Antimicrobial therapies administrated during the Third Plague Pandemic in Europe.

Plague raged in Europe for over 1400 years and was responsible for three major pandemics. Today, plague still poses a serious threat to global public health and surveillance is imperative. Plague is still present in natural reservoirs on several continents, including Africa, Asia and the Americas, and sometimes causes local cases and epidemics. The Third Plague Pandemic caused millions of deaths worldwide, including in Europe. Plague arrived in Europe in the autumn of 1896 mostly through maritime trade routes, where it spread with several epidemic events until 1945, when, in the port city of Taranto, the last known outbreak was recorded. In this paper, we present an overview of the natural history and pathogenicity of Yersinia pestis, the bacterium responsible for plague, its spread from Asia to Europe during the Third Pandemic, and the therapies used to treat and prevent the disease in Europe, with particular focus on the case of Taranto. In Taranto, the Pasteur Institute's antiserum antimicrobial therapy, and vaccination were used to treat and stop the advance of the bacterium, with mixed results.

"Heal the sick": Health status and caregiving during the 17th-18th century in Northern Italy (St. Biagio cemetery, Ravenna).

OBJECTIVE: The study of health-related care provision in archeology gives important indications on the culture and community organization of past populations. This study aims to assess the health status of the skeletal assemblage recovered from the burial site of St. Biagio (Ravenna, 17th-18th Centuries); next, we identified likely instances of need for and receipt of caregiving in response to the condition, to examine evidence of community attitudes toward disease and disability. MATERIALS AND METHODS: The skeletal assemblage is composed of 133 individuals in a generally good state of preservation. Sex and age-at-death were estimated through classical anthropological methods. Health status was inferred through the biological index of frailty (BIF) and paleopathological analysis was performed through macroscopic and radiographic investigations. The "bioarcheology of care" approach was applied to individuals who showed evidence of impairment and disability. RESULTS: The skeletal assemblage of St. Biagio was equally represented by males and females (50% males), with a higher percentage of adults (83.4%) than subadults (10.5%), and this is reflected in the high life expectancy at birth (40.3 years). No significant differences in health status emerged between age groups and sexes, with a generally high percentage of joint diseases, antemortem trauma, and infectious diseases. Evidence of care and compassion was found in some individuals with a high degree of impairment or disability, as in the case of probable Angelman syndrome. DISCUSSION: This study provided important insights into the biological and social aspects of an Early Modern population in Northern Italy, showing that people with functional and/or visible abnormalities were probably cared for in life and were presumably considered full members of the society.

Technical note: Application and potentiality of quantitative ultrasonometry for the evaluation of bone mineral density status.

The evaluation of bone mineral density (BMD) is an important task in paleopathology. Techniques commonly applied in bone quantity assessment, such as DXA or radiogrammetry (XR), suffer from several limitations when applied to skeletal remains. In recently published research, we developed a new methodology and new reference curves for the evaluation of BMD on human skeletal remains, applying for the first time Quantitative Ultrasonometry (QUS), a user-friendly, portable, and reliable clinical technique. This study aims to apply this new methodology to an archeological sample and to compare the results with those obtained through XR. We apply QUS and XR to a sample of 104 adults from Medieval Italian cemeteries. Fragility fractures were recorded. Descriptive statistics and comparisons between sexes, age-at-death cohorts, and individuals with and without fragility fractures were performed. Moreover, univariate and multivariate logistic regression models were used to define the parameters most predictive of fracture risk in past populations. The comparison between sexes showed no significant results concerning BMD parameters, whereas a decrease in BMD with increasing age is confirmed. The comparison between fracture and non-fracture individuals and the logit model demonstrated that QUS parameters, especially UBPI, are more reliable predictors of fracture risk in comparison to XR. Our results confirmed that QUS is a valuable technique that can be efficiently applied to archeological remains, also considering its portability. We also propose a modification of the previously published QUS standard curves, to easily assess osteopenia and osteoporosis in archeological material.

No evidence for persistent natural plague reservoirs in historical and modern Europe.

Caused by Yersinia pestis, plague ravaged the world through three known pandemics: the First or the Justinianic (6th-8th century); the Second (beginning with the Black Death during c.1338-1353 and lasting until the 19th century); and the Third (which became global in 1894). It is debatable whether Y. pestis persisted in European wildlife reservoirs or was repeatedly introduced from outside Europe (as covered by European Union and the British Isles). Here, we analyze environmental data (soil characteristics and climate) from active Chinese plague reservoirs to assess whether such environmental conditions in Europe had ever supported "natural plague reservoirs". We have used new statistical methods which are validated through predicting the presence of modern plague reservoirs in the western United States. We find no support for persistent natural plague reservoirs in either historical or modern Europe. Two factors make Europe unfavorable for long-term plague reservoirs: 1) Soil texture and biochemistry and 2) low rodent diversity. By comparing rodent communities in Europe with those in China and the United States, we conclude that a lack of suitable host species might be the main reason for the absence of plague reservoirs in Europe today. These findings support the hypothesis that long-term plague reservoirs did not exist in Europe and therefore question the importance of wildlife rodent species as the primary plague hosts in Europe.

Sex Differences in Body Image Perception and Ideals: Analysis of Possible Determinants.

The study analyzed the differences between sexes in body image perception and body ideals to assess possible dissatisfaction and misinterpretation in the body image considered attractive for the other sex. Moreover, the influence of anthropometric traits and sports practice on body dissatisfaction and misjudgment was evaluated. Using a cross-sectional design, 960 Italian university students were investigated. Anthropometric characteristics were measured directly. Assessment of body image perception was performed using Thompson and Gray's silhouettes. We developed two new indexes to assess the possible discrepancy between (1) the perceived silhouette of one's body and that of the same sex deemed attractive to the other sex (FAD); (2) the silhouette is deemed attractive to the opposite sex and the average attractive silhouette selected by the opposite sex (AMOAD). As expected, females showed greater dissatisfaction with their bodies than males concerning both their own ideal and the silhouette they considered attractive to the opposite sex. Although both sexes misjudged the attractive silhouette for the opposite sex, women were found to be more wrong. According to the outcomes of multivariate regression models, stature, body composition parameters, amount of sport, sex, and FAD were significant predictors of dissatisfaction and misjudgment. In addition to action aimed at correcting misperceptions, the study revealed the importance of sports participation in improving the perception and acceptance of one's body image.

Belly fat or bloating? New insights into the physical appearance of St Anthony of Padua.

Over the centuries, iconographic representations of St Anthony of Padua, one of the most revered saints in the Catholic world, have been inspired by literary sources, which described the Saint as either naturally corpulent or with a swollen abdomen due to dropsy (i.e. fluid accumulation in the body cavities). Even recent attempts to reconstruct the face of the Saint have yielded discordant results regarding his outward appearance. To address questions about the real appearance of St Anthony, we applied body mass estimation equations to the osteometric measurements taken in 1981, during the public recognition of the Saint's skeletal remains. Both the biomechanical and the morphometric approach were employed to solve some intrinsic limitations in the equations for body mass estimation from skeletal remains. The estimated body mass was used to assess the physique of the Saint with the body mass index. The outcomes of this investigation reveal interesting information about the body type of the Saint throughout his lifetime.

Bioarchaeological insights into the last plague of Imola (1630-1632).

The plague of 1630-1632 was one of the deadliest plague epidemics to ever hit Northern Italy, and for many of the affected regions, it was also the last. While accounts on plague during the early 1630s in Florence and Milan are frequent, much less is known about the city of Imola. We analyzed the full skeletal assemblage of four mass graves (n = 133 individuals) at the Lazaretto dell'Osservanza, which date back to the outbreak of 1630-1632 in Imola and evaluated our results by integrating new archival sources. The skeletons showed little evidence of physical trauma and were covered by multiple layers of lime, which is characteristic for epidemic mass mortality sites. We screened 15 teeth for Yersinia pestis aDNA and were able to confirm the presence of plague in Imola via metagenomic analysis. Additionally, we studied a contemporaneous register, in which a friar recorded patient outcomes at the lazaretto during the last year of the epidemic. Our multidisciplinary approach combining historical, osteological and genomic data provided a unique opportunity to reconstruct an in-depth picture of the last plague of Imola through the city's main lazaretto.

Assessing the origins of the European Plagues following the Black Death: A synthesis of genomic, historical, and ecological information.

The second plague pandemic started in Europe with the Black Death in 1346 and lasted until the 19th century. Based on ancient DNA studies, there is a scientific disagreement over whether the bacterium, Yersinia pestis, came into Europe once (Hypothesis 1) or repeatedly over the following four centuries (Hypothesis 2). Here, we synthesize the most updated phylogeny together with historical, archeological, evolutionary, and ecological information. On the basis of this holistic view, we conclude that Hypothesis 2 is the most plausible. We also suggest that Y. pestis lineages might have developed attenuated virulence during transmission, which can explain the convergent evolutionary signals, including pla decay, that appeared at the end of the pandemics.

The biological index of frailty: A new index for the assessment of frailty in human skeletal remains.

OBJECTIVE: Frailty is the physiological stress that individuals suffer during their life. In past populations, frailty is conventionally assessed through the occurrence of different biomarkers of biological stress. Some efforts have been made to propose indexes that combine all biomarkers. However, these indices have some critical limitations: they cannot be used on incomplete skeletons, do not consider the severity and/or healing of lesions, and assign equal importance to different biomarkers. To address these limitations, we propose a new index to assess frailty in skeletal individuals. MATERIAL AND METHODS: By statistically analyzing a large amount of osteological data available from the Museum of London, and using a Logit model, we were able to define a different weight for each reported biomarker of frailty, based on their importance in increasing the risk of premature death for the individuals. RESULTS: The biological index of frailty (BIF) is the weighted mean of all biomarkers scored on the individuals, according to a different degree of importance assigned to each one. It also considers the severity and healing of the biomarkers when this is relevant to diagnose frailty. We applied BIF on a sample of Monastics and Non-Monastics from medieval England and compared it with the skeletal index of frailty (SFI). DISCUSSION: BIF is the first frailty index that gives a different weight to each skeletal biomarker of stress, considers both severity and healing of the lesions, and can be applied on partial skeletal remains. The comparison with SFI showed that BIF is applicable to a larger number of skeletal individuals, revealing new differences between the Monastic and the Non-Monastic groups.

Autopsy or anatomical dissection: evidence of a craniotomy in a 17th-eighteenth century burial site (Ravenna, Italy).

Surgical procedures undergone in life, autopsies and anatomical preparations can all leave clearly identifiable traces on human skeletal remains. Several studies on skeletons from archeological contexts have identified traces of these practices. However, the distinction between medical/forensic autopsy and anatomical dissections for scientific research can be challenging. We report the case of a middle-aged female skeleton from the cemetery of the church of San Biagio (Ravenna, Italy), dating back to the 17th-19th centuries, that shows signs of a complete craniotomy. In an attempt to clarify the reason for this practice, we analyzed all pathological and non-pathological markers on the skeleton. We carried out anthropological analyses and osteometric measurements to determine the biological profile and the cranial capacity of the individual. Paleopathological investigation and analyses of traumatic injury patterns were carried out using both a morphological and a microscopic approach. While we observed that the craniotomy was performed with a rip saw, we identified perimortem blunt force trauma to the frontal bone and an osteolytic lesion on the inner surface of the frontal bone. No other pathology was recognizable on the skeleton. Our differential diagnosis confidently proved that the craniotomy was due to an autoptsy procedure and was not the result of an anatomical dissection. We believe that, among other possible reasons, failed surgery could likely be the motive behind the ordering of the autopsy.

A genomic and historical synthesis of plague in 18th century Eurasia.

Plague continued to afflict Europe for more than five centuries after the Black Death. Yet, by the 17th century, the dynamics of plague had changed, leading to its slow decline in Western Europe over the subsequent 200 y, a period for which only one genome was previously available. Using a multidisciplinary approach, combining genomic and historical data, we assembled Y. pestis genomes from nine individuals covering four Eurasian sites and placed them into an historical context within the established phylogeny. CHE1 (Chechnya, Russia, 18th century) is now the latest Second Plague Pandemic genome and the first non-European sample in the post-Black Death lineage. Its placement in the phylogeny and our synthesis point toward the existence of an extra-European reservoir feeding plague into Western Europe in multiple waves. By considering socioeconomic, ecological, and climatic factors we highlight the importance of a noneurocentric approach for the discussion on Second Plague Pandemic dynamics in Europe.

Handgrip Strength in Young Adults: Association with Anthropometric Variables and Laterality.

The measurement of handgrip strength (HGS) is an indicator of an individual's overall strength and can serve as a predictor of morbidity and mortality. This study aims to investigate whether HGS is associated with handedness in young adults and if it is influenced by anthropometric characteristics, body composition, and sport-related parameters. We conducted a cross-sectional study on a sample of 544 young Italian adults aged 18-30 years. We measured HGS using a dynamometer and collected data on handedness and physical activity, along with anthropometric measurements. In both sexes, the HGS of the dominant side was significantly greater than that of the non-dominant side. Furthermore, in ambidextrous individuals, the right hand was stronger than the left. A comparison between the lowest and the highest tercile of HGS highlighted its significant association with anthropometric and body composition parameters in both sexes. Moreover, sex, dominant upper arm muscle area, arm fat index, fat mass, and fat-free mass were found to be significant predictors of HGS by multiple regression analysis. Our findings suggest that HGS is especially influenced by body composition parameters and handedness category. Therefore, HGS can be used as a proxy for unhealthy conditions with impairment of muscle mass, provided that the dominance in the laterality of the subject under examination is taken into account.

COVID-19 and Individual Genetic Susceptibility/Receptivity: Role of ACE1/ACE2 Genes, Immunity, Inflammation and Coagulation. Might the Double X-chromosome in Females Be Protective against SARS-CoV-2 Compared to the Single X-Chromosome in Males?

In December 2019, a novel severe acute respiratory syndrome (SARS) from a new coronavirus (SARS-CoV-2) was recognized in the city of Wuhan, China. Rapidly, it became an epidemic in China and has now spread throughout the world reaching pandemic proportions. High mortality rates characterize SARS-CoV-2 disease (COVID-19), which mainly affects the elderly, causing unrestrained cytokines-storm and subsequent pulmonary shutdown, also suspected micro thromboembolism events. At the present time, no specific and dedicated treatments, nor approved vaccines, are available, though very promising data come from the use of anti-inflammatory, anti-malaria, and anti-coagulant drugs. In addition, it seems that males are more susceptible to SARS-CoV-2 than females, with males 65% more likely to die from the infection than females. Data from the World Health Organization (WHO) and Chinese scientists show that of all cases about 1.7% of women who contract the virus will die compared with 2.8% of men, and data from Hong Kong hospitals state that 32% of male and 15% of female COVID-19 patients required intensive care or died. On the other hand, the long-term fallout of coronavirus may be worse for women than for men due to social and psychosocial reasons. Regardless of sex- or gender-biased data obtained from WHO and those gathered from sometimes controversial scientific journals, some central points should be considered. Firstly, SARS-CoV-2 has a strong interaction with the human ACE2 receptor, which plays an essential role in cell entry together with transmembrane serine protease 2 (TMPRSS2); it is interesting to note that the ACE2 gene lays on the X-chromosome, thus allowing females to be potentially heterozygous and differently assorted compared to men who are definitely hemizygous. Secondly, the higher ACE2 expression rate in females, though controversial, might ascribe them the worst prognosis, in contrast with worldwide epidemiological data. Finally, several genes involved in inflammation are located on the X-chromosome, which also contains high number of immune-related genes responsible for innate and adaptive immune responses to infection. Other genes, out from the RAS-pathway, might directly or indirectly impact on the ACE1/ACE2 balance by influencing its main actors (e.g., ABO locus, SRY, SOX3, ADAM17). Unexpectedly, the higher levels of ACE2 or ACE1/ACE2 rebalancing might improve the outcome of COVID-19 in both sexes by reducing inflammation, thrombosis, and death. Moreover, X-heterozygous females might also activate a mosaic advantage and show more pronounced sex-related differences resulting in a sex dimorphism, further favoring them in counteracting the progression of the SARS-CoV-2 infection.

Body image perception and body composition: assessment of perception inconsistency by a new index.

BACKGROUND: A correct perception of the body image, as defined by comparison with actual anthropometric analyses, is crucial to ensure the best possible nutritional status of each individual. Bioimpedance analysis (BIA) represents a leading technique to assess body composition parameters and, in particular, the fat mass. This study examined the self-perception of body image at various levels of adiposity proposing a new index. METHODS: We investigated 487 young Italian adults (mean age of males: 21.9 ± 2.4 years; mean age of females: 21.0 ± 2.2 years). Each subject could choose, on the Contour Drawing Rating Scale, the silhouette that he/she considered most resembling his/her perceived body image as well as his/her ideal body image. On each subject, we performed anthropometric measurements and determined the values of Fat mass and  %Fat with BIA. A new index, FAIFAT (Feel fat status minus Actual fat status Inconsistency), was developed to evaluate possible fat status perception inconsistencies by BIA. RESULTS: Based on ideal and feel body image comparison, women showed higher dissatisfaction than men and preferred slimmer silhouettes. FAIFAT values indicated that the fat status perception was correct in the majority of the examined individuals and only three subjects showed a serious misperception. CONCLUSIONS: Our findings suggest that FAIFAT is an appropriate index for assessing the perceived fat status from the body image when compared with data obtained by BIA. In a population, the use of this index will allow the correct identification of groups at risk for eating disorders.

An investigative strategy for assessment of injuries in forensic anthropology.

In a forensic context, identification of skeletal injuries' and traumas' timing may be of fundamental relevance to understand the events related to the life and death of an individual. In this study, we propose a new evaluation form to facilitate the detection of traumas and interpret them as ante-, peri- or post-mortem injuries. We describe the use of this form with the analysis of two skeletonized individuals. Bone injuries on their skeletons were caused by diverse sharp weapons and differed for the timing they have occurred, as revealed by macroscopic, radiographic and microscopic assays. Thanks to its completeness and user-friendly approach, the evaluation form here proposed may greatly facilitate the analysis and interpretation of injuries found on skeletons under forensic investigation.

Metagenomic analysis of dental calculus in ancient Egyptian baboons.

Dental calculus, or mineralized plaque, represents a record of ancient biomolecules and food residues. Recently, ancient metagenomics made it possible to unlock the wealth of microbial and dietary information of dental calculus to reconstruct oral microbiomes and lifestyle of humans from the past. Although most studies have so far focused on ancient humans, dental calculus is known to form in a wide range of animals, potentially informing on how human-animal interactions changed the animals' oral ecology. Here, we characterise the oral microbiome of six ancient Egyptian baboons held in captivity during the late Pharaonic era (9th-6th centuries BC) and of two historical baboons from a zoo via shotgun metagenomics. We demonstrate that these captive baboons possessed a distinctive oral microbiome when compared to ancient and modern humans, Neanderthals and a wild chimpanzee. These results may reflect the omnivorous dietary behaviour of baboons, even though health, food provisioning and other factors associated with human management, may have changed the baboons' oral microbiome. We anticipate our study to be a starting point for more extensive studies on ancient animal oral microbiomes to examine the extent to which domestication and human management in the past affected the diet, health and lifestyle of target animals.

New Evidence of Prehistoric Neurosurgery in Italy: The Case of Castello Del Tartaro.

Archaeological evidence of trepanation during the European Bronze Age is numerous and testifies a wide application of neurosurgical practices during prehistory. In some particular cases, trepanation may be associated with other peculiar evidence concerning funerary practices. The aim of this paper is to present the case of a woman from the Recent Bronze Age site of Castello del Tartaro (Verona, Italy), who was buried in a prone position and whose skeletal remains presented evidence of probable frontal trepanation. The association between a deviant burial and trepanation could be of interest in better understanding the history and perception of neurosurgical practices during prehistory.

Historical and genomic data reveal the influencing factors on global transmission velocity of plague during the Third Pandemic.

Quantitative knowledge about which natural and anthropogenic factors influence the global spread of plague remains sparse. We estimated the worldwide spreading velocity of plague during the Third Pandemic, using more than 200 years of extensive human plague case records and genomic data, and analyzed the association of spatiotemporal environmental factors with spreading velocity. Here, we show that two lineages, 2.MED and 1.ORI3, spread significantly faster than others, possibly reflecting differences among strains in transmission mechanisms and virulence. Plague spread fastest in regions with low population density and high proportion of pasture- or forestland, findings that should be taken into account for effective plague monitoring and control. Temperature exhibited a nonlinear, U-shaped association with spread speed, with a minimum around 20 °C, while precipitation showed a positive association. Our results suggest that global warming may accelerate plague spread in warm, tropical regions and that the projected increased precipitation in the Northern Hemisphere may increase plague spread in relevant regions.