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To investigate variation in ancient DNA recovery of Brucella melitensis, the causative agent of brucellosis, from multiple tissues belonging to one individual 14 samples were analyzed from the mummified remains of the Blessed Sante, a 14 th century Franciscan friar from central Italy, with macroscopic diagnosis of probable brucellosis. Shotgun sequencing data from was examined to determine the presence of Brucella DNA. Three of the 14 samples contained authentic ancient DNA, identified as belonging to B. melitensis. A genome (23.81X depth coverage, 0.98 breadth coverage) was recovered from a kidney stone. Nine of the samples contained reads classified as B. melitensis (7−169), but for many the data quality was insufficient to withstand our identification and authentication criteria. We identified significant variation in the preservation and abundance of B. melitensis DNA present across multiple tissues, with calcified nodules yielding the highest number of authenticated reads. This shows how greatly sample selection can impact pathogen identification. Our results demonstrate variation in the preservation and recovery of pathogen DNA across tissues. This study highlights the importance of sample selection in the reconstruction of infectious disease burden and highlights the importance of a holistic approach to identifying disease. Study focuses on pathogen recovery in a single individual. Further analysis of how sampling impacts aDNA recovery will improve pathogen aDNA recovery and advance our understanding of disease in past peoples [ABSTRACT FROM AUTHOR]

To evaluate and differentially diagnose erosive skeletal lesions located on multiple joints of an individual archaeologically recovered in 2017. Skeletal remains of a well-preserved skeleton dating to the 12th–13th centuries from the medieval church of San Biagio in Cittiglio (Varese, northern Italy). Macroscopic and radiographic imaging. Erosive marginal symmetrical lesions are present on the metatarsophalangeal, metacarpophalangeal and interphalangeal joints of an adult male, aged 55–75 years. Osteolytic changes, in the form of pocket erosions, surface resorptions and pseudocyst formations, are also macroscopically observed on some carpal and tarsal bones and on several large peripheral joints. A careful differential diagnosis of the lesions and their macroscopic and radiological appearance is suggestive of a case of rheumatoid arthritis-like polyarthropathy. This case contributes to the debate regarding the antiquity of erosive polyarthropathies, providing additional evidence for the existence of these diseases in the Old World prior to the European discovery of the Americas. Small sample size limits discussion of the scope of the disease in antiquity. This case highlights the need for further macroscopic, radiographic, and biomolecular studies of pre-modern European skeletal samples to investigate the hypothesized pre-existence of these pathological conditions in Europe prior to 1492. [ABSTRACT FROM AUTHOR]

Abstract This paper provides a critical literature review concerning paleopathological evidence of multiple myeloma discovered both in the Old and in the New World. A critical assessment of the bioarchaeological and paleopathological documentary sources permitted to identify a total of 25 ascertained cases of multiple myeloma from different geographical areas in the world ranging from Prehistoric times up to the Contemporary age. The distribution of multiple myeloma findings in past times shows that the majority of cases have been discovered in the Old World (n = 18) and extend back to the Middle Ages, while the evidences in the New World (n = 7) seems to date back to the pre-Columbian era. The demographic profile suggests a sex ratio of 1.3:1, while 91.7% of affected individuals (n = 24) are adults. This critical review also discusses the diagnostic criteria and methodological issues commonly attempted in paleo-oncological research, with particular regard to the differential diagnosis of multiple myeloma. As such, the main focus of this work is to present a comprehensive and exhaustive scrutiny of the skeletal manifestations identified as multiple myeloma in order to improve the accuracy of diagnoses within the field of paleopathology. [ABSTRACT FROM AUTHOR]

During the archaeological excavations conducted in the 13th century cemetery of the Church of Sant'Agostino in Poggibonsi (Tuscany, Italy), a skull with evidence of neurosurgical intervention was brought to light. The skull, belonging to an adult male, shows two traumatic lesions produced by bladed instruments. The first lesion, located on the anterior part of the parietal bones, involved only the outer cranial table; bone remodeling indicates that the individual survived the injury for a long time. The second lesion, located on the frontal bone, involved all the thickness of the bone; the absence of reparative processes allows a diagnosis of peri mortem lesion. To treat this wound, the patient underwent surgical intervention. In fact, in correspondence to the lesion, an oval bone loss, with clean and well-defined cutting edges, can be interpreted as the result of a trepanation, probably performed to clean the wound and to remove any bone splinters. Half of the bone “rondella” was found in situ; it can be hypothesized that the surgeon decided to replace the bony piece to protect the brain. However, the surgical intervention failed, and the patient died soon afterwards. Trepanation for the treatment of cranial traumas is described by several medical classical and medieval authors, whose texts were available in the 13th century. This case represents rare Middle Ages evidence of neurosurgery used to treat a bone injury. [ABSTRACT FROM AUTHOR]

During the late Middle Ages and the Renaissance autopsy started to be practised for medico-legal purposes in order to investigate the causes of death. The other reason for dissecting a body was embalming, a diffused custom typical of the elitarian classes. The exploration of the Medici tombs in the Basilica of San Lorenzo in Florence offered the opportunity to investigate the practice of autopsy on these aristocratic personages of the Renaissance and Early Modern Age. A total of 25 currently skeletonized individuals, almost all of whom formerly artificial mummies, were exhumed. Accurate examination of the skeletons revealed evident signs of autoptic practices such as horizontal and oblique craniotomies, longitudinal and transversal cuts of the sternum, and sectioning of the sternal extremities of the ribs. In this group, women were treated differently to men at autopsy, as only men underwent craniotomy; autopsy and embalming were carried out also for the illegitimate members of the family and for subaldults. The extremely rich documentary archives of the Medici family confirm that the corpses were in several cases submitted to autopsy. The present study offers important direct information on the 16–18th century autoptic practices that the court surgeons in Florence performed on the members of the elite class. [ABSTRACT FROM AUTHOR]

Archaeological excavations carried out at the castle of Monte di Croce near Florence brought to light a small cemetery complex belonging to the castle church, dated back to the 11th–12th centuries. An elite stone tomb contained the skeletal remains of a male aged 35–45 years with obvious pathology of the right tibia. The proximal metaphysis and the upper half of the diaphysis appear massively enlarged as a result of severe chronic periostitis. A transverse section illustrates complete obliteration of the medullary cavity by new spongy bone, with some large cavitations. The primary, but completely remodeled tibial shaft is still recognizable. This finding and the strong sclerotic reaction with some central cavitations rule out any form of bone tumor and indicate a chronic inflammatory disease. The morphological and radiological picture and the tibial localization suggest a diagnosis of chronic sclerosing osteomyelitis of Garré, a rare form of chronic osteomyelitis characterized by an intense periosteal reaction with little or no suppuration. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Ever since the Late Medieval Ages historico-medical literature has attested the use of cranium humanun as an ingredient in pharmacological preparations for the treatment of epilepsy. Some authors suggest the use of pulverized bone obtained from individuals who died a violent death and were not buried. Materials and methods The skeletal remains of hundreds of male inhabitants from Otranto, killed by the Ottomans in a mass execution on 14 August, 1480, are preserved in the Chapel of Martyrs in Otranto Cathedral (Apulia, southern Italy). The so-called “martyrs of Otranto” were beatified in 1771 and canonized by Pope Francis on 12 May, 2013. A cranial vault with 16 holes of different sizes, with regular rounded shape, was noticed among the skeletal remains, symmetrically arranged behind five large rectangular windows. Eight of the 16 holes, which exposed the diploe without reaching the endocranial surface, are incomplete perforations, while 8 holes are complete perforations; no evidence of bone reaction is visible. Results The lesions are the result of a multiple trepanation performed by using an instrument equipped with a large rounded tip. This tool could not produce bone discs, but only bone powder. It is impossible to establish with certainty the reasons for these multiple trepanations, but several hypotheses can be advanced, ranging from experimental surgery to a procedure designed to obtain relics. However, saint bones are very likely to have been regarded as having medicinal properties. As a matter of fact the martyrs of Otranto died a violent death and were not buried, and the pulverized bone obtained from their skulls might have been considered a particularly powerful ingredient for pharmacological preparations, as attested in the historico-medical literature. Conclusions The skull of Otranto might represent a unique evidence of multiple trepanations carried out to obtain bone powder as ingredient for therapeutic preparations. [ABSTRACT FROM AUTHOR]

Abstract: Documentary sources show that painful joint disease afflicted several members of the Medici family, which dominated Renaissance Florence in Italy. The term frequently reported in contemporary archives to indicate these morbid episodes is “gout.” Paleopathology allows us to verify the nosological information obtained from the written documents and to clarify the nature of the rheumatological condition that afflicted the Medici. A paleopathological study carried out on the skeletal remains of several members of the Medici family buried in the basilica of S. Lorenzo in Florence demonstrated that the “gout” of the Medici was truly a uric acid gout only in Ferdinand I (1549–1609), whose left foot showed peculiar lesions. Genetic and environmental factors, with particular regard to diet, may have been involved in the etiology of this disease, which in Ferdinand was associated with diffuse idiopatic skeletal hyperostosis (DISH). DISH was observed also in the column of Cosimo the Elder (1389–1464) and Cosimo I (1519–1574); a link between the incidence of DISH and high social status, especially in terms of lifestyle and nutritional patterns, has been suggested and the present study seems to further confirm this association. Finally, rheumatoid arthritis (RA) was diagnosed in Cosimo the Elder, Piero “the Gouty” (1416–1469) and Cardinal Carlo (1596–1666); as for Carlo, macroscopic and radiological findings were supported by molecular results which revealed that he was bearing the specificity HLA-DR4 predisposing to RA. The coexistence of DISH and RA attested in Cosimo the Elder can be interpreted as coincidental. In conclusion, the term “gout” as used in Renaissance texts has to be regarded as the clinical manifestation of a number of different joint diseases. In the case of the Medici family in Florence, these included DISH, rheumatoid arthritis and uric acid gout. [Copyright &y& Elsevier]

Summary: King Ferrante I of Aragon, leading figure of the Italian Renaissance, died in 1494. The autopsy of his mummy revealed a tumor infiltrating the small pelvis. We examined the histologic and molecular features of this ancient tumor to investigate its primary origin. Hematoxylin-eosin, Van Gieson, and Alcian Blue staining showed neoplastic cells infiltrating muscular fibers and forming pseudo-glandular lumina disseminated in fibrous stroma with scarce mucus. A strong immunoreactivity of the neoplastic cells was shown for pancytokeratins and proliferating cell nuclear antigen. Molecular fingerprints were investigated by examining K-ras, BRAF, and microsatellite instability in ancient tumor DNA. Sequencing analysis showed G-to-A transition in codon 12 of K-ras. BRAF mutations and microsatellite instability were not observed. Because the presence of K-ras codon 12 mutation could be associated with exposure to chemical carcinogens, possibly present in some food items, paleodietary reconstruction of the King Ferrante I was carried out by carbon (δ 13C ) and nitrogen (δ 15N) stable isotopes analysis. δ 13C and δ 15N values found in bone collagen of the King were consistent with a massive intake of animal proteins. Overall, our data show that the tumor of Ferrante I was a mucinous adenocarcinoma with molecular fingerprints characteristic of colorectal carcinogenesis linked to K-ras pathway. Paleodietary reconstruction and historical chronicles indicate a strong consumption of meat by the King. The possible abundance of dietary carcinogens, related to meat consumption, could explain the K-ras mutation causing the colorectal tumor that killed Ferrante I more than 5 centuries ago. [Copyright &y& Elsevier]

Venosa-Notarchirico is a musealized Lower Paleolithic site in southern Italy (Basilicata), where a human femoral shaft was discovered in 1985. The fossil specimen can be evaluated in the new light of excavations started in 2016, which provide a more updated and extensive picture of the site, including the crucial Ar/Ar date of 661-614 ka for the human specimen. This makes the fossil diaphysis from Venosa-Notarchirico (Vn-H1) the oldest fossil hominin found so far in the Italian peninsula, associated with the earliest evidence of genuine Acheulean in Europe. In this paper, we report a comparative morphometric analysis of this femur, as well as a paleopathological reappraisal of the periosteal alteration that affects the specimen, supported by an unpublished histological analysis. Vn-H1 represents the proximal two-thirds of a right femur lacking the epiphyseal region. We argue it belonged to an immature individual, possibly a juvenile (late adolescent). Its features suggest that the specimen may refer to an archaic (i.e. , non-modern) human species, also showing morphological differences compared to fossil samples of the Neanderthal lineage. We also support the identification of a pathological condition affecting Vn-H1, particularly evident in some preserved portions of the mid-shaft as described here. Its etiology is discussed after differential diagnosis, which led us to suggest an alteration of inflammatory origin, viewed as a nonspecific periosteal response. This pathology may have been roughly concomitant with the death of the individual. • Vn-H1 represents the oldest human fossil specimen ever found in Italy within one of the earliest Acheulean sites in Europe. • The age of Vn-H1, dated Ar/Ar at 661-614 ka, takes advantage of the recent new excavations at the Venosa-Notarchirico site. • Both morphology and morphometry of the human specimen suggest an age at death of the individual to the late adolescence. • Palaeopathological observations, supported by unpublished histological data, suggest the nature of the periosteal alteration. [ABSTRACT FROM AUTHOR]

We present a case of a giant bladder stone, 7.5 cm in diameter, found in the pelvis of a 19th-century natural mummy from Borgo Cerreto (central Italy). We used microchemical energy-dispersive x-ray spectroscopy analysis and x-ray diffraction to define the mineral composition of the stone and obtain information about its internal structure. Chemical analysis showed a mixed composition. The internal layers contained mostly ammonium acid urate, whereas the external layers were composed of magnesium ammonium phosphate (struvite). Our research suggests a metabolic origin for the calculosis, with superimposed infection. [Copyright &y& Elsevier]