First direct dating of the Late Neanderthal remains from Subalyuk Cave in Northern Hungary.

The Subalyuk hominin remains were uncovered in 1932 in a cave of the same name in the Bükk Mountains, near the village of Cserépfalu in Borsod-Abaúj-Zemplén County, Northern Hungary. The remains represent two individuals, an adult and a young child who have been described in a few publications since their discovery, providing substantial anthropological data and general assessments of their Neanderthal affiliation. They were associated with Late Mousterian industry. Thus, the Bükk Mountains gain importance in the discussion concerning the contribution of East Central European sites to the debate on the peopling history of Europe during the Late Middle to Early Upper Palaeolithic transition. In this paper, we summarize the archaeological and chronological context of the two individuals, and publish the first direct dating results that place them among the Last Neanderthals of Central Europe.

The paleopathology and paleoepidemiology of Upper paleolithic tuberculosis: Review of evidence and hypotheses.

Molecular phylogeny work has shown that tuberculosis is ancient human-adapted infection predating the Neolithic period. They also show that the Upper Paleolithic is a key period of emergence of the MTB complex strains, contemporary with the exit of modern man from Africa. Despite the richness of Upper Paleolithic sites in Eurasia and the relative abundance of human remains, the only proven case of Paleolithic tuberculosis has been described so far date from the Azilian, a culture of the European Final Paleolithic, which is more recent than the ancient Neolithic sites of the Near East, area that currently hold the record for the oldest paleopathological evidence of tuberculosis. The purpose of this review is to present evidence for the existence of tuberculosis in the Paleolithic and to list hypotheses explaining the weak demonstrative contribution of paleopathology for pre-Neolithic periods.

Upper Paleolithic tuberculosis: A probable case illustrated by paleoimaging methods (Azilian site of Les Iboussières, France).

The aim of this paper is to present the results of µCT-scan and 3D imaging analyses of two skeletal lesions observed on human remains of one of the last European hunter-gatherers from the late Paleolithic (Azilian period): a sacroiliac osteoarthritis and a femoral lesion suggestive of a soft tissue abscess imprint. These two skeletal elements (fused left sacrum and coxal bone, and right femur) displayed osteometric criteria indicating that they belonged to the same individual. These two associated lesions are consistent with a low-grade osteoarticular infection, and suggest a diagnosis of pelvic tuberculosis with a cold abscess of the thigh. If molecular confirmation is obtained, this case would be the first evidence of tuberculosis among Upper Palaeolithic populations.

Oldest evidence of tuberculosis in the Mediterranean islands: From the mainland to Cyprus.

Recent studies combining macroscopical observations and microCT analysis strongly suggested the diagnosis of tuberculosis for a child from the site of Khirokitia (Cyprus, 7th - early 6th millennium cal. BC), whose age at death is between 5 and 7 years. Many single primary burials were discovered at the site where the dead (MNI = 243) are buried in the same way, whatever their age. Nevertheless, the burial of this child presents a unique feature on the site (a male Ovis trophy marking the limit of the burial pit), probably indicating specific attention for this young deceased. This case is the oldest known in the Mediterranean islands and presents a particular interest from a paleoepidemiological point of view. Indeed, considering, on the one hand, the settlement pattern of the island of Cyprus by migrants from the Near East, and on the other hand, the presence of human tuberculosis in the Near East as early as about 10,500 years BP, it is very likely that the prehistoric migrants brought the disease from mainland to Cyprus.

Re-examination of the Subalyuk Neanderthal remains uncovers signs of probable TB infection (Subalyuk Cave, Hungary).

In 1932, skeletal remains of two Neanderthal individuals, a young adult female and a 3-4-year-old child, were discovered in Subalyuk Cave in Northern Hungary [1,2]. Results of the anthropological examination were published some years after this important discovery. Methodological progress encouraged re-examination of the material during the last few years. Radiocarbon dating revealed a chronological age of 39,732-39,076 cal. BP for the adult female and 36,117-35,387 cal. BP for the child [3]. Morphological paleopathological studies of these Neanderthal remains uncovered distinct evidence of skeletal infections. Alterations of the adult individual's sacrum suggest probable early-stage sacroiliitis, while several vertebral bodies indicate superficial osseous remodelling of infectious origin. Traces of pathological lesions were observed on the endocranial surface of the child's skull, reflecting a reaction of meningeal tissues, a consequence of a probable TB-related meningeal infectious process. Results of recent paleomicrobiological examinations - lipid biomarker and aDNA studies - support the morphological diagnosis of probable TB infections [4].

Inner ear modifications in Dar-es-Soltane II H5 (Morocco): A case of labyrinthitis ossificans.

OBJECTIVE: This paper presents the inner ear modifications in Dar-es-Soltane II H5, an Aterian fossil possibly dated to 100 ka. MATERIAL: The remains consist of a large portion of the cranium including the face, the left frontal and temporal bones, part of the left parietal bone and greater wing of the sphenoid. METHODS: The bony labyrinth anatomy was investigated on existing micro-CT data acquired by the MPI-EVA. RESULTS: The observation of micro-CT sections revealed a partial filling of the semi-circular canals that raises question about its origin. A careful examination of the micro-CT sections shows that the elements present in the semicircular canals were denser than the sediments observed in other regions and cavities of the temporal bone. CONCLUSIONS: The current evidence suggests a pathological origin of this condition with partial ossification of the membranous labyrinth. The differential diagnosis indicates a case of labyrinthitis ossificans in its early stages. SIGNIFICANCE: This pathological condition can be responsible for permanent hearing loss and is associated with dizziness and vertigo. Along with the Singa skull, Dar-es-Soltane II H5 represents one of the oldest known cases of labyrinthitis ossificans. LIMITATIONS: The early stage of disease and the absence of the right temporal bone limit conclusions about the degree of disability of the individual and their dependence on the rest of the group. SUGGESTIONS FOR FURTHER RESEARCH: To carry out a paleopathological study of all the fossils from Dar-es-Soltane II.

[Antoine Deidier, his experimental approach to the contagious nature of plague in Marseille in 1720]. / Antoine Deidier, son approche expérimentale de la contagiosité de la peste a Marseille en 1720.

Born in 1670 Deidier became a medical doctor at the age of 21. The son-in-law, of Vieussens, he took care of the inhabitants of Marseilles during the plague of 1720. A contagionist and an experimenter, he was considered as a strange scientist by his colleagues. It is time now to rehabilitate his memory.

Was the rise of TB contemporaneous with the industrial revolution? Epidemiological evolution of TB in France (17th-20th centuries) inferred from osteoarchaeological and historical archives.

OBJECTIVE: The development of tuberculosis is classically associated with the rise of the Industrial Revolution. Our objective is to test this epidemiological hypothesis for populations in France between the 18th and 20th centuries using osteoarchaeological and historical sources. MATERIALS: Osteoarchaeological sources include two skeletal collections from plague epidemics in Provence (1590 and 1722) representing a total of 349 individuals and medical archives dating 1750-1930 from Paris, Lyon, Marseille, Montpellier. METHODS: Paleoepidemiological analysis (crude prevalence rate) of the archeological data, and epidemiological analysis of historical data included the proportional mortality rate of tuberculosis (PMR-TB) and the mortality rate by tuberculosis (MR-TB). RESULTS: Mean prevalence of TB before the 19th century was approximately 30 %, according to osteoarchaeological data. Historical sources showed that pulmonary TB was responsible for 33 % of total deaths in the city of Marseille during the second half of the 18th century and represented about 20 % of deaths in the four French cities during the 19th century. The mortality rate was 6.5 per thousand inhabitants in the 18th century (Marseille) and stable at 4-5 ‰ during the 19th century before, during, and after the Industrial Revolution period, with the exception of years 1870-1871 (French-Prussian war), when it increased. CONCLUSIONS: Population increase contemporary to the industrialization process did not increase the mortality rate by tuberculosis in France. SIGNIFICANCE: The epidemiological assertion that tuberculosis increased with the Industrial Revolution in cities must be reevaluated. In France, and perhaps in other cities, it was an endemic disease at least a century before, and associated with a higher mortality rate. LIMITATIONS: Reliability and biases inherent to archaeological and historical data prior and during the Industrial Revolution must be taken into account. SUGGESTIONS FOR FURTHER RESEARCH: Extension of research to all the French territories (rural and urban areas) is advised.

Are the identified collections of immature skeletons dating from the Industrial Revolution good references for paleoauxological studies? Cases studies from England & France.

OBJECTIVE: Skeletal collections of immature individuals identified by age and sex serve as reference material for studying development in past populations. Several of these collections were established during the Industrial Revolution (IR), a period known for its difficult living conditions in industrial cities. We question if these collections represent useful comparisons from which to explore the natural history of human growth. MATERIALS: Immature individuals from two skeletal collections contemporaneous to the IR period were studied: 71 children from the Spitalfields (UK) and 108 from the Strasbourg (F) collections. Among them we selected mandibles of individuals aged from 0 to 30 months, representing 32 and 52 individuals, respectively. METHODS: We scored the dental development of first and second left deciduous molars according to (Moorrees et al., 1963) stages, from X-rays (Spitalfields) or CT-scans (Strasbourg) data and compared it with the modern reference pattern from the Lewis Growth Records by covariance analysis (ANCOVA). RESULTS: Statistical differences exist in the dental development timeline between the 3 samples. This mainly concerns a delay in the root formation in IR samples that related to post-natal living conditions. CONCLUSIONS: The delay in dental development timeline suggests that growth processes were impacted during IR in England and France, probably due to stressful living conditions. SIGNIFICANCE: keletal collections dating from the IR period in Europe might be not the most appropriate referencesl for studying the natural history of human growth. LIMITATIONS: This study focus on dental development only. SUGGESTIONS FOR FURTHER RESEARCH: Exploring the skeletal growth pattern in other skeletal collections, pre or post-dating the IR, is advised.

Can the palaeoepidemiology of rickets during the industrialisation period in France be studied through bioarchaeological grey literature and French medico-historical literature of the 18th-early 20th centuries? Preliminary examination of a complex topic.

OBJECTIVE: This study explores whether data relating to rickets from the French medico-historical literature (FMHL) and bioarchaeological grey literature are useful in evaluating its epidemiology during the industrialisation of France. Unlike other European countries such as England, industrialisation in France was a slow and continuous process with two phases: the first in 1830-1870 and the second in 1870-1914. MATERIALS AND METHODS: A bibliographical analysis of 2800 FMHL sources from the 18th to the early 20th centuries and 50 archaeological excavation reports from the last 21 years was undertaken. RESULTS: The FMHL data is very heterogeneous and predominantly dates to the second phase of industrialisation. The bioarchaeological data is very incomplete and predominantly relates to the period before industrialisation. At the same time, knowledge improvement and institutional changes to protect children could explain more systematic registration of cases of rickets. CONCLUSIONS: No solid conclusions can be made regarding the prevalence of rickets at present, however these data hold great potential. SIGNIFICANCE: In comparison to England, no systematic investigation of rickets prevalence during the period of industrialisation in France has been undertaken to date. LIMITATIONS: The lack of archaeological excavations from this period and the limited paleopathological analysis of the sites excavated have contributed to our current lack of understanding regarding the impact of industrialization on the prevalence of rickets on the French population. SUGGESTIONS FOR FURTHER WORK: The FMHL data needs to be homogenized and osteoarchaeological collections need to be restudied with a common protocol focusing on signs of vitamin D deficiency.

A unique case of skeletal dysplasia in an adult male in Late Iron Age Switzerland.

OBJECTIVE: We report a probable case of multiple skeletal dysplasia observed in a Late Iron Age young adult male. MATERIALS: The individual studied belongs to a Late Iron Age necropolis from Switzerland. The skeletal elements are well preserved METHODS: Macroscopic and radiographic assessment. RESULTS: The individual shows evidence of both craniofacial and mandibular deformation. Developmental defects are also visible with effects on the general shape and articular surfaces of both humeri, as well as the left femur and tibia. CONCLUSION: We propose that the lesions observed are manifestations of skeletal dysplasia, such as pseudo-achondroplasia or multiple epiphyseal dysplasia. SIGNIFICANCE: This is the first recorded case of multiple skeletal dysplasia in an Iron Age necropolis in Switzerland, questioning the integration of physically compromised individuals in La Tène society. LIMITATIONS: Examination of other skeletal dysplasias from archaeological contexts provides support for this diagnosis. SUGGESTIONS FOR FUTURE RESEARCH: The integration of individuals with disabilities in La Tène societies is still poorly understood and further research is needed to better characterize these communities.

Subsistence activities and the sexual division of labor in the European Upper Paleolithic and Mesolithic: evidence from upper limb enthesopathies.

Studies of cultural artifacts and faunal remains from European Upper Paleolithic and Mesolithic sites indicate a shift in hunter gatherer subsistence strategies, involving an intensification and diversification of resource exploitation relative to earlier foragers during the Tardiglacial and Postglacial periods. This trend has been recognized as well through the analysis of non-pathological skeletal adaptations of the upper limbs of European Upper Paleolithic human fossils. These paleoanthropological studies of adaptive bone modeling also raise the question of female use of throwing-based weapon technology in the Upper Paleolithic. Here, we studied another type of osteological marker of activity, enthesopathies, of the upper limb remains of 37 European Upper Paleolithic and Mesolithic human fossils, with the goal of testing two hypotheses: 1) that activity levels were heightened at the end of Upper Paleolithic and into the Mesolithic relative to earlier foragers of the Gravettian, and 2) that there was an absence of a marked sexual division of labor in European hunter-gatherers during this time span. Our results are consistent with the first hypothesis; upper limb enthesopathies are significantly less frequent in the Gravettian group, but raise doubts about the second hypothesis. Four males exhibit lesions that can be confidently associated with throwing activities, while no females exhibit such lesions.

Enthesopathies as occupational stress markers: evidence from the upper limb.

Enthesopathies--that is, "musculo-skeletal stress markers"--are frequently used to reconstruct past lifestyles and activity patterns. Relatively little attention has been paid in physical anthropology to methodological gaps implicit in this approach: almost all methods previously employed neglect current medical insights into enthesopathies and the distinction between healthy and pathological aspects has been arbitrary. This study presents a new visual method of studying fibrocartilaginous enthesopathies of the upper limb (modified from Villotte: Bull Mém Soc Anthropol Paris n.s. 18 (2006) 65-85), and application of this method to 367 males who died between the 18th and 20th centuries, from four European identified skeletal collections: the Christ Church Spitalfields Collection, the identified skeletal collection of the anthropological museum of the University of Coimbra, and the Sassari and Bologna collections of the museum of Anthropology, University of Bologna. The analysis, using generalized estimating equations to model repeated binary outcome variables, has established a strong link between enthesopathies and physical activity: men with occupations involving heavy manual tasks have significantly (P-value < 0.001) more lesions of the upper limbs than nonmanual and light manual workers. Probability of the presence of an enthesopathy also increases with age and is higher for the right side compared with the left. Our study failed to distinguish significant differences between the collections when adjusted for the other effects. It appears that enthesopathies can be used to reconstruct past lifestyles of populations if physical anthropologists: 1) pay attention to the choice of entheses in their studies and 2) use appropriate methods.

Five millennia of Bartonella quintana bacteraemia.

During the two World Wars, Bartonella quintana was responsible for trench fever and is now recognised as an agent of re-emerging infection. Many reports have indicated widespread B. quintana exposure since the 1990s. In order to evaluate its prevalence in ancient populations, we used real-time PCR to detect B. quintana DNA in 400 teeth collected from 145 individuals dating from the 1st to 19th centuries in nine archaeological sites, with the presence of negative controls. Fisher's exact test was used to compare the prevalence of B. quintana in civil and military populations. B. quintana DNA was confirmed in a total of 28/145 (19.3%) individuals, comprising 78 citizens and 67 soldiers, 20.1% and 17.9% of which were positive for B. quintana bacteraemia, respectively. This study analysed previous studies on these ancient samples and showed that the presence of B. quintana infection followed the course of time in human history; a total of 14/15 sites from five European countries had a positive prevalence. The positive rate in soldiers was higher than those of civilians, with 20% and 18.8%, respectively, in the 18th and 19th centuries, but the difference in frequency was not significant. These results confirmed the role of dental pulp in diagnosing B. quintana bacteraemia in ancient populations and showed the incidence of B. quintana in both civilians and soldiers.

Medical genetic polymorphisms as markers of evolutionary forces within the human genome: hypotheses focusing on natural selection in the Basque population.

Natural selection, drift, and gene flow are the three major evolutionary forces at the origin of genetic diversity among human populations. To further explore these mechanisms, we present an innovative approach using various medical genetic markers and focusing on the Basque population. From this study we can confirm the important role of drift in this endogamous human group and can report some disorders related to founder effects. Most important, the peculiar distribution of various polymorphisms, such as blood group O, factor V Leiden, DF508, C282Y, and CCR5 D32 mutations, which are implicated in resistance to infection, hemostasis, or iron conservation, could be interpreted as an adaptive profile. Multidisciplinary data have shown that the Neolithic period arrived significantly later in this southwestern corner of Europe. We hypothesize that the long-lasting Paleolithic mode of life, especially regarding nutrition and microbial exposure, was at the origin of this selective pressure within this population of ancient local ancestry. This approach could open new avenues in the field of population genetics.

Paleoepidemiology of vertebral degenerative disease in a Pre-Columbian Muisca series from Colombia.

Major manifestations of vertebral degenerative joint disease were observed on a Pre-Columbian Muisca series from the Soacha Cemetery (11th to 13th centuries) Colombia, South America. In total, 1,646 vertebrae of 83 individuals were examined. Osteophytes, vertebral body joint surface contour change ("lipping"), and vertebral body pitting were evaluated for each vertebral body. For apophyseal joints, joint surface contour change, pitting, and eburnation were recorded. Two methods of frequency calculation and five for vertebral degenerative disease diagnosis were applied and compared, allowing discussion of methodological considerations. Our study showed that 83% of individuals and 32% of vertebrae were classified as positive when diagnosed by the presence of at least one of the following manifestations: osteophytes, vertebral body joint surface contour change ("lipping"), apophyseal joint surface contour change, or eburnation (method called "Pitting excluded"). No significant differences were found between the sexes. In the youngest cohort (15-30 years), 65% of individuals and 10% of vertebrae exhibit at least one of the previously mentioned manifestations. High prevalences suggest a high level of physical activity beginning in childhood which may have accelerated the aging process in this Pre-Columbian population. Historical data are compatible with this hypothesis.

DNA-based typing of Kell, Kidd, MNS, Dombrock, Colton, and Yt blood group systems in the French Basques.

The Basques demonstrate peculiar characteristics regarding blood group systems. Although ABO, Rhesus, and Duffy have been extensively studied in this population, the distribution of other groups remains largely unknown. Therefore, we evaluated the frequency of less-explored- or still noninvestigated blood groups using DNA-based assays and interpreted these data in the view of population genetics. Polymorphisms of KEL (Kell), SLCA14A1 (Kidd), GYPA/GYPB (MNS), ART4 (Dombrock), AQP1 (Colton), and ACHE (Yt) blood group genes were determined from a sample of more than 100 autochthonous French Basques using allele-specific primer PCR (PCR-ASP) methods. Our results were compared with those previously obtained by the use of serology from both Basque and non-Basque European populations. MNS*1 and JK*1 allele frequencies were comparable with those reported from Basque samples. Conversely, the KEL*1 allele frequency differed significantly. To our knowledge, this is the first time that the other three systems are studied in the Basque population. DO*1 and CO*1 allele frequencies, being respectively 0.35 and 0.96, were significantly inferior to those published from various European populations. There were some discrepancies regarding these six blood systems when comparing molecular typing with serology. These findings may be explained by differences in either criteria for individual selection or technical assays. Nevertheless, these results constitute additional data to be included in the chapter of Basque biological anthropology.

Trabecular bone microarchitecture analysis, a way for an early detection of genetic dwarfism? Case study of a dwarf mother's offspring.

A 66 year-old woman with a disproportionate dwarfism and who bore seven children was discovered at the Middenbeemster archaeological site (The Netherlands). Three are perinates and show no macroscopic or radiological evidence for a FGFR3 mutation causing hypo-or achondroplasia. This mutation induces dysfunction of the growth cartilage, leading to abnormalities in the development of trabecular bone. Because the mutation is autosomal dominant, these perinates have a 50% risk of having been affected. This study determines whether trabecular bone microarchitecture (TBMA) analysis is useful for detecting genetic dwarfism. Proximal metaphyses of humeri were µCT-scanned with a resolution of 7-12 µm. Three volumes of interest were segmented from each bone with TIVMI© software. The TBMA was quantified in BoneJ© using six parameters on which a multivariate analysis was then performed. Two of the Middenbeemster perinates show a quantitatively different TBMA organization. These results and the family's medical history suggest a diagnosis of genetic dwarfism for this two perinates. This study provides evidence to support the efficacy of µCT for diagnosing early-stage bone disease.

Paleopathology of Human Infections: Old Bones, Antique Books, Ancient and Modern Molecules.

Paleopathology studies the traces of disease on human and animal remains from ancient times. Infectious diseases have been, for over a century, one of its main fields of interest. The applications of paleogenetics methods to microbial aDNA, that started in the 90s combined to the recent development of new sequencing techniques allowing 'paleogenomics' approaches, have completely renewed the issue of the infections in the past. These advances open up new challenges in the understanding of the evolution of human-pathogen relationships, integrated in "One Health" concept.In this perspective, an integrative multidisciplinary approach combining data from ancient texts and old bones to those of old molecules is of great interest for reconstructing the past of human infections. Despite some too optimistic prediction of their eradication in the late 20th century, some of these ancient human diseases, such as plague, leprosy or tuberculosis, are still present and continue their evolution at the beginning of this 21rst century. Better know the past to predict a part of the future of human diseases remains, more than ever, the motto of the paleopathological science.