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A bonctermi munkavégzés speciális esetekben a megszokottól eltérő munkavédelmi kihívásokat rejthet magában. Ezen esetek közé tartozik, ha az elhunyt olyan fertőző betegségben szenvedett, vagy olyan vegyi, esetleg sugárzóanyaggal szennyeződött halálát megelőzően, amely a post mortem vizsgálati folyamat során egészségügyi kockázatot jelent a végrehajtó állománynak. A kockázatok minimalizálása, valamint a környezet épsége, a személyzet egészségének védelme érdekében ilyenkor mind a boncterem infrastrukturális elemeihez sorolható berendezések alkalmazásával, mind pedig egyéni védőfelszerelések használatával kell a szükséges post mortem eljárásokat kivitelezni. Jelen tanulmányban a légzésvédelem lehetőségeit mutatom be és tekintem át, a fontosabb bonctermi veszélyek tükrében.

This study investigated the potential adaptive aspects of mind wandering (MW), a common phenomenon in which individuals shift their attention from external tasks to internal thoughts. Despite the well-documented negative effects of MW on cognitive performance and links to psychiatric conditions, there is a scarcity of direct evidence of its potential benefits. In our preregistered study, we simultaneously assessed visuomotor task performance as well as the capability to extract probabilistic information from the environment while assessing task focus (on-task vs. MW). We found that MW facilitated the extraction of hidden, but predictable patterns from a stream of visual inputs. Moreover, MW influenced speed/accuracy tradeoff by shifting participants towards a faster but less accurate response style. These findings suggest that MW may have functional relevance in human cognition and everyday functioning by shaping behavior and predictive processes. Overall, our results highlight the importance of considering the adaptive aspects of MW, and its potential to enhance cognitive abilities.

Purpose We aimed at examining both the incidence and extent of different lung perfusion abnormalities as well as the relationship between them on Tc-99m macroaggregated albumin (MAA) perfusion-only SPECT/CT scans in COVID-19 patients. Methods Ninety-one patients (71.4 ± 13.9 years; range: 29–98 years, median age: 74 years; 45 female and 46 male) with confirmed SARS-CoV-2 virus infection were included in this retrospective study. After performing perfusion-only Tc-99m MAA SPECT/CT scans, visual, semi-quantitative assessment of the subsequent perfusion abnormalities was carried out: mismatch lesions (MM; activity defects on SPECT images identical to apparently healthy parenchyma on CT images), matched lesions (MA; activity defects with corresponding parenchymal lesions on CT scans), and reverse mismatch lesions (RM; parenchymal lesions with preserved or increased tracer uptake). Lesion-based and patient-based analysis were performed to evaluate the extent, severity, and incidence of each perfusion abnormality. Statistical tests were applied to investigate the association between the experienced perfusion impairments. Results Moderately severe parenchymal lesions were detected in 87 (95.6%) patients. Although, 50 (54.95%) patients were depicted to have MM lesions, the whole patient cohort was mildly affected by this abnormality. MA lesions of average moderate severity were seen in most of the patients (89.01%). In 65 (71.43%) patients RM lesions were found with mild severity on average. Positive association was detected between total CT score and total RM score and between total CT score and total MA score. Significantly higher total CT scores were experienced in the subgroup, where RM lesions were present. Conclusions Heterogeneous perfusion abnormalities were found in most of COVID-19 patients: parenchymal lesions with normal, decreased or increased perfusion and perfusion defects in healthy lung areas. These phenomena may be explained by the failure of the hypoxic pulmonary vasoconstriction mechanism and presence of pulmonary thrombosis and embolism.

A katasztrófák világszerte emelkedő esetszámban állítják kihívás elé az általuk érintett régiókat, nemzeteket. A globalizációnak, a bővülő ipari-technológiai szektornak, valamint a sugárzó anyagok széles körű, nukleáris létesítményekben történő alkalmazását is felölelő felhasználásának köszönhetően az esetlegesen bekövetkező káresemények vonatkozásában veszélyes vegyi, biológiai, radiológiai és nukleáris ágensek is fontos szerephez juthatnak. Jelen tanulmány célja, hogy halálos áldozatokkal is járó, múltban lezajlott vegyi, biológiai, radiológiai és nukleáris katasztrófák példáján bemutassa ezek mind az élettelen, mind az élő környezetre gyakorolt károsító képességét, egyúttal feltárva és összegezve komplex hatásmechanizmusaikat.

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Background Comparison of the performance of a conventional, Anger-system, general-purpose SPECT/CT (AnyScan SC FLEX) vs. an Anger-system dedicated cardiac SPECT (CardioC) camera for gated myocardial perfusion imaging. Method Fifty patients were enrolled into the study. Of these, myocardial perfusion scintigraphy with 450 MBq SestaMIBI (Mediradiopharma) was performed after dipyridamole stress testing in 43, and at rest in the remaining 7 patients. ECG-gated SPECT acquisition was undertaken with both cameras, with a scanning time of 16 minutes. Within 45 to 60 minutes of the intravenous administration of the radiopharmaceutical, imaging was done first with the CardioC and then – after 30 minutes on average – with the AnyScan SC FLEX camera. The sensitivity of the systems (uptake of the radiotracer by the heart), severity of perfusion defects (SS), and parameters of left ventricular volume and wall motion (EF, EDV, ESV, SV, and cardiac mass) were determined quantitatively with both cameras. All these indices were then compared and the results were subjected to statistical analysis. Results Sensitivity (the scintillation counts recorded within the ROI cardiac projection) was 17.8% (median) higher with the AnyScan FLEX than with the CardioC camera (p 0.1). The EF obtained after attenuation correction was significantly lower than without AC. The volume estimates significantly depended on the camera and reconstruction method (p

Rationale Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and interaction and restricted, repetitive behaviors. The unmet medical need in ASD is considerable since there is no approved pharmacotherapy for the treatment of these deficits in social communication, interaction, and behavior. Cariprazine, a dopamine D3-preferring D3/D2 receptor partial agonist, is already approved for the treatment of schizophrenia and bipolar I disorder in adults; investigation in patients with ASD is warranted. Objectives The aim of this study was to investigate the effects of cariprazine, compared with risperidone and aripiprazole, in the rat prenatal valporic acid (VPA) exposure model on behavioral endpoints representing the core and associated symptoms of ASD. Methods To induce the ASD model, time-mated Wistar rat dams were treated with VPA during pregnancy. Male offspring were assigned to groups and studied in a behavioral test battery at different ages, employing social play, open field, social approach-avoidance, and social recognition memory tests. Animals were dosed orally, once a day for 8 days, with test compounds (cariprazine, risperidone, aripiprazole) or vehicle before behavioral assessment. Results Cariprazine showed dose-dependent efficacy on all behavioral endpoints. In the social play paradigm, only cariprazine was effective. On the remaining behavioral endpoints, including the reversal of hyperactivity, risperidone and aripiprazole displayed similar efficacy to cariprazine. Conclusions In the present study, cariprazine effectively reversed core behavioral deficits and hyperactivity present in juvenile and young adult autistic-like rats. These findings indicate that cariprazine may be useful in the treatment of ASD symptoms.

The NMR pulse sequence design strategy of NORD (NO Relaxation Delay) is extended to design of two new three-module experiments, NORD {HMBC}-{HSQC-TOCSY}-{TOCSY} and NORD {HMBC}-{2BOB}-{TOCSY}, each delivering four spectra - HMBC, HSQC, TOCSY, and either HSQC-TOCSY or H2BC. Compared to individual recording of these spectra particularly the sensitivity of the least sensitive module, HMBC, is enhanced by designing the homonuclear TOCSY module to allow buildup of magnetization pertinent to HMBC during its execution. Effectively, the sensitivity of the heteronuclear modules is boosted at the expense of the inherently much higher TOCSY sensitivity, thus resulting in a significant saving in spectrometer time.

Background: Cariprazine is a dopamine D3-preferring D3/D2 receptor partial agonist compound recently introduced to treat schizophrenia and bipolar disorder. Although cariprazine is clinically classified as a low-somnolence drug, to date no detailed polysomnographic study is available on its effect on sleep. Aims: This study examined the acute systemic effects of cariprazine on the rat sleep architecture and electroencephalography spectral power. Methods: Sprague Dawley rats were recorded during their normal sleep period for four hours, and their sleep stages were classified. Results: Cariprazine (0.3 mg/kg i.p.) reduced the time spent in rapid eye movement (REM) sleep and increased REM latency. This dose of cariprazine decreased the gamma (40–80 Hz) band frequency oscillations and increased the theta (4–9 Hz) and alpha (9–15 Hz) frequencies during the wake periods but not during slow-wave sleep. The 0.03 mg/kg dose of cariprazine only increased the alpha power during the wake periods, while the 0.003 mg/kg dose was without any effect. Conclusion: Taken together, the present results suggest that the REM-suppressing effect of cariprazine may be related to its effectiveness in improving depressive symptoms, as various drugs with similar REM-reducing properties effectively treat the depressive state, whereas the gamma power-reducing effect of cariprazine may be indicative of its efficacy in schizophrenia or mania, as similar effects have been observed with other D2 and 5-HT2 receptor antagonist drugs. These data contribute to our understanding of the complex mechanism of action that may stand behind the clinical efficacy of cariprazine.

Background N-methyl-D-aspartate (NMDA) receptor activation requires the binding of a co-agonist on the glycine-binding site. D-serine is the main endogenous co-agonist of NMDA receptors, and its availability significantly depends on the activity of the metabolic enzyme D-amino acid oxidase (DAAO). Inhibition of DAAO increases the brain levels of D-serine and modulates a variety of physiological functions, including cognitive behavior. Methods Here, we examined the effects of a novel 4-hydroxypyridazin-3(2H)-one derivative DAAO inhibitor, Compound 30 (CPD30), on passive avoidance learning and on neuronal firing activity in rats. Results D-serine administration was applied as reference, which increased cognitive performance and enhanced hippocampal firing activity and responsiveness to NMDA after both local and systemic application. Similarly to D-serine, CPD30 (0.1 mg/kg) effectively reversed MK-801–induced memory impairment in the passive avoidance test. Furthermore, local iontophoretic application of CPD30 in the vicinity of hippocampal pyramidal neurons significantly increased firing rate and enhanced their responses to locally applied NMDA. CPD30 also enhanced hippocampal firing activity after systemic administration. In 0.1- to 1.0-mg/kg doses, CPD30 increased spontaneous and NMDA-evoked firing activity of the neurons. Effects of CPD30 on NMDA responsiveness emerged faster (at 10 minutes post-injection) when a 1.0-mg/kg dose was applied compared with the onset of the effects of 0.1 mg/kg CPD30 (at 30 minutes post-injection). Conclusions The present results confirm that the inhibition of DAAO enzyme is an effective strategy for cognitive enhancement. Our findings further facilitate the understanding of the cellular mechanisms underlying the behavioral effects of DAAO inhibition in the mammalian brain.

Background: Cariprazine, the novel dopamine (DA) D3-preferring D3/D2 and serotonin (5-HT)1A receptor partial agonist, has activity as an adjunctive therapy in major depressive disorder (MDD). Aims: This study aims to investigate the effects of chronic cariprazine administration in combination with the selective serotonin reuptake inhibitor escitalopram on the activity of monoaminergic systems. Methods: Rats received cariprazine alone and in adjunct to escitalopram for 2 and 14 days and the firing activity of dorsal raphe nucleus 5-HT, locus coeruleus norepinephrine (NE) and ventral tegmental area DA neurons was assessed. 5-HT and NE neurotransmission in hippocampus pyramidal neurons was evaluated by assessing tonic activation of their 5-HT1A, and α1- and α2-adrenergic receptors, using their selective antagonists. Results: Two and 14-day cariprazine regimens increased the firing rate of NE, but not 5-HT and DA neurons. Addition of cariprazine to escitalopram reversed the inhibitory effect of escitalopram on NE but not 5-HT and DA neurons. In the hippocampus, there was an increase in neurotransmission at 5-HT1A receptors in cariprazine-treated rats, but no change in overall NE transmission by either regimen. Conclusion: Cariprazine increased NE neuronal firing and reversed the escitalopram-induced inhibition of these neurons. Despite a lack of effect on 5-HT neuronal firing activity, there was an increase in tonic activation of hippocampus 5-HT1A receptors by cariprazine alone but not with the combination. These effects provide a possible rationale for the clinical efficacy of cariprazine as an adjunctive strategy in patients with MDD.

Absztrakt: A 2019. év végén, elsőként a kínai Vuhan városában megjelenő, SARS-CoV-2 béta-koronavírus okozta járványt 2020. március 11-én világjárvánnyá minősítette az Egészségügyi Világszervezet. Magyarországon 2020. március 4-én jelentették az első megerősített COVID–19-esetet, s március 15-én vesztette életét az első, új típusú koronavírussal fertőzött beteg. Az elhunyt halálának pillanatában nem állt rendelkezésre központi, egységes irányelv, mely tisztázta volna a szükséges óvintézkedések körét, illetve egyértelmű leírást nyújtott volna a tetem biztonságos kezeléséhez. A halottak patológiai osztályra való szállítása, tárolása, esetleges boncolása, majd végső nyughelyre helyezése, ezek mikéntje számtalan kérdést vet fel. A fertőző betegségekre, illetve a halottakkal kapcsolatos teendőkre vonatkozó hatályos jogszabályok nem tartalmaznak elégséges információt egy COVID–19-fertőzött beteg halála utáni feladatok végrehajtását illetően. Az országos tisztifőorvos március 19-én felfüggesztette a boncolások elvégzését, a törvényszéki boncolások kivételével, azonban a szállítás, tárolás továbbra is problémát jelent. Bár 2020. március 21-én az Emberi Erőforrások Minisztériuma Egészségügyi Szakmai Kollégiumának Patológia Tagozata kiadott egy hivatalos eljárásrendet, az ebben foglalt ajánlások a szakirodalom szűkebb spektrumát reprezentálják, több helyütt kiegészítésre szorulnak. Sajnálatosan a nemzetközi szakirodalomban szintén – a fontosságához mérten – alulreprezentált a post mortem eljárásokra vonatkozó adat. További problémát jelent, hogy a járványok okozta krízishelyzetek áldozatainak kezelésére írt cikkekben a fellelhető algoritmusok a magyarországitól eltérő jogi környezet mellett eltérő szervezeti és erőforrásbeli lehetőségekkel számolnak, mely körülmények a hazai adaptálást jelentősen nehezítik. Cikkünkben a szakirodalmi összefoglaláson túl a COVID–19-gyanús, valószínűsített és megerősített páciensek kezelésében részt vevő egészségügyi dolgozók, valamint a potenciálisan érintett patológiai osztályok számára kivitelezhető, az ellátók biztonságát növelő javaslatokat, ajánlásokat fogalmazunk meg.* Orv Hetil. 2020; 161(17): 713–722.

Introduction As of early 2022, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic still represents a worldwide medical emergency situation. The ongoing vaccination programs can slow down the spread of the virus; however, from time to time, the newly emerging variants of concern and antivaccination movements carry the possibility for the disease to remain in our daily lives. After the appearance of SARS-CoV-2, there was scholarly debate whether the virus was of natural origin, or it emerged from a laboratory, some even thinking the agent’s potential biological weapon properties suggest the latter scenario. Later, the bioweapon theory was dismissed by the majority of experts, but the question remains that despite its natural origin, how potent a biological weapon the SARS-CoV-2 virus can become over time. Materials and Methods Based on 12 bioweapon threat assessment criteria already published in 2018, we performed a literature search and review, focusing on relevant potential bioweapon properties of the virus SARS-CoV-2. Instead of utilizing a survey among experts, we tried to qualify and quantify characteristics according to the available data found in peer-reviewed papers. We also identified other key elements not mentioned in the original 12 bioweapon criteria, which can play an important role in assessing future biological weapons. Results According to the international literature we analyzed, SARS-CoV-2 is a moderately infectious agent (ID50 estimated between 100 and 1,000), with high infection-to-disease ratio (35%–45% rate of asymptomatic infected) and medium incubation period (1–34 days, mean 6–7 days). Its morbidity and mortality rate can be categorized as medium (high morbidity rate with significant mortality rate). It can be easily produced in large quantities, has high aerosol stability, and has moderate environmental stability. Based on laboratory experiments and statistical model analysis, it can form and is contagious with droplet nuclei, and with spray technique utilization, it could be weaponized effectively. Several prophylactic countermeasures are available in the form of vaccines; however, specific therapeutic options are much more limited. In connection with the original assessment criteria, the SARS-CoV-2 only achieved a “0” score on the ease of detection because of readily available, relatively sensitive, and specific rapid antigen tests. Based on the pandemic experience, we also propose three new assessment categories: one that establishes a mean to measure the necessary quarantine restrictions related to a biological agent, another one that can represent the personal protective equipment required to work safely with a particular agent, and a third one that quantifies the overall disruptive capability, based on previous real-life experiences. These factors could further specify the threat level related to potential biological weapons. Conclusions Our results show that the virus can become a potent bioweapon candidate in the future, achieving a total score of 24 out of 36 on the original 12 criteria. The SARS-CoV-2 has already proven its pandemic generating potential and, despite worldwide efforts, still remains an imminent threat. In order to be prepared for the future possibility of the virus arising as a bioweapon, we must remain cautious and take the necessary countermeasures.

Bioleaching of mineral phases plays a crucial role in the mobility and availability of various elements, including selenium. Therefore, the leachability of selenium associated with the surfaces of ferric and manganese oxides and oxyhydroxides, the prevailing components of natural geochemical barriers, has been studied in the presence of filamentous fungus. Both geoactive phases were exposed to selenate and subsequently to growing fungus Aspergillus niger for three weeks. This common soil fungus has shown exceptional ability to alter the distribution and mobility of selenium in the presence of both solid phases. The fungus initiated the extensive bioextraction of selenium from the surfaces of amorphous ferric oxyhydroxides, while the hausmannite (Mn3O4) was highly susceptible to biodeterioration in the presence of selenium. This resulted in specific outcomes regarding the selenium, iron, and manganese uptake by fungus and residual selenium concentrations in mineral phases as well. The adverse effects of bioleaching on fungal growth are also discussed. Web of Science 7 10 art. no. 810

Cariprazine is an approved antipsychotic and antidepressant which is a dopamine (DA) D3-preferring D3/D2 receptor partial agonist, serotonin (5-HT) 5-HT1A receptor partial agonist, and 5-HT2B and 5-HT2A receptor antagonist, a profile unique for atypical antipsychotic drugs. The purpose of this study was to clarify the effects of cariprazine and selective D3 receptor ligands on neurotransmitter efflux in the rat nucleus accumbens (NAC) and ventral hippocampus (HIP), brain regions important for reality testing, rewarded behavior, and cognition. In vivo microdialysis was performed in awake, freely moving rats after administration of cariprazine; (+)-PD-128907 [(4aR,10bR)-3,4a,4,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin-9-ol hydrochloride], a D3 receptor-preferring agonist; and SB-277011A [trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolininecarboxamide hydrochloride], a selective D3 receptor antagonist, alone or combined, and extracellular levels of multiple neurotransmitters and metabolites were measured in the NAC and HIP by ultraperformance liquid chromatography with tandem mass spectrometry. Cariprazine increased DA, norepinephrine (NE), and 5-HT efflux in both regions, whereas it increased glycine (Gly) and glutamate efflux only in the NAC and efflux of DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) only in the HIP. Similarly, SB-277011A increased DA, NE, DOPAC, and HVA, but not 5-HT, efflux in the NAC and HIP, and acetylcholine efflux in the HIP. Most of these effects of cariprazine and SB-277011A were fully or partially attenuated by the D3 receptor agonist (+)-PD-128907, suggesting these effects of cariprazine are related to its D3 receptor partial agonism, and that this mechanism, leading to diminished stimulation of D3 receptors, may contribute to its efficacy in both schizophrenia and bipolar disorder. The possible role of Gly in the action of cariprazine is discussed. SIGNIFICANCE STATEMENT: The novel atypical antipsychotic drug cariprazine increased nucleus accumbens and hippocampal neurotransmitter efflux, similar to the actions of the D3 receptor antagonist SB-277011A [trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolininecarboxamide hydrochloride]. The D3 receptor-preferring agonist (+)-PD-128907 [(4aR, 10bR)-3,4a,4,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin-9-ol hydrochloride], diminished the effects of both compounds on neurotransmitter efflux in both regions. These results suggested D3 receptor partial agonist activity of cariprazine, producing functional antagonism, may contribute to its efficacy in schizophrenia and bipolar disorder.

Introduction Cariprazine, a dopamine D3-preferring D3/D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist, has two major human metabolites, desmethyl-cariprazine (DCAR) and didesmethyl-cariprazine (DDCAR). The metabolite pharmacology was profiled to understand the contribution to cariprazine efficacy. Methods In vitro receptor binding and functional assays, electrophysiology, animal models, microdialysis, and kinetic-metabolism approaches were used to characterize the pharmacology of DCAR and DDCAR. Results Similar to cariprazine, both metabolites showed high affinity for human D3, D2L, 5-HT1A, 5-HT2A, and 5-HT2B receptors, albeit with higher selectivity than cariprazine for D3 versus D2 receptors. In [35S]GTPγS binding assays, cariprazine and DDCAR were antagonists in membranes from rat striatum and from cells expressing human D2 and D3 receptors, and were partial agonists in membranes from rat hippocampus. In cAMP signaling assays, cariprazine, DCAR, and DDCAR acted as partial agonists at D2 and D3 receptors; cariprazine and DDCAR were full agonists, whereas DCAR was a partial agonist at 5-HT1A receptors. Cariprazine, DCAR, and DDCAR were pure antagonists at human 5-HT2B receptors. Cariprazine and DDCAR increased rat striatal dopamine and reduced cortical serotonin turnover. Cariprazine and DDCAR showed similar in vivo D3 receptor occupancy in rat brain; however, cariprazine was more potent for D2 receptor occupancy. Both cariprazine and DDCAR dose-dependently but partially suppressed the spontaneous activity of midbrain dopaminergic neurons in rats, with the parent compound being more potent but shorter acting than its metabolite. Consistent with the D2 receptor occupancy profile, DDCAR was 3- to 10-fold less potent than cariprazine in rodent models of antipsychotic-like activity. Following acute cariprazine administration, DDCAR was detected in the rodent brain but at much lower levels than cariprazine. Conclusion Overall, in vitro and in vivo pharmacological profiles of DCAR and DDCAR demonstrated high similarity with cariprazine, suggesting that the major metabolites of cariprazine contribute significantly to its clinical efficacy.

Treating patients with DLBCL remains a challenge, as the response to first-line immunochemotherapy is somewhat unpredictable. The International Prognostic Index (IPI) is one of the most widely used methods for assessing prognosis. Interim PET/CT (iPET/CT) can play an important role in the early identification of 'non-responder' patients before the end of treatment examination. In this study, we retrospectively analyzed 104 newly diagnosed DLBCL patients treated with R-CHOP-like regimens who underwent iPET/CT imaging during therapy. There was a significant difference in 2-year OS between patients with negative iPET/CT and those with positive iPET/CT. Patients who had positive iPET/CT showed inferior 2-year PFS compared to those with negative iPET/CT. According to IPI, there was a statistically significant difference in 2-year OS and PFS between patients in the lower and higher risk groups. However, these patients can be further subdivided according to iPET/CT. The iPET/CT results in the present study clearly separate good- and poor-prognosis patients according to differences in 2-year OS, both in the lower and higher IPI risk groups. These results are in agreement with those of previous studies that demonstrated that iPET/CT has high negative predictive value, clearly identifying good-prognosis patients even within the poor-prognosis IPI group.

Ferric oxyhydroxides are natural scavengers of antimony, thus, they contribute significantly to antimony immobilization in soils and sediments. Recent studies, however, usually omit microbial influence on geochemically stable antimony-ferric oxyhydroxide association. Therefore, we have evaluated fungal contribution to antimony mobility during static cultivation of common soil fungus Aspergillus niger in presence of ferric oxyhydroxides. Our results indicate distinguished effect of fungus on antimony distribution at two different antimony concentrations that were used for antimony pre-adsorbtion onto ferric oxyhydroxides prior to the inoculation. Approximately 36% of antimony was bioextracted by fungus from antimony bearing ferric oxyhydroxide after 14-day cultivation when the 8.9 mg·L−1 antimony concentration was used for pre-adsorption. However, no statistically significant change of antimony content in ferric oxyhydroxides was observed after cultivation when initial 48 mg·L−1 antimony concentration was used for pre-adsorption. As Mossbauer spectroscopy and XRD analysis indicated, nanosized akageneite, goethite, and lepidocrocite enhanced their crystallinity during cultivation, while hematite was identified only after the cultivation. Nevertheless, presence of ferric oxyhydroxides at both initial concentrations enabled transformation of antimony into volatile derivatives, and almost 9.5% of antimony was biovolatilized after cultivation. These results contribute significantly to environmental geochemistry of antimony-ferric oxyhydroxides association and highlight the importance of microbial activity in relation to ferric component of natural geochemical barriers.

Cariprazine, the novel dopamine (DA) DThis study aims to investigate the effects of chronic cariprazine administration in combination with the selective serotonin reuptake inhibitor escitalopram on the activity of monoaminergic systems.Rats received cariprazine alone and in adjunct to escitalopram for 2 and 14 days and the firing activity of dorsal raphe nucleus 5-HT, locus coeruleus norepinephrine (NE) and ventral tegmental area DA neurons was assessed. 5-HT and NE neurotransmission in hippocampus pyramidal neurons was evaluated by assessing tonic activation of their 5-HTTwo and 14-day cariprazine regimens increased the firing rate of NE, but not 5-HT and DA neurons. Addition of cariprazine to escitalopram reversed the inhibitory effect of escitalopram on NE but not 5-HT and DA neurons. In the hippocampus, there was an increase in neurotransmission at 5-HTCariprazine increased NE neuronal firing and reversed the escitalopram-induced inhibition of these neurons. Despite a lack of effect on 5-HT neuronal firing activity, there was an increase in tonic activation of hippocampus 5-HT

The outbreak caused by SARS-CoV-2 beta-coronavirus, first identified in Wuhan, China, was declared a pandemic by the World Health Organization on 11th March, 2020. In Hungary, the first confirmed COVID-19 case was reported on 4th March, 2020, and on 15th March, the first fatality related to the infection was announced. At the moment of the latter event, there was no central, standardized guideline, which could explain the necessary precautions, and provide an unequivocal description on how to handle the dead body. The procedure of transportation, storage, occurent autopsy or final disposition of the deceased raise a lot of questions, especially on how to carry out these tasks. Legislation related to infectious diseases and decedent management in general do not provide enough information on how to perform duties in a COVID-19 fatality case. The chief medical officer suspended the execution of autopsies, except in cases of unnatural death, since 19th March, however, the transportation and storage of fatalities can still be a problem. The Department of Pathology of the Healthcare Professional College of the Ministry of Human capacities published a procedure on recommended post-mortem duties on 21st March, but the suggested protocols only represent a narrow spectrum of international recommendations. Therefore supplementation may be necessary. Sadly, post-mortem protocols, in spite of their importance, are also underrepresented in the international literature. A further problem, wich makes adoptability difficult, is that available foreign guidelines and algorithms are optimized for different legislation, and organisations, resources not available in our country. In this article, besides providing a summary of literature, we would also like to make practical recommendations which may increase the safety of healthcare providers participating in the treatment or pathological duties with COVID-19 suspected, probable and confirmed cases. Orv Hetil. 2020; 161(17): 713–722.A 2019. év végén, elsőként a kínai Vuhan városában megjelenő, SARS-CoV-2 béta-koronavírus okozta járványt 2020. március 11-én világjárvánnyá minősítette az Egészségügyi Világszervezet. Magyarországon 2020. március 4-én jelentették az első megerősített COVID–19-esetet, s március 15-én vesztette életét az első, új típusú koronavírussal fertőzött beteg. Az elhunyt halálának pillanatában nem állt rendelkezésre központi, egységes irányelv, mely tisztázta volna a szükséges óvintézkedések körét, illetve egyértelmű leírást nyújtott volna a tetem biztonságos kezeléséhez. A halottak patológiai osztályra való szállítása, tárolása, esetleges boncolása, majd végső nyughelyre helyezése, ezek mikéntje számtalan kérdést vet fel. A fertőző betegségekre, illetve a halottakkal kapcsolatos teendőkre vonatkozó hatályos jogszabályok nem tartalmaznak elégséges információt egy COVID–19-fertőzött beteg halála utáni feladatok végrehajtását illetően. Az országos tisztifőorvos március 19-én felfüggesztette a boncolások elvégzését, a törvényszéki boncolások kivételével, azonban a szállítás, tárolás továbbra is problémát jelent. Bár 2020. március 21-én az Emberi Erőforrások Minisztériuma Egészségügyi Szakmai Kollégiumának Patológia Tagozata kiadott egy hivatalos eljárásrendet, az ebben foglalt ajánlások a szakirodalom szűkebb spektrumát reprezentálják, több helyütt kiegészítésre szorulnak. Sajnálatosan a nemzetközi szakirodalomban szintén – a fontosságához mérten – alulreprezentált a post mortem eljárásokra vonatkozó adat. További problémát jelent, hogy a járványok okozta krízishelyzetek áldozatainak kezelésére írt cikkekben a fellelhető algoritmusok a magyarországitól eltérő jogi környezet mellett eltérő szervezeti és erőforrásbeli lehetőségekkel számolnak, mely körülmények a hazai adaptálást jelentősen nehezítik. Cikkünkben a szakirodalmi összefoglaláson túl a COVID–19-gyanús, valószínűsített és megerősített páciensek kezelésében részt vevő egészségügyi dolgozók, valamint a potenciálisan érintett patológiai osztályok számára kivitelezhető, az ellátók biztonságát növelő javaslatokat, ajánlásokat fogalmazunk meg.* Orv Hetil. 2020; 161(17): 713–722.

The aim of this work was to evaluate the transformation of manganese oxide (hausmannite) by microscopic filamentous fungus Aspergillus niger and the effects of the transformation on mobility and bioavailability of arsenic. Our results showed that the A. niger strain CBS 140837 greatly affected the stability of hausmannite and induced its transformation into biogenic crystals of manganese oxalates&mdash, falottaite and lindbergite. The transformation was enabled by fungal acidolysis of hausmannite and subsequent release of manganese ions into the culture medium. While almost 45% of manganese was bioextracted, the arsenic content in manganese precipitates increased throughout the 25-day static cultivation of fungus. This significantly decreased the bioavailability of arsenic for the fungus. These results highlight the unique A. niger strain&rsquo, s ability to act as an active geochemical factor via its ability to acidify its environment and to induce formation of biogenic minerals. This affects not only the manganese speciation, but also bioaccumulation of potentially toxic metals and metalloids associated with manganese oxides, including arsenic.

Cariprazine, an orally active and potent dopamine D3–preferring D3/D2 receptor partial agonist, is approved to treat adults with schizophrenia (in the United States and Europe) and manic or mixed episodes associated with bipolar I disorder (in the United States). Cariprazine also displays partial agonism at serotonin [5-hydroxytryptamine (5-HT)] 5-HT1A receptors and antagonism at 5-HT2A and 5-HT2B receptors in vitro. The study objective was to determine whether cariprazine leads to functional alterations of monoamine systems in vivo via electrophysiological recordings from anesthetized rats. Dorsal raphe nucleus (DRN), locus coeruleus (LC), and hippocampus pyramidal neurons were recorded, and cariprazine was administered systemically or locally through iontophoresis. In the DRN, cariprazine completely inhibited the firing activity of 5-HT neurons, which was fully reversed by the 5-HT1A receptor antagonist, WAY100635. In the LC, cariprazine reversed the inhibitory effect of the preferential 5-HT2A receptor agonist, 2,5-dimethoxy-4-iodoamphetamine, on norepinephrine (NE) neurons (ED50 = 66 µg/kg) but did not block the inhibitory effect of the α2-adrenergic receptor agonist, clonidine. Cariprazine, iontophorized into the hippocampus, diminished pyramidal neuronal firing through activation of 5-HT1A receptors, while its concomitant administration did not dampen the suppressant effect of 5-HT. These results indicate that, in vivo, cariprazine acted as a 5-HT1A autoreceptor agonist in the DRN, a 5-HT2A receptor antagonist in modulating the firing activity of LC NE neurons, and a full agonist at 5-HT1A receptors mediating the electrophysiological effect of 5-HT on pyramidal neurons. The modulatory actions of cariprazine on these monoaminergic systems may contribute to its therapeutic effectiveness in patients with depressive episodes.

Absztrakt: Bevezetes: A primer kozponti idegrendszeri diffuz nagy B-sejtes lymphoma ritka betegseg. Az első vonalbeli autolog transzplantacioval elert biztato eredmenyek ellenere a relabalo betegek...

Aim Cariprazine, a dopamine D3 -preferring D3 /D2 receptor partial agonist, is FDA approved for the treatment of schizophrenia and acute manic or mixed episodes of bipolar disorder. This study used in vivo electrophysiological techniques in anesthetized rats to determine cariprazine's effect on dopaminergic cell activity in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Methods Extracellular recordings of individual dopaminergic neurons were performed after oral or intravenous administration of cariprazine, the D3 receptor antagonist SB 277011A, the D2 receptor antagonist L741,626, and/or the D3 receptor agonist PD 128,907. Results Acute oral treatment with cariprazine significantly increased and chronic cariprazine significantly decreased the number of spontaneously firing dopaminergic neurons in the VTA, but not in the SNc. Intravenous administration of cariprazine partially but significantly inhibited dopaminergic neuronal firing in both regions, which was prevented by L741,626 but not SB 277011A. In both VTA and SNc, cariprazine, SB 277011A, and L741,626 significantly antagonized the suppression of dopamine cell firing elicited by PD 128,907. Conclusions Cariprazine significantly modulates the number of spontaneously active VTA dopamine neurons and moderately suppresses midbrain dopamine neuronal activity. The contribution of dopamine D2 receptors to cariprazine's in vivo effects is prevalent and that of D3 receptors is less apparent.

This work aimed to examine the bioleaching of manganese oxides at various oxidation states (MnO, MnO·Mn2O3, Mn2O3 and MnO2) by a strain of the filamentous fungus Aspergillus niger, a frequent soil representative. Our results showed that the fungus effectively disintegrated the crystal structure of selected mineral manganese phases. Thereby, during a 31-day static incubation of oxides in the presence of fungus, manganese was bioextracted into the culture medium and, in some cases, transformed into a new biogenic mineral. The latter resulted from the precipitation of extracted manganese with biogenic oxalate. The Mn(II,III)-oxide was the most susceptible to fungal biodeterioration, and up to 26% of the manganese content in oxide was extracted by the fungus into the medium. The detected variabilities in biogenic oxalate and gluconate accumulation in the medium are also discussed regarding the fungal sensitivity to manganese. These suggest an alternative pathway of manganese oxides’ biodeterioration via a reductive dissolution. There, the oxalate metabolites are consumed as the reductive agents. Our results highlight the significance of fungal activity in manganese mobilization and transformation. The soil fungi should be considered an important geoactive agent that affects the stability of natural geochemical barriers.

Natural ferric ochres that precipitate in streambeds at abandoned mining sites are natural scavengers of various metals and metalloids. Thus, their chemical and structural modification via microbial activity should be considered in evaluation of the risks emerging from probable spread of contamination at mining sites. Our results highlight the role of various aspergilli strains in this process via production of acidic metabolites that affect mobility and bioavailability of coprecipitated contaminants. The Mössbauer analysis revealed subtle structural changes of iron in ochres, while the elemental analysis of non-dissolved residues of ochres that were exposed to filamentous fungi suggest coinciding bioextraction of arsenic and antimony with extensive iron mobilisation. However, the zinc bioextraction by filamentous fungi is less likely dependent on iron leaching from ferric ochres. The strain specific bioextraction efficiency and subsequent bioaccumulation of mobilised metals resulted in distinct tolerance responses among the studied soil fungal strains. However, regardless the burden of bioextracted metal(loid)s on its activity, the Aspergillus niger strain has shown remarkable capability to decrease pH of its environment and, thus, bioextract significant and environmentally relevant amounts of potentially toxic elements from the natural ochres.

Cariprazine is an approved antipsychotic and antidepressant which is a dopamine (DA) D

Synthesis of tetravalent thio- and selenogalactopyranoside-containing glycoclusters using azide-alkyne click strategy is presented. Prepared compounds are potential ligands of Pseudomonas aeruginosa lectin PA-IL. P. aeruginosa is an opportunistic human pathogen associated with cystic fibrosis, and PA-IL is one of its virulence factors. The interactions of PA-IL and tetravalent glycoconjugates were investigated using hemagglutination inhibition assay and compared with mono- and divalent galactosides (propargyl 1-thio- and 1-seleno-&beta, d-galactopyranoside, digalactosyl diselenide and digalactosyl disulfide). The lectin-carbohydrate interactions were also studied by saturation transfer difference NMR technique. Both thio- and seleno-tetravalent glycoconjugates were able to inhibit PA-IL significantly better than simple d-galactose or their intermediate compounds from the synthesis.

Purinergic P2X3 receptors are trimeric ligand-gated ion channels whose antagonism is an appealing yet challenging and not fully validated drug development idea. With the aim of identification of an orally active, potent human P2X3 receptor antagonist compound that can penetrate the central nervous system, the compound collection of Gedeon Richter was screened. A hit series of tricyclic compounds was subjected to a rapid, two-step optimization process focusing on increasing potency, improving metabolic stability and CNS penetrability. Attempts resulted in compound 65, a potential tool compound for testing P2X3 inhibitory effects in vivo.

The trigeminovascular system has a pivotal role in the pathomechanism of migraine. The aim of the present study was to further develop existing models of migraine making them more suitable for testing the effects of compounds with presumed antimigraine activity in anaesthetised rats. Simultaneous recording of ongoing activity of spontaneously active neurons in the trigeminocervical complex as well as their discharges evoked by electrical stimulation of the dura mater via activation of A- and C-sensory fibres were carried out. Effects of sumatriptan, propranolol and topiramate were evaluated prior to and after application of a mixture containing inflammatory mediators on the dura. Propranolol (10 mg/kg s.c) and topiramate (30 mg/kg s.c.) resulted in a tendency to decrease the level of both spontaneous and evoked activity, while sumatriptan (1 mg/kg s.c.) did not exhibit any effect on recorded parameters. Application of an inflammatory soup to the dura mater boosted up spontaneous activity, which could be significantly attenuated by propranolol and topiramate but not by sumatriptan. In addition, all compounds prevented the delayed increase of spontaneous firing. In contrast to the ongoing activity, evoked responses were not augmented by inflammatory mediators. Nevertheless, inhibitory effect of propranolol and topiramate was evident when considering A- or C-fibre responses. Findings do not support the view that electrically evoked responses are useful for the measurement of trigeminal sensitization. It is proposed however, that inhibition of enhanced firing (immediate and/or delayed) evoked by inflammatory mediators as an endpoint have higher predictive validity regarding the clinical effectiveness of compounds.

Introduction: Cariprazine, a dopamine D3-preferring D3/D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist, has two major human metabolites, desmethyl-cariprazine (DCAR) and didesmethyl-cariprazine (DDCAR). The metabolite pharmacology was profiled to understand the contribution to cariprazine efficacy. Methods In vitro receptor binding and functional assays, electrophysiology, animal models, microdialysis, and kinetic-metabolism approaches were used to characterize the pharmacology of DCAR and DDCAR. Results Similar to cariprazine, both metabolites showed high affinity for human D3, D2L, 5-HT1A, 5-HT2A, and 5-HT2B receptors, albeit with higher selectivity than cariprazine for D3 versus D2 receptors. In [35S]GTPγS binding assays, cariprazine and DDCAR were antagonists in membranes from rat striatum and from cells expressing human D2 and D3 receptors, and were partial agonists in membranes from rat hippocampus. In cAMP signaling assays, cariprazine, DCAR, and DDCAR acted as partial agonists at D2 and D3 receptors; cariprazine and DDCAR were full agonists, whereas DCAR was a partial agonist at 5-HT1A receptors. Cariprazine, DCAR, and DDCAR were pure antagonists at human 5-HT2B receptors. Cariprazine and DDCAR increased rat striatal dopamine and reduced cortical serotonin turnover. Cariprazine and DDCAR showed similar in vivo D3 receptor occupancy in rat brain; however, cariprazine was more potent for D2 receptor occupancy. Both cariprazine and DDCAR dose-dependently but partially suppressed the spontaneous activity of midbrain dopaminergic neurons in rats, with the parent compound being more potent but shorter acting than its metabolite. Consistent with the D2 receptor occupancy profile, DDCAR was 3- to 10-fold less potent than cariprazine in rodent models of antipsychotic-like activity. Following acute cariprazine administration, DDCAR was detected in the rodent brain but at much lower levels than cariprazine. Conclusion Overall, in vitro and in vivo pharmacological profiles of DCAR and DDCAR demonstrated high similarity with cariprazine, suggesting that the major metabolites of cariprazine contribute significantly to its clinical efficacy., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/GuoqH4I3abg

Cariprazine, an orally active and potent dopamine D

In: Középiskolai Kémiai Lapok (KöKéL) vol. 45. issue 5. ISSN 0139-3715 (print), 2498-5198 (online)

A simplified automobile door gap model, defined at the Third Computational Aeroacoustics (CAA) Workshop on Benchmark Problems (Category 6) was investigated. After a thorough mesh study compressible and incompressible simulations were carried out and various turbulence models were tried. The influence of three dimensional effects and boundary layer thickness effects were examined too. In case of compressible simulations stability problems were encountered with the non-reflective boundary condition of CFX (beta version at the time of the simulations). It was found that for deep cavities incompressible simulations are not applicable. In spite of the diculties a good agreement between measurements and simulations was found when the flow speed was 50m/s. In case of 26.8m/s flow speed it was found that the presence of the upper channel wall, not taken into account by the previous authors simulating this problem plays an important role – a hitherto unexplained peak in the measured spectrum appeared this way in the simulation.