First modern human settlement recorded in the Iberian hinterland occurred during Heinrich Stadial 2 within harsh environmental conditions.

As the south-westernmost region of Europe, the Iberian Peninsula stands as a key area for understanding the process of modern human dispersal into Eurasia. However, the precise timing, ecological setting and cultural context of this process remains controversial concerning its spatiotemporal distribution within the different regions of the peninsula. While traditional models assumed that the whole Iberian hinterland was avoided by modern humans due to ecological factors until the retreat of the Last Glacial Maximum, recent research has demonstrated that hunter-gatherers entered the Iberian interior at least during Solutrean times. We provide a multi-proxy geoarchaeological, chronometric and paleoecological study on human-environment interactions based on the key site of Peña Capón (Guadalajara, Spain). Results show (1) that this site hosts the oldest modern human presence recorded to date in central Iberia, associated to pre-Solutrean cultural traditions around 26,000 years ago, and (2) that this presence occurred during Heinrich Stadial 2 within harsh environmental conditions. These findings demonstrate that this area of the Iberian hinterland was recurrently occupied regardless of climate and environmental variability, thus challenging the widely accepted hypothesis that ecological risk hampered the human settlement of the Iberian interior highlands since the first arrival of modern humans to Southwest Europe.

Does Enzymatic Debridement Allow Us To Perform Conservative Treatment On Clinically Deep Hand Burns? A Retrospective Review.

The hands are one of the main locations of burns. In deep second-degree and third-degree burns, the gold standard of treatment is surgical debridement and subsequent coverage, which can result in suboptimal aesthetic and functional results. The aim of our study is to assess whether treatment by initial enzymatic debridement (NexoBrid®) of deep second-degree and third-degree burns prevents the need for surgery. We carried out a retrospective study of 53 hands with deep burns treated in our centre from May 2015 to December 2016. Two experts evaluated the initial photographs of the burns and classified them as surgical or nonsurgical (interobserver kappa index = 0.83). These assessments were compared with the actual need for surgery on each hand. Sixteen of the 32 (50%) hands that the experts considered surgical spontaneously epithelialized. Four of the 17 hands (23.5%) that were not considered surgical required a split-thickness skin graft for healing. Enzymatic debridement helps to preserve viable tissue, which reduces the number and extension of surgical interventions, thus favouring better results.

Les mains sont une des principales localisations de brûlures. Dans les brûlures du 2e degré profond et du 3e degré, le traitement de référence est l'excision chirurgicale suivie d'un geste de couverture, et donne des résultats fonctionnels ou esthétiques pas toujours parfaits. Le but de notre étude est d'évaluer si le débridement enzymatique (NexoBrid®) des brûlures du 2e degré profond et du 3e degré permet d'éviter les gestes chirurgicaux. Nous avons mené une étude rétrospective sur 53 mains présentant des brûlures profondes traitées dans notre centre entre mai 2004 et décembre 2016. Deux experts ont évalué les photographies initiales et classé les brûlures en « chirurgicales ¼ ou « non chirurgicales ¼ (coefficient Kappa inter-opérateur = 0,83). Ces évaluations ont été comparées à la nécessité réelle de prise en charge chirurgicale pour chacune des mains. 16 des 32 mains (50%) que les experts avaient jugées « chirurgicales ¼ ont cicatrisé spontanément. 4 des 17 mains (23,5%) qui ont été considérée comme « non chirurgicales ¼ ont nécessité une greffe de peau mince pour obtenir la cicatrisation. Le débridement enzymatique permet de conserver les tissus viables, ce qui diminue le nombre et l'importance des gestes chirurgicaux, et donc favorise l'obtention de meilleurs résultats.

Uncommon burn complication: skin nocardiosis.

Skin nocardiosis is an uncommon form of cutaneous infection caused by Nocardia. More than 100 different species have been isolated and they mainly inhabit soil and water. Cutaneous affection can be divided into primary and secondary forms. Cell culture is the most used diagnosis method and trimethoprim-sulfamethoxazole the antibiotic treatment.We present a patient diagnosed with skin nocardiosis whose way of inoculation has not been described in the literature. However in future this kind of infection will probably increase due to the increasing interest in phytotherapy. Physicians should be aware of clinical manifestation, diagnosis and treatment.

La nocardiose cutanée est une infection inhabituelle à Nocardia, dont il a été recensé plus de 100 espèces, d'habitat tellurique et hydrique. Les nocardioses cutanées peuvent être primaires ou secondaires. L'identification se fait en culture et le traitement classique est triméthoprime- sulfaméthoxazole. Nous présentons un cas de nocardiose cutanée secondaire d'origine inhabituelle. Ce type d'infection va probablement devenir plus fréquent en raison de l'intérêt croissant pour la phytothérapie si bien que les médecins devraient être avertis de ses manifestations clinique, du diagnostic et du traitement.

Actualización de las recomendaciones para la evaluación y tratamiento de la osteoporosis asociada a enfermedades endocrinas y nutricionales. Grupo de trabajo de osteoporosis y metabolismo mineral de la SEEN / Update of recommendations for evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions. Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology

Objetivo: Actualizar las recomendaciones previas formuladas por el Grupo de trabajo de osteoporosis y metabolismo mineral de la Sociedad Española de Endocrinología y Nutrición (SEEN) para la evaluación y el tratamiento de la osteoporosis asociada a diferentes enfermedades endocrinas y alteraciones nutricionales. Participantes: Miembros del Grupo de trabajo de osteoporosis y metabolismo mineral de la SEEN. Métodos: Las recomendaciones se formularon de acuerdo al sistema Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) para establecer tanto la fuerza de las recomendaciones como el grado de evidencia. Se realizó una búsqueda sistemática en PubMed de las nuevas acerca de cada enfermedad usando las siguientes palabras clave asociadas al nombre de cada proceso patológico: AND osteoporosis, fractures, bone mineral density, bone markers y treatment. Se revisaron artículos escritos en inglés con fechas de inclusión comprendidas entre el 18 de octubre de 2011 y el 30 de octubre de 2014. Tras la formulación de las recomendaciones estas se discutieron de forma conjunta por el Grupo de trabajo.Conclusiones: Esta actualización resume los nuevos datos acerca de la evaluación y tratamiento de la osteoporosis en las enfermedades endocrinas y nutricionales que se asocian a baja masa ósea o a un aumento del riesgo de fractura.(AU)

Objective: To update previous recommendations developed by the Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology and Nutrition for the evaluation and treatment of osteoporosis associated to different endocrine and nutritional diseases. Participants: Members of the Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology and Nutrition. Methods: Recommendations were formulated according to the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the following terms associated to the name of each condition: AND "osteoporosis", "fractures", "bone mineral density", and "treatment". Papers in English with publication date between 18 October 2011 and 30 October 2014 were included. The recommendations were discussed and approved by all members of the Working Group. Conclusions: This update summarizes the new data regarding evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions.(AU)

Punta-onda continua del sueño lento / No disponible

No disponible

Earliest known use of marine resources by Neanderthals.

Numerous studies along the northern Mediterranean borderland have documented the use of shellfish by Neanderthals but none of these finds are prior to Marine Isotopic Stage 3 (MIS 3). In this paper we present evidence that gathering and consumption of mollusks can now be traced back to the lowest level of the archaeological sequence at Bajondillo Cave (Málaga, Spain), dated during the MIS 6. The paper describes the taxonomical and taphonomical features of the mollusk assemblages from this level Bj(19) and briefly touches upon those retrieved in levels Bj(18) (MIS 5) and Bj(17) (MIS 4), evidencing a continuity of the shellfishing activity that reaches to MIS 3. This evidence is substantiated on 29 datings through radiocarbon, thermoluminescence and U series methods. Obtained dates and paleoenvironmental records from the cave include isotopic, pollen, lithostratigraphic and sedimentological analyses and they are fully coherent with paleoclimate conditions expected for the different stages. We conclude that described use of shellfish resources by Neanderthals (H. neanderthalensis) in Southern Spain started ∼150 ka and were almost contemporaneous to Pinnacle Point (South Africa), when shellfishing is first documented in archaic modern humans.

Nutrición en el tratamiento y prevención de enfermedades crónicas / Nutrition in the treatment and prevention of chronic diseases

Las enfermedades crónicas precisan soporte nutricional. Éste es especialmente importante en aquellas enfermedades en cuya etiopatogenia la dieta desempeña un papel relevante; las dietas, si bien no son curativas, forman parte de la estrategia terapéutica. El asesoramiento dietético debe ser realizado por un experto, ya que, por un lado, todavía no son bien conocidos los requerimientos de determinados nutrientes (y se modifican según se dispone de más información) y, por otro, la indicación de dietas restrictivas implica riesgo de deficiencias nutricionales. Por ello, la tendencia actual es evitar dietas excesivamente restrictivas. Asimismo, es sumamente importante el control nutricional de los pacientes que precisan dietas especiales. Se necesitan programas de educación para pediatras y demás grupos sanitarios que informen sobre la importancia de la alimentación y su papel en la prevención de enfermedades (AU)

HSP90 and checkpoint-dependent lengthening of the G2 phase observed in plant cells under hypoxia and cold.

Proliferating cells of Allium cepa L. roots became adapted to hypoxia (5% oxygen) and cold (10 degrees C) by acquiring new steady-state kinetics of growth. The cell cycle time increased from the 17.6 h in control meristems up to 29.7 and 69.0 h under hypoxia and cold conditions, respectively. Acclimation of the proliferating cells was stress specific. No acclimation took place after 24 h of heat treatment (40 degrees C). Under cold treatment, all cycle phases enlarged uniformly. However, under hypoxia, while the G(1) and S cycle phases roughly doubled in their timing, the expected checkpoint-dependent lengthening of G(2) did not take place. This failure in lengthening G(2) in response to hypoxia correlated with a failure in the overinduction of a single peptide with a molecular mass of about 134 kDa which is among those recognised by an HSP90 antibody. Moreover, the presence of this large peptide of the HSP90 family proved to be a marker for cell proliferation. It was always absent from the contiguous differentiated cells of the root. Lastly, the mitochondrial chaperonin recognized by an HSP60 antibody in these roots not involved in photosynthesis was always higher in the proliferating than in the nonproliferating cells.

[Hypophosphatemia in parenteral nutrition: prevention and associated risks factors]. / Hipofosfatemia en nutrición parenteral: prevención y factores de riesgo asociados.

AIM: To determine the incidence of hypophosphatemia in parenterally fed patients, the phosphate amount necessary to prevent this complication and associated risks factors. SETTING: Observational study, not controlled, in a third level hospital. PATIENTS: In-patients with parenteral nutrition with at least a complete laboratory work-up. INTERVENTION: For a complete year, days on parenteral nutrition, administered phosphate and plasmatic ionised calcium levels, y-glutamiltranspeptidase, glucose, phosphate, pre-albumin, urea, and leukocytes were recorded. A multiple stepwise regression analysis and logistic regression are used for data analysis. RESULTS: Eight hundred and twenty seven determinations, corresponding to 401 patients, were included. Significant variables (p < 0.05) were: administered phosphate and ionised calcium serum levels, glucose, pre-albumin, and urea; regression coefficients were 0.004 (95%CI: 0.002 to 0.006), -0.156 (95%CI: -0.270 to 0.037), -0.014 (95%IC: -0.022 to 0.009), 0.005 (95%CI: 0.002 to 0.009) and 0.019 (95%CI: 0.016 to 0.022), respectively; the constant was 1.0735 (95%CI: 0.939 to 1.2079). The risk for developing hypophosphatemia decreased from 0.65 (95%CI: 0.33 to 1.26) to 0.16 (95%CI: 0.078 to 0.35) when administered phosphate varied from the span 7.5-17.5 mmol to values higher than 27.5 mmol. CONCLUSIONS: It is necessary to routinely supplement nutrition with phosphate since its content in commercially available lipidic emulsions is not sufficient to prevent hypophosphatemia in the majority of patients with parenteral nutrition. Phosphate intake must be sufficient to restore the intracellular phosphate deficit and to compensate for the plasmatic phosphate fall, with special attention to poorly nourished, hyperglycaemic or with renal failure patients. Phosphate intakes around 27-37 mmol dramatically decrease the incidence of hypophosphatemia in studied patients, with no recorded cases of severe hypophosphatemia.

Evaluation of the mutagenicity of antimalarial products isolated from Solanum nudum (Solanaceae).

Diosgenone is a major component of the hexane extract from the plant Solanum nudum (Solanaceae). The products from degraded and acetylated diosgenone that showed in vitro antimalarial activity against the FCB-2 strain of Plasmodium falciparum and methanol, dichloromethane and ethereal extracts of Solanum nudum were tested for their mutagenic activity using the Ames test with the TA-97a, TA-98, TA-100 and TA-102 strains of Salmonella typhimurium. These compounds were not mutagenic at the tested concentrations.

Nutrient removal and sludge production in the coagulation-flocculation process.

Nutrient removal and sludge production in the coagulation-flocculation process, applied to a slaughterhouse effluent, have been studied. Fe2(SO4)3, Al2(SO4)3 and polyaluminium chloride were used as coagulants. Inorganic products were used as coagulant aids: activated silica, powdered activated carbon and precipitated calcium carbonate and synthetic polyelectrolytes: cationic polyacrylamide, polyacrilic acid, anionic polyacrylamide and polyvinyl alcohol. Performances were measured under optimum conditions for the products used. They were found after studying the different variables which influence the process. Phosphorus removal is very high (approximately 100% for the orthophosphate and between 98.93% and 99.90% for the total phosphorus). Ammonia nitrogen removal is very low although appreciable performances are observed for albuminoid nitrogen (73.9-88.77%). The use of coagulant aids reduces the volume of the sludge produced up to 41.6%.

Antimalarial activity of neurolenin B and derivates of Eupatorium inulaefolium (Asteraceae).

Dried stems and leaves of Eupatorium inulaefolium (Austroeupatorium inulaefolium) (Asteraceae) were used to obtain four crude extracts (hexane, dichloromethane, methanol and ethanol). Two fractions were obtained from the hexane extract (S1 and S2) and three compounds (neurolenin B, lobatin A and lobatin B) from the dichloromethane extract. The ethanol, hexane, dichloromethane and methanol extracts, two fractions from the hexane extract (S1 and S2), and neurolenin B were evaluated in vitro against Plasmodium falciparum, FCB-2 strain. Two extracts (dichloromethane and methanol), the S2 fraction and neurolenin B showed statistically significant antiplasmodial activity.

Antitumor and antiviral activity of Colombian medicinal plant extracts.

Extracts of nine species of plants traditionally used in Colombia for the treatment of a variety of diseases were tested in vitro for their potential antitumor (cytotoxicity) and antiherpetic activity. MTT (Tetrazolium blue) and Neutral Red colorimetric assays were used to evaluate the reduction of viability of cell cultures in presence and absence of the extracts. MTT was also used to evaluate the effects of the extracts on the lytic activity of herpes simplex virus type 2 (HSV-2). The 50% cytotoxic concentration (CC50) and the 50% inhibitory concentration of the viral effect (EC50) for each extract were calculated by linear regression analysis. Extracts from Annona muricata, A. cherimolia and Rollinia membranacea, known for their cytotoxicity were used as positive controls. Likewise, acyclovir and heparin were used as positive controls of antiherpetic activity. Methanolic extract from Annona sp. on HEp-2 cells presented a CC50 value at 72 hr of 49.6x10(3)mg/ml. Neither of the other extracts examined showed a significant cytotoxicity. The aqueous extract from Beta vulgaris, the ethanol extract from Callisia grasilis and the methanol extract Annona sp. showed some antiherpetic activity with acceptable therapeutic indexes (the ratio of CC50 to EC50). These species are good candidates for further activity-monitored fractionation to identify active principles.

Antitumor and Antiviral Activity of Colombian Medicinal Plant Extracts

Extracts of nine species of plants traditionally used in Colombia for the treatment of a variety of diseases were tested in vitro for their potential antitumor (cytotoxicity) and antiherpetic activity. MTT (Tetrazolium blue) and Neutral Red colorimetric assays were used to evaluate the reduction of viability of cell cultures in presence and absence of the extracts. MTT was also used to evaluate the effects of the extracts on the lytic activity of herpes simplex virus type 2 (HSV-2). The 50 percent cytotoxic concentration (CC50) and the 50 percent inhibitory concentration of the viral effect (EC50) for each extract were calculated by linear regression analysis. Extracts from Annona muricata, A. cherimolia and Rollinia membranacea, known for their cytotoxicity were used as positive controls. Likewise, acyclovir and heparin were used as positive controls of antiherpetic activity. Methanolic extract from Annona sp. on HEp-2 cells presented a CC50 value at 72 hr of 49.6x103mg/ml. Neither of the other extracts examined showed a significant cytotoxicity. The aqueous extract from Beta vulgaris, the ethanol extract from Callisia grasilis and the methanol extract Annona sp. showed some antiherpetic activity with acceptable therapeutic indexes (the ratio of CC50 to EC50). These species are good candidates for further activity-monitored fractionation to identify active principles

10-Oximeguanacone, the first nitrogenated acetogenin derivative found to be a potent inhibitor of mitochondrial complex I.

A new 10-keto bis-tetrahydrofuran acetogenin, guanacone (1), has been isolated from a cytotoxic extract of Annona aff. spraguei seeds. The 10-oximeguanacone derivative 1f is the first bioactive nitrogenated acetogenin found to be a very potent inhibitor of complex I. In addition, a SAR study of guanacone analogues is reported based on the titration of the NADH oxidase and NADH:ubiquinone oxidoreductase activities.

Phosphorylation of connexin43 and the regulation of neonatal rat cardiac myocyte gap junctions.

The functional state of gap junctions and the state of phosphorylation of connexin43 (Cx43), the major gap junction protein in rat heart, were evaluated in primary cultures of neonatal rat cardiocytes. Functional coupling was greatly reduced after treatment with staurosporine (ST), a protein kinase inhibitor. The ST-induced reduction in cell coupling was reversed by activation of protein kinase C (PKC) with 12-O-tetradecanoylphorbol 13-acetate (TPA). The cellular distribution of Cx43, as detected by immunofluorescence, was not grossly affected by either ST alone or ST plus TPA. Although immunoblot analysis did not detect significant changes in the relative amounts of the unphosphorylated and individual phosphorylated forms of Cx43 after each treatment, the level of 32P-incorporation into Cx43 of radiolabeled cells was significantly affected. Consistent with their known properties, treatment with ST reduced, and combined treatment with TPA and ST increased, the level of 32P-incorporation into Cx43. Two-dimensional tryptic phosphopeptide maps of 32P-labeled Cx43 indicated that a distinct subset of the phosphopeptides that are present under basal conditions were affected by ST or ST/TPA treatments, with TPA-induced phosphorylation occurring at the ST-sensitive sites. However, the ST/TPA-sensitive tryptic phosphopeptides did not comigrate with others that were derived from in vitro phosphorylation by PKC of a recombinant C-terminal Cx43 peptide (Cx43[243-382]). Although a PKC-dependent mechanism appears to be involved in the regulation of functional coupling between neonatal rat cardiocytes, PKC itself may not be the final mediator of Cx43 phosphorylation.

Effects of cGMP-dependent phosphorylation on rat and human connexin43 gap junction channels.

The effects of 8-bromoguanosine 3':5'-cyclic monophosphate (8Br-cGMP), a membrane-permeant activator of protein kinase G (PKG), were studied on rat and human connexin43 (Cx43), the most abundant gap junction protein in mammalian heart, which were exogenously expressed in SKHep1 cells. Under dual whole-cell voltage-clamp conditions, 8Br-cGMP decreased gap junctional conductance (gj) in rat Cx43-transfected cells by 24.0 +/- 3.7% (mean +/- SEM, n = 5), whereas gj was not affected in human Cx43-transfected cells by the same treatment. The relaxation of gj in response to steps in transjunctional voltage observed in rat Cx43 transfectants was best fitted with three exponentials. Time constants and amplitudes of the decay phases changed in the presence of 8Br-cGMP. Single rat and human Cx43 gap junction channels were resolved in the presence of halothane. Under control conditions, three single-channel conductance states (gammaj) of about 20, 40-45 and 70 pS were detected, the events of the intermediate size being most frequently observed. In the presence of 8Br-cGMP, the gammaj distribution shifted to the lower size in rat Cx43 but not in human Cx43 transfectants. Immunoblot analyses of Cx43 in subconfluent cultures of rat Cx43 or human Cx43 transfectants showed that 8Br-cGMP did not induce changes in the electrophoretic mobility of Cx43 in either species. However, the basal incorporation of [32P] into rat Cx43 was significantly altered by 8Br-cGMP, whereas this incorporation of [32P] into human Cx43 was not affected. We conclude that 8Br-cGMP modulates phosphorylation of rat Cx43 in SKHep1 cells, but not of human Cx43. This cGMP-dependent phosphorylation of rat Cx43 is associated with a decreased gj, which results from both an increase in the relative frequency of the lowest conductance state and a change in the kinetics of these channels.

[The usefulness of dual-energy radiographic densitometry (DO) in establishing the composition of calculi]. / Utilidad de la densitometría radiográfica de energía dual (DO) en el establecimiento de la composición litiásica.

Dual-energy radiographic bone densitometry is utilized to determine the bone mineral content in patients with osteoporosis. The present in vitro experimental study investigated the usefulness of densitometry in determining stone composition and in evaluating the mineral and non mineral phases of the calculus. For the study we analyzed 114 calculi of 6 different chemical composition (calcium oxalate monohydrate, calcium oxalate dihydrate, magnesium ammonium phosphate, phosphate carbonate, uric acid and phosphate oxalate). The phosphate carbonate calculi had the highest mineral density, whereas the uric acid calculi had the lowest and contained more water. Although densitometry appears to be of little value in determining stone composition, it provides information on the mineral and non mineral phases of the calculus.

Displacement activity of bisbenzylisoquinoline alkaloids at striatal 3H-SCH 23390 and 3H-raclopride binding sites.

Fifteen bisbenzylisoquinoline alkaloids (BBIQ) with one ether bridge (thaligrisine [1], berbamunine [2], dimethylgrisabine [3], pampulhamine [4], and methyl-dauricine [5]), with two ether bridges (homoaromoline, isotetrandrine, and obaberine), with one ether bridge and one biphenyl bridge (oxandrine, dimethylpseudoxandrine, pseudoxandrine, and antioquine) or secoderivatives (secoobaberine, secoantioquine, and secolucidine), were tested for their ability to displace 3H-raclopride or 3H-SCH 23390 from their specific dopaminergic binding sites to rat striatal membranes. The most active compounds were found in the group of BBIQs with one ether bridge. Inactive or weakly active compounds were found in this group of BBIQs with one ether bridge and in the other groups. Analysis of tridimensional representations indicates that the differnt activities among the BBIQs with one ether bridge could be related to strong differences between the spatial occupancy of these compounds according to their stereochemistry.