Functional Activities Research Articles

Study on the Impact of Hormone Therapy for Prostate Cancer on the Quality of Life and the Psycho-Relational Sphere of Patients: ProQoL.

Prostate cancer and its treatment, particularly androgen deprivation therapy (ADT), can profoundly impact patients' quality of life. The aim of the prospective observational study reported here was to evaluate the effects of ADT on various aspects of quality of life in men with prostate cancer at a community-based hospital in Southern Italy. Eligible men initiating hormonal therapy were recruited between December 2021 and December 2023. Data were collected at baseline (T0) and after 3months (T1) and 6months (T2) of ADT using standardized questionnaires (European Organization for Research and Treatment of Cancer [EORTC] QLQ-C30, EORTC QLQ-PR25) and semi-structured interviews. Of the 52 participants, 43 completed all three assessments. The EORTC QLQ-C30 showed a statistically significant worsening in physical functioning (mean score decrease from 83.8 at T0 to 76.7 at T2; p < 0.001), increased fatigue (from 23.7 to 35.2; p < 0.001), and insomnia (from 23.7 to 31.8; p = 0.048) following ADT initiation. The QLQ-PR25 revealed a significant decline in sexual functioning (from 59 to 26.9; p < 0.001) and sexual activity (from 27.3 to 12; p = 0.001). Interviews revealed a significant rise in the number of patients reporting depressed mood. Interviews also highlighted a worsening in body image perception and sexuality, increased feelings of dependence, and challenges in the social and relational spheres. ADT significantly impacts various aspects of quality of life in men with prostate cancer, particularly physical functioning, fatigue, sexual function, body image, and emotional well-being. These results underscore the critical importance of a comprehensive, patient-centered approach that addresses both the physical and psychosocial aspects of care.

Predictors, Diagnoses, and Costs of Emergency Department Visits among Home Care Clients

ObjectivesTo examine factors, diagnoses, and costs associated with emergency department (ED) visits among home care clients. DesignA prospective 1-year follow-up study. Settings and ParticipantsMore information is needed regarding the reasons and costs associated with ED visits by home care clients. Participants were persons aged ≥65 years living in Eastern Finland and receiving regular home care services (n = 293). MethodsData collection included clients’ demographics, health status (Charlson Comorbidity Index), medication use, assessments of physical (Timed Up and Go) and cognitive functioning (Mini-Mental State Examination), Basic and Instrumental Activities of Daily Living, mood (Geriatric Depression Scale, GDS-15) and health-related quality of life [HRQoL, EuroQol (EQ-5D-3 L)]. Logistic regression and univariate analyses of variance were conducted. The costs (total and per person-year) of ED visits were calculated. ResultsThe number of ED visits was 775 during the follow-up (mean 350 days). The likelihood of ED visits was reduced by better HRQoL and increased by a higher GDS-15 score, longer TUG times, and a history of heart failure and decreased glomerular infiltration. The most common primary diagnoses for ED visits were heart failure (8.4%), atrial fibrillation (4.0%), respiratory infection (4.0%), and cystitis (3.5%). The total costs of all ED visits during the follow-up were 251,247 € and internal medicine and surgery accounted for 142,726 € and 89,212 € of the cost, respectively. The costs per person-year were 981 €. Conclusions and ImplicationsHRQoL, depressive symptoms, mobility, and heart and renal failure were associated with the number of ED visits. The most common reasons for ED visits were chronic heart conditions and infectious diseases and the highest costs were incurred by internal medicine treatment. With advanced care planning and active symptom screening and cooperation of home care nurses and physicians, some of the ED visits, for example due to heart failure, might be preventable.

Potential Neuroprotective Role of Neurotrophin in Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major global health issue that affects millions of people every year. It is caused by any form of external force, resulting in temporary or permanent impairments in the brain. The pathophysiological process following TBI usually involves excitotoxicity, mitochondrial dysfunction, oxidative stress, inflammation, ischemia, and apoptotic cell death. It is challenging to find treatment for TBI due to its heterogeneous nature, and no therapeutic interventions have been approved thus far. Neurotrophins may represent an alternative approach for TBI treatment because they influence various functional activities in the brain. The present review highlights recent studies on neurotrophins shown to possess neuroprotective roles in TBI. Neurotrophins, specifically brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) have demonstrated reduced neuronal death, alleviated neuroinflammatory responses and improved neurological functions following TBI via their immunomodulatory, anti-inflammatory and antioxidant properties. Further studies are required to ensure the efficacy and safety of neurotrophins to be used as TBI treatment in clinical settings.

Diversity, Distribution and Structural Prediction of the Pathogenic Bacterial Effectors EspN and EspS.

Many Gram-negative enterobacteria translocate virulence proteins (effectors) into intestinal epithelial cells using a type III secretion system (T3SS) to subvert the activity of various cell functions possess. Many T3SS effectors have been extensively characterized, but there are still some effector proteins whose functional information is completely unknown. In this study, two predicted effectors of unknown function, EspN and EspS (Escherichia coli secreted protein N and S), were selected for analysis of translocation, distribution and structure prediction. The TEM1 (β-lactamase) translocation assay was performed, which showed that EspN and EspS are translocated into host cells in a T3SS-dependent manner during bacterial infection. A phylogenetic tree analysis revealed that homologs of EspN and EspS are widely distributed in pathogenic bacteria. Multiple sequence alignment revealed that EspN and its homologs share a conserved C-terminal region (673-1133 a.a.). Furthermore, the structure of EspN (673-1133 a.a.) was also predicted and well-defined, which showed that it has three subdomains connected by a loop region. EspS and its homologs share a sequence-conserved C-terminal (146-291 a.a.). The predicted structure of EspS (146-291 a.a.) is composed of a β-sheet consisting of four β-strands and several short helices, which has a TM score of 0.5014 with the structure of the Vibrio cholerae RTX cysteine protease domain (PDBID: 3eeb). These results suggest that EspN and EspS may represent two important classes of T3SS effectors associated with pathogen virulence, and our findings provide important clues to understanding the potential functions of EspN and EspS.

The impact of group cognitive behavioral psychotherapy on disease severity and psychosocial functioning in patients with inflammatory bowel disease: a randomized controlled study.

Patients with inflammatory bowel disease (IBD) often report symptoms of anxiety and depression as well as impaired quality of life (QoL). To date, there are few studies on the effect of psychotherapy on psychological functioning and clinical outcome in patients with IBD. The aim of this prospective, randomized, controlled study was to investigate the effect of a brief psychotherapeutic intervention on psychological distress, QoL, sexual functioning, and inflammation and disease activity indices in patients with IBD. Participants were randomized to receive either group cognitive behavioral therapy or treatment as usual (controls) and were assessed at baseline and after six months using psychometric instruments to assess psychological distress, QoL, and sexual functioning. In addition, laboratory measurements, including levels of C-reactive protein (CRP), cytokines and calprotectin, and calculations of disease activity indices were performed during the two study periods. 80 participants took part in the study. Patients who received psychotherapy reported a significant decrease in anxiety and depression symptoms, a significant improvement in physical functioning, general health, vitality, social functioning and mental health, a decrease in physical pain and a decrease in role limitations caused by emotional problems. CRP levels and the Crohn's disease activity index (CDAI) also decreased significantly at follow-up compared to controls. Group cognitive behavioral therapy is proving to be an important component of holistic care for IBD patients, as it can significantly improve not only patients' psychosocial functioning but also their clinical course by inhibiting inflammation and reducing disease activity.

Development and validation of MyCommunication-Adults, a self-report communicative participation measure.

People with communication problems experience challenges in participation. Optimizing communicative participation for this population is an important outcome of speech and language therapy. Participation experiences are best assessed from the patient's perspective, using a patient-reported outcome measure (PROM). The Communicative Participation Item Bank (CPIB) has been developed to identify perceived problems in communicative participation. However, previous research has shown that the item bank does not cover all domains and concepts of communicative participation, contains general communication items, and is not suitable for all people with communication problems. To develop a comprehensive PROM aimed at measuring communicative participation for all adults with communication problems and test its content validity. An initial pool of 242 items was based on three sources: relevant content from an earlier literature review and concept elicitation study, and the translation of the items of the CPIB. This item pool was pilot-tested for comprehensibility and comprehensiveness using cognitive debriefing interviews in adults with different communication problems (speech, language, voice, hearing and cognitive communication disorders). This resulted in a second version of the item bank. The content validity of this version was tested in a group of professionals. The last (third) version of 133 items was tested for content validity in a second, new group of adults with various communication problems. The initial pool of 242 items was developed and pilot-tested in 27 adults with different communication problems. After modifications, 161 items remained, which were tested in a content validity study with 25 people with different communication problems and five professionals (in the field of speech and language therapy and speech and language research). The professionals considered 91.9% of the item bank relevant and comprehensible, and comprehensive by adding two items. The item bank was then considered relevant, comprehensible and comprehensive by the group of adults with communication problems. A total of 133 items remained in the item bank, related to the International Classification of Functioning, Disability and Health (ICF) Activities and Participation domains 'mobility', 'self-care', 'domestic life', 'interpersonal interactions and relationships', 'major life areas' and 'community, social and civic life'. MyCommunication-Adults is an item bank for measuring communicative participation in adults with communication difficulties. The next step is to test the psychometric properties of the item bank, in order to establish a final item bank. The refined description of the construct of communicative participation can already be used for participation-focused goal-setting between individuals with communication problems and speech and language therapists. What is already known on the subject The CPIB was developed to measure communicative participation in community-dwelling adults with communication problems. The item bank does not cover all domains and concepts of communicative participation, contains general communication items and not all questions seem to be relevant for specific target groups (e.g., hearing population). What this paper adds to the existing knowledge This study presents a refined description of the construct of communicative participation and the development of a new comprehensive PROM aimed at measuring this construct for all adults with communication difficulties. The development of the PROM is based on a previously conducted literature review and concept elicitation study. This study describes the development process of this new PROM, called MyCommunication-Adults, and the assessment of its content validity. What are the potential or actual clinical implications of this work? The refined description of the construct of communicative participation can be used for participation-focused goal-setting between individuals with communication problems and speech and language therapists.

Potential applications of microbial genomics in nuclear non-proliferation.

As nuclear technology evolves in response to increased demand for diversification and decarbonization of the energy sector, new and innovative approaches are needed to effectively identify and deter the proliferation of nuclear arms, while ensuring safe development of global nuclear energy resources. Preventing the use of nuclear material and technology for unsanctioned development of nuclear weapons has been a long-standing challenge for the International Atomic Energy Agency and signatories of the Treaty on the Non-Proliferation of Nuclear Weapons. Environmental swipe sampling has proven to be an effective technique for characterizing clandestine proliferation activities within and around known locations of nuclear facilities and sites. However, limited tools and techniques exist for detecting nuclear proliferation in unknown locations beyond the boundaries of declared nuclear fuel cycle facilities, representing a critical gap in non-proliferation safeguards. Microbiomes, defined as "characteristic communities of microorganisms" found in specific habitats with distinct physical and chemical properties, can provide valuable information about the conditions and activities occurring in the surrounding environment. Microorganisms are known to inhabit radionuclide-contaminated sites, spent nuclear fuel storage pools, and cooling systems of water-cooled nuclear reactors, where they can cause radionuclide migration and corrosion of critical structures. Microbial transformation of radionuclides is a well-established process that has been documented in numerous field and laboratory studies. These studies helped to identify key bacterial taxa and microbially-mediated processes that directly and indirectly control the transformation, mobility, and fate of radionuclides in the environment. Expanding on this work, other studies have used microbial genomics integrated with machine learning models to successfully monitor and predict the occurrence of heavy metals, radionuclides, and other process wastes in the environment, indicating the potential role of nuclear activities in shaping microbial community structure and function. Results of this previous body of work suggest fundamental geochemical-microbial interactions occurring at nuclear fuel cycle facilities could give rise to microbiomes that are characteristic of nuclear activities. These microbiomes could provide valuable information for monitoring nuclear fuel cycle facilities, planning environmental sampling campaigns, and developing biosensor technology for the detection of undisclosed fuel cycle activities and proliferation concerns.

The dynamic role of the left dlPFC in neurovisceral integration: Differential effects of theta burst stimulation on vagally mediated heart rate variability and cognitive-affective processing.

Adapting to the ever-changing demands of the environment requires a complex interplay between cognitive-affective, neuronal, and autonomic processes. Vagally mediated heart rate variability (vmHRV) is positively associated with both cognitive-affective functioning and prefrontal cortex (PFC) activity. Accordingly, the Neurovisceral Integration Model has posited a shared role of the PFC in the regulation of cognitive-affective processes and autonomic nervous system (ANS) activity. While there are numerous correlational findings in this regard, no study so far has investigated whether the manipulation of PFC activity induces changes in vmHRV and cognitive-affective processing in an inter-dependent manner. In a sample of 64 participants, we examined the effects of continuous (cTBS; n = 21) and intermittent theta-burst stimulation (iTBS; n = 20) compared to sham stimulation (n = 23) over the left dorsolateral PFC (dlPFC) on vmHRV and cognitive-affective processing within an emotional stop-signal task (ESST). Our results revealed that both resting vmHRV and vmHRV reactivity predicted cognitive-affective processing. Furthermore, we found a dampening effect of cTBS on resting and on-task vmHRV, as well as an enhancing effect of iTBS on ESST performance. Our results show no direct association between vmHRV changes and ESST performance alterations following stimulation. We interpret our results in the light of a hierarchical model of neurovisceral integration, suggesting a dynamical situation-dependent recruitment of higher-order cortical areas like the dlPFC in the regulation of the ANS. In conclusion, our results highlight the complex interplay between PFC activity, autonomic regulation, and cognitive-affective processing, emphasizing the need for further research to understand the causal dynamics of the underlying neural mechanisms.

Comparison of water- vs. land-based exercise for improving functional capacity and quality of life in patients living with and beyond breast cancer (the AQUA-FiT study): a randomized controlled trial.

Patients living with and beyond breast cancer frequently exhibit several side effects that can impact quality of life and physical functioning way beyond diagnosis and cancer therapies. Traditional on-land exercise has shown to be effective in reducing several symptoms of BC but little is known about the role of water-based exercise in improving physical and psychological well-being. To compare land- vs. water-based exercise training for BC survivors to improve Health-Related Quality of Life (HRQoL), cancer-related fatigue (CRF), physical functioning, body composition and physical activity in patients with BC. A randomised, parallel group (1:1) controlled trial was conducted between 2020 and 2022. Patients were randomly allocated to complete a similar exercise training twice weekly during 12 weeks either on land (LG) using traditional gym equipment or in a swimming pool (WG) using body-weight exercises and water-suitable accessories. Both groups were supervised and monitored by an experienced physiotherapist. Main outcome was HRQoL (EORTC QLQ C30 and B23 module) and CRF measured with the Piper Scale. Secondary variables included functional capacity with the 6 Minutes Walking Test (6MWT), upper and lower body strength (handgrip strength and 30″ Sit-to-Stand (STS) test), body composition and objectively measured physical activity. 28 patients were assessed and randomised during the study period. One patient did not receive the allocated intervention due to skin issues and one patient was dropped out during the intervention. A significant effect of time was found for both symptom severity (F(2,52) = 6.46, p = 0.003) and overall functioning (F1.67,43.45 = 5.215, p =0 .013) but no interaction was found between group and time. No effects were reported for CRF. Similar findings were reported for functional capacity (time effect F1.231,32.019 = 16.818, p < 0.001) and lower body strength (time effect F2,52 = 15.120, p < 0.001) as well as fat mass (time effect F2,52 = 4.38, p = 0.017). Notably, a significant time per group interaction was reported for physical activity (F2,52 = 6.349, p =0.003) with patients in the WG significantly improving PA levels over time while patients in the LG exhibited a marked decreased. Exercise training either in water or on land can decrease symptom severity and improve functionality and body composition. Water-based training seems more effecting than land-based exercise to improve physical activity patterns over time.

The Need to Adapt the Psychiatric Clinical Assessment to the Digital Age: A Practical Approach.

The use of electronic devices and social media is becoming a ubiquitous part of most people's lives. Although researchers are exploring the sequelae of such use, little attention has been given to the importance of digital media use in routine psychiatric assessments of patients. The nature of technology use is relevant to understanding a patient's lifestyle and activities, the same way that it is important to evaluate the patient's occupation, functioning, and general activities. The authors propose a framework for psychiatric inquiry into digital media use, emphasizing that such inquiry should focus on quality of use, including emotional and behavioral consequences, rather than simply the amount of use.

Consistent and Scalable Bayesian Joint Variable and Graph Selection for Disease Diagnosis Leveraging Functional Brain Network

We consider the joint inference of regression coefficients and the inverse covariance matrix for covariates in high-dimensional probit regression, where the predictors are both relevant to the binary response and functionally related to one another. A hierarchical model with spike and slab priors over regression coefficients and the elements in the inverse covariance matrix is employed to simultaneously perform variable and graph selection. We establish joint selection consistency for both the variable and the underlying graph when the dimension of predictors is allowed to grow much larger than the sample size, which is the first theoretical result in the Bayesian literature. A scalable Gibbs sampler is derived that performs better in high-dimensional simulation studies compared with other state-of-art methods. We illustrate the practical impact and utilities of the proposed method via a functional MRI dataset, where both the regions of interest with altered functional activities and the underlying functional brain network are inferred and integrated together for stratifying disease risk.

The Contribution of Mast Cells to the Regulation of Elastic Fiber Tensometry in the Skin Dermis of Children with Marfan Syndrome.

Marfan syndrome (MFS) is a hereditary condition accompanied by disorders in the structural and regulatory properties of connective tissue, including elastic fibers, due to a mutation in the gene encodes for fibrillin-1 protein (FBN1 gene) and the synthesis of abnormal fibrillin-1 glycoprotein. Despite the high potential of mast cells (MCs) to remodel the extracellular matrix (ECM), their pathogenetic significance in MFS has not been considered yet. The group of patients with Marfan syndrome included two mothers and five children (three girls aged 4, 11, and 11 and two boys aged 12 and 13). Normal skin was examined in two children aged 11 and 12. Histochemical, monoplex, and multiplex immunohistochemical techniques; combined protocols of simultaneous histochemical and immunohistochemical staining (the results of staining were assessed using light, epifluorescence, and confocal microscopy); and bioinformatics algorithms for the quantitative analysis of detected targets were used to evaluate mast cells and their relationship with other cells from extracellular structures in the skin dermis. Analysis of the skin MC population in children with Marfan syndrome revealed a considerably increased number of intra-organic populations with the preservation of the specific Tryptase+Chymase+CPA3+ protease profile typical of the skin. The features of the MC histotopography phenotype in MFS consisted of closer colocalization with elastic fibers, smooth muscle cells, and fibroblasts. MCs formed many intradermal clusters that synchronized the activity of cell functions in the stromal landscape of the tissue microenvironment with the help of spatial architectonics, including the formation of cell chains and the creation of fibrous niches. In MCs, the expression of specific proteases, TGF-β, and heparin increased, with targeted secretion of biologically active substances relative to the dermal elastic fibers, which had specific structural features in MFS, including abnormal variability in thickness along their entire length, alternating thickened and thinned areas, and uneven surface topography. This paper discusses the potential role of MCs in strain analysis (tensometry) of the tissue microenvironment in MFS. Thus, the quantitative and qualitative rearrangements of the skin MC population in MFS are aimed at altering the stromal landscape of the connective tissue. The results obtained should be taken into account when managing clinical signs of MFS manifested in other pathogenetically critical structures of internal organs, including the aorta, tendons, cartilage, and parenchymal organs.

Synthesis, dispersion, functionalization, biological and antioxidant activity of metal oxide nanoparticles: Review

Metal oxide nanoparticles (MONPs) have garnered significant interest due to their remarkable properties with applications in diverse fields like human health, agriculture, and general community health. This has led to their widespread use across various scientific and industrial sectors. We focused on four specific types of MONPs: iron oxide, gadolinium oxide, titanium dioxide, and zinc oxide nanoparticles due to their advantages over other metal oxides and noble metals, including cost-effectiveness, biocompatibility, and versatility. This review aimed to highlight examples of MONPs with various implementations and provide a comprehensive revision on the synthesis, dispersion, functionalization, biological and antioxidant activity of the selected MONPs. In this context, we demonstrated the applications of MONPs in various relevant domains and the impact of surface functionalization on the mechanical, optical, and electrical properties of MONPs, particularly in biological and antioxidant activities. Moreover, the volumetric, viscometric, and optical characteristics of MONPs dispersions and their stability challenges were significantly illustrated. The opportunities for MONPs in the global market based on market statistical studies were introduced in order to explore the current and future prospects for MONPs in the commercial market. This review paper offers a thorough and novel perspective on the synthesis, properties, functionalization, and applications of selected MONPs, along with their market potential, making it a valuable resource for researchers and industry professionals. Our revision has sparked interest in the scientific pursuit of uncomplicated and intuitive ideas that make use of regenerative options.

Factors associated with change in activities of daily living performance in home health care patients with diabetes

Older adults with diabetes are at risk for impairments in activities of daily living (ADL) performance. Home health (HH) services help patients regain their ability to perform ADLs following hospitalization, but there may be disparities in ADL improvement. We aimed to identify factors associated with change in ADL performance from the start of HH care to discharge in HH patients with diabetes age ≥65. This secondary analysis used Outcome and Assessment Information Set-D data collected by a HH agency. The sample (n = 1350) had a mean age of 76.3 (SD 7.3). Black/African American race and bowel incontinence/ostomy were associated with less ADL improvement. The following factors were associated with greater ADL improvement: having a caregiver who needed training/support, surgical wounds, pain that interfered with activity, confusion, and better scores in prior functioning. Overall, most patients improved their ADL performance while receiving HH care, but there are disparities that should be addressed.

Features of the neutrophil granulocyte phenotype in children with infectious mononucleosis

The course of infectious diseases caused by viruses, and their common outcome is determined by the activity of the inflammatory reaction which occurs both at the local and systemic levels. However, the features of neutrophil functions during inflammatory reaction are virtually unknown in the patients with infectious mononucleosis (IM), caused by Epstein–Barr virus (EBV). Hence, the aim of our study was to evaluate some characteristics of phenotypic spectrum of blood neutrophils in children with IM. Patients and methods. We examined 84 children aged 3 to 11 years with EBV infection with moderate or severe clinical course of the disease. All patients exhibited a positive test for EBV DNA in blood lymphocytes and appropriate serological markers of acute EBV infection. The control group consisted of 40 conditionally healthy children at the similar age range. The study of neutrophil phenotype was carried out by flow cytometry using direct immunofluorescence of whole peripheral blood samples. A study of the neutrophil phenotype with a combination of two functional antigens (CD64 and CD32) has revealed that in children with IM, regardless of age, the main fraction of blood neutrophils are double-negative cells, whereas in healthy children it consists of CD64-CD32+ neutrophils. The main fraction of neutrophils in the paired combination of CD64 and CD11b antigens in sick children aged 3-6 and 7-11 years was similar to the healthy controls (CD64-CD11b+), but with a change in the content of minor cell fractions. The number of CD64-CD15+ neutrophils (main fraction of cells in healthy children) proved to be significantly reduced in the IM patients of both age groups. However, we have revealed a marked increase in the level of double-negative cells for the CD64 and CD15 antigens. At the same time, the content of double-negative neutrophils for these markers was also increased in IM children of both age groups. The cells with CD11b-CD15+ and CD11b+CD15+ phenotypes comprised the main fractions in IM, as studied by a paired combination of CD11b and CD15 antigens; in healthy children – only CD11b+CD15+ neutrophils are detected. The phenotypic changes of neutrophils during IM suggest a decreased migratory ability of cells with high activity of proinflammatory functions. The established ontogenetic features of the neutrophil phenotype are significantly changed in the children with IM, probably, due to specific immunopathogenesis of the viral infection. The detected changes in phenotypic composition of neutrophils associated with IM may be caused both by the features of protective reaction of innate immune cells and pathogenic effects of the virus itself upon blood neutrophils.

An Updated Review on Possible Therapeutic Role of Vincamine Via 5-HT Receptors in the Treatment of Depression

Background: Serotonin is a neurotransmitter that regulates neuronal activity and a variety of cognitive functions, and medicines that target serotonin receptors are frequently utilized in psychiatry and neurology. Clinical and preclinical research on the role of serotonin in major depressive disorder is growing. These findings demonstrate the intricacy of serotonin transmission across multiple receptors, in a variety of brain areas, and across the lifespan. The serotonin transporter's significance in major depressive disorder has been highlighted in geneenvironment association studies, as well as its participation in the mechanism of the most successful antidepressant medications, selective serotonin reuptake inhibitors. While most of the 15 known serotonin receptors have been linked to depression or depressive-like behaviour, the serotonin 1A (5-HT) and 1B (5-HT) receptors have received the most attention. Objectives: The primary goal of this study is to review the antidepressant effect of herbal medications by modifying serotonin receptors in the future. Result: Human brain imaging and genetic studies suggest that 5-HT and 5-HT receptors play a role in major depressive disorder and antidepressant treatment response. The availability of tissue-specific and inducible knockout mice lines in rodents has allowed for the detection of 5- HT and 5-HT receptor involvement throughout development and in cell-type specific ways. It may be found that herbal drugs will be effective as the serotonin reuptake inhibitors. Conclusion: This and other future preclinical pharmacology studies show that these receptors' autoreceptor and heteroreceptor populations play different roles in modulating depressionrelated behaviour and antidepressant responses, as well as having different functions during early postnatal development versus adulthood. According to analysis of our research findings, alkaloids may have some therapeutic promise as natural antidepressants. Given their widespread distribution in nature, alkaloids might be a cheap way to treat depression.

Physical Functioning, Physical Activity, and Variability in Gait Performance during the Six-Minute Walk Test.

Instrumenting the six-minute walk test (6MWT) adds information about gait quality and insight into fall risk. Being physically active and preserving multi-directional stepping abilities are also important for fall risk reduction. This analysis investigated the relationship of gait quality during the 6MWT with physical functioning and physical activity. Twenty-one veterans (62.2 ± 6.4 years) completed the four square step test (FSST) multi-directional stepping assessment, a gait speed assessment, health questionnaires, and the accelerometer-instrumented 6MWT. An activity monitor worn at home captured free-living physical activity. Gait measures were not significantly different between minutes of the 6MWT. However, participants with greater increases in stride time (ρ = -0.594, p < 0.01) and stance time (ρ = -0.679, p < 0.01) during the 6MWT reported lower physical functioning. Neither physical activity nor sedentary time were related to 6MWT gait quality. Participants exploring a larger range in stride time variability (ρ = 0.614, p < 0.01) and stance time variability (ρ = 0.498, p < 0.05) during the 6MWT required more time to complete the FSST. Participants needing at least 15 s to complete the FSST meaningfully differed from those completing the FSST more quickly on all gait measures studied. Instrumenting the 6MWT helps detect ranges of gait performance and provides insight into functional limitations missed with uninstrumented administration. Established FSST cut points identify aging adults with poorer gait quality.

TYPES OF ALLUSIONS IN BOHDAN TOMENCHUK’S POETRY ABOUT THE WAR

The paper examines allusions in Bohdan Tomenchuk’s poetry collection “Embroider, Mother, a bulletproof vest.” The various types of allusions are grouped based on their functions (activation of historical memory, adherence to literary tradition, text-structuring), themes (historical, mythological), and typology (ranging from nominal and quotation-type to associative). An attempt was made to differentiate the concept of allusion from quotation and reminiscence, while also juxtaposing it with intertext and intertextuality for comparison. In the poet’s texts about the modern Russian-Ukrainian war, the references to literary works are accompanied by numerous allusions to historical reality. These are references of the nominal type (topographical or proper names connected with certain historical events in the reader's mind). The author's distinctive approach involves overlapping different types of allusions, namely those of historical and literary nature, as well as historical and mythological. Behind a direct allusion, an associative one may emerge, linking to a text from a different time period through shared words, phrases, or thematic aura. The involvement of allusion in Tomenchuk’s poetry often occurs on the basis of the allegation (the new text ‘absorbs’ the previous one, without entering into a controversy with the original text). In this case, we deal with intertext (a text within a text). When an allusion entering a new text gets engaged in a dialogue with the original text, we deal with intertextuality as a process of textual interaction. By involving an allusion, the author makes it an element of the structure that serves as an impetus for the reader to navigate within a receptive context, searching among known texts relevant for interpreting the allusion while disregarding distant ones. Intertextuality engages cognition here. Sometimes allusion is not just an element of a structure but a structural principle, and it is proper to name it a structuring allusion. Various allusions in B. Tomenchuk’s poetry make it possible to fit the widest range of emotions and thoughts in a small textual space, to integrate the new experience of war into a broad historical and literary canvas with a biblical and mythological background.

Serotonin signalling in cancer: Emerging mechanisms and therapeutic opportunities

AbstractBackgroundSerotonin (5‐hydroxytryptamine) is a multifunctional bioamine serving as a neurotransmitter, peripheral hormone and mitogen in the vertebrate system. It has pleiotropic activities in central nervous system and gastrointestinal function via an orchestrated action of serotonergic elements, particularly serotonin receptor‐mediated signalling cascades. The mitogenic properties of serotonin have garnered recognition for years and have been exploited for repurposing serotonergic‐targeted drugs in cancer therapy. However, emerging conflicting findings necessitate a more comprehensive elucidation of serotonin's role in cancer pathogenesis.Main body and conclusionHere, we provide an overview of the biosynthesis, metabolism and action modes of serotonin. We summarise our current knowledge regarding the effects of the peripheral serotonergic system on tumourigenesis, with a specific emphasis on its immunomodulatory activities in human cancers. We also discuss the dual roles of serotonin in tumour pathogenesis and elucidate the potential of serotonergic drugs, some of which display favourable safety profiles and impressive efficacy in clinical trials, as a promising avenue in cancer treatment.Key points Primary synthesis and metabolic routes of peripheral 5‐hydroxytryptamine in the gastrointestinal tract. Advanced research has established a strong association between the serotonergic components and carcinogenic mechanisms. The interplay between serotonergic signalling and the immune system within the tumour microenvironment orchestrates antitumour immune responses. Serotonergic‐targeted drugs offer valuable clinical options for cancer therapy.

N6-methyladenosine methylation analysis of circRNAs in acquired middle ear cholesteatoma.

Middle ear cholesteatoma is a chronic middle ear disease characterized by severe hearing loss and adjacent bone erosion, resulting in numerous complications. This study sought to identify pathways involved in N6-methyladenosine (m6A) modification of circRNA in middle ear cholesteatoma. A m6A circRNA epitranscriptomic microarray analysis was performed in middle ear cholesteatoma tissues (n = 5) and normal post-auricular skin samples (n = 5). Bioinformatics analyses subsequently explored the biological functions (Gene Ontology, GO) and signaling pathways (Kyoto Encyclopedia of Genes and Genomes, KEGG) underlying middle ear cholesteatoma pathogenesis. Methylated RNA immunoprecipitation qPCR (MeRIP-qPCR) was performed to verify the presence of circRNAs with m6A modifications in middle ear cholesteatoma and normal skin samples. Microarray analysis identified 3,755 circRNAs as significantly differentially modified by m6A methylation in middle ear cholesteatoma compared with the normal post-auricular skin. Among these, 3,742 were hypermethylated (FC ≥ 2, FDR < 0.05) and 13 were hypomethylated (FC ≤ 1/2, FDR < 0.05). GO analysis terms with the highest enrichment score were localization, cytoplasm, and ATP-dependent activity for biological processes, cellular components, and molecular functions respectively. Of the eight hypermethylated circRNA pathways, RNA degradation pathway has the highest enrichment score. Peroxisome Proliferator-Activated Receptor (PPAR) signaling pathway was hypomethylated. To validate the microarray analysis, we conducted MeRIP-qPCR to assess the methylation levels of five specific m6A-modified circRNAs: hsa_circRNA_061554, hsa_circRNA_001454, hsa_circRNA_031526, hsa_circRNA_100833, and hsa_circRNA_022382. The validation was highly consistent with the findings from the microarray analysis. Our study firstly presents m6A modification patterns of circRNAs in middle ear cholesteatoma. This finding suggests a direction for circRNA m6A modification research in the etiology of cholesteatoma and provides potential therapeutic targets for the treatment of middle ear cholesteatoma.