Animals' reactions to novel objects vary not only with zoological taxa and their ecology but also in the types of presented stimuli, the context, and individual characteristics. Behavioral reactions can vary from extremely neophobic (avoiding novel objects) to extremely neophilic (intense exploration of novel objects); most often, a mixture of these behavioral patterns appears. In primates, reactions toward novel objects vary according to species, age, sex, population, and the types of objects. Most experiments in this field have used a free exploration design with food or non-food objects. Here, we tested the reactions of captive male rhesus macaques using various stimuli, motivation levels, rewards, and time limits. We found that the monkeys explored and manipulated novel objects in various contexts, with little evidence of a neophobic response; however, environment, types of stimuli, and other parameters of the test can significantly affect monkeys' reactions.

• MeSH
• chování zvířat * MeSH
• Macaca mulatta fyziologie   MeSH
• odměna MeSH
• pátrací chování * MeSH
• zvířata v ZOO MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: Propose a methodology to identify COVID-19 associated deaths using healthcare billing records and evaluate its effectiveness by comparing the results with excess mortality data from 2020 to 2022 and confirmed COVID-19 deaths. METHODS: A retrospective quantitative analysis was conducted by merging healthcare billing records with cause of death data. The term "COVID-19 associated death" was defined as any death occurring within a defined timeframe following a confirmed contact with COVID-19. This category includes individuals who died directly due to COVID-19, with COVID-19 as a contributing factor, or as an aftermath of a COVID-19 infection, as well as those who died from other causes but had previously contracted COVID-19. This broader definition provides a more comprehensive measure of excess mortality compared to the officially confirmed COVID-19 deaths attributed to the virus. RESULTS: We identified 35,399 COVID-19 associated deaths during the 3-year pandemic in Slovakia compared to 21,395 confirmed COVID-19 deaths. CONCLUSION: The identification of COVID-19 associated deaths with our methodology offers a more accurate explanation for the notably high excess mortality observed in Slovakia (31,789 deaths) during the pandemic, relative to the EU27. Given the high level of excess mortality, the officially confirmed deaths are likely underestimated, and the presented methodology provides a more precise measure of mortality. Additionally, healthcare billing records prove valuable in identifying these deaths at the individual patient level using claims data of health insurance companies, which is crucial for implementing targeted preventive measures and improving preparedness for future pandemics.

• MeSH
• COVID-19 * mortalita   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• pandemie MeSH
• příčina smrti * MeSH
• retrospektivní studie MeSH
• SARS-CoV-2 MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Slovenská republika MeSH

This review highlights recent therapeutic advances in systemic therapies for prostate cancer (PCa). RECENT FINDINGS: Progress in PCa therapeutics has been made during the past year with the approval of a vaccine therapy, second-line chemotherapy, and reported survival advantage for a CYP (17,20) lyase inhibitor in castration-resistant prostate cancer (CRPC). This report will summarize the recently reported and expected data for PCa trials including an evaluation of intermittent vs. continuous androgen deprivation therapy. Denosumab is shown to support bone mineral density in hormonal sensitive PCa patients. Targeting of androgen-dependent pathways in CRPC postchemotherapy has been shown to improve survival with the lyase inhibitor abiraterone, and lead to prostate-specific antigen and objective responses with an androgen receptor antagonist (MDV3100). However, the addition of bevacizumab to docetaxel/prednisone in treating metastatic CRPC failed to provide a survival benefit. Cabazitaxel in metastatic CRPC postdocetaxel did demonstrate a survival benefit. Provenge, an autologous dendritic cell-based vaccine, demonstrated a reduction in the risk of death in metastatic CRPC. Other immunotherapy agents, including Prostvac and ipilimumab are under investigation. We also discuss the receptor tyrosine kinase inhibitor XL184 and poly (ADP-ribose) polymerase inhibitors which are in early clinical trials. SUMMARY: Recent advances in androgen targeting, chemotherapy, immunotherapy, and other targeted therapies have led to significant improvements in the care of CRPC patients.

• MeSH
• inhibitory enzymů farmakologie   MeSH
• kastrace MeSH
• lidé MeSH
• nádory prostaty enzymologie   terapie   MeSH
• PARP inhibitory MeSH
• poly(ADP-ribosa)polymerasy MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• tyrosinkinasy antagonisté a inhibitory   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• přehledy MeSH

Spatial tasks in rodents are commonly used to study general mechanisms of cognition. We review two groups of novel spatial tasks for rodents and discuss how they can extend our understanding of mechanisms of spatial cognition. The first group represents spatial tasks in which the subject does not locomote. Locomotion influences neural activity in brain structures important for spatial cognition. The tasks belonging to the first group make it possible to study cognitive processes without the interfering impact of locomotion. The second group represents tasks in which the subject approaches or avoids a moving object. Despite this topic is intensively studied in various animal species, little attention has been paid to it in rodents. Both groups of the tasks are powerful tools for addressing novel questions about rodent cognition.

• MeSH
• bludiště - učení fyziologie   MeSH
• hipokampus fyziologie   MeSH
• kognice * fyziologie   MeSH
• krysa rodu rattus MeSH
• pohybová aktivita MeSH
• prostorové chování * fyziologie   MeSH
• psychologické testy * MeSH
• učení vyhýbat se fyziologie   MeSH
• vnímání prostoru * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

OBJECTIVE: This study was undertaken to evaluate safety and biocompatibility of a novel biodegradable polydioxanone stent in a rabbit tracheal model. Metallic and silicone stents represent standard therapeutic approaches for hollow organ stenosis, although complications have been reported repeatedly. Biodegradable stents could reduce the risks associated with this procedure while still achieving the purpose of maintaining lumen patency. METHODS: A commercially available polydioxanone suture strand with a long safety record was used to manufacture the self-expanding stents. The polydioxanone stents were then implanted bronchoscopically and under fluoroscopic guidance into the tracheas of white rabbits (N = 25). Periodic clinical examination was performed. Histopathologic examination concluded the study for the 5 experimental groups at 3, 4, 5, 10, and 15 weeks after implantation. RESULTS: There were no unexpected deaths and no stent displacements during the study. The animals remained in good condition, without stent debris expectoration. Macroscopic examination revealed that the tracheal lumen stayed open. Histologic examination showed that tracheal damage score was highest 5 weeks after stenting, including in-stent necrosis of the epithelium. Stent degradation was complete with no remnants after 10 weeks, leaving the trachea completely healed at 15 weeks after implantation. CONCLUSIONS: This animal airway model has demonstrated acceptable safety and biocompatibility of this novel biodegradable polydioxanone stent. We suggest that polydioxanone stenting be used for further clinical studies for cases in which complete stent degradation after temporary airway treatment is desirable.

• MeSH
• bronchoskopie škodlivé účinky   přístrojové vybavení   MeSH
• časové faktory MeSH
• fluoroskopie MeSH
• intervenční radiografie metody   MeSH
• králíci MeSH
• modely u zvířat MeSH
• polydioxanon MeSH
• protézy - design MeSH
• stenty MeSH
• testování materiálů MeSH
• trachea patologie   radiografie   chirurgie   MeSH
• vstřebatelné implantáty MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH

OBJECTIVES: The ASD2 (Acute Extravascular Defibrillation, Pacing, and Electrogram) study evaluated the ability to adequately sense, pace, and defibrillate patients with a novel implantable cardioverter-defibrillator (ICD) lead implanted in the substernal space. BACKGROUND: Subcutaneous ICDs are an alternative to a transvenous defibrillator system when transvenous implantation is not possible or desired. An alternative extravascular system placing a lead under the sternum has the potential to reduce defibrillation energy and the ability to deliver pacing therapies. METHODS: An investigational lead was inserted into the substernal space via a minimally invasive subxiphoid access, and a cutaneous defibrillation patch or subcutaneous active can emulator was placed on the left mid-axillary line. Pacing thresholds and extracardiac stimulation were evaluated. Up to 2 episodes of ventricular fibrillation were induced to test defibrillation efficacy. RESULTS: The substernal lead was implanted in 79 patients, with a median implantation time of 12.0 ± 9.0 min. Ventricular pacing was successful in at least 1 vector in 76 of 78 patients (97.4%), and 72 of 78 (92.3%) patients had capture in ≥1 vector with no extracardiac stimulation. A 30-J shock successfully terminated 104 of 128 episodes (81.3%) of ventricular fibrillation in 69 patients. There were 7 adverse events in 6 patients causally (n = 5) or possibly (n = 2) related to the ASD2 procedure. CONCLUSIONS: The ASD2 study demonstrated the ability to pace, sense, and defibrillate using a lead designed specifically for the substernal space.

• MeSH
• defibrilátory implantabilní * škodlivé účinky   statistika a číselné údaje   MeSH
• elektrokardiografie MeSH
• implantace protézy škodlivé účinky   metody   mortalita   statistika a číselné údaje   MeSH
• kardiostimulace umělá * škodlivé účinky   statistika a číselné údaje   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mediastinum chirurgie   MeSH
• prospektivní studie MeSH
• senioři MeSH
• srdeční arytmie terapie   MeSH
• sternum chirurgie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinická studie MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

OBJECTIVES: This first-in-human feasibility study was undertaken to translate the novel low-voltage MultiPulse Therapy (MPT) (Cardialen, Inc., Minneapolis, Minnesota), which was previously been shown to be effective in preclinical studies in terminating atrial fibrillation (AF), into clinical use. BACKGROUND: Current treatment options for AF, the most common arrhythmia in clinical practice, have limited success. Previous attempts at treating AF by using implantable devices have been limited by the painful nature of high-voltage shocks. METHODS: Forty-two patients undergoing AF ablation were recruited at 6 investigational centers worldwide. Before ablation, electrode catheters were placed in the coronary sinus, right and/or left atrium, for recording and stimulation. After the induction of AF, MPT, which consists of up to a 3-stage sequence of far- and near-field stimulation pulses of varied amplitude, duration, and interpulse timing, was delivered via temporary intracardiac leads. MPT parameters and delivery methods were iteratively optimized. RESULTS: In the 14 patients from the efficacy phase, MPT terminated 37 of 52 (71%) of AF episodes, with the lowest median energy of 0.36 J (interquartile range [IQR]: 0.14 to 1.21 J) and voltage of 42.5 V (IQR: 25 to 75 V). Overall, 38% of AF terminations occurred within 2 seconds of MPT delivery (p < 0.0001). Shorter time between AF induction and MPT predicted success of MPT in terminating AF (p < 0.001). CONCLUSIONS: MPT effectively terminated AF at voltages and energies known to be well tolerated or painless in some patients. Our results support further studies of the concept of implanted devices for early AF conversion to reduce AF burden, symptoms, and progression.

• MeSH
• elektrická defibrilace MeSH
• elektrody MeSH
• fibrilace síní * chirurgie   MeSH
• lidé MeSH
• srdeční síně MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Minnesota MeSH

BACKGROUND: Breath detection, i.e. its precise delineation in time is a crucial step in lung function data analysis as obtaining any clinically relevant index is based on the proper localization of breath ends. Current threshold or smoothing algorithms suffer from severe inaccuracy in cases of suboptimal data quality. Especially in infants, the precise analysis is of utmost importance. The key objective of our work is to design an algorithm for accurate breath detection in severely distorted data. METHODS: Flow and gas concentration data from multiple breath washout test were the input information. Based on universal physiological characteristics of the respiratory tract we designed an algorithm for breath detection. Its accuracy was tested on severely distorted data from 19 patients with different types of breathing disorders. Its performance was compared to the performance of currently used algorithms and to the breath counts estimated by human experts. RESULTS: The novel algorithm outperformed the threshold algorithms with respect to their accuracy and had similar performance to human experts. It proved to be a highly robust and efficient approach in severely distorted data. This was demonstrated on patients with different pulmonary disorders. CONCLUSION: Our newly proposed algorithm is highly robust and universal. It works accurately even on severely distorted data, where the other tested algorithms failed. It does not require any pre-set thresholds or other patient-specific inputs. Consequently, it may be used with a broad spectrum of patients. It has the potential to replace current approaches to the breath detection in pulmonary function diagnostics.

• MeSH
• algoritmy * MeSH
• diagnóza počítačová metody   MeSH
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• počítačové zpracování signálu * MeSH
• předškolní dítě MeSH
• respirační funkční testy MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

With the development of light microscopy, it is becoming increasingly easy to obtain detailed multicolor fluorescence volumetric data. The need for their appropriate visualization has become an integral part of fluorescence imaging. Virtual reality (VR) technology provides a new way of visualizing multidimensional image data or models so that the entire 3D structure can be intuitively observed, together with different object features or details on or within the object. With the need for imaging advanced volumetric data, demands for the control of virtual object properties are increasing; this happens especially for multicolor objects obtained by fluorescent microscopy. Existing solutions with universal VR controllers or software-based controllers with the need to define sufficient space for the user to manipulate data in VR are not usable in many practical applications. Therefore, we developed a custom gesture-based VR control system with a custom controller connected to the FluoRender visualization environment. A multitouch sensor disk was used for this purpose. Our control system may be a good choice for easier and more comfortable manipulation of virtual objects and their properties, especially using confocal microscopy, which is the most widely used technique for acquiring volumetric fluorescence data so far.

• MeSH
• gesta * MeSH
• konfokální mikroskopie MeSH
• software MeSH
• virtuální realita * MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Hydrazide-hydrazones have been known as scaffold with various biological activities including inhibition of acetyl- (AChE) and butyrylcholinesterase (BuChE). Cholinesterase inhibitors are mainstays of dementias' treatment. OBJECTIVE: Twenty-five iodinated hydrazide-hydrazones and their analogues were designed as potential central AChE and BuChE inhibitors. METHODS: Hydrazide-hydrazones were synthesized from 4-substituted benzohydrazides and 2-/4- hydroxy-3,5-diiodobenzaldehydes. The compounds were investigated in vitro for their potency to inhibit AChE from electric eel and BuChE from equine serum using Ellman's method. We calculated also physicochemical and structural parameters for CNS delivery. RESULTS: The derivatives exhibited a moderate dual inhibition with IC50 values ranging from 15.1-140.5 and 35.5 to 170.5 μmol.L-1 for AChE and BuChE, respectively. Generally, the compounds produced a balanced or more potent inhibition of AChE. N'-[(E)-(4-Hydroxy-3,5-diiodophenyl)methylidene]-4- nitrobenzohydrazide 2k and 4-fluoro-N'-(2-hydroxy-3,5-diiodobenzyl)benzohydrazide 3a were the most potent inhibitors of AChE and BuChE, respectively. Structure-activity relationships were established, and molecular docking studies confirmed interaction with enzymes. CONCLUSION: Many novel hydrazide-hydrazones showed lower IC50 values than rivastigmine against AChE and some of them were comparable for BuChE to this drug used for the treatment of dementia. They interact with cholinesterases via non-covalent binding into the active site. Based on the BOILEDEgg approach, the majority of the derivatives met the criteria for blood-brain-barrier permeability.

• MeSH
• acetylcholinesterasa metabolismus   MeSH
• butyrylcholinesterasa metabolismus   MeSH
• cholinesterasové inhibitory chemická syntéza   chemie   farmakologie   MeSH
• Electrophorus MeSH
• hydraziny chemická syntéza   chemie   farmakologie   MeSH
• hydrazony chemická syntéza   chemie   farmakologie   MeSH
• koně MeSH
• molekulární struktura MeSH
• simulace molekulového dockingu MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH