Climate change, human health, and resilience in the Holocene.

Climate change is an indisputable threat to human health, especially for societies already confronted with rising social inequality, political and economic uncertainty, and a cascade of concurrent environmental challenges. Archaeological data about past climate and environment provide an important source of evidence about the potential challenges humans face and the long-term outcomes of alternative short-term adaptive strategies. Evidence from well-dated archaeological human skeletons and mummified remains speaks directly to patterns of human health over time through changing circumstances. Here, we describe variation in human epidemiological patterns in the context of past rapid climate change (RCC) events and other periods of past environmental change. Case studies confirm that human communities responded to environmental changes in diverse ways depending on historical, sociocultural, and biological contingencies. Certain factors, such as social inequality and disproportionate access to resources in large, complex societies may influence the probability of major sociopolitical disruptions and reorganizations-commonly known as "collapse." This survey of Holocene human-environmental relations demonstrates how flexibility, variation, and maintenance of Indigenous knowledge can be mitigating factors in the face of environmental challenges. Although contemporary climate change is more rapid and of greater magnitude than the RCC events and other environmental changes we discuss here, these lessons from the past provide clarity about potential priorities for equitable, sustainable development and the constraints of modernity we must address.

Pneumatosis intestinalis: a rare endoscopic feature of colonic ischemia.

A 71-year-old male was admitted on intensive care unit after endovascular aneurysm repair of ruptured infrarenal abdominal aortic aneurysm. 2 weeks later, he had multiple episodes of bloody diarrhea. Colonoscopy revealed diffuse dusky mucosal coloration with loss of vasculature pattern, diseased haustrations, and diffuse areas of pneumatosis, suggestive of severe colonic ischemia.

Triple-sized intragastric balloon due to spontaneous hyperinflation.

A 38-year-old female with medical history of breast cancer, hypertension, diabetes mellitus and obesity (body max index 55kg/m2), was admitted to the emergency room with complains of nausea and vomits. Three weeks prior to the presentation, she placed an intragastric balloon (IGB) (Orbera365™, Apollo endosurgery Inc., Austin, TX), for weight loss, filled with 600ml solution of saline and methylene blue dye. Upon physical examination, she was dehydrated and presented with a bulging of the upper abdominal wall associated with mild abdominal pain. Laboratory tests showed severe metabolic alkalosis, hypocalcemia and hypokalemia. Abdominal x-ray revealed gastric distension with an increased size IGB, measuring 164.3*145.6*144.1 mm (estimated volume of 1800mL), with an air-fluid level. Upper endoscopy revealed the balloon stuck in the antrum. A catheter needle was used to puncture and deflate the balloon. Once deflated it was removed with endoscopic forceps. The fluid was not sent for microbiologic culture. After IGB removal, hydroelectrolytic disturbances were resolved and oral feeding was promptly resumed without further complications.

Artificial intelligence for automatic diagnosis of biliary stricture malignancy status in single-operator cholangioscopy: a pilot study.

BACKGROUND AND AIMS: The diagnosis and characterization of biliary strictures (BSs) is challenging. The introduction of digital single-operator cholangioscopy (DSOC) that allows direct visual inspection of the lesion and targeted biopsy sampling significantly improved the diagnostic yield in patients with indeterminate BSs. However, the diagnostic efficiency of DSOC remains suboptimal. Convolutional neural networks (CNNs) have shown great potential for the interpretation of medical images. We aimed to develop a CNN-based system for automatic detection of malignant BSs in DSOC images. METHODS: We developed, trained, and validated a CNN-based on DSOC images. Each frame was labeled as a normal/benign finding or as a malignant lesion if histopathologic evidence of biliary malignancy was available. The entire dataset was split for 5-fold cross-validation. In addition, the image dataset was split for constitution of training and validation datasets. The performance of the CNN was measured by calculating the area under the receiving operating characteristic curve (AUC), sensitivity, specificity, and positive and negative predictive values. RESULTS: A total of 11,855 images from 85 patients were included (9695 malignant strictures and 2160 benign findings). The model had an overall accuracy of 94.9%, sensitivity of 94.7%, specificity of 92.1%, and AUC of .988 in cross-validation analysis. The image processing speed of the CNN was 7 ms per frame. CONCLUSIONS: The developed deep learning algorithm accurately detected and differentiated malignant strictures from benign biliary conditions. The introduction of artificial intelligence algorithms to DSOC systems may significantly increase its diagnostic yield for malignant strictures.

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.

Clinical and endoscopic findings in gastrointestinal amyloidosis: a single-center experience.

Gastrointestinal involvement occurs in approximately 4% of cases of systemic amyloidosis. The most common site of amyloid deposition is small bowel, followed by stomach, colorectum and esophagus. Although rare, gastrointestinal amyloidosis may be associated with severe complications including gastrointestinal bleeding or perforation and may be mistaken for malignancy.

Elemental Composition in Female Dry Femora Using Portable X-Ray Fluorescence (pXRF): Association with Age and Osteoporosis.

Pathophysiological conditions can modify the skeletal chemical concentration. This study analyzes the elemental composition in two anatomical regions from dry femoral bone using a portable X-Ray Fluorescence (pXRF) and evaluates its impact in the bone mineral density (BMD). The left femora of 97 female skeletons (21-95 years old individuals) from the Coimbra Identified Skeletal Collection were studied. Diagenetic biases were discarded at the outset and BMD was determined with Dual-energy X-ray absorptiometry. Chemical measurements were performed at the midpoint of the femoral neck and at the midshaft using a pXRF device, and comparisons were made considering the age and the BMD values. Only elements with a Technical Measurement Error ≤ 5% were selected: P, S, Ca, Fe, Zn, As, Sr, Pb and the Ca/P ratio. Statistically significant differences were found between regions, with higher concentrations of P, Ca, Zn and S at the midshaft, and the Ca/P ratio at the femoral neck. The concentration of P is higher in individuals < 50 years, while S and Ca/P ratio increase in individuals ≥ 50 years. The decrease of P with age can be simultaneously related to the decline of its concentration in osteoporosis. Decreased BMD is also associated with higher levels of S and Pb. Osteoporosis enhances the absorption of osteolytic elements in specific locations. This fast and non-destructive technique has proved effective for the comprehension of chemical changes related to bone mass loss. This study highlights the potential of identified skeletal collections to improve the knowledge about bone fragility.

Test of the auricular surface sex estimation method in fetuses and non-adults under 5 years old from the Lisbon and Granada Reference Collections.

Non-adult sex estimation is an active field of forensic inquiry as morphological variations between males and females are subtle, but observable, even from intrauterine development. The objectives of this study are threefold: to test the validity of the auricular surface method for sex estimation (Int J Osteoarchaeol 27:898-911, 2017) in fetuses and children under the age of 5 years old; to evaluate if health conditions, reported as the cause of death, influence its accuracy; and to detect possible secular trends in sexual dimorphism. One-hundred and ninety-seven skeletal individuals from the Lisbon and Granada Identified Collections were studied. Individuals were divided according to the hormonal peaks (< 0, 0-2, < 2, and 2.1-5 years old), cause, and year of death (before and after 1960). As in previous studies, two ratios (FI/CF and DE/AD) and two qualitative variables (OM and MRS) showed the highest frequencies of correct estimation (0.81-0.86). The correct sex allocations increased when the discriminant function (0.85) and logistic regression (0.86) were applied. Males of the age groups < 0 and 2.1-5 years were all correctly sexed by both formulae, and the same was observed for the female probabilities of adequate allocation. The cause and year of death were identified as variables without statistical significance. It is proposed that this method can be incorporated with confidence into the multifactorial laboratory protocols for non-adult sex estimation from skeletal remains.

Evaluation of the auricular surface method for non-adult sex estimation on the Lisbon documented collection.

OBJECTIVES: Sex is usually not estimated in skeletonized non-adult individuals because sexual dimorphism is considered minimal before puberty. In 2017, a new approach based on the shape of the auricular surface was proposed, showing that this anatomic area of the ilium is dimorphic. This study tests the reproducibility and evaluates the accuracy of the method in a bigger sample. MATERIALS AND METHODS: Thirty males and 31 females from the Lisbon Collection (1 day-18 years old) were analyzed by two researchers, one experienced, and the other without previous knowledge of the method. The sample was divided into three groups according to prepubertal and pubertal hormonal peaks (<2, 0-12, and 13-18 years old). Two metric variables (DE/AD and FI/CF ratios), two morphological features (Overall Morphology, OM and Morphology of the Retroauricular End of the Superior Demiface, MRS), and two formulae were tested based on the adequate results obtained in the original article. RESULTS: Data shows a low interobserver error (ICC > 0.92; K > 0.74). Morphological features provide better results than the metrics (DE/AD = 77.05%; FI/CF = 73.77%; OM = 80.33%; MRS = 85.24%). The discriminant function correctly classified 86.66% of the males and the logistic regression, 83.33%. The method was equally reliable in 0-12 and 13-18 years-old age groups and more accurate in males. The accuracy of most of the variables reached 100% for males under 2 years-old, and the probabilities were higher than for older individuals. The percentages of correct estimations are not influenced by the age, year, and cause of death. DISCUSSION: Despite the relatively small sample size, this study confirms the usefulness of the auricular surface for non-adult sexual estimation, especially for those younger than 2 years old. Additional validation tests in documented individuals from other geographic regions are suggested.

Sample-specific odontometric sex estimation: A method with potential application to burned remains.

Metric features are often the only preserved sexually dimorphic features to allow sex estimation in burned human remains, but this is complicated by heat-induced dimensional changes. The potential of odontometry for sex estimation was investigated. A sample of permanent lower second pre-molars from 20 males and 20 females was experimentally burned at 900°C to assess heat-induced changes in the sexual dimorphism of seven dimensions of the cementum-enamel junction and the root. Four of them, cementum-enamel junction perimeter; mesiodistal, buccolingual and perimeter at the mid-root level, were investigated for the first time. Also, five measurements combining some of the isolated standard measurements were investigated. Additionally, 10 permanent upper central incisors and 10 permanent lower first molars were experimentally burned at 400°C and 700° C to document heat-induced dimensional changes and serve as comparison with the 900°C sample. Results showed that most of the standard measurements, although presenting significant sex differences, were not reliable enough to allow for correct sex classifications close to 100% both before and after the burning. Nonetheless, the perimeter at the cementum-enamel junction and the combined measurements of the mesiodistal and buccolingual diameters, at the same level, were quite promising in the post-burning analysis with correct sex classifications above 80%. At 900°C, females were slightly more affected by shrinkage in this measure than males thus artificially increasing sexual dimorphism after burning. Therefore, and although additional research is needed, this feature was not discarded as having potential for skeletal sex estimation.

Bone Diagenesis and its Implication for Disease Diagnosis: The Relevance of Bone Microstructure Analysis for the Study of Past Human Remains.

When bone is exposed to the burial environment it may experience structural changes induced by multiple agents. The study of postmortem alterations is important to differentiate decomposition phenomena from normal physiological processes or pathological lesions, as well as to assess bone tissue quality. Microscopy is of great utility to evaluate the integrity of bone microstructure and it provides significant data on long-term bone decomposition. A total of 18 human bone sections (eight archeological and ten retrieved from an identified skeletal collection) were selected for analysis under plane light and polarized light. The aim of this exploratory study was to analyze the impact of diagenesis and taphonomy on the bone microstructure, as well as on the differential diagnosis of pathological conditions. The results showed that the microscopy approach to bone tissues contributed materially as an aid in the detailed description of the main diagenetic changes observed. It showed that gross inspection does not provide a realistic assessment of bone tissue preservation, which can impact in the characterization of lesions present and subsequent disease diagnosis. Therefore, researchers should continue to consider the application of histological techniques if the aim is to comprehend tissue integrity and its association with decomposition or disease.

Schmorl's nodes in a historic adult skeletal sample (19th to 20th centuries): An analysis of age, sex and occupation.

OBJECTIVE: This study explores the interplay between age-at-death, sex and occupation and the presence, location and severity of Schmorl's nodes. MATERIALS: Vertebral columns of 327 individuals, 180 (55.1%) males and 147 (44.9%) females, with age-at-death between 20 and 65 years old, with known occupation. METHODS: Schmorl's nodes were recorded as present/absent and by location and severity. RESULTS: In this sample, 58.7% (192/327) of individuals were affected by Schmorl's nodes, 75.6% (136/180) were males and 38.1% (56/147) were females, with statistically significant differences (p=0.000). Schmorl's nodes were most commonly found on the T7-L2 (77.1% of all Schmorl's nodes) vertebrae and at the center (73.4%) of the vertebral body surface. Age and occupational categories did not correlate with prevalence, quantity or severity. CONCLUSIONS: Males appear more prone to develop Schmorl's nodes than females. In this study, the prevalence of Schmorl's nodes does not increase with age, nor with the type of occupation held by males. SIGNIFICANCE: This study rejects the purported associations between prevalence of Schmorl's nodes and age and physical stress. LIMITATIONS: It is unknown whether individuals had the same occupation throughout their lives or for how long they performed it. Additionally, it is impossible to access when the individual developed the Schmorl's node. SUGGESTIONS FOR FURTHER RESEARCH: Evaluate the onset of Schmorl's nodes in individuals under 20 and explore possible links between vertebral morphology and the occurrence of Schmorl's nodes.

Elemental analysis using portable X-ray fluorescence: Guidelines for the study of dry human bone.

OBJECTIVE: X-ray fluorescence (XRF) is a non-destructive technique that measures the elemental concentration of different materials, including human bone. Recently, it began to be applied to paleopathological studies due to the development of portable devices and their relative ease of use. However, the lack of uniform procedures hampers comparability and reproducibility. This paper aims to provide guidelines for an efficient and standardized evaluation of bone elemental composition with a portable XRF (pXRF) device. MATERIALS: This technical note is based on the application of the Thermo Scientific Niton XL3t 900 GOLDD+. METHODS: This work includes suggestions for the choice and preparation of human bone samples, both from archaeological context and documented collections, and methodological procedures in pXRF setup, such as choice of calibration, assessment of accuracy, and analysis run time. Additionally, recommendations for data validation and statistical analysis are also included. CONCLUSIONS: This technique has great potential in paleopathology since bone chemical variations may be associated with different pathological conditions, environmental contamination (e.g., lead), and/or administered treatments, such as mercury. Following an expected increase in the number of studies, it is essential to establish good practices that allow results from different researchers to be comparable. SIGNIFICANCE: X-ray fluorescence is a non-destructive technique that measures small concentrations (ppm) of elements from magnesium (12Mg) through bismuth (83Bi). LIMITATIONS: pXRF does not detect elements lighter than Mg, and its lower energy excitation penetrates less than other techniques. SUGGESTIONS FOR FURTHER RESEARCH: Other research groups should test these guidelines and comment on their usefulness and replicability.

The Role of Fe, S, P, Ca, and Sr in Porous Skeletal Lesions: A Study on Non-adult Individuals Using pXRF.

Portable X-ray fluorescence is a new tool in the study of human bone. This research aims to investigate if variations in bone elemental concentrations are related with porous skeletal lesions (PSLs). One hundred well-preserved non-adult skeletons aged 0-11 years were selected from the archaeological site Convent of São Domingos, Lisbon (18th-19th century). Measuring a standard reference material and calculating the technical error of measurement assured elemental data reliability. Moreover, measuring soil samples excluded possible contamination of bones with elements from the soil, except for Pb. Additionally, the Ca/P ratio indicates maintenance of bone integrity. Cribra cranii, orbitalia, humeralis, and femoralis were recorded as present/absent, and the estimated intra-/inter-observer errors were low. The multivariate analysis found higher odds of having cribra orbitalia (OR = 1.76; CI = 0.97-3.20) and cribra femoralis (OR = 1.42; CI = 0.73-2.74) in individuals with lower Fe and higher S. Furthermore, higher levels of P, Ca, and Sr increased the odds of individuals developing cribra femoralis (OR = 2.30; CI = 1.23-4.29). Age also correlated with increased odds of exhibiting cribra orbitalia (OR = 1.86; CI = 0.94-3.68), cribra femoralis (OR = 6.97; CI = 2.78-17.45), and cribra humeralis (OR = 8.32; CI = 2.71-25.60). These findings suggest a shared etiology for these three cribras, contrasting with the higher Fe levels in individuals with cribra cranii. Lower Fe and higher S levels in individuals with cribra suggest a complex etiology, possibly involving conditions like megaloblastic or chronic disease anemia(s). Age-related elemental changes support the hypothesis that age influences cribra frequencies. This study highlights PSL complexity and opens new avenues for research.

Using portable X-ray fluorescence elemental analysis to explore porous skeletal lesions: Interplay of sex, age at death, and cause of death.

OBJECTIVES: Search for possible associations between bone elemental concentration and the presence of porous skeletal lesions (PSLs), considering the sex, age, and cause of death (COD) of the individuals. MATERIALS AND METHODS: The sample comprised 107 non-adult individuals (56 females, 51 males) aged 0-20 (x̄ = 13.2, SD = 5.8) from the Coimbra and Lisbon Identified Skeletal Collections. Cribra cranii, orbitalia, humeralis, and femoralis were recorded as present/absent, and elemental concentrations were assessed by portable x-ray fluorescence (pXRF). A multivariate statistical approach was applied. RESULTS: Well-preserved skeletons with minimal diagenesis showed no sex-related elemental variations or PSL associations. In contrast, age-at-death correlated with elevated Ca, P, Sr, and Pb levels. Cribra cranii increased with age while other cribra declined post-adolescence. Higher concentrations of Fe and lower of S were linked to cribra cranii. Respiratory infections as COD increased the odds of expressing cribra femoralis (OR = 5.25, CI = 1.25-15.14), cribra cranii (OR = 2.91, CI = 0.97-8.69), and cribra orbitalia (OR = 2.76, CI = 1.06-7.24). DISCUSSION: Feasible pXRF results and low cribra intraobserver error assure replicability. Elevated Ca, P, and Sr in older individuals may relate to skeletal growth, while increased Pb suggests bioaccumulation. Cribra's increase with age reflects different rates of marrow conversion and bone remodeling. Higher Fe and lower S in individuals with cribra cranii possibly reflects poor nutrition, early alcohol use, and sideroblastic anemia, aligning with 19th-20th-century Portugal's living conditions. Respiratory infections increased cribra expression, revealing intricate interplays among inflammation, anemia(s), marrow expansion, and diet. This research highlights a complex scenario and blazes a new path for cribra interpretation.

Bovine serum albumin nanoparticles containing Poly (I:C) can enhance the neutralizing antibody response induced by envelope protein of Orthoflavivirus zikaense.

Since the Orthoflavivirus zikaense (ZIKV) has been considered a risk for Zika congenital syndrome development, developing a safe and effective vaccine has become a high priority. Numerous research groups have developed strategies to prevent ZIKV infection and have identified the domain III of the ZIKV envelope protein (zEDIII) as a promising target. Subunit antigens are often poorly immunogenic, necessitating the use of adjuvants and/or delivery systems to induce optimal immune responses. The subject of nanotechnology has substantial expansion in recent years in terms of research and applications. Nanoparticles could be used as drug delivery systems and to increase the immunogenicity and stability of a given antigen. This work aims to characterize and validate the potential of a vaccine formulation composed of domain zEDIII and bovine serum albumin nanoparticles containing polyinosinic-polycytidylic acid (NPPI). NPPI were uptake in vitro by immature bone marrow dendritic cells and histological analysis of the skin of mice treated with NPPI showed an increase in cellularity. Immunization assay showed that mice immunized with zEDIII in the presence of NPPI produced neutralizing antibodies. Through the passive transfer of sera from immunized mice to ZIKV-infected neonatal mice, it was demonstrated that these antibodies provide protection, mitigating weight loss, clinical or neurological signs induced by infection, and significantly increased survival rates. Protection was further substantiated by the reduction in the number of viable infectious ZIKV, as well as a decrease in inflammatory cytokines and tissue alterations in the brains of infected mice. Taken together, data presented in this study shows that NPPI + zEDIII is a promising vaccine candidate for ZIKV.

Changes in mortality by tuberculosis in non-industrialized Coimbra (Portugal): Trends between 1861 and 1914.

Considering that before antibiotics and vaccination the course of tuberculosis depended mostly on the patient's immune response, this study tested the hypothesis that the mortality profile remained similar during the transition from the 19th to 20th century. The biographical data of the individuals buried in the Coimbra Municipal Cemetery of Conchada were analysed, and the records of those who were born in the city and had tuberculosis registered as the cause of death were analysed using SPSS. The years of death were grouped: 1861-1870 (n = 124, 22.5%), 1871-1880 (n = 234, 42.4%), and 1910-1914 (5 years, n = 194, 35.1%). Mortality by tuberculosis has increased over the years. A total of 552 individuals, 242 females (43.8%) and 310 males (56.2%) died of tuberculosis (p < 0.05). The mean age at death (min = 11 days, max = 86 years) decreased over time, respectively 51.8, 53.1, and 35.8 years-old for individuals >20. Deaths by pulmonary tuberculosis (n = 38, 1861-1870; n = 115, 1910-1914) and meningeal tuberculosis (n = 0, 1861-1870; n = 48, 1910-1914) increased over time, whereas scrofula decreased (n = 23, 1861-1870; n = 3, 1910-1914). Only a 12 years-old male (0.2%) died of bone tuberculosis. Infant (0-3 years-old) mortality occurred mainly (50.5%,48/95) between July and October. The hypothesis tested was not confirmed. Death by tuberculosis has increased, which may be a consequence of population growth, deterioration of the living conditions, and/or changes in bacterial virulence and/or in the host immune system.

Methods for sex estimation of prepubertal individuals (< 12 years old): bibliographic review and future directions.

Sex estimation is essential in both bioarchaeological and forensic research. Based on bibliographical research, this study aims to systematize and compare the existing methods and glance at the future on this research topic. The survey in Web of Science and Google Scholar revealed 37 papers describing the generation of original procedures, and 25 validation studies. The results show that the pelvis, namely the ilium, is the most analyzed anatomical region, followed by the deciduous teeth, the cranium, the mandible, and the long bones. The morphometric approaches are addressed in greater proportion, both as original methods (n = 19) or validations (n = 24). Only one of the 19 approaches that require expensive equipment (conventional radiology, computer tomography, geometric morphometrics and 3D modelling) was tested. Most of them were generated during the 21st century; however, 24 have not been tested yet. Comparing all the methods tested, the percentages of correctly estimated cases are always lower in validation studies. It is suggested that the most promising ones be tested in documented samples by a group of researchers. Thus, the interobserver error would be evaluated and may also lead to new methodological proposals and refinements.