This paper evaluates the first Recovery College in Slovakia, a revolutionary approach to mental health care based on the recovery concept. These colleges offer comprehensive educational programs led by individuals with personal and/or professional experience in mental health care. The main goal is to help individuals become experts in their own care; instead of prevalent paternalistic care of patients and clients who need to be told how to manage their mental health problems; it brings about a paradigm shift in the way people who experience mental illness are viewed. We used mixed research. We utilized the standardized Recovery Assessment Scale questionnaire (measuring the effect of courses on subjective recovery rates) and semi-structured interviews with staff and students of the first Recovery College in Slovakia. Interviews were focused on fulfilling the goals and principles of Recovery Colleges (Education, Co-production, Strengths-based approach, Progress and empowerment, Inclusion, Community focus and Person-centered approach). Both tools demonstrate positive changes in the lives of staff and students of the first Recovery College in Slovakia, especially when it comes to self-stigma reduction, the increase of self-responsibility, and recognizing personal strengths. The article provides a unique insight into the newly established Recovery College. It could serve as a source of inspiration.

• Keywords
• Recovery College,
• MeSH
• Mental Health MeSH
• Empowerment MeSH
• Humans MeSH
• Recovery of Function * MeSH
• Health Care Surveys MeSH
• Self Concept MeSH
• Mental Health Services * organization & administration   MeSH
• Peer Group MeSH
• Patient Education as Topic methods   MeSH
• Check Tag
• Humans MeSH
• Geographicals
• Slovakia MeSH

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a progressive disease characterized by disproportionate ventricular enlargement at brain imaging with gait disturbance and an increased risk of falling. Gait assessment is a key feature in the diagnosis of iNPH and characterization of post-surgical outcomes. RESEARCH QUESTION: How do gait parameters change 24 h after CSF tap test (CSFTT) and after ventriculoperitoneal shunt surgery? METHODS: The PRISMA guidelines were used to perform the systematic review. We conducted a search of the following electronic databases: PubMed, Medline, Web of Science and EBSCO. We included studies focusing on gait changes occurring 24 h after a CSFTT or after ventriculoperitoneal shunt surgery in patients with iNPH. All articles were assessed for methodological quality using an adapted version of The Standard Quality Assessment Criteria for Evaluating Primary Research Papers checklist. RESULTS: Twenty-seven studies were included in the systematic review. Studies were highly heterogeneous due to lack of standardization of CSFTT or shunt surgery methodology, with varying amounts of CSF removed during the tap test (20-50 ml) and varying time of outcome assessment after shunt surgery. Dynamic equilibrium measurements are generally used to assess preoperative levels of cardinal symptoms and postoperative outcomes in iNPH. The most sensitive spatio-temporal parameter assessed 24 h after CSFTT was self-selected walking speed followed by stride length, which increased significantly. Cadence is hence not suitable to consider in the evaluation of effect of CSFTT and shunt surgery. Changes in balance-related gait parameters after CSFTT and shunt surgery are still a controversial area of research. CONCLUSION: Gait assessment is a key feature in the diagnosis of iNPH and characterization of post-surgical outcomes. Dynamic equilibrium measurements are generally used to assess preoperative levels of cardinal symptoms and postoperative outcomes in iNPH, but quantitative and standardized gait analysis procedures are missing. Changes in balance-related gait parameters after CSFTT might be useful in deciding whether to perform shunt surgery in iNPH patients who hope for improvement in gait ability. The dual-task paradigm after CSFTT could improve the clinical evaluation of higher level frontal gait disturbances in patients with suspected iNPH before shunting.

• MeSH
• Gait * physiology   MeSH
• Humans MeSH
• Hydrocephalus, Normal Pressure * surgery   physiopathology   cerebrospinal fluid   diagnosis   MeSH
• Cerebrospinal Fluid Shunts MeSH
• Spinal Puncture methods   MeSH
• Ventriculoperitoneal Shunt MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Systematic Review MeSH

Nemoc štěpu proti hostiteli (graft versus host disease, GvHD) stále představuje zásadní, život ohrožující komplikaci po alogenní transplantaci krvetvorných buněk (allogeneic stem cell transplantation, aloSCT). Reakce štěpu proti hostiteli obecně se rozvine až u 50 % pacientů po aloSCT, klinicky významná stadia (stadium III-IV akutní GvHD či extenzivní chronická GvHD) se vyskytují až u 20 % pacientů po aloSCT od HLA shodného dárce, incidence GvHD pak vzrůstá s každou další HLA neshodou. Uváděná mortalita GvHD se pohybuje kolem 10 % případů. Standardem léčby GvHD je systémová kortikoterapie, která je úspěšná u přibližně 60 % pacientů s lehkými formami GvHD a pouze u přibližně 30 % pacientů s těžkou GvHD obecně. Kortikoterapie v kombinaci s dalšími imunosupresivními léky po aloSCT prohlubuje imunodeficit fragilních transplantovaných pacientů, a kromě nesporných benefitů má četné závažné dlouhodobé nežádoucí účinky. V rámci snahy o zlepšení péče o pacienty s GvHD se tak do praxe dostávají nové molekuly, působící proti GvHD jinými, více zacílenými mechanismy. Zásadním reprezentantem těchto molekul je ruxolitinib, inhibitor Janusových kináz 1 a 2 (JAK1/2). Ruxolitinib je nyní standardem léčby u pacientů se steroid-refrakterní akutní i chronickou GvHD.

Graft versus host disease (GvHD) remains a major life-threatening complication after allogeneic hematopoietic cell transplantation (alloSCT). GvHD generally develops in up to 50% of patients after alloSCT and clinically significant stages (stage III-IV acute GvHD or extensive chronic GvHD) occur in up to 20% of patients after alloSCT from an HLA-matched donor. The incidence of GvHD increases with each additional HLA mismatch. The reported mortality rate of GvHD is around 10%. The standard treatment for GvHD is systemic corticotherapy, which is successful in approximately 60% of patients with mild forms of GvHD and only in approximately 30% of patients with severe GvHD in general. Corticotherapy in combination with other immunosuppressive drugs after alloSCT exacerbates immunodeficiency in fragile transplanted patients and has numerous serious long-term side effects in addition to its undeniable benefits. Thus, in an effort to improve the care of GvHD patients, new molecules that counteract GvHD by different, more targeted mechanisms are coming into use. A major representative of these molecules is ruxolitinib, a Janus tyrosine kinase 1/2 (JAK 1/2) inhibitor that interferes with GvHD mechanisms at multiple levels. Ruxolitinib is now the standard of care for patients with steroid-refractory acute and chronic GvHD.

• Keywords
• ruxolitinib,
• MeSH
• Molecular Targeted Therapy classification   methods   MeSH
• Transplantation, Homologous classification   methods   MeSH
• Immunosuppression Therapy MeSH
• Janus Kinase Inhibitors * pharmacology   classification   adverse effects   therapeutic use   MeSH
• Clinical Studies as Topic MeSH
• Humans MeSH
• Graft vs Host Disease * diagnosis   drug therapy   MeSH
• Hematopoietic Stem Cell Transplantation methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Cíl: Protože kardiovaskulární onemocnění jsou příčinou závažné morbidity a mortality, je třeba zjišťovat jejich přítomnost a začít je včas léčit. Proto byla pro stanovení rizika vypracována řada stupnic, v současnosti se však rutinně nepoužívá žádný biochemický marker pro stanovení kardiovaskulárního rizika. Ateroskleróza je nejzávažnější příčinou rozvoje kardiovaskulárních onemocnění a v patofyziologii aterosklerózy hraje jistou úlohu zánět cév. Řada studií prokázala, že mnoho kroků v procesu rozvoje tohoto zánětu ovlivňují hodnoty YKL-40 v séru. Evropská kardiologická společnost používá pro stanovení desetiletého kardiovaskulárního rizika skórovací systém SCORE2. V naší studii jsme zkoumali vztah mezi algoritmem pro toto riziko a hodnotou biochemického markeru YKL-40 v séru. Materiál a metody: Do studie bylo zařazeno 87 dobrovolníků ve věku 40–70 let, kteří se dostavili na naši kliniku, v minulosti neprodělali kardiovaskulární příhodu, měli však rizikové faktory pro rozvoj kardiovaskulárního onemocnění. Pomocí predikčního modelu SCORE2 bylo stanoveno jejich kardiovaskulární riziko a současně změřeny hodnoty YKL-40 v séru. Tyto hodnoty se mění s věkem bez ohledu na přítomnost či nepřítomnost nemoci, což platilo pro naši studii stejně jako pro jiné studie. Abychom eliminovali toto paradigma, hodnotili jsme hodnoty YKL-40 v séru pomocí statistického modelu společně s věkem. Výsledky: Naše základní analýza nezjistila významný vztah mezi hodnotami YKL-40 a všemi parametry v algoritmu predikčního modelu SCORE2. Nicméně po porovnání výsledku analýzy s výsledkem statistického modelu s použitím věku se ukázalo se, že hodnota YKL-40 představuje biochemický marker, který lze použít, podobně jako systém SCORE2, při stanovování kardiovaskulárního rizika (R2 : 0,72; p < 0,001).

Objective: Since cardiovascular diseases are a cause of serious morbidity and mortality, it is important to detect and treat them in advance. For this reason, many risk scales have been created, but there is currently no biochemical marker in routine use to estimate cardiovascular risk. Atherosclerosis is the most important reason for the development of cardiovascular disease, and vascular inflammation plays a role in the pathophysiology of atherosclerosis. It has been observed in many studies that the serum YKL-40 level has an effect on many steps in the development process of this inflammation. SCORE2 are used by the European Society of Cardiology to estimate 10-year cardiovascular risk. In our study, we investigated the relationship between this risk algorithm and the serum YKL-40 level, which is a biochemical marker. Material and methods: 87 volunteers between the ages of 40-70 who applied to our clinic, who had not yet experienced a cardiovascular event but had risk factors for cardiovascular diseases, were included in the study. SCORE2 cardiovascular disease risk was calculated for the patients and serum YKL-40 levels were gaged. Serum YKL-40 levels change with age, regardless of the disease, in our study as in many studies. In order to eliminate this paradigm, we examined serum YKL-40 levels with a statistical model that evaluates them jointly with age. Results: We could not detect a significant relationship with YKL-40 levels in the basal analysis performed by considering all parameters of SCORE2 algorithm. However, result of the statistical model that we evaluated with age, we found that the YKL-40 level is a biochemical parameter that can be used like SCORE2 in cardiovascular disease risk estimation (R2 : 0.72, p < 0.001).

• MeSH
• Biomarkers blood   MeSH
• Adult MeSH
• Cardiovascular Diseases blood   prevention & control   MeSH
• Middle Aged MeSH
• Humans MeSH
• Prognosis MeSH
• Chitinase-3-Like Protein 1 * blood   MeSH
• Heart Disease Risk Factors * MeSH
• Aged MeSH
• Statistics as Topic MeSH
• Health Status Indicators MeSH
• Age Factors MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Clinical Study MeSH

BACKGROUND AND OBJECTIVES: Disentangling brain aging from disease-related neurodegeneration in patients with multiple sclerosis (PwMS) is increasingly topical. The brain-age paradigm offers a window into this problem but may miss disease-specific effects. In this study, we investigated whether a disease-specific model might complement the brain-age gap (BAG) by capturing aspects unique to MS. METHODS: In this retrospective study, we collected 3D T1-weighted brain MRI scans of PwMS to build (1) a cross-sectional multicentric cohort for age and disease duration (DD) modeling and (2) a longitudinal single-center cohort of patients with early MS as a clinical use case. We trained and evaluated a 3D DenseNet architecture to predict DD from minimally preprocessed images while age predictions were obtained with the DeepBrainNet model. The brain-predicted DD gap (the difference between predicted and actual duration) was proposed as a DD-adjusted global measure of MS-specific brain damage. Model predictions were scrutinized to assess the influence of lesions and brain volumes while the DD gap was biologically and clinically validated within a linear model framework assessing its relationship with BAG and physical disability measured with the Expanded Disability Status Scale (EDSS). RESULTS: We gathered MRI scans of 4,392 PwMS (69.7% female, age: 42.8 ± 10.6 years, DD: 11.4 ± 9.3 years) from 15 centers while the early MS cohort included 749 sessions from 252 patients (64.7% female, age: 34.5 ± 8.3 years, DD: 0.7 ± 1.2 years). Our model predicted DD better than chance (mean absolute error = 5.63 years, R2 = 0.34) and was nearly orthogonal to the brain-age model (correlation between DD and BAGs: r = 0.06 [0.00-0.13], p = 0.07). Predictions were influenced by distributed variations in brain volume and, unlike brain-predicted age, were sensitive to MS lesions (difference between unfilled and filled scans: 0.55 years [0.51-0.59], p < 0.001). DD gap significantly explained EDSS changes (B = 0.060 [0.038-0.082], p < 0.001), adding to BAG (ΔR2 = 0.012, p < 0.001). Longitudinally, increasing DD gap was associated with greater annualized EDSS change (r = 0.50 [0.39-0.60], p < 0.001), with an incremental contribution in explaining disability worsening compared with changes in BAG alone (ΔR2 = 0.064, p < 0.001). DISCUSSION: The brain-predicted DD gap is sensitive to MS-related lesions and brain atrophy, adds to the brain-age paradigm in explaining physical disability both cross-sectionally and longitudinally, and may be used as an MS-specific biomarker of disease severity and progression.

• MeSH
• Deep Learning * MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Magnetic Resonance Imaging * MeSH
• Brain * diagnostic imaging   pathology   MeSH
• Neurodegenerative Diseases diagnostic imaging   MeSH
• Cross-Sectional Studies MeSH
• Retrospective Studies MeSH
• Multiple Sclerosis * diagnostic imaging   pathology   MeSH
• Aging * pathology   physiology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

Cílem projektu je vyvinout koncepčně novou třídu biodegradovatelných responzivních kontrastních látek, které jsou určené pro 1H/31P magnetickou rezonanci (MR). Unikátnost těchto kontrastních látek obsahující sloučeniny fosforu s navázaným gadoliniem nebo železem spočívá v přepnutí z 1H na 31P MR kontrast jako odpověď na vnější biochemické změny. Činidlo obsahující současně fosfor a gadolinium nebo železo vykazuje pouze vlastnosti T1 kontrastní látky u 1H MR zobrazování a poskytuje anatomické informace, protože Gd3+/Fe3+ způsobuje rozšíření 31P MR signálu, a proto není fosforový MR signál detekovatelný. Pokud bude vazba mezi fosforem a Gd3+/Fe3+ přerušena prostřednictvím biochemického podnětu, Gd3+/Fe3+ se uvolní, 31P MR signál ve spektru se zúží a proto bude detekovatelný pomocí 31P MR. Výhodou je, že 1H a 31P MR se může jednoduše kombinovat během jednoho experimentu a proto tato kontrastní látka může poskytovat nejen anatomickou, ale i funkční diagnostickou informaci.; The aim of this project is to develop a conceptually new class of biodegradable phosphorus-containing contrast agents for 1H/31P magnetic resonance (MR). The main advantage of these contrast agents, which contain phosphorus compounds connected by biodegradable linkers to Gd3+ or Fe3+, is their ability to switch between 1H and 31P MR contrast in response to external biochemical changes. The contrast agents act solely as T1 contrast agents for 1H MR to provide anatomical information. As the 31P signal gets widen due to the presence paramagnetic of Gd3+/Fe3+ ions in their vicinity, it becomes undetectable by 31P MR. If the link is cleaved in response to an external biochemical stimulus, the paramagnetic switch is released, with the 31P signal appearing. Both 1H and 31P MR imaging can be easily combined within the same experiment, providing both anatomical and functional information.

• Keywords
• kontrastní látka, contrast agent, Responzivní kontrastní látky, Drug delivery systémy, 1H/31P magnetická resonance, Responsive contrast agents, Drug delivery systems, 1H/31P magnetic resonance, 31P zobrazování magnetickou rezonancí, funkční nanodiagnostika, 31P magnetic resonance imaging, functional nanodiagnostics,

• NML Publication type
• závěrečné zprávy o řešení grantu AZV MZ ČR

Prevence a léčba krvácení nebo trombózy je u pacientů s jaterní cirhózou spojena s řadou úskalí, zažitých představ a zavedených stereotypů. V odborné veřejnosti přetrvává falešné paradigma, že změny hemostázy provázející jaterní cirhózu mají apriori krvácivý charakter. Ve skutečnosti se spolu s jaterním onemocněním vyvíjí nová hemostatická rovnováha. Problém je, že je křehká a snadno se vlivem vnitřních pohnutek nebo vnějších zásahů bortí. Výsledkem může být krvácení stejně jako trombóza. K těmto neblahým důsledkům mohou přispět i neadekvátní lékařské intervence vedené ve snaze upravit patologické výsledky koagulačních testů nebo trombocytopenii. Předložené doporučení pro klinickou praxi bylo vypracováno s cílem poskytnout praktické pokyny pro interpretaci výsledků laboratorních vyšetření hemostázy a počtu destiček, resp. shrnout současné názory na hemostázu u jaterní cirhózy, pravidla úpravy trombocytopenie a změn v koagulačním systému před invazivními výkony a pravidla tromboprofylaxe u hospitalizovaných pacientů. Hlavním východiskem je doporučení Evropské asociace pro studium jater „Clinical Practice Guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis“.

Prevention and treatment of bleeding or thrombosis in patients with liver cirrhosis is associated with a number of pitfalls, perceived ideas and established stereotypes. A false paradigm persists in the professional community that changes in haemostasis accompanying liver cirrhosis are a priori bleeding. In fact, a new haemostatic balance develops along with liver disease. The problem is that it is fragile and easily disrupted by internal drives or external interventions. The result can be bleeding as well as thrombosis. Inadequate medical interventions conducted in an attempt to correct pathological coagulation abnormalities or thrombocytopenia may contribute to these unfortunate consequences. The present guideline for clinical practice was developed to provide practical guidelines for the interpretation of the results of laboratory tests of haemostasis and platelet count, to summarize current views on haemostasis in liver cirrhosis, rules for the correction of thrombocytopenia and changes in the coagulation system before invasive procedures as well as rules for thromboprophylaxis in hospitalized patients. The main starting point is the recommendation of the European Association for the Study of the Live "Clinical Practice Guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis".

• MeSH
• Hemostasis * drug effects   MeSH
• Risk Assessment methods   MeSH
• Platelet Aggregation Inhibitors therapeutic use   MeSH
• Liver Cirrhosis * complications   MeSH
• Blood Loss, Surgical * nursing   prevention & control   MeSH
• Humans MeSH
• Practice Guidelines as Topic MeSH
• Thrombocytopenia etiology   therapy   MeSH
• Thrombotic Stroke drug therapy   MeSH
• Blood Coagulation Tests methods   MeSH
• Check Tag
• Humans MeSH

STUDY QUESTION: How are ART and IUI regulated, funded, and registered in European countries, and how has the situation changed since 2018? SUMMARY ANSWER: Of the 43 countries performing ART and IUI in Europe, and participating in the survey, specific legislation exists in only 39 countries, public funding varies across and sometimes within countries (and is lacking or minimal in four countries), and national registries are in place in 33 countries; only a small number of changes were identified, most of them in the direction of improving accessibility, through increased public financial support and/or opening access to additional subgroups. WHAT IS KNOWN ALREADY: The annual reports of the European IVF-Monitoring Consortium (EIM) clearly show the existence of different approaches across Europe regarding accessibility to and efficacy of ART and IUI treatments. In a previous survey, some coherent information was gathered about how those techniques were regulated, funded, and registered in European countries, showing that diversity is the paradigm in this medical field. STUDY DESIGN, SIZE, DURATION: A survey was designed using the SurveyMonkey tool consisting of 90 questions covering several domains (legal, funding, and registry) and considering specific details on the situation of third-party donations. New questions widened the scope of the previous survey. Answers refer to the situation of countries on 31 December 2022. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: All members of the EIM were invited to participate. The received answers were checked and initial responders were asked to address unclear answers and to provide any additional information considered relevant. Tables resulting from the consolidated data were then sent to members of the Committee of National Representatives of ESHRE, requesting a second check. Conflicting information was clarified by direct contact. MAIN RESULTS AND THE ROLE OF CHANCE: Information was received from 43 out of the 45 European countries where ART and IUI are performed. There were 39 countries with specific legislation on ART, and artificial insemination was considered an ART technique in 33 of them. Accessibility is limited to infertile couples only in 8 of the 43 countries. In 5 countries, ART and IUI are permitted also for treatments of single women and all same sex couples, while a total of 33 offer treatment to single women and 19 offer treatment to female couples. Use of donated sperm is allowed in all except 2 countries, oocyte donation is allowed in 38, simultaneous donation of sperm and oocyte is allowed in 32, and embryo donation is allowed in 29 countries. Preimplantation genetic testing (PGT)-M/SR (for monogenetic disorders, structural rearrangements) is not allowed in 3 countries and PGT-A (for aneuploidy) is not allowed in 10; surrogacy is accepted in 15 countries. Except for marital/sexual situation, female age is the most frequently reported limiting criterion for legal access to ART: minimal age is usually set at 18 years and the maximum ranges from 42 to 54 with some countries not using numeric definition. Male maximum age is set in very few countries. Where third-party donors are permitted, age is frequently a limiting criterion (male maximum age ranging from 35 to 50; female maximum age from 30 to 37). Other legal restrictions in third-party donation are the number of children born from the same donor (or, in some countries, the number of families with children from the same donor) and, in 12 countries, there is a maximum number of oocyte donations. How countries deal with the anonymity is diverse: strict anonymity, anonymity just for the recipients (not for children when reaching legal adulthood age), a mixed system (anonymous and non-anonymous donations), and strict non-anonymity. Inquiring about donors' genetic screening showed that most countries have enforced either mandatory or scientific recommendations that exclude the most prevalent genetic diseases, although, again, diversity is evident. Reimbursement/compensation systems exist in more than 30 European countries, with around 10 describing clearly defined maximum amounts considered acceptable. Public funding systems are extremely variable. One country provides no financial assistance to ART/IUI patients and three offer only minimal support. Limits to the provision of funding are defined in the others i.e. age (female maximum age is the most used), existence of previous children, BMI, maximum number of treatments publicly supported, and techniques not entitled for funding. In a few countries reimbursement is linked to a clinical policy. The definitions of the type of expenses covered within an IVF/ICSI cycle, up to which limit, and the proportion of out-of-pocket costs for patients are also extremely dissimilar. National registries of ART are in place in 33 out of the 43 countries contributing to the survey and a registry of donors exists in 19 of them. When comparing with the results of the previous survey, the main changes are: (i) an extension of the beneficiaries of ART techniques (and IUI), evident in nine countries; (ii) public financial support exists now in Albania and Armenia; (iii) in Luxembourg, the only ART centre expanded its on-site activities; (iv) donor-conceived children are entitled to know the donor identity in six countries more than in 2018; and (v) four more countries have set a maximum number of oocyte donations. LIMITATIONS, REASONS FOR CAUTION: Although the responses were provided by well-informed and committed individuals and submitted to double checking, no formal validation by official bodies was in place. Therefore, possible inaccuracies cannot be excluded. The results presented are a cross-section in time, and ART and IUI frameworks within European countries undergo continuous modification. Finally, some domains of ART activity were deliberately left out of the scope of this survey. WIDER IMPLICATIONS OF THE FINDINGS: Our results offer a detailed updated view of the ART and IUI situation in European countries. It provides extensive answers to many relevant questions related to ART usage at the national level and could be used by institutions and policymakers at both national and European levels. STUDY FUNDING/COMPETING INTEREST(S): The study has no external funding, and all costs were covered by ESHRE. There were no competing interests.

• MeSH
• Reproductive Techniques, Assisted * legislation & jurisprudence   economics   statistics & numerical data   MeSH
• Fertilization in Vitro economics   legislation & jurisprudence   MeSH
• Humans MeSH
• Surveys and Questionnaires MeSH
• Registries * MeSH
• Insemination, Artificial economics   legislation & jurisprudence   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Europe MeSH

As species adapt to climatic changes, temperature-dependent functions of p53 in development, metabolism and cancer will adapt as well. Structural analyses of p53 epitopes interacting in response to environmental stressors, such as heat, may uncover physiologically relevant functions of p53 in cell regulation and genomic adaptations. Here we explore the multiple p53 elephant paradigm with an experimentally validated in silico model showing that under heat stress some p53 copies escape negative regulation by the MDM2 E3 ubiquitin ligase. Multiple p53 isoforms have evolved naturally in the elephant thus presenting a unique experimental system to study the scope of p53 functions and the contribution of environmental stressors to DNA damage. We assert that fundamental insights derived from studies of a historically heat-challenged mammal will provide important insights directly relevant to human biology in the light of climate change when 'heat' may introduce novel challenges to our bodies and health.

• Publication type
• Journal Article MeSH
• Review MeSH

Fibrilace síní (FS) je nejčastější setrvalou arytmií v dospělé populaci a významným způsobem zatěžuje pacienty i systém zdravotní péče. Management FS se dá zjednodušeně rozdělit na dvě strategie – kontrola frekvence a kontrola rytmu. Optimální léčebná strategie je již několik dekád opakovaně studována. Současně platný doporučený postup Evropské kardiologické společnosti pro léčbu FS na podkladě výsledků mnoha randomizovaných studií doporučuje pro většinu pacientů s FS kontrolu frekvence. Modernější antiarytmika a větší dostupnost a technologický pokrok katetrizačních ablací FS vedly k uskutečnění nových studií. Z nich nejzásadnější byla EAST‐AFNET 4, jejíž výsledky a výsledky dalších následujících studií ve prospěch kontroly rytmu podnítily aktuální změnu paradigmatu léčby FS. Tento článek přináší přehled obou léčebných strategií, evidenci pro časnou kontrolu rytmu, rozbor studie EAST‐AFNET 4, která se stala v této oblasti zásadním milníkem, a shrnutí současných doporučených postupů.

Atrial fibrillation (AF) is the most common sustained arrhythmia in the adult population, having a significant impact on both the patients and healthcare system. AF management may be easily divided in two strategies – frequency control and rhythm control. The optimal treatment strategy has been repeatedly studied in the past decades. Based on many randomized studies, the current guidelines of the European Society of Cardiology recommend frequency control for most patients with AF. More modern antiarrhythmics and easier access to catheter ablations together with technological progress have led to the completion of new trials. The most important of those, EAST‐AFNET 4, the results of which (along with other trials) favored rhythm control, inspired a recent paradigm change in the treatment of AF. This article summarizes both treatment strategies, evidence supporting early rhythm control, the pivotal EAST‐AFNET 4 analysis, and current guidelines as well.

• Keywords
• studie EAST-AFNET 4,
• MeSH
• Anti-Arrhythmia Agents pharmacology   therapeutic use   MeSH
• Atrial Fibrillation * diagnosis   prevention & control   MeSH
• Catheter Ablation methods   MeSH
• Humans MeSH
• Disease Management MeSH
• Randomized Controlled Trials as Topic MeSH
• Heart Rate * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH