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.

Non-metric dental analysis of human interactions around the Pyrenees during the Neolithic and their biological impact.

BACKGROUND: Interactions across the Pyreneans during the Middle-Neolithic (V-IV millennium BCE) have been described for a long time. Nevertheless, except for a few examples and attempts to describe them, the biological impact of these interactions on the human groups' make-up is not yet understood. The present work analyzes the biological affinities of different groups from both sides of these mountains that represent the Populations of the Middle- and Late-Neolithic by means of the dental morphology. METHODS: We present novel dental morphological data of 221 individuals from 11 archaeological sites. These data have been analyzed and compared to those from previously published twenty Iberian sites and one French site. Data were recovered following the ASUDAS protocol, and MMD biological measure was calculated between groups. RESULTS: Our results suggest that there were some differences between the analyzed populations. These differences were observed at each side of the Pyrenees, but also across them. Concretely, the coastal groups across the mountains show more affinities between each other than the inland groups. In addition, the differences between groups decreased by the end of the Neolithic. CONCLUSIONS: Therefore, our results indicate that the intense trade activities registered in the coastal area between both sides of the Pyrenees would have had the greatest biological impacts in the homogenisation of the groups. Although less intense, the across mountain network and coastal to mountain area trade networks to the south of Pyreneans, also influenced the biological make-up of the groups.

Growing up in Ancient Sardinia: Infant-toddler dietary changes revealed by the novel use of hydrogen isotopes (δ2H).

Detailed information about the lives and deaths of children in antiquity is often in short supply. Childhood dietary histories are, however, recorded and maintained in the teeth of both juveniles and adults. Primary tooth dentinal collagen does not turn over, preserving a sequential record of dietary changes. The use of nitrogen (δ15N) and carbon (δ13C) isotope values of incrementally sampled dentin are used in the study of breastfeeding practices but evidence for the addition of weaning foods, both in terms of mode and, particularly, duration, has remained analytically inaccessible to date. Here, we demonstrate how the novel use hydrogen isotope (δ2H) values of sequentially micro-sampled dentin collagen, measured from individuals excavated from a Punic cemetery, in Sardinia, Italy, can serve as a proxy for weaning food type and duration in ancient childhood diet. The weaning rate and age, based on the decline in δ15N and δ13C values of permanent first molars and the concomitant increase in δ2H, appears to be broadly similar among six individuals. Hydrogen isotopes vary systematically from a low value soon after birth, rising through early childhood. The early post-birth values can be explained by the influence of 2H-depleted lipids from mother's breastmilk and the later δ2H rise is consistent with, among other things, a substantial portion of boiled foodstuffs, such as the higher δ2H values observed in porridge. Overall δ2H in dentin shows great promise to elucidate infant and childhood feeding practices, and especially the introduction of supplementary foods during the weaning process.

Altered functional connectivity of the subthalamus and the bed nucleus of the stria terminalis in obsessive-compulsive disorder.

BACKGROUND: The assessment of inter-regional functional connectivity (FC) has allowed for the description of the putative mechanism of action of treatments such as deep brain stimulation (DBS) of the nucleus accumbens in patients with obsessive-compulsive disorder (OCD). Nevertheless, the possible FC alterations of other clinically-effective DBS targets have not been explored. Here we evaluated the FC patterns of the subthalamic nucleus (STN) and the bed nucleus of the stria terminalis (BNST) in patients with OCD, as well as their association with symptom severity. METHODS: Eighty-six patients with OCD and 104 healthy participants were recruited. A resting-state image was acquired for each participant and a seed-based analysis focused on our two regions of interest was performed using statistical parametric mapping software (SPM8). Between-group differences in FC patterns were assessed with two-sample t test models, while the association between symptom severity and FC patterns was assessed with multiple regression analyses. RESULTS: In comparison with controls, patients with OCD showed: (1) increased FC between the left STN and the right pre-motor cortex, (2) decreased FC between the right STN and the lenticular nuclei, and (3) increased FC between the left BNST and the right frontopolar cortex. Multiple regression analyses revealed a negative association between clinical severity and FC between the right STN and lenticular nucleus. CONCLUSIONS: This study provides a neurobiological framework to understand the mechanism of action of DBS on the STN and the BNST, which seems to involve brain circuits related with motor response inhibition and anxiety control, respectively.

Prehistoric funerary complexity in northern Iberia studied by using dental morphology.

During the Neolithic Age and afterwards, several funerary practices coexisted in the northeast of the Iberian Peninsula from the Mediterranean to the Atlantic. According to archaeological data, there was a coexistence of sepulchral caves and megalithic monuments at the end of the Neolithic, following the dominance of open-air pit burials during the Middle Neolithic. The aim of this work is to analyze the biological relationships between individuals representing those cultures, based on their dental morphology - the first such attempt. This study presents data of 156 individuals from this period, and will allow elucidate the population dynamics including the role of migrations and other factors. The results indicate that there were no significant differences between the groups living in Atlantic and Mediterranean areas. Moreover, pairwise comparisons for each trait only show two significant results. This lack of differences could be related to trade activities between the two basins, which would contribute to individual exchanges between groups. Furthermore, according to biological affinities, trade activities along the Mediterranean Sea had a more marked influence over the Catalan populations than those from the Atlantic basin. There are no biological differences between groups representing the open-air pit culture and the sepulchral caves in each area. Finally, the megalithic groups from the Atlantic basin differ the most from the surrounding populations. This could be indicative of a slightly different biological origin of the people related to this culture.

First insight into the Neolithic subsistence economy in the north-east Iberian Peninsula: paleodietary reconstruction through stable isotopes.

OBJECTIVES: The study of subsistence strategies among Neolithic communities in north-east Iberia, late-fifth to early-fourth millennia cal BC, enables a more in-depth study of the activities and behavior of the inhabitants of this region, where paleodiets have been little studied. The objectives of this study are, therefore, to determine the diet and subsistence patterns of those communities and to consider whether any relation existed between their subsistence strategies and environmental, geographic, and/or social factors. MATERIALS AND METHODS: Bone samples from 25 middle Neolithic human individuals at seven archeological sites and comparative faunal samples were analyzed, and compared with contemporary series in Mediterranean Europe. Carbon and nitrogen isotope ratios (δ13 C and δ15 N) of bone collagen were studied to determine the dietary patterns. RESULTS: Dietary habits proved to be similar between communities, apart from some interpopulational variations in subsistence strategies. Their diet was based on C3 terrestrial resources with a major vegetal protein component. DISCUSSION: The reported variations in interpopulational subsistence strategies among the compared Mediterranean societies do not seem to be directly related to the settlement region. Together with archeological data, this indicates the influence of socioeconomic factors in the Neolithic human diet. A general tendency toward a lesser use of aquatic resources is seen in this period in Iberia and the rest of the Mediterranean, as also documented for contemporary communities in the west and north of Europe. The data obtained will be important for further studies of socioeconomic patterns in European Neolithic societies.

Brain structural correlates of obsessive-compulsive disorder with and without preceding stressful life events.

Objectives There is growing evidence supporting a role for stressful life events (SLEs) at obsessive-compulsive disorder (OCD) onset, but neurobiological correlates of such effect are not known. We evaluated regional grey matter (GM) changes associated with the presence/absence of SLEs at OCD onset. Methods One hundred and twenty-four OCD patients and 112 healthy controls were recruited. Patients were split into two groups according to the presence (n = 56) or absence (n = 68) of SLEs at disorder's onset. A structural magnetic resonance image was acquired for each participant and pre-processed with Statistical Parametric Mapping software (SPM8) to obtain a volume-modulated GM map. Between-group differences in sociodemographic, clinical and whole-brain regional GM volumes were assessed. Results SLEs were associated with female sex, later age at disorder's onset, more contamination/cleaning and less hoarding symptoms. In comparison with controls, patients without SLEs showed GM volume increases in bilateral dorsal putamen and the central tegmental tract of the brainstem. By contrast, patients with SLEs showed specific GM volume increases in the right anterior cerebellum. Conclusions Our findings support the idea that neuroanatomical alterations of OCD patients partially depend on the presence of SLEs at disorder's onset.

A case of bilateral macrodontia of mandibular second premolars from a Chalcolithic context in the Iberian Peninsula.

Isolated macrodontia, consisting of the gigantism of a single tooth, is an extremely rare condition. Only 16 cases of isolated macrodontia of mandibular second premolars have been reported to date. Although the aetiology of this phenomenon remains unknown, many authors have related it to the control of the apoptotic process, leading to the patterning and size of dental cusps. There is not a clear genetic inheritance pattern since only two of those 16 cases correspond to close relatives. To our knowledge, there have been no reports of isolated macrodontia of mandibular second premolars in archaeological remains. Cova del Pantà de Foix site is a Chalcolithic sepulchral cave situated in the North-East of the Iberian Peninsula in which the remains of at least 30 individuals were recovered. Most of these individuals show several signs of environmental stressors. The current study presents the first case of isolated bilateral macrodontia of mandibular premolars from an archaeological context, corresponding to a young male individual discovered in this site. This condition could be the last consequence of environmental factors epigenetically affecting apoptosis processes in early tooth development and a possible genetic predisposition to show a shape-deviation in the dentition.

The emergence of mesolithic cemeteries in SW Europe: insights from the El Collado (Oliva, Valencia, Spain) radiocarbon record.

Located on the Iberian Mediterranean coast, El Collado is an open-air site where a rescue excavation was conducted over two seasons in 1987 and 1988. The archaeological work excavated a surface area of 143 m2 where 14 burials were discovered, providing skeletal remains from 15 individuals. We have obtained AMS dates for 10 of the 15 individuals by means of the direct dating of human bones. The ranges of the probability distribution of the calibrated dates suggest that the cemetery was used during a long period of time (781-1020 years at a probability of 95.4%). The new dates consequently set back the chrono-cultural attribution of the cemetery from the initial proposal of Late Mesolithic to an older date in the Early Mesolithic. Therefore, El Collado becomes the oldest known cemetery in the Iberian Peninsula, earlier than the numerous Mesolithic funerary contexts documented on the Atlantic façade such as the Portuguese shell-middens in the Muge and Sado Estuaries or the funerary sites on the northern Iberian coast.

Brain regions related to fear extinction in obsessive-compulsive disorder and its relation to exposure therapy outcome: a morphometric study.

BACKGROUND: The size of particular sub-regions within the ventromedial prefrontal cortex (vmPFC) has been associated with fear extinction in humans. Exposure therapy is a form of extinction learning widely used in the treatment of obsessive-compulsive disorder (OCD). Here we investigated the relationship between morphometric measurements of different sub-regions of the vmPFC and exposure therapy outcome in OCD. METHOD: A total of 74 OCD patients and 86 healthy controls underwent magnetic resonance imaging (MRI). Cortical thickness and volumetric measurements were obtained for the rostral anterior cingulate cortex (rACC), the medial orbital frontal cortex and the subcallosal cortex. After MRI acquisition, patients were enrolled in an exposure therapy protocol, and we assessed the relationship between MRI-derived measurements and treatment outcome. Baseline between-group differences for such measurements were also assessed. RESULTS: Compared with healthy controls, OCD patients showed a thinner left rACC (p = 0.008). Also, left rACC thickness was inversely associated with exposure therapy outcome (r - 0.32, p = 0.008), and this region was significantly thinner in OCD patients who responded to exposure therapy than in those who did not (p = 0.006). Analyses based on regional volumetry did not yield any significant results. CONCLUSIONS: OCD patients showed cortical thickness reductions in the left rACC, and these alterations were related to exposure therapy outcome. The precise characterization of neuroimaging predictors of treatment response derived from the study of the brain areas involved in fear extinction may optimize exposure therapy planning in OCD and other anxiety disorders.

Interaction of SLC1A1 gene variants and life stress on pharmacological resistance in obsessive-compulsive disorder.

Genetic and environmental factors seem to interact and influence both the onset and the course of obsessive-compulsive disorder (OCD), but the role of glutamate transporter variants (SLC1A1) in pharmacological resistance is not known. We aimed to assess whether genetic variants in SLC1A1 and life stress at onset of the disorder interact and modulate pharmacological resistance in OCD. A single-marker association study of several single-nucleotide polymorphisms in the SLC1A1 genomic region was performed in a sample of 238 OCD patients. For the most strongly associated SNP (rs3087879), one copy of the risk allele increased the probability of higher treatment resistance (odds ratio=2.42; 95% confidence interval=1.39-4.21; P=0.0018), but only in OCD patients without life stress at onset of the disorder. These results suggest a gene-by-environment interaction effect on treatment resistance in OCD and strengthen the existing evidence of the role of the glutamatergic system in the phenomenology of OCD.

Stratigraphic context and direct dating of the Neandertal mandible from Cova del Gegant (Sitges, Barcelona).

Stratigraphic study of the Cova del Gegant's sedimentary fill revealed different cycles of accumulation of typical interior cave and delta facies. A precise chronology for these deposits, the faunal remains and stone tools contained therein was obtained by radiocarbon, U-Th and OSL. Our results indicate that the Upper Pleistocene archaeological sequence dates between 49.3 +/- 1.8 ka BP, the U-Th age of the overlying flowstone, and 60.0 +/- 3.9 ka BP, the OSL age of the basal deposits. We have also directly dated the site's Neandertal mandible to 52.3 +/- 2.3 ka by U-Th.

Análisis de un Hospital de Día Médico Polivalente en base al cálculo de os indicadores de empleo de recursos / Analysis of a general medical day hospital baed on th calculation of use of resources indicators

El Hospital de Día (HD) es una de las principales aternativas a la hospitalización convencinal. El óptim aprovechamiento de sus recursos mejora la gestión hospitalaria con disminución de losingresos hospitalarios, reducción de los costes económicos y permite un mayor confort a los pacientes y familiares. El obejtivo de este trabajo es el de aalizar la organiación y funcionamiento de un Hospital de Día Médico olivalente en base al cálculo de indicadores de empleo de recursos (AU)

A Day Hospital (DH) is one of the major alternativs to conventional hositalization. The optimal use of its resoures mproves hosital management by decreasing hospital admissions, reducing costs and allowing form greater comfort for patients and families. This paper enabes us to conclude that ther is an underutiliation of DHs on certain days and certain hours, while at other times and days there is an excessive workload. All this leads to a decline in the equity and quality of care. To optimize the DH, we propose the implementation of a rrengineering of the rganizational process (AU)

A Neandertal mandible from the Cova del Gegant (Sitges, Barcelona, Spain).

A human mandible from the site of Cova del Gegant is described here for the first time and compared with other Middle and Upper Pleistocene representatives of the genus Homo from Europe and Southwest Asia. The specimen was recovered from sediments which also yielded Mousterian stone tools and Pleistocene fauna. The preserved morphology of the mandible, particularly in the region of the mental foramen, clearly aligns it with the Neandertals, making the Cova del Gegant the only known site in Catalonia documenting diagnostic human skeletal remains in association with Middle Paleolithic stone tools. This represents an important new addition to the human fossil record from the Iberian Peninsula and joins the Bañolas mandible in documenting the course of human evolution in the northern Mediterranean region of Spain.

Allogeneic stem cell transplantation with reduced-intensity conditioning is potentially feasible as an outpatient procedure.

Allogeneic stem cell transplantation (allo-SCT) after a reduced-intensity conditioning (RIC) protocol is associated with decreased short-term toxicity. This suggests that the procedure could be performed on an outpatient basis. We analysed the incidence and risk factors of grade >or=2 conditioning-related toxicities (CRTs) as a hallmark for hospital admission, in 41 consecutive patients allografted from an HLA identical sibling after RIC. The RIC regimen consisted of fludarabine plus melphalan for lymphoid malignancies, and fludarabine plus busulphan for myeloid malignancies. In all, 11 patients (27%) did not experience any toxicity. The more frequent CRTs observed were neutropenic fever and gastrointestinal toxicity. The median duration of hospitalisation was 27 (range, 17-50) days. If allo-SCT had been planned as an outpatient procedure and admission indicated only in the case of >or=2 CRTs, the inpatient period would have decreased to 9 (range, 0-33) days (P<0.001). No risk factors for CRTs were identified. Allo-SCT after an RIC regimen is a well-tolerated procedure. Our results warrant a prospective pilot trial of nonmyeloablative allo-SCT performed in the outpatient setting.

Clinical applicability of the new EORTC/MSG classification for invasive pulmonary aspergillosis in patients with hematological malignancies and autopsy-confirmed invasive aspergillosis.

Diagnosis of invasive pulmonary aspergillosis (IPA) is often difficult. Recently, the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) has proposed new criteria for the classification of invasive fungal infections. We have studied the clinical applicability of this classification in 22 patients with hematological malignancies who had IPA at autopsy. While alive, according to the EORTC/MSG criteria, only 2 patients were classified as having proven IPA, 6 as probable, 13 as possible, and 1 was unclassifiable. Of the patients, 64% had no microbiological or major clinical criteria before death. Although the EORTC/MSG criteria are an important step forward in the standardization of definitions used for IPA in clinical research studies, most patients who die with extensive lung disease only reach a level of possible or probable IPA during life, further highlighting that these guidelines should not be used for clinical decision-making.

Mouth-washings with recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) do not improve grade III-IV oropharyngeal mucositis (OM) in patients with hematological malignancies undergoing stem cell transplantation. Results of a randomized double-blind placebo-controlled study.

We investigated whether daily oral washings with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) solution improved grade III-IV oropharyngeal mucositis (OM) in patients with hematological malignancies undergoing stem cell transplantation. Forty-one consecutive patients (21 males and 20 females, median age (range) 44 (16-69) years) were prospectively randomized to perform daily mouth-washes with either a 400 microg rhGM- CSF (Molgramostin, Schering-Plough) solution (group A, n = 18) or with a saline solution (group B, n = 23). Primary end-points were the intensity of OM, night rest quality and characteristics of food intake. Secondary end-points were need for and duration of parenteral nutrition, oral and intravenous analgesic requirements, incidence of viral or fungal oral infections and development of neutropenic fever. No differences were found between the placebo and rhGM-CSF-treated groups regarding overall duration of OM, maximum grade, reduction in at least one grade of OM (nine patients (56%) in group A vs 13 patients (68%) in group B), reduction of spontaneous or swallowing-induced pain, improvement in oral food intake, use of parenteral nutrition or use of systemic analgesics. In conclusion, mouth-washings with a 400 microg of rhGM-CSF solution do not improve severe OM in hematological patients undergoing stem cell transplantation.

Invasive fungal infections in hematology: new trends.

Invasive fungal infections (IFI) are among the most feared complications of patients being treated for a hematological malignancy. Currently, most serious IFI occur in patients with acute leukemia and after allogeneic hematopoietic stem cell transplantation. Although Candida albicans and Aspergillusspp. continue to be the main pathogens, the proportion of patients infected by non-albicans species of Candida and other yeasts and by other filamentous fungi is rising in most institutions. Risk factors for the various IFI differ, and it is thus of utmost importance to realize that not all patients are the same with respect to the risk for developing the various IFI. Recent advances in diagnosis now allow the use of very sensitive imaging techniques with an extremely low negative predictive value. Among the novel microbiologic methods, the galactomannan antigen test is now commercially available for routine use in the diagnosis of aspergillosis, while DNA fungal detection is still experimental. For the first time, clinicians now have a broad range of antifungals to chose from, with special emphasis on amphotericin B preparations, novel broad-spectrum azoles, and the echinocandins. However, the exact place of these agents in treating different IFI will need to be found in the near future.

Sistema de monitorización continua de glucosa: una nueva herramienta para mejorar el control metabólico de los pacientes diabéticos / Continous glucose monitoring system: a new tool to improve glycemic control of diabetic patients

Recientemente se ha comercializado en España un nuevo sistema de monitorización continua de glucosa, que permite conocer de forma muy detallada el perfil de glucosa de los pacientes diabéticos durante las 24 h del día. Se trata de un sistema portátil de pequeño tamaño que el paciente lleva implantado un mínimo de 72 h y que se compone básicamente de un sensor que se inserta en el tejido subcutáneo del abdomen conectado a un monitor, que registra cada 5 min la concentración de glucosa del tejido intersticial. Los datos registrados son posteriormente visualizados y analizados en un ordenador mediante el software adecuado. Diferentes estudios han demostrado una excelente correlación entre los valores de glucosa determinados por el sensor y los de glucemia capilar y venosa. Asimismo, varios trabajos han demostrado la utilidad de la información suministrada por el sistema para iniciar o modificar el tratamiento de los pacientes y, en consecuencia, para mejorar su control metabólico. En esta revisión se describen las características del sistema, su funcionamiento, la información que proporciona y la utilidad del mismo en diferentes situaciones (AU)

Factors determining the actual received dose intensity in a program of multicyclic dose-intensive alternating chemotherapy with sequential stem cell support.

Dose intensity has been related to clinical outcome in several solid tumors. We studied the influence of clinical and cellular parameters on dose intensity received in a series of 53 patients with metastatic breast cancer or advanced ovarian cancer. They received courses of cisplatin 120 mg/m(2) plus etoposide 600 mg/m(2) alternating every 14 days with ifosfamide 8 g/m(2) plus paclitaxel 200--350 mg/m(2). Blood stem cell support was administered after every course except for the first one. Patients with excellent mobilization underwent immunomagnetic selection of CD34+ cells. We found a significant inverse correlation between the CD34+ cell dose infused and the delay for the administration of the next cycle. A CD34+ cell dose between 1.5 and 5 x 10(6)/kg per cycle was found to be feasible and was followed by a median delay of 1 day (not different from doses above 5 x 10(6)/kg). Three factors independently predicted the actually received dose intensity in a multiple regression model (R(2) = 0.4): previous autologous transplantation, eligibility for immunomagnetic selection (excellent response to mobilization) and median CD34+ cell dose received along the treatment.