BACKGROUND: Various explicit screening tools, developed mostly in central Europe and the USA, assist clinicians in optimizing medication use for older adults. The Turkish Inappropriate Medication use in oldEr adults (TIME) criteria set, primarily based on the STOPP/START criteria set, is a current explicit tool originally developed for Eastern Europe and subsequently validated for broader use in Central European settings. Reviewed every three months to align with the latest scientific literature, it is one of the most up-to-date tools available. The tool is accessible via a free mobile app and website platforms, ensuring convenience for clinicians and timely integration of updates as needed. Healthcare providers often prefer to use their native language in medical practice, highlighting the need for prescribing tools to be translated and adapted into multiple languages to promote optimal medication practices. OBJECTIVE: To describe the protocol for cross-cultural and language validation of the TIME criteria in various commonly used languages and to outline its protocol for clinical validation across different healthcare settings. METHODS: The TIME International Study Group comprised 24 geriatric pharmacotherapy experts from 12 countries. In selecting the framework for the study, we reviewed the steps and outcomes from previous research on cross-cultural adaptations and clinical validations of explicit tools. Assessment tools were selected based on both their validity in accurately addressing the relevant issues and their feasibility for practical implementation. The drafted methodology paper was circulated among the study group members for feedback and revisions leading to a final consensus. RESULTS: The research methodology consists of two phases. Cross-cultural adaptation/language validation phase follows the 8-step approach recommended by World Health Organization. This phase allows regions or countries to make modifications to existing criteria or introduce new adjustments based on local prescribing practices and available medications, as long as these adjustments are supported by current scientific evidence. The second phase involves the clinical validation, where participants will be randomized into two groups. The control group will receive standard care, while the intervention group will have their treatment evaluated by clinicians who will review the TIME criteria and consider its recommendations. A variety of patient outcomes (i.e., number of hospital admissions, quality of life, number of regular medications [including over the counter medications], geriatric syndromes and mortality) in different healthcare settings will be investigated. CONCLUSION: The outputs of this methodological report are expected to promote broader adoption of the TIME criteria. Studies building on this work are anticipated to enhance the identification and management of inappropriate medication use and contribute to improved patient outcomes.
PURPOSE: MRI-only adaptive brachytherapy (MRI-ABT) is the state-of-the-art for treating locally advanced cervical cancer (LACC) in combination with concurrent chemoradiotherapy. We aimed to evaluate the pattern of pelvic recurrence after the treatment. MATERIAL AND METHODS: A total of one hundred LACC patients were treated between January 2017 and December 2023 with concurrent chemoradiotherapy of 45 Gy in 25 fractions ± boost to lymphadenopathy (up to a maximum dose of 60 Gy in 25 fractions) with concurrent weekly cisplatin chemotherapy at the dose of 40 mg/m2/week, and MR-ABT. RESULTS: At a median follow-up of 30.2 months, there were 2 local recurrences (2%) and 9 regional pelvic recurrences (9%). The median time to local/regional recurrence was 11 months (range 6-21). For all stages, the 3-year local control was 97.66%, and the 3-year pelvic control was 89.45%. Twenty-four patients died during follow-up; the 3-year overall survival was 75.11%, and the 3-year disease-free survival was 70.97%. CONCLUSION: MRI-ABT combined with external beam radiotherapy and concurrent chemotherapy for LACC demonstrates excellent local and regional pelvic control. Most local/regional recurrences occur inside or at the edge of the external-beam irradiated field. Recurrences inside the field of brachytherapy are rare. Distant recurrences are the predominant cause of death in LACC patients treated with definitive CRT and MRI-ABT.
- MeSH
- Brachytherapy * methods MeSH
- Chemoradiotherapy * MeSH
- Cisplatin therapeutic use MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Recurrence, Local * radiotherapy MeSH
- Magnetic Resonance Imaging * MeSH
- Uterine Cervical Neoplasms * radiotherapy diagnostic imaging pathology MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
The precise measurement of cell temperature and an in-depth understanding of thermogenic processes are critical in unraveling the complexities of cellular metabolism and its implications for health and disease. This review focuses on the mechanisms of local temperature generation within cells and the array of methods developed for accurate temperature assessment. The contact and noncontact techniques are introduced, including infrared thermography, fluorescence thermometry, and other innovative approaches to localized temperature measurement. The role of thermogenesis in cellular metabolism, highlighting the integral function of temperature regulation in cellular processes, environmental adaptation, and the implications of thermogenic dysregulation in diseases such as metabolic disorders and cancer are further discussed. The challenges and limitations in this field are critically analyzed while technological advancements and future directions are proposed to overcome these barriers. This review aims to provide a consolidated resource for current methodologies, stimulate discussion on the limitations and challenges, and inspire future innovations in the study of cellular thermodynamics.
- MeSH
- Humans MeSH
- Temperature MeSH
- Thermogenesis * physiology MeSH
- Thermography * methods MeSH
- Thermometry methods MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Mezinárodní vzdělávací program Erasmus+ nabízí studentům jedinečnou příležitost prohloubit své odborné dovednosti a zároveň poznat odlišné kultury. Tento článek reflektuje zkušenosti studentek Střední zdravotnické školy Hradec Králové, které se v únoru 2025 zúčastnily dvoutýdenní stáže ve vesnici Delpitiya na Srí Lance. Text se zaměřuje na kulturní, náboženské, gastronomické a vzdělávací aspekty tohoto pobytu, přičemž analyzuje specifika místního prostředí a jeho vliv na osobní a profesní rozvoj účastnic. Článek zkoumá náboženskou rozmanitost Srí Lanky, upozorňuje na charakteristiku místní kuchyně, zkoumá postupy předškolního vzdělávání a popisuje volnočasové aktivity, které obohatily interkulturní kompetence studentů. Prostřednictvím přímé interakce s místní komunitou si studenti zvýšili svou adaptabilitu, empatii a rozšířili své perspektivy, což dokazuje hodnotu programů mezinárodní mobility pro budoucí zdravotnické pracovníky.
The international Erasmus+ educational program offers students a unique opportunity to deepen their professional skills while experiencing different cultures. This article reflects the experiences of students from the Secondary Medical School of Hradec Králové, who participated in a two-week internship in the village of Delpitiya, Sri Lanka, in February 2025. It focuses on cultural, religious, gastronomic, and educational aspects of their stay, analyzing the specifics of the local environment and its impact on their personal and professional growth. The article explores the religious diversity of Sri Lanka, highlights the characteristics of local cuisine, examines preschool education practices, and describes leisure activities that enriched the students’ intercultural competencies. Through direct interaction with the local community, students enhanced their adaptability, empathy, and broadened their perspectives, demonstrating the value of international mobility programs for future healthcare professionals.
Autoři popisují případ 35letého HIV negativního muže s vysoce zánětlivou (kerion-like) formou tinea barbae přenesenou pohlavním stykem. Jeho sexuální partner měl méně zánětlivou formu tinea corporis lokalizovanou převážně perianálně, pubogenitálně a v tříslech. U obou mužů byl kultivačním a molekulárně-genetickým vyšetřením prokázán T. mentagrophytes genotyp VII. Jedná se o nedávno popsaný genotyp s možnou adaptací nebo mutací usnadňující přenos z člověka na člověka, včetně sexuálního kontaktu. Tinea barbae byla klinicky a mykologicky vyléčena po 7 týdnech užívání perorálního itrakonazolu.
The authors describe the case of a 35-year-old HIV-negative man with a highly inflammatory (kerion-like) form of sexually transmitted tinea barbae. His sexual partner had a less inflammatory form of tinea corporis localized predominantly perianally, pubogenitally and in the groin. Both men were found to have T. mentagrophytes genotype VII by culture and molecular genetic testing. This is a recently described genotype with a possible adaptation or mutation facilitating human-to-human transmission, including sexual contact. Tinea barbae was clinically and mycologically cured after 7 weeks of oral therapy with itraconazole.
- MeSH
- Dermatomycoses diagnosis etiology drug therapy MeSH
- Adult MeSH
- Itraconazole administration & dosage therapeutic use MeSH
- Humans MeSH
- Microbiological Techniques MeSH
- Face pathology MeSH
- Sexually Transmitted Diseases MeSH
- Tinea Capitis diagnosis etiology drug therapy MeSH
- Tinea * diagnosis etiology drug therapy MeSH
- Trichophyton isolation & purification MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
The perception of a voice in the absence of an external auditory source-an auditory verbal hallucination-is a characteristic symptom of schizophrenia. To better understand this phenomenon requires integration of findings across behavioural, functional, and neurochemical levels. We address this with a locally adapted MEGA-PRESS sequence incorporating interleaved unsuppressed water acquisitions, allowing concurrent assessment of behaviour, blood-oxygenation-level-dependent (BOLD) functional changes, Glutamate + Glutamine (Glx), and GABA, synchronised with a cognitive (flanker) task. We acquired data from the anterior cingulate cortex (ACC) of 51 patients with psychosis (predominantly schizophrenia spectrum disorder) and hallucinations, matched to healthy controls. Consistent with the notion of an excitatory/inhibitory imbalance, we hypothesized differential effects for Glx and GABA between groups, and aberrant dynamics in response to task. Results showed impaired task performance, lower baseline Glx and positive association between Glx and BOLD in patients, contrasting a negative correlation in healthy controls. Task-related increases in Glx were observed in both groups, with no significant difference between groups. No significant effects were observed for GABA. These findings suggest that a putative excitatory/inhibitory imbalance affecting inhibitory control in the ACC is primarily observed as tonic, baseline glutamate differences, rather than GABAergic effects or aberrant dynamics in relation to a task.
- MeSH
- Gyrus Cinguli metabolism physiopathology MeSH
- Adult MeSH
- gamma-Aminobutyric Acid * metabolism MeSH
- Glutamine metabolism MeSH
- Hallucinations * metabolism physiopathology MeSH
- Cognition * physiology MeSH
- Glutamic Acid * metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Young Adult MeSH
- Psychotic Disorders * metabolism physiopathology MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
PURPOSE: We aimed to find predictive tumour characteristics as detected by interim positron-emission tomography/magnetic resonance imaging (PET/MRI) in cervical cancer patients. We also investigated the type of interim response. Furthermore, we compared the investigated parameters with disease-free (DFS) and overall survival (OS) outcomes. METHODS: We evaluated 108 patients treated between August 2015 and January 2023 with external-beam radiotherapy (EBRT) and image-guided adaptive brachytherapy (IGABT) who had undergone pretreatment staging, subsequent mid-treatment evaluation after completed EBRT and definitive restaging 3 months after completing the whole treatment using PET/MRI. Patients were then divided into two groups based on the RECIST and PERCIST criteria: responders (achieving complete metabolic response, CMR) and non-responders (non-CMR). These two groups were compared using selected parameters obtained at pre-PET/MRI and mid-PET/MRI. The early response to treatment as evaluated by mid-PET/MRI was categorized into three types: interim complete metabolic response, interim nodal response and interim nodal persistence. RESULTS: Mid-TLG‐S (the sum of total lesion glycolysis for the primary tumour plus pelvic and para-aortic lymph nodes) parameter showed the best discriminatory ability for predicting non-CMR. The second factor with significant discriminatory ability was mid-MTV‐S (the sum of the metabolic tumour volume of the primary tumour plus pelvic and para-aortic lymph nodes). The strongest factor, mid-TLG‐S, showed a sensitivity of 40% and a specificity of 90% at a threshold value of 70. We found a statistically significant association of DFS and OS with the following parameters: number of chemotherapy cycles, early response type and CMR vs. non-CMR. CONCLUSION: We were able to identify thresholds for selected parameters that can be used to identify patients who are more likely to have worse DFS and OS. The type of early response during concurrent chemoradiotherapy (CCRT) was also significantly associated with DFS and OS. These aspects represent an important contribution to the possible stratification of patients for subsequent individualised adjuvant treatment.
- MeSH
- Brachytherapy MeSH
- Chemoradiotherapy * methods MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging * MeSH
- Multimodal Imaging * MeSH
- Uterine Cervical Neoplasms * therapy diagnostic imaging pathology mortality MeSH
- Positron-Emission Tomography * MeSH
- Disease-Free Survival MeSH
- Radiotherapy, Image-Guided MeSH
- Aged MeSH
- Neoplasm Staging MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Standardem léčby lokálně či regionálně pokročilého karcinomu hrdla dělohy je definitivní chemoradioterapie, která kombinuje systémovou chemoterapii platinou se zevní radioterapií, kterou následuje intrakavitární, tzv. uterovaginální brachyterapie. Současným standardem brachyterapie karcinomu hrdla dělohy je MR navigovaná 4D-adaptivní brachyterapie. Díky MR navigaci je při každé frakci brachyterapie jasně patrný aktuální rozsah reziduálního nádorového postižení a pokrytí cílových objemů intrakavitární aplikací do dělohy. U více než třetiny pacientek však nejde cílové struktury pokrýt terapeutickou dávkou záření vzhledem k rozsahu onemocnění, aniž by bylo možné současně dodržet bezpečné dávkové limity na okolní zdravé tkáně. Ideálním řešením takové situace je využití možnosti intersticiální aplikace jehel do míst nepokrytých samotnou intrakavitární aplikací. Standardně dodávané aplikátory pro uterovaginální brachyterapii již intersticiální aplikaci obvykle umožňují, případně lze pro aplikaci intersticiálních jehel využít 3D tiskem vyrobené či upravené aplikátory. Cílem tohoto článku je ukázat praktický postup aplikace intersticiální brachyterapie v léčbě karcinomu hrdla dělohy ve Fakultní nemocnici v Hradci Králové.
The standard treatment for locally or regionally advanced cervical cancer is definitive chemoradiotherapy, which combines systemic cisplatin chemotherapy with external-beam radiotherapy followed by intracavitary, so-called uterovaginal brachytherapy. The current standard of brachytherapy for cervical cancer is MR-guided 4D-adaptive brachytherapy. Thanks to MR navigation, the current extent of residual tumor involvement and the coverage of target volumes by intracavitary application into the uterus is visible during each brachytherapy fraction. In more than a third of patients, however, it is impossible to cover the target structures with a therapeutic dose of radiation due to the extent of the disease, without observing safe dose limits for the surrounding healthy tissues simultaneously. The ideal solution to such a situation is to use the interstitial application of needles in places not covered by the pure intracavitary application. The standard supplied applicators for uterovaginal brachytherapy usually allow interstitial application or 3D-printed or modified applicators can be used for the application of interstitial needles. This article aims to show the practical procedure of using interstitial brachytherapy in the treatment of cervical cancer at the University Hospital in Hradec Králové.
- MeSH
- Brachytherapy * methods instrumentation MeSH
- Chemoradiotherapy methods MeSH
- Humans MeSH
- Magnetic Resonance Imaging methods MeSH
- Uterine Cervical Neoplasms * drug therapy radiotherapy MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Review MeSH
The exon junction complex (EJC) is a key player in metazoan mRNA quality control and is placed upstream of the exon-exon junction after splicing. Its inner core is composed of Magoh, Y14, eIF4AIII and BTZ and the outer core of proteins involved in mRNA splicing (CWC22), export (Yra1), translation (PYM) and nonsense mediated decay (NMD, UPF1/2/3). Trypanosoma brucei encodes only two genes with introns, but all mRNAs are processed by trans-splicing. The presence of three core EJC proteins and a potential BTZ homologue (Rbp25) in trypanosomes has been suggested to adapt of the EJC function to mark trans-spliced mRNAs. We analysed trypanosome EJC components and noticed major differences between eIF4AIII and Magoh/Y14: (i) whilst eIF4AIII is essential, knocking out both Magoh and Y14 elicits only a mild growth phenotype (ii) eIF4AIII localization is mostly nucleolar, while Magoh and Y14 are nucleolar and nucleoplasmic but excluded from the cytoplasm (iii) eIF4AIII associates with nucleolar proteins and the splicing factor CWC22, but not with Y14 or Magoh, while Magoh and Y14 associate with each other, but not with eIF4AIII, CWC22 or nucleolar proteins. Our data argue against the presence of a functional EJC in trypanosomes, but indicate that eIF4AIII adopted non-EJC related, essential functions, while Magoh and Y14 became redundant. Trypanosomes also possess homologues to the NMD proteins UPF1 and UPF2. Depletion of UPF1 causes only a minor reduction in growth and phylogenetic analyses show several independent losses of UPF1 and UPF2, as well as complete loss of UPF3 in the Kinetoplastida group, indicating that UPF1-dependent NMD is not essential. Regardless, we demonstrate that UPF1 depletion restores the mRNA levels of a PTC reporter. Altogether, we show that the almost intron-less trypanosomes are in the process of losing the canonical EJC/NMD pathways: Y14 and Magoh have become redundant and the still-functional UPF1-dependent NMD pathway is not essential.
- MeSH
- Eukaryotic Initiation Factor-4A metabolism genetics MeSH
- Exons genetics MeSH
- RNA, Messenger genetics metabolism MeSH
- Nonsense Mediated mRNA Decay * MeSH
- Protozoan Proteins * metabolism genetics MeSH
- RNA Splicing MeSH
- Trypanosoma brucei brucei * metabolism genetics MeSH
- Publication type
- Journal Article MeSH
In cryo-electron microscopy, accurate particle localization and classification are imperative. Recent deep learning solutions, though successful, require extensive training datasets. The protracted generation time of physics-based models, often employed to produce these datasets, limits their broad applicability. We introduce FakET, a method based on neural style transfer, capable of simulating the forward operator of any cryo transmission electron microscope. It can be used to adapt a synthetic training dataset according to reference data producing high-quality simulated micrographs or tilt-series. To assess the quality of our generated data, we used it to train a state-of-the-art localization and classification architecture and compared its performance with a counterpart trained on benchmark data. Remarkably, our technique matches the performance, boosts data generation speed 750×, uses 33× less memory, and scales well to typical transmission electron microscope detector sizes. It leverages GPU acceleration and parallel processing. The source code is available at https://github.com/paloha/faket/.
