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As a contribution to improving understanding of the mechanisms and relationships that exist within shallow peatland ecosystems, we report the results of monitoring five-years’ recovery after restoration of a forestry-drained sloping rich fen site in the Central Sudetes in south-west Poland. Over the last 100 years, drainage ditches installed for forestry management purposes have affected the hydrology, soil and vegetation of this site. Spruce stands were present until 2010, when restoration started with blocking of ditches and clearcutting/removal of trees. The main objective of our study was to determine the effects of these restoration activities on aspects of hydrology and soil condition. We hypothesised that the five years following restoration could provide sufficient time to improve: 1) water table level and water quality, and 2) the physical and chemical properties of the organic soil. Restoration had a positive effect on water table level as early as two years after implementation of drain blocking and reduction of tree cover. However, five years was not sufficient time to reverse the decline in water quality. The concentrations of labile carbon forms in water, as well as water colour (Abs400), were similar in 2010 and 2015. Due to peatland rewetting and peat swelling a decrease in peat bulk density was observed. However, this outcome was identified only in the bottom organic soil horizons. This, in turn, affected the thickness of the peat layer and the altitude of the soil surface. Five years of recovery is insufficient to stop the mineralisation of organic matter, as indicated by lower TOC/TN values, slightly higher concentrations of labile forms of carbon, and the W1 index of secondary transformation.

Abstract Perceptual decisions should depend on sensory evidence. However, such decisions are also influenced by past choices and outcomes. These choice history biases may reflect advantageous strategies to exploit temporal regularities of natural environments. However, it is unclear whether and how observers can adapt their choice history biases to different temporal regularities, to exploit the multitude of temporal correlations that exist in nature. Here, we show that male mice adapt their perceptual choice history biases to different temporal regularities of visual stimuli. This adaptation was slow, evolving over hundreds of trials across several days. It occurred alongside a fast non-adaptive choice history bias, limited to a few trials. Both fast and slow trial history effects are well captured by a normative reinforcement learning algorithm with multi-trial belief states, comprising both current trial sensory and previous trial memory states. We demonstrate that dorsal striatal dopamine tracks predictions of the model and behavior, suggesting that striatal dopamine reports reward predictions associated with adaptive choice history biases. Our results reveal the adaptive nature of perceptual choice history biases and shed light on their underlying computational principles and neural correlates.

One important need in the context of peatland restoration is to gain knowledge of soil organic matter quality and current soil-forming process in degraded peatlands. The aim of this study was to evaluate the impact of long-term drainage on soil transformation processes. In autumn 2012, soil survey and sampling was carried out on five shallow peatlands in the Central Sudeten Mountains (Poland) which had been drained for forestry use in the late 1800s or early 1900s. Four organic soils (Histosols) and one organo-mineral soil (Histic Gleysol) were studied. The surface soil horizons were mainly transformed due to long-term forestry drainage. Increased aeration of these layers had enhanced their content of labile forms of carbon and they were undergoing secondary transformation. Soil transformation was more advanced in fen peatlands than in transitional mire or raised bogs. Only the fens exhibited characteristic evidence of the moorsh-forming process. Further drying of these soils will negatively affect their rewetting potential and significantly reduce the effective application of restoration treatments. In order to reduce organic matter transformation and loss from the investigated peatland areas, their drainage ditches should be blocked. Additionally, some trees should be removed from their central areas to reduce evapotranspiration.

The water oxidation reaction in photosystem II (PS II) produces most of the molecular oxygen in the atmosphere, which sustains life on Earth, and in this process releases four electrons and four protons that drive the downstream process of CO2 fixation in the photosynthetic apparatus. The catalytic center of PS II is an oxygen-bridged Mn4Ca complex (Mn4CaO5) which is progressively oxidized upon the absorption of light by the chlorophyll of the PS II reaction center, and the accumulation of four oxidative equivalents in the catalytic center results in the oxidation of two waters to dioxygen in the last step. The recent emergence of X-ray free-electron lasers (XFELs) with intense femtosecond X-ray pulses has opened up opportunities to visualize this reaction in PS II as it proceeds through the catalytic cycle. In this review, we summarize our recent studies of the catalytic reaction in PS II by following the structural changes along the reaction pathway via room-temperature X-ray crystallography using XFELs. The evolution of the electron density changes at the Mn complex reveals notable structural changes, including the insertion of OX from a new water molecule, which disappears on completion of the reaction, implicating it in the O—O bond formation reaction. We were also able to follow the structural dynamics of the protein coordinating with the catalytic complex and of channels within the protein that are important for substrate and product transport, revealing well orchestrated conformational changes in response to the electronic changes at the Mn4Ca cluster.

Fatigue and dyspnea are the most commonly reported long-term complaints in individuals previously infected with SARS-CoV-2. This study aimed to comprehensively evaluate diaphragm muscle function in post-COVID-19 patients and investigate whether potential diaphragm dysfunction contributes to physical functioning impairment. A total of 46 patients who qualified for pulmonary rehabilitation were examined. Diaphragm muscle function parameters were evaluated using ultrasonography, while the severity of dyspnea, aerobic capacity, and the amount of energy used by the body during physical activity were assessed using the six-minute walk test, mMRC scale, and Metabolic Equivalent Task (MET), respectively. We identified that 69.5% of patients had diaphragm atrophy and 6.5% had diaphragm paralysis. The percentage of atrophy was not related to age, gender, BMI, oxygen therapy usage during the COVID-19 infection course, and disease severity. Patients who experienced cough, fever, and no loss of smell during the COVID-19 course had significantly greater diaphragm inspiratory thickness values, while patients with cough and no smell disorders had a significantly lower percentage of diaphragm atrophy. Diaphragm functional parameters were strongly associated with selected variables of exercise tolerance, such as distance in the six-minute walk test, oxygen saturation levels, fatigue, and exertion on the Borg scale. In conclusion, diaphragm muscle dysfunction is a serious long-term post-COVID-19 consequence and can be viewed as a major contributing factor to prolonged functional impairments.

Background: Severe atopic dermatitis (AD) is a complex disease requiring systemic treatment. This study aimed to assess the effectiveness of combined therapy consisting of dupilumab and sublingual dust mite allergen immunotherapy (SLIT-HDM) in patients with severe AD and HDM allergies. Methods: Patients diagnosed with severe AD were included in this randomised, placebo-controlled, double-blind 12-month trial; they received SLIT for HDMs and/or dupilumab for 12 months and were compared with patients on cyclosporine. The primary outcomes for the treatment arms were changes in the Eczema Area and Severity Index (EASI), body surface area (%BSA), and Investigator Global Assessment (IsGA) over 12 months. The secondary outcomes were the proportion of patients who achieved IsGA success and reduced medication scores. Results: Significant improvements were observed in all analysed groups after 12 months of therapy based on the EASI, %BSA, and IsGA. However, the most substantial changes were observed in the groups treated with dupilumab or a combination of SLIT-HDM and dupilumab. Additionally, the proportion of patients who achieved an IsGA reduction was significantly greater in the group receiving combination therapy than in the other groups (9/14 [64% of the group receiving SLIT-HDM] vs. 11/14 [73% of the group receiving dupilumab] vs. 15/17 [88% of the group receiving dupilumab and SLIT-HDM] vs. 7/13 [53% of the group receiving cyclosporine]) (p < 0.05). Conclusions: In patients with severe AD and HDM allergies, combination treatment with dupilumab and allergen immunotherapy for HDMs may increase the therapeutic benefit over treatment with these methods separately.

This review paper describes the energy-upgraded Continuous Electron Beam Accelerator Facility (CEBAF) accelerator. This superconducting linac has achieved 12 GeV beam energy by adding 11 new high-performance cryomodules containing 88 superconducting cavities that have operated cw at an average accelerating gradient of 20 MV/m. After reviewing the attributes and performance of the previous 6 GeV CEBAF accelerator, we discuss the upgraded CEBAF accelerator system in detail with particular attention paid to the new beam acceleration systems. In addition to doubling the acceleration in each linac, the upgrade included improving the beam recirculation magnets, adding more helium cooling capacity to allow the newly installed modules to run cold, adding a new experimental hall, and improving numerous other accelerator components. We review several of the techniques deployed to operate and analyze the accelerator performance and document system operating experience and performance. In the final portion of the document, we present much of the current planning regarding projects to improve accelerator performance and enhance operating margins, and our plans for ensuring CEBAF operates reliably into the future. For the benefit of potential users of CEBAF, the performance and quality measures for the beam delivered to each of the experimental halls are summarized in the Appendix.

When facing an unfamiliar environment, animals need to explore to gain new knowledge about which actions provide reward, but also put the newly acquired knowledge to use as quickly as possible. Optimal reinforcement learning strategies should therefore assess the uncertainties of these action-reward associations and utilise them to inform decision making. We propose a novel model whereby direct and indirect striatal pathways act together to estimate both the mean and variance of reward distributions, and mesolimbic dopaminergic neurons provide transient novelty signals, facilitating effective uncertainty-driven exploration. We utilised electrophysiological recording data to verify our model of the basal ganglia, and we fitted exploration strategies derived from the neural model to data from behavioural experiments. We also compared the performance of directed exploration strategies inspired by our basal ganglia model with other exploration algorithms including classic variants of upper confidence bound (UCB) strategy in simulation. The exploration strategies inspired by the basal ganglia model can achieve overall superior performance in simulation, and we found qualitatively similar results in fitting model to behavioural data compared with the fitting of more idealised normative models with less implementation level detail. Overall, our results suggest that transient dopamine levels in the basal ganglia that encode novelty could contribute to an uncertainty representation which efficiently drives exploration in reinforcement learning.

One of the key problems the brain faces is inferring the state of the world from a sequence of dynamically changing stimuli, and it is not yet clear how the sensory system achieves this task. A well-established computational framework for describing perceptual processes in the brain is provided by the theory of predictive coding. Although the original proposals of predictive coding have discussed temporal prediction, later work developing this theory mostly focused on static stimuli, and key questions on neural implementation and computational properties of temporal predictive coding networks remain open. Here, we address these questions and present a formulation of the temporal predictive coding model that can be naturally implemented in recurrent networks, in which activity dynamics rely only on local inputs to the neurons, and learning only utilises local Hebbian plasticity. Additionally, we show that temporal predictive coding networks can approximate the performance of the Kalman filter in predicting behaviour of linear systems, and behave as a variant of a Kalman filter which does not track its own subjective posterior variance. Importantly, temporal predictive coding networks can achieve similar accuracy as the Kalman filter without performing complex mathematical operations, but just employing simple computations that can be implemented by biological networks. Moreover, when trained with natural dynamic inputs, we found that temporal predictive coding can produce Gabor-like, motion-sensitive receptive fields resembling those observed in real neurons in visual areas. In addition, we demonstrate how the model can be effectively generalized to nonlinear systems. Overall, models presented in this paper show how biologically plausible circuits can predict future stimuli and may guide research on understanding specific neural circuits in brain areas involved in temporal prediction.

Abstract A muon collider would enable the big jump ahead in energy reach that is needed for a fruitful exploration of fundamental interactions. The challenges of producing muon collisions at high luminosity and 10 TeV centre of mass energy are being investigated by the recently-formed International Muon Collider Collaboration. This Review summarises the status and the recent advances on muon colliders design, physics and detector studies. The aim is to provide a global perspective of the field and to outline directions for future work.

Objectives: The exact mechanisms of deep brain stimulation (DBS) are still an active area of investigation, in spite of its clinical successes. This is due in part to the lack of understanding of the effects of stimulation on neuronal rhythms. Entrainment of brain oscillations has been hypothesised as a potential mechanism of neuromodulation. A better understanding of entrainment might further inform existing methods of continuous DBS, and help refine algorithms for adaptive methods. The purpose of this study is to develop and test a theoretical framework to predict entrainment of cortical rhythms to DBS across a wide range of stimulation parameters. Materials and Methods: We fit a model of interacting neural populations to selected features characterising PD patients' off-stimulation finely-tuned gamma rhythm recorded through electrocorticography. Using the fitted models, we predict basal ganglia DBS parameters that would result in 1:2 entrainment, a special case of sub-harmonic entrainment observed in patients and predicted by theory. Results: We show that the neural circuit models fitted to patient data exhibit 1:2 entrainment when stimulation is provided across a range of stimulation parameters. Furthermore, we verify key features of the region of 1:2 entrainment in the stimulation frequency/amplitude space with follow-up recordings from the same patients, such as the loss of 1:2 entrainment above certain stimulation amplitudes. Conclusion: Our results reveal that continuous, constant frequency DBS in patients may lead to nonlinear patterns of neuronal entrainment across stimulation parameters, and that these responses can be predicted by modelling. Should entrainment prove to be an important mechanism of therapeutic stimulation, our modelling framework may reduce the parameter space that clinicians must consider when programming devices for optimal benefit.

Osteoporosis is a multifactorial systemic skeletal disease that is characterized by a low bone mineral density (BMD) and the microarchitectural deterioration of bone tissue, leading to bone fragility. The search for new genes that may play an important role in the regulation of bone mass and the development of osteoporosis is ongoing. Recently, it was found that altering the activity of the endothelin-1-converting enzyme encoded by the ECE1 gene may affect bone mineral density (BMD). Another gene involved in the process of osteoblast differentiation and maturation is believed to be PPARG (peroxisome proliferator-activated receptor gamma). This participates in regulating the transformation of stem cells and affects the process of bone formation and resorption. Therefore, we analyzed the association of the ECE1 and PPARG variants with osteopenia and osteoporosis risk in the Polish population. This study included a group (n = 608) of unrelated Polish women (245 individuals with osteoporosis (aged: 57 ± 9), 109 individuals with osteopenia (aged: 53 ± 8) and 254 healthy controls (aged: 54 ± 8)). The real-time PCR technique was used to determine the genetic variants for rs213045 (-338G>T) and rs213046 (-839A>C) of the ECE1 gene and rs1801282 (Pro12Ala, C>G) of the PPARG gene. Analysis of the PPARG rs1801282 variants did not show any association with the risk of osteoporosis and osteopenia. However, in the densitometric results, lower median Z-score values were observed for the T allele compared to the G allele for the rs213045 variant of the ECE1 gene (−1.11 ± 1.07 vs. −0.78 ± 1.21, p = 0.021). Moreover, the TT genotype for the rs213045 variant was more common in women with osteopenia (13.8%, OR = 2.82, p < 0.05) and osteoporosis (7.8%, OR = 1.38, p > 0.05) compared to the control group (5.5%). Additionally, our results suggested that the T allele of rs213045 was more common in women with osteopenia compared to the controls. We further observed that the haplotype containing two major GA alleles of ECE1 (rs213045, rs213046) could reduce the risk of osteopenia in our population. Finally, we found that women with osteoporosis had statistically significantly lower body mass and BMI values compared to the control group. Our results suggest that the ECE1 rs213045 variant may increase the risk of osteopenia. However, the data obtained require confirmation in further studies.

Overhead lines are used to transmit electricity from where it is generated to the receiving stations. The correct design of an overhead line affects public safety, because it should ensure the required clearances between conductors and the ground and objects located in the space under the overhead line. The temperature of conductors in overhead lines depends on the load current and weather conditions, and affects the sag and tension of the conductors. Calculations of sags and tensions of overhead conductors can be performed using simplified calculation methods that do not consider insulator sets. In some situations, this approach may cause calculation errors. This article discusses algorithms for calculating overhead conductor tensions and sags in the tensioning sections of high-voltage overhead lines, accounting for and excluding insulator sets. The analysis is carried out for different lengths of tensioning sections and various thermal and mechanical states of the conductors.

The FUT2 gene encodes an enzyme called α-1,2-fucosyltransferase, which is involved in the formation of blood group antigens AB0(H) and is also involved in the processes of vitamin B12 absorption and its transport between cells. FUT2 gene polymorphisms are associated with vitamin B12 levels in the body. Vitamin B12 deficiency associated with hyperhomocysteinemia is a major risk factor for cardiovascular diseases (CVDs), which are one of the main causes of death in patients after kidney transplantation. The aim of our study was to determine the impact of the rs602662 (G>A) polymorphism of the FUT2 gene on the functionality of transplanted kidneys and the risk of CVD in patients after kidney transplantation. The study included 402 patients treated with immunosuppression (183 patients taking cyclosporine (CsA) and 219 patients taking tacrolimus (TAC)). The analysis of the FUT2 rs602662 (G>A) polymorphism was performed using real-time PCR. Patients with CsA were more likely to be underweight (1.64% vs. 0.91%) and obese (27.87% vs. 15.98%), while those taking TAC were more likely to be of normal weight (39.27%) or overweight (43.84%). No statistically significant differences were observed comparing the mean blood pressure, both systolic and diastolic. The renal profile showed a higher median urea nitrogen concentration in patients with CsA (26.45 mg/dL (20.60–35.40) vs. 22.95 mg/dL (17.60–33.30), p = 0.004). The observed frequency of rs602662 alleles of the FUT2 gene was similar in the analyzed groups. The A allele was present in 43.7% of patients with CsA and 41.1% of those taking TAC (OR = 0.898; 95% CI: 0.678–1.189; p = 0.453). In the group with CsA, the GG genotype was present in 32.2% of patients, the GA in 48.1% and the AA in 19.7%. A similar distribution was obtained in the TAC group: GG—33.8%, GA—50.2%, and AA—16.0%. An association of genotypes containing the G allele with a higher incidence of hypertension was observed. The G allele was present in 65% of people with hypertension and in 56% of patients with normal blood pressure (p = 0.036). Moreover, the evaluation of the renal parameters showed no effect of the FUT2 polymorphism on the risk of organ rejection because the levels of creatinine, eGFR, potassium, and urea nitrogen were prognostic of successful transplantation. Our results suggest that the rs6022662 FUT2 polymorphism may influence the risk of cardiovascular diseases.

The EUROnu project has studied three possible options for future, high intensity neutrino oscillation facilities in Europe. The first is a Super Beam, in which the neutrinos come from the decay of pions created by bombarding targets with a 4 MW proton beam from the CERN High Power Superconducting Proton Linac. The far detector for this facility is the 500 kt MEMPHYS water Cherenkov, located in the Fréjus tunnel. The second facility is the Neutrino Factory, in which the neutrinos come from the decay of μ^{+} and μ^{-} beams in a storage ring. The far detector in this case is a 100 kt magnetized iron neutrino detector at a baseline of 2000 km. The third option is a Beta Beam, in which the neutrinos come from the decay of beta emitting isotopes, in particular ^{6}He and ^{18}Ne, also stored in a ring. The far detector is also the MEMPHYS detector in the Fréjus tunnel. EUROnu has undertaken conceptual designs of these facilities and studied the performance of the detectors. Based on this, it has determined the physics reach of each facility, in particular for the measurement of CP violation in the lepton sector, and estimated the cost of construction. These have demonstrated that the best facility to build is the Neutrino Factory. However, if a powerful proton driver is constructed for another purpose or if the MEMPHYS detector is built for astroparticle physics, the Super Beam also becomes very attractive.

In recent decades, neglected tropical diseases and poverty-related diseases have become a serious health problem worldwide. Among these pathologies, human African trypanosomiasis, and malaria present therapeutic problems due to the onset of resistance, toxicity problems and the limited spectrum of action. In this drug discovery process, rhodesain and falcipain-2, of Trypanosoma brucei rhodesiense and Plasmodium falciparum, are currently considered the most promising targets for the development of novel antitrypanosomal and antiplasmodial agents, respectively. Therefore, in our study we identified a novel lead-like compound, i.e., inhibitor 2b, which we proved to be active against both targets, with a Ki = 5.06 µM towards rhodesain and an IC50 = 40.43 µM against falcipain-2.

Fly ashes produced in huge amounts during coal combustion requires proper management. The purpose of this study was to determine the impact of fly ash from burning hard coal used in large doses (250, 500, 1000 and 2000 t ha−1) on soil properties and vegetation of fresh mixed coniferous forest within 43 years from the ash application. The experiment was established in the Podzols in the forest habitat of Czułów, Katowice Forest district, Upper Silesia, Poland. Eight tree species were planted in ridges created by ploughing: Pinus sylvestris, P. nigra, Larix decidua, Betula pendula, Quercus robur, Q., Acer pseudoplatanus and Fagus sylvatica. The changes in soil morphology caused significant transformations in the physical and chemical properties of the soil such as soil texture, pH, macronutrients (P, K and Mg) content and C:N ratio. Increasing of ash doses changed the granulometric composition of the soil levels from loamy sand (250 t/ha−1) to silt loam (2000 t ha−1). Initially, the acidic Podzols were alkalized under the influence of the fly ash and then acidified, possibly due to the impact of accumulated litter layers, and the reaction of organic soil horizons changed from strongly acidic (250–1000 t ha−1) to alkalis (2000 t/ha−1). The macronutrients content increased in proportion to the fly ash dose, but the subsequent acidification resulted in a gradual decrease in the macronutrients share in the soil layers. The value of the C:N ratio grew after the ash application and then it gradually reduced, even by half. The transformations of soil horizons’ properties also increased the capacity of the soil sorption complex (CEC). All these processes led to a change in the trophic status of the habitat expressed by the soil habitat index (SIG) and the initial coniferous forest site can be classified as a mixed forest habitat even with the lowest ash dose used. The composition of plant communities developed forty years after the ash application was similar at the lower ash doses and the most frequent and abundant tree species were L. decidua, P. nigra and P. silvestris. B. pendula was previously co-dominant, but it was eliminated from the tree stands during the experiment. Planted trees characteristic of late stages of succession, such as Q. robur, Q. rubra, F. sylvatica and A. pseudoplatanus either did not survive or remained in very low quantities. The herb and moss layers developed in the process of spontaneous colonization, and together with the trees led to phytostabilisation of the bare substrates. After acidification of the topsoil horizons, the herb layers consisted mostly of coniferous, mixed, and deciduous forest species, and the most frequent or abundant were Lysimachia europea and Pteridium aquilinum. The moss layers were represented by coniferous forest flora. At the ash dose of 2000 t ha−1, Tilia cordata settled in one of the seral stages of spontaneous succession and this species dominated in the community and formed a dense tree stand. After the soil acidification, a shift from calcicole to calcifuge plant strategy took place among species of the herbaceous layer. The transformations of plant communities’ composition occurred in relation to changes in the soil properties.

Introduction: The process of aging is a progressive, patterned, and accumulative set of time-related changes resulting from a mix of genetic, epigenetic, and environmental factors, that are constantly evolving, and that lead the human body to be more prone to defects and susceptible to disease, and at last to death. On the molecular level, the accumulation of free radical reactions that constantly go on in every cell and tissue is thought to be the main culprit behind the process of aging [1]. These reactions amassed over time, hamper immune responses to external factors, cause homeostatic imbalance and lead to chronic pro-inflammatory status in body cells. This process has been dubbed “inflammaging” [2]. Physical activity, along with a balanced diet and a healthy lifestyle as a whole, has long been thought to be crucial in retaining health and good quality of life. Aim of the study: A review of current knowledge about the process of aging, a summary of underlying pathologies, and current preventive protocols, with a focus on physical activity as a preventative measure in combating illness and age-related pathologies. Methods and materials: A review of chosen literature in the PubMed database, MDPI database, and GoogleScholar was conducted using the following keywords: “aging pathophysiology”, “physical exercise in the aging process”, “aging process underlying conditions”, “molecular biology of aging”, “cell lifespan”, “cell longevity”. Results and conclusions: Physical activity helps decelerate the process of aging, both physical and cognitive, through various pathways in the human body.

Introduction and purpose of the study: With the gradual increase in travel, new challenges are arising in the health sector, especially with regard to infectious diseases. Growing number of Poles choose countries on other continents as their holiday destination. The aim of this study was to examine the health behaviour of Poles in relation to their travel destinations within Europe, Asia and Africa. Of particular importance were pre-travel consultations, awareness of recommended and mandatory vaccinations and malaria prevention. Material and method: The study was based on an analysis of data from a specially constructed, online questionnaire. It was completed by 237 people. Pearson’s χ2 test, T-student and ANOVA were used to analyse the survey results. The processing of the data obtained, statistical calculations and graphs were performed using the R programme. Results and conclusions: Travellers to Asian or African countries were significantly more likely to seek information on the infectious diseases their travel destination was at risk of than travellers to European countries. In addition, recommended vaccinations were significantly more frequently administered prior to travelling to Africa or Asia than before travelling within Europe. No statistically significant differences were found between travellers to Asia or Africa in terms of seeking information on the infectious diseases, having a pre-travel consultation or being administered recommended vaccinations. With regards to malaria-prone regions, travellers to Africa were more than twice as likely to take antimalarial drugs than travellers to Asia. Mandatory vaccinations were significantly more common than recommended vaccinations, although despite the obligation some travellers still chose not to receive them.

Introduction: Hearing loss affects 15% of Poles, i.e. more than 5.7 million people. Despite this, it is still underdiagnosed and insufficiently often treated. As its incidence increases significantly with age, this issue will only affect more people with a rapidly ageing population. Hearing loss has a number of different negative consequences, significantly reducing patients' quality of life, but it is also a problem for society as a whole. Aim of the study: Review of current knowledge on hearing loss, detailing pathophysiology, prevention, screening, diagnosis and treatment. Methods and materials: A review of chosen literature in the PubMed database, Scopus, and Google Scholar using the keywords of “hearing loss”, „ conductive hearing loss”, “sensorineural hearing loss”, “hearing loss in adults”, “diagnosing hearing loss” and „hearing loss treatment”. Results: Hearing loss is categorized as conductive, sensorineural or mixed, with the most common being presbyacusis. Although it is a multi-factorial condition, reducing exposure to excessive noise is most important. There is no consensus on screening in adults. Various diagnostic methods exist with tonal audiometry being the most important. Conductive hearing loss is potentially amendable surgically, while in case of sensorineural hearing loss, hearing aids are the most common treatment method. Satisfactory results in the treatment of severe hearing loss and deafness can be achieved with cochlear implants. Recent research offers hope for the future of hearing loss treatment. Conclusions: Timely diagnosis, which can be performed with relatively simple tools, is of the utmost importance. There are a number of treatment methods, which must be individually selected with the patient's participation, that yield good results.

Introduction: The word “psychedelic” derives from the Greek language and can be loosely translated as “mind manifesting” which is to convey that these substances allow the mind to unleash its hidden potential. Psilocybin is considered to be a “classic psychedelic” and is most commonly found in the form of so-called “magic mushrooms”. Due to its unique properties psilocybin has been used during religious ceremonies and rituals for centuries and more recently also explored in a medical context. Nowadays many studies are being carried out to prove the efficacy of its use in the treatment of various psychiatric disorders. Aim of study: Review of the current knowledge on the subject of psilocybin applied in the treatment of psychiatric disorders, such as major depressive disorder, treatment-resistant depression and addiction. Methods and materials: A review of chosen literature was carried out in the PubMed database and Google Scholar using the following phrases: psilocybin, psychedelics, psychedelic-assisted therapy, major depressive disorder, addiction. Results: Recent studies suggest that psilocybin may be an effective form of treatment for cancer-related psychiatric distress, treatment-resistant depression and addiction. There are some reports of psilocybin being useful when treating obsessive-compulsive disorder and cluster headaches. Conclusions: More large-scale, randomized, placebo-controlled studies are required to prove these promising findings. Psychological support is crucial during the treatment with psilocybin.

Introduction: Post-traumatic stress disorder (PTSD) is a common health issue of complex etiology significantly deteriorating functioning in everyday life. It may develop as a result of exposure to traumatic events like traffic accidents, war experience, sexual abuse and domestic violence. Current methods of treatment consist of trauma-oriented psychotherapy supported by selective serotonin reuptake inhibitors (SSRIs). Their efficacy is far from satisfactory thus a search for alternative methods is necessary. 3,4-Methylenedioxymethamphetamine (MDMA) commonly known as “ecstasy” seems to have promising results in the treatment of PTSD. Aim of study: Review of current knowledge about MDMA-assisted therapy in PTSD, its possible mechanisms of action, efficacy and safety. Methods and materials: A review of chosen literature from in PubMed database, GoogleScholar database in the years 2000-2023 was conducted using the following keywords: “PTSD epidemiology”, “PTSD pathophysiology”, “PTSD neural activity”, “PTSD brain activity”, “MDMA PTSD”, “MDMA brain activity”, “MDMA neural activity”, “MDMA neurotoxicity”, “MDMA PTSD therapy”, “MDMA safety”, “MDMA caffeine” Results: MDMA-assisted therapy has promising effects in PTSD treatment and its safety profile is satisfactory. The improvement in symptoms occurs most likely due to its modulating activity on brain structures responsible for threat detection and emotion processing. Conclusions: Further research is necessary to assess MDMA-assisted therapy in PTSD, especially direct comparison of its efficacy versus first-line treatment SSRIs and assessment of its long-term-safety.

Introduction and purpose of work: Vitamin D has a significant impact on the functioning of the human body. Vitamin D deficiency is a public health problem worldwide in all age groups including Poland. Supplementation is recommended in the general population with the use of cholecalciferol and should be individualized depending on age, body weight, the sun exposure, diet, and lifestyle. The aim of study was to analyze vitamin D supplementation habits among polish students in two divided groups: medical students and non-medical students. Methods: The tool used to carry out the research was a specially constructed, online questionnaire. The survey was completed by 244 students, 126 of whom supplement vitamin D. Pearson’s χ2 test was used to analyze the survey’s results. The processing of the obtained data, statistical calculation and graphs were made using the R program. Results and conclusions: Students of medical faculties are more likely to take vitamin D supplements than students of other faculties. They are significantly more likely to adjust the dose of supplementation to the current guidelines. In 87% of students who tested the level of vitamin D in the blood serum and remember their result, the level of the parameter is ≥30 ng/ml (75 nmol/L), which is below the optimal level for this particular age group. Supplementation improves the quality of life, the benefits of supplementation were noticed by 71.4% of all students. It is necessary to promote the prophylactic habit of vitamin D supplementation.

Introduction: Vitiligo is a systemic, chronic, hypopigmented dermatosis of unclear background. The disease is characterized by the selective loss or dysfunction of melanocytes. As a result we can observe various, well and non-squamous depigmentation areas of different size and shape. The pathogenesis of vitiligo is not fully understood, however, the current view is that the etiopathology of this disease is complex Purpose of the study: Current treatment models are often nonspecific, so it is important to understand the pathomechanism that can help with vitiligo lesions. It will also sensitize researchers to the search for new therapeutic options Material and methods: Collected scientific articles and guidelines available online of high substantive value. Expressions that were searched in databases: vitiligo, etiology, leptin, pathogenesis, reactive oxygen species, oxidative stress Results and conclusions: The scientific papers and researches cited in the article show that the major role is played by cellular stress and reactive oxygen forms, secondary inflammation or environmental factors. Cellular stress activates autoimmune and autoinflammatory mechanisms that destroy pigment cells. Therefore, there are probably even more mechanisms contributing to the development of vitiligo. Illness can affect the patient 's quality of life. In recent years, there has been significant progress in understanding the pathogenesis of vitiligo. Effective treatment of vitiligo remains a difficult challenge for both scientists and dermatologists.

Introduction: Thromboangiitis obliterans (Buerger's disease) is a segmental, multilocular, nonatherosclerotic inflammatory disease that most commonly affects small and medium sized arteries, veins and nerves of the extremities. The disease is spread worldwide and mainly affects young male tobacco smokers. Aim of study: In this review we gather and summarize available knowledge about pathogenesis, diagnosis and methods of treatment of Thromboangiitis obliterans. Methods and materials: Search of the articles in PubMed and GoogleScholar databases was performed using following keywords: Thromboangitis obliterans; Buerger's disease; Thromboangitis Obliterans pathogenesis; Thromboangitis Obliterans diagnosis; Thromboangitis Obliterans treatment; Thromboangitis Obliterans pathophysiology; Thromboangitis Obliterans symptoms; Thromboangitis Obliterans epidemiology; Thromboangitis Obliterans risk factors; The most relevant to the topic articles were included. Summary: Even though the causes of the disease remain unclear and treatment is still difficult, there are new experimental methods of treatment being researched that may bring a breakthrough in the future.

Introduction: Sjogren’s syndrome (SS) is a systemic chronic inflammatory autoimmune disease of unknown etiology that primarily affects exocrine glands. Most commonly Sjogren’s syndrome presents with dryness of the mouth and eyes, but it can also affect major organs and systems of the body and increase the risk of non-Hodgkin lymphoma. Due to non-specific symptoms that pose diagnostic challenges and a lack of standardized screening tools and classification criteria, the global incidence and prevalence of the disease are hard to evaluate. Studies estimate that Sjogren’s syndrome affects between 400,000 to 3.1 million adults worldwide and most likely is a condition significantly underdiagnosed. Aim of the study: Review of current knowledge about Sjogren’s dry eye disease, underlying pathologies, diagnostic problems, and current treatment options with a focus on the most recent advancements in therapy. Methods and materials: A review of chosen literature in the PubMed database, MDPI database, and GoogleScholar in the years 2000-2023 was conducted using the following keywords: “Sjogren’s syndrome”, “Sjogren’s syndrome ophthalmology”, “Sjogren’s dry eye syndrome”, “Sjogren’s syndrome associated dry eye”, “Lymphoma in Sjogren’s syndrome”, “Diagnosing Sjogren’s syndrome dry eye”, “Sjogren’s syndrome epidemiology”. Results: Sjogren’s syndrome is a far from rare autoimmune disease that affects many organs of the body and can significantly lower quality of life and increase mortality and morbidity. Due to its surreptitious symptom onset, Sjogren’s syndrome is commonly underdiagnosed. New diagnostic and treatment modalities for Sjogren’s syndrome dry eye are on the horizon. Conclusions: Standardized, internationally recognized criteria and a high level of clinical suspiciousness are needed for a timely and accurate diagnosis of Sjogren’s syndrome. Quick diagnosis is a significant facilitating factor for maintaining a high quality of life in Sjogren’s syndrome dry eye.

The neural mechanisms determining the speed of decisions and movements in the human brain remain poorly understood. Here, the authors reveal that the subthalamic nucleus causally controls decision and movement speed independently for each hemisphere.

Abstract Hyperandrogenism is the most common endocrine disorder in women, characterized by an imbalance in normal estrogen and androgen levels in the blood. Androgens influence bone mineral density, body mass composition, muscle mass, mental state, and the regulation of sexual function.. The aim of the study was to assess the effect of estrogen receptor α gene (ESR1) polymorphisms on selected markers of bone metabolism and hormonal parameters in women with hyperandrogenism. The study group included 80 young women with hyperandrogenism who underwent measurements of bone mineral density (BMD), and determination of hormonal and metabolic parameters. Enzyme immunoassays were used to measure leptin, sRANKL (soluble receptor activator of nuclear factor-kB ligand), osteoprotegerin and 25-OH vitamin D total levels. An analysis of ESR1 gene polymorphisms was performed using the real-time PCR method. A relationship was demonstrated between the concentration of free estradiol (FEI) and the concentration of 17-OH-progesterone, and the ESR1 gene polymorphisms: rs3020314 (p = 0.031, p = 0.026 respectively) and rs1884051 (p = 0.033, p = 0.026 respectively). In conclusion, the ESR gene polymorphisms may be associated with hormonal disturbances in the concentration of estrogens and androgens, in hyperandrogenism in young women which may indirectly affect bone mineral density. However, no statistically significant relationships between the studied polymorphisms and the selected parameters of mineral metabolism have been demonstrated..

Luminosity-driven channeling extraction has been observed for the first time in a 900 GeV study at the Fermilab Tevatron. This experiment, Fermilab E853, demonstrated that useful TeV level beams can be extracted from a superconducting accelerator during high luminosity collider operations without unduly affecting the background at the collider detectors. Multipass extraction was found to increase the efficiency of the process significantly. The beam extraction efficiency was about 25%. Studies of time dependent effects found that the turn-to-turn structure was governed mainly by accelerator beam dynamics. Based on the results of this experiment, it is feasible to construct a parasitic 5–10 MHz proton beam from the Tevatron collider.

Adapting actions to changing goals and environments is central to intelligent behavior. There is evidence that the basal ganglia play a crucial role in reinforcing or adapting actions depending on their outcome. However, the corresponding electrophysiological correlates in the basal ganglia and the extent to which these causally contribute to action adaptation in humans is unclear. Here, we recorded electrophysiological activity and applied bursts of electrical stimulation to the subthalamic nucleus, a core area of the basal ganglia, in 16 patients with Parkinson's disease (PD) on medication using temporarily externalized deep brain stimulation (DBS) electrodes. Patients as well as 16 age- and gender-matched healthy participants attempted to produce forces as close as possible to a target force to collect a maximum number of points. The target force changed over trials without being explicitly shown on the screen so that participants had to infer target force based on the feedback they received after each movement. Patients and healthy participants were able to adapt their force according to the feedback they received (P < 0.001). At the neural level, decreases in subthalamic beta (13 to 30 Hz) activity reflected poorer outcomes and stronger action adaptation in 2 distinct time windows (Pcluster-corrected < 0.05). Stimulation of the subthalamic nucleus reduced beta activity and led to stronger action adaptation if applied within the time windows when subthalamic activity reflected action outcomes and adaptation (Pcluster-corrected < 0.05). The more the stimulation volume was connected to motor cortex, the stronger was this behavioral effect (Pcorrected = 0.037). These results suggest that dynamic modulation of the subthalamic nucleus and interconnected cortical areas facilitates adaptive behavior.

Abstract Introduction We assess risks differently when they are explicitly described, compared to when we learn directly from experience, suggesting dissociable decision‐making systems. Our needs, such as hunger, could globally affect our risk preferences, but do they affect described and learned risks equally? On one hand, decision‐making from descriptions is often considered flexible and context sensitive, and might therefore be modulated by metabolic needs. On the other hand, preferences learned through reinforcement might be more strongly coupled to biological drives. Method Thirty‐two healthy participants (females: 20, mean age: 25.6 ± 6.5 years) with a normal weight (Body Mass Index: 22.9 ± 3.2 kg/m2) were tested in a within‐subjects counterbalanced, randomized crossover design for the effects of hunger on two separate risk‐taking tasks. We asked participants to choose between two options with different risks to obtain monetary outcomes. In one task, the outcome probabilities were described numerically, whereas in a second task, they were learned. Result In agreement with previous studies, we found that rewarding contexts induced risk‐aversion when risks were explicitly described (F1,31 = 55.01, p

Osteoporosis is a multifactorial and polygenic disease caused by an imbalance between osteoclastogenesis and osteoblastogenesis, leading to a decrease in bone mineral density and the occurrence of disorders in the microarchitecture and metabolism of bone tissue. In postmenopausal women, there is a significant decrease in the production of estrogens, which play a key role in maintaining proper bone mineral density. Estrogens have an inhibitory effect on the development and activity of osteoclasts by reducing the synthesis of pro-resorption cytokines and stimulating the expression of osteoprotegerin (OPG). Osteoprotegerin is a cytokine that prevents bone loss by inhibiting the process of osteoclastogenesis, reducing bone resorption. The aim of our study was to determine the influence of the rs3102735 (−163A>G), rs3134070 (−245T>G), rs207361 (−950T>C), rs7844539 (6890A>C), and rs2073618 (1181G>C) polymorphisms of the OPG gene on the risk of osteoporosis and osteopenia in postmenopausal Polish women. The study included 802 unrelated women (osteoporosis: n = 317, osteopenia: n = 110, controls: n = 375) at postmenopausal age (54.7 ± 8.6 years). Genetic analysis was performed using real-time PCR. BMD values as well as clinical and bone parameters with the tested polymorphisms were analyzed among the study population. Analysis of the PPARG rs1801282 variants did not show any association with the risk of osteoporosis and osteopenia. However, for the OPG rs207361 polymorphism, we observed a statistically significant association with the risk of osteoporosis, suggesting that the OPG rs207361 variant may be one of the genetic markers associated with the pathogenesis of osteoporosis.

Ovarian cancer (OC) is one of the biggest problems in gynecological oncology and is one of the most lethal cancers in women worldwide. Most patients with OC are diagnosed at an advanced stage; therefore, there is an urgent need to find new biomarkers for this disease. Gene expression profiling is proving to be a very effective tool for exploring new molecular markers for OC patients, although the relationship between such markers and patient survival and clinical outcomes is still elusive. Moreover, polymorphisms in genes encoding both apoptosis-associated proteins and oncoproteins may serve as key markers of cancer susceptibility. The aim of our study was to analyze the polymorphisms and expressions of the BCL2, BAX and c-MYC genes in a group of 198 women, including 98 with OC. The polymorphisms and mRNA expressions of the BCL2, BAX and c-MYC genes were analyzed using real-time PCR. The analysis of the BAX (rs4645878; G>A) and c-MYC (rs4645943; C>T) polymorphisms showed no association with ovarian cancer risk. The BCL2 polymorphism (rs2279115; C>A) showed a significant difference in the frequency of genotypes between the studied groups (CC: 23.47% vs. 16.00%, AA: 25.51% vs. 37.00%; p = 0.046; OR = 1.61). Furthermore, the expression levels of the BCL2 and c-MYC genes showed a decrease at the transcript level for OC patients compared to the control group (BCL2: 17.46% ± 3.26 vs. 100% ± 8.32; p < 0.05; c-MYC: 37.56% ± 8.16 vs. 100% ± 9.12; p < 0.05). No significant changes in the mRNA level were observed for the BAX gene (104.36% ± 9.26 vs. 100% ± 9.44; p > 0.05). A similar relationship was demonstrated in the case of the protein expressions of the studied genes. These findings suggest that the CC genotype and C allele of the BCL2 polymorphism could be genetic risk factors for OC development. A gene expression analysis indicated that BCL2 and c-MYC are associated with OC risk.

Background The application of allergen immunotherapy (AIT) in combination with biological agents has been found to increase both the safety and efficacy of the desensitisation procedure in patients with food and insect venom allergy. The aim of our study was to compare the effectiveness of AIT in patients with house dust mite (HDM)-driven asthma treated with and without omalizumab. Materials and methods The study was a placebo-controlled, three-armed, randomised, parallel-group, multicentre trial that included 52 patients with HDM-driven asthma. Only patients with monosensitisation to HDM were included. The study compared three patterns of therapy: omalizumab alone, HDM subcutaneous immunotherapy (SCIT-HDM)+ omalizumab, and SCIT alone. The main outcomes were evaluate the Asthma Control Questionnaire (ACQ) score, number of asthma exacerbations and reduction in the daily dose of inhaled steroids during 12 months of observation. Results All variants of therapy led to significantly improved ACQ scores and reduction of asthma exacerbations in all study groups after 12 months of treatment. A statistically significant reduction in the daily doses of inhaled corticosteroids in the group with omalizumab alone (650±150 µg versus 500±50 µg for p=0.003) or SCIT-HDM+omalizumab (550±250 µg versus 375±75 µg for p=0.001) was observed, favouring the latter group. Conclusion The efficacy of AIT for HDM-driven asthma is significantly increased by the combination of allergen vaccine with omalizumab.