Versatility of microglial bioenergetic machinery under starving conditions

Microglia are highly dynamic cells in the brain. Their functional diversity and phenotypic versatility brought microglial energy metabolism into the focus of research. Although it is known that microenvironmental cues shape microglial phenotype, their bioenergetic response to local nutrient availability remains unclear. In the present study effects of energy substrates on the oxidative and glycolytic metabolism of primary - and BV-2 microglial cells were investigated. Cellular oxygen consumption, glycolytic activity, the levels of intracellular ATP/ADP, autophagy, mTOR phosphorylation, apoptosis and cell viability were measured in the absence of nutrients or in the presence of physiological energy substrates: glutamine, glucose, lactate, pyruvate or ketone bodies. All of the oxidative energy metabolites increased the rate of basal and maximal respiration. However, the addition of glucose decreased microglial oxidative metabolism and glycolytic activity was enhanced. Increased ATP/ADP ratio and cell viability, activation of the mTOR and reduction of autophagic activity were observed in glutamine-supplemented media. Moreover, moderate and transient oxidation of ketone bodies was highly enhanced by glutamine, suggesting that anaplerosis of the TCA-cycle could stimulate ketone body oxidation. It is concluded that microglia show high metabolic plasticity and utilize a wide range of substrates. Among them glutamine is the most efficient metabolite. To our knowledge these data provide the first account of microglial direct metabolic response to nutrients under short-term starvation and demonstrate that microglia exhibit versatile metabolic machinery. Our finding that microglia have a distinct bioenergetic profile provides a critical foundation for specifying microglial contributions to brain energy metabolism

Komplex endovascularis rekonstrukciók az aortaíven : műtéti esetbemutatások

Az aortaívet érintő aortabetegségek miatt végzett endovascularis rekonstrukciók (thoracic endovascular aneurysm repair – TEVAR) során a sztentgraft proximalis rögzítése az ívben vagy az aorta ascendensen van. Ilyen esetben hagyományosan nyitott műtéttel előzetesen biztosítjuk a lefedésre kerülő supraaorticus ágak keringését (ún. ’de branching’ műtétek). Nyitott műtétre nem alkalmas betegek esetén azonban az ágak endovascularis módszerekkel történő megtartására kényszerülünk. Tanulmányunkban ezen komplex endovascularis aortaívrekonstrukciók lehető ségeit mutatjuk be. A párhuzamos graftokat jellemzően sürgősségi körülmények között alkalmazzuk. Az ascendensen történő proximalis rögzítés esetén a jobb arteria (a.) carotisról indított ’debranching’ és a truncus brachiocephalicus párhuzamos grafttal történő biztosításával kombinált hibrid műtétet végeztünk. Létfontosságú ér véletlen lefedésével járó TEVAR esetén sürgősséggel végezhetünk konverziót például a bal a. carotis communis keringésének gyors hely reállítására. A bal a. subclavia előzetes revascularisatiója nélkül végzett sürgősségi TEVAR után ritkán jelentkező bal felső végtagi ischaemia esetén utólagos konverziót végezhetünk a bal a. subclavia lumenének helyreállítására ugyan csak párhuzamos grafttal. A kisgörbületen elhelyezkedő, saccularis morfológiájú penetráló aortafekélyek sikeres kirekesztését segítheti egyedi gyártású graft alkalmazása, melyen a nagygörbületen lévő supraaorticus érszájadék köré kivágást, ún. ’scallop’ot helyezünk a graft proximalis végéhez, megnövelve így a proximalis nyak hosszát. Elektív körülmények között ugyancsak egyedileg gyártott elágazó graftot is alkalmazhatunk, melynek során akár mindhárom ág megtartható az ascendensről induló proximalis rögzítés mellett, így arra alkalmas anatómia esetén endovascularis ívcserére is lehetőségünk van

Krónikus aortadissectio talaján kialakult thoracoabdominalis aneurysma endovascularis kezelése fenesztrált sztentgrafttal = Fenestrated endovascular repair of a thoracoabdominal aortic aneurysm in chronic dissection

Thoracoabdominal aortic aneurysms developing in the chronic phase of an aortic dissection require multidisciplinary approach, experienced operators and advanced technology. The mortality and morbidity rate of these multistage operations were reduced with the latest technical achievements in endovascular repair, but they are still significant. Fenestrated endovascular aortic repair, an alternative of thoracoabdominal open repair, is associated with less mortal-ity and morbidity, shorter hospital stay. Using fenestrated devices in aortic dissection is usually technically demanding due to the dissection membrane. We report the case of a 56-year-old woman, who underwent ascending aortic repair due to type A aortic dissection. During the follow-up, a large thoracoabdominal aneurysm developed involving also the arch. We performed a three-stage operation starting with the open repair of the aortic arch using a 'frozen ele-phant trunk' device followed by a thoracic endovascular aortic repair of the descending aorta. The final stage was a fenestrated endovascular aortic repair, which is the first use of this technique in aortic dissection in Hungary

Molecular Characterization of Novel Mycoviruses in Seven Umbelopsis Strains

The presence of viruses is less explored in Mucoromycota as compared to other fungal groups such as Ascomycota and Basidiomycota. Recently, more and more mycoviruses are identified from the early-diverging lineages of fungi. We have determined the genome of 11 novel dsRNA viruses in seven different Umbelopsis strains with next-generation sequencing (NGS). The identified viruses were named Umbelopsis ramanniana virus 5 (UrV5), 6a (UrV6a); 6b (UrV6b); 7 (UrV7); 8a (UrV8a); 8b (UrV8b); Umbelopsis gibberispora virus 1 (UgV1); 2 (UgV2) and Umbelopsis dimorpha virus 1a (UdV1a), 1b (UdV1b) and 2 (UdV2). All the newly identified viruses contain two open reading frames (ORFs), which putatively encode the coat protein (CP) and the RNA-dependent RNA polymerase (RdRp), respectively. Based on the phylogeny inferred from the RdRp sequences, eight viruses (UrV7, UrV8a, UrV8b, UgV1, UgV2, UdV1a, UdV1b and UdV2) belong to the genus Totivirus, while UrV5, UrV6a and UrV6b are placed into a yet unclassified but well-defined Totiviridae-related group. In UrV5, UgV1, UgV2, UrV8b, UdV1a, UdV2 and UdV1b, ORF2 is predicted to be translated as a fusion protein via a rare +1 (or-2) ribosomal frameshift, which is not characteristic to most members of the Totivirus genus. Virus particles 31 to 32 nm in diameter could be detected in the examined fungal strains by transmission electron microscopy. Through the identification and characterization of new viruses of Mucoromycota fungi, we can gain insight into the diversity of mycoviruses, as well as into their phylogeny and genome organization

Effectiveness and Waning of Protection With Different SARS-CoV-2 Primary and Booster Vaccines During the Delta Pandemic Wave in 2021 in Hungary (HUN-VE 3 Study)

BackgroundIn late 2021, the pandemic wave was dominated by the Delta SARS-CoV-2 variant in Hungary. Booster vaccines were offered for the vulnerable population starting from August 2021.MethodsThe nationwide HUN-VE 3 study examined the effectiveness and durability of primary immunization and single booster vaccinations in the prevention of SARS-CoV-2 infection, Covid-19 related hospitalization and mortality during the Delta wave, compared to an unvaccinated control population without prior SARS-CoV-2 infection.ResultsThe study population included 8,087,988 individuals who were 18–100 years old at the beginning of the pandemic. During the Delta wave, after adjusting for age, sex, calendar day, and chronic diseases, vaccine effectiveness (VE) of primary vaccination against registered SARS-CoV-2 infection was between 11% to 77% and 18% to 79% 14–120 days after primary immunization in the 16–64 and 65–100 years age cohort respectively, while it decreased to close to zero in the younger age group and around 40% or somewhat less in the elderly after 6 months for almost all vaccine types. In the population aged 65–100 years, we found high, 88.1%–92.5% adjusted effectiveness against Covid-19 infection after the Pfizer-BioNTech, and 92.2%–95.6% after the Moderna booster dose, while Sinopharm and Janssen booster doses provided 26.5%–75.3% and 72.9%–100.0% adjusted VE, respectively. Adjusted VE against Covid-19 related hospitalization was high within 14–120 days for Pfizer-BioNTech: 76.6%, Moderna: 83.8%, Sputnik-V: 78.3%, AstraZeneca: 73.8%, while modest for Sinopharm: 45.7% and Janssen: 26.4%. The waning of protection against Covid-19 related hospitalization was modest and booster vaccination with mRNA vaccines or the Janssen vaccine increased adjusted VE up to almost 100%, while the Sinopharm booster dose proved to be less effective. VE against Covid-19 related death after primary immunization was high or moderate: for Pfizer-BioNTech: 81.5%, Moderna: 93.2%, Sputnik-V: 100.0%, AstraZeneca: 84.8%, Sinopharm: 58.6%, Janssen: 53.3%). VE against this outcome also showed a moderate decline over time, while booster vaccine types restored effectiveness up to almost 100%, except for the Sinopharm booster.ConclusionsThe HUN-VE 3 study demonstrated waning VE with all vaccine types for all examined outcomes during the Delta wave and confirmed the outstanding benefit of booster vaccination with the mRNA or Janssen vaccines, and this is the first study to provide clear and comparable effectiveness results for six different vaccine types after primary immunization against severe during the Delta pandemic wave

Photocatalytic Properties of TiO2@Polymer and TiO2@Carbon Aerogel Composites Prepared by Atomic Layer Deposition

Monolithic structured TiO2/aerogel composites were prepared from resorcinol-formaldehyde polymer aerogel (RFA) and its carbon aerogel (RFCA) derivative. A resorcinol-formaldehyde hydrogel was synthesized in a sol-gel reaction and transformed into polymer aerogel by supercritical drying. The RFA was converted to carbon aerogel by pyrolysis at 900 °C in dry N2. Amorphous and crystalline TiO2 layers were grown from TiCl4 and H2O precursors by atomic layer deposition (ALD) at 80 °C and 250 °C, respectively, on both RFA and RFCA. The substrates and the composites were studied by N2 adsorption, TG/DTA-MS, Raman, SEM-EDX and TEM techniques. Their photocatalytic activity was compared in the UV catalyzed decomposition reaction of methyl orange dye

Systematic transcriptomic and phenotypic characterization of human and murine cardiac myocyte cell lines and primary cardiomyocytes reveals serious limitations and low resemblances to adult cardiac phenotype

Background Cardiac cell lines and primary cells are widely used in cardiovascular research. Despite increasing number of publications using these models, comparative characterization of these cell lines has not been performed, therefore, their limitations are undetermined. We aimed to compare cardiac cell lines to primary cardiomyocytes and to mature cardiac tissues in a systematic manner. Methods and results Cardiac cell lines (H9C2, AC16, HL-1) were differentiated with widely used protocols. Left ventricular tissue, neonatal primary cardiomyocytes, and human induced pluripotent stem cell-derived cardiomyocytes served as reference tissue or cells. RNA expression of cardiac markers (e.g. Tnnt2, Ryr2) was markedly lower in cell lines compared to references. Differentiation induced increase in cardiac- and decrease in embryonic markers however, the overall transcriptomic profile and annotation to relevant biological processes showed consistently less pronounced cardiac phenotype in all cell lines in comparison to the corresponding references. Immunocytochemistry confirmed low expressions of structural protein sarcomeric alpha-actinin, troponin I and caveolin-3 in cell lines. Susceptibility of cell lines to sI/R injury in terms of viability as well as mitochondrial polarization differed from the primary cells irrespective of their degree of differentiation. Conclusion Expression patterns of cardiomyocyte markers and whole transcriptomic profile, as well as response to sI/R, and to hypertrophic stimuli indicate low-to-moderate similarity of cell lines to primary cells/cardiac tissues regardless their differentiation. Low resemblance of cell lines to mature adult cardiac tissue limits their potential use. Low translational value should be taken into account while choosing a particular cell line to model cardiomyocytes

Substantial variation across geographic regions in the obesity prevalence among 6–8 years old Hungarian children (COSI Hungary 2016)

Abstract Background There have been previous representative nutritional status surveys conducted in Hungary, but this is the first one that examines overweight and obesity prevalence according to the level of urbanization and in different geographic regions among 6–8-year-old children. We also assessed whether these variations were different by sex. Methods This survey was part of the fourth data collection round of World Health Organization (WHO) Childhood Obesity Surveillance Initiative which took place during the academic year 2016/2017. The representative sample was determined by two-stage cluster sampling. A total of 5332 children (48.4% boys; age 7.54 ± 0.64 years) were measured from all seven geographic regions including urban (at least 500 inhabitants per square kilometer; n = 1598), semi-urban (100 to 500 inhabitants per square kilometer; n = 1932) and rural (less than 100 inhabitants per square kilometer; n = 1802) areas. Results Using the WHO reference, prevalence of overweight and obesity within the whole sample were 14.2, and 12.7%, respectively. According to the International Obesity Task Force (IOTF) reference, rates were 12.6 and 8.6%. Northern Hungary and Southern Transdanubia were the regions with the highest obesity prevalence of 11.0 and 12.0%, while Central Hungary was the one with the lowest obesity rate (6.1%). The prevalence of overweight and obesity tended to be higher in rural areas (13.0 and 9.8%) than in urban areas (11.9 and 7.0%). Concerning differences in sex, girls had higher obesity risk in rural areas (OR = 2.0) but boys did not. Odds ratios were 2.0–3.4 in different regions for obesity compared to Central Hungary, but only among boys. Conclusions Overweight and obesity are emerging problems in Hungary. Remarkable differences were observed in the prevalence of obesity by geographic regions. These variations can only be partly explained by geographic characteristics. Trial registration Study protocol was approved by the Scientific and Research Ethics Committee of the Medical Research Council (61158–2/2016/EKU)