Angelman Syndrome (AS) is a neurodevelopmental disorder caused by the loss of function of ubiquitin-protein ligase E3A (UBE3A), resulting in marked changes in synaptic plasticity. In AS mice, a dysregulation of Ca2+/calmodulin-dependent protein kinase II alpha (CaMKIIα) was previously described. This has been convincingly validated through genetic rescue of prominent phenotypes in mouse cross-breeding experiments. Selective ligands that specifically stabilize the CaMKIIα central association (hub) domain and affect different conformational states in vitro are now available. Two of these ligands, 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) and (E)-2-(5-hydroxy-2-phenyl-5,7,8,9-tetrahydro-6H-benzo[7]annulen-6-ylidene)acetic acid (Ph-HTBA), confer neuroprotection after ischemic stroke in mice where CaMKIIα is known to be dysregulated. Here, we sought to investigate whether pharmacological modulation with these prototypical CaMKIIα hub ligands presents a viable approach to alleviate AS symptoms. We performed an in vivo functional evaluation of AS mice treated for a total of 14 days with either HOCPCA or Ph-HTBA (7 days pre-treatment and 7 days of behavioural assessment). Both compounds were well-tolerated but unable to revert robust phenotypes of motor performance, anxiety, repetitive behaviour or seizures in AS mice. Biochemical experiments subsequently assessed CaMKIIα autophosphorylation in AS mouse brain tissue. Taken together our results indicate that pharmacological modulation of CaMKIIα via the selective hub ligands used here is not a viable treatment strategy in AS.

• MeSH
• Angelman Syndrome * drug therapy   genetics   MeSH
• Behavior, Animal drug effects   MeSH
• Phenotype * MeSH
• Ligands MeSH
• Disease Models, Animal * MeSH
• Brain drug effects   metabolism   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Neuroprotective Agents pharmacology   MeSH
• Calcium-Calmodulin-Dependent Protein Kinase Type 2 * metabolism   MeSH
• Ubiquitin-Protein Ligases metabolism   genetics   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Úvod: Atypický fibroxantóm (AFX) je zriedkavý mezenchýmový nádor kože s nejasným histogenetickým pôvodom a neurčitým biologickým správaním. Charakteristický je výraznou štrukturálnou variabilitou, ktorá spôsobuje pri bioptickom vyšetrení značné diagnostické rozpaky. Stanovenie diagnózy sa nezaobíde bez použitia širokého spektra imunohistochemických markerov. Kazuistika: 79-ročný muž s anamnézou viacpočetných keratinocytových karcinómov kože pozoroval vznik ďalšej tumoróznej lézie na ľavom líci, ktorá imponovala ako bazocelulárny karcinóm. Odstránená bola totálnou chirurgickou excíziou. Tumor pozostával z pomerne ohraničeného intradermálne rastúceho nodulu tvoreného populáciou pleomorfných nádorových buniek so svetlou cytoplazmou. Imunohistochemicky bol pozitívny na vimentín, CD163, CD68, CD10 a CD99. Histomorfologický obraz a imunofenotyp zodpovedali svetlobunkovému variantu AFX. Po stanovení diagnózy bol pacient ďalej sledovaný onkodermatológom bez ďalšej terapeutickej intervencie. Záver: Svetlobunkový AFX je veľmi zriedkavý nádor postihujúci preferenčne oblasť hlavy u starších mužov. Zvyčajne je ťažko diagnostikovateľný, pretože imituje široké spektrum primárnych aj sekundárnych nádorov kože. Vždy musí byť správne odlíšený od iných kožných malignít so svetlobunkovou diferenciáciou, ktoré majú omnoho agresívnejšie biologické správanie, horšiu prognózu a vyžadujú úplne inú liečebnú stratégiu.

Introduction: Atypical fibroxanthoma (AFX) is a rare mesenchymal skin tumor of unknown histogenesis and unclear biological behaviour. It is characterized by marked structural variability, which causes great diagnostic embarrassment during biopsy examination. Establishing a correct diagnosis can not be done without using a wide spectrum of immunohistochemical markers. Case report: A 79-year-old man with a history of multiple keratinocytic skin carcinomas noticed another lesion arising in the left cheek. It looked like basal cell carcinoma and was completely removed by surgical excision. The tumor consisted of a relatively circumscribed intradermal nodule composed of pleomorphic neoplastic cell population with clear cytoplasm. It immunohistochemically expressed vimentin, CD163, CD68, CD10 and CD99. A pathologic diagnosis of clear cell AFX was done. After establishing the diagnosis, the patient was followed-up by an oncodermatologist without further therapeutic intervention. Conclusion: Clear cell AFX is a unique tumor preferentially affecting the head region in older men. It is usually difficult to diagnose because it mimics a wide range of primary and secondary skin neoplasms. It must always be correctly distinguished from other cutaneous malignancies with clear cell differentiation, which have a much more aggressive biological behaviour, worse prognosis and require a completely different therapeutic strategy.

• Keywords
• atypický fibroxantom,
• MeSH
• Immunohistochemistry methods   MeSH
• Humans MeSH
• Skin Neoplasms * surgery   diagnosis   MeSH
• Aged MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Case Reports MeSH

Our study intends to specify the impact of the singular pandemic stressors on the population and also quantify the contribution of different predictors of depression; some of them are stronger than others, and this research shows how the whole effect is divided into single items. This research included a structured online survey using data from 11,340 respondents from six European countries during the first months of the pandemic. The statistical analysis focused on how behavioural patterns appear in different groups of the population and how they mark the psychological wellbeing of these groups with regard to various factors. We targeted social media's role and analyzed the impact of its consumption on symptoms of depression in different groups divided by age and other characteristics. The analysis creates a mosaic of lifestyle choices and other characteristics that manifest different effects on depression inside selected groups whereas several groups generated by the cluster analysis are less vulnerable to their effect than others. Regarding our findings, the perceived reality through information sources and the manner of their processing seems to be more significant than the tangible reality (poor self-reported health correlated with depression more strongly than intrinsic health limitations).

• Publication type
• Journal Article MeSH

Panická porucha negativně ovlivňuje kvalitu života pacienta. Poruchu charakterizují somatické projevy masivní úzkosti. Ty se úzce spojují s autonomním nervovým systémem (ANS), který ovlivňuje reakce těla na vnější i vnitřní podněty. Cílem článku je zmapovat propojení panické poruchy a autonomního nervového systému a možnosti terapeutického zásahu. Zdroje pro tento souborný článek byly čerpány z databází PubMed a Web of Science, vydaných mezi lety 1991 až 2022. Další informace byly získány ze zdrojů článků použitých v primárním výběru. Výrazné somatické symptomy a zejména kardiovaskulární symptomy jsou charakteristické rysy panických záchvatů. Ukazuje se, že u pacientů s panickou poruchou se může projevovat autonomní dysfunkce a snížená variabilita srdeční frekvence (HRV). Intenzivní míra úzkosti a celkový arousal vedou k redukci tonu nervus vagus a zvýšení aktivity sympatiku, což způsobuje celkové snížení HRV, ve srovnání s kontrolními skupinami. Hodnocení dopadu léčby panické poruchy na HRV vyžaduje další studie. Předběžně se zdá, že antidepresiva snižují HRV nebo mají zanedbatelný vliv, a naopak po úspěšné kognitivně­‐behaviorální terapii (KBT) dochází ke zlepšení regulace neuro­‐kardiální kontroly hodnocené HRV. U pacientů s panickou poruchou dochází k narušení funkce autonomního nervového systému. Do regulace ANS může příznivě zasáhnout úspěšně léčba pomocí KBT. Další výzkum je potřebný ke zhodnocení účinnosti biofeedbacku, aerobního cvičení a psychofarmak.

Panic disorder negatively affects the patient's quality of life. Somatic manifestations of massive anxiety characterize the disorder. These are closely related to the autonomic nervous system (ANS), which influences the body's responses to external and internal stimuli. The article aims to map the connection between panic disorder and the autonomic nervous system and the possibilities of therapeutic intervention. Sources for this review article were drawn from the PubMed and Web of Science databases, published between 1991 and 2022. Additional information was obtained from the sources of the articles used in the primary selection. Marked somatic and cardiovascular symptoms are characteristic features of panic attacks. Patients with panic disorder may exhibit autonomic dysfunction and reduced heart rate variability (HRV). Intense anxiety and general arousal levels reduce vagus nerve tone and increase sympathetic activity, causing an overall decrease in HRV compared to control groups. Evaluation of the impact of panic disorder treatment on HRV requires further studies. Preliminarily, it seems that antidepressants reduce HRV or have a negligible effect, and on the contrary, after successful cognitive-behavioural therapy, there is an improvement in the regulation of neuro-cardiac control assessed by HRV. In patients with panic disorder, the function of the autonomic nervous system is impaired. Successful treatment with CBT can have a beneficial effect on the regulation of the ANS. Further research is needed to evaluate the effectiveness of biofeedback, aerobic exercise, and psychotropic drugs.

• MeSH
• Autonomic Nervous System * physiology   pathology   MeSH
• Cognitive Behavioral Therapy MeSH
• Humans MeSH
• Panic Disorder * physiopathology   therapy   MeSH
• Heart Rate MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Schizofrenie je závažná dlouhodobá psychotická porucha vyznačující se pozitivními i negativními symptomy, závažnými poruchami chování a deficitem kognitivních funkcí. Příčina této poruchy není zcela jasná, ale předpokládá se, že je multifaktoriální a zahrnuje jak dědičné, tak vnější faktory. Vzhledem k tomu, že lidský mozek reguluje veškeré chování, zaměřily se studie schizofrenie na identifikaci změn v neurobiologii a biochemii mozku. Mozek je orgánem nejvíce bohatým na lipidy (lipidy tvoří přibližně 50 % suché hmotnosti mozku). Výsledky četných studií prokázaly významný pokles polynenasycených mastných kyselin (PUFA), zejména kyseliny dokosahexaenové (DHA) v periferní krvi a také v mozku pacientů se schizofrenií v různých vývojových fázích poruchy. Nedostatek PUFA je spojován s psychotickými symptomy a kognitivními deficity u schizofrenie. Tato zjištění vedla k řadě klinických studií zkoumajících, zda by suplementace PUFA ve stravě mohla zlepšit průběh onemocnění u pacientů se schizofrenií. Výsledky jsou nekonzistentní, což lze přičíst zejména heterogenitě sledovaných pacientů. Zda se však, že pacienti s nízkými hladinami PUFA premorbidní, prodromálně nebo v časných stadiích schizofrenie by mohli mít z léčby PUFA prospěch. Každopádně je potřeba více kontrolovaných klinických studií.

Schizophrenia is a serious long-term psychotic disorder marked by positive and negative symptoms, severe behavioral problems and cognitive function deficits. The cause of this disorder is not completely clear, but is suggested to be multifactorial, involving both inherited and environmental factors. Since human brain regulates all behaviour, studies have focused on identifying changes in neurobiology and biochemistry of brain in schizophrenia. Brain is the most lipid rich organ (approximately 50 % of brain dry weight). Results from numerous studies have shown significant decreases of PUFAs, in particular, DHA as well as brain of schizophrenia patients at different developmental phases of the disorder. PUFA deficiency has been associated to psychotic symptoms and cognitive deficits in schizophrenia. These findings have led to a number of clinical trials examining whether dietary PUFA supplementation could improve the course of illness in patients with schizophrenia. Results are inconsistent. Some report beneficial whereas others show not effective. The discrepancy can be attributed to the heterogeneity of patient population. In this review, results from recent experimental and clinical studies, which focus on illustrating the role of PUFAs in the development of schizophrenia were examined. It suggests that patients with low PUFA levels before onset of disease, prodromally, or in the early stages of schizophrenia might benefit from lipid treatments, but more controlled clinical trials are warranted.

• MeSH
• Humans MeSH
• Brain physiology   drug effects   MeSH
• Fatty Acids, Omega-3 * metabolism   deficiency   therapeutic use   MeSH
• Schizophrenia * drug therapy   pathology   MeSH
• Check Tag
• Humans MeSH

Mice respond to a cage change (CC) with altered activity, disrupted sleep and increased anxiety. A bi-weekly cage change is, therefore, preferred over a shorter CC interval and is currently the prevailing routine for Individually ventilated cages (IVCs). However, the build-up of ammonia (NH3) during this period is a potential threat to the animal health and the literature holds conflicting reports leaving this issue unresolved. We have therefor examined longitudinally in-cage activity, animal health and the build-up of ammonia across the cage floor with female and male C57BL/6 mice housed four per IVC changed every other week. We used a multicentre design with a standardised husbandry enabling us to tease-out features that replicated across sites from those that were site-specific. CC induce a marked increase in activity, especially during daytime (~50%) when the animals rest. A reduction in density from four to two mice did not alter this response. This burst was followed by a gradual decrease till the next cage change. Female but not male mice preferred to have the latrine in the front of the cage. Male mice allocate more of the activity to the latrine free part of the cage floor already the day after a CC. A behaviour that progressed through the CC cycle but was not impacted by the type of bedding used. Reducing housing density to two mice abolished this behaviour. Female mice used the entire cage floor the first week while during the second week activity in the latrine area decreased. Measurement of NH3 ppm across the cage floor revealed x3 higher values for the latrine area compared with the opposite area. NH3 ppm increases from 0-1 ppm to reach ≤25 ppm in the latrine free area and 50-100 ppm in the latrine area at the end of a cycle. As expected in-cage bacterial load covaried with in-cage NH3 ppm. Histopathological analysis revealed no changes to the upper airways covarying with recorded NH3 ppm or bacterial load. We conclude that housing of four (or equivalent biomass) C57BL/6J mice for 10 weeks under the described conditions does not cause any overt discomfort to the animals.

• MeSH
• Ammonia * MeSH
• Housing, Animal * MeSH
• Time Factors MeSH
• Animal Husbandry MeSH
• Bedding and Linens MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH

PURPOSE OF THE STUDY The paper aims to evaluate the effect of COVID-19 pandemic on a change in the number of major trauma cases, their mechanism and length of hospital stay as seen by a Level I Trauma Centre. MATERIAL AND METHODS The retrospective study included a total of 755 major trauma patients (ISS ≥ 16) treated at our Level I Trauma Centre in the period 2018-2019 ("pre-COVID-19 time") and 2020-2021 ("COVID-19 time"). The effect of COVID-19 infection on the change in the number and nature of major trauma, mechanism of injury, length of treatment during prehospital care, length of hospital stay, and mortality. RESULTS Of the total number of 755 patients with major trauma, in the "pre-COVID-19 time" 399 patients were treated, while in the "COVID-19 time" it was 356 patients (p = 0.10). The mechanism of major trauma did not change, road traffic accidents prevailed (61% vs. 56%, p = 0.25), the proportion of injuries due to falls from height increased (25% vs. 32.5%, p = 0.08), a significant decrease was observed in the category of severe skiing injuries (7 vs. 2, p = 0.003). The severity of injuries evaluated by Injury Severity Score remained unchanged (25 vs. 25, p = 0.08), but an increased number of patients with traumatic brain injury (TBI) marked by the Abbreviate Injury Score (AIS) ≥ 4 was observed (38 vs. 56, p = 0.03). The total length of a hospital stay shortened (18 vs. 15 days, p = 0.04), but the mortality rate spiked (52 vs. 73 patients, p = 0.08). DISCUSSION In the "COVID-19 time", the total number of major trauma cases dropped just like in the other European countries. Despite restrictive measures imposing mobility restrictions, no change was reported in the mechanism of injury, with traffic accidents still prevalent, except for skiing injuries. Unlike the US, we did not see an increase in penetrating injuries due to interpersonal violence or suicidal behaviour. However, there was an increase in the percentage of patients with an isolated TBI as a result of a fall from height. An increase in mortality was reported due to an increase in severe TBI. The length of hospital stay was reduced as a result of efforts to maintain hospital bed availability. CONCLUSIONS During the COVID-19 pandemic, compared to the two years immediately preceding, no significant decrease in the number of major trauma cases was reported, despite the introduction of restrictive measures. The proportion of road traffic injuries remained the same, whereas the number of falls from height slightly increased, which consequently led to an increase in the number of severe TBI. The number of penetrating injuries due to acts of violence did not increase, but due to the lockdown there was a significant decrease in severe skiing-related injuries. The anti-epidemic measures in place did not prolong the pre-hospital care for severely injured patients. Key words: major trauma, Injury Severity Score, COVID-19, mechanism of injury.

• MeSH
• COVID-19 * epidemiology   MeSH
• Communicable Disease Control MeSH
• Humans MeSH
• Pandemics MeSH
• Wounds, Penetrating * MeSH
• Retrospective Studies MeSH
• Trauma Centers MeSH
• Check Tag
• Humans MeSH
• Publication type
• English Abstract MeSH
• Journal Article MeSH

• MeSH
• Internal Medicine MeSH
• Publication type
• Textbook MeSH

• Conspectus
• Lékařské vědy. Lékařství
• NML Fields
• vnitřní lékařství
• NML Publication type
• kolektivní monografie

Inflamatorní myofibroblastický tumor (IMT) dělohy je vzácný, ale zřejmě poddiagnostikovaný nádor. Většinou se chová benigně, přesto menší část může lokálně recidivovat a výjimečně i metastazovat. V této práci prezentujeme případ uterinního IMT u 66leté pacientky, který byl původně diagnostikován jako děložní leiomyosarkom. Pacientka zemřela s odstupem několika měsíců v důsledku rozsáhlé lokální recidivy nádoru a metastáz do skeletu. Makroskopicky se jednalo o objemný tumor měkké konzistence a jílovité barvy. Nádor rostl lokálně agresivně s omezením na myometrium. Mikroskopicky byla léze tvořena polymorfní vřetenobuněčnou proliferací s výraznými jadernými atypiemi a početnými mitózami. Přítomny byly drobné geografické nekrózy. Ze znaků typických pro IMT byly zastiženy pouze fokální mírné lymfocytární infiltráty, myxoidní stroma zcela chybělo. Imunohistochemicky nádorové buňky silně a difúzně exprimovaly ALK (anaplastic lymphoma kinase). Molekulárně genetickými metodami byla prokázána genová fúze PPP1CB-ALK. Adekvátní diagnostika uterinních IMT je klíčová s ohledem na možnost léčit pacientky s agresivními tumory pomocí ALK inhibitorů. Nejnovější poznatky ukazují, že IMT dělohy představuje histomorfologicky poměrně heterogenní skupinu lézí ukrývajících se často mezi STUMP (hladkosvalové tumory nejistého maligního potenciálu) a leiomyosarkomy. Jediným spolehlivým diagnostickým znakem těchto nádorů se zdá být přítomnost přestavby genu ALK. Nabízí se tak vhodná screeningová metoda k detekci děložních IMT založená na imunohistochemickém a molekulárně genetickém průkazu alterace ALK genu.

Inflammatory myofibroblastic tumor (IMT) of the uterus is rare but probably underdiagnosed tumor. It is usually benign but small fraction of cases may locally recur or rarely metastasize. Herein, we present a case report of 66-year-old patient with uterine IMT originally diagnosed as leiomyosarcoma of the uterus. The patient died within few months due to local tumor progression with skeletal metastases. Macroscopically, this was a voluminous locally aggressive yellowish- grey tumor of soft consistency limited to myometrium. Microscopically, the tumor was characterized by polymorphic spindle cell proliferation with marked nuclear atypia and numerous mitoses. Small geographic necroses was noticed. Typical histologic features of IMT were represented by lymphocytic infiltrate which was only very small and focal. Myxoid stroma was absent. Immunohistochemically, there was strong and diffuse cytoplasmic positivity of ALK (anaplastic lymphoma kinase). The presence of PPP1CB-ALK fusion transcript was confirmed by molecular-genetic methods. Proper diagnosis of uterine IMT is of importance as there is an option of targeted ALK inhibitor therapy in cases of aggressive tumor behaviour. Currently it is thought that histomorphology of uterine IMT may overlap with that of leiomyosarcoma and STUMP (smooth muscle tumor of uncertain malignant potential). The presence of ALK rearrangement is probably the only reliable diagnostic marker. Thus, ALK immunohistochemistry followed by molecular-genetic testing seems to represent suitable screening tool for the detection of uterine IMT.

• Keywords
• inflamatorní myofibroblastický tumor, mezenchymální tumory s ALK přestavbou,
• MeSH
• Leiomyosarcoma diagnosis   MeSH
• Humans MeSH
• Uterine Neoplasms * diagnosis   drug therapy   surgery   MeSH
• Aged MeSH
• Protein-Tyrosine Kinases antagonists & inhibitors   therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Narušené vztahy s rodiči jsou v psychickém dozrávání dítěte závažným patogenním činitelem, jenž se uplatňuje ponejvíce v období puberty a adolescence. Kazuistika pacienta v doléčovacím programu po ústavní léčbě, absolvované z důvodů závislosti na alkoholu, dokumentuje nikoli neznámý fenomén vlivu dysfunkční, potažmo tragickou ztrátou poznamenané rodiny, především v kontextu neustálého hledání odpovědí na elementární otázky, kde je ve společnosti mé místo, kam se mám/chci v životě ubírat, jak se vypořádávat (nejen) s mezilidskými vztahy. Kazuistika byla sepsána na základě půlročního sledování pacienta v doléčovacím programu psychoterapeutického stacionáře. Součástí kazuistiky je systematická práce se životní křivkou. V textu jsou použity autentické záznamy (přímá řeč pacienta, parafráze přímé řeči), aby byl co možná nejpřiléhavěji vystižen pacientův stav rozpoložení.

A child's disrupted relationship with its parents is a serious pathogenic factor in its mental maturation which is most prevalent during puberty and adolescence. This case study of a patient in an after-care programme following residential alcohol treatment documents the effect of a dysfunctional family marked by a tragic loss. This may be particularly reflected in his constantly seeking answers to fundamental questions, such as those concerning his place in society, what to do with his life, and how to deal with (among others) interpersonal relationships. The case study was written on the basis of a six-month follow-up of a patient in an after-care programme of a psychotherapeutic centre. The case study includes systematic work with the life curve. Authentic records (the patient's direct speech or paraphrases of his direct speech) are used in the text to provide an accurate description of the patient's feelings and state of mind.