This review describes our experience with native tissue repair of the visceral pelvic fascia, the perineum, and anal sphincters in women. We propose that complex repair of the pelvic floor should consider vaginal support in all three anatomical Delancey's levels, together with more caudal structures-the external and internal anal sphincters. Original illustrations were created to facilitate the understanding of the complex anatomy of common multi-level defects. As the integrity of connective tissue adds to various aspects of the delicate function of the female pelvic floor, it is complete and as perfect as possible repair is a common goal of both gynecologists and colorectal specialists.
- MeSH
- Anal Canal * surgery MeSH
- Fascia MeSH
- Gynecologic Surgical Procedures * methods MeSH
- Humans MeSH
- Pelvic Floor Disorders * surgery MeSH
- Pelvic Floor * surgery MeSH
- Perineum surgery MeSH
- Pelvic Organ Prolapse * surgery MeSH
- Vagina surgery MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Several studies have demonstrated the positive effects of mindfulness and self-compassion on employee well-being, mental health, and resilience. The objective of this observational study was to explore the mutual relationships among the dimensions of self-compassion and particular characteristics of work-related well-being: work engagement, workaholism (excessive and compulsive work), and job boredom in a population of early career workers. In this quantitative cross-sectional study, 286 master's students with proper working experience were examined; results from 244 respondents were suitable for further data analysis. The Self-compassion Scale, Utrecht Work Engagement Scale, Dutch Work Addiction Scale, and Dutch Boredom Scale were administered. Spearman's rank correlation analysis found a positive relationship between work engagement and excessive work and a negative relationship between work engagement and job boredom. Furthermore, a positive correlation was identified between compulsive work and negative subscales of the Self-compassion Scale. Structural equation modeling indicated that workaholism was a mediator between the negative scales of self-compassion and work engagement with job boredom. In conclusion, the negative aspects of self-compassion (isolation, self-judgment, and over-identification) are related to the symptoms of workaholism in young workers. Self-compassion-based interventions could help prevent the negative effects of compulsive and excessive work. Possible age-related explanations for the positive relationship between work engagement and workaholism (i.e., excessive work) are discussed. Future longitudinal research could identify the dynamics of the connection between self-compassion and work-related well-being from a long-term perspective.
- Publication type
- Journal Article MeSH
BACKGROUND: Modafinil is primarily used to treat narcolepsy but is also used as an off-label cognitive enhancer. Functional magnetic resonance imaging studies indicate that modafinil modulates the connectivity of neocortical networks primarily involved in attention and executive functions. However, much less is known about the drug's effects on subcortical structures. Following preliminary findings, we evaluated modafinil's activity on the connectivity of distinct cerebellar regions with the neocortex. We assessed the spatial relationship of these effects with the expression of neurotransmitter receptors/transporters. METHODS: Patterns of resting-state functional magnetic resonance imaging connectivity were estimated in 50 participants from scans acquired pre- and postadministration of a single (100 mg) dose of modafinil (n = 25) or placebo (n = 25). Using specific cerebellar regions as seeds for voxelwise analyses, we examined modafinil's modulation of cerebellar-neocortical connectivity. Next, we conducted a quantitative evaluation of the spatial overlap between the modulation of cerebellar-neocortical connectivity and the expression of neurotransmitter receptors/transporters obtained by publicly available databases. RESULTS: Modafinil increased the connectivity of crus I and vermis IX with prefrontal regions. Crus I connectivity changes were associated with the expression of dopaminergic D2 receptors. The vermis I-II showed enhanced coupling with the dorsal anterior cingulate cortex and matched the expression of histaminergic H3 receptors. The vermis VII-VIII displayed increased connectivity with the visual cortex, an activity associated with dopaminergic and histaminergic neurotransmission. CONCLUSIONS: Our study reveals modafinil's modulatory effects on cerebellar-neocortical connectivity. The modulation mainly involves crus I and the vermis and spatially overlaps the distribution of dopaminergic and histaminergic receptors.
- MeSH
- Adult MeSH
- Humans MeSH
- Magnetic Resonance Imaging * MeSH
- Young Adult MeSH
- Modafinil * pharmacology administration & dosage MeSH
- Cerebellum * drug effects diagnostic imaging metabolism MeSH
- Neocortex drug effects metabolism diagnostic imaging MeSH
- Neural Pathways drug effects metabolism MeSH
- Wakefulness-Promoting Agents pharmacology MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
BACKGROUND: Lipopolysaccharide (LPS)-induced inflammation of lung tissues triggers irreversible alterations in the lung parenchyma, leading to fibrosis and pulmonary dysfunction. While the molecular and cellular responses of immune and connective tissue cells in the lungs are well characterized, the specific epithelial response remains unclear due to the lack of representative cell models. Recently, we introduced human embryonic stem cell-derived expandable lung epithelial (ELEP) cells as a novel model for studying lung injury and regeneration. METHODS: ELEPs were derived from the CCTL 14 human embryonic stem cell line through activin A-mediated endoderm specification, followed by further induction toward pulmonary epithelium using FGF2 and EGF. ELEPs exhibit a high proliferation rate and express key structural and molecular markers of alveolar progenitors, such as NKX2-1. The effects of Escherichia coli LPS serotype O55:B5 on the phenotype and molecular signaling of ELEPs were analyzed using viability and migration assays, mRNA and protein levels were determined by qRT-PCR, western blotting, and immunofluorescent microscopy. RESULTS: We demonstrated that purified LPS induces features of a hybrid epithelial-to-mesenchymal transition in pluripotent stem cell-derived ELEPs, triggers the unfolded protein response, and upregulates intracellular β-catenin level through retention of E-cadherin within the endoplasmic reticulum. CONCLUSIONS: Human embryonic stem cell-derived ELEPs provide a biologically relevant, non-cancerous lung cell model to investigate molecular responses to inflammatory stimuli and address epithelial plasticity. This approach offers novel insights into the fine molecular processes underlying lung injury and repair.
- MeSH
- Cell Line MeSH
- Antigens, CD metabolism MeSH
- Endoplasmic Reticulum * metabolism drug effects MeSH
- Epithelial-Mesenchymal Transition * drug effects MeSH
- Epithelial Cells * drug effects metabolism cytology MeSH
- Cadherins * metabolism MeSH
- Humans MeSH
- Human Embryonic Stem Cells * cytology MeSH
- Lipopolysaccharides * pharmacology MeSH
- Lung * cytology MeSH
- Thyroid Nuclear Factor 1 MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Úvod: V důsledku metabolických dějů dochází v živých strukturách k endogenní produkci chemiluminiscence, kterou také označujeme jako biologickou autochemiluminiscenci (BAL). Generování BAL je úzce spojeno s oxidačními procesy, tvorbou volných radikálů a obecně oxidačně-redukční homeostázou zkoumaného biologického materiálu. BAL byla již dříve studována v savčích buněčných modelech a tkáních. Doposud ovšem nebyl tento jev popsán v případě struktur zubní tkáně. Kromě endogenně generované BAL lze BAL indukovat i exogenně, a to jak fyzikálními (UV záření, mechanické poškození, teplo), tak i chemickými (oxidační činidla, např. H2O2) a biotickými (patogeny) faktory. Metodika: V předložené práci byla zkoumána endogenně produkovaná i exogenně indukovaná BAL v povrchových a vnitřních strukturách semiretinovaných a retinovaných třetích molárů, které byly indikovány k extrakci zubním lékařem pro jejich nevhodné uložení v čelisti u dvou pacientů (žena, 21 let, muž, 22 let). Detekce BAL byla provedena po mechanickém odstranění zubního plaku rotačním kartáčkem. Pomocí piezoelektrické pily byly připraveny podélné řezy vedené tak, aby došlo k odhalení všech vnitřních částí zubu. Takto připravené vzorky – celého vnitřního řezu a vnější části celého zubu – byly podrobeny detekci BAL ve světlotěsné komoře za použití fotonásobičového modulu. Následně byly vzorky ošetřeny roztokem oxidačního činidla 3% H2O2 a redukčního činidla 10 mM TCEP (tris(karboxyethyl)fosfin). Výsledky: U obou vzorků zubu bylo prokázáno, že produkují BAL. Produkce endogenní chemiluminiscence byla pozorována ve vnitřních strukturách zubu (18 600 pulzů/600 s), která byla přibližně 2,7krát vyšší než BAL detekovaná na povrchových strukturách zubu (6 900 pulzů/600 s). Po ošetření H2O2 došlo k významnému (až 14násobnému) nárůstu BAL pro vnitřní struktury zubu ve srovnání s bazální intenzitou endogenně produkované BAL. Aplikace TCEP (negativní kontrola) vedla k mírnému potlačení produkce BAL. Závěr: Výsledky této pilotní studie ukazují, že BAL může být produkována nejenom měkkými tkáněmi, ale i tvrdou zubní tkání. Získané výsledky by mohly být využity k výzkumu metabolické aktivity a reaktivity vnitřních i vnějších částí zubu, a to především v kontextu výzkumu oxidačněredukční homeostázy. Detekce BAL by také mohla být aplikována pro vývoj nových zobrazovacích technik.
Introduction: As a result of metabolic processes, the endogenous production of chemiluminescence occurs in living biological structures, which we also refer to as biological autochemiluminescence (BAL). The generation of BAL is closely connected with oxidation processes, the formation of free radicals, and in general the redox homeostasis of the investigated biological material. BAL has previously been studied in mammalian cells and tissues. So far, however, this phenomenon has not been described in dental tissue structures. In addition to endogenously generated BAL, BAL can be exogenously induced by physical (UV radiation, mechanical damage, heat), chemical (oxidizing agents, e.g. H2O2) or biotic (pathogens) factors. Methods: Endogenously and exogenously induced BAL were investigated on the surface and internal structures of semi-impacted and impacted third molars, which were indicated for extraction by a dentist due to their inappropriate placement in the jaw in two patients (a 21-year-old woman and a 22-year-old man). BAL detection was performed with samples after dental plaque was mechanically removed with a rotating brush. Using a piezosurgery unit with a saw headpiece, longitudinal sections were made to reveal all internal parts of the tooth. The samples prepared in this way – the entire internal section and the external part of the entire tooth – were subjected to BAL detection in a dark chamber using H7360-01 PMT photomultiplier. Subsequently, the samples were treated with a solution of the oxidizing agent 3% H2O2 or the reducing agent 10 mM TCEP (tris(carboxyethyl)phosphine). Results: Both tooth samples were shown to produce BAL. Endogenous chemiluminescence production was observed in the internal structures of the tooth (18,600 counts/600 s), which was 2.7-fold higher than the BAL detected on the tooth outer surfaces (6,900 counts/600 s). After H2O2 treatment, there was a significant (up to 14-fold) increase in BAL for internal tooth structures compared to the basal intensity of endogenously produced BAL. The application of TCEP (negative control) resulted in a residual suppression of BAL production. Conclusion: The results of this pilot study show that BAL can be produced not only by soft tissues but also by hard dental tissue. The obtained results could be used for further research of the metabolic activity and reactivity of the inner and outer parts of the tooth, especially in the context of redox biology research. BAL detection could also be applied in the development of new imaging techniques.
Recent advances in protein 3D structure prediction using deep learning have focused on the importance of amino acid residue-residue connections (i.e., pairwise atomic contacts) for accuracy at the expense of mechanistic interpretability. Therefore, we decided to perform a series of analyses based on an alternative framework of residue-residue connections making primary use of the TOP2018 dataset. This framework of residue-residue connections is derived from amino acid residue pairing models both historic and new, all based on genetic principles complemented by relevant biophysical principles. Of these pairing models, three new models (named the GU, Transmuted and Shift pairing models) exhibit the highest observed-over-expected ratios and highest correlations in statistical analyses with various intra- and inter-chain datasets, in comparison to the remaining models. In addition, these new pairing models are universally frequent across different connection ranges, secondary structure connections, and protein sizes. Accordingly, following further statistical and other analyses described herein, we have come to a major conclusion that all three pairing models together could represent the basis of a universal proteomic code (second genetic code) sufficient, in and of itself, to "encode" for both protein folding mechanisms and protein-protein interactions.
- MeSH
- Amino Acids * chemistry genetics MeSH
- Databases, Protein MeSH
- Humans MeSH
- Models, Molecular * MeSH
- Proteins * chemistry genetics metabolism MeSH
- Proteomics * MeSH
- Protein Folding * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
The Roma people have a complex demographic history shaped by their recent dispersal from a South Asian origin into Europe, accompanied by continuous population bottlenecks and gene flow. After settling in the Balkans around 1,000 years ago, the Roma gradually dispersed across Europe, and approximately 500 years ago, they established in the Iberian Peninsula what is now one of the largest Roma populations in Western Europe. Focusing specifically on the Iberian Roma, we conducted the most comprehensive genome-wide analysis of European Roma populations to date. Using allele frequency and haplotype-based methods, we analysed 181 individuals to investigate their genetic diversity, social dynamics, and migration histories at both continental and local scales. Our findings demonstrate significant gene flow from populations encountered during the Roma's dispersal and confirm their South Asian origins. We show that, between the 14th and 19th centuries, the Roma spread westward from the Balkans in various waves, with multiple admixture events. Furthermore, our findings refute previous hypotheses of a North African dispersal route into Iberia and genetic connections to Jewish populations. The Iberian Roma exhibit ten times greater genetic differentiation compared to non-Roma Iberians, indicating significant regional substructure. Additionally, we provide the first genetic evidence of assortative mating within Roma groups, highlighting distinct mating patterns and suggesting a gradual shift towards increased integration with non-Roma individuals. This study significantly enhances our understanding of how demographic history and complex genetic structure have shaped the genetic diversity of Roma populations, while also highlighting the influence of their evolving social dynamics.
- MeSH
- Gene Frequency MeSH
- Genetic Variation MeSH
- Haplotypes MeSH
- Polymorphism, Single Nucleotide MeSH
- Humans MeSH
- Human Migration MeSH
- Genetics, Population * MeSH
- Roma * genetics MeSH
- Gene Flow MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Spain MeSH
Aim: The study aimed to assess the connection of psychological resilience, pain self-efficacy and quality of life in people with chronic kidney disease (CKD) on hemodialysis. Design: A cross-sectional study design was chosen. Methods: Data were collected from 361 adults receiving hemodialysis in hospital and private settings in a Southern European country over six months. This was done in a semi-structured interview using the Connor-Davidson Resilience Scale (CD-RISC), the Pain Self-Efficacy Questionnaire (PSEQ), and the Kidney Disease Quality of Life (KDQOL-36) questionnaire. Results: The results indicated that the higher the resilience, the higher the pain self-efficacy. In addition, pain self-efficacy was found to have a positive effect on minimising both the symptoms and burden of the disease, leading to better quality of life. Conclusion: The present study showed that the level of resilience was proportional to pain self-efficacy with limited effect of demographic parameters. In addition, both resilience and pain self-efficacy affected health-related quality of life in people on hemodialysis. Using up-to-date assessment tools and implementing appropriate pharmacological and non-pharmacological interventions in everyday clinical practice can improve the quality of life of people on hemodialysis.
Background: Coordinated rehabilitation plays a crucial role in helping patients with acquired brain injury (ABI) to return to active lives. Cooperation between occupational therapists (OTs) and social workers (SWs) is very important during the hospital-to-home transition. Aim: The primary objective of the project was to map the coordinated rehabilitation of individuals after ABI within their social environment, aiming to help patients reclaim their lives despite the limitations of ABI. The purpose of this article is to identify and describe the impact of medical-social rehabilitation relative to interprofessional cooperation between OTs and SWs in the patient's home environment. The focus is on identifying the critical elements needed to maximize specialist collaboration. Methods: The research was designed as an experimental qualitative study with auxiliary quantitative indicators in 17 case studies. The study included semi-structured interviews. In addition, the FIM system® and WHODAS 2.0 were used to objectify patient status monitored over time in individual cases. Results: Five critical elements of cooperation were identified: (1) Quality of life, (2) Self-sufficiency, (3) Evaluation of the home, physical, and social environment, (4) Indication of aids, barrier-free modifications, and their financing, (5) Connection of health and social areas. After coordinated intervention, patients reported a gradual increase in their quality of life and self-sufficiency. The next continuity of rehabilitation services is very desirable, at least for maintaining the effect. Conclusion: Specialist cooperation prevents patients from getting lost in the complicated systems of health and social services. It maximizes access to and effectiveness of these services, including the availability of financial aid and psychological support.
- MeSH
- Occupational Therapy * methods MeSH
- Case Reports as Topic MeSH
- Quality of Life MeSH
- Humans MeSH
- Interdisciplinary Communication MeSH
- Independent Living education MeSH
- Social Work methods MeSH
- Brain Injuries, Traumatic * rehabilitation MeSH
- Check Tag
- Humans MeSH
- Publication type
- Clinical Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Slovakia MeSH
INTRODUCTION: Deep brain stimulation (DBS) of the internal globus pallidus (GPi) is a well-established, effective treatment for dystonia. Substantial variability of therapeutic success has been the one of the drivers of an ongoing debate about proper stimulation site and settings, with several indications of the notional sweet spot pointing to the lower GPi or even subpallidal area. METHODS: The presented patient-blinded, random-order study with cross-sectional verification against healthy controls enrolled 17 GPi DBS idiopathic, cervical or generalised dystonia patients to compare the effect of the stimulation in the upper and lower GPi area, with the focus on sensorimotor network connectivity and local activity measured using functional magnetic resonance. RESULTS: Stimulation brought both these parameters to levels closer to the state detected in healthy controls. This effect was much more pronounced during the stimulation in the lower GPi area or beneath it than in slightly higher positions, with stimulation-related changes detected by both metrics of interest in the sensorimotor cortex, striatum, thalamus and cerebellum. CONCLUSIONS: All in all, this study not only replicated the results of previous studies on GPi DBS as a modality restoring sensorimotor network connectivity and local activity in dystonia towards the levels in healthy population, but also showed that lower GPi area or even subpallidal structures, be it white matter or even small, but essential nodes in the zona incerta as nucleus basalis of Meynert, are important regions to consider when programming DBS in dystonia patients.
- MeSH
- Adult MeSH
- Dystonic Disorders therapy physiopathology diagnostic imaging MeSH
- Dystonia therapy physiopathology diagnostic imaging MeSH
- Globus Pallidus * diagnostic imaging physiopathology MeSH
- Deep Brain Stimulation * methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging * methods MeSH
- Cross-Sectional Studies MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH