Threshold of viability
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The aim of this prospective study was to assess the duration of culture-viable SARS-CoV-2 and to monitor the emergence of mutations in a cohort of 23 kidney transplant recipients (KTRs) from June 2022 to June 2023. Combined nares/oropharyngeal swabs were collected weekly starting as soon as possible after symptom onset. The time from symptom onset to a negative culture was 11 days (interquartile range, 8-14), while the time to negative reverse transcriptase quantitative polymerase chain reaction was 18 days (interquartile range, 15-30). Beyond the first swab, 21.7% had a positive culture, and 8.7% replicated viable virus for longer than 30 days. T cell depletion (rate ratio, 2.5; 95% confidence interval [95% CI], 1.9-3.3; P < .001) and time from transplantation (rate ratio, 0.93; 95% CI, 0.90-0.97; P = .006) were associated with the time of viable virus shedding. A cycle threshold value of 24.2 demonstrated a 91.3% negative predictive value of viability (95% credible interval [95% CrI], 76-100). The odds of viability decreased by 69% per week of infection (odds ratio, 0.31; 95% CrI, 0.12-0.76). Overall, ribonucleic acid sequencing did not show accelerated molecular evolution though mutation rate could be increased in molnupiravir-treated KTRs. In conclusion, viable SARS-CoV-2 is eliminated rapidly, the risk of virus evolution is low, and prolonged self-isolation is generally unnecessary for most KTRs.
- MeSH
- COVID-19 * virologie epidemiologie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- molekulární evoluce * MeSH
- mutace MeSH
- příjemce transplantátu * MeSH
- prospektivní studie MeSH
- SARS-CoV-2 * genetika izolace a purifikace fyziologie MeSH
- senioři MeSH
- transplantace ledvin * MeSH
- vylučování virů * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
Electroencephalography (EEG) experiments typically generate vast amounts of data due to the high sampling rates and the use of multiple electrodes to capture brain activity. Consequently, storing and transmitting these large datasets is challenging, necessitating the creation of specialized compression techniques tailored to this data type. This study proposes one such method, which at its core uses an artificial neural network (specifically a convolutional autoencoder) to learn the latent representations of modelled EEG signals to perform lossy compression, which gets further improved with lossless corrections based on the user-defined threshold for the maximum tolerable amplitude loss, resulting in a flexible near-lossless compression scheme. To test the viability of our approach, a case study was performed on the 256-channel binocular rivalry dataset, which also describes mostly data-specific statistical analyses and preprocessing steps. Compression results, evaluation metrics, and comparisons with baseline general compression methods suggest that the proposed method can achieve substantial compression results and speed, making it one of the potential research topics for follow-up studies.
- MeSH
- dospělí MeSH
- elektroencefalografie * metody MeSH
- komprese dat * metody MeSH
- lidé MeSH
- neuronové sítě * MeSH
- počítačové zpracování signálu MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
In the era of COVID-19 pandemic, organ transplantation programs were facing serious challenges. The lung transplantation donor pool was extremely limited and SARS-CoV-2 viral load assessment has become a crucial part of selecting an optimal organ donor. Since COVID-19 is a respiratory disease, the viral load is thought to be more important in lung transplantations as compared to other solid organ transplantations. We present two challenging cases of potential lung donors with a questionable COVID-19 status. Based on these cases, we suggest that the cycle threshold (Ct) value should always be requested from the laboratory and the decision whether to proceed with transplantation should be made upon complex evaluation of diverse criteria, including the nasopharyngeal swab and bronchoalveolar lavage PCR results, the Ct value, imaging findings and the medical history. However, as the presence of viral RNA does not ensure infectivity, it is still to be clarified which Ct values are associated with the viral viability. Anti-SARS-CoV-2 IgA antibodies may support the diagnosis and moreover, novel methods, such as quantifying SARS-CoV-2 nucleocapsid antigen in serum may provide important answers in organ transplantations and donor selections.
- MeSH
- bronchoalveolární lavážní tekutina virologie MeSH
- COVID-19 diagnóza virologie MeSH
- dárci tkání * MeSH
- dospělí MeSH
- hodnocení rizik MeSH
- lidé středního věku MeSH
- lidé MeSH
- plíce chirurgie virologie MeSH
- prediktivní hodnota testů MeSH
- rizikové faktory MeSH
- SARS-CoV-2 izolace a purifikace MeSH
- testování na COVID-19 MeSH
- transplantace plic * škodlivé účinky MeSH
- virová nálož MeSH
- výběr dárců * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Many studies reported good performance of nasopharyngeal swab-based antigen tests for detecting SARS-CoV-2-positive individuals; however, studies independently evaluating the quality of antigen tests utilizing anterior nasal swabs or saliva swabs are still rare, although such tests are widely used for mass testing. In our study, sensitivities, specificities and predictive values of seven antigen tests for detection of SARS-CoV-2 (one using nasopharyngeal swabs, two using anterior nasal swabs and four using saliva) were evaluated. In a setting of a high-capacity testing center, nasopharyngeal swabs for quantitative PCR (qPCR) were taken and, at the same time, antigen testing was performed in accordance with manufacturers' instructions for the respective tests. In samples where qPCR and antigen tests yielded different results, virus culture was performed to evaluate the presence of the viable virus. Sensitivities and specificities of individual tests were calculated using both qPCR and qPCR corrected for viability as the reference. In addition, calculations were also performed for data categorized according to the cycle threshold and symptomatic status. The test using nasopharyngeal swabs yielded the best results (sensitivity of 80.6% relative to PCR and 91.2% when corrected for viability) while none of the remaining tests (anterior nasal swab or saliva-based tests) came even close to the WHO criteria for overall sensitivity. Hence, we advise caution when using antigen tests with alternative sampling methods without independent validation.
- Publikační typ
- časopisecké články MeSH
Mitochondrial ATP synthase is responsible for production of the majority of cellular ATP. Disorders of ATP synthase in humans can be caused by numerous mutations in both structural subunits and specific assembly factors. They are associated with variable pathogenicity and clinical phenotypes ranging from mild to the most severe mitochondrial diseases. To shed light on primary/pivotal functional consequences of ATP synthase deficiency, we explored human HEK 293 cells with a varying content of fully assembled ATP synthase, selectively downregulated to 15-80% of controls by the knockdown of F1 subunits γ, δ and ε. Examination of cellular respiration and glycolytic flux revealed that enhanced glycolysis compensates for insufficient mitochondrial ATP production while reduced dissipation of mitochondrial membrane potential leads to elevated ROS production. Both insufficient energy provision and increased oxidative stress contribute to the resulting pathological phenotype. The threshold for manifestation of the ATP synthase defect and subsequent metabolic remodelling equals to 10-30% of residual ATP synthase activity. The metabolic adaptations are not able to sustain proliferation in a galactose medium, although sufficient under glucose-rich conditions. As metabolic alterations occur when the content of ATP synthase drops below 30%, some milder ATP synthase defects may not necessarily manifest with a mitochondrial disease phenotype, as long as the threshold level is not exceeded.
- MeSH
- buněčné klony MeSH
- genový knockdown MeSH
- glykolýza MeSH
- HEK293 buňky MeSH
- inhibiční koncentrace 50 MeSH
- lidé MeSH
- mitochondriální protonové ATPasy nedostatek metabolismus MeSH
- oxidační stres MeSH
- termodynamika MeSH
- viabilita buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Bacterial infection associated with medical implants is a major threat to healthcare. This work reports the fabrication of Copper(II)-Chitosan (Cu(II)-CS) complex coatings deposited by electrophoretic deposition (EPD) as potential antibacterial candidate to combat microorganisms to reduce implant related infections. The successful deposition of Cu(II)-CS complex coatings on stainless steel was confirmed by physicochemical characterizations. Morphological and elemental analyses by scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX) spectroscopy verified the uniform distribution of copper in the Chitosan (CS) matrix. Moreover, homogeneous coatings without precipitation of metallic copper were confirmed by X-ray diffraction (XRD) spectroscopy and SEM micrographs. Controlled swelling behavior depicted the chelation of copper with polysaccharide chains that is key to the stability of Cu(II)-CS coatings. All investigated systems exhibited stable degradation rate in phosphate buffered saline (PBS)-lysozyme solution within seven days of incubation. The coatings presented higher mechanical properties with the increase in Cu(II) concentration. The crack-free coatings showed mildly hydrophobic behavior. Antibacterial assays were performed using both Gram-positive and Gram-negative bacteria. Outstanding antibacterial properties of the coatings were confirmed. After 24 h of incubation, cell studies of coatings confirms that up to a certain threshold concentration of Cu(II) were not cytotoxic to human osteoblast-like cells. Overall, our results show that uniform and homogeneous Cu(II)-CS coatings with good antibacterial and enhanced mechanical stability could be successfully deposited by EPD. Such antibiotic-free antibacterial coatings are potential candidates for biomedical implants.
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- biokompatibilní potahované materiály * MeSH
- chemické jevy * MeSH
- chitosan chemie MeSH
- difrakce rentgenového záření MeSH
- elektroforéza * MeSH
- lidé MeSH
- měď chemie MeSH
- mikrobiální testy citlivosti MeSH
- nanostruktury chemie ultrastruktura MeSH
- spektroskopie infračervená s Fourierovou transformací MeSH
- viabilita buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Background: The initial core infarct volume predicts treatment outcome in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). According to the literature, CT perfusion (CTP) is able to evaluate cerebral parenchymal viability and assess the initial core in AIS. We prospectively studied whether limited-coverage CTP with automated core calculation correlates with the final infarct volume on follow-up non-enhanced CT (NECT) in patients successfully treated by mechanical thrombectomy. Methods: We enrolled 31 stroke patients (20 women aged 74.4±12.9 years and 11 men aged 66±15.4 years; median initial NIHSS score 15.5) with occlusion of the medial cerebral artery and/or the internal carotid artery that were treated by successful mechanical thrombectomy. CTP performed in a 38.6 mm slab at the level of basal ganglia was included in the CT stroke protocol, but was not used to determine indication for mechanical thrombectomy. The infarction core volume based on CTP was automatically calculated using dedicated software with a threshold defined as cerebral blood flow <30% of the value in the contralateral healthy hemisphere. The final infarction volume was measured on 24-hour follow-up NECT in the same slab with respect to CTP. Pearson and Spearman correlation coefficients and robust linear regression were used for comparison of both volumes, P values <0.05 were considered as statistically significant. Results: The median time from stroke onset to CT was 77 minutes (range, 31-284 minutes), and the median time from CT to vessel recanalization was 95 minutes (range, 55-215 minutes). The mean CTP-calculated core infarct volume was 24.3±19.2 mL (median 19 mL, range 1-79 mL), while the mean final infarct volume was 21.5±39.5 mL (median 8 mL; range 0-210 mL). Only a weak relationship was found between the CTP-calculated core and final infarct volume [Pr(29) =0.32, P=0.078; rho =0.40, P=0.028]. Regression analysis showed CTP significantly overestimated lower volumes. Conclusions: In our prospective study, the infarction core calculated using limited-coverage CTP only weakly correlated with the final infarction volume measured on 24-hour follow-up NECT; moreover, CTP significantly overestimated lower volumes. Our results do not support the use of limited-coverage CTP for guiding treatment recommendations in patients with AIS.
- Publikační typ
- časopisecké články MeSH
Fruit of Terminalia chebula Retz. (Combretaceae) has male contraceptive folk medicine reputation but its molecular aspect regarding hypotesticular activity is still in dark. The study focused the hypotesticular efficacy of the most potent fraction out of n-hexane, chloroform and ethyl acetate fractions of hydro-methanolic (3:2) extract of Terminalia chebula in connection with male herbal contraceptive development. Treatment with above fractions of Terminalia chebula showed a significant diminution in the activities of androgenic key enzymes (Δ5, 3β-HSD, 17β-HSD) and inhibition in serum testosterone level in compare to the control. Significant up regulation of testicular Bax gene and down regulation of Bcl-2 gene indicated the hypotesticular activity of these fractions. Flow-cytometric study focused a significant diminution in sperm viability and sperm mitochondrial status after the treatment with different fractions. Out of these, ethyl acetate fraction showed most promising hypotesticular effect without impairing any toxicity in general which highlighted that the fraction may contains antitesticular agent(s) in threshold levels compare to other fractions as it decreases spermiological, testicular genomic sensors and elevates sperm apoptotic sensors that may lead to male contraception.
- MeSH
- látky blokující spermatogenezi * chemie izolace a purifikace MeSH
- modely u zvířat MeSH
- potkani Wistar MeSH
- průtoková cytometrie MeSH
- rostlinné extrakty MeSH
- spermie účinky léků MeSH
- Terminalia chemie MeSH
- testis enzymologie chemie účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
Trypanosoma brucei is an extracellular parasite that alternates between an insect vector (procyclic form) and the bloodstream of a mammalian host (bloodstream form). While it was previously reported that mitochondrial release factor 1 (TbMrf1) is essential in cultured procyclic form cells, we demonstrate here that in vitro bloodstream form cells can tolerate the elimination of TbMrf1. Therefore, we explored if this discrepancy is due to the unique bioenergetics of the parasite since procyclic form cells rely on oxidative phosphorylation; whereas bloodstream form cells utilize glycolysis for ATP production and FoF1-ATPase to maintain the essential mitochondrial membrane potential. The observed disruption of intact bloodstream form FoF1-ATPases serves as a proxy to indicate that the translation of its mitochondrially encoded subunit A6 is impaired without TbMrf1. While these null mutants have a decreased mitochondrial membrane potential, they have adapted by increasing their dependence on the electrogenic contributions of the ADP/ATP carrier to maintain the mitochondrial membrane potential above the minimum threshold required for T. brucei viability in vitro. However, this inefficient compensatory mechanism results in avirulent mutants in mice. Finally, the depletion of the codon-independent release factor TbPth4 in the TbMrf1 knockouts further exacerbates the characterized mitchondrial phenotypes.
- MeSH
- fyziologická adaptace * MeSH
- membránový potenciál mitochondrií genetika MeSH
- mitochondriální proteiny genetika metabolismus MeSH
- mitochondrie * genetika metabolismus MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- oxidativní fosforylace MeSH
- protonové ATPasy genetika metabolismus MeSH
- protozoální proteiny genetika metabolismus MeSH
- stadia vývoje * MeSH
- Trypanosoma brucei brucei * genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Pozadí a cíl studie: Potřeba intubace na porodním sále je u extrémně nezralých novorozenců vysoká a negativně závislá na gestačním stáří. Inflační manévr je fyziologický koncept, který může snížit potřebu intubací na porodním sále i u nejnezralejších novorozenců, a tak pozitivně ovlivnit jejich vývoj. Metoda: Retrospektivní analýza prospektivně sbíraných dat nezralých novorozenců stabilizovaných po porodu na výzkumném resuscitačním lůžku, které umožňuje pořizování dvou simultánních videozáznamů. Data byla získávána od roku 2010. Nezralí novorozenci narození před 30. týdnem těhotenství byli stabilizováni podle standardu neonatologického oddělení vytvořeného na základě ILCOR doporučení z roku 2010. V roce 2013 byl do protokolu zahrnut inflační manévr prováděný tlakem 25 cm H2O po dobu 15–20 sekund. Primárním výstupem byla potřeba intubace na porodním sále v období před a po zavedení inflačního manévru. Sledována byla rovněž mortalita a závažná novorozenecká morbidita v obou skupinách. Výsledky: Po zavedení inflačního manévru se snížila potřeba akutní intubace na porodním sále. U skupiny extrémně nezralých novorozenců narozených před 25. týdnem těhotenství bylo snížení statisticky významné (18/25, 72 % vs. 8/24, 33 %; p < 0,007). Hraničně významně se snížila i potřeba umělé plicní ventilace v prvních 72 hodinách života (9/24, 37 % vs. 16/25, 64 %; p = 0,064) a výskyt závažného intraventrikulárního krvácení (3/24, 12 % vs. 9/25, 36 %; p = 0,055). Naopak významně se zvýšil výskyt otevřené tepenné dučeje indikované k léčbě (10/24, 41 % vs. 4/25, 16 %; p < 0,05). Závěr: Zavedení inflačního manévru do klinické praxe snížilo potřebu intubací na porodním sále zvláště u nezralých novorozenců porozených na hranici viability, což se mohlo příznivě promítnout i do snížení výskytu jejich kraniální morbidity. Povzbudivé výsledky by měly být potvrzeny v randomizovaných studiích zaměřených na tuto populaci.
Background and objective: The need for intubation in the delivery room is high and negatively dependent on gestational age in extremely preterm infants. Sustained inflation manoeuvre (SIM) is a physiological concept that can reduce the need for intubation in the delivery room and thus positively influence long-term outcome of extremely premature infants. Method: Retrospective analysis of prospectively collected data of premature infants stabilised after delivery in a unique research resuscitation bed, which allows two simultaneous video recordings. Data has been collected since 2010. Infants born at < 30 weeks of gestation were resuscitated according to the internal guideline based on the ILCOR recommendation. In 2013, SIM with a pressure of 25 cm H2O for 15–20 seconds was implemented to the resuscitation procedure. The primary outcome was the need for intubation in the delivery room before and after the introduction of the SIM. The incidence of death before discharge and severe neonatal morbidity were also compared. Results: After the introduction of the SIM, the need for intubation in the delivery room was reduced. For a subgroup of infants born at < 25 weeks of gestation age was a statistically significant reduction (18/25, 72% versus 8/24, 33%, p<0.007). There was a significant reduction in the need for artificial ventilation in the first 72 hours of life (9/24, 37% versus 16/25, 64%, p=0.064) and severe intraventricular hemorrhage (3/24, 12% vs. 9/25, 36%, p=0.055). In contrast, the incidence of patent ductus arteriosus significantly increased (10/24, 41% vs. 4/25, 16%, p<0.05). Conclusion: The introduction of SIM to the clinical practice has reduced the need for intubation in the delivery room, especially in extremely preterm infants born on the threshold of the viability, which could have a positive effect on reducing the incidence of cranial morbidity. Promising results should be confirmed in randomised trials focusing on this unique, fragile population.
- Klíčová slova
- inflační manévr,
- MeSH
- intenzivní péče o novorozence metody MeSH
- lidé MeSH
- novorozenci extrémně nezralí * MeSH
- novorozenec MeSH
- porod MeSH
- porodní sály MeSH
- resuscitační péče metody MeSH
- retrospektivní studie MeSH
- trvalý přetlak v dýchacích cestách * metody využití MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH