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Elites played a pivotal role in the formation of post-Roman Europe on both macro- and microlevels during the Early Medieval period. History and archaeology have long focused on their description and identification based on written sources or through their archaeological record. We provide a different perspective on this topic by integrating paleogenomic, archaeological, and isotopic data to gain insights into the role of one such elite group in a Langobard period community near Collegno, Italy dated to the 6-8th centuries CE. Our analysis of 28 newly sequenced genomes together with 24 previously published ones combined with isotope (Sr, C, N) measurements revealed that this community was established by and organized around a network of biologically and socially related individuals likely composed of multiple elite families that over time developed into a single extended pedigree. The community also included individuals with diverse genetic ancestries, maintaining its diversity by integrating newcomers and groups in later stages of its existence. This study highlights how shifts in political power and migration impacted the formation and development of a small rural community within a key region of the former Western Roman Empire after its dissolution and the emergence of a new kingdom. Furthermore, it suggests that Early Medieval elites had the capacity to incorporate individuals from varied backgrounds and that these elites were the result of (political) agency rather than belonging to biologically homogeneous groups.
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Arqueologia , Mundo Romano , Humanos , Mundo Romano/história , Itália , História Medieval , Migração Humana/história , História AntigaRESUMO
Our knowledge of how society viewed leprosy and treated its victims in the past is still scarce, especially in geographical regions and archaeological periods from where no written sources are available. To fill in some research gaps, we provide the comparative analysis of five previously described, probable cases with leprosy from the Avar-period Trans-Tisza region (Hungary). The five skeletons were subject to a detailed macromorphological (re-)evaluation. Where possible, the biological and social consequences of having leprosy were reconstructed based on the observed bony changes and mortuary treatment, respectively. The retrospective, macromorphology-based diagnosis of leprosy could be established in three cases only. Based on the detected skeletal lesions, all of them suffered from near-lepromatous or lepromatous leprosy. The disease resulted in aesthetic repercussions and functional implications, which would have been disadvantageous for these individuals, and limited or changed their possibilities to participate in social situations. They could have even required heavy time investment from their respective communities. The analysis of the mortuary treatment of the confirmed leprosy cases revealed no evidence of a social stigma. These findings indicate that the afflicted have not been systematically expulsed or segregated, at least in death, in the Early Middle Ages of the Carpathian Basin.
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From AD 567-568, at the onset of the Avar period, populations from the Eurasian Steppe settled in the Carpathian Basin for approximately 250 years1. Extensive sampling for archaeogenomics (424 individuals) and isotopes, combined with archaeological, anthropological and historical contextualization of four Avar-period cemeteries, allowed for a detailed description of the genomic structure of these communities and their kinship and social practices. We present a set of large pedigrees, reconstructed using ancient DNA, spanning nine generations and comprising around 300 individuals. We uncover a strict patrilineal kinship system, in which patrilocality and female exogamy were the norm and multiple reproductive partnering and levirate unions were common. The absence of consanguinity indicates that this society maintained a detailed memory of ancestry over generations. These kinship practices correspond with previous evidence from historical sources and anthropological research on Eurasian Steppe societies2. Network analyses of identity-by-descent DNA connections suggest that social cohesion between communities was maintained via female exogamy. Finally, despite the absence of major ancestry shifts, the level of resolution of our analyses allowed us to detect genetic discontinuity caused by the replacement of a community at one of the sites. This was paralleled with changes in the archaeological record and was probably a result of local political realignment.
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Arqueologia , DNA Antigo , Características da Família , Pradaria , Linhagem , Adulto , Feminino , Humanos , Masculino , Arqueologia/métodos , Ásia/etnologia , Cemitérios/história , Consanguinidade , DNA Antigo/análise , Europa (Continente)/etnologia , Características da Família/etnologia , Características da Família/história , Genômica , História Medieval , Política , Adolescente , Adulto JovemRESUMO
In recent years, our knowledge of leprosy in the past has substantially been enriched. Nonetheless, much still remains to be discovered, especially in regions and periods from where no written sources are available. To fill in some research gaps, we provide the comparative analysis of eight Avar-period leprosy cases from the Danube-Tisza Interfluve (Hungary). In every case, to reconstruct the biological consequences of leprosy, the detected bony changes were linked with palaeopathological and modern medical information. To reconstruct the social consequences of being affected by leprosy, conceptualisation of the examined individuals' treatment in death was conducted. In every case, the disease resulted in deformation and disfigurement of the involved anatomical areas (rhinomaxillary region, feet, and/or hands) with difficulties in conducting certain physical activities. These would have been disadvantageous for the examined individuals and limited or changed their possibilities to participate in social situations. The most severe cases would have required continuous support from others to survive. Our findings indicate that, despite their very visible disease and associated debility, the examined communities did not segregate leprosy sufferers but provided and cared for them, and maintained a strong enough social network that made their survival possible even after becoming incapable of self-sufficiency.
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Hanseníase , Mycobacterium tuberculosis , Humanos , Hungria , Lacunas de Evidências , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , SulfacetamidaRESUMO
As the collapse of the Western Roman Empire accelerated during the 4th and 5th centuries, arriving "barbarian" groups began to establish new communities in the border provinces of the declining (and eventually former) empire. This was a time of significant cultural and political change throughout not only these border regions but Europe as a whole.1,2 To better understand post-Roman community formation in one of these key frontier zones after the collapse of the Hunnic movement, we generated new paleogenomic data for a set of 38 burials from a time series of three 5th century cemeteries3,4,5 at Lake Balaton, Hungary. We utilized a comprehensive sampling approach to characterize these cemeteries along with data from 38 additional burials from a previously published mid-6th century site6 and analyzed them alongside data from over 550 penecontemporaneous individuals.7,8,9,10,11,12,13,14,15,16,17,18,19 The range of genetic diversity in all four of these local burial communities is extensive and wider ranging than penecontemporaneous Europeans sequenced to date. Despite many commonalities in burial customs and demography, we find that there were substantial differences in genetic ancestry between the sites. We detect evidence of northern European gene flow into the Lake Balaton region. Additionally, we observe a statistically significant association between dress artifacts and genetic ancestry among 5th century genetically female burials. Our analysis shows that the formation of early Medieval communities was a multifarious process even at a local level, consisting of genetically heterogeneous groups.
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Arqueologia , Cemitérios , Humanos , Feminino , Cemitérios/história , Cultura , Sequência de Bases , Europa (Continente)RESUMO
Vagal nerve stimulation (VNS) holds a strong basis as a potentially effective treatment modality for chronic heart failure, which explains why a multicenter VNS study in heart failure with reduced ejection fraction is ongoing. However, more detailed information is required on the effect of acetylcholine (ACh) on repolarization in Purkinje and ventricular cardiac preparations to identify the advantages, risks, and underlying cellular mechanisms of VNS. Here, we studied the effect of ACh on the action potential (AP) of canine Purkinje fibers (PFs) and several human ventricular preparations. In addition, we characterized the effects of ACh on the L-type Ca2+ current (ICaL) and AP of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and performed computer simulations to explain the observed effects. Using microelectrode recordings, we found a small but significant AP prolongation in canine PFs. In the human myocardium, ACh slightly prolonged the AP in the midmyocardium but resulted in minor AP shortening in subepicardial tissue. Perforated patch-clamp experiments on hiPSC-CMs demonstrated that 5 µM ACh caused an ≈15% decrease in ICaL density without changes in gating properties. Using dynamic clamp, we found that under blocked K+ currents, 5 µM ACh resulted in an ≈23% decrease in AP duration at 90% of repolarization in hiPSC-CMs. Computer simulations using the O'Hara-Rudy human ventricular cell model revealed that the overall effect of ACh on AP duration is a tight interplay between the ACh-induced reduction in ICaL and ACh-induced changes in K+ currents. In conclusion, ACh results in minor changes in AP repolarization and duration of canine PFs and human ventricular myocardium due to the concomitant inhibition of inward ICaL and outward K+ currents, which limits changes in net repolarizing current and thus prevents major changes in AP repolarization.
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Even though rodents are accessible model animals, their electrophysiological properties are deeply different from those of humans, making the translation of rat studies to humans rather difficult. We compared the mechanisms of ventricular repolarization in various animal models to those of humans by measuring cardiac ventricular action potentials from ventricular papillary muscle preparations using conventional microelectrodes and applying selective inhibitors of various potassium transmembrane ion currents. Inhibition of the IK1 current (10 µmol/L barium chloride) significantly prolonged rat ventricular repolarization, but only slightly prolonged it in dogs, and did not affect it in humans. On the contrary, IKr inhibition (50 nmol/L dofetilide) significantly prolonged repolarization in humans, rabbits, and dogs, but not in rats. Inhibition of the IKur current (1 µmol/L XEN-D0101) only prolonged rat ventricular repolarization and had no effect in humans or dogs. Inhibition of the IKs (500 nmol/L HMR-1556) and Ito currents (100 µmol/L chromanol-293B) elicited similar effects in all investigated species. We conclude that dog ventricular preparations have the strongest translational value and rat ventricular preparations have the weakest translational value in cardiac electrophysiological experiments.
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Canais de Potássio , Potássio , Potenciais de Ação , Animais , Cães , Coração/fisiologia , Ventrículos do Coração , Humanos , Miocárdio/metabolismo , Potássio/metabolismo , Coelhos , RatosRESUMO
The Avars settled the Carpathian Basin in 567/68 CE, establishing an empire lasting over 200 years. Who they were and where they came from is highly debated. Contemporaries have disagreed about whether they were, as they claimed, the direct successors of the Mongolian Steppe Rouran empire that was destroyed by the Turks in â¼550 CE. Here, we analyze new genome-wide data from 66 pre-Avar and Avar-period Carpathian Basin individuals, including the 8 richest Avar-period burials and further elite sites from Avar's empire core region. Our results provide support for a rapid long-distance trans-Eurasian migration of Avar-period elites. These individuals carried Northeast Asian ancestry matching the profile of preceding Mongolian Steppe populations, particularly a genome available from the Rouran period. Some of the later elite individuals carried an additional non-local ancestry component broadly matching the steppe, which could point to a later migration or reflect greater genetic diversity within the initial migrant population.
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Povo Asiático , DNA Antigo , Genética Populacional , Povo Asiático/genética , Genoma , História Antiga , Migração Humana/história , Humanos , EnxofreRESUMO
Vagal nerve stimulation (VNS) has a meaningful basis as a potentially effective treatment for heart failure with reduced ejection fraction. There is an ongoing VNS randomized study, and four studies are completed. However, relatively little is known about the effect of acetylcholine (ACh) on repolarization in human ventricular cardiomyocytes, as well as the effect of ACh on the rapid component of the delayed rectifier K+ current (IKr). Here, we investigated the effect of ACh on the action potential parameters in human ventricular preparations and on IKr in human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). Using standard microelectrode technique, we demonstrated that ACh (5 µM) significantly increased the action potential duration in human left ventricular myocardial slices. ACh (5 µM) also prolonged repolarization in a human Purkinje fiber and a papillary muscle. Optical mapping revealed that ACh increased the action potential duration in human left ventricular myocardial slices and that the effect was dose-dependent. Perforated patch clamp experiments demonstrated action potential prolongation and a significant decrease in IKr by ACh (5 µM) in hiPSC-CMs. Computer simulations of the electrical activity of a human ventricular cardiomyocyte showed an increase in action potential duration upon implementation of the experimentally observed ACh-induced changes in the fully activated conductance and steady-state activation of IKr. Our findings support the hypothesis that ACh can influence the repolarization in human ventricular cardiomyocytes by at least changes in IKr.
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BACKGROUND AND PURPOSE: The aim of the present study was to study the antiarrhythmic effects and cellular mechanisms of desethylamiodarone (DEA), the main metabolite of amiodarone (AMIO), following acute and chronic 4-week oral treatments (25-50 mg·kg-1 ·day-1 ). EXPERIMENTAL APPROACH: The antiarrhythmic effects of acute iv. (10 mg·kg-1 ) and chronic oral (4 weeks, 25 mg·kg-1 ·day-1 ) administration of DEA were assessed in carbachol and tachypacing-induced dog atrial fibrillation models. Action potentials were recorded from atrial and right ventricular tissue following acute (10 µM) and chronic (p.o. 4 weeks, 50 mg·kg-1 ·day-1 ) DEA application using the conventional microelectrode technique. Ionic currents were measured by the whole cell configuration of the patch clamp technique in isolated left ventricular myocytes. Pharmacokinetic studies were performed following a single intravenous dose (25 mg·kg-1 ) of AMIO and DEA intravenously and orally. In chronic (91-day) toxicological investigations, DEA and AMIO were administered in the oral dose of 25 mg·kg-1 ·day-1 ). KEY RESULTS: DEA exerted marked antiarrhythmic effects in both canine atrial fibrillation models. Both acute and chronic DEA administration prolonged action potential duration in atrial and ventricular muscle without any changes detected in Purkinje fibres. DEA decreased the amplitude of several outward potassium currents such as IKr , IKs , IK1 , Ito , and IKACh , while the ICaL and late INa inward currents were also significantly depressed. Better drug bioavailability and higher volume of distribution for DEA were observed compared to AMIO. No neutropenia and less severe pulmonary fibrosis was found following DEA compared to that of AMIO administration. CONCLUSION AND IMPLICATIONS: Chronic DEA treatment in animal experiments has marked antiarrhythmic and electrophysiological effects with better pharmacokinetics and lower toxicity than its parent compound. These results suggest that the active metabolite, DEA, should be considered for clinical trials as a possible new, more favourable option for the treatment of cardiac arrhythmias including atrial fibrillation.
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Amiodarona , Fibrilação Atrial , Potenciais de Ação , Amiodarona/análogos & derivados , Amiodarona/farmacologia , Animais , Antiarrítmicos/farmacologia , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/metabolismo , Cães , Átrios do Coração , Miócitos CardíacosRESUMO
Ibuprofen is a widely used nonsteroidal anti-inflammatory drug, which has recently been associated with increased cardiovascular risk, but its electrophysiological effects have not yet been properly studied in isolated cardiac preparations. We studied the effects of ibuprofen on action potential characteristics and several transmembrane ionic currents using the conventional microelectrode technique and the whole-cell configuration of the patch-clamp technique on cardiac preparations and enzymatically isolated ventricular myocytes. In dog (200 µM; n = 6) and rabbit (100 µM; n = 7) papillary muscles, ibuprofen moderately but significantly prolonged repolarization at 1 Hz stimulation frequency. In dog Purkinje fibers, repolarization was abbreviated and maximal rate of depolarization was depressed in a frequency-dependent manner. Levofloxacin (40 µM) alone did not alter repolarization, but augmented the ibuprofen-evoked repolarization lengthening in rabbit preparations (n = 7). In dog myocytes, ibuprofen (250 µM) did not significantly influence IK1, but decreased the amplitude of Ito and IKr potassium currents by 28.2% (60 mV) and 15.2% (20 mV), respectively. Ibuprofen also depressed INaL and ICa currents by 19.9% and 16.4%, respectively. We conclude that ibuprofen seems to be free from effects on action potential parameters at lower concentrations. However, at higher concentrations it may alter repolarization reserve, contributing to the observed proarrhythmic risk in patients.
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Potenciais de Ação/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/efeitos adversos , Arritmias Cardíacas/diagnóstico , Ventrículos do Coração/efeitos dos fármacos , Ibuprofeno/efeitos adversos , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Arritmias Cardíacas/induzido quimicamente , Cães , Relação Dose-Resposta a Droga , Ventrículos do Coração/citologia , Humanos , Ibuprofeno/administração & dosagem , Masculino , Microeletrodos , Miócitos Cardíacos , Técnicas de Patch-Clamp , Ramos Subendocárdicos/efeitos dos fármacos , CoelhosRESUMO
Activation of the parasympathetic nervous system has been reported to have an antiarrhythmic role during ischemia-reperfusion injury by decreasing the arrhythmia triggers. Furthermore, it was reported that the parasympathetic neurotransmitter acetylcholine is able to modulate the ATP-dependent potassium current (I K-ATP), a crucial current activated during hypoxia. However, the possible significance of this current modulation in the antiarrhythmic mechanism is not fully clarified. Action potentials were measured using the conventional microelectrode technique from canine left ventricular papillary muscle and free-running Purkinje fibers, under normal and hypoxic conditions. Ionic currents were measured using the whole-cell configuration of the patch-clamp method. Acetylcholine at 5 µmol/L did not influence the action potential duration (APD) either in Purkinje fibers or in papillary muscle preparations. In contrast, it significantly lengthened the APD and suppressed the Purkinje-ventricle APD dispersion when it was administered after 5 µmol/L pinacidil application. Carbachol at 3 µmol/L reduced the pinacidil-activated I K-ATP under voltage-clamp conditions. Acetylcholine lengthened the ventricular action potential under simulated ischemia condition. In this study, we found that acetylcholine inhibits the I K-ATP and thus suppresses the ventricle-Purkinje APD dispersion. We conclude that parasympathetic tone may reduce the arrhythmogenic substrate exerting a complex antiarrhythmic mechanism during hypoxic conditions.
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Potenciais de Ação/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Ventrículos do Coração/efeitos dos fármacos , Agonistas Muscarínicos/farmacologia , Potássio/metabolismo , Ramos Subendocárdicos/efeitos dos fármacos , Animais , Cães , Ventrículos do Coração/citologia , Ramos Subendocárdicos/citologiaRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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The decline of the Roman rule caused significant political instability and led to the emergence of various 'Barbarian' powers. While the names of the involved groups appeared in written sources, it is largely unknown how these changes affected the daily lives of the people during the 5th century AD. Did late Roman traditions persist, did new customs emerge, and did both amalgamate into new cultural expressions? A prime area to investigate these population and settlement historical changes is the Carpathian Basin (Hungary). Particularly, we studied archaeological and anthropological evidence, as well as radiogenic and stable isotope ratios of strontium, carbon, and nitrogen of human remains from 96 graves at the cemetery of Mözs-Icsei dulo. Integrated data analysis suggests that most members of the founder generation at the site exhibited burial practises of late Antique traditions, even though they were heterogeneous regarding their places of origin and dietary habits. Furthermore, the isotope data disclosed a nonlocal group of people with similar dietary habits. According to the archaeological evidence, they joined the community a few decades after the founder generation and followed mainly foreign traditions with artificial skull modification as their most prominent characteristic. Moreover, individuals with modified skulls and late Antique grave attributes attest to deliberate cultural amalgamation, whereas burials of largely different isotope ratios underline the recipient habitus of the community. The integration of archaeological and bioarchaeological information at the individual level discloses the complex coalescence of people and traditions during the 5th century.
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Arqueologia , Mundo Romano/história , Mudança Social/história , Adolescente , Restos Mortais/anatomia & histologia , Restos Mortais/fisiologia , Cemitérios , Criança , Pré-Escolar , Comportamento Alimentar , Feminino , História Antiga , Humanos , Hungria , Lactente , Recém-Nascido , Masculino , Crânio/anatomia & histologia , Crânio/fisiologia , Adulto JovemRESUMO
After 568 AD the Avars settled in the Carpathian Basin and founded the Avar Qaganate that was an important power in Central Europe until the 9th century. Part of the Avar society was probably of Asian origin; however, the localisation of their homeland is hampered by the scarcity of historical and archaeological data. Here, we study mitogenome and Y chromosomal variability of twenty-six individuals, a number of them representing a well-characterised elite group buried at the centre of the Carpathian Basin more than a century after the Avar conquest. The studied group has maternal and paternal genetic affinities to several ancient and modern East-Central Asian populations. The majority of the mitochondrial DNA variability represents Asian haplogroups (C, D, F, M, R, Y and Z). The Y-STR variability of the analysed elite males belongs only to five lineages, three N-Tat with mostly Asian parallels and two Q haplotypes. The homogeneity of the Y chromosomes reveals paternal kinship as a cohesive force in the organisation of the Avar elite strata on both social and territorial level. Our results indicate that the Avar elite arrived in the Carpathian Basin as a group of families, and remained mostly endogamous for several generations after the conquest.
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Arqueologia , Povo Asiático/genética , Cromossomos Humanos Y , Consanguinidade , DNA Mitocondrial , Família , Genética Populacional , Europa Oriental , Feminino , Haplótipos , Humanos , Masculino , Repetições de MicrossatélitesRESUMO
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are membrane proteins encoded by four genes (HCN1-4) and widely distributed in the central and peripheral nervous system and in the heart. HCN channels are involved in several physiological functions, including the generation of rhythmic activity, and are considered important drug targets if compounds with isoform selectivity are developed. At present, however, few compounds are known, which are able to discriminate among HCN channel isoforms. The inclusion of the three-methylene chain of zatebradine into a cyclohexane ring gave a compound (3a) showing a 5-fold preference for HCN4 channels, and ability to selectively modulate Ih in different tissues. Compound 3a has been tested for its ability to reduce Ih and to interact with other ion channels in the heart and the central nervous system. Its preference for HCN4 channels makes this compound useful to elucidate the contribution of this isoform in the physiological and pathological processes involving hyperpolarization-activated current.
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From the first century AD, Europe has been interested by population movements, commonly known as Barbarian migrations. Among these processes, the one involving the Longobard culture interested a vast region, but its dynamics and demographic impact remains largely unknown. Here we report 87 new complete mitochondrial sequences coming from nine early-medieval cemeteries located along the area interested by the Longobard migration (Czech Republic, Hungary and Italy). From the same areas, we sampled necropoleis characterized by cultural markers associated with the Longobard culture (LC) and coeval burials where no such markers were found, or with a chronology slightly preceding the presumed arrival of the Longobards in that region (NLC). Population genetics analysis and demographic modeling highlighted a similarity between LC individuals, as reflected by the sharing of quite rare haplogroups and by the degree of genetic resemblance between Hungarian and Italian LC necropoleis estimated via a Bayesian approach, ABC. The demographic model receiving the strongest statistical support also postulates a contact between LC and NLC communities, thus indicating a complex dynamics of admixture in medieval Europe.
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DNA Antigo/análise , DNA Mitocondrial/genética , Genoma Mitocondrial/genética , Migração Humana/história , Teorema de Bayes , Cemitérios , República Tcheca , Haplótipos/genética , História Medieval , Humanos , Hungria , ItáliaRESUMO
Despite centuries of research, much about the barbarian migrations that took place between the fourth and sixth centuries in Europe remains hotly debated. To better understand this key era that marks the dawn of modern European societies, we obtained ancient genomic DNA from 63 samples from two cemeteries (from Hungary and Northern Italy) that have been previously associated with the Longobards, a barbarian people that ruled large parts of Italy for over 200 years after invading from Pannonia in 568 CE. Our dense cemetery-based sampling revealed that each cemetery was primarily organized around one large pedigree, suggesting that biological relationships played an important role in these early medieval societies. Moreover, we identified genetic structure in each cemetery involving at least two groups with different ancestry that were very distinct in terms of their funerary customs. Finally, our data are consistent with the proposed long-distance migration from Pannonia to Northern Italy.
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Genômica , Migração Humana/história , Paleontologia/história , Comportamento Social , Arqueologia , Cemitérios , Geografia , História Medieval , Humanos , Filogenia , Análise de Componente Principal , Isótopos de EstrôncioRESUMO
Racemic mexiletine is a widely used antiarrhythmic agent that blocks sodium channels. The effects of R-(-) and S-(+) mexiletine stereoisomers on maximum rate of depolarization ([Formula: see text]), conduction time, and repolarization have not yet been investigated in isolated cardiac preparations. We studied the effect of the R-(-) and S-(+) mexiletine on rabbit cardiac action potential parameters by using the conventional microelectrode technique. Both enantiomers at 20 µmol/L of therapeutically and experimentally relevant concentration, significantly depressed the [Formula: see text] at fast heart rates (BCLs 300-700 ms). R-(-) mexiletine has more potent inhibitory effect than S-(+) mexiletine. Both R-(-) and S-(+) mexiletine significantly inhibited the [Formula: see text] of early extrasystoles measured at 70 ms diastolic interval induced by S1-S2 stimuli. R-(-) mexiletine has more pronounced inhibitory effect than S-(+) mexiletine. Both R-(-) and S-(+) mexiletine increased significantly the ERP/APD90 ratio. The time constant (τ) of recovery of [Formula: see text] was found to be τ = 376.0 ± 77.8 ms for R-(-) mexiletine and τ = 227.1 ± 23.4 ms for S-(+) mexiletine, which indicates a slower offset kinetics for R-(-) mexiletine from sodium channels than that of the S-(+) enantiomer. These data suggest that R-(-) mexiletine might be a more potent antiarrhythmic agent than S-(+) mexiletine.
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Fenômenos Eletrofisiológicos/efeitos dos fármacos , Coração/efeitos dos fármacos , Coração/fisiologia , Mexiletina/química , Mexiletina/farmacologia , Rotação , Animais , Masculino , Potenciais da Membrana/efeitos dos fármacos , Coelhos , EstereoisomerismoRESUMO
Chest pain is a common symptom in patients who visit Emergency Departments. The main task is to exclude life-threatening diseases such as acute coronary syndrome, pulmonary embolization and dissection of thoracic aorta. The authors present the history of a patient, who had an intense chest pain for 7 hours. In accordance with the diagnostic algorithm of chest pain, ECG, blood collection, chest X-ray and chest computed tomography angiography were performed. Acute coronary syndrome, pulmonary embolization and dissection of the thoracic aorta were excluded, however, chest computed tomography CT revealed a huge hiatal hernia as an incidental finding. An emergency surgical repair was performed and the patient recovered without any complications. The authors emphasize that the diagnostic algorithms focus on the confirmation or rejection of possible life threatening diseases in case of chest pain. However, it should be kept in mind that rarer causes may occur, which may require involvement of the relevant disciplines and multidisciplinary thinking. Orv. Hetil., 2016, 157(36), 1445-1448.