BACKGROUND: Rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) are autoimmune illnesses characterised by chronic inflammation demonstrating differential associations with psychiatric conditions. OBJECTIVE: In this matched-cohort study, we aimed to investigate whether the associations between these inflammatory illnesses and mental disorders are predominantly the consequence of the burden of the former or whether common causes might underpin the susceptibility to both. METHODS: Using Czech national inpatient care data, we identified individuals with RA or axSpA during the years 1999-2012. We investigated the occurrence of psychiatric outcomes up to 2017 using stratified Cox proportional hazards models. In evidence triangulation, we assessed the potential moderation by age at inflammatory illness, the associations relative to counterparts with other similarly burdensome chronic illnesses and the temporal ordering of conditions. FINDINGS: Both RA and axSpA were associated with mood and anxiety disorders and behavioural syndromes. In evidence triangulation, the associations with depression showed a decreasing age-at-inflammatory-illness gradient in RA; the association between RA and depression was stronger than that between other chronic illnesses and depression; and excluding prevalent depression attenuated the RA-depression association. RA showed consistent inverse associations with schizophrenia and Alzheimer's disease. CONCLUSIONS: Common aetiologies might be involved in increasing the risk of developing both RA and depression. The consistent inverse associations between RA and schizophrenia and between RA and Alzheimer's disease suggest that at least part of these associations might also be a consequence of shared aetiologies as well as potential medication effects. CLINICAL IMPLICATIONS: People with autoimmune arthritides are more likely to experience mood and anxiety disorders, even relative to counterparts with other similarly burdensome chronic illnesses.
- MeSH
- dospělí MeSH
- duševní poruchy * epidemiologie imunologie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- revmatoidní artritida * epidemiologie imunologie psychologie komplikace MeSH
- senioři MeSH
- spondylartritida imunologie epidemiologie psychologie MeSH
- zánět epidemiologie imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: The exact positioning of the dominant hand at the time of manual perineal protection (MPP) is not clearly specified. The main aim of this work was to identify the place on the perineum where pressure needs to be applied to achieve optimal forward fetal head displacement away from the anal sphincters using the bregma to posterior fourchette distance (BFD) and the perineal body length (PBL). METHODS: This was a two-center prospective cohort study. Term cephalic singleton nulliparous women having spontaneous vaginal delivery were considered eligible for recruitment into the study. Once crowning was diagnosed and just prior the initiation of manual perineal protection (MPP) or cutting an episiotomy, the BFD and PBL were measured using a standardized measurement protocol. RESULTS AND DISCUSSION: A total of 100 women (50 women in each center) were recruited into the study. The overall mean BFD was 2.8 ± 0.5 cm. The overall mean PBL was 4.4 ± 0.8 cm. There were no statistically significant differences between the measurements taken in both units regarding BFD or PBL (p = 0.81 and 0.10 respectively). There was a weak correlation between both measurements. Based on our measured parameters, it seems that the most effective point to apply perineal pressure to displace the head away from the anus is approximately 1 - 1.5 cm anterior to the anal margin. CONCLUSION: Measurements generated by this study will form the bases of future biomechanical studies to confirm their validity.
- MeSH
- anální kanál fyziologie MeSH
- dospělí MeSH
- epiziotomie * statistika a číselné údaje metody MeSH
- hlava * MeSH
- lidé MeSH
- mladý dospělý MeSH
- perineum * MeSH
- prospektivní studie MeSH
- těhotenství MeSH
- tlak MeSH
- vedení porodu metody MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Routine outcome monitoring (ROM) has become an increasingly utilized tool in therapeutic practice that has the potential to improve therapy outcomes. This study aimed to synthesize the findings of existing qualitative studies investigating how clinicians use ROM in their work with clients. A systematic search of qualitative studies on clinicians' experience with the use of ROM in mental health services was conducted via PsycInfo, PsycArticles, Medline, Web of Science, and Scopus databases. Qualitative meta-analysis was used to synthesize the finding of the primary studies. Forty-seven studies met the inclusion criteria. The analysis resulted in 21 meta-categories organized into six clusters, namely (1) obtaining clinically relevant information, (2) adapting treatment, (3) facilitating communication, (4) enhancing the therapeutic relationship, (5) facilitating change in clients, and (6) personalized usage of ROM. The meta-analysis revealed that clinicians utilized ROM in diverse ways, including both informational and communicational functions. From the clinicians' perspective, ROM was an element that, on the one hand, introduced additional structure and standardization in treatment and, on the other hand, allowed for greater flexibility and tailoring of treatment.
- MeSH
- duševní poruchy terapie MeSH
- hodnocení výsledků zdravotní péče MeSH
- komunikace MeSH
- kvalitativní výzkum MeSH
- lidé MeSH
- postoj zdravotnického personálu MeSH
- psychoterapeuti * MeSH
- psychoterapie * organizace a řízení normy MeSH
- služby péče o duševní zdraví organizace a řízení normy MeSH
- vztahy mezi zdravotnickým pracovníkem a pacientem MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
Changes in cellular physiology and proteomic homeostasis accompanied the initiation and progression of colorectal cancer. Thus, ubiquitination represents a central regulatory mechanism in proteome dynamics. However, the complexity of the ubiquitinating network involved in carcinogenesis remains unclear. This study revealed the tumor-suppressive role of the ubiquitin ligase Cullin4A (CUL4A) in the intestine. We showed that simultaneous loss of CUL4A and hyperactivation of the Wnt pathway promotes tumor development in the distal colon. This tumor development is caused by an accumulation of the inactive SMAD3, a TGF-β pathway mediator. Depletion of CUL4A resulted in stabilization of HUWE1, which attenuated SMAD3 function. We showed a correlation between the intracellular localization of CUL4A and colorectal cancer progression, where nuclear CUL4A localization correlates with advanced colorectal cancer progression. In summary, we identified CUL4A as an important regulator of SMAD3 signal transduction competence in a HUWE1-dependent manner and demonstrated a critical role for the crosstalk between ubiquitination and the Wnt/TGF-β signaling pathways in gastrointestinal homeostasis.
- MeSH
- HCT116 buňky MeSH
- kolorektální nádory * patologie genetika metabolismus MeSH
- kulinové proteiny * metabolismus genetika MeSH
- lidé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádorové supresorové proteiny * metabolismus genetika MeSH
- protein Smad3 * metabolismus genetika MeSH
- regulace genové exprese u nádorů MeSH
- signální dráha Wnt MeSH
- ubikvitinace MeSH
- ubikvitinligasy * metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In this review, we emphasize the significance of the Liebeskind-Srogl cross-coupling reaction, a palladium-catalyzed process involving the reaction between a thioester and a boronic acid. This reaction has emerged as a fundamental technique in synthetic methodologies aimed at the development of biologically active compounds. The Liebeskind-Srogl cross-coupling method has become an essential approach in chemistry, facilitating the diversification of complex structures that would be significantly more challenging to synthesize through alternative approaches. In this review, we aim to outline the numerous possibilities for preparing a wide range of derivatives, each with notable biological potential.
DC-SIGN, a C-type lectin receptor expressed on immune cells, is considered a promising target for immunomodulatory and antiviral therapies. While mannose-based glycomimetics have been extensively studied as DC-SIGN ligands, fucose-based strategies remain underexplored. This study explores the fucosylation of linear alcohols and sugars using eight different fucosyl donors, aiming at designing strategies for the development of fucose-based glycomimetics targeting DC-SIGN. Four types of leaving groups and two different acyl-based protecting groups on the donors were tested. The glycosylation of 3-azidopropan-1-ol exclusively yielded the β-anomer, demonstrating high stereoselectivity. The azido group in the product is versatile, allowing for direct click chemistry reactions or reduction to an amine for further functionalization. Both types of reactions were demonstrated in a model reaction. In the glycosylation of a sugar, a disaccharide moiety of Lewis X antigen was selected as a target molecule. Only one of the eight tested fucosyl donors worked well in this reaction and provided the product in a reasonable yield. The disaccharide was also equipped with the 3-azidopropyl linker, facilitating future modifications. Finally, NMR studies confirmed compatibility of the linker with canonical Ca2+-dependent carbohydrate binding to DC-SIGN, suggesting potential for further development of fucose-based glycomimetics targeting this C-type lectin receptor.
- MeSH
- fukosa * chemie MeSH
- glykosidy * chemie chemická syntéza farmakologie metabolismus MeSH
- glykosylace MeSH
- lektiny typu C * metabolismus antagonisté a inhibitory MeSH
- lidé MeSH
- molekulární struktura MeSH
- molekuly buněčné adheze * metabolismus antagonisté a inhibitory MeSH
- receptory buněčného povrchu * metabolismus antagonisté a inhibitory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND OBJECTIVE: We present a summary of the 2025 update for the European Association of Urology (EAU) guidelines for upper urinary tract urothelial carcinoma (UTUC). The aim is to provide practical recommendations on the clinical management of UTUC with a focus on diagnosis, treatment, and follow-up. METHODS: For the 2025 guidelines on UTUC, new and relevant evidence was identified, collated, and appraised via a structured assessment of the literature. Databases searched included Medline, EMBASE, and the Cochrane Libraries. Recommendations within the guidelines were developed by the panel to prioritise clinically important care decisions. The strength of each recommendation was determined according to a balance between desirable and undesirable consequences of alternative management strategies, the quality of the evidence (including the certainty of estimates), and the nature and variability of patient values and preferences. KEY FINDINGS AND LIMITATIONS: Key recommendations emphasise the importance of thorough diagnosis, treatment, and follow-up for patients with UTUC. The guidelines stress the importance of appropriate treatment taking into account patient values and preferences. Key updates in the 2025 UTUC guidelines include: significant changes to the recommendations for UTUC diagnosis; complete revision of the sections addressing risk stratification, ureteroscopy, and the surgical approach for radical nephroureterectomy; addition of four new recommendations, two related to kidney-sparing management of localised low-risk UTUC and a further two related to management of high-risk nonmetastatic UTUC; a review and adaptation of recommendation for UTUC follow-up; and addition of a new section addressing quality indicators for UTUC management. CONCLUSIONS AND CLINICAL IMPLICATIONS: This overview of the 2025 EAU guidelines on UTUC offers valuable insights into risk factors, diagnosis, classification, treatment, and follow-up for UTUC. The guidelines contain information on the management of individual patients according to the current best evidence and are designed for effective integration in clinical practice.
- MeSH
- karcinom z přechodných buněk * terapie diagnóza MeSH
- lidé MeSH
- nádory ledvin * terapie diagnóza MeSH
- nádory močovodu * terapie diagnóza MeSH
- společnosti lékařské MeSH
- urologie normy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- směrnice pro lékařskou praxi MeSH
- Geografické názvy
- Evropa MeSH
BACKGROUND AND OBJECTIVE: The European Association of Urology (EAU) renal cell carcinoma (RCC) guideline panel has updated their evidence-based guidelines and recommendations for the management of RCC. Here we present a summary of the 2025 RCC guidelines updated with standardised methodology to provide reproducible evidence for the management of RCC. METHODS: For the 2025 update, a literature search was performed covering the period from May 1, 2023 to May 1, 2024 using the Medline, EMBASE, and Cochrane Libraries. The data search focused on meta-analyses, systematic reviews, randomised controlled trials (RCTs), and retrospective or controlled comparator-arm studies. Evidence was synthesised as outlined for all EAU guidelines. KEY FINDINGS AND LIMITATIONS: Clinical practise recommendations were updated in all chapters of the RCC guidelines on the basis of a structured literature search. The studies included were predominantly retrospective with matched or unmatched cohorts based on single- or multi-institutional data. Several prospective studies and RCTs provided data that resulted in recommendations based on higher levels of evidence. Specifically, updates include new recommendations on stereotactic body radiotherapy for localised RCC, adjuvant therapy, systemic therapy for clear-cell RCC in later lines, other subtypes, and a new chapter on hereditary RCC. CONCLUSIONS AND CLINICAL IMPLICATIONS: The 2025 RCC guidelines have been updated by a multidisciplinary panel of experts using methodological standards to provide a contemporary evidence base for the management of RCC.
- MeSH
- karcinom z renálních buněk * terapie diagnóza MeSH
- lidé MeSH
- nádory ledvin * terapie diagnóza MeSH
- společnosti lékařské MeSH
- urologie normy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- směrnice pro lékařskou praxi MeSH
- Geografické názvy
- Evropa MeSH
Recent research highlights horizontal mitochondrial transfer as a key biological phenomenon linked to cancer onset and progression. The transfer of mitochondria and their genomes between cancer and non-cancer cells shifts our understanding of intercellular gene trafficking, increasing the metabolic fitness of cancer cells and modulating antitumor immune responses. This process not only facilitates tumor progression but also presents potential therapeutic opportunities.
BACKGROUND: The hypothalamus (HT) plays a crucial role in regulating eating behaviors. Disruptions in its function have been linked to the development of weight-related disorders. Nevertheless, its characterization remains a challenge. OBJECTIVES: We assessed the structural alterations of individual HT nuclei related to eating behaviors in patients with weight-related disorders, and their association with body mass index (BMI) and severity of eating disorders. METHODS: Forty-four young females with normal weight (HC, n = 21), restrictive anorexia nervosa (AN, n = 13), and living with obesity (OB, n = 10) were explored in vivo using 7-T high-resolution (0.6 mm isotropic voxel) T1 quantitative magnetic resonance imaging (MRI). Volumes and quantitative T1 values of individual HT nuclei were compared after whole-brain normalization using nonparametric tests (corrected for multiple comparisons for groups and regions). We investigated the parameters associated with BMI and eating disorders, such as MRI parameters of HT nuclei, ghrelin and leptin levels, depression, and anxiety using multivariate nonlinear partial least square (NIPALS). RESULTS: Both AN and OB showed higher volumes of HT relative to HC (Zscores: 0.78 ± 1.06; 1.43 ± 1.51). AN showed significantly higher volumes and T1 values of the right paraventricular nucleus (PaVN) (volume Zscore: 1.82 ± 1.45; T1 Zscore: 3.76 ± 4.67), and higher T1 values of the left PaVN (Zscore: 2.25 ± 2.37) and right periventricular nuclei (Zscore: 3.73 ± 4.81). NIPALS models showed that lower BMI in AN was associated with structural alterations of the bilateral PaVN, right anterior commissure, and left fornix (FX). Higher BMI in OB was associated with structural alterations within the right PaVN, bilateral FX, left posterior hypothalamic nucleus, right lateral HT, and right anterior hypothalamic area. Finally, the severity of eating disorders was associated with larger structural alterations within the bilateral PaVN, bilateral arcuate hypothalamic nuclei, right bed nucleus of stria terminalis, left medial preoptic nucleus, and right tubero-mammillary hypothalamic nucleus. CONCLUSIONS: Weight-related disorders are associated with significant micro and macrostructural alterations in HT nuclei involved in eating behaviors.
- MeSH
- dospělí MeSH
- hypothalamus * diagnostické zobrazování patologie MeSH
- index tělesné hmotnosti MeSH
- leptin krev MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- mentální anorexie * diagnostické zobrazování patologie MeSH
- mladiství MeSH
- mladý dospělý MeSH
- obezita * diagnostické zobrazování patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
