Electrochemically reduced graphene oxide on CoCr biomedical alloy: Characterization, macrophage biocompatibility and hemocompatibility in rats with graphene and graphene oxide.

Electrochemically reduced graphene oxide (ErGO) films on a biomedical grade CoCr alloy have been generated and characterized in order to study their possible application for use on joint prostheses. The electrodeposition process was performed by cyclic voltammetry. The characterization of the ErGO films on CoCr alloys by XPS revealed sp2 bonding and the presence of CO and CO residual groups in the graphene network. Biocompatibility studies were performed with mouse macrophages J774A.1 cell cultures measured by the ratio between lactate dehydrogenase and mitochondrial activities. An enhancement in the biocompatibility of the CoCr with the ErGO films was obtained, a result that became more evident as exposure time increased. Macrophages on the CoCr with the ErGO were well-distributed and conserved the characteristic cell shape. In addition, vimentin expression was unaltered in comparison with the control, results that indicated an improvement in the CoCr biocompatibility with the ErGO on the material surface. The in vivo response of graphene and graphene oxide was assessed by intraperitoneal injection in wistar rats. Red blood cells are one of the primary interaction sites so hemocompatibility tests were carried out. Rats inoculated with graphene and graphene oxide showed red blood cells of smaller size with a high content in hemoglobin.

Dependency relationships among ear characters in a Spanish sample, its forensic interest.

The aim of this paper is to provide information on dependency relationships between the morphological characters of the external ear and their importance in physical identification. At present, there is a lack of population data in this field, and little research has been published. Our study sample consisted of 281 Spanish university students of European descent aged between 18 and 31 years old. We analysed a total of 562 ears. For a large number of characters, we found a dependency between anatomically related characters, confirming our hypothesis. For example, we found relationships between ear shape and protrusion, between rolling of the superior and posterior helix, and between the upper and lower parts of the scapha. However, our results also indicated that some anatomically related characters did not present relationships. Thus, we found no dependency between contour shape of the supero-posterior helix and rolling of the posterior helix or between intertragic incisure shape and tragus or antitragus shape. In addition, we found that some characters that are not anatomically related also showed relationships. These included rolling of the superior helix and intertragic incisure shape, and contour shape of the superior helix and the inferior part of the scapha. These results are of great importance and should be taken into account in forensic applications.

Porous aerogel and core/shell nanoparticles for controlled drug delivery: A review.

This review presents the methods and general strategies for the synthesis of porous aerogels and core/shell nanoparticles with efficient and controlled drug delivery. Different mechanisms of drug delivery are also discussed, which are influenced by the porosity, surface area, pH and surface functionalization of the aerogel and core/shell nanoparticles. Various porous inorganic, organic, and hybrid systems were compared. In addition, the main physical and chemical characteristics of these porous nanoparticles which enhance the drug loading on the porous nanoparticles were discussed.

Morphological variability of the earlobe in a Spanish population sample.

This article shows the morphological variability of the earlobe in a Spanish population of European origin. The frequencies of four lobe characteristics (attachment, contour, modeling, and size) and their degree of expression were studied. The relationship among the characteristics and the differences involving sex and laterality were also considered. The least frequent morphology, and of main use in solving forensic cases, was the very small size with triangle-pulled contour into the skin and crossed-discontinuous modeling. The most frequent morphology, and most clinically useful, was the medium-sized lobe with free-arched contour and eminent or cross-continuous modeling. The characteristics were all symmetric. Size and modeling showed sexual dimorphism. Some characteristics were associated with each other: attachment with contour and modeling and the contour with modeling and size. The least frequent peculiarities were sharp lobe and virgule. The literature is scarce on this matter, practically non-existent for some characteristics, especially modeling and peculiarities. For the first time, the associations of the ear characteristics were analyzed, and this information could be applied to forensic identification.

Study of overall and local electrochemical responses of oxide films grown on CoCr alloy under biological environments.

The interaction of the physiological medium and living tissues with the implant surfaces in biological environments is regulated by biopotentials that induce changes in the chemical composition, structure and thickness of the oxide film. In this work, oxide films grown on CoCr alloys at 0.5 V vs Ag/AgCl and 0.7 V vs Ag/AgCl have been characterized through overall and localized electrochemical techniques in a phosphate buffer solution and 0.3% hyaluronic acid. Nanopores of 10-50nm diameter are homogeneously distributed along the surface in the oxide film formed at 0.7 V vs Ag/AgCl. The distribution of the Constant Phase Element studied by local electrochemical impedance spectroscopy showed a three-dimensional (3D) model on the oxide films grown at 0.5 V vs Ag/AgCl and 0.7 V vs Ag/AgCl. This behaviour is especially noticeable in oxide films grown at 0.7 V vs Ag/AgCl, probably due to surface inhomogeneities, and resistive properties generated by the potentiostatic growth of the oxide film.

In vivo study of viral haemorrhagic septicaemia virus and infectious pancreatic necrosis virus coexistence in Senegalese sole (Solea senegalensis).

The effect of IPNV-VHSV coinfection and superinfection on the mortality caused by both viruses in Senegalese sole has been analysed. No effect was observed after coinfection. However, a clear viral interference was recorded between a primary IPNV and a subsequent VHSV infection, which led to a survival increase in the infected sole of 50% points when compared with fish infected only with VHSV. The significantly higher Mx transcriptional values in the fish pre-exposed to IPNV (at least at first days after superinfection) and the increased daily mortality when low Mx transcriptional levels were recorded suggest that Mx may be involved in the protective effect against VHSV infection. However, in fish subjected to VHSV primary/IPNV secondary infection, no interference was observed.

Gilthead seabream (Sparus aurata) Mx gene promoters respond differentially to IPNV and VHSV infections in RTG-2 cells.

The understanding of virus-host interactions relies on the knowledge of the regulatory mechanisms of the type I interferon (IFN I)-stimulated genes (ISGs). Among ISGs, those coding Mx proteins play a main role due to their direct antiviral activity. The study of these genes in gilthead seabream is interesting, since this species displays high natural resistance to viral diseases, being asymptomatic carrier of infectious pancreatic necrosis virus (IPNV) and viral haemorrhagic septicaemia virus (VHSV). Gilthead seabream has three Mx genes (Mx1, Mx2, and Mx3), encoding proteins with a wide spectrum of antiviral activity. The structure of the three promoters (pMx1, pMx2 and pMx3) has been previously disclosed, and their response to poly I:C in RTG-2 cells characterized. To further analyze these promoters, their response to two viral infections has been evaluated in the present study. For that purpose, RTG-2 cells transiently transfected with the luciferase gene under the control of each promoter were inoculated with either IPNV or VHSV at two different doses. The highest and lowest fold induction values were recorded for pMx2 and pMx3, respectively. The promoter induction was always stronger after VHSV inoculation than in IPNV-inoculated cells. In addition, the higher dose of VHSV tested induced higher response of the three promoters, whereas in IPNV-infected cells the highest induction was recorded after inoculation with the lower viral dose. To further study the response of the Mx2 promoter, RTG-2 cells stably transfected with the luciferase gene under the control of pMx2 were stimulated with poly I:C and subsequently infected with IPNV or VHSV. Interestingly, IPNV infection inhibited the induction caused by poly I:C, suggesting an antagonistic activity of IPNV on Mx2 transcription. In contrast, VHSV infection did not alter the response triggered by poly I:C. These results highlight the specific regulation that controls the activity of each promoter, and support the existence of complex interactions between host cells, specific Mx promoters, and viruses, which are responsible for the final outcome of a viral infection.

Practical application of brief cognitive tests.

INTRODUCTION: Brief cognitive tests (BCT) may help detect cognitive impairment (CI) in the clinical setting. Several BCT have been developed and/or validated in our country, but we lack specific recommendations for use. DEVELOPMENT: Review of studies on the diagnostic accuracy of BCT for CI, using studies conducted in Spain with BCT which take less than 20 min. We provide recommendations of use based on expert consensus and established on the basis of BCT characteristics and study results. CONCLUSION: The Fototest, the Memory Impairment Screen (MIS) and the Mini-Mental State Examination (MMSE) are the preferred options in primary care; other BCT (Clock Drawing Test [CDT], test of verbal fluency [TVF]) may also be administered in cases of negative results with persistent suspected CI or concern (stepwise approach). In the specialised care setting, a systematic assessment of the different cognitive domains should be conducted using the Montreal Cognitive Assessment, the MMSE, the Rowland Universal Dementia Assessment, the Addenbrooke's Cognitive Examination, or by means of a stepwise or combined approach involving more simple tests (CDT, TVF, Fototest, MIS, Memory Alteration Test, Eurotest). Associating an informant questionnaire (IQ) with the BCT is superior to the BCT alone for the detection of CI. The choice of instruments will depend on the patient's characteristics, the clinician's experience, and available time. The BCT and IQ must reinforce - but never substitute - clinical judgment, patient-doctor communication, and inter-professional dialogue.

Estimated prevalence of dementia based on analysis of drug databases in the Region of Madrid (Spain).

INTRODUCTION: The progressive rise in dementia prevalence increases the need for rapid methods that complement population-based prevalence studies. OBJECTIVE: To estimate the prevalence of dementia in the population aged 65 and older based on use of cholinesterase inhibitors and memantine. METHODS: Descriptive study of use and prescription of cholinesterase inhibitors and/or memantine in 2011 according to 2 databases: Farm@drid (pharmacy billing records for the Region of Madrid) and BIFAP (database for pharmacoepidemiology research in primary care, with diagnosis and prescription records). We tested the comparability of drug use results from each database using the chi-square test and prevalence ratios. The prevalence of dementia in Madrid was estimated based on the dose per 100 inhabitants/day, adjusting the result for data obtained from BIFAP on combination treatment in the general population (0.37%) and the percentage of dementia patients undergoing treatment (41.13%). RESULTS: Cholinesterase inhibitors and memantine were taken by 2.08% and 0.72% of Madrid residents aged 65 and older was respectively. Both databases displayed similar results for use of these drugs. The estimated prevalence of dementia in individuals aged 65 and older is 5.91% (95% CI%, 5.85-5.95) (52 287 people), and it is higher in women (7.16%) than in men (4.00%). CONCLUSIONS: The estimated prevalence of dementia is similar to that found in population-based studies. Analysing consumption of specific dementia drugs can be a reliable and inexpensive means of updating prevalence data periodically and helping rationalise healthcare resources.

Synergistic effects in the antiviral activity of the three Mx proteins from gilthead seabream (Sparus aurata).

Due to their direct antiviral activity, Mx proteins play a main role in the response mediated by type I interferon against viral infections. The study on gilthead seabream Mx proteins is especially interesting, since this species is unusually resistant to viral diseases, being asymptomatic carrier of several viruses pathogenic to other fish species. Gilthead seabream has three Mx proteins (Mx1, Mx2 and Mx3) that, separately, display antiviral activity against a wide range of viruses, showing interesting differences in their antiviral specificities. In this work, the possible synergy between the three Mx isoforms has been studied using in vitro systems consisting of CHSE-214 cells stably expressing two or the three gilthead seabream Mx proteins. The antiviral activity of these Mx combinations has been tested against the Infectious Pancreatic Necrosis Virus (IPNV), the Viral Haemorrhagic Septicaemia Virus (VHSV), the European Sheatfish Virus (ESV) and the Lymphocystis Disease Virus (LCDV). A synergistic effect of the Mx proteins was only detected against ESV, no synergy was observed against LCDV, and a negative interference was detected against the two RNA viruses tested, IPNV and VHSV, as viral replication was higher in cells expressing certain Mx combinations than in cells expressing these proteins separately. These results suggest a functional interaction between gilthead seabream Mx isoforms, which results in a higher or lower antiviral activity depending on the virus tested, thus supporting the idea of complex virus-host interactions and finely tuned mechanisms controlling the antiviral activity of Mx proteins.

Analysis of metallic traces from the biodegradation of endomedullary AZ31 alloy temporary implants in rat organs after long implantation times.

AZ31 alloy has been tested as a biodegradable material in the form of endomedullary implants in female Wistar rat femurs. In order to evaluate the accumulation of potentially toxic elements from the biodegradation of the implant, magnesium (Mg), aluminium (Al), zinc (Zn), manganese (Mn) and fluorine (F) levels have been measured in different organs such as kidneys, liver, lungs, spleen and brain. Several factors that may influence accumulation have been taken into account: how long the implant has been in place, whether or not the bone is fractured, and the presence of an MgF2 protective coating on the implant. The main conclusions and the clinical relevance of the study have been that AZ31 endomedullary implants have a degradation rate of about 60% after 13 months, which is fully compatible with fracture consolidation. Neither bone fracture nor an MgF2 coating seems to influence the accumulation of trace elements in the studied organs. Aluminium is the only alloying element in this study that requires special attention. The increase in Al recovered from the sampled organs represents 3.95% of the amount contained in the AZ31 implant. Al accumulates in a statistically significant way in all the organs except the brain. All of this suggests that in long-term tests AZ31 may be a suitable material for osteosynthesis.

[Relationship between physical activity and hemodynamic parameters in adults]. / Relación entre la actividad física y parámetros hemodinámicos en adultos.

OBJECTIVES: To analyze the relationship between physical activity, as assessed by accelerometer, with central and peripheral augmentation index and carotid intima media thickness (IMT) in adults. METHODS: This study analyzed 263 subjects who were included in the EVIDENT study. Physical activity was assessed during 7 days using the ActigraphGT3X accelerometer (counts/min). Carotid ultrasound was used to measure carotid IMT. The Sphygmo Cor System was used to measure central and peripheral augmentation index (CAIx and PAIx). RESULTS: Mean age 55.85±12 years; 59.30% female; 26.7 body mass index and blood pressure 120/77mmHg. Mean physician activity counts/min was 244.37 and 2.63±10.26min/day of vigorous or very vigorous activity. Physical activity showed an inverse correlation with PAIx (r=-0.179; P<.01) and vigorous activity day time with IMT(r=-0.174; P<.01), CAIx (r=-0.217; P<.01) and PAIx (r=-0.324; P<.01). After adjusting for confounding factors in the multiple regression analysis, the inverse association of CAIx with counts/min and the time spent in vigorous/very vigorous activity was maintained. CONCLUSION: The results suggest that both physical activity and time spent in vigorous or vigorous activity are associated with the central augmentation index in adults.

Anthropological study of ear tubercles in a Spanish sample.

The ear has been used since the 19th century as a valuable instrument in personal identification. Its special interest is due to the morphological complexity of the structures involved. The aim of the present investigation is to establish the morphological variability of the helix tubercles in a sample of the Spanish European population (303 individuals between 18 and 72 years old). The frequencies of appearance of each type of tubercle and its degree of expression, as well as the possible relationship with sex, age, and laterality, are determined. Three of the tubercles are relatively frequent in the sample: tubercle of the root of the superior helix (31.7%), tubercle of the anterior helix (27.6%), and the Darwin's tubercle (18.2%). The least frequent helix tubercles are those located on the superior helix (2.7%) and the inferior tubercles at the root of the helix (6%). For all sites, tubercles with the greatest degree of expression are the least frequent. No sexual dimorphism or age differences have been found except for the tubercle of the anterior helix. Overall, tubercles show good symmetry. A relation of dependency among some of the tubercles of the helix has been found.

Fracture bone healing and biodegradation of AZ31 implant in rats.

The ideal temporary implant should offer enough mechanical support to allow healing of the fracture and then biodegrade and be resorbed by metabolic mechanisms without causing any toxic effect. The aim of this research has been to simultaneously study in situ bone healing and the biodegradation of AZ31 Mg alloy as an osteosynthesis material. The in vivo study was carried out in AZ31 implants with and without Mg-fluoride coating inserted in un-fractured and fractured femurs of Wistar rats for long experimentation time, from 1 to 13 months, by means of computed tomography, histological and histomorphometric analysis. Tomography analysis showed the bone healing and biodegradation of AZ31 implants. The fracture is healed in 100% of the animals, and AZ31 maintains its mechanical integrity throughout the healing process. Biodegradation was monitored, quantifying the evolution of gas over time by 3D composition of tomography images. In all the studied groups, gas pockets disappear with time as a result of the diffusion process through soft tissues. Histomorphometric studies reveal that after 13 months the 46.32% of AZ31 alloy has been resorbed. The resorption of the coated and uncoated AZ31 implants inserted in fractured femurs after 1, 9 and 13 months does not have statistically significant differences. There is a balance between the biodegradation of AZ31 and bone healing which allows the use of AZ31 to be proposed as an osteosynthesis material.

Experimental susceptibility of European sea bass and Senegalese sole to different betanodavirus isolates.

The susceptibility of juvenile European sea bass and Senegalese sole to three VNNV isolates (a reassortant RGNNV/SJNNV, as well as the parental RGNNV and SJNNV genotypes) has been evaluated by challenges using two inoculation ways (bath and intramuscular injection). The results demonstrate that these two fish species are susceptible to all the VNNV isolates tested. In European sea bass, RGNNV caused the highest cumulative mortality, reaching maximum values of viral RNA and titres. Although the SJNNV isolate did not provoke mortality or clinical signs of disease in this fish species, viral production in survivor fish was determined; on the other hand the reassortant isolate did cause mortality and clinical signs of disease, although less evident than those recorded after RGNNV infection. These results suggest that the changes suffered by the SJNNV RNA2 segment of the reassortant isolate, compared to the parental SJNNV, may have involved host-specificity and/or virulence determinants for European sea bass. Regarding Senegalese sole, although the three isolates caused 100% mortality, the reassortant strain provoked the most acute symptoms, and more quickly, especially in the bath challenge. This was also the isolate showing less difference between the number of RNA copies and viral titre, reaching the highest titres of infective viral particles in nervous tissue of infected animals. The RGNNV isolate produced the lowest values of infective viral particles. All these results suggest that the RGNNV and the reassortant isolates are the most suited for infecting European sea bass and Senegalese sole, respectively.

Glycemic index, glycemic load, and pulse wave reflection in adults.

BACKGROUND AND AIMS: Diets with a high glycemic index (GI), high glycemic load (GL), or both, increase the risk of cardiovascular disease. This study examined the association of GI and GL in a regular diet with the peripheral augmentation index (i.e., a marker of vascular aging) in a sample of adults. METHODS AND RESULTS: Cross-sectional study. The findings presented in this manuscript are a subanalysis of the EVIDENT study whose purpose was to analyze the relationship between lifestyle and arterial aging. For the sample population, 1553 individuals aged 20-80 years were selected through random sampling from the patients of general practitioners at six health centers in Spain. GI and GL for each patient's diet were calculated from a previously validated, semi-quantitative, 137-item food frequency questionnaire. The peripheral augmentation index corrected for a heart rate of 75 bpm (PAIx75) was measured with pulse-wave application software (A-Pulse CASP). Based on a risk factor adjusted regression model, for every 5 unit increase in GI, the PAIx75 increased by 0.11 units (95% CI: 0.04-0.19). Similarly, for every increase in 10 units in GL, the PAIx75 increased by 1.13 (95% CI: 0.21-2.05). High PAIx75 values were observed in individuals with diets in the third GI tertile (i.e., the highest), and lower PAIx75 values in those with diets in the first tertile (i.e., the lowest), (93.1 vs. 87.5, respectively, p = 0.001). CONCLUSIONS: GI and GL were directly associated with PAIx75 values in adults without cardiovascular diseases regardless of age, gender, physical activity, and other confounders.

Consumption trends for specific drugs used to treat dementia in the region of Madrid (Spain) from 2002 to 2012.

INTRODUCTION: Analysing drug consumption in large population groups lets us observe consumption trends and compare them between different settings. OBJECTIVE: to analyse the time trends for consumption and costs of specific drugs used to treat dementia in the region of Madrid (Spain) and compare trends by sex and age cohort. METHODS: Descriptive study of cholinesterase inhibitors (N06DA) and memantine (N06DX01) dispensed in Madrid between 2002 and 2012 and covered by the Spain's national health system. Consumption was calculated by analysing changes in DDD (defined daily doses) to find total and yearly increases. The cost was estimated based on DDD price. To compare consumption rates by age and sex, we calculated DDD per 100 inhabitants/day. RESULTS: Between 2002 and 2012, consumption of drugs used to treat dementia increased sixfold. During this period, cholinesterase inhibitors accounted for 76.70% of the drugs consumed and memantine, 23.30%. The estimated cost rose by a by a factor of 5.7 over 11 years (or by a factor of 4 taking into account the use of generic drugs). In 2012, 2.42% of the patients aged 65 or over consumed cholinesterase inhibitors (women 2.82%, men 1.83%) and 0.90% consumed memantine (women 1.10%, men 0.61%). Consumption increased in age cohorts up to 86 to 90 (5.84% for cholinesterase inhibitors and 2.33% for memantine) and declined thereafter. CONCLUSIONS: Consumption of cholinesterase inhibitors and memantine gradually increased, but consumption in 2012 did not reach levels equivalent to dementia prevalence figures. Pharmaceutical expenditure restraint measures may temporarily slow the cost increase temporarily but if the same trend of consumption persists, costs will rise.

Modeling in vivo corrosion of AZ31 as temporary biodegradable implants. Experimental validation in rats.

In this paper, two complementary approaches, mathematical modeling and experimental results are combined to identify variables that affect the in vivo biodegradation of magnesium implants. The in vivo corrosion behavior of AZ31 alloy proposed for temporary applications as fixation of bone fractures has been modeled solving the Laplace equation by finite element method (FEM). Bar-shaped AZ31 implants of 1mm diameter and 20mm length were inserted in Wistar rat femurs with and without a fracture. The presence of gas around AZ31 implants inside the femurs has been detected in situ at the epiphysis and in fractured areas by computerized tomography (CT). Examining some in vivo conditions, the model confirms that magnesium-alloy devices have different biodegradation behavior, depending on the thickness of electrolyte at the implantation site and can be used for predicting the biodegradation behavior.

Relationship between electrocardiographic left ventricular hypertrophy criteria and vascular structure and function parameters in hypertensive patients.

The objective of this study was to determine the electrocardiographic left ventricular hypertrophy (LVH) criterion that best correlated with vascular structure and function parameters in hypertensive patients. A cross-sectional study involving 347 hypertensive patients was performed. The mean age of the subjects was 54.9±11.8 years, and 61% were male. Electrocardiography was used to detect LVH based on the evaluation of 10 criteria, and we defined the voltage-duration product (VDP) complex criterion. The vascular structure was evaluated according to carotid intima-media thickness (C-IMT), and vascular function was evaluated according to pulse wave velocity (PWV), the ambulatory arterial stiffness index (AASI), the home arterial stiffness index, and the peripheral (PAIx) and central (CAIx) augmentation indices. LVH according to at least some electrocardiographic criteria was recorded in 29.10% of the patients (34.10% of females; 25.90% of males). The vascular structure and function parameters showed higher values in the hypertensive patients with LVH. The criterion most closely correlated with C-IMT was Lewis-VDP (r=0.257); with PWV and AASI, the criterion was the Framingham-adjusted Cornell voltage (r=0.228 and r=0.195, respectively); and with CAIx and PAIx, the criterion was Novacode (r=0.226 and r=0.277, respectively). In the multivariate analysis, the association of the vascular structure and function parameters, the VDP complex (multiple linear regression) and the presence of LVH (logistic regression) disappeared after adjusting for age, sex and antihypertensive drugs. The relationship between the electrocardiographic criteria used to detect LVH in hypertensive patients and the vascular structure and function parameters were fundamentally conditioned by age and antihypertensive drug treatment.