Vzteklina patří bezesporu mezi nejvíce nebezpečnou, ve 100 % případů letální virovou infekci přenášenou zvířaty na člověka. Ve více než 150 zemích, kde se endemicky vyskytuje, je nejčastější riziko expozice po poranění psem. Obzvlášť nebezpečné je pokousání netopýrem. Ročně nemoci podlehne zhruba 60 tisíc osob, nejvíce v oblastech Afriky a Asie. Preventivní možnosti k zabránění vzniku onemocnění zahrnují očkování v rámci preexpoziční profylaxe (PrEP) a včasné a důsledné zahájení postexpoziční profylaxe (PEP). V letech 2019–2021 provedl Poradní výbor pro očkovací postupy (Advisory Committee on Immunization Practices, ACIP, USA) několik aktualizací doporučení pro PrEP včetně následujících: předefinování kategorií rizika nákazy vzteklinou, nahrazení třídávkového vakcinačního schématu (D0, D7, D21 nebo D28) dvoudávkovým schématem (D0 a D7), zajištění dlouhodobé protilátkové protektivity jedince flexibilními možnostmi, méně časté nebo žádné kontroly koncentrace protilátek u některých rizikových skupin, stanovení minimální přijatelné koncentrace protilátek proti vzteklině na hodnotu 0,5 IU/ml, zajištění účinného očkování některých zvláštních skupin obyvatelstva. V případě PEP zůstávají postupy stejné jako doposud. Na základě charakteru poranění, druhu zvířete a časovém odstupu od aplikace PrEP, byla-li v minulosti podána, se expozice dělí do několika kategorií podle závažnosti. Podle stanovené kategorie se následně v rámci PEP aplikuje buďto pouze vakcína, nebo vakcína současně s podáním antirabického imunoglobulinu. Postupy jsou shodné pro všechny včetně dětí a těhotných žen, jelikož se jedná o život zachraňující úkon.

Rabies is undoubtedly one of the most dangerous viral infections transmitted by animals to humans, being lethal in 100% of cases. In more than 150 countries where it is endemic, the most common risk of exposure is from a dog bite. Bat bites are particularly dangerous. Approximately 60,000 people die each year, mostly in areas of Africa and Asia. Preventive options to avoid the disease include vaccination as a part of preexposure prophylaxis (PrEP) and early and consistent initiation of postexposure prophylaxis (PEP). In 2019–2021, the Advisory Committee on Immunization Practices (ACIP, USA) made several updates to the PrEP recommendations, including the following: redefining the risk categories for rabies infection, replacing the three-dose vaccination schedule (D0, D7, D21 or D28) with a two-dose schedule (D0 and D7), ensuring long-term antibody protection of individuals with flexible options, less frequent or no antibody concentration checks for certain at-risk groups, setting the minimum acceptable rabies antibody concentration at 0.5 IU/ml, and ensuring effective vaccination of certain special populations. In the case of PEP, the procedures remain the same as before. Based on the nature of the injury, the type of animal, and the time interval since PrEP was administered, if previously administered, exposures are divided into several categories according to severity. Depending on the category determined, either the vaccine alone or the vaccine concurrently with the administration of rabies immunoglobulin is subsequently administered as part of PEP. The procedures are the same for everyone, including children and pregnant women, as they are life-saving.

Kliešťová encefalitída (KE) je opomínaná neuroinvazívna antropozoonóza. Väčšina prípadov KE má mierny priebeh, ale u niektorých pacientov s encefalitídou sa vyvinú dlhodobé neurologické alebo neuropsychické následky. Uvádzame fatálny prípad KE z endemickej oblasti. Prípad sa vyskytol u muža v strednom veku bez epidemiologických dôkazov o uhryznutí kliešťom alebo konzumácii surových mliečnych výrobkov a ktorý nebol očkovaný proti KE. Cieľom tohto príspevku je upozorniť na potrebu lepšej znalosti rizikových faktorov spojených s kliešťovou encefalitídou s dlhodobými následkami, zlepšiť manažment prípadov a podnietiť vývoj nových vakcinačných stratégií. Podľa našich vedomostí ide o prvý hlásený prípad zriedkavej fatálnej KE u muža stredného veku bez závažných komorbidít na Slovensku.

Tick-borne encephalitis (TBE) is a neglected zoonotic neuroinvasive disease. Most cases of TBE have a mild course, but some patients with encephalitis develop long-term neurological or neuropsychic sequelae. We report a fatal case of TBE in a patient living in an endemic area. The case occurred in a middle-aged man with no epidemiological evidence of tick bites, no consumption of raw dairy products, and who was not vaccinated against TBE. The aim of this paper is to draw attention to the need for better information of the risk factors associated with TBE with the long-term sequelae, to improve case management and to stimulate the development of new vaccination strategies. To our knowledge, this is the first reported case of rare fatal TBE in a middle-aged man with no severe comorbidities in Slovakia.

• MeSH
• Disease Outbreaks statistics & numerical data   MeSH
• Fatal Outcome MeSH
• Encephalitis, Tick-Borne * mortality   MeSH
• Comorbidity MeSH
• Middle Aged MeSH
• Drug-Related Side Effects and Adverse Reactions MeSH
• Zoonoses epidemiology   MeSH
• Check Tag
• Middle Aged MeSH
• Male MeSH
• Publication type
• Case Reports MeSH
• Geographicals
• Slovakia MeSH

Glioblastomas are aggressive brain tumors for which effective therapy is still lacking, resulting in dismal survival rates. These tumors display significant phenotypic plasticity, harboring diverse cell populations ranging from tumor core cells to dispersed, highly invasive cells. Neuron navigator 3 (NAV3), a microtubule-associated protein affecting microtubule growth and dynamics, is downregulated in various cancers, including glioblastoma, and has thus been considered a tumor suppressor. In this study, we challenge this designation and unveil distinct expression patterns of NAV3 across different invasion phenotypes. Using glioblastoma cell lines and patient-derived glioma stem-like cell cultures, we disclose an upregulation of NAV3 in invading glioblastoma cells, contrasting with its lower expression in cells residing in tumor spheroid cores. Furthermore, we establish an association between low and high NAV3 expression and the amoeboid and mesenchymal invasive phenotype, respectively, and demonstrate that overexpression of NAV3 directly stimulates glioblastoma invasive behavior in both 2D and 3D environments. Consistently, we observed increased NAV3 expression in cells migrating along blood vessels in mouse xenografts. Overall, our results shed light on the role of NAV3 in glioblastoma invasion, providing insights into this lethal aspect of glioblastoma behavior.

• MeSH
• Phenotype * MeSH
• Glioblastoma * pathology   genetics   metabolism   MeSH
• Neoplasm Invasiveness * genetics   MeSH
• Humans MeSH
• Membrane Proteins MeSH
• Microtubules metabolism   MeSH
• Mice MeSH
• Cell Line, Tumor MeSH
• Brain Neoplasms * pathology   genetics   metabolism   MeSH
• Cell Movement genetics   physiology   MeSH
• Nerve Tissue Proteins metabolism   genetics   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Methoxphenidine (MXP) is classified as a new psychoactive substance that has recently emerged on the illicit drug market. Understanding the pharmacological and behavioural profiles of newly emerging drugs is essential for a better understanding of their psychotropic effects and potential toxicity. Therefore, in this study, we investigated a broad range of effects of acute MXP administration: pharmacokinetics in the brain and serum; behaviour (open field and prepulse inhibition), systemic toxicity (lethal dose; LD 50), and histopathology changes in parenchymal organs of Wistar rats. MXP rapidly crossed the blood-brain barrier, reaching peak median concentrations in both serum and brain 30 min post-administration, followed by an elimination phase with a half-life of 2.15 h. Locomotor activity in the open field test displayed a dose-response effect at low to moderate doses (10-20 mg/kg MXP). At higher doses (40 mg/kg), locomotor activity decreased. All doses of MXP significantly disrupted prepulse inhibition and the effect was present during the onset of its action as well as 60 min after treatment. Additionally, MXP demonstrated moderate acute toxicity, with an estimated LD50 of 500 mg/kg when administered subcutaneously. In summary, MXP exhibited a profile similar to typical dissociative anesthetics, producing stimulant and anxiogenic effects at lower doses, sedative effects at higher doses, and disrupting sensorimotor gating. The accumulation of MXP in brain tissue is likely to contribute to acute intoxication in humans, potentially leading to negative experiences. Our findings highlight the potentially dangerous effects of recreational MXP use and underscore the risks of inducing serious adverse health outcomes.

• MeSH
• Behavior, Animal drug effects   MeSH
• Rats MeSH
• Lethal Dose 50 MeSH
• Brain drug effects   metabolism   MeSH
• Piperidines pharmacokinetics   pharmacology   MeSH
• Motor Activity drug effects   MeSH
• Rats, Wistar * MeSH
• Prepulse Inhibition drug effects   MeSH
• Open Field Test drug effects   MeSH
• Dose-Response Relationship, Drug * MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review insulin, which has at least one plausible mechanism for slowing ALS progression. However, pre-clinical studies are limited and there have been no trials in PALS yet. Insulin use in patients without a metabolic need may cause very serious and potentially lethal side effects. While further studies to evaluate potential benefits may be warranted, at this time we cannot endorse insulin treatment to slow ALS progression.

• MeSH
• Amyotrophic Lateral Sclerosis * drug therapy   MeSH
• Insulin adverse effects   MeSH
• Humans MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Metastatický duktální karcinom pankreatu (metastatic pancreatic ductal adenocarcinoma – mPDAC) patří mezi maligní onemocnění s nejvyšší letalitou. Dnešní terapeutické možnosti zahrnují podle doporučení Evropské společnosti pro klinickou onkologii (ESMO) v 1. linii dublet chemoterapii gemcitabin + nab-paklitaxel (Gem/Nab-P) nebo modifikovaný režim FOLFIRINOX (mFOLFIRINOX) a u pacientů v horším celkovém stavu monoterapii gemcitabinem. Nepřímé srovnání základních studií s Gem/Nab-P a mFOLFIRINOX v porovnání s gemcitabinem v monoterapii (PRODIGE-4 a MPACT) naznačilo delší celkové přežití (overall survival – OS) u pacientů s mFOLFIRINOX. Je ale třeba vzít v úvahu, že do studie MPACT s Gem/Nab-P byli zařazováni pacienti s celkově horším výkonnostním stavem. Přímé porovnání těchto režimů chemoterapie chybělo. Nepřímá porovnání z reálné praxe ukazují jejich srovnatelnou účinnost z hlediska OS, přežití bez progrese i podílu léčebných odpovědí, konzistentně odlišný je profil bezpečnosti. Nedávno publikovaná studie fáze II/III GENERATE, která přímo porovnávala Gem/Nab-P a mFOLFIRINOX u nepředléčených pacientů s mPDAC, prokázala významně delší OS u pacientů léčených Gem/Nab-P přesahující 17 měsíců při nižší incidenci nehematologické toxicity. Výsledky vyvolaly na kongresu ESMO 2023 živou diskuzi. Porovnání Gem/Nab-P a mFOLFIRINOX se ve své prezentaci na konferenci PragueONCO 2024 věnoval i prof. Prager, který vyzdvihl minimálně srovnatelnou účinnost obou režimů a lepší bezpečnost Gem/Nab-P a doložil přínos Gem/Nab-P také u pacientů starších 70 let a pacientů s výkonnostním stavem (performance status – PS) podle Eastern Cooperative Oncology Group (ECOG) PS 2. Je třeba také vzít v úvahu, že volba 1. linie léčby určuje terapeutické možnosti ve 2. linii. Při aplikaci Gem/Nab-P lze dnes ve 2. linii využít pegylovaný lipozomální irinotekan (nal-IRI) v kombinaci s 5-fluorouracilem a leukovorinem (5-FU/LV), který prokázal prodloužení OS v porovnání s 5-FU/LV ve studii III. fáze NAPOLI-1. U pacientů předléčených režimem mFOLFIRINOX lze ve 2. linii využít gemcitabin nebo Gem/Nab-P. Včasné vyšetření molekulárních prediktivních parametrů umožní identifikovat případy, pro které je k dispozici vhodná cílená léčba nebo imunoterapie.

Background: Metastatic pancreatic ductal carcinoma (mPDAC) is one of the most lethal malignancies. The European Society for Medical Oncology (ESMO) guidelines recommend a gemcitabine doublet + nab-paclitaxel (Gem/Nab-P) or a modified FOLFIRINOX regimen (mFOLFIRINOX) as options for systemic chemotherapy. Gemcitabine monotherapy is an option for patients in a worse performance status (PS). Indirect comparisons of pivotal trials with Gem/Nab-P and mFOLFIRINOX vs. gemcitabine monotherapy (PRODIGE-4 and MPACT) indicated longer overall survival (OS) in patients treated with mFOLFIRINOX. However, it should be taken into account that the MPACT study with Gem/Nab-P included patients with an overall worse performance status. A direct comparison of these chemotherapy regimens was lacking. Indirect comparisons from real practice show their comparable effectiveness in terms of OS, progression-free survival and overall response rate. The safety profile is consistently different. The recently published phase II/III GENERATE trial, which directly compared Gem/Nab-P and mFOLFIRINOX in treatment-na?ve mPDAC patients, demonstrated significantly longer OS in Gem/Nab-P-treated patients exceeding 17 months with a lower incidence of non-hematologic toxicity. The results sparked a lively discussion at the ESMO 2023 Congress. The comparison of Gem/Nab-P and mFOLFIRINOX was also addressed by prof. Prager in his presentation at the PragueONCO 2024 conference. Prager, who highlighted comparable efficacy of both regimens and better safety of Gem/Nab-P and demonstrated the benefit of Gem/Nab-P also in patients older than 70 years and those with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2. It should also be taken into account that the choice of first line treatment determines the therapeutic options in the 2nd line. If the Gem/Nab-P regimen is used in the first line, pegylated liposomal irinotecan (nal-IRI) in combination with 5-fluorouracil and leucovorin (5-FU/LV) can be used in the second line. This regimen demonstrated prolongation of OS compared to 5-FU/LV in phase III study NAPOLI-1. In patients pretreated with the mFOLFIRINOX regimen, gemcitabine monotherapy or Gem/Nab-P can be used in the second line. Early examination of molecular predictive parameters will enable the identification of cases for which appropriate targeted therapy or immunotherapy is available.

• Keywords
• studie GENERATE, FOLFIRINOX,
• MeSH
• Carcinoma, Pancreatic Ductal drug therapy   mortality   secondary   MeSH
• Gemcitabine * pharmacology   therapeutic use   MeSH
• Irinotecan pharmacology   classification   therapeutic use   MeSH
• Drug Therapy, Combination methods   MeSH
• Humans MeSH
• Survival Rate MeSH
• Paclitaxel * pharmacology   therapeutic use   MeSH
• Antineoplastic Combined Chemotherapy Protocols pharmacology   therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Multicenter Study MeSH

OBJECTIVES: Due to Albendazole's relatively low efficacy and bioavailability, Echinococcosis has proven a challenge to manage successfully, with several studies investigating ways to improve the outcome, mainly showing mixed results. We, therefore, aimed to evaluate whether Sulfonated Graphene Oxide (S-GO), as nanocarriers, could improve the mentioned outcome. METHODS: Echinococcus protoscoleces were divided into four groups based on the agent they received, which comprised control, S-GO, Albendazole, and Albendazole-loaded S-GO (S-GO-Albendazole). Then, the Bax and Bcl-2 gene expression levels and the number of surviving protoscoleces in each group were determined. RESULTS: Bax gene expression increased by 121% in the 50 μg/ml concentration of the S-GO-Albendazole, while Bcl-2 gene expression decreased by 64%. Moreover, S-GO-Albendazole was approximately 18% more effective at neutralizing protoscoleces than Albendazole and 14% and 31% more effective at improving the expression of the mentioned genes, respectively (p < 0.05). In addition, the number of surviving protoscoleces after exposure to the mentioned concentration reduced by approximately 99%. CONCLUSIONS: S-GO, despite not having significant lethality on protoscoleces, significantly increased the lethality of Albendazole and, therefore, is a suitable nanocarrier. However, we recommend conducting in vivo and clinical studies to more accurately determine this nanocomplex's potential and side effects.

• Publication type
• Journal Article MeSH

Úvod: Endoskopická vakuová terapie (EVT) se stala důležitým nástrojem v léčbě defektů jícnu, jako jsou dehiscence anastomóz, píštěle a perforace. Studie prezentuje první zkušenosti s EVT v Ústřední vojenské nemocnici v Praze. Metody: Byla provedena retrospektivní analýza dat pacientů léčených EVT pro defekty jícnu v období od května 2020 do května 2024. Zahrnuti byli pacienti s dokončenou léčbou a 30denním sledováním. EVT byla zahájena v kombinaci s jinou endoskopickou/chirurgickou metodou, nebo bez nich. Primárním cílem byla úspěšnost uzávěru defektu, sekundárními cíli byly délka a charakteristika léčby, 30denní letalita a komplikace. Výsledky: Z celkem dvanácti léčených pacientů dokončilo deset pacientů (osm mužů, průměrný věk 65,2 let) 30denní sledování. V devíti z deseti případů byla příčinou defektu jícnu dehiscence po operaci jícnu, jeden pacient měl spontánní perforaci jícnu. Úspěšný uzávěr s použitím, nebo bez použití dalších endoskopických či chirurgických léčebných metod byl dosažen u osmi z deseti pacientů (80 %). Průměrná délka léčby byla 18,9 ± 11,1 dne a průměrný početEso-SPONGE na pacienta byl 5,1 ± 3,4. Léčbu pouze pomocí EVT měli dva pacienti z deseti, osm z deseti mělo kombinaci s jinou modalitou. Celková hospitalizační letalita byla 30 %, 30denní letalita 20 %. U dvou pacientů (20 %) se rozvinula stenóza v místě anastomózy a původního defektu, jiné komplikace léčby nebyly zaznamenány. Závěr: EVT se prokázala jako efektivní a bezpečná metoda v léčbě defektů jícnu, avšak její úspěšnost je často dosažena v kombinaci s jinými léčebnými modalitami, zejm. s chirurgickou přídatnou drenáží. Léčba je založena na multioborové spolupráci. Většina pacientů vyžadovala kombinovaný léčebný přístup.

Introduction: Endoscopic vacuum therapy (EVT) has become an important tool in the treatment of esophageal defects such as anastomotic leaks, fistulas and perforations. The study presents the first experience with EVT at the Military University Hospital in Prague. Methods: A retrospective analysis of data from patients treated for esophageal defects using EVT from May 2020 to May 2024 was performed. Patients with completed treatment and 30-day fol low-up were included. EVT was initiated without or in combination with another endoscopic/surgical method. The primary endpoint of the analysis was the success rate of defect closure, the secondary objectives were the duration and characteristics of treatment, 30-day lethality and complications of EVT. Results: Overall, 12 patients have been treated during the study period, of which10 patients (8 men, mean age 65.2 years) completed a 30-day fol low-up and were included into the analysis. In 9/10 cases, the cause of the esophageal defect was anastomotic leak after esophageal surgery, 1 patient had spontaneous esophageal perforation. Successful closure with or without the use of other endoscopic or surgical treatment methods was achieved in 8/10 patients (80%). The mean duration of treatment was 18.9 ± 11.1 days, and the mean number of Eso-SPONGEs used per patient was 5.1 ± 3.4. Two patients (2/10) were treated with EVT alone, 8/10 in combination with another modality. The overall hospitalization lethality was 30%, the 30-day lethality was 20%. Two patients (20%) developed stricture at the site of anastomotic defect, but we have not experienced any ther complications of EVT treatment. Conclusion: EVT has proven to be an effective and safe method for the treatment of esophageal defects, but its success is often achieved in combination with other treatment modalities, especially surgical adjunctive drainage.The treatment is based on multidisciplinary approach and most patients required combination of treatment modalitites.

• Keywords
• endoskopická vakuová terapie,
• MeSH
• Surgical Wound Dehiscence therapy   MeSH
• Esophagus * pathology   MeSH
• Gastroscopy * methods   MeSH
• Humans MeSH
• Esophageal Perforation therapy   MeSH
• Retrospective Studies MeSH
• Check Tag
• Humans MeSH

AIM: This study aimed to investigate the phenolic composition, antioxidant capacity, and toxicity of aqueous extracts of Calamintha nepeta L. leaves and their potential vasorelaxant effects. METHODS: Aqueous extracts of Calamintha nepeta L. were prepared by three extraction methods: decoction, infusion, and maceration. The total phenolic contents of the extracts and their antioxidant properties were investigated. The toxicity was evaluated by Artemia salina lethality bioassay. The decoction extract was analyzed by HPLC for its chemical profile and was also used to evaluate the vasorelaxant effect on thoracic aortic rings isolated from healthy Sprague Dawley rats. Pre-contraction was induced by phenylephrine, followed by cumulative doses of the extract (0.001 up to 250 μg/ml). RESULTS: Aqueous extracts of Calamintha nepeta L. showed noticeable radical scavenging and chelating activities. However, the decoction extract exhibited the most powerful antioxidant capacity. No toxicity was recorded for the extracts obtained by decoction and infusion. Caffeic acid, quercetin, and rosmarinic acid were the main identified compounds. Notably, the aqueous extract obtained by decoction induced significant relaxation in endothelium-intact aortic rings at lower concentrations, and at higher concentrations in denuded aortic rings. CONCLUSION: This study reveals that Calamintha nepeta L. extracted with a decoction method possesses potent antioxidant capacity and has an endothelium-dependent vasorelaxant effect.

• MeSH
• Antioxidants * pharmacology   chemistry   isolation & purification   MeSH
• Aorta, Thoracic drug effects   MeSH
• Artemia drug effects   MeSH
• Phenols pharmacology   isolation & purification   chemistry   MeSH
• Rats MeSH
• Plant Leaves chemistry   MeSH
• Rats, Sprague-Dawley * MeSH
• Plant Extracts * pharmacology   chemistry   MeSH
• Vasodilator Agents * pharmacology   chemistry   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Leucocytozoon infection has been observed to impact the reproductive ecology and physiology of avian hosts, but its influence on nestling survival remains unclear. We investigated the effect of Leucocytozoon infection intensity, determined through triplicate PCR sample analyses, on the survival of 256 boreal owl (Aegolius funereus) nestlings during an 8-yr study. Contrary to our expectations, the survival probability of boreal owl nestlings was not influenced by their Leucocytozoon infection intensity. Nestling age and Leucocytozoon infection intensity in male and female parents also did not impact nestling survival. Instead, food abundance and hatching order were the key factors influencing nestling survival. Additionally, we observed a significantly higher Leucocytozoon infection intensity in male parents compared to female parents and nestlings. We suggest a distinct division of parental roles may lead females and nestlings staying within the nest boxes (cavities) to experience lower exposure to potential vectors transmitting blood parasites than their male counterparts. Our study shows that Leucocytozoon disease may not be lethal for boreal owl chicks, exhibiting a below-average infection intensity compared to their male parents.

• MeSH
• Haemosporida physiology   MeSH
• Microsporidiosis veterinary   MeSH
• Bird Diseases * parasitology   mortality   MeSH
• Strigiformes * physiology   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH