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.

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.

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.

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.