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The incidence of PAC is relatively infrequent among pregnant women. However, it has gradually increased in recent years, becoming a challenging area for clinicians that should take into account in the same way maternal benefits and fetal potential risks correlated to the antineoplastic treatment. None of the antineoplastic drugs is completely risk-free during the pregnancy, the timing of exposure and transplacental transfer properties influence the toxicity of the fetus. Despite the lack of guidelines about the management of PAC, several studies have described the use and the potential fetal and neonatal adverse events of antineoplastic drugs during pregnancy. We provide a review of the available literature about the transplacental passage and fetal effects of chemotherapy and targeted agents, to guide the clinicians in the most appropriate choices for the management of PAC.

BRAF is a component of the MAPK and PI3K/AKT/mTOR pathways that play a crucial role in cellular proliferation, differentiation, migration, and angiogenesis. Pediatric central nervous system tumors very often show mutations of the MAPK pathway, as demonstrated by next-generation sequencing (NGS), which now has an increasing role in cancer diagnostics. The MAPK mutated pathway in pediatric CNS tumors is the target of numerous drugs, approved or under investigation in ongoing clinical trials. In this review, we describe the main aspects of MAPK and PI3K/AKT/mTOR signaling pathways, with a focus on the alterations commonly involved in tumorigenesis. Furthermore, we reported the main available data about current BRAF and MEK targeted therapies used in pediatric low-grade gliomas (pLLGs), pediatric high-grade gliomas (pHGGs), and other CNS tumors that often present BRAF or MEK mutations. Further molecular stratification and clinical trial design are required for the treatment of pediatric CNS tumors with BRAF and MEK inhibitors.

The prognosis of high-risk neuroblastoma (NB) continues to be poor. The early development of resistance often leads to disease recurrence. In the present study, an innovative induction regimen, including an intensive initial radio-chemotherapy sequence based on the use of iodine-131-metaiodobenzylguanidine (131-I-MIBG), was investigated. The duration of the regimen lasted only one month. Fifteen newly diagnosed patients aged >18 months with high-risk NB were treated with cisplatin, etoposide, cyclophosphamide, and vincristine, followed on day 10 by 131-I-MIBG (dose: 12–18.3 mCi/kg). Cisplatin and vincristine were administered on day 20 and 21 followed by the re-administration of vincristine, cyclophosphamide, and doxorubicin on day 29 and 30. Non-hematologic toxicity was not observed. Moderate hematologic toxicity was present probably attributable to chemotherapy. The evaluation of response was performed approximately 50 days after the initiation of treatment, yielding four complete responses, eight very good partial responses, one partial response, and two non-responses. Importantly, a complete metastatic response was achieved in 87% of patients. The present pilot study, which includes 131-I-MIBG, allows for a highly effective continuous exposure of tumor cells to both chemotherapy and radiotherapy. Furthermore, early high-dose chemotherapy followed by stem cell rescue may achieve high levels of tumor cell clearance and improve the prognosis of high-risk NB.

Brain tumors are the most frequent type of solid neoplasms in children with a recognized 5-year survival rate between 57% and 65%. The survival rate progressively increased in the last few years, due to the improvements in their treatment based on chemotherapy, radiotherapy, and surgery. At the same time, at long term follow-up, clinicians should carefully evaluate comorbidities and long-term sequelae secondary to the disease and its treatment. Growth hormone deficiency (GHD) is an endocrinopathy commonly found among pediatric cancer survivors, with a negative effect on the child’s final height and entire metabolism. GH replacement therapy (GHRT), with a synthetic hormone analog, may improve the growth rate and finally adult height, ameliorating the quality of life after cancer treatment. However, in clinical practice, GHRT is adopted with caution for fear of cancer recurrence or the onset of second malignancies. In our review, we perform a focus on the GH structure and function, comparing benefits and risks of GHRT, derived from the analysis of the data currently available in the literature.

The improvement in childhood cancer treatments resulted in a marked improvement in the survival of pediatric cancer patients. However, as survival increased, it was also possible to observe the long-term side effects of cancer therapies. Among these, metabolic syndrome is one of the most frequent long-term side effects, and causes high mortality and morbidity. Consequently, it is necessary to identify strategies that allow for early diagnosis. In this review, the pathogenetic mechanisms of metabolic syndrome and the potential new biomarkers that can facilitate its diagnosis in survivors of pediatric tumors are analyzed.

Introduction: Hematological abnormalities are common in children with down syndrome (DS), mainly during childhood. Areas covered: DS newborns can develop hematological benign conditions that resolve spontaneously within 1 –2 months. However, about 10% of them can present transient abnormal myelopoiesis (TAM), characterized by the presence of circulating blasts. About 80% of DS neonates with TAM undergo spontaneous resolution of both clinical and laboratory abnormalities within 3–6 months after birth. However, some newborns with TAM may develop acute myeloid leukemia associated with DS (ML-DS), usually after an interval without signs of leukemia. GATA1 mutations are stable molecular markers that may monitor the presence of minimal residual disease (MRD) after TAM resolution. Moreover, DS children have a 10–20-fold increased risk of developing acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). The predisposition to develop leukemia occurs both in children with complete trisomy 21 and in those with mosaic trisomy, suggesting an important role of chromosome 21 in leukemogenesis. Expert opinion: In contrast to the excellent prognosis of ML-DS obtained likewise with low doses of chemotherapy, DS-ALL patients show worse outcomes than non-DS children, therefore advances and risk-stratified treatment adjustments are mandatory for this particular set of patients.

The human oral cavity harbors the second most abundant microbiota after the gastrointestinal tract, with over 700 species currently identified in the oral microflora. The oral microbiota develops from intrauterine life and after birth is continuously shaped by several influencing factors. The perturbation of the diversity and proportions of species within the oral microbiota leads to dysbiosis and associated increased risk of local and systemic diseases. In children who receive chemotherapy for cancer, oral mucositis is a common and painful side effect that decreases quality of life (QoL) and treatment adherence. The oral microbiota undergoes a substantial dysbiosis as an effect of cancer and its treatment, characterized by lower richness and less diversity. Furthermore, this dysbiosis seems to promote pro-inflammatory cytokine release and pro-apoptotic mediators, enhancing the oral tissue damage. Further studies on the role of the oral microbiota in the pathogenesis of oral mucositis should be performed among children with cancer who receive chemotherapy, to find preventive and protective factors against the pathogenesis of oral mucositis.

Local adaptation of animals to the environment can abruptly become a burden when faced with rapid climatic changes such as those foreseen for the Italian peninsula over the next 70 years. Our study investigates the genetic structure of the Italian goat populations and links it with the environment and how genetics might evolve over the next 50 years. We used one of the largest national datasets including > 1000 goats from 33 populations across the Italian peninsula collected by the Italian Goat Consortium and genotyped with over 50 k markers. Our results showed that Italian goats can be discriminated in three groups reflective of the Italian geography and its geo-political situation preceding the country unification around two centuries ago. We leveraged the remarkable genetic and geographical diversity of the Italian goat populations and performed landscape genomics analysis to disentangle the relationship between genotype and environment, finding 64 SNPs intercepting genomic regions linked to growth, circadian rhythm, fertility, and inflammatory response. Lastly, we calculated the hypothetical future genotypic frequencies of the most relevant SNPs identified through landscape genomics to evaluate their long-term effect on the genetic structure of the Italian goat populations. Our results provide an insight into the past and the future of the Italian local goat populations, helping the institutions in defining new conservation strategy plans that could preserve their diversity and their link to local realities challenged by climate change

Pain is one of the main symptoms reported by sick children, particularly by those suffering from cancer. Opioids are very useful in controlling this symptom but they are burdened with significant side effects that limit their use in children. Buprenorphine is a strong opioid that, due to its particular pharmacological characteristics, ensures excellent pain relief with fewer side effects than other opioids. The transdermal formulation allows for good pain control associated with optimal compliance by patients and few limitations on daily life. Unfortunately, transdermal buprenorphine use remains off-label for the control of chronic pain in children; therefore, it is desirable that new studies can validate its use in the paediatric population. This review aims to analyse the clinical advantages of transdermal buprenorphine in the paediatric population and the possible side effects registered in daily clinical practice.

Vincristine-induced peripheral neurotoxicity (VIPN) is a very common side effect of vincristine chemotherapy among pediatric patients with cancer. Neuropathy may be sensory, motor and/or autonomic, with consequent reduction, delay or discontinuation of vincristine-chemotherapy, but also pain, disability, reduced quality of life of patients and an increase in medical costs. Vincristine acts out its antineoplastic function by altering the normal assembly and disassembly of microtubules, with their consequent mitosis block and death. Vincristine leads to VIPN through a complex mechanism of damage, which occurs not only on the microtubules, but also on the endothelium and the mitochondria of nerve cells. Furthermore, both patient-related risk factors (age, race, ethnicity and genetic polymorphisms) and treatment-related risk factors (dose, time of infusion and drug–drug interactions) are involved in the pathogenesis of VIPN. There is a lack of consensus about the prophylaxis and treatment of VIPN among pediatric oncologic patients, despite several molecules (such as gabapentin, pyridoxine and pyridostigmine, glutamic acid and glutamine) having been already investigated in clinical trials. This review describes the molecular mechanisms of VIPN and analyzes the risk factors and the principal drugs adopted for the prophylaxis and treatment of VIPN in pediatric patients with cancer.

No abstract available

Prognosis of metastatic neuroblastoma is very poor. Its treatment includes induction chemotherapy, surgery, high‐dose chemotherapy, radiotherapy, and maintenance with retinoic acid, associated with the anti‐GD2 monoclonal antibody (ch14.18) dinutuximab. Immunotherapy determined a significant improvement in survival rate and is also utilized in relapsed and resistant neuroblastoma patients. Five courses of dinutuximab 100 mg/m2 are usually administered as a 10‐ day continuous infusion or over 5 consecutive days every 5 weeks. Dinutuximab targets the disialoganglioside GD2, which is highly expressed on neuroblastoma cells and minimally present on the surface of normal human neurons, peripheral pain fibers, and skin melanocytes. Anti GD2 antibodies bind to surface GD2 and determine the lysis of neuroblastoma cells induced by immune response via the antibody‐dependent cellular cytotoxicity and the complement‐dependent cytotoxicity. Dinutuximab has significant side effects, including neuropathic pain, peripheral neuropathy, hypersensitivity reactions, capillary leak syndrome, photophobia, and hypotension. The most important side effect is neuropathic pain, which is triggered by the same antibody–antigen immune response, but generates ectopic activity in axons, which results in hyperalgesia and spontaneous pain. Pain can be severe especially in the first courses of dinutuximab infusion, and requires the administration of gabapentin and continuous morphine infusion. This paper will focus on the incidence, mechanisms, characteristics, and treatment of neuropathic pain and peripheral neuropathy due to dinutuximab administration in neuroblastoma patients.

Background: During the Neolithic expansion, cattle accompanied humans and spread from their domestication centres to colonize the ancient world. In addition, European cattle occasionally intermingled with both indicine cattle and local aurochs resulting in an exclusive pattern of genetic diversity. Among the most ancient European cattle are breeds that belong to the so-called Podolian trunk, the history of which is still not well established. Here, we used genome-wide single nucleotide polymorphism (SNP) data on 806 individuals belonging to 36 breeds to reconstruct the origin and diversification of Podolian cattle and to provide a reliable scenario of the European colonization, through an approximate Bayesian computation random forest (ABC-RF) approach. Results: Our results indicate that European Podolian cattle display higher values of genetic diversity indices than both African taurine and Asian indicine breeds. Clustering analyses show that Podolian breeds share close genomic relationships, which suggests a likely common genetic ancestry. Among the simulated and tested scenarios of the colonization of Europe from taurine cattle, the greatest support was obtained for the model assuming at least two waves of diffusion. Time estimates are in line with an early migration from the domestication centre of non-Podolian taurine breeds followed by a secondary migration of Podolian breeds. The best fitting model also suggests that the Italian Podolian breeds are the result of admixture between different genomic pools. Conclusions: This comprehensive dataset that includes most of the autochthonous cattle breeds belonging to the so-called Podolian trunk allowed us not only to shed light onto the origin and diversification of this group of cattle, but also to gain new insights into the diffusion of European cattle. The most well-supported scenario of colonization points to two main waves of migrations: with one that occurred alongside with the Neolithic human expansion a

Local breeds represent an underestimated resource in terms not only of their important cultural and economical role in marginal areas, but also because they often own a potential genetic pool well adapted to extreme conditions. This fact is of increasing interest, especially when considering climate global challenges where peculiar and uncommon traits could be advantageous. In this study, we genotyped 24 individuals belonging to the small residual Pagliarola sheep population using the OvineSNP50K array, in order to compare its genomic architecture with other 21 Italian local breeds. Moreover, we performed the fixation index (FST) outlier analysis to identify genes most differentiated between Pagliarola and Merino-derived Italian breeds. All population genetic analyses highlighted that Pagliarola breed represents a distinct genetic unit showing a genetic relationship with Merino-derived breeds underlying the close cultural connection between these breeds related to transhumance. However, Pagliarola breed resulted to be divided into two different sub-populations, named Pagliarola 1 (PAG-1) and Pagliarola 2 (PAG-2). Genetic diversity indices and inbreeding estimated from runs of homozygosity (FROH) indicated that while PAG-1 showed among the highest values, PAG-2 turned out strongly inbred, probably as a consequence of a founder effect. The FST outlier analysis identified the 5 most differentiated single nucleotide polymorphisms, two of which mapping within known genes (MACF1 and GLIS1) reported to be linked to feed efficiency and local adaption. All these information strongly suggest that proper conservation measures should be implemented in order to recover the Pagliarola population and its fundamental local products.HIGHLIGHTS All population genetic analyses highlighted that Pagliarola breed represent a distinct genetic unit, and clusters with the Merino-derived Italian breeds. The breed resulted to be divided into two different sub-populations. For the two Pagliaro

The COVID-19 pandemic has substantially stressed health care systems globally, subsequently reducing cancer care services and delaying treatments. Pediatric populations infected by COVID-19 have shown mild clinical symptoms compared to adults, perhaps due to decreased susceptibility. Several scientific societies and governments have released information on the management of patients with cancer, wherein they warn against exposure to SARS-CoV-2 infection and suggest continuing treatment. To determine the best diagnostic and therapeutic approach, multidisciplinary tumor boards should convene regularly, including through conference calls and telematics platforms. A prompt diagnostic workup may reduce children's suffering and prevent loss of confidence in the health care system among parents. Moreover, ensuring adequate support and information regarding measures for preventing SARS-CoV-2 infection in pediatric patients and their families is essential for avoiding panic and excessive stress, allowing early reporting of any suspected symptoms of cancer and, in turn, facilitating early diagnosis and prompt modulation of treatment.

Introduction: In recent years, the use of intensive regimens for the treatment of pediatric cancer has led to a marked improvement in patient survival. However, these treatments are associated with an increase in toxic effects. Among these side effects, mucositis (inflammation of the oral cavity) significantly affect the success of treatment. The aim of this study was to assess the prevalence of mucositis in a pediatric population with solid tumor and undergoing chemotherapy, identify the risk factors that influence its occurrence, and verify the usefulness of pain rating scales. Methods: We registered episodes of mucositis which occurred in a sample of 84 consecutive children with solid tumors between 1 January, 2012 and 30 April, 2018. The World Health Organization (WHO) oral mucositis grading scale and the modified Wong–Baker FACES Pain Rating Scale (WBS) were used to assess the severity of each episode. Moreover, data on the treatments used and blood count results were collected. Results: The prevalence of mucositis in our population was 50%, without statistically significant difference according to sex and a higher prevalence observed in patients aged >10 years. The presence of neutropenia, higher number of cycles of chemotherapy, and co-existence of lymphomas and sarcomas were identified as factors favoring the occurrence of mucositis. The WBS showed results superimposed on the WHO oral mucositis grading scale in choosing the intensity and duration of mucositis treatment. Conclusion: Oral mucositis is a common complication of chemotherapy against childhood malignancies. The WHO oral mucositis scale is a valuable tool for assessing its severity in pediatric patients. Furthermore, WBS can be used as an assessment tool to establish the therapy to be adopted for patients in whom direct evaluation of the oral cavity is not possible.

Medulloblastoma (MB) is the first primary central nervous system cancer of infancy. During the last thirty years, there has been an evolution of its treatment: although chemotherapy and radiotherapy have improved the prognosis, surgery remains a determinant key-factor for therapeutic outcome. The search of an effective adjuvant treatment along with a reduced toxicity is difficult. Following treatment with surgery, chemotherapy and radiotherapy, the prognosis for infants and young children with MB is still unfavourable and burdened by an high risk of neurocognitive deficits. The biological features of MB are not fully characterized, but now there are important directions for research. Clinical and molecular prognostic markers can be used to create a disease risk classification. In our review we resume the main features of MB, including clinical, histopathologic and molecular aspects and discuss on the therapeutic options for its treatment.

Temozolomide, an alkylating drug first adopted to treat patients with malignant gliomas, is actually an antineoplastic drug used in various regimens against childhood tumors. Treatment with temozolomide is an effective therapy for different childhood tumor types: brain tumors, neuroblastomas, Ewing’s sarcoma, and rhabdomyosarcomas. Temozolomide has been used both as monotherapy and in polychemotherapy in combination with epipodophyllotoxins, camptothecin analogues, platinum compounds, vinca alkaloids and radiotherapy. The present study analyzes the treatment schedules including temozolomide in different cancer pathologies by comparing the results, in order to evaluate the efficacy of each treatment modality

Temozolomide (TMZ) is an alkylating drug, belonging to the family of derivatives of Imidazotetrazinone. Pre-clinical studies showed that TMZ has a good bioavailability after oral administration and is able to cross the blood-brain barrier. Due to these peculiar pharmaco-dynamic features, TMZ has been first adopted in the treatment of malignant brain tumors. The clinical use of TMZ has shown that the drug has a negligible toxicity and its antitumor activity is “schedule-dependent”. Therefore, many schedules of TMZ administration have been developed in order to investigate and ameliorate its antitumoral efficacy. A higher response rate was detected when the TMZ total dose is administered over 5 days. Recently, the activity of TMZ in combination with different antineoplastic agents is under investigation in children and adults in order to test its activity in malignant tumours other than brain tumors.

Carboplatin is characterized by a subcellular mechanism of action similar to that of cisplatin although its clinical spectrum of side effects differs somewhat from that of cisplatin. Its half-life is 170 ± 34 minutes and is independent of dose; myelosuppression represents its dose-limiting toxicity. Many studies have shown that carboplatin has no clinically apparent nephrotoxicity or neurotoxicity; therefore, carboplatin may be an alternative to cisplatin in clinical circumstances where the renal or neural toxicities are dose-limiting considerations. In patients with normal renal function, carboplatin can be administered up to 600 mg/sqm with leukopenia and thrombocytopenia reversing within 14 days of drug administration. In our review, we describe the pharmacological profile and the toxicities related to the use of carboplatin for the treatment of children with cancer.

Reggiana is an autochthonous cattle breed reared mainly in the province of Reggio Emilia, located in the North of Italy. Reggiana cattle (originally a triple-purpose population largely diffused in the North of Italy) are characterised by a typical solid red coat colour. About 2500 cows of this breed are currently registered to its herd book. Reggiana is now considered a dual-purpose breed even if it is almost completely dedicated to the production of a mono-breed branded Protected Designation of Origin Parmigiano-Reggiano cheese, which is the main driver of the sustainable conservation of this local genetic resource. In this study, we provided the first overview of genomic footprints that characterise Reggiana and define the diversity of this local cattle breed. A total of 168 Reggiana sires (all bulls born over 35 years for which semen was available) and other 3321 sires from 3 cosmopolitan breeds (Brown, Holstein and Simmental) were genotyped with the Illumina BovineSNP50 panel. ADMIXTURE analysis suggested that Reggiana breed might have been influenced, at least in part, by the other three breeds included in this study. Selection signatures in the Reggiana genome were identified using three statistical approaches based on allele frequency differences among populations or on properties of haplotypes segregating in the populations (fixation index (FST); integrated haplotype score; cross-population extended haplotype homozygosity). We identified several regions under peculiar selection in the Reggiana breed, particularly on bovine chromosome (BTA) 6 in the KIT gene region, that is known to be involved in coat colour pattern distribution, and within the region of the LAP3, NCAPG and LCORL genes, that are associated with stature, conformation and carcass traits. Another already known region that includes the PLAG1 gene (BTA14), associated with conformation traits, showed a selection signature in the Reggiana cattle. On BTA

Despite advances in the treatment of brain tumors, the prognosis of children with recurrent malignant brain tumors remains poor. Etoposide (VP-16), an inhibitor of nuclear enzyme deoxyribonucleic acid (DNA)-topoisomerase II, has shown activity in brain tumors. Its efficacy appears schedule dependent but, to date, the most effective schedule of administration has not been well defined. Temozolomide (TMZ), like VP-16, penetrates the blood-brain barrier and has activity against malignant brain tumors. This novel alkylating agent is rapidly absorbed and is highly bioavailable after oral administration. The antitumor activity of TMZ has been shown to be schedule dependent. Based on the evidence of different mechanisms of cytotoxicity, TMZ and VP-16 have been utilized in combination in patients with malignant brain tumors. This review evaluates the results derived from the combination use of TMZ and oral VP-16. The reported data suggest potential activity of oral VP-16 and TMZ alone or in combination. Further clinical trials are needed to explore and confirm their promising activity in relapsed brain neoplasms.

Introduction: Platinum compounds, which are considerably effective for the treatment of childhood malignancies, have significantly contributed to the increase in long-term survival of children with cancer. Unfortunately, children receiving cisplatin-based chemotherapy have been known to be at risk for severe disabling adverse effects, such as nephrotoxicity. Methods: A literature research of the MEDLINE PubMed database was conducted to identify articles published between 1980 and 2019 reviewing “Cisplatin AND mannitol.” Results: The primary pharmacodynamics and clinical characteristics of cisplatin were described, focusing on its renal toxic effects and potential preventive strategies, in order to improve clinical outcomes among children with cancer aged 1 to 14 years. Currently, selecting either hydration alone or hydration plus mannitol for preventing nephrotoxicity has been controversial considering the lack of guidelines to provide treatment recommendations both among adults and children. Conclusions: Appropriate knowledge regarding the pharmacokinetics and toxicological profile of cisplatin may help physicians prevent renal toxicity. Unfortunately, published data regarding the nephroprotective utility of adding mannitol appear to be inconclusive. As such, appropriate hydration remains the main fundamental strategy for reducing the risk of cisplatin-induced nephrotoxicity. Considering the increasing number of children safely cured of their tumours, it is imperative that those treated with cisplatin receive the most appropriate nephroprotective strategy for reducing the negative impact of platinum compounds on quality of life.

Infantile haemangiomas (IHs) are the most common benign tumours of childhood; despite the benign histology, prognosis depends on severity of visceral involvement, with a mortality rate ranging from 50 to 90%. In this paper, we describe two infants with multifocal infantile haemangiomatosis and hepatic involvement. This condition should receive appropriate management as it can be potentially lethal due to the high risk of systemic complications such as cardiac or fulminant hepatic failure and abdominal compartment syndrome. Both cases presented with liver involvement, but only the infant who had an excellent response to propranolol is still alive. A review of current therapeutic approaches is also presented even though there are, at present, no uniform guidelines for treatment, despite the relative frequency of infantile haemangiomatosis and the potential severe complications.

Background: In the Neolithic, domestic sheep migrated into Europe and subsequently spread in westerly and northwesterly directions. Reconstruction of these migrations and subsequent genetic events requires a more detailed characterization of the current phylogeographic differentiation. Results: We collected 50 K single nucleotide polymorphism (SNP) profiles of Balkan sheep that are currently found near the major Neolithic point of entry into Europe, and combined these data with published genotypes from southwest-Asian, Mediterranean, central-European and north-European sheep and from Asian and European mouflons. We detected clines, ancestral components and admixture by using variants of common analysis tools: geography-informative supervised principal component analysis (PCA), breed-specific admixture analysis, across-breed $f_{4}$ f 4 profiles and phylogenetic analysis of regional pools of breeds. The regional Balkan sheep populations exhibit considerable genetic overlap, but are clearly distinct from the breeds in surrounding regions. The Asian mouflon did not influence the differentiation of the European domestic sheep and is only distantly related to present-day sheep, including those from Iran where the mouflons were sampled. We demonstrate the occurrence, from southeast to northwest Europe, of a continuously increasing ancestral component of up to 20% contributed by the European mouflon, which is assumed to descend from the original Neolithic domesticates. The overall patterns indicate that the Balkan region and Italy served as post-domestication migration hubs, from which wool sheep reached Spain and north Italy with subsequent migrations northwards. The documented dispersal of Tarentine wool sheep during the Roman period may have been part of this process. Our results also reproduce the documented 18th century admixture of Spanish Merino sheep into several central-European breeds. Conclusions: Our results contribute to a better understanding of the events th