A genetic probe into the ancient and medieval history of Southern Europe and West Asia.

Literary and archaeological sources have preserved a rich history of Southern Europe and West Asia since the Bronze Age that can be complemented by genetics. Mycenaean period elites in Greece did not differ from the general population and included both people with some steppe ancestry and others, like the Griffin Warrior, without it. Similarly, people in the central area of the Urartian Kingdom around Lake Van lacked the steppe ancestry characteristic of the kingdom's northern provinces. Anatolia exhibited extraordinary continuity down to the Roman and Byzantine periods, with its people serving as the demographic core of much of the Roman Empire, including the city of Rome itself. During medieval times, migrations associated with Slavic and Turkic speakers profoundly affected the region.

Ancient DNA from Mesopotamia suggests distinct Pre-Pottery and Pottery Neolithic migrations into Anatolia.

We present the first ancient DNA data from the Pre-Pottery Neolithic of Mesopotamia (Southeastern Turkey and Northern Iraq), Cyprus, and the Northwestern Zagros, along with the first data from Neolithic Armenia. We show that these and neighboring populations were formed through admixture of pre-Neolithic sources related to Anatolian, Caucasus, and Levantine hunter-gatherers, forming a Neolithic continuum of ancestry mirroring the geography of West Asia. By analyzing Pre-Pottery and Pottery Neolithic populations of Anatolia, we show that the former were derived from admixture between Mesopotamian-related and local Epipaleolithic-related sources, but the latter experienced additional Levantine-related gene flow, thus documenting at least two pulses of migration from the Fertile Crescent heartland to the early farmers of Anatolia.

The genetic history of the Southern Arc: A bridge between West Asia and Europe.

By sequencing 727 ancient individuals from the Southern Arc (Anatolia and its neighbors in Southeastern Europe and West Asia) over 10,000 years, we contextualize its Chalcolithic period and Bronze Age (about 5000 to 1000 BCE), when extensive gene flow entangled it with the Eurasian steppe. Two streams of migration transmitted Caucasus and Anatolian/Levantine ancestry northward, and the Yamnaya pastoralists, formed on the steppe, then spread southward into the Balkans and across the Caucasus into Armenia, where they left numerous patrilineal descendants. Anatolia was transformed by intra-West Asian gene flow, with negligible impact of the later Yamnaya migrations. This contrasts with all other regions where Indo-European languages were spoken, suggesting that the homeland of the Indo-Anatolian language family was in West Asia, with only secondary dispersals of non-Anatolian Indo-Europeans from the steppe.

Wild cereal grain consumption among Early Holocene foragers of the Balkans predates the arrival of agriculture.

Forager focus on wild cereal plants has been documented in the core zone of domestication in southwestern Asia, while evidence for forager use of wild grass grains remains sporadic elsewhere. In this paper, we present starch grain and phytolith analyses of dental calculus from 60 Mesolithic and Early Neolithic individuals from five sites in the Danube Gorges of the central Balkans. This zone was inhabited by likely complex Holocene foragers for several millennia before the appearance of the first farmers ~6200 cal BC. We also analyzed forager ground stone tools (GSTs) for evidence of plant processing. Our results based on the study of dental calculus show that certain species of Poaceae (species of the genus Aegilops) were used since the Early Mesolithic, while GSTs exhibit traces of a developed grass grain processing technology. The adoption of domesticated plants in this region after ~6500 cal BC might have been eased by the existing familiarity with wild cereals.

Before humans invented agriculture and the first farmers appeared in southwestern Asia, other ancient foragers (also known as hunter-gatherers) in southeastern Europe had already developed a taste for consuming wild plants. There is evidence to suggest that these foragers were intensely gathering wild cereal grains before the arrival of agriculture. However, until now, the only place outside southwestern Asia this has been shown to have occurred is in Greece, and is dated around 20,000 years ago. In the past, researchers proposed that forager societies in the Balkans also consumed wild cereals before transitioning to agriculture. But this has been difficult to prove because plant foods are less likely to preserve than animal bones and teeth, making them harder to detect in prehistoric contexts. To overcome this, Cristiani et al. studied teeth from 60 individuals found in archaeological sites between Serbia and Romania, which are attributed to the Mesolithic and Early Neolithic periods. Food particles extracted from crusty deposits on the teeth (called the dental calculus) were found to contain structures typically found in plants. In addition, Cristiani et al. discovered similar plant food residues on ground stone tools which also contained traces of wear associated with the processing of wild cereals. These findings suggest that foragers in the central Balkans were already consuming certain species of wild cereal grains 11,500 years ago, before agriculture arrived in Europe. It is possible that sharing knowledge about plant resources may have helped introduce domesticated plant species in to this region as early as 6500 BC. This work challenges the deep-rooted idea that the diet of hunter-gatherers during the Palaeolithic and Mesolithic periods primarily consisted of animal proteins. In addition, it highlights the active role the eating habits of foragers might have played in introducing certain domesticated plant species that have become primary staples of our diet today.

Quantitative impact analysis of remote ischemic conditioning and capsaicin application on human skin microcirculation.

BACKGROUND: Improvement of skin microcirculation would be beneficial in transplanted tissues and thus, there is a demand for effective, reliable and harmless angiogenic treatments. The aim of this study was to assess the effect of capsaicin application (CA), the remote effect of capsaicin application (REC), the impact of remote ischemic conditioning (RIC), and the impact of combined remote ischemic conditioning with capsaicin application (Comb) on human skin microcirculation. METHODS: Perfusion changes were assessed using a laser Doppler device (easyLDI, Aimago Lausanne). 30 healthy volunteers were enrolled and divided into two groups: 1) CA and REC: perfusion was assessed on both forearms after application of capsaicin cream on one forearm with an exposure time of 40 minutes. 2) RIC and Comb: perfusion of one forearm was assessed after four cycles of 5 min blood occlusion and 5 min reperfusion using a tourniquet on the contralateral upper arm and application of capsaicin on the ipsilateral forearm. Baseline skin perfusion measurements of both forearms were carried out initially and were used as intra-individual reference. RESULTS: 1) Skin perfusion significantly increased after capsaicin application (CA = +328.3% , p > 0.05). There was no remote skin perfusion change due to capsaicin (REC). 2) RIC significantly improves skin perfusion (RIC = +20.0% , p < 0.05). The combination of RIC and CA does not improve skin perfusion compared to CA alone (Comb). CONCLUSIONS: The conditioning techniques RIC and CA showed a significant increase in human skin perfusion, CA being superior to RIC. However, the combination of CA and RIC showed no additional improvement potential as compared to CA alone. Furthermore, a remote effect of capsaicin application could not be demonstrated. These results encourage to analyze if the conditioning treatments are also beneficial for transplanted tissue survival.

Transition from nerve stimulator to sonographically guided axillary brachial plexus anesthesia in hand surgery: block quality and patient satisfaction during the transition period.

OBJECTIVES: Sonographic guidance for peripheral nerve anesthesia has proven increasingly successful in clinical practice; however, fears that a change to sonographically guided regional anesthesia may impair the block quality and operating room work flow persist in certain units. In this retrospective cohort study, block quality and patient satisfaction during the transition period from nerve stimulator to sonographic guidance for axillary brachial plexus anesthesia in a tertiary referral center were investigated. METHODS: Anesthesia records of all patients who had elective surgery of the wrist or hand during the transition time (September 1, 2006-August 25, 2007) were reviewed for block success, placement time, anesthesiologist training level, local anesthetic volume, and requirement of additional analgesics. Postoperative records were reviewed, and patient satisfaction was assessed by telephone interviews in matched subgroups. RESULTS: Of 415 blocks, 341 were sonographically guided, and 74 were nerve stimulator guided. Sonographically guided blocks were mostly performed by novices, whereas nerve stimulator-guided blocks were performed by advanced users (72.3% versus 14%; P < .001). Block performance times and success rates were similar in both groups. In sonographically guided blocks, significantly less local anesthetics were applied compared to nerve stimulator-guided blocks (mean ± SD, 36.1 ± 7.1 versus 43.9 ± 6.1 mL; P< .001), and less opioids were required (fentanyl, 66.1 ± 30 versus 90 ± 62 µg; P< .001). Interviewed patients reported significantly less procedure-related discomfort, pain, and prolonged procedure time when block placement was sonographically guided (2% versus 20%; P = .002). CONCLUSIONS: Transition from nerve stimulator to sonographic guidance for axillary brachial plexus blocks did not change block performance times or success rates. Patient satisfaction was improved even during the early institutional transition period.

Evaluation of a porcine whole-limb heterotopic autotransplantation model.

BACKGROUND: Recently performed vascularized composite tissue allotransplantations (CTAs) stimulate the ongoing research in the area of whole-limb transplantation. A reliable in vivo animal model is required for investigations in vascularized whole-limb CTA. The model should allow in vivo assessment in whole-limb preservation, allograft and xenograft response, and host immunomodulation. The goal of this study is to describe and evaluate the in vivo feasibility and reproducibility of a whole-limb porcine model as a basis for future research in this field. MATERIALS AND METHODS: In seven large white pigs, one forelimb was amputated under anesthesia and autotransplanted heterotopically with an arc of rotation of 180° and partially placed in a subcutaneous pocket. Clinical parameters were monitored and muscle biopsies were analyzed using ultrastructural morphological assessment of mitochondria quality after an observation period of 7 days. RESULTS: All animals could fully mobilize postoperatively without restrictions. At sacrifice, the anastomosed pedicle vessels of the limb were patent in six animals. In one pig, venous thrombosis could be observed. Muscle response was triggered following direct electrostimulation in six replanted limbs. The replanted extremities gained 12.97% weight within 7 days postreplantation compared with the amputation baseline values (P = 0.464 while maintaining normal compartment pressures at sacrifice (8.25 ± 5.31 cmH(2)O, P = 0.60). The ultrastructural evaluation of mitochondria morphology revealed intact mitochondria without signs of ischemia/reperfusion damage. CONCLUSION: This porcine model proved feasible, reliable, and reproducible for whole-limb autotransplantation. It presents significant potential in future preclinical research of whole-limb CTA transplantation.

Effect of laser soldering irradiation on covalent bonds of pure collagen.

Laser tissue welding and soldering is being increasingly used in the clinical setting for defined surgical procedures. The exact induced changes responsible for tensile strength are not yet fully investigated. To further improve the strength of the bonding, a better understanding of the laser impact at the subcellular level is necessary. The goal of this study was to analyze whether the effect of laser irradiation on covalent bonding in pure collagen using irradiances typically applied for tissue soldering. Pure rabbit and equine type I collagen were subjected to laser irradiation. In the first part of the study, rabbit and equine collagen were compared using identical laser and irradiation settings. In the second part of the study, equine collagen was irradiated at increasing laser powers. Changes in covalent bonding were studied indirectly using the sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) technique. Tensile strengths of soldered membranes were measured with a calibrated tensile force gauge. In the first experiment, no differences between the species-specific collagen bands were noted, and no changes in banding were found on SDS-PAGE after laser irradiation. In the second experiment, increasing laser irradiation power showed no effect on collagen banding in SDS-PAGE. Finally, the laser tissue soldering of pure collagen membranes showed virtually no determinable tensile strength. Laser irradiation of pure collagen at typical power settings and exposure times generally used in laser tissue soldering does not induce covalent bonding between collagen molecules. This is true for both rabbit and equine collagen proveniences. Furthermore, soldering of pure collagen membranes without additional cellular components does not achieve the typical tensile strength reported in native, cell-rich tissues. This study is a first step in a better understanding of laser impact at the molecular level and might prove useful in engineering of combined collagen-soldering matrix membranes for special laser soldering applications.

Current trends in local anesthesia in cosmetic plastic surgery of the head and neck: results of a German national survey and observations on the use of ropivacaine.

BACKGROUND: The goal of this study was to evaluate at the national level the current practice in the use of local anesthetics in cosmetic head and neck surgery and to compare the results with the novel local anesthesia technique used in the authors' department over the past 2 years. METHODS: A questionnaire was posted to all 211 board-certified members of the Association of German Plastic Surgeons. The questions related to the daily practice in rhinoplasty, blepharoplasty, otoplasty, face lift, and forehead lift. The focus was laid on anesthesia techniques, local anesthetics, vasoconstricting agents, dosages, activity onset, observed side effects, mean duration of each procedure type, and surgeon satisfaction with the anesthetic used. RESULTS: A total of 86 questionnaires (40.8 percent) were returned. The overall analysis revealed that local anesthetics were used in 88.9 percent of all cosmetic procedures of the head and neck. Prilocaine 1% (Xylonest; AstraZeneca, Wedel, Germany) was the most frequently used local anesthetic (32.0 percent), followed by lidocaine 1% (Xylocaine; AstraZeneca) and mepivacaine 1% (Scandicaine; AstraZeneca). Ropivacaine 0.2% (Naropin; AstraZeneca) was used only by 1.1 percent and ropivacaine 0.75% only by 0.9 percent (including two of the authors). Approximately half of the respondents (47.2 percent) used epinephrine 1:100,000 for vasoconstriction. In face lifts, the necessity of repeated "top-up" infiltration was reported in more than half (54.7 percent) of the procedures. Ten percent of surgeons surpassed the maximum recommended dosages when working without ropivacaine. Overall adverse cardiovascular effects were reported in 5.9 percent of rhinoplasties and 8.1 percent of face lifts performed mostly with prilocaine and lidocaine. No adverse cardiovascular reactions or overdoses were noticed with the use of ropivacaine. CONCLUSIONS: The survey showed a clear trend toward the increasing use of local anesthetics in cosmetic surgery of the head and neck. Although the use of prilocaine and lidocaine prevailed, adverse cardiovascular reactions in up to 8.1 percent seem high for cosmetic procedures. Furthermore, the need of additional intraoperative top-up infiltration adds to an uncontrolled cumulative effect and patient discomfort. On the basis of their positive 2 years of experience with ropivacaine, the authors strongly believe that ropivacaine offers significant advantages, both in efficacy and prolonged duration of analgesia, while reducing the risk for adverse side effects due to lesser toxicity. This observation deserves further investigation in an established comparative study.