consequences of reduced sialylation on mucociliary transport (MCT). Reduced sialylation contributed to a lower charged MUC5B form and decreased polymer expansion. The inhibition of total mucin sialylation de novo impaired MCT in primary human bronchial epithelial cells and rat airways, and specific α-2,3 sialylation blockade was sufficient to recapitulate these findings. Finally, we show that ST3 beta-galactoside alpha-2,3-sialyltransferase (ST3Gal1) expression is downregulated in CF and partially restored by correcting CFTR via Elexacaftor/Tezacaftor/Ivacaftor treatment. Overall, this study demonstrates the importance of mucin sialylation in mucus clearance and identifies decreased sialylation by ST3Gal1 as a possible therapeutic target in CF and potentially other muco-obstructive diseases.

Abstract Triple-negative breast cancer (TNBC) represents aggressive phenotype with limited treatment options due to the lack of drug targets. Natural compounds are extensively studied regarding their potential to alter the efficacy of cancer treatment Among them sulforaphane – an isothiocyanate of natural origin, was shown to be a hormetic compound, that may exert divergent effects: cytoprotective or cytotoxic depending on its concentrations. Thus, the aim of this study was to determine the effect of its low, dietary concentrations on the proliferation and migration of the TNBC cells in the in vivo and in vitro 2D and 3D model. Results of the in vivo experiment showed up to 31% tumor growth inhibition after sulforaphane treatment associated with lowered proliferating potential of cancer cells, reduced areas of necrosis, and changed immune cell type infiltration, showing less malignant type of tumor in contrast to the non-treated group. Also, the study revealed that sulforaphane decreased the number of lung metastases. The in vitro study confirmed that SFN inhibited cell migration, but only in cells derived from 3D spheroids, not from 2D in vitro cultures. The results show a specific role of sulforaphane in the case of cells released from the TNBC primary tumor and its environment.

Abstract Diffusion tensor imaging (DTI) metrics and tractography can be biased due to low signal-to-noise ratio (SNR) and systematic errors resulting from image artifacts and imperfections in magnetic field gradients. The imperfections include non-uniformity and nonlinearity, effects caused by eddy currents, and the influence of background and imaging gradients. We investigated the impact of systematic errors on DTI metrics of an isotropic phantom and DTI metrics and tractography of a rat brain measured at high resolution. We tested denoising and Gibbs ringing removal methods combined with the B matrix spatial distribution (BSD) method for magnetic field gradient calibration. The results showed that the performance of the BSD method depends on whether Gibbs ringing is removed and the effectiveness of stochastic error removal. Region of interest (ROI)-based analysis of the DTI metrics showed that, depending on the size of the ROI and its location in space, correction methods can remove systematic bias to varying degrees. The preprocessing pipeline proposed and dedicated to this type of data together with the BSD method resulted in an even − 90% decrease in fractional anisotropy (FA) (globally and locally) in the isotropic phantom and − 45% in the rat brain. The largest global changes in the rat brain tractogram compared to the standard method without preprocessing (sDTI) were noticed after denoising. The direction of the first eigenvector obtained from DTI after denoising, Gibbs ringing removal and BSD differed by an average of 56 and 10 degrees in the ROI from sDTI and from sDTI after denoising and Gibbs ringing removal, respectively. The latter can be identified with the amount of improvement in tractography due to the elimination of systematic errors related to imperfect magnetic field gradients. Based on the results, the systematic bias for high resolution data mainly depended on SNR, but the influence of non-uniform gradients could also be seen. After denoising, the BSD method was able to further correct both the metrics and tractography of the diffusion tensor in the rat brain by taking into account the actual distribution of magnetic field gradients independent of the examined object and uniquely dependent on the scanner and sequence. This means that in vivo studies are also subject to this type of errors, which should be taken into account when processing such data.

Abstract Fetal alcohol spectrum disorders (FASD) are a severe developmental condition resulting from exposure to alcohol during pregnancy. The aim of this study was to examine the concentrations of hormones involved in appetite regulation—ghrelin, leptin, and putative peptide YY-3 (PYY)—in the serum of individuals with FASD. Additionally, we investigated the relationship between these hormone levels and clinical indicators. We conducted an enzyme-linked immunosorbent assay on samples collected from 62 FASD patients and 23 individuals without the condition. Our results revealed a significant decrease in leptin levels among FASD patients compared to the control group (5.124 vs. 6.838 ng/mL, p = 0.002). We revealed no statistically significant differences in the levels of other hormones studied (ghrelin and PYY). Comparisons of hormone levels were also conducted in three subgroups: FAS, neurobehavioral disorders associated with prenatal alcohol exposure and FASD risk, as well as by sex. Assignment to FASD subgroups indicated changes only for leptin. Sex had no effect on the levels of hormones. Moreover, the levels of leptin showed a negative correlation with cortisol levels and a positive correlation with BMI and proopiomelanocortin. Alterations in appetite regulation can contribute to the improper development of children with FASD, which might be another factor that should be taken into consideration in the proper treatment of patients.

Depression is the most prevalent mental health condition. It’s estimated that nearly 5% of adults suffer from this disorder globally. Depression is marked by ongoing sadness and a loss of interest or pleasure in activities that were once enjoyable or fulfilling. It can also lead to disruptions in sleep and eating patterns. Common symptoms include fatigue and difficulty concentrating. According to WHO diabetes is a chronic, metabolic disease characterized by elevated levels of blood glucose which leads to the damage of the heart, blood vessels, eyes, kidneys and nerves. Nowadays the occurrence of diabetes mellitus, obesity and depression is getting higher and higher. Both conditions stand as prominent health issues in today’s society. Recent pandemic, wars, problems of the current world can cause depression and anxiety disorders. The fast-paced nature of our lives, work-life balance issues, sedentary habits, and time constraints can lead to opting for fast food and neglecting a healthy diet. People with diabetes are more prone to experiencing depression. Moreover, a significant portion of cases remains underdiagnosed.

Introduction and aim of the study: Thiamine is a water-soluble vitamine, which bioactive form is necessary for energy metabolism in all cells. Deficiency of thiamine may be caused by malnutrition, alcoholism and certain diseases and it leads to an acute neuropsychiatric disorder called Wernicke encephalopathy. Untreated patients can develop a residual syndrome called Korsakoff syndrome. The aim of our study is to present current knowledge of history, pathophysiology, causes, symptoms and treatment of vitamine B1 depletion and Wernicke-Korsakoff’s syndrome. Material and methods: Our review is based on the analysis of materials collected in „Pubmed”, „Google Scholar” and other scientific articles using keywords: „thiamine”, „thiamine deficiency”, „Wernicke encephalopathy”, „Korsakoff syndrome”. Conclusions: Despite numerous studies, Wernicke encephalopathy is still difficult to diagnose. Attention should be paid to the possibility of vitamin B1 deficiency in people who are at risk of it like alcoholics, malnourished or psychiatric patients. Wernicke encephalopathy is an acute neuropsychiatric disorder so the treatment should be started as soon as possible to reduce the risk of developing Korsakoff syndrome.

Introduction and purpose: A collection of symptoms known as cerebral palsy first manifest in early childhood and result in profound physical impairment. Cerebral palsy is thought to affect 1 in 500 live births, or roughly 17 million people worldwide. The type of cerebral palsy determines the clinical symptoms. Movement coordination disorders, epilepsy, muscle weakness, and feeding difficulties are the most common symptoms. The purpose of this article is to familiarize readers with the options for nutritional therapy for cerebral palsy patients. Material and methods The following review was based on articles from the PubMed and Google Scholar databases. Key search terms included cerebral palsy; nutrition; treatment; gut microbiota.. State of knowledge Early identification of malnutrition symptoms and appropriate interventions, such as the implantation of a percutaneous endoscopic gastrostomy tube in patients who are unable to swallow food, are the cornerstones of nutritional therapy for cerebral palsy patients. Dysphagia is a major problem in the population of patients with cerebral palsy, and multidisciplinary therapy is necessary for them. Patients' serum vitamin D levels are also influenced by their diet; 50% of those with cerebral palsy have a deficiency in this nutrient. Conclusions For people with cerebral palsy, nutrition is very important. Premature death may arise from malnutrition brought on by the disease's advancement. As a result, individuals with cerebral palsy need to receive specialized care

Introduction: Duchenne muscular dystrophy is a genetic X-linked recessive disorder. This condition is characterized by progressive loss of muscle tissue. Thus, it results in deterioration and inability to perform basic motor skills such as independent movement or breathing. Due to progressive muscle weakness, patients with advanced stages of DMD require mechanical ventilation, feeding, and rehabilitation. Furthermore, alterations in cardiac muscle lead to cardiomyopathy. Despite advanced supportive treatment, DMD is a fatal disease. Purpose: The aim of the paper is to present, using a case study description, the current standards of treatment for patients with Duchenne muscular dystrophy as well as the current state of knowledge and new discoveries regarding this medical condition. Material and methods The patient's medical records were analyzed and available literature in PubMed was reviewed to write this article using the keywords: „Duchenne muscular dystrophy”; „cardiomyopathy”; „mechanical ventilation”; „gene therapy”; Conclusions Early detection of respiratory and circulatory insufficiency improves the patient's quality of life. Many patients with an advanced stage of Duchenne muscular dystrophy need specialized treatment, for example, in the intensive care unit. Therefore there is an urgent need for new treatment methods, such as gene therapies, which can slow down or break the course of the disease. New discoveries and the implementation of new treatment standards can enhance the quality of life for patients and extend their lifespans.

Introduction and purpose: The number of invented and produced medications has increased over recent years. Besides their positive impact on health, they invariably provide various kinds of side effects. This review is focused on malignant neuroleptic syndrome, a rare condition with no fully confirmed pathogenesis, which at least partially can be explained as an adverse effect of blocking dopamine receptors. Even though it usually affects psychiatric or neurological patients, doctors of all medical specializations should stay alert, as the condition can often lead to premature death. Brief description of knowledge: The main symptoms associated with NMS are hypertonia, hyperpyrexia, autonomic instability and altered consciousness. They can appear in any configuration, sometimes followed by less characteristic manifestations. It should be primarily differentiated from serotonin syndrome, malignant hyperpyrexia and catatonia, mostly through the interview of those who have taken medications and undergone surgeries, as there are not any specific lab tests available. Fundamental treatment methods consist of neuroleptic withdrawal, intensive supportive care, drug administration and eventually ECT. Summary: NMS is an uncommon, severe disease that should be carefully considered in patients treated with neuroleptics. Due to its rarity and sudden onset, it appears to be problematic to conduct widespread research and studies, so there are still no concrete, consistent and unquestioned guidelines on recognizing and treating the condition.

Abstract A new azo polymer containing photoisomerizable azo pyridine functionalities was synthesized via Mitsunobu reaction of 4-(4-hydroxyphenylazo)pyridine with poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (p(HEMA-co-MMA)) for creating new photochromic materials. The resulting polymer with azo pyridine side groups was characterized for structural, thermal, and optical properties. UV–vis, 1H NMR and IR spectroscopies confirmed that all hydroxyl groups in p(HEMA-co-MMA) were substituted with azo dye. The obtained azo copolymer exhibited high thermal stability (around 240 °C) and a glass transition temperature (113 °C), promising for applications. The trans-to-cis isomerization upon UV irradiation and the thermal back reaction of the azo chromophore in the copolymer in the solid state was studied. A photostationary state with 50% content of cis-isomers upon 6 min of UV irradiation was reached, and during 48 h dark relaxation at ambient temperature, all cis-isomers converted to the trans form. Additionally, the possibility of efficient photogeneration of surface relief gratings with high amplitude of azo copolymer surface modulation was demonstrated.

Abstract Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of tumors that exhibit an unpredictable and broad spectrum of clinical presentations and biological aggressiveness. Surgical resection is still the only curative therapeutic option for localized PanNET, but the majority of patients are diagnosed at an advanced and metastatic stage with limited therapeutic options. Key factors limiting the development of new therapeutics are the extensive heterogeneity of PanNETs and the lack of appropriate clinically relevant models. In that context, genomic sequencing of human PanNETs revealed recurrent mutations and structural alterations in several tumor suppressors. Here, we demonstrated that combined loss of MEN1, ATRX, and PTEN, tumor suppressors commonly mutated in human PanNETs, triggers the development of high-grade pancreatic neuroendocrine tumors in mice. Histopathological evaluation and gene expression analyses of the developed tumors confirm the presence of PanNET hallmarks and significant overlap in gene expression patterns found in human disease. Thus, we postulate that the presented novel genetically defined mouse model is the first clinically relevant immunocompetent high-grade PanNET mouse model.

Abstract Blended Intensive Programmes (BIP’s) represent a valuable tool for gathering knowledge and summarising the latest trends in medicine and dentistry. Blended education has been found, even before the COVID-19 pandemic, to increase the level of education and stimulate effective learning for postgraduate healthcare professionals. Interprofessional education is critical for preparing students to enter the health workforce, where teamwork and collaboration are important competencies. This article outlines the key points of the Blended Intensive Programme’s implementation in dental education organised by Wroclaw Medical University in Poland. BIP involved professors from 12 universities or research institutions from Europe and South America and 28 participants from 8 countries. The course was taught remotely and in person. In addition, it included a visit to the university and practical classes with artificial simulation and practice in dentistry. A structured questionnaire enabled measuring the evaluation of students’ perception of the COVID-19 education before and after the pandemic. The European Region Action Scheme for the Mobility of University Students (ERASMUS) was fundamental to carrying out the BIP with the participation of several countries, allowing the exchange of knowledge, assessing the impact of the pandemic on dental universities, and strengthening international collaborations and the future project of research, education and clinical assistance. We conclude that hybrid teaching programmes broaden the learning spectrum in dental studies by allowing transnational and interdisciplinary approaches that make students aware of the importance of their work within the framework of the general health approach, as this differs from country to country.

Abstract Identifying disease predictors through advanced statistical models enables the discovery of treatment targets for schizophrenia. In this study, a multifaceted clinical and laboratory analysis was conducted, incorporating magnetic resonance spectroscopy with immunology markers, psychiatric scores, and biochemical data, on a cohort of 45 patients diagnosed with schizophrenia and 51 healthy controls. The aim was to delineate predictive markers for diagnosing schizophrenia. A logistic regression model was used, as utilized to analyze the impact of multivariate variables on the prevalence of schizophrenia. Utilization of a stepwise algorithm yielded a final model, optimized using Akaike’s information criterion and a logit link function, which incorporated eight predictors (White Blood Cells, Reactive Lymphocytes, Red Blood Cells, Glucose, Insulin, Beck Depression score, Brain Taurine, Creatine and Phosphocreatine concentration). No single factor can reliably differentiate between healthy patients and those with schizophrenia. Therefore, it is valuable to simultaneously consider the values of multiple factors and classify patients using a multivariate model.

Abstract The present study investigated several properties such as friction, hardness, penetration work, and cutting forces in soaps formulated with apple and carrot pomace at varying concentrations of 5%, 10%, and 15%. To gain insights into the molecular-level alterations within the formulated soap samples, they were spectroscopically analyzed using Fourier-transform infrared spectroscopy. The sliding friction analyses revealed that the investigated extrudate additives had no significant impact on the frictional forces of the soaps. However, notable differences were observed in the cutting force, hardness, and penetration work between the control and pomace-added samples. Excluding the control samples, no statistically significant distinctions were found between the cutting force, hardness, and work of penetration of soaps containing apple pomace and carrot pomace. Moreover, the quantity of pomace incorporated did not induce any significant variations in the results. The obtained samples were characterised at the molecular level using FTIR Fourier transform infrared spectroscopy. On the other hand, alterations in band intensities suggested improved molecular packing of the compounds within the samples due to the presence of the additives.

Introduction: Mental disorders are common and still growing problem around the globe. Significantly decreasing quality of life, they are often source of true suffering for patients and their families leading to further health issues or even dramatic outcomes resulting in death. As public awareness rises, more and more people understand risks and tend to look for help as fast as possible. Currently available treatment methods are not always efficient enough to deal with more complex cases. Therefore it is important to look for new therapy options incrementing chances of fast and successful treatment. Results: Studies showed that psilocybin is not only able to lower depression and anxiety scores in patients with major depressive disorders or with serious life-threatening conditions but also proved this effect to be long-lasting. At the same time, no or little adverse side effects were noticed. Conclusions: Psilocybin is potentially a good method for depression treatment in some groups of patients. It should be considered if other, better known therapies show little or no effects.

Introduction and purpose : Type 2 diabetes is currently a serious problem worldwide. Each year, the number of individuals with carbohydrate metabolism disorders is increasing. This is due to an unhealthy lifestyle, lack of physical activity, and a diet rich in highly processed foods. Currently, the treatment of type 2 diabetes is based on the use of oral antidiabetic medications, with the first choice often being a derivative of biguanides, such as metformin. Berberine has been used in China for many years as a hypoglycemic agent, and its efficacy is compared to metformin preparations. This paper focuses on the benefits of using berberine in patients with prediabetes or type 2 diabetes and compares the effects of berberine preparations to classical medications used in diabetes treatment. Material and methods : The literaue was reviewed in PubMed and Google Scholar scientific database in 2013-2023 using the following keywords : berberine, diabetes mellitus type 2, hyperlipidemia, hyperglicemia Conclusions : The studies included in this manuscript have shown that berberine is a promising agent for adjunctive treatment in type 2 diabetes. It exhibits a range of positive effects such as lowering blood glucose levels, improving lipid profile, with no serious adverse effects reported. However, further research is needed to confirm these findings and develop an effective treatment plan.

Introduction and purpose Cariprazine is an atypical antipsychotic drug approved for the treatment of schizophrenia, as well as manic and mixed episodes associated with bipolar disorder. It functions as a dopamine multifunctional agent, a partial agonist at dopamine and serotonin receptors. Unlike the majority of antipsychotics, which primarily target positive symptoms through dopaminergic antagonism, often neglecting negative, cognitive, and affective symptoms, the unique cariprazine's pharmacological profile, particularly potent blockade of D3 dopamine receptors, suggests the potential for numerous clinical applications. The aim of this study is to present current knowledge of cariprazine, focusing particularly on its mechanism of action, potential applications, adverse effects, and pharmacokinetic properties that could impact its clinical use. Methods and materials A review of the literature available in the PubMed database was performed using the key words: cariprazine; atypical antipsychotic drug; antipsychotic medication; schizophrenia treatment; bipolar disorder treatment; mania treatment; depression treatment, dopamine agonist. Conclusions Cariprazine demonstrates a unique pharmacological profile, offering potential benefits in managing a wide range of psychiatric disorders, including schizophrenia, bipolar disorder (mania, depression, mixed episodes), unipolar depression, and co-occurring substance use disorders. Clinical studies have shown efficacy in reducing symptoms and improving negative and cognitive function, with a favorable metabolic profile, minimal impact on cardiovascular system, and generally mild adverse effect profile. However, further research is necessary to explore its full therapeutic potential and optimize its clinical use in diverse patient populations.

Вiotic factors may be the driving force of plastic fragmentation along with abiotic factors. Since understanding the processes of biodegradation and biological depolymerization of plastic is important, a new methodological approach was proposed in this study to investigate the role of marine invertebrate digestive enzymes in plastic biodegradation. The aim of this study is to evaluate the possibility of enzymatic biodegradation of polyethylene fragments in the digestive gland homogenate of marine invertebrates differing in their feeding type (Strongylocentrotus nudus, Patiria pectinifera, Mizuhopecten yessoensis). Significant changes are found in the functional groups of the polymer after 3 days of incubation in the digestive gland homogenates of the studied marine invertebrates. A significant increase in the calculated CI (carbonyl index) and COI (сarbon-oxygen index) indices compared to the control sample was observed. The results suggest that digestive enzymes of studied organisms may play an important role in the biogeochemical cycling of plastic.

Introduction and purpose: Post-traumatic stress disorder is a psychiatric condition following an extreme event that causes a near death of an involved individual. Since conventional treatments using selective serotonin reuptake inhibitors do not consistently yield therapeutic success, alternative substances are being explored as potential solutions. This study aims to compile information regarding the outcomes of utilizing psychedelics in individuals diagnosed with PTSD. Brief description of the state of knowledge: In July 2023, after a number of clinical trials and 20-year-long efforts to overturn the impact of a prohibition, Australia became the first country to allow doctors, in clinical development and under strict control, to use the 3,4-methyl​enedioxy​methamphetamine (MDMA) commonly known as ecstasy, as well as psylocybin in patients with post-traumatic stress disorder or depression [8]. There is a noticeable annual growth of inquiries on PubMed involving the keywords "psychedelics" and "therapeutic", amounting to 92 in 2000 and topped by 738 searches in 2023, whereas the total number of results consists of 8415 positions. Therapeutic effects of psychedelics are becoming more recognized over time. Summary: Post-Traumatic Stress Disorder (PTSD) is a complex condition that affects both the psychological and somatic aspects of the body. Thus, a multidimensional intervention is indicated. The use of psychedelics might contribute to improvements not only in the severity of PTSD but also in depression or pain. Further research on a larger group of participants should be carried out to assess the potential role of psychedelics in conventional medicine in the future, alongside psychotherapy.

Introduction and purpose: Chronic pain is a struggle itself and also a symptom in many common conditions. Its complexity requires diverse treatment methods including some that might seem unconventional, for example, horse riding. This study gathers information about the use of equine assisted therapy in pain relief. Brief description of the state of knowledge: Hippotherapy is known as an important part of care for patients with cerebral palsy, attention deficit and autism. The rhythmical, multidimensional movements of the horse are transmitted to the rider’s pelvis and help in strengthening and stretching the muscles which result in better posture stabilization and balance. The positive effects of equine assisted therapy are not limited to only physical ones but positive social, cognitive and psychological effects can be observed as well. In order to lower the cost and time of the therapy, horse riding simulators were invented. So far, horse riding has been tested as a pain relief tool in entities like nonspecific low back pain, multiple sclerosis and arthritis. Summary: Horse riding sessions had beneficial effects on pain levels among patients with nonspecific back pain and arthritis. There is a need to conduct further research in order to properly compare the use of real horses versus horse simulators. Hippotherapy was well perceived by different patient groups so maybe it has the potential to be an important part of pain management in various conditions.

Abstract The aim of this study was to assess the prevalence of hypertension and to investigate risk factors linked to hypertension in older adults. An observational study was conducted in a group of adults between 60 and 85 years of age, living in south-eastern Poland. In line with the specific inclusion criteria, 80 women and 29 men were enrolled for the study (109 adults). Participants’ body weight, height, and body fat percentage (BFP) were assessed using a bioelectrical impedance analysis, blood pressure was measured using automated oscillometric sphygmomanometer, moderate-to-vigorous physical activity (MVPA) and sedentary time were assessed using a tri-axial accelerometer, whereas data related to socio-economic and lifestyle factors were collected using a self-report technique. Arterial hypertension was found at a rate of 16% in participants with normal body weight, 22% in those with overweight and 85% in those with obesity. Body mass index (BMI) and BFP correlated significantly with systolic blood pressure (SBP) and diastolic blood pressure (DBP). The highest median SBP and DBP values were found in the group of participants with obesity, and the lowest values were identified in those with normal body weight. Out of all the investigated socio-economic risk factors linked to hypertension, education level was the only one that showed significant associations. A logistic regression analysis was performed to check which factors were most strongly associated with hypertension in the study group. The stepwise method showed that hypertension was more common in participants with a higher BMI, and BFP and in those who did not meet MVPA recommendation.

Abstract Statistics show that the inhabitants of Poland are producing increasingly more household waste. This article attempts to determine the current level of development of Poland in the field of waste management concerning other EU countries and partner countries; identify trends in the mass of generated, segregated, and mixed municipal waste; and obtain an idea of the attitude of the Polish population toward sorting waste at the source to bring the country to a higher level of waste management. The empirical base is statistical data published on the website of the EU Data Explorer and the Central Statistical Office. The ranking of countries was determined by the TOPSIS method using a synthetic indicator based on the selected diagnostic features. The significance of the obtained ranks was tested using the non-parametric Friedman test (p

Abstract The digital environment can pose health risks through exposure to unhealthy content. Yet, little is known about its relation to children’s cognitive functioning. This study investigates the association between digital media (DM) exposure and children’s cognitive functioning. This cross-sectional study is based on examinations of children aged 8–18 years (N = 8673) of the I.Family cohort (2013–2014). Exposure to television, computer, smartphone and internet was self-reported (hours/day). Media multitasking (MMT) was defined as simultaneous use of computers with other digital or non-screen-based activities. Standard instruments were used to assess cognitive inflexibility (score: 0–39), decision-making ability (− 100 to + 100) and impulsivity (12–48). Adjusted regression coefficients and 99.9%CIs were calculated by generalized linear mixed-effects models. In total, 3261 participants provided data for impulsivity, 3441 for cognitive inflexibility and 4046 for decision-making. Exposure to smartphones and media multitasking were positively associated with impulsivity (βsmartphone = 0.74; 99.9%CI = 0.42–1.07; βMMT = 0.73; 99.9%CI = 0.35–1.12) and cognitive inflexibility (βsmartphone = 0.32; 99.9%CI = -0.02–0.66; βMMT = 0.39; 99.9%CI = 0.01–0.77) while being inversely associated with decision-making ability. Extensive smartphone/internet exposure combined with low computer/medium TV exposure was associated with higher impulsivity and cognitive inflexibility scores, especially in girls. DM exposure is adversely associated with cognitive functioning in children and adolescents. Children require protection against the likely adverse impact of digital environment.

Abstract Ultra-high dose rate (UHDR) radiotherapy (RT) or FLASH-RT can potentially reduce normal tissue toxicity. A small animal irradiator that can deliver FLASH-RT treatments similar to clinical RT treatments is needed for pre-clinical studies of FLASH-RT. We designed and simulated a novel small animal FLASH irradiator (SAFI) based on distributed x-ray source technology. The SAFI system comprises a distributed x-ray source with 51 focal spots equally distributed on a 20 cm diameter ring, which are used for both FLASH-RT and onboard micro-CT imaging. Monte Carlo simulation was performed to estimate the dosimetric characteristics of the SAFI treatment beams. The maximum dose rate, which is limited by the power density of the tungsten target, was estimated based on finite-element analysis (FEA). The maximum DC electron beam current density is 2.6 mA/mm2, limited by the tungsten target's linear focal spot power density. At 160 kVp, 51 focal spots, each with a dimension of $$2\times 20$$ 2 × 20 mm2 and 10° anode angle, can produce up to 120 Gy/s maximum DC irradiation at the center of a cylindrical water phantom. We further demonstrate forward and inverse FLASH-RT planning, as well as inverse-geometry micro-CT with circular source array imaging via numerical simulations.

Given the persistent safety incidents in operating rooms (ORs) nationwide (approx. 4,000 preventable harmful surgical errors per year), there is a need to better analyze and understand reported patient safety events. This study describes the results of applying the Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) supported by the Teamwork Evaluation of Non-Technical Skills (TENTS) instrument to analyze patient safety event reports at one large academic medical center. Results suggest that suboptimal behaviors stemming from poor communication, lack of situation monitoring, and inappropriate task prioritization and execution were implicated in most reported events. Our proposed methodology offers an effective way of programmatically sorting and prioritizing patient safety improvement efforts.

Introduction Curcumin, the active ingredient in turmeric, is gaining increasing attention due to its potential health benefits, especially in the context of its immunomodulatory and anticancer properties. Aim of the study The aim of this review was to discuss recent findings regarding the impact of curcumin on the immune system and its potential applications in anticancer therapy. Materials and methods The paper was created based on the Pubmed and Scholar database. The literature was reviewed using the keywords: „curcumin”, „immunomodulatory effects”, „cytokines”, „anticancer”, „apoptosis”, „cell proliferation”, „radiosensitizing”. Results Studies have confirmed that curcumin, especially in the form of nanocurcumin, exhibits significant immunomodulatory effects. It reduces the number of Th17 cells, increases Treg cells, and regulates the expression of pro-inflammatory cytokines, which is crucial in controlling autoimmune reactions. Furthermore, it demonstrates anticancer activity by inhibiting the growth of cancer cells, stimulating apoptosis, and enhancing the effectiveness of anticancer therapy. Conclusions Despite promising results, further research on the safety of curcumin therapy, particularly in the long term, is essential. Limitations associated with bioavailability and pharmacokinetics suggest the need for the development of formulations with increased bioavailability to maximize the potential benefits of curcumin in the treatment of various disorders.

Introduction and purpose Acute appendicitis, a common surgical abdominal ailment, mostly affects individuals in their second or third decade of life, with an annual incidence of about 100 cases per 100,000 persons. This literature review aims to synthesize evidence from diverse sources, summarizing optimal practices for clinical implementation. Surgical intervention, achieving almost 100% cure rates, remains the gold standard, emphasizing challenges in patient qualification for non-surgical approachesNon-operative treatment, considered safe for uncomplicated cases, involves antibiotic therapy, with concerns about antibiotic resistance. Summarizing the current understanding of antibiotic therapy of appendicitis seeks to enhance its effective use, decrease adverse incidents in patients, and contribute to the overall safety of both patients and healthcare providers. Material and methods The following review of studies was based on articles obtained from the PubMed and Google Scholar databases. Key search terms included acute appendicitis, acute appendicitis conservative treatment, appendectomy, surgical abdominal diaseases, antibiothic therapy. Conclusions The literature review highlights the existing challenges in the management of acute appendicitis, acknowledging the efficacy of both methods. While surgical intervention with high cure rates, the increasing popularity of non-operative therapy encourages optimism for comprehensive research in the future. The need for large, randomized studies comparing long-term clinical effectiveness is emphasized, aiming to inform decision-making and optimize patient outcomes.

Introduction Viloxazine is an antidepressant medication classified as an SNRI (serotonin and norepinephrine reuptake inhibitor). In April 2021, it received FDA approval in the United States for the treatment of ADHD in children aged 6 to 17. Subsequently, in May 2022, it was also approved for the treatment of adults with ADHD [1]. Viloxazine, available in extended-release capsules, represents novel non-stimulant medication option for patients with ADHD. Aim of the study Our aim was to review the viloxazine in the fields of ADHD treatment, summarize current knowledge and analyze the first treatment results. Methods and materials A review of the literature available in the PubMed database was performed, using the key words: „Viloxazine" ; „ADHD treatment" ; „ADHD”, „attention deficit hyperactivity disorder”, „attention deficit hyperactivity disorder treatment”; „ADHD non-stimulant treatment”; „ADHD non-stimulant”; „ADHD non-stimulant drugs”, „SPN-812” Conclusion Viloxazine presents a promising non-stimulant alternative for ADHD treatment with more favorable pharmacokinetics, new way of possible administration and fewer adverse effects, particularly within the cardiovascular system, than other available ADHD medication options. While these findings are encouraging, continual research is imperative to establish the long-term safety profile.

Introduction In contemporary medicine, increasing attention is being devoted to alternative forms of therapy. Immersing oneself in cold water, cryotherapy, or cold showers are practices that have long sparked interest due to their potential health benefits. Aim of the study The aim of this comprehensive review is to analyze the impact of cold exposure on the human body, with particular emphasis on its effects on the nervous system. Through the synthesis of available research, the paper seeks to identify health benefits and areas requiring further investigation in the context of various cold application practices. Materials and methods An analysis of scientific articles available in the Pubmed and Google Scholar databases was conducted. Publications from recent years that most relevantly addressed the discussed topic were utilized for this study. The search process involved the use of the following keywords: “cold,” “cold showering,” “cold water,” “cryotherapy.” Results The results of the literature review unequivocally indicate a positive, multifaceted impact of cold on the human body, particularly with an emphasis on the nervous system. Significant therapeutic effects observed in various fields suggest that the application of cold may be a promising alternative in promoting health and treating numerous medical conditions. Summary The focused literature review on the impact of cold on the human body, especially the nervous system, presents various therapies such as cryotherapy or cold water immersion, emphasizing their beneficial effects on the nervous, cardiovascular, endocrine, lymphatic, musculoskeletal, and joint systems. However, despite the observed benefits, further research is needed to gain a more detailed understanding of the mechanisms of action and to ensure the safety of these practices.

Introduction and purpose Polycystic ovary syndrome is a common reproductive disorder, accompanied primarily by hyperandrogenism and insulin resistance. Myo-inositol (MI) and D-chiro-inositol (DCI), have emerged as potential therapeutic agents due to their role as insulin sensitizers. This article examines the effects of inositol therapy on fertility in women with PCOS and its role in assisted reproductive technology (ART). Studies suggest that inositols alleviate irregular menstruation, reduce androgen levels and positively affect ovulation rates. MI supplementation has also shown positive effects during controlled ovarian hyperstimulation and IVF procedures, reducing the required FSH dose and cycle length. However, despite positive results on ovulation and menstrual regularity, the article indicates the need for further studies to establish inositol as standard ART therapy in patients with PCOS. Material and methods The following review was based on articles from the PubMed and Google Scholar databases. Key search terms included polycystic ovary syndrome; assisted reproductive treatment, insulin resistance, inositols, Myo-inositol, D-chiro-inositol. Conclusions Inositols are a promising therapeutic option for women with PCOS. They have been shown to have positive effects on improving insulin sensitivity and fertility. However, despite inositol's safety and easy availability, the ideal dose and timing of use, the appropriate MI/DCI ratio, as well as the potential side effects of excess DCI and the problem of inositol resistance, require further comprehensive studies.

Introduction and purpose Migraine is a common disease mostly affecting women. It has a huge influence on patients’ life strongly decreasing its quality by cause of repetitive headache episodes and often comes with unpleasant and burdensome symptoms like photophobia, nausea or vomiting. This article focuses on migraine treatment, especially on new drugs. Primary drugs used in migraine attacks are non-steroid anti-inflammatory drugs (NSAI) and triptans. Because of their side effects and impact on internal organs, these substances are often contraindicated or inefficient. The same applies to triptans, which cannot be used by patients with cardiovascular diseases. Due to the need of a new migraine treatment path development, new remedies have been found, bringing hope for patients who could not use prior options. They are divided into two groups: ditans (lasmiditan), which are 5-HT1F serotonin receptor agonists and gepants (ubrogepant, rimegepant, atogepant and zavegepant), which are CGRP receptor antagonists. A summary of the current state of knowledge is intended to increase the awareness of physicians and patients when selecting the appropriate treatment. Material and methods The following review was based on articles obtained from the PubMed and Google Scholar databases. Key search terms included migraine, ditans, gepants, migraine treatment. Conclusions Drugs described in this study clearly show the new pathway of migraine treatment and prevention. They are safer and show more benefits than substances currently used. They can also be used in wider range of patients with conditions marked as contraindications for current schemes. However more research is still needed to fully describe their characteristics.

Abstract Health literacy is an asset for and indicator of adolescents’ health and wellbeing, and should therefore be monitored and addressed across countries. This study aimed to develop and validate a shorter version of the original 10-item health literacy for school-aged children instrument in a cross-national context, using data from the health behaviour in school-aged children 2017/18 survey. The data were obtained from 25 425 adolescents (aged 13 and 15 years) from seven European countries. Determination was made of the best item combination to form a shorter version of the health literacy instrument. Thereafter, the structural validity, reliability, measurement invariance, and criterion validity of the new 5-item instrument were examined. Confirmatory factor analysis showed a good model fit to the data across countries and in the total sample, confirming the structural validity (CFI = 0.995, TLI = 0.989, SRMR = 0.011, RMSEA = 0.031). The internal consistency of the instrument was at a good level across countries (α = 0.87–0.98), indicating that the instrument provided reliable scores. Configural and metric invariance was established across genders, ages, and countries. Scalar invariance was achieved for age and gender groups, but not between countries. This indicated that the factor structure of the scale was similar, but that there were differences between the countries in health literacy levels. Regarding criterion validity, structural equation modelling showed a positive association between health literacy and self-rated health in all the participating countries. The new instrument was found to be valid and reliable for the purposes of measuring health literacy among adolescents in a cross-national context.

An unhealthy diet often is a cause of obesity, chronic inflammation, and metabolic disruption in multiple organs. However, the direct influence of elevated lipid or sugar consumption on liver, pancreatic, and sperm mitochondria is not well understood. The aim of the study was to investigate the functional activity of mitochondria of liver, pancreatic acinar cells, and sperm cells in rats on a short-term (7 weeks) diet with high fat or high fat and high sugar content. Male Wistar rats were on a basic, high-fat or high-fat high-sugar diet for 7 weeks. At the end of the experiment, visceral fat mass, blood glucose and lipids were measured. Mitochondrial functional activity was evaluated with oxygen consumption assay. In isolated pancreatic acinar cells, NAD(P)H autofluorescence and mitochondrial membrane potential were also studied. No difference in body mass was observed between the 3 groups at the end of the experiment. Visceral fat mass was slightly but significantly elevated in rats on a high-fat high-sugar diet. Both diets did not affect plasma glucose or triglyceride levels but caused a modest elevation of total plasma cholesterol. Respiration and oxidative phosphorylation of isolated liver mitochondria were not affected by any experimental diet. In pancreatic acinar cells, a high-fat diet caused a significant decrease of basal respiration by ~15%, but no effects were observed on the maximal rate of uncoupled respiration, mitochondrial membrane potential, or NAD(P)H autofluorescence. In these cells, a ketone body 3-hydroxybutyrate caused elevation of uncoupled respiration and NAD(P)H level irrespectively of the diet. Diets did not cause any change in sperm concentration, viability or motility. Surprisingly, in animals on a high-fat high-sugar diet, a significant increase in both basal and maximal respiration of sperm cells was observed. Collectively, these data show that while the elevated fat and sugar content in the diet does not cause significant obesity, no detrimental effects on mitochondria of the liver, pancreas, and sperm cells are observed.

Abstract Riverine predacious beetles (RPB) (Carabidae, Staphylinidae) are highly diverse and numerous elements of riverine ecosystems. Their historical and contemporary distribution and diversity are highly dependent on natural flow regimes and topography of watercourses. Despite broad knowledge of their ecology, data on population genetic diversity and connectivity are lacking. This study aimed to fill this gap in order to solve two principal hypotheses assuming (i) congruence of phylogeographic patterns observed for RPB indicating that they share a common history and the ecological adaptations to the dynamic environment, (ii) genetic structuration of populations according to river basins. The Carpathian populations of four ground beetles and three rove beetles were examined using cytochrome oxidase and arginine kinase sequencing. There are substantial differences in RPB demographic history and current genetic diversity. Star-like phylogeny of Bembidion and complex haplotype networks of Paederus/Paederidus, with some haplotypes being drainage-specific and others found in distant populations, indicate a general lack of isolation by distance. Signs of recent demographic expansion were detected for most RPB with the latest population collapse for some rove beetles. To some extent, migration of examined species has to be limited by watersheds. Observed phylogeographic patterns are essential for correctly understanding RPB meta-population functioning.

Background Compensatory health beliefs may serve as one of many self-regulatory strategies that individuals employ to maintain healthy lifestyles. Past research with samples from a general population has shown, however, that compensatory beliefs are ineffective in this regard and may even lead to inaction in future health-related behaviors such as eating healthily or being active. To better understand this phenomenon, in the present study, changes in compensatory health beliefs regarding various life domains were examined in a group of pregnant women. Participants and procedure In a longitudinal study design, 166 women completed questionnaires in the first (t1), the second (t2), and the third (t3) tri-mester of their pregnancies. We assessed the level of their self-control as a trait (t1, t2, t3), compensatory health beliefs (t1, t2, t3), and unhealthy snacking (t3). Results As predicted, self-control as a trait decreased and the levels of compensatory beliefs increased over time. A linear mixed ef-fects analysis showed that self-control was the best predictor of compensatory beliefs in the third trimester. Finally, com-pensatory health beliefs in the third trimester mediated the effect of self-control at the beginning of pregnancy on un-healthy snacking in the third trimester. Conclusions It appears important to support pregnant women in opting for constructive self-regulatory strategies, especially in their final trimesters, when coping resources are exhausted by the challenges of this period.

Abstract Telomere dysfunction is a notable event observed in many cancers contributing to their genomic instability. A major factor controlling telomere stability is the human telomerase reverse transcriptase catalytic subunit (hTERT). Telomere shortening has been observed in multiple myeloma (MM), a plasma cell malignancy with a complex and heterogeneous genetic background. In the present study, we aimed to analyse telomere length and hTERT genetic variants as potential markers of risk and survival in 251 MM patients. We found that telomere length was significantly shorter in MM patients than in healthy individuals, and patients with more advanced disease (stage III according to the International Staging System) had shorter telomeres than patients with less advanced disease. MM patients with hTERT allele rs2736100 T were characterized with significantly shorter progression-free survival (PFS). Moreover, allele rs2736100 T was also found to be less common in patients with disease progression in response to treatment. hTERT rs2853690 T was associated with higher haemoglobin blood levels and lower C-reactive protein. In conclusion, our results suggest that telomere length and hTERT genetic variability may affect MM development and can be potential prognostic markers in this disease.

Abstract Ranunculus acris L. is a native species widely distributed throughout Europe and is invasive in nonnative areas, causing substantial economic losses in pasture productivity. The present study examined the effects of sodic salinity on the growth and functioning of this species. Salinity stresses the germination process and seedling growth, indicating that the studied species experience serious limitations at 60–90 mmol dm−3 NaCl and cannot establish in habitats where salinity is equal to or greater than 150 mmol dm−3 NaCl. R. acris is tuned to subsaline habitats characteristic of temperate meadows, as its growth and functioning were the best when the plants were treated with 30 mmol dm−3 NaCl. Increasing salinity (60 and 90 mmol dm−3 NaCl) hampered growth, leaf morphology and photosynthesis but not mineral nutrition, as Na accumulation seemed to be the most outlined effect of NaCl application. Changes in leaf morphological characteristics coordinated well with Na content in those organs, which indicates that leaf appearance can be easily catchable sign of progressing salinity. Ultimately, progressing salinity reduces the competitiveness of the studied species, shifting its strategy to ruderal behavior, but under subsaline conditions, the strategy of this species seems to be most balanced.

Abstract The major cause of soil degradation (contamination, erosion, compaction) is closely linked to agriculture, i.e., unsustainable agriculture practices, which are reflected in the depletion of the soil organic carbon pool, loss in soil biodiversity, and reduction of C sink capacity in soils. Therefore, the agricultural practice of applying carbon-rich materials into the soil is an attractive solution for climate change mitigation and soil ecosystem sustainability. The paper aimed to evaluate the effectiveness of the addition of organic-mineral mixtures to the mineral salts (NPK), including the exogenous organic matter (lignite) mixed with zeolite-carbon (NaX-C) or zeolite-vermiculite (NaX-Ver) composites in the restoration of soils contaminated with PAHs. The addition of zeolite composites to fertilizer resulted in a significant reduction in soil PAH levels and a corresponding reduction in plant tissue content, without compromising yields, compared to the control and separate application of NPK. A Significant correlation between PAHs and pHH2O, pHKCl, EC and dehydrogenase activity (DhA) was found in soils. The addition of zeolite composites with lignite significantly reduced the content of PAHs in straws, especially following the application of NaX-C. However, in the case of grains, the highest percentage reduction in comparison to NPK was observed for the highest dose of NaX-Ver.

Background. The vast majority of malignant neoplasms of the oral mucosa refer to squamous cell carcinomas. The development of squamous cell carcinoma of the oral mucosa is often promoted by previous potentially malignant diseases, with oral leukoplakia dominating among them.Objective. To determine the clinical significance of the pathogenicity of somatic mutations in oral mucosal leukoplakia.Methods. The study material included 24 samples of abnormal epithelium of the oral mucosa from leukoplakia patients. QIAamp DNA FFPE Tissue Kit (Qiagen, Germany) was used for deoxyribonucleic acid (DNA) extraction from the samples. DNA sequencing was performed using IlluminaNextSeq 550 sequencer and TruSight™ Oncology 500 DNA Kit For Use with NextSeq (Illumina, USA). All DNA extractions from biological samples, preparation and sequencing of DNA libraries were performed step-by-step in strict accordance with the guidelines provided with the respective reagent kits. Bioinformatics analysis was carried out using specific software Illumina Base Space (Illumina, USA) and Galaxy Project (The Galaxy Community, a non-profit international project) according to current guidelines. The desired power of the study accounted for 90%. Two Proportions Z test was performed by means of The Sample Size Calculation of Statistica 12 (StatSoft, Inc.) with the set option “one-tailed hypothesis”, because it was initially assumed that pathogenic (oncogenic) genetic variants occur in the tissue of oral leukoplakia much more frequently than in the human reference genome used for sequence alignment.Results. The pathogenic somatic mutations in the TP53, KRAS, APC, NRAs and BRAF genes, identified in this study, alone or in combination, are highly likely (hazard ratio 3000-11000) to be associated with the development of oral mucosal leukoplakia and low-grade epithelial dysplasia. The multiplicity of pathogenic and likely pathogenic genetic variants associated with epithelial dysplasia, as well as the fact that a number of variants do not occur in all patients, suggests that the same histotype of oral mucosal dysplasia may develop under the influence of different mutations.Conclusion. The pathogenic and likely pathogenic variants of the TP53, KRAS, APC, NRAS and BRAF genes, identified in this study, alone or in combination, are highly likely (hazard ratio 3000–11000) to be associated with the development of leukoplakia and low-grade epithelial dysplasia.

Gender-affirming hormone therapy (GAHT) plays a significant role in the medical care of transgender individuals, helping to align their physical characteristics with their gender identity. While numerous studies have investigated the impact of GAHT on adults, research focusing on its effects on the quality of life (QoL) of transgender youth is limited. In this opinion paper, we aim to address selected challenges associated with gender-affirming medical care, such as (1) the necessity for evidence-based youth gender-affirming medical care, (2) the urge to explore different approaches to gender-affirming medical care diversely in transgender youth research, and (3) understanding the challenges of the detransition process (which refers to stopping or reversing gender-affirming medical or surgical treatments), as well as suggest possible solutions for meaningful progress. Notably, the available evidence underlines a positive impact of GAHT on various aspects of QoL of transgender youth, such as mental health and social functioning, by alleviating gender dysphoria, improving body satisfaction, and facilitating appearance congruence (the degree to which an individual’s physical appearance represents their gender identity). However, challenges related to methodological limitations, as well as ethical considerations, and several sociocultural factors highlight the need for further research to better understand the long-term effects of GAHT on the QoL of transgender youth. Ethical considerations, such as ensuring informed consent and weighing potential benefits against risks, are pivotal in guiding healthcare decisions. Additionally, navigating these ethical responsibilities amid sociocultural contexts is crucial for providing inclusive and respectful care to transgender youth. Addressing these research gaps is, therefore, crucial to developing successful healthcare programmes, raising awareness, and promoting the holistic well-being of transgender youth through comprehensive and affirming care.

This study investigates the impact of Epstein–Barr virus (EBV) infection on children’s proteomes across different phases of the disease, utilising seventy-nine blood samples categorised into three groups: EBV-naive patients, acute infectious mononucleosis (IM) cases, and convalescents followed up for 12 months post-IM. The aim is to identify proteins influenced by EBV infection, shedding light on the chronic processes triggered by the virus. The results reveal thirty-nine proteins distinguishing between naive patients and those with IM, including actin, lumican, peroxiredoxin-2, fibulin-1, gelsolin, and alpha-2-macroglobulin, which are involved in immune responses, cell adhesion, and inflammation. Elevated oxidative stress markers like peroxiredoxin-2 in IM patients suggest potential links to EBV’s induction of reactive oxygen species. Increased levels of apolipoproteins A-I, A-IV, C-IV, and M during IM imply associations with viral infection, while complement system proteins (C1q, C1r, and C8 gamma chain) are also elevated, reflecting their role in the immune response and viral clearance. This study’s focus on children provides unique insights into EBV’s impact on young populations, emphasising proteomics’ role in uncovering protein associations and understanding the virus’s long-term consequences. However, specific relationships between identified proteins and EBV infection require further investigation.

Introduction: Comorbid insomnia and obstructive sleep apnea (COMISA) is not a well-identified sleep disorder, despite having a significant impact on health. This study investigates the relationship between sleep bruxism (SB) and sleep architecture in patients with COMISA, obstructive sleep apnea (OSA), and in those without any sleep disorders. Methods: 119 patients were included in the study and divided into three groups: OSA, COMISA, and a control group. Polysomnographic (PSG) examination provided parameters related to sleep architecture, OSA, and characteristics of SB. Results: The bruxism episode index (BEI) and other SB parameters were not found to be statistically different between the three groups (p > 0.05). There was no statistical difference in measured sleep architecture between the COMISA and OSA groups (p > 0.05). In comparison to the control group, participants in the COMISA group were found to have an increased apnea–hypopnea index (AHI), oxygen desaturation index (ODI), respiratory disturbance index (RDI), all arousals (AA), and respiratory arousals (RA) (p < 0.05). Among COMISA patients, AA and RA were shown to have a positive linear correlation with the number of bradycardia events per hour (r = 0.49, r = 0.48, p < 0.05). Conclusions: SB does not occur in patients with COMISA more frequently than in patients with OSA or those without any sleep disorders. PSG parameters are not specific for COMISA; therefore, in order to differentiate this disorder from OSA alone, a comprehensive patient assessment has to be performed.

(1) Background: Gilles de la Tourette Syndrome (TS) is a neurodevelopmental disorder characterized by motor and vocal tics. Attention deficit and hyperactivity disorder (ADHD) is a common comorbidity of TS that adds further impairment. Cognitive-behavioural therapy (CBT) has shown efficacy in treating tics, yet its effectiveness in individuals with TS and comorbid ADHD remains unclear. Also, it is suggested that ADHD characteristics like executive dysfunction and inattention could hinder the response to CBT. This study aims to compare the response to CBT for tics and its maintenance six months post-therapy among TS individuals with and without ADHD symptoms. (2) Methods: In this study, 55 TS participants who completed 14-week CBT for tics were split into high (TS+) or low (TS−) ADHD symptomatology groups. Outcomes were evaluated using the Yale Global Tic Severity Scale (YGTSS) regarding global tic severity and motor and vocal tic frequency post-CBT and at a 6-month follow-up. (3) Results: No significant group difference was found regarding improvements post-CBT (n = 55), nor the maintenance six months later (n = 45). (4) Conclusions: ADHD symptoms may not hinder the response to CBT or its maintenance, suggesting that TS individuals with ADHD symptoms may not require specialized CBT interventions.

Abstract This exploratory observational study aimed to evaluate whether the blood levels of serotonin and enzymes involved in serotonin synthesis are associated with sleep breathing parameters. A total of 105 patients were included in this study, who were subjected to single-night polysomnography with simultaneous audio–video recordings. Peripheral blood samples were collected to estimate the serum levels of serotonin, tryptophan hydroxylase 1 (TPH1), and aromatic l-amino acid decarboxylase (AADC). Results showed a negative correlation between blood serotonin levels, and oxygen desaturation index (ODI) (p = 0.027), central apnea (p = 0.044) and obstructive apnea (OA) (p = 0.032) scores. Blood TPH1 levels were negatively correlated with average (p = 0.003) and minimal saturation (p = 0.035) and positively correlated with apnea–hypopnea index (p = 0.010), OA (p = 0.049), and hypopnea index (p = 0.007) scores. A tendency to sleep-disordered breathing seemed to co-occur with lower blood serotonin and higher TPH1 levels. Clinical Trial Registration : www.ClinicalTrials.gov , identifier NCT04214561