The chronicle of headache treatment throughout human history from trepanation to perisutural botulinum toxin injections.

To provide a historic snapshot as regards the evolution of headache treatment throughout the human history, i.e. starting from trepanation to perisutural botulinum toxin (BoNT) injections. Ancient surgeons had aimed to reach the cranium with trepanation (a surgical operation) for headache. As BoNT inhibits the release of nociceptive and pro-inflammatory neuropeptides, it has been recently suggested as an effective alternative in the prophylactic treatment of chronic migraine headache. Chronic migraine is a complex neurological disorder for which the underlying pathophysiology is yet not totally explained. According to the generally accepted hypotheses, peripheral neurogenic activation and central trigeminal sensitization are the two main mechanisms through which its pain develops. Since the headache most commonly occurs around the perisutural areas, and as the primary pathogenesis stem from the meningeal nerve fibers; collateral sensorial branches of the meningeal nerves can be optimal paths to transport BoNT inside the cranium. Concerning the therapeutic efficacy, we anticipate that perisutural injections would be technically challenging with blind techniques and actually possible only if performed under an imaging guidance, e.g. very conveniently with high frequency ultrasound.

The effect of different socio-economic and working conditions on body size and proportions: A case study on adults from Samsun, Turkey.

Conditions in the early stages of life shape body size and proportions. This study includes individuals who came from different socio-economic conditions and worked in physically demanding jobs in childhood. By determining the body sizes of these individuals and evaluating the proportional relationships between several groups, the goal was to understand the effect levels of socio-economic levels and working conditions on the body. For this purpose, an anthropometric study was conducted on 623 males and females between the ages of 20 and 45 living in Samsun, Turkey. The study sample consisted of four different groups. It was divided into two main groups of high and low socio-economic level, and the low socio-economic group was divided into two subgroups of heavy-worker and nonheavy-worker. The results demonstrated that socio-economic differences in the size and proportions of the individuals were statistically significant (p<0.05). The high socio-economic group had the highest values in all measures. External factors affected the lower limbs more than the upper limbs. The measurement most affected by these factors was leg length. Longer legs characterized the high socio-economic group, while longer arms characterized both low socio-economic groups. The relative differences observed can be said to derive from the distal limbs. This finding was valid for both sexes. The average values were close to each other in the low socio-economic group, for which the aim was to comprehend the effects of heavy working conditions. However, differences in proportional relationships were more significant. In this context, it was seen that heavy labour also affected growth, in addition to the well-known factors encountered during the growth period, such as nutrition, health, and illness. The observed changes were more significant in males than in females. Thus, it can be said that males were more affected by physiological and physical conditions.

Spatial and temporal heterogeneity in human mobility patterns in Holocene Southwest Asia and the East Mediterranean.

We present a spatiotemporal picture of human genetic diversity in Anatolia, Iran, Levant, South Caucasus, and the Aegean, a broad region that experienced the earliest Neolithic transition and the emergence of complex hierarchical societies. Combining 35 new ancient shotgun genomes with 382 ancient and 23 present-day published genomes, we found that genetic diversity within each region steadily increased through the Holocene. We further observed that the inferred sources of gene flow shifted in time. In the first half of the Holocene, Southwest Asian and the East Mediterranean populations homogenized among themselves. Starting with the Bronze Age, however, regional populations diverged from each other, most likely driven by gene flow from external sources, which we term "the expanding mobility model." Interestingly, this increase in inter-regional divergence can be captured by outgroup-f3-based genetic distances, but not by the commonly used FST statistic, due to the sensitivity of FST, but not outgroup-f3, to within-population diversity. Finally, we report a temporal trend of increasing male bias in admixture events through the Holocene.

A genomic snapshot of demographic and cultural dynamism in Upper Mesopotamia during the Neolithic Transition.

Upper Mesopotamia played a key role in the Neolithic Transition in Southwest Asia through marked innovations in symbolism, technology, and diet. We present 13 ancient genomes (c. 8500 to 7500 cal BCE) from Pre-Pottery Neolithic Çayönü in the Tigris basin together with bioarchaeological and material culture data. Our findings reveal that Çayönü was a genetically diverse population, carrying mixed ancestry from western and eastern Fertile Crescent, and that the community received immigrants. Our results further suggest that the community was organized along biological family lines. We document bodily interventions such as head shaping and cauterization among the individuals examined, reflecting Çayönü's cultural ingenuity. Last, we identify Upper Mesopotamia as the likely source of eastern gene flow into Neolithic Anatolia, in line with material culture evidence. We hypothesize that Upper Mesopotamia's cultural dynamism during the Neolithic Transition was the product not only of its fertile lands but also of its interregional demographic connections.

Archaeogenetic analysis of Neolithic sheep from Anatolia suggests a complex demographic history since domestication.

Sheep were among the first domesticated animals, but their demographic history is little understood. Here we analyzed nuclear polymorphism and mitochondrial data (mtDNA) from ancient central and west Anatolian sheep dating from Epipaleolithic to late Neolithic, comparatively with modern-day breeds and central Asian Neolithic/Bronze Age sheep (OBI). Analyzing ancient nuclear data, we found that Anatolian Neolithic sheep (ANS) are genetically closest to present-day European breeds relative to Asian breeds, a conclusion supported by mtDNA haplogroup frequencies. In contrast, OBI showed higher genetic affinity to present-day Asian breeds. These results suggest that the east-west genetic structure observed in present-day breeds had already emerged by 6000 BCE, hinting at multiple sheep domestication episodes or early wild introgression in southwest Asia. Furthermore, we found that ANS are genetically distinct from all modern breeds. Our results suggest that European and Anatolian domestic sheep gene pools have been strongly remolded since the Neolithic.

Human inbreeding has decreased in time through the Holocene.

The history of human inbreeding is controversial.1 In particular, how the development of sedentary and/or agricultural societies may have influenced overall inbreeding levels, relative to those of hunter-gatherer communities, is unclear.2-5 Here, we present an approach for reliable estimation of runs of homozygosity (ROHs) in genomes with ≥3× mean sequence coverage across >1 million SNPs and apply this to 411 ancient Eurasian genomes from the last 15,000 years.5-34 We show that the frequency of inbreeding, as measured by ROHs, has decreased over time. The strongest effect is associated with the Neolithic transition, but the trend has since continued, indicating a population size effect on inbreeding prevalence. We further show that most inbreeding in our historical sample can be attributed to small population size instead of consanguinity. Cases of high consanguinity were rare and only observed among members of farming societies in our sample. Despite the lack of evidence for common consanguinity in our ancient sample, consanguineous traditions are today prevalent in various modern-day Eurasian societies,1,35-37 suggesting that such practices may have become widespread within the last few millennia.

Variable kinship patterns in Neolithic Anatolia revealed by ancient genomes.

The social organization of the first fully sedentary societies that emerged during the Neolithic period in Southwest Asia remains enigmatic,1 mainly because material culture studies provide limited insight into this issue. However, because Neolithic Anatolian communities often buried their dead beneath domestic buildings,2 household composition and social structure can be studied through these human remains. Here, we describe genetic relatedness among co-burials associated with domestic buildings in Neolithic Anatolia using 59 ancient genomes, including 22 new genomes from Asikli Höyük and Çatalhöyük. We infer pedigree relationships by simultaneously analyzing multiple types of information, including autosomal and X chromosome kinship coefficients, maternal markers, and radiocarbon dating. In two early Neolithic villages dating to the 9th and 8th millennia BCE, Asikli Höyük and Boncuklu, we discover that siblings and parent-offspring pairings were frequent within domestic structures, which provides the first direct indication of close genetic relationships among co-burials. In contrast, in the 7th millennium BCE sites of Çatalhöyük and Barcin, where we study subadults interred within and around houses, we find close genetic relatives to be rare. Hence, genetic relatedness may not have played a major role in the choice of burial location at these latter two sites, at least for subadults. This supports the hypothesis that in Çatalhöyük,3-5 and possibly in some other Neolithic communities, domestic structures may have served as burial location for social units incorporating biologically unrelated individuals. Our results underscore the diversity of kin structures in Neolithic communities during this important phase of sociocultural development.

Application of ATR-FTIR spectroscopy and chemometrics for the discrimination of human bone remains from different archaeological sites in Turkey.

Examining diagenetic parameters such as the organic carbonate contents and the crystallinity of bone apatite quantify the post-mortem alteration of bone. Burial conditions are one of the factors that can influence the diagenesis process. We studied the changes to the organic and mineral components and crystallinity of human bone remains from five Medieval sites in Turkey: Hakemi Use, Komana, Iznik, Oluz Höyük and Tasmasor using Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) and principal component analysis (PCA). Analysis of spectral band ratios related to organic and mineral components of bone demonstrated differences in the molecular content in the skeletal remains from the five sites. In order to examine the degree of carbonation of a phosphate matrix, curve-fitting procedures were applied to the carbonate band. We found that the infrared crystallinity index appears to not be sensitive to carbonate content at room temperature for the bone remains studied here. The recrystallization process in bone remains behaved differently among the archaeological sites. The results demonstrate that the burial environments differently affect the organic and mineral components of archaeological bone remains.

Emergence of human-adapted Salmonella enterica is linked to the Neolithization process.

It has been hypothesized that the Neolithic transition towards an agricultural and pastoralist economy facilitated the emergence of human-adapted pathogens. Here, we recovered eight Salmonella enterica subsp. enterica genomes from human skeletons of transitional foragers, pastoralists and agropastoralists in western Eurasia that were up to 6,500 yr old. Despite the high genetic diversity of S. enterica, all ancient bacterial genomes clustered in a single previously uncharacterized branch that contains S. enterica adapted to multiple mammalian species. All ancient bacterial genomes from prehistoric (agro-)pastoralists fall within a part of this branch that also includes the human-specific S. enterica Paratyphi C, illustrating the evolution of a human pathogen over a period of 5,000 yr. Bacterial genomic comparisons suggest that the earlier ancient strains were not host specific, differed in pathogenic potential and experienced convergent pseudogenization that accompanied their downstream host adaptation. These observations support the concept that the emergence of human-adapted S. enterica is linked to human cultural transformations.

Amino acid 15 N analysis reveals change in the importance of freshwater resources between the hunter-gatherer and farmer in the Neolithic upper Tigris.

OBJECTIVE: The inhabitants of several sites in the Upper Tigris Valley, such as Hakemi Use, domesticated animals and cereals during the Pottery Neolithic period, while the inhabitants in this valley were hunter-gatherers in the Pre-Pottery Neolithic period, consuming freshwater and terrestrial food resources. However, there is considerable uncertainty surrounding whether or not changes in dietary food composition accompanied the shift in food production away from foraging. In order to reveal the impact of the development of agriculture on the human diet over the Pre-Pottery and Pottery Neolithic periods in this region, we analyzed the isotopic compositions of amino acids from the farmers at the Hakemi Use Pottery Neolithic site, and compared them with those from the Pre-Pottery hunter-gatherers in the close region. MATERIALS AND METHODS: Herein, we report the nitrogen isotopic compositions of amino acids, as well as both carbon and nitrogen isotopic compositions of bulk collagen, from human and faunal remains collected from Hakemi Use. RESULTS: Whereas freshwater resources were consumed by hunter-gatherers in this region during the Pre-Pottery period, the δ15 N values of glutamic acid (δ15 NGlu ) and phenylalanine (δ15 NPhe ) suggest that freshwater food resources were rarely consumed by inhabitants following the development of agriculture. DISCUSSION: Despite living in similar settings by the Tigris as its inhabitants during the Pre-Pottery period, the farmers of the Pottery Neolithic period depended less on freshwater resources for their diets relative to the hunter-gatherers of the Pre-Pottery Neolithic period.

The Demographic Development of the First Farmers in Anatolia.

The archaeological documentation of the development of sedentary farming societies in Anatolia is not yet mirrored by a genetic understanding of the human populations involved, in contrast to the spread of farming in Europe [1-3]. Sedentary farming communities emerged in parts of the Fertile Crescent during the tenth millennium and early ninth millennium calibrated (cal) BC and had appeared in central Anatolia by 8300 cal BC [4]. Farming spread into west Anatolia by the early seventh millennium cal BC and quasi-synchronously into Europe, although the timing and process of this movement remain unclear. Using genome sequence data that we generated from nine central Anatolian Neolithic individuals, we studied the transition period from early Aceramic (Pre-Pottery) to the later Pottery Neolithic, when farming expanded west of the Fertile Crescent. We find that genetic diversity in the earliest farmers was conspicuously low, on a par with European foraging groups. With the advent of the Pottery Neolithic, genetic variation within societies reached levels later found in early European farmers. Our results confirm that the earliest Neolithic central Anatolians belonged to the same gene pool as the first Neolithic migrants spreading into Europe. Further, genetic affinities between later Anatolian farmers and fourth to third millennium BC Chalcolithic south Europeans suggest an additional wave of Anatolian migrants, after the initial Neolithic spread but before the Yamnaya-related migrations. We propose that the earliest farming societies demographically resembled foragers and that only after regional gene flow and rising heterogeneity did the farming population expansions into Europe occur.

Organized violence in Anatolia: A retrospective research on the injuries from the Neolithic to Early Bronze Age.

The question of the presence of organized violence in the Neolithic settlements in Middle East has been debated. This paper presents possible examples of organized violence from the Neolithic period, representing early examples of settlements in Anatolia, to the Early Bronze Age, which provides the early instances of central authority. Most injuries detected among Neolithic populations in Anatolia have been associated with daily activities. Although individual examples of interpersonal violence exist among Neolithic and Chalcolithic populations in Anatolia, but they are far from representing organized violence. On the other hand the Early Bronze Age populations present clear evidence of perimortem wounds, mass burials, high frequency of cranial fractures, walls surrounding cities, and metal weapons in Anatolia. This suggests an increased evidence of organized violence in EBA Anatolia. Based on bioarchaeological data, it is concluded that violence in these settlements resulted from one or more ecological and social factors. However, each settlement might have peculiar reason for fighting.

Geometric morphometric study and cluster analysis of late Byzantine and modern human crania.

Inter-population variation of cranial morphology, which plays an important role in human evolution studies and biological research, can be studied morphologically and metrically. Geometric morphometry compares body forms using specific landmarks determined by anatomical prominences. The aim of this study was to identify cranial shape differences between the crania of Byzantium period humans and modern humans. Variability in cranial shape was examined using the geometric morphometric technique based on landmark coordinates. Landmark coordinate data were collected from two-dimensional digital photogrammetry and were analyzed using generalized Procrustes analysis, hierarchical clustering and thin-plate spline analysis.