White plague among the "forgotten people" from the Barbaricum of the Carpathian Basin-Cases with tuberculosis from the Sarmatian-period (3rd-4th centuries CE) archaeological site of Hódmezovásárhely-Kenyere-ér, Bereczki-tanya (Hungary).

Tuberculosis (TB) is a bacterial infection that is well-known in the palaeopathological record because it can affect the skeleton and consequently leaves readily identifiable macroscopic alterations. Palaeopathological case studies provide invaluable information about the spatio-temporal distribution of TB in the past. This is true for those archaeological periods and geographical regions from when and where no or very few TB cases have been published until now-as in the Sarmatian period (1st-5th centuries CE) in the Barbaricum of the Carpathian Basin. The aim of our paper is to discuss five newly discovered TB cases (HK199, HK201, HK225, HK253, and HK309) from the Sarmatian-period archaeological site of Hódmezovásárhely-Kenyere-ér, Bereczki-tanya (Csongrád-Csanád county, Hungary). Detailed macromorphological evaluation of the skeletons focused on the detection of bony changes likely associated with different forms of TB. In all five cases, the presence of endocranial alterations (especially TB-specific granular impressions) suggests that these individuals suffered from TB meningitis. Furthermore, the skeletal lesions observed in the spine and both hip joints of HK225 indicate that this juvenile also had multifocal osteoarticular TB. Thanks to the discovery of HK199, HK201, HK225, HK253, and HK309, the number of TB cases known from the Sarmatian-period Carpathian Basin doubled, implying that the disease was likely more frequent in the Barbaricum than previously thought. Without the application of granular impressions, the diagnosis of TB could not have been established in these five cases. Thus, the identification of TB in these individuals highlights the importance of diagnostics development, especially the refinement of diagnostic criteria. Based on the above, the systematic macromorphological (re-)evaluation of osteoarchaeological series from the Sarmatian-period Carpathian Basin would be advantageous to provide a more accurate picture of how TB may have impacted the ancestral human communities of the Barbaricum.

The genetic origin of Huns, Avars, and conquering Hungarians.

Huns, Avars, and conquering Hungarians were migration-period nomadic tribal confederations that arrived in three successive waves in the Carpathian Basin between the 5th and 9th centuries. Based on the historical data, each of these groups are thought to have arrived from Asia, although their exact origin and relation to other ancient and modern populations have been debated. Recently, hundreds of ancient genomes were analyzed from Central Asia, Mongolia, and China, from which we aimed to identify putative source populations for the above-mentioned groups. In this study, we have sequenced 9 Hun, 143 Avar, and 113 Hungarian conquest period samples and identified three core populations, representing immigrants from each period with no recent European ancestry. Our results reveal that this "immigrant core" of both Huns and Avars likely originated in present day Mongolia, and their origin can be traced back to Xiongnus (Asian Huns), as suggested by several historians. On the other hand, the "immigrant core" of the conquering Hungarians derived from an earlier admixture of Mansis, early Sarmatians, and descendants of late Xiongnus. We have also shown that a common "proto-Ugric" gene pool appeared in the Bronze Age from the admixture of Mezhovskaya and Nganasan people, supporting genetic and linguistic data. In addition, we detected shared Hun-related ancestry in numerous Avar and Hungarian conquest period genetic outliers, indicating a genetic link between these successive nomadic groups. Aside from the immigrant core groups, we identified that the majority of the individuals from each period were local residents harboring "native European" ancestry.

Maternal Lineages from 10-11th Century Commoner Cemeteries of the Carpathian Basin.

Nomadic groups of conquering Hungarians played a predominant role in Hungarian prehistory, but genetic data are available only from the immigrant elite strata. Most of the 10-11th century remains in the Carpathian Basin belong to common people, whose origin and relation to the immigrant elite have been widely debated. Mitogenome sequences were obtained from 202 individuals with next generation sequencing combined with hybridization capture. Median joining networks were used for phylogenetic analysis. The commoner population was compared to 87 ancient Eurasian populations with sequence-based (Fst) and haplogroup-based population genetic methods. The haplogroup composition of the commoner population markedly differs from that of the elite, and, in contrast to the elite, commoners cluster with European populations. Alongside this, detectable sub-haplogroup sharing indicates admixture between the elite and the commoners. The majority of the 10-11th century commoners most likely represent local populations of the Carpathian Basin, which admixed with the eastern immigrant groups (which included conquering Hungarians).

Coarctatio aortae: management from infancy to adulthood. / A coarctatio aortae kezelése újszülöttkortól a felnottkorig.

The surgical management of congenital heart defects is changing continuously due to technical development. Aortic coarctation is one of the most frequent congenital heart diseases often with serious symptoms. The authors review the different surgical techniques (end-to-end anastomosis, pathplasty, interposition) and present the up-to-date procedures from infancy to adulthood. We assess the results, the benefits and disadvantages of the different procedures based on our and international experiences. The greatest surgical challenges are the management of the serious hypoplastic aortic arch in infancy and later evolving restenosis and complications (aneurysm, dissection). Nowadays, the management of aortic coarctation is very difficult because the surgical procedures are different in infancy, childhood and adult age. In the latter two cases, it is necessary to apply catheter interventions, too, the correct timing of which also present great challenges nowadays. Orv Hetil. 2020; 161(21): 861-866.

Neuronal Nitric Oxide Mediates the Anti-inflammatory Effects of Intestinal Ischemic Preconditioning.

BACKGROUND: Ischemic preconditioning (IPC) can provide a defense against ischemia-reperfusion (IR)-induced acute inflammation and barrier dysfunction in many organs. Because nitric oxide (NO) has been implicated as a trigger or mediator in the IPC mechanism and because neuronal NO synthase (nNOS) is a dominant isoform of NOS in the gastrointestinal tract, our aim was to investigate the role of nNOS in IPC-induced protection after mesenteric IR. MATERIALS AND METHODS: Intestinal IR was induced in sodium pentobarbital-anesthetized dogs by clamping the superior mesenteric artery for 60 min followed by 2 h of reperfusion (IR group; n = 7). In further groups, IPC was used (three cycles of 5-min ischemia/5-min reperfusion periods) before IR in the presence or absence of selective inhibition of nNOS with 7-nitroindazole (5 mg/kg, intravenously, in a bolus 15 min before IPC, n = 6 each). Changes in mesenteric vascular resistance, intramucosal pH (pHi), and small bowel motility were monitored. Plasma nitrite/nitrate levels, intestinal NO synthase activity, leukocyte accumulation, mast cell degranulation, and histologic injury were also determined. RESULTS: Ischemia significantly decreased mesenteric vascular resistance and pHi, whereas IR induced a temporary bowel hypermotility and acute inflammatory reaction. IPC facilitated pHi recovery, attenuated motility dysfunction, elevated NOS-dependent NO production, and reduced leukocyte accumulation, mast cell degranulation, and mucosal injury. Pretreatment with 7-nitroindazole halted the IPC-induced increase in NO availability, pHi recovery, and the anti-inflammatory and morphologic effects. CONCLUSIONS: Our data demonstrate that NO generated by intestinal nNOS plays a pivotal role in IPC-linked tissue protection by inhibiting an IR-related acute inflammatory response.

Infective endocarditis complicated with coronary artery septic embolization: is it worth to be mentioned? Case presentation and review of the literature.

Coronary artery septic embolization is a rare, but severe complication of infective endocarditis involving the leftside of the valves. The first case mentioned in the literature was a postmortem finding of a left anterior descending coronary artery occlusion by a vegetation fragment. Since this case, there have been several therapeutic strategies published with this clinical setting including medical treatment, percutaneous coronary angioplasty addressing coronary occlusion, surgical intervention for both the infected valve and coronary embolization, and hybrid procedures with transcatheter septic embolus aspiration followed by surgical valvular interventions. Out of the three interventions mentioned, the latter provided the best results and was in concordance with results observed in a case of mitral valve infected endocarditis complicated with acute occlusion of the left anterior descending coronary artery in patient whose comorbidities included hypertrophic obstructive cardiomyopathy. A transcatheter left anterior descending coronary artery embolus aspiration was performed , followed by a surgical mitral valve replacement and septal myectomy with an uneventful postoperative course. Although rare, this severe complication of infective endocarditis has a specific clinical course and therapeutic strategy, and in our opinion, it could be mentioned as a separate entity among embolic complications of infective endocarditis in future guidelines. Previously published cases suggest that the hybrid intervention might be the therapy of choice for this clinical setting; however, larger studies are necessary for confirmation.

Proteomics Analysis of Thermoplasma Quinone Droplets.

A novel type of lipid droplet/lipoprotein (LD/LP) particle from Thermoplasma acidophilum has been identified recently, and based on biochemical evidences, it was named Thermoplasma Quinone Droplet (TaQD). The major components of TaQDs are menaquinones, and to some extent polar lipids, and the 153 amino acid long Ta0547 vitellogenin-N domain protein. In this paper, the aim is to identify TaQD proteome components with 1D-SDS-PAGE/LC-MS/MS and cross reference them with Edman degradation. TaQD samples isolated with three different purification methods-column chromatography, immunoprecipitation, and LD ultracentrifugation-are analyzed. Proteins Ta0093, Ta0182, Ta0337, Ta0437, Ta0438, Ta0547, and Ta1223a are identified as constituents of the TaQD proteome. The majority of these proteins is uncharacterized and has low molecular weight, and none of them is predicted to take part in lipid metabolism. Bioinformatics analyses does not predict any interaction between these proteins, however, there are indications of interactions with proteins taking part in lipid metabolism. Whether if TaQDs provide platform for lipid metabolism and the interactions between TaQD proteins and lipid metabolism proteins occur in the reality remain for further studies.

Lipoprotein-like particles in a prokaryote: quinone droplets of Thermoplasma acidophilum.

Cytosolic, globular droplets with an average diameter of 50 nm were observed in vitrified Thermoplasma acidophilum cells by means of cryo-electron tomography. These droplets were isolated by column chromatography and immunoprecipitation protein purification methods. Subsequent chemical and biochemical analyses identified lipid and protein components, respectively. Two major lipid components, comigrating menaquinones at the solvent front and the slower migrating Thermoplasma polar lipid U4, were detected by TLC experiments. The major protein component was identified as the 153 amino acid long Ta0547 vitellogenin-N domain protein. This domain has been found so far exclusively in large lipid transport proteins of vertebrates and non-vertebrates. Blast protein database homology searches with Ta0547 did not return any eukaryal hits; homologous sequences were found only in thermo-acidophilic archaeons. However, a profile-sequence domain search performed with the vitellogenin-N domain (PF01347) hmm-profile against the T. acidophilum proteome returned Ta0547 as hit. Electron microscopy appearance of isolated droplets resembled to lipoprotein particles. However, no (tetraether) lipid layer could be detected on the droplets surface, rather hydrophobic compounds of the electron dense lumen were surrounded by a denser discontinuous protein boundary. Based on described features, these particles qualify for a novel lipoprotein particle category, what we nominated Thermoplasma Quinone Droplet.

[Early experiences with the Sorin Perceval S arteficial biological valve]. / Kezdeti tapasztalatok a Sorin Perceval S aorta biológiai billentyu beültetésével.

OBJECTIVES: We examined the Sorin Perceval S artificial biological valve implantation techniques, and present the initial experiences in our unit. METHODS: In the last 1.5 years, 27 patients had been implanted with Sorin Perceval S biological arteficial valve due to aortic valve disease. The device was mainly used in high-risk patients, in reoperative circumstances, in cases of calcified aortic root, and in elderly patients. RESULTS: The valve implantation time, aortic cross clamp time is shorter, but the risk of the operation cannot be eliminated entirely, because of the high risk patients' severe comorbidities. Furthermore, we performed echocardiography in the postoperative period, which demonstrated that the valve function is excellent, the valve fitted tightly in the anulus, and there was no paravalvular leakage. CONCLUSIONS: The Sorin Perceval S biological arteficial aortic valve is safe to use in high risk patients, and the surgical procedure is easier in case of partial sternotomy, too.

[Surgical management of congenital heart defects beyond the age of 60]. / Veleszületett szívhibák sebészi kezelése 60 éves kor felett.

INTRODUCTION: The population with congenital heart disease is increasing and ageing. AIM: The aim of the authors was to examine the outcome of surgical management of congenital heart diseases beyond the age of 60 years. METHOD: Between 2013 and 2015, 77 adults were operated (36 younger, and 41 older than forty years, including 12 patients aged over 60 years. The numbers of procedures were as follows (in brackets the number of operations in the three age groups): Ross surgery 5 (3, 2, 0); aortic valve replacement 19 (12, 1, 6); subaortic membrane resection 1 (0, 0, 1); Bentall/ascending aortic plasty 8 (4, 3, 1); myectomy with or without mitral valve replacement in left ventricular outflow obstruction 5 (0, 3, 2); aortic coarctation 1 (1, 0, 0); ligation of ductus arteriosus 2 (1, 1, 0); reconstruction of right ventricular outflow tract with biological valve 4 (0, 3, 1); homograft 5 (5, 0, 0); BioValsalva graft 1 (0, 1, 0); primary reconstruction of complete atrioventricular septum defect 3 (1, 2, 0); valve replacement 2 (1, 1, 0); ventricular septum defect 10 (4, 6, 0); atrial septum defect closure 5 (2, 3, 0); total cavopulmonal anastomosis 1 (1, 0, 0); valve replacement in congenital transposition of great arteries 1 (0, 1, 0), Ebstein operation with valve plasty 2 (0, 1, 1); valve replacement 2 (1, 0, 1). RESULTS: There was no operative mortality, while early mortality occurred in one patient with total cavopulmonal anastomosis due to multiorgan failure. CONCLUSIONS: Congenital heart defects can be operated beyond the age of 60 years with good results in a tertiary heart centre having great experience in the management of congenital and acquired heart disease.

Enhancing recombinant protein solubility with ubiquitin-like small archeal modifying protein fusion partners.

A variety of protein expression tags with different biochemical properties has been used to enhance the yield and solubility of recombinant proteins. Ubiquitin, SUMO (small ubiquitin-like modifier) and prokaryotic ubiquitin like MoaD (molybdopterin synthase, small subunit) fusion tags are getting more popular because of their small size. In this paper we report on the use of ubiquitin-like small archaeal modifier proteins (SAMPs) as fusion tags since they proved to increase expression yield, stability and solubility in our experiments. Equally important, they did not co-purify with proteins of the expression host and there was information that their specific JAB1/MPN/Mov34 metalloenzyme (JAMM) protease can recognize the C-terminal VSGG sequence when SAMPs fused, either branched or linearly to target proteins, and cleave it specifically. SAMPs and JAMM proteases from Haloferax volcanii, Thermoplasma acidophilum, Methanococcoides burtonii and Nitrosopumilus maritimus were selected, cloned, expressed heterologously in Escherichia coli and tested as fusion tags and cleaving proteases, respectively. Investigated SAMPs enhanced protein expression and solubility on a wide scale. T. acidophilum SAMPs Ta0895 and Ta01019 were the best performing tags and their effect was comparable to the widely used maltose binding protein (MBP) and N utilization substance protein A (NusA) tags. Moreover, H. volcanii SAMP Hvo_2619 contribution was mediocre, whereas M. burtonii Mbur_1415 could not be expressed. Out of four investigated JAMM proteases, only Hvo_2505 could cleave fusion tags. Interestingly, it was found active not only on its own partner substrate Hvo_2619, but it also cleaved off Ta0895.

[Successful surgical management of aortico-left ventricular tunnel using modern noninvasive diagnostic imaging methods]. / Aorta-bal kamra tunnel sikeres sebészi kezelése modern noninvazív képalkotó diagnosztika alapján.

Aortico-left ventricular tunnel is a rare congenital cardiac defect, which bypasses the aortic valve via the paravalvar connection from the aorta to the left ventricle. The authors present the case of a 14-year-old boy with aortico-left ventricular tunnel in whom the aortic orifice arose from the right aortic sinus and was closed by a pericardial patch. The diagnosis was confirmed by combined two-dimensional and real time three-dimensional echocardiogram and magnetic resonance imaging. This is the first case, in which these complex diagnostic imaging methods have been used in the pre- and postoperative management of this defect. Optimally the new transthoratic three-dimensional echocardiography would be needed to define the anatomy and functional consequences of the aortico-left ventricular tunnel and in the postoperative follow-up.

[Perspectives in the management of congenital heart defects in adult patients]. / Perspektívák a veleszületett szívhibák felnottkori sebészi kezelésében.

Due to improving results in congenital heart surgery, the number of adult patients with congenital heart defect is increasing. The question is: what kind of problems can be managed in this patient-group? The authors review the different problems of management of congenital heart defects in adults based on national and international literature data. Simple defects recognised in adults, postoperative residual problems, changing of small grafts and valves, correction of primary or operated coarctation aortae can be usually managed without problems. A very close follow-up is necessary to establish the correct period for heart transplantation in patients with transposition of great arteries with Senning/Mustard operation, and univentricular heart corrected with "Fontan-circulation" type surgical procedure. The authors conclude that although the number of patients increases, only a few congenital heart diseases may cause problems. It seems important (1) to monitor asymptomatic patient who underwent operation (Fallot-IV, Ross procedure, etc.), (2) follow up regularly patients who underwent Senning/Mustard procedure (magnetic resonance imaging, echocardiography, brain natriuretic peptide measurement), (3) define the proper period of preparation for heart transplantation of patients with a univentricular heart, with special attention to the possibility of multiorgan (lung, liver, etc.) failure. Due to the improvement of foetal diagnosis of congenital heart defects, the number of patients with complex congenital heart defects is decreasing. The standard management of these patients could be primary heart transplantation in infancy.

The first transformation method for the thermo-acidophilic archaeon Thermoplasma acidophilum.

A transformation method yielding up to 10(4) transformants per µg circular DNA was developed for Thermoplasma acidophilum. The method is based on a natural DNA uptake process in which T. acidophilum cells keep their integrity and turn competent at pH 3.5 and 58°C. Shuttle vector maintenance could not be detected, since the used Nov(R) gyraseB gene integrated into its chromosomal counterpart by homologous recombination.

Non-random distribution of interleukin receptors on the cell surface.

Spatial organization of cell surface proteins plays a key role in the process of transmembrane signalling. Receptor clustering and changes in their cell surface distribution are often determining factors in the final outcome of ligand-receptor interactions. There are several techniques for assessing the distribution of protein molecules. Fluorescence resonance energy transfer (FRET) is an excellent tool for determining distance relationships of cell surface molecules. However, it does not provide information on the distribution of molecular clusters. Different kinds of microscopies fill this gap. The evaluation of the images provided by the listed techniques is often questionable. Herein we show the applicability of Ripley's K(t) function as a tool for analyzing the cell surface receptor patterns (Y. Nakamura, et al., Nature 1994, 369, 330-333). We have implemented an effective image processing algorithm for fast localization of gold labels on biological samples. We investigated spatial organization of Interleukin-2R alpha and -15R alpha (IL-2R alpha and IL-15R alpha) on a human CD4+leukaemia T-cell line, Kit225 FT7.10 by using transmission electron microscopy (TEM). TEM analysis showed co-clustering of the two types of alpha-chains even on the few-hundred-nanometer scale. The analysis of our data may contribute to our understanding the action of the IL-2/IL-15 receptor system in T-cell function.

Synthesis of 5-(1-H or 1-alkyl-5-oxopyrrolidin-3-yl)-8-hydroxy-[1,6]-naphthyridine-7-carboxamide inhibitors of HIV-1 integrase.

HIV-1 integrase catalyzes the insertion of viral DNA into the genome of the host cell. Integrase inhibitor N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide selectively inhibits the strand transfer process of integration. 4-Substituted pyrrolidinones possessing various groups on the pyrrolidinone nitrogen were introduced at the 5-position of the naphthyridine scaffold. These analogs exhibit excellent activity against viral replication in a cell-based assay. The preparation of these compounds was enabled by a three-step, two-pot reaction sequence from a common butenolide intermediate.

Ribonucleoprotein-masked nicks at 50-kbp intervals in the eukaryotic genomic DNA.

By using a microscopic approach, field inversion single-cell gel electrophoresis, we show that preformed single-strand discontinuities are present in the chromatin of resting and proliferating mammalian and yeast cells. These single-strand breaks are primarily nicks positioned at approximately 50-kbp intervals throughout the entire genome that could be efficiently labeled in situ by DNA polymerase I holoenzyme but not by Klenow fragment and terminal transferase unless after ribonucleolytic treatments. The RNA molecules involved appear to comprise R-loops, recognized by the S9.6 RNA/DNA hybrid-specific antibody. By using the breakpoint cluster region of the Mixed Lineage Leukemia (MLL) gene as a model, we have found that the number of manifest nicks detected by FISH performed after field inversion single-cell gel electrophoresis depends on epigenetic context, but the difference between germ-line and translocated MLL alleles is abolished by protease treatment. Our data imply that the double-stranded genomic DNA is composed of contiguous rather than continuous single strands and reveal an aspect of higher-order chromatin organization with ribonucleoprotein-associated persistent nicks defining approximately 50-kbp domains.

[Teaching of microsurgery--in service of research and clinical practice]. / Mikrosebészeti oktatás a kutatás és a klinikai gyakorlat szolgálatában.

We analyse the improving role of teaching microsurgery, the advantages of the microsurgical models in research and clinical practice. We summarize our experience in teaching basic microsurgery according to Furka's model in the last 15 years. The main characteristics of the principles are: activity, synchronism, video assistance, self-control, individualization, analysis. We show the curriculum of the courses for researchers and participants in graduate and postgraduate education, which consists dry-training on models followed by surgical interventions on rats. Summarizing of our practices: to learn the basic microsurgical techniques the participants need endurance, patience, and have to work hard. Effectiveness of the education is most successful if we organize small groups, if one teacher deals with a maximum of two or three candidates.

[Metastasis of breast cancer presenting in the appendix]. / Meglepetést okozó appendix avagy primer emlorák metasztázisa okozta appendicitis.

A 45 year-old woman was referred to the Emergency Department of Jósa András County Hospital with typical history and signs of appendicitis. Other than abdominal findings during physical examination we discovered a palpable mass in the right breast. The patient was transferred to the Department of Surgery and she was operated on, appendicectomy was performed. Following the uncomplicated postoperative course investigations were carried out to diagnose the mass in the right breast (mammography, ultrasound, chest X-ray, bone scan). The pathology report of the appendix suggested the possibility of a metastasis of ductal breast carcinoma in the perforated appendix. Probably the inflammation was caused by the infiltration of the appendix wall leading to perforation. Following the investigations a right-sided mastectomy was performed with dissection of axillary lymph nodes. Immunohistochemical examination definitely proved that the metastasis in the appendix originated from the breast tumour.