Eating through time: Understanding dietary practices across late prehistory in the northeastern Iberian Peninsula.

OBJECTIVE: This study seeks to contribute to the current understanding of dietary variation in the late Prehistory of the northeastern Iberian Peninsula by examining buccal dental microwear patterns alongside archeological data from the same populations. MATERIALS AND METHODS: Teeth from 84 adult individuals from eight distinct samples spanning the Middle-Late Neolithic to the Middle Bronze Age (Cova de l'Avi, Cova de Can Sadurní, Cova de la Guineu, Cova Foradada, Cova del Trader, Roc de les Orenetes, Cova del Gegant, Cova dels Galls Carboners) were analyzed using optical microscopy to examine buccal dental microwear patterns. RESULTS: The analysis did not reveal clear chronological contrasts in the dietary habits of these samples. Nevertheless, significant differences emerged among the samples, leading to their classification into two distinct sets based on the abrasiveness of the diet informed by the microwear patterns. These findings offer similarities and differences among samples in the Iberian Peninsula, shedding light on the diverse lifestyles of these individuals. DISCUSSION: Integrating our new results with other available proxies points to a multifaceted specialization in dietary patterns among these samples, influenced by factors such as habitat, resource selection, and available technology. By contextualizing the results within the broader context of the Iberian Peninsula, this research discerns shared characteristics and distinctive adaptations in the dietary practices and subsistence strategies of these groups. Ultimately, this study contributes to a deeper understanding of the intricate interplay between culture and environment in shaping human diets throughout late Prehistory.

The Effect of Different Decontamination Methods on the Micro-Tensile Bond Strength of CAD/CAM Resin-Based Blocks to Resin Cement.

INTRODUCTION: This study evaluates the impact of decontamination methods on Microtensile bond strength (µTBS) between resin cement and resin blocks. METHODS: Twenty CAD/CAM resin blocks from two manufacturers were wet-polished, sandblasted, and ultrasonically cleaned. After blood and saliva contamination, blocks were divided into subgroups: control, water rinsing, acid etching, alkaline cleaning paste, or 10-MDP containing cleaner. Resin-based cement was then applied. After 24 hours, the blocks were sectioned to obtain bars for testing. Half of the specimens were tested immediately for µTBS, and the other half underwent artificial aging. The surfaces of the blocks were inspected with a scanning electron microscope (SEM). Three-way ANOVA was performed for µTBS values (α=0.05). RESULTS: In one of the substrates, the positive control subgroup obtained the highest value (56,01 MPa, SD:6,96) followed by 10-MDP cleaner and universal cleaning paste, when immediately tested, with significant differences respect to the water rinsing (p⟨0.041) and acid etching (p⟨0.048) groups. After thermocycling, higher values were found in the 10-MDP cleaner (47,57 MPa, SD:8,15), but differences were not significant. In the other substrate group, the 10-MDP cleaner subgroup showed highest bond strengths (64,46 MPa SD: 10,92) at the initial test. After thermocycling, 10-MDP cleaner (58,66 MPa, SD: 9,93) gave the highest µTBS value. Significant differences between water rinsing group and the rest of subgroups (p⟨0.001), and between 10-MDP cleaner and the positive control group (p⟨0.006) were observed. CONCLUSION: Cleaning after contamination improves bonding. 10-MDP containing cleaner can help to restore initial µTBS value and maintain it in the long-term.

Biochemical algorithm to identify individuals with ALPL variants among subjects with persistent hypophosphatasaemia.

BACKGROUND: Hypophosphatasia (HPP) is a rare and underdiagnosed condition characterized by deficient bone and teeth mineralization. The aim of this study was first, to evaluate the diagnostic utility of employing alkaline phosphatase (ALP) threshold levels to identify adults with variants in ALPL among individuals with persistently low ALP levels and second, to determine the value of also including its substrates (serum pyridoxal-5'-phosphate-PLP-and urinary phosphoetanolamine-PEA) for this purpose in order to create a biochemical algorithm that could facilitate the diagnostic work-up of HPP. RESULTS: The study population comprised 77 subjects with persistent hypophosphatasaemia. They were divided into two groups according to the presence (+GT) or absence (-GT) of pathogenic ALPL variants: 40 +GT and 37 -GT. Diagnostic utility measures were calculated for different ALP thresholds and Receiver Operating Characteristic (ROC) curves were employed to determine PLP and PEA optimal cut-off levels to predict the presence of variants. The optimal threshold for ALP was 25 IU/L; for PLP, 180 nmol/L and for PEA, 30 µmol/g creatinine. Biochemical predictive models were assessed using binary logistic regression analysis and bootstrapping machine learning technique and results were then validated. For ALP < 25 UI/L (model 1), the area under curve (AUC) and the 95% confidence intervals (CI) was 0.68 (95% CI 0.63-0.72) and it improved to 0.87 (95% CI 0.8-0.9), when PEA or PLP threshold levels were added (models 2 and 3), reaching 0.94 (0.91-0.97) when both substrates were included (model 4). The internal validation showed that the addition of serum PLP threshold levels to the model just including ALP improved significantly sensitivity (S) and negative predictive value (NPV) - 100%, respectively- with an accuracy (AC) of 93% in comparison to the inclusion of urinary PEA (S: 71%; NPV 75% and AC: 79%) and similar diagnostic utility measures as those observed in model 3 were detected when both substrates were added. CONCLUSIONS: In this study, we propose a biochemical predictive model based on the threshold levels of the main biochemical markers of HPP (ALP < 25 IU/L and PLP > 180 nmol/L) that when combined, seem to be very useful to identify individuals with ALPL variants.

Quantification of bone marrow edema by MRI of the sacroiliac joints in patients diagnosed with axial spondyloarthritis: results from the ESPeranza cohort.

OBJECTIVE: To evaluate whether the quantification of bone marrow edema (BMO) of the sacroiliac (SI) joints by magnetic resonance imaging (MRI) improves capacity for axial spondyloarthritis (axSpA) classification in comparison with the assessment of sacroiliitis by Assessment of SpondyloArthritis international Society (ASAS) classification criteria. METHOD: This prospective study from the ESPeranza cohort involved 66 subjects with an available MRI of the SI joints at baseline. This subgroup includes patients with axSpA (n = 28), peripheral spondyloarthritis (n = 10), and other diagnoses that were not spondyloarthritis (n = 28). Measures of diagnostic usefulness [area under the curve (AUC), sensitivity, specificity, Youden's J statistic, positive and negative likelihood ratios (LR+ and LR-)] were calculated for MRI of the SI joints according to ASAS criteria and for MRI quantified by means of SCAISS (Spanish tool for semi-automatic quantification of sacroiliac inflammation by MRI in spondyloarthritis). This analysis was stratified in patients who were human leucocyte antigen (HLA)-B27 positive and negative. RESULTS: The AUC value with BMO quantification was 0.919 [95% confidence interval (CI) 0.799-1] for HLA-B27-positive patients and 0.884 (95% CI 0.764-1) for HLA-B27-negative patients. A SCAISS cut-off point of 80 units obtained a specificity of 94.4% and LR+ 7.5, while assessment by ASAS criteria showed a specificity value of 90% and LR+ 6.4. CONCLUSION: For patients with suspected axSpA, quantification of BMO improves the predictive capacity of MRI of the SI joints, for both HLA-B27-positive and HLA-B27-negative patients. Axial spondyloarthritis (axSpA) has a dramatic impact on physical function and quality of life (1). Despite its significant impact, patients with axSpA are normally diagnosed several years after presenting symptoms (2). In this respect, magnetic resonance imaging (MRI) of the sacroiliac (SI) joints has gained significance over the past decade, particularly in the early stages of the disease. Nowadays, imaging tests and human leucocyte antigen (HLA)-B27 testing are among the most important diagnostic procedures for patients with suspected axSpA.

Can we identify individuals with an ALPL variant in adults with persistent hypophosphatasaemia?

BACKGROUND: Hypophosphatasia (HPP) is an inborn error of metabolism characterized by low levels of serum alkaline phosphatase (ALP). Scarce evidence exists about features that should signal the potential association between hypophosphatasaemia and HPP in adults. The aim of this study is to estimate the prevalence of ALPL variants in subjects with persistent hypophosphatasaemia and determine the associated clinical and laboratory features. For this cross-sectional study, laboratory records of 386,353 subjects were screened by measurement of ALP activity. A total of 85 (0.18%) subjects with persistent hypophosphatasaemia (≥2 serum alkaline phosphatase-ALP-measurements ≤35 IU/L and none > 45 IU/L) were included (secondary causes previously discarded). ALPL genetic testing and a systematized questionnaire to retrieve demographic, clinical and laboratory data were performed. Descriptive analysis and logistic regression models were employed to identify the clinical and laboratory characteristics associated with ALPL variants. RESULTS: Forty subjects (47%) had a variant(s) in ALPL. With regard to clinical characteristics, the presence of an ALPL variant was significantly associated only with musculoskeletal pain (OR: 7.6; 95% IC: 1.9-30.9). Nevertheless, a trend to present more dental abnormalities (OR: 3.6; 95% IC: 0.9-13.4) was observed. Metatarsal stress fractures were also more frequent (4 vs 0; p < 0.05) in this group. Regarding laboratory features, median ALP levels were lower in subjects with ALPL variants (26 vs 29 IU/L; p < 0.005). Interestingly, the threshold of ALP levels < 25 IU/L showed a specificity, positive predictive value and positive likelihood ratio of 97.8, 94.4% and 19.8 to detect a positive ALPL test, respectively. CONCLUSIONS: In subjects with persistent hypophosphatasaemia -secondary causes excluded- one out of two presented ALPL variants. Musculoskeletal pain and ALP levels < 25 IU/L are associated with this variant(s). In this scenario, ALP levels < 25 IU/L seem to be very useful to identify individuals with the presence of an ALPL variant.

Animal Board Invited Review: Sheep birth distribution in past herds: a review for prehistoric Europe (6th to 3rd millennia BC).

In temperate latitudes sheep have a seasonal reproductive behaviour, which imposes strong constraints on husbandry in terms of work organization and availability of animal products. During the last 50 years, researchers have focused on understanding the mechanisms driving small ruminants' reproduction cycles and finding ways to control them. This characteristic is inherited from their wild ancestor. However, the history of its evolution over the 10 millennia that separates present day European sheep from their Near Eastern ancestors' remains to be written. This perspective echoes archaeologists' current attempts at reconstructing ancient pastoral societies' socio-economical organization. Information related to birth seasonality may be retrieved directly from archaeological sheep teeth. The methodology consists of reconstructing the seasonal cycle record in sheep molars, through sequential analysis of the stable oxygen isotope composition (δ 18O) of enamel. Because the timing of tooth development is fixed within a species, inter-individual variability in this parameter reflects birth seasonality. A review of the data obtained from 10 European archaeological sites dated from the 6th to the 3rd millennia BC is provided. The results demonstrate a restricted breeding season for sheep: births occurred over a period of 3 to 4 months, from late winter to early summer at latitudes 43°N to 48°N, while a later onset was observed at a higher latitude (59°N). All conclusions concurred with currently held expectations based on present day sheep physiology, which, aside from the historical significance, contributes to the reinforcing of the methodological basis of the approach. Further study in this area will permit regional variability attributable to technical choices, within global schemes, to be fully reported.

Multimodal analgesia and regional anaesthesia. / Analgesia multimodal y anestesia regional.

Multimodal analgesia provides quality analgesia, with fewer side effects due to the use of combined analgesics or analgesic techniques. Regional anaesthesia plays a fundamental role in achieving this goal. The different techniques of regional anaesthesia that include both peripheral and central blocks in either a single dose or in continuous infusion help to modulate the nociceptive stimuli that access the central level. The emergence of the ultrasound as an effective system to perform regional anaesthesia techniques has allowed the development of new regional anaesthesia techniques that formerly could not be carried out since only neurostimulation or skin references were used. It is essential to take into account that even with effective blocking it is advisable to associate other drugs by other routes, in this way we will be able to reduce the required doses individually and attempt to achieve a synergistic, not purely additive, effect.

Effect of highly active anti-retroviral therapy and hepatitis C virus co-infection on serum levels of pro-inflammatory and immunoregulatory cytokines in human immunodeficiency virus-1-infected individuals.

This study aimed to determine the effect of highly active anti-retroviral therapy (HAART) and hepatitis C virus (HCV) co-infection on peripheral levels of interleukin (IL)-2, IL-10, IL-12 (p70), IL-18 and soluble tumour necrosis factor receptor type II (sTNFRII). Serum levels were monitored for a 1-year period in 25 patients infected with human immunodeficiency virus-1 (HIV-1) who were naive for HAART at the initiation of the study, and in four HIV-1-infected long-term non-progressors. Serum levels of both IL-18 and sTNFRII at baseline were significantly higher in HIV-1-infected patients than in controls. Baseline levels of IL-18 and sTNFRII were not significantly different in long-term non-progressors compared with the other patients. HCV co-infected patients had significantly higher levels of IL-18 and sTNFRII at each time-point compared with patients who were not co-infected with HCV. Irrespective of HCV status, response to HAART resulted in a significant decrease in the levels of both IL-18 and sTNFRII, particularly among patients who achieved HIV viral suppression, but the net decrease observed at the end of follow-up was lower in patients co-infected with HCV. No information was obtained from IL-2, IL-10 and IL-12 (p70) measurements. The data suggest that analysis of serum levels of IL-18 and sTNFRII may be a valuable tool for evaluating the response to HAART, and perhaps for assessing the degree of immune restoration achieved by HAART responders. The results also highlight the relevance of considering the HCV infection status of HIV-1-infected patients in order to avoid misinterpretation of IL-18 and sTNFRII measurements.

A novel solenoid fold in the cell wall anchoring domain of the pneumococcal virulence factor LytA.

Choline binding proteins are virulence determinants present in several Gram-positive bacteria. Because anchorage of these proteins to the cell wall through their choline binding domain is essential for bacterial virulence, their release from the cell surface is considered a powerful target for a weapon against these pathogens. The first crystal structure of a choline binding domain, from the toxin-releasing enzyme pneumococcal major autolysin (LytA), reveals a novel solenoid fold consisting exclusively of beta-hairpins that stack to form a left-handed superhelix. This unique structure is maintained by choline molecules at the hydrophobic interface of consecutive hairpins and may be present in other choline binding proteins that share high homology to the repeated motif of the domain.