Spina bifida, the normal, the pathological and the in-between: first evidence from a forensic osteological collection.

Spina bifida (SB), a rare congenital disorder, is often mentioned as an individualizing factor in Forensic Anthropology. A lack of empirical data regarding SB is noticed in the scientific literature. Moreover, within the scope of anthropological research on SB disparities in terminology, classification systems, and methodological approaches result in incomparable results. The wide range (1,2%-50%) of "spina bifida occulta" reported prevalences is a good example. This research aims to analyze and debate the standard diagnostic criteria of SB on human skeletal remains, and attempts to elaborate on an universal system, premised on the distinction between SB as a pathology, and cleft neural arch (CNA) as an anatomical variant, according to Barnes (1994, p. 360 [1). A study-base of 209 individuals (88 males; 121 females; 44-99 years old) from the 21st Century Identified Skeletal Collection from the University of Coimbra (CEI/XXI) was macroscopically analyzed, focusing on the sacrum and remaining vertebrae. Four individuals presented complete posterior opening of the sacral canal (2,6%[4/156]). The observed bone changes, combined with the analysis of the entire skeleton, indicate that CNA, rather than SB linked to a neural tube defect, is the most reliable explanation for these cases. Overall, CNA was observed on 11 skeletons (7.05% of 156). The viability and applicability of the developed methodology for the identification of SB/CNA in forensic and/or osteological contexts are discussed, as well as the possibility of a lower prevalence of SB occulta, in the general population, than speculated before. HIGHLIGHTS: • Spina bifida has been studied so far under different methodologies, classification systems and nomenclature, leading to unstandardized and incomparable data. • Spina bifida as a pathological manifestation of a neural tube defect, as opposed to cleft neural arch as a simple form of skeletal variation. • Both spina bifida and complete sacral cleft fit the criteria of an individualizing trait in Forensic Anthropology.

Time burnt away: The impact of heat-induced changes on skeletal age-at-death diagnostic features.

This paper investigates the established notion that bone calcination has a major impact on age estimation while low-intensity burns have a mere negligible impact. Few systematic researches have been carried out so far about this topic so the true impact of heat-induced changes on diagnostic age features is mostly unknown. The agreement between pre-burning and post-burning observations of age features was investigated on 51 human skeletons (22 males and 29 females with ages-at-death ranging from 61 to 93 years old) subjected to experimental burns. These skeletons belong to the 21st Century Identified Skeletal Collection housed at the Laboratory of Forensic Anthropology of the Department of Life Sciences, University of Coimbra, Portugal. The Suchey-Brooks method based on the pubic symphysis and the method developed on the auricular surface by Buckberry and Chamberlain (2002) were scrutinized. The Suchey-Brooks method provided better agreement between pre- and post-burn observations than the method from Buckberry and Chamberlain (2002). However, it became clear that heat-induced changes affected both methods regardless of heat intensity since both calcined bones and bones burnt at lower intensities often showed less than perfect agreement. Therefore, this research demonstrates that the analysis of age-at-death can be impaired in burnt bones, even those not subjected to calcination, with clear impact for forensic and archaeological investigations.

Mycobacterium leprae diversity and population dynamics in medieval Europe from novel ancient genomes.

BACKGROUND: Hansen's disease (leprosy), widespread in medieval Europe, is today mainly prevalent in tropical and subtropical regions with around 200,000 new cases reported annually. Despite its long history and appearance in historical records, its origins and past dissemination patterns are still widely unknown. Applying ancient DNA approaches to its major causative agent, Mycobacterium leprae, can significantly improve our understanding of the disease's complex history. Previous studies have identified a high genetic continuity of the pathogen over the last 1500 years and the existence of at least four M. leprae lineages in some parts of Europe since the Early Medieval period. RESULTS: Here, we reconstructed 19 ancient M. leprae genomes to further investigate M. leprae's genetic variation in Europe, with a dedicated focus on bacterial genomes from previously unstudied regions (Belarus, Iberia, Russia, Scotland), from multiple sites in a single region (Cambridgeshire, England), and from two Iberian leprosaria. Overall, our data confirm the existence of similar phylogeographic patterns across Europe, including high diversity in leprosaria. Further, we identified a new genotype in Belarus. By doubling the number of complete ancient M. leprae genomes, our results improve our knowledge of the past phylogeography of M. leprae and reveal a particularly high M. leprae diversity in European medieval leprosaria. CONCLUSIONS: Our findings allow us to detect similar patterns of strain diversity across Europe with branch 3 as the most common branch and the leprosaria as centers for high diversity. The higher resolution of our phylogeny tree also refined our understanding of the interspecies transfer between red squirrels and humans pointing to a late antique/early medieval transmission. Furthermore, with our new estimates on the past population diversity of M. leprae, we gained first insights into the disease's global history in relation to major historic events such as the Roman expansion or the beginning of the regular transatlantic long distance trade. In summary, our findings highlight how studying ancient M. leprae genomes worldwide improves our understanding of leprosy's global history and can contribute to current models of M. leprae's worldwide dissemination, including interspecies transmissions.

Differential diagnosis of a diffuse sclerosis in an identified male skull (early 20th century Coimbra, Portugal): A multimethodological approach for the identification of osteosclerotic dysplasias in skeletonized individuals.

OBJECTIVE: This work aims to discuss the difficulties in diagnosing osteosclerotic changes in skeletonized individuals and to raise awareness of osteosclerotic dysplasias as a group of rare ancient diseases. MATERIALS: The skull of a 62-year-old male individual from the International Exchange Skull Collection, curated by the University of Coimbra, who died in 1928 presenting albuminous nephritis (Bright disease)/uraemia as the registered cause of death. METHODS: The skull was macroscopically and radiologically examined and bone elemental analysis was investigated. The genealogy and medical records of the individual were also searched. RESULTS: The lesions are in accordance with an osteosclerotic process possibly pointing to osteosclerosis, osteosclerotic metaphyseal dysplasia, or dysosteosclerosis, but osteoclasia with hyperphosphatasia, endosteal hyperostosis, sclerosteosis, or osteopathia striata with cranial sclerosis cannot be ruled out. CONCLUSIONS: Representativeness of the skeleton is a crucial feature in diagnosing rare diseases and, to avoid a misdiagnosis, the final diagnosis should include a group of diseases rather than a definite disease. SIGNIFICANCE: Difficulties in diagnosing rare diseases are discussed and best approaches in the study osteosclerotic dysplasias in skeletonized individuals are offered in the light of current clinical knowledge. LIMITATIONS: The absence of the postcranial skeleton and of pathognomonic lesions associated with osteosclerotic dysplasias limits diagnosis. Although rare diseases often have a genetic basis, specific genetic testing for the diagnosis of rare diseases in paleopathological cases are not yet available. SUGGESTIONS FOR FURTHER RESEARCH: Future genetic studies might help narrow down the diagnosis.

Cancers as rare diseases: Terminological, theoretical, and methodological biases.

OBJECTIVE: Was cancer a rare disease in the past? Our objective is to consider the various terminological, theoretical, and methodological biases that may affect perceptions of the rarity of cancer in the past. MATERIALS AND METHODS: We discuss relevant malignant neoplastic biomedical and paleopathological literature and evaluate skeletal data. We selected 108 archaeological sites (n = 151 cancer cases) with published malignant neoplasms and that were amenable to calculating cancer crude prevalence. Furthermore, datasets from four medieval/postmedieval Portuguese and 12 postmedieval UK sites were used to compare age-adjusted rates for metastatic bone disease and tuberculosis. RESULTS: In the literature review, mean cancer crude prevalence (1.2 %; 95 % CI = 0.96-1.4) exceeded the threshold for a rare disease (RD). Age-standardized rates of MBD and TB were not markedly different in the sites surveyed. CONCLUSIONS: Methodological, theoretical and historical factors contribute to assumptions that cancers were rare diseases. The assumption that cancers are extremely rare in the paleopathological literature was not fully supported. Cancer is a heterogeneous concept, and it is important to view it as such. If a disease is considered rare, we may fail to recognize it or dismiss it as unimportant in the past. SIGNIFICANCE: We present a re-evaluation of the idea that cancer is a rare disease. We present a more nuanced way of comparing rates of pathological conditions in archaeological contexts. LIMITATIONS: Variation in the amount of useable information in published literature on malignant neoplasms. SUGGESTIONS FOR FURTHER RESEARCH: More large-scale studies of cancer in the past alongside comparative studies of cancer prevalence with other assumed rare diseases.

The first probable evidence of leprosy in a male individual (17th-19th century AD) unearthed in Northern Portugal (Travanca, Santa Maria da Feira).

OBJECTIVE: This study describes the first evidence of a probable paleopathological case of leprosy from northern Portugal. MATERIALS: An adult male, skeleton 403, exhumed from the Christian cemetery associated with the church dedicated to Saint Mamede (Travanca, Santa Maria da Feira), dated from the 17th-19th century AD. METHODS: Standard bioarchaeological methods were used for sex and age-at-death determinations, and leprosy-related bone lesions were identified through macroscopic analysis guided by paleopathological diagnostic criteria. RESULTS: The macroscopic observation revealed probable leprosy-related skeletal lesions, namely tenuous rhinomaxillary changes, bilateral proliferative periosteal reactions on the tibiae and fibulae, as well as concentric atrophy, acro-osteolysis and ankyloses of foot bones. CONCLUSIONS: Skeleton 403 represents a probable case of leprosy according to the nature and distribution pattern of bony lesions observed. SIGNIFICANCE: This finding fills an important gap in the history of leprosy in Portugal. Although historical sources show that the majority of leprosaria were located in the northern part of the country, suggesting that leprosy was more prevalent in this area of Portugal in the past, no paleopathological evidence of this disease was reported for this region to date. Furthermore, the inhumation of a leprosy sufferer in a 17th-19th century AD Christian parish cemetery is deeply imbued with social meaning. SUGGESTION FOR FUTURE RESEARCH: The future detailed study of the remaining skeletons unearthed from the cemetery of the Church of São Mamede will hopefully reveal further osteological evidence of leprosy in addition to the application of ancient DNA analysis to confirm the presence of the pathogen of this disease. Also, further documentary research is needed in order to expand appreciation of the epidemiological and social impact of leprosy in the 17th-19th century AD Portugal.

"Sex change" in skeletal remains: Assessing how heat-induced changes interfere with sex estimation.

The true impact of heat-induced changes in human bone regarding their sex estimation has not been comprehensively documented having a potentially negative impact on forensic anthropology. The objective of this paper was to evaluate how heat exposure affects sex estimation based on both morphological and metric features. The study focused in both low-to-medium intensity burns and high intensity burns. Selected sexually dimorphic features were analysed in 51 experimentally burnt skeletons from the 21st Century Identified Skeletal Collection. Bones were burnt to maximum temperatures between 450 °C and 1050 °C achieved after 75 to 257 min. Morphological methods tested in this study comprised the recommendations for hipbone features from Buikstra and Ubelaker (1994) and from Bruzek (2002). On the other hand, metric references tested here were the ones from Wasterlain (2000), Curate et al. (2016) and Gonçalves et al. (2013) focused on the humerus, femur, calcaneus and talus. Agreement was tested with Gwet's AC1 test and was further assessed by calculating the relative amount of perfect agreements. Results demonstrated that heat-induced changes affected not only the scoring of morphological features burnt at high temperatures but also the scoring of features burnt at lower intensities. On the other hand, metric features were only considerably affected in high intensity burns, no major changes being documented for low-to-medium intensity burns. For low-to-medium intensity burns, the Bruzek and Curate et al. methods revealed a better agreement between the pre- and post-burning scores. For high intensity burns, better agreement was obtained by using the Bruzek (2002) and Gonçalves et al. (2013) methods. As expected, heat-induced warping, fracture and metric change had a major impact on the pre- and post-observations' agreement. Contrary to what has been systematically assumed over the years, this impact is also quite substantial in bones burnt at low-to-medium burn intensities so caution is advised during the analysis of this kind of burnt skeletal material.

Bullying entre os jovens: relações com o preconceito e a autoestima / Bullying among young people: relation with prejudice and self-esteem

Esta pesquisa objetivou investigar a ocorrência do bullying e suas relações com o preconceito e a autoestima dos estudantes de escolas públicas. Participaram 284 estudantes, e os instrumentos utilizados foram a Escala de Autoidentificação de Bullying, a Escala de Manifestação de Preconceito, a Escala de Autoestima de Rosenberg e um questionário sociodemográfico. Nos resultados, verificou-se que quanto maior a ocorrência de bullying, mais o preconceito se manifesta (ρ = 0,261; p<0,05). Entre os alvos do bullying, constatou-se que quanto mais o estudante sofre agressões, menores serão os níveis de autoestima (ρ= -0,218; p<0,05). Em suma, os dados demonstraram que o bullying é um risco à qualidade de vida dos participantes e requer cuidados, como planos de intervenções, com foco em minimizar suas ações e romper com a cristalização da percepção de serem "brincadeiras" ou uma solução para os conflitos inter e intrapessoais.

This research aimed to investigate the occurrence of bullying and its relation with prejudice and self-esteem of students from public schools. A total of 284 students from public schools participated in the study and the instruments used were the Bullying Self-Identification Scale, the Prejudice Manifestation Scale, the Rosenberg Self-Esteem Scale, and a sociodemographic questionnaire. The results showed that the greater the occurrence of bullying, the more the prejudice is manifested (ρ = 0.261; p <0.05). Among the targets of bullying, it was found that the more the student is attacked , the lower the levels of self-esteem (ρ = -0,218; p <0,05). In short, data demonstrated that bullying is a risk to the participants' quality of life and requires attention, such as intervention plans, focused on minimizing its actions and breaking with the crystallization of the perception that it is "just a joke" or a solution for inter- and intrapersonal conflicts.

Esta investigación tuvo como objetivo averiguar la ocurrencia del bullying y su relación con el prejuicio y la autoestima de los estudiantes de las escuelas públicas. Participaron 284 estudiantes y los instrumentos utilizados fueron la Escala de Autoidentificación del Bullying, la Escala de Manifestación de Prejuicios, la Escala de Autoestima de Rosenberg y un cuestionario sociodemográfico. En los resultados se encontró que cuanto mayor es la ocurrencia de bullying, más se manifiesta el prejuicio (ρ = 0,261; p <0,05). Entre los objetivos del bullying, se encontró que cuanto más agresión sufre el alumno, menores son los niveles de autoestima (ρ = -0,218; p <0,05). En definitiva, los datos demostraron que el bullying es un riesgo para la calidad de vida de los participantes y requiere cuidados, como planes de intervención, con un enfoque en minimizar sus acciones y romper con la cristalización de la percepción de ser "juegos" o una solución para conflictos inter e intrapersonales.

Bullying, preconceito e autoestima: discutindo as principais relações e distinções / Bullying, prejudiceand self-esteem: discussing the main relationships and distinctions

O preconceito e o bullying são duas formas de violência escolar que podem atingir diferentes grupos socioculturais. São entendidos, na literatura científica, como fenômenos que causam prejuízos emocionais, cognitivos e comportamentais nos alvos da agressão, afetando a avaliação, ou autoestima, fator importante para o desenvolvimento individual e as relações interpessoais. Neste estudo, foi realizada uma revisão narrativa não-sistemática que objetivou apresentar e discutir os principais conceitos, relações e distinções entre preconceito, bullying e autoestima. Foi realizado um levantamento no banco de dados da Scielo, Pepsic e periódicos CAPES, através da plataforma CAFe, de artigos científicos, dissertações, teses e livros, que promoviam o debate dos construtos apresentados, por meio dos descritores em português. Os resultados demonstraram que o preconceito e o bullying são fenômenos articulados que afetam, negativamente, a convivência, representando um perigo às escolas, devido as práticas agressivas serem percebidas como “brincadeiras”, ocasionando a naturalização entre os grupos. Além disso, notou-se que a autoestima é uma variável importante no enfrentamento dessas condutas, por ser um indicativo para a criação de habilidades sociais que favorecem a saúde mental dos envolvidos.(AU)

Prejudice and bullying are two forms of school violence that can affect different socio-cultural groups. They are understood, in the scientific literature, as phenomena that cause emotional, cognitive, and behavioral damages in the targets of aggression, affecting the evaluation, or self-esteem, an important factor for individual development and interpersonal relationships. In this study, a non-systematic narrative review was carried out that aimed to present and discuss the main concepts, relationships, and distinctions between prejudice, bullying and self-esteem. A survey was carried out in the database of Scielo, Pepsic and CAPES journals, through the CAFe platform, of scientific articles, dissertations, theses, and books, which promoted the debate of the constructs presented, through the descriptors in Portuguese. The results showed that prejudice and bullying are articulated phenomena that negatively affect coexistence, representing a danger to schools, due to the aggressive practices being perceived as “games”, causing naturalization between groups. In addition, it was noted that self-esteem is an important variable in coping with these behaviors, as it is indicative for the creation of social skills that favor the mental health of those involved.(AU)

The human cingulum: From the limbic tract to the connectionist paradigm.

The cingulum is a core component of the limbic lobe and part of the circuit that was described by Papez where environmental experiences become endowed with emotional awareness. Recent techniques for the study of cerebral connectivity have updated this fasciculus' morphology and led to the acknowledgment that its involvement in superior functions goes far beyond emotion processing. Long and robust, the cingulum is a long association fasciculus with terminations in all cerebral lobes. These observations plead for a pivotal rethinking of its role in the human brain and lead to the conclusion that to merely consider it as the main fasciculus of the limbic system was actually a reductionism. This paper summarizes the key facts regarding why the cingulum is now perceived as a primary interconnecting apparatus in the medial aspect of the cerebral hemisphere.

Cardiac allograft vasculopathy: Incidence and predictors in a single-center cohort.

INTRODUCTION AND AIMS: Cardiac allograft vasculopathy (CAV) is one of the most significant complications after orthotopic heart transplantation. We aimed to investigate the incidence and predictors of CAV in a large cohort of orthotopic heart transplantation patients. METHODS: We conducted a retrospective analysis on a prospective cohort of 233 patients who underwent transplantation between November 2003 and May 2014. Baseline clinical data and invasive coronary angiograms (n=712) performed as part of the follow-up program were analyzed by two independent investigators. RESULTS: We included 157 male and 45 female patients with a median age of 66 years. A third of patients had previous ischemic heart disease, 30% peripheral arterial disease, 37% hypertension and 47% dyslipidemia, and 17% were smokers. Acute moderate or severe rejection occurred in 42 patients during the first year. Over a median follow-up of 2920 days, 18% were diagnosed with CAV, with an incidence of 2.91 cases per 100 person-years. Predictors of CAV were previous ischemic heart disease (HR 2.32, 95% CI 1.21-4.45, p=0.01), carotid artery disease (HR 2.44, 95% CI 1.27-4.71, p<0.01), and donor age (HR 1.04, 95% CI 1.00-1.07, p=0.01). CONCLUSION: In a single-center cohort of orthotopic heart transplantation patients, predictors of CAV were previous ischemic heart disease, carotid artery disease and donor age.

Closure of bronchopleural fistula by a septal occluder device: a case for close collaboration between heart and lung specialists.

We present the case of a 66-year-old woman who underwent right inferior lobectomy for pulmonary carcinoma and developed persistent bronchopleural fistula (BPF) that was not amenable to surgical intervention (two surgical failures). The patient presented with a persistent cough and dyspnoea, which was treated with a hybrid procedure using fluoroscopy and bronchoscopy. A 7 mm Amplatzer septal occluder device (ASOD) was successfully inserted into the BPF. Two weeks after the procedure, a small fistula developed, which was treated by endoscopically guided biologic glue embolisation. At 2-month, 6-month and 12-month follow-up visits, clinical examinations and endoscopic imaging confirmed the complete occlusion of the BPF. Obvious migration of the ASOD was not apparent, and the patient has remained asymptomatic. The success of an endoscopic BPF closure with the use of hybrid techniques was achieved because of a collaborative effort by a multidisciplinary team.

Patient-specific 3D printing simulation to guide complex coronary intervention.

The field of three-dimensional printing applied to patient-specific simulation is evolving as a tool to enhance intervention results. We report the first case of a fully simulated percutaneous coronary intervention in a three-dimensional patient-specific model to guide treatment. An 85-year-old female presented with symptomatic in-stent restenosis in the ostial circumflex and was scheduled for percutaneous coronary intervention. Considering the complexity of the anatomy, patient setting and intervention technique, we elected to replicate the coronary anatomy using a three-dimensional model. In this way, we simulated the intervention procedure beforehand in the catheterization laboratory using standard materials. The procedure was guided by optical coherence tomography, with pre-dilatation of the lesion, implantation of a single drug-eluting stent in the ostial circumflex and kissing balloon inflation to the left anterior descending artery and circumflex. Procedural steps were replicated in the real patient's treatment, with remarkable parallelism in angiographic outcome and luminal gain at intracoronary imaging. In this proof-of-concept report, we show that patient-specific simulation is feasible to guide the treatment strategy of complex coronary artery disease. It enables the surgical team to plan and practice the procedure beforehand, and possibly predict complications and gain confidence.

Absence of evidence or evidence of absence? A discussion on paleoepidemiology of neoplasms with contributions from two Portuguese human skeletal reference collections (19th-20th century).

Biological, sociocultural, demographic and environmental factors are major contributors to the contemporary burden of oncological diseases. Although cancer's current epidemiological landscape is fairly well known, its past occurrence and history seem more obscure. In order to test the hypothesis that paleopathological diagnosis is an adequate measure of the prevalence of malignant neoplasms in human remains, 131 skeletons (78 females, 53 males, age-at-death range: 15-93 years) from Coimbra and Lisbon Identified Skeletal Collections, 19th/20th century (Portugal), were examined. The cause of death for all of the selected skeletons was a malignant neoplasm, as recorded in the collection's documental files. Through the application of standard paleopathological protocols, it was determined that 17.6% (n = 23) of the skeletons had unequivocal osseous signs of metastatic and/or neoplastic lesions. Forty-five percent (n = 59) had manifest osseous lesions, however the lesional patterns were not clearly pathognomonic. Although all of the analyzed individuals were documented as having succumbed to malignant neoplastic disease, a total of 37.4% (n = 49) of the individuals did not exhibit osseous abnormalities. Individuals with breast cancer often exhibited lesions. This study presents a quantitative estimate of the accuracy of paleopathological diagnosis; as well as a theoretical reflection on the burden of cancer in the past. We emphasize the need for a paradigm shift while thinking about the future of paleo-oncology.

Heart transplant coronary artery disease: Multimodality approach in percutaneous intervention.

Coronary artery disease is the most important cause of late morbidity and mortality after heart transplantation. It is usually an immunologic phenomenon termed cardiac allograft vasculopathy, but can also be the result of donor-transmitted atherosclerosis. Routine surveillance by coronary angiography should be complemented by intracoronary imaging, in order to determine the nature of the coronary lesions, and also by assessment of their functional significance to guide the decision whether to perform percutaneous coronary intervention. We report a case of coronary angiography at five-year follow-up after transplantation, using optical coherence tomography and fractional flow reserve to assess and optimize treatment of coronary disease in this challenging population.