Fluorinated Man9 as a High Mannose Mimetic to Unravel Its Recognition by DC-SIGN Using NMR.

Lectins are capable of reading out the structural information contained in carbohydrates through specific recognition processes. Determining the binding epitope of the sugar is fundamental to understanding this recognition event. Nuclear magnetic resonance (NMR) is a powerful tool to obtain this structural information in solution; however, when the sugar involved is a complex oligosaccharide, such as high mannose, the signal overlap found in the NMR spectra precludes an accurate analysis of the interaction. The introduction of tags into these complex oligosaccharides could overcome these problems and facilitate NMR studies. Here, we show the preparation of the Man9 of high mannose with some fluorine tags and the study of the interaction with its receptor, dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN). This fluorinated ligand has allowed us to apply heteronuclear two-dimensional (2D) 1H,19F STD-TOCSYreF NMR experiments, using the initial slope approach, which has facilitated the analysis of the Man9/DC-SIGN interaction, unequivocally providing the binding epitope.

Non-invasive assessment of muscle compartment elasticity by pressure-related ultrasound in pediatric trauma: a prospective clinical study in 25 cases of forearm shaft fractures.

BACKGROUND: Soft-tissue swelling after limb fractures in pediatric patients is well known to be a risk factor for developing acute compartment syndrome (ACS). Clinical assessment alone is uncertain in specific cases. Recently, we proposed a non-invasive ultrasound-based method to objectify muscle compartment elasticity for monitoring. We hypothesize a strong correlation between the soft-tissue swelling after stabilization of upper limb fractures and the compartment elasticity objectified with a novel ultrasound-based approach in pediatric trauma. PATIENTS AND METHODS: In a prospective clinical study, children suffering forearm fractures but not developing an ACS were included. The muscle compartment elasticity of the m. flexor carpi ulnaris was assessed after surgical intervention by a non-invasive, ultrasound-based method resulting in a relative elasticity (RE in %) in both the control (healthy limb) and study group (fractured limb). Soft-tissue swelling was categorized in four different levels (0-3) and correlated with the resulting RE (%). RESULTS: The RE in the study group (15.67%, SD ± 3.06) showed a significantly decreased level (p < 0.001) compared with the control (22.77%, SD ± 5.4). The categorized grade of soft-tissue swelling resulted in a moderate correlation with the RE (rs = 0.474). CONCLUSIONS: The presented study appears to represent a novel approach to assess the posttraumatic pressure changes in a muscle compartment after fracture stabilization non-invasively. In this first clinical study in pediatric cases, our measurement method represents a low-cost, easy, and secure approach that has the potential to substitute invasive measurement of suspected ACS in muscle compartment conditions. Further investigations in lager cohorts are required to prove its daily clinical practicability and to confirm the expected reliability.

Structural Requirements for Ga3+ Coordination in Synthetic Analogues of the Siderophore Piscibactin Deduced by Chemical Synthesis and Density Functional Theory Calculations.

Stereoselective total synthesis of several analogues of piscibactin (Pcb), the siderophore produced by different pathogenic Gram-negative bacteria, was performed. The acid-sensitive α-methylthiazoline moiety was replaced by a more stable thiazole ring, differing in the configuration of the OH group at the C-13 position. The ability of these Pcb analogues to form complexes with Ga3+ as a mimic of Fe3+ showed that the configuration of the hydroxyl group at C-13 as 13S is crucial for the chelation of Ga3+ to preserve the metal coordination, while the presence of a thiazole ring instead of the α-methylthiazoline moiety does not affect such coordination. A complete 1H and 13C NMR chemical shift assignment of the diastereoisomer mixtures around C9/C10 was done for diagnostic stereochemical disposition. Additionally, density functional theory calculations were performed not only for confirming the stereochemistry of the Ga3+ complex among the six possible diastereoisomers but also for deducing the ability of these to form octahedral coordination spheres with gallium. Finally, the lack of antimicrobial activity of Pcb and Pcb thiazole analogue Ga3+ complexes against Vibrio anguillarum agrees with one of the roles of siderophores in protecting pathogens from metal ion toxicity. The efficient metal coordination shown by this scaffold suggests its possible use as a starting point for the design of new chelating agents or vectors for the development of new antibacterials that exploit the "Trojan horse" strategy using the microbial iron uptake mechanisms. The results obtained will be of great help in the development of biotechnological applications for these types of compounds.

Sex-dependent worsening of NMDA-induced responses, anxiety, hypercortisolemia, and organometry of early peripheral immunoendocrine impairment in adult 3xTg-AD mice and their long-lasting ontogenic modulation by neonatal handling.

The neuroimmunomodulation hypothesis for Alzheimer's disease (AD) postulates that alterations in the innate immune system triggered by damage signals result in adverse effects on neuronal functions. The peripheral immune system and neuroimmunoendocrine communication are also impaired. Here we provide further evidence using a longitudinal design that also studied the long-lasting effects of an early life sensorial intervention (neonatal handling, from postnatal day 1-21) in 6-month-old (early stages of the disease) male and female 3xTg-AD mice compared to age- and sex-matched non-transgenic (NTg) mice with normal aging. The behavioral patterns elicited by the direct exposure to an open field, and the motor depression response evoked by NMDA (25 mg/kg, i.p) were found correlated to the organometry of peripheral immune-endocrine organs (thymus involution, splenomegaly, and adrenal glands' hypertrophy) and increased corticosterone levels, suggesting their potential value for diagnostic and biomonitoring.The NMDA-induced immediate and depressant motor activity and endocrine (corticosterone) responses were sensitive to sex and AD-genotype, suggesting worse endogenous susceptibility/neuroprotective response to glutamatergic excitotoxicity in males and in the AD-genotype. 3xTg-AD females showed a reduced immediate response, whereas the NTg showed higher responsiveness to subsequent NMDA-induced depressant effect than their male counterparts. The long-lasting ontogenic modulation by handling was shown as a potentiation of NMDA-depressant effect in NTg males and females, while sex × treatment effects were found in 3xTg-AD mice. Finally, NMDA-induced corticosterone showed sex, genotype and interaction effects with sexual dimorphism enhanced in the AD-genotype, suggesting different endogenous vulnerability/neuroprotective capacities and modulation of the neuroimmunoendocrine system.

Social environment as a modulator of immunosenescence.

Immune system aging, a process known as immunosenescence, involves a striking rearrangement affecting all immune cells, resulting in an increased rate of infections and a major incidence of autoimmune diseases and cancer. Nonetheless, differences in how individuals of the same chronological age carry out this immunosenescence establishment and thus the aging rate have been reported. In the context of neuroimmunoendocrine communication and its role in the response to stress situations, growing evidence suggests that social environments profoundly influence all physiological responses, especially those linked to immunity. Accordingly, negative contexts (loneliness in humans/social isolation in rodents) were associated with immune impairments and decreased lifespan. However, positive social environments have been correlated with adequate immunity and increased lifespan. Therefore, the social context in which an individual lives is proposed as a decisive modulator of the immunosenescence process and, consequently, of the rate of aging. In this review, the most important findings regarding how different social environments (negative and positive) modulate immunosenescence and therefore the aging rate, as well as the role of stress responses, hormesis, and resilience in these environments will be explained. Finally, several possible molecular mechanisms underlying the effects of negative and positive environments on immunosenescence will be suggested.

Improvement of several stress response and sleep quality hormones in men and women after sleeping in a bed that protects against electromagnetic fields.

BACKGROUND: The electromagnetic fields (EMFs) emitted by the technologies affect the homeostatic systems (nervous, endocrine, and immune systems) and consequently the health. In a previous work, we observed that men and women, after 2 months of using a bed with a registered HOGO system, that prevents and drain EMFs, improved their immunity, redox and inflammatory states and rejuvenated their rate of aging or biological age. Since, EMFs can act as a chronic stressor stimulus, and affect the sleep quality. The objective of this work was to study in men and women (23-73 years old) the effect of sleeping for 2 months on that bed in the blood concentrations of several hormones related to stress response and sleep quality as well as to corroborate the rejuvenation of their biological age. METHODS: In 18 men and women, plasma concentration of cortisol, dehydroepiandrosterone (DHEA), catecholamines (epinephrine, norepinephrine and dopamine), serotonin, oxytocin and melatonin were analyzed before and after 2 months of using the HOGO beds. A group of 10 people was used as placebo control. In another cohort of 25 men (20 experimental and 5 placebo), the effects of rest on the HOGO system on the concentration of cortisol and testosterone in plasma were studied. In all these volunteers, the biological age was analyzed using the Immunity Clock model. RESULTS: There is a significant increase in plasma concentration of DHEA, norepinephrine, serotonin, oxytocin, and melatonin as well as in testosterone, after resting for 2 months in that bed with the EMFs avoiding system. In addition, decreases in Cortisol/DHEA and Testosterone/cortisol ratio and plasma dopamine concentration were observed. No differences were found in placebo groups. In all participants that slept on HOGO beds, the biological age was reduced. CONCLUSIONS: Sleeping in a bed that isolates from EMFs and drain them can be a possible strategy to improve the secretion of hormones related to a better response to stress and sleep quality, which means a better endocrine system, and consequently better homeostasis and maintenance of health. This fact was confirmed with the slowdown in the rate of aging checked with a rejuvenation of the biological age.

Prematurely aging female mice improve their behavioural response, immunity, redox state, and lifespan after a short social interaction with non-prematurely aging mice.

Adult prematurely aging mice (PAM), characterized by inadequate stress response, show premature immunosenescence and shorter lifespan compared to adult exceptional non-PAM (E-NPAM). Aging can be influenced by lifestyle factors, such as social environment. The continuous cohabitation of female PAM with E-NPAM improved behavioral responses, immunity, redox state, and longevity of PAM, but caused deterioration in E-NPAM. The objective of this study was to investigate whether the social interaction of only 15 min/day for 2 months of PAM with E-NPAM, can produce that improvement in PAM without causing deterioration in E-NPAM. After that short social interaction PAM and E-NPAM were submitted to behavioral tests and peritoneal leukocytes were collected to assess immune functions, oxidative and inflammatory state parameters as well as catecholamine concentrations. The lifespan of each animal was recorded. Plasmatic concentration of oxytocin was also studied. Results showed that PAM presented better behavioral responses, immunity and oxi-inflammatory state after interacting with E-NPAM, and consequently a longer lifespan. E-NPAM, in general, did not show any changes after interaction with PAM, not affecting their longevity either. In conclusion, a short social interaction between PAM and E-NPAM could be an excellent strategy for improving the health state and longevity of PAM without causing deleterious effect on E-NPAM.

Fucodendropeptides induce changes in cells of the immune system in food allergic patients via DC-SIGN receptor.

Food allergy induced by lipid transfer proteins (LTPs) of Rosacea fruit family, such as peach, is becoming an important health problem in the Mediterranean area. Current treatments, such as allergen specific immunotherapy (AIT) with allergenic extracts show promising, but in many cases, they need an improvement in homogeneity, availability and induction of tolerant responses. Peptide-based vaccines containing adjuvants, such as carbohydrates for C-type lectin receptors (CLRs) are presented as an alternative approach. In this work, we have prepared fucosylated glycodendropeptides (GDPs) functionalized with Pru p 3 peptides via click chemistry. These GDPs, DnFuc9Prup3, induced changes in moDC maturation and lymphocyte proliferation in food allergic patients, indicating specific recognition via DC-SIGN receptor. From these data, D4Fuc9Prup3 can be considered a promising candidate for specific immunotherapy development.

FrpA is the outer membrane piscibactin transporter in Vibrio anguillarum: structural elements in synthetic piscibactin analogues required for transport.

Piscibactin (Pcb) is a labile siderophore widespread among Vibrionaceae. Its production is a major virulence factor of some fish pathogens such as Photobacterium damselae subsp. piscicida and Vibrio anguillarum. Although FrpA was previously suggested as the putative outer membrane transporter (OMT) for ferri-piscibactin, its role in piscibactin uptake was never demonstrated. In this work, we generated mutants of V. anguillarum defective in FrpA and analyzed their ability to use piscibactin as iron source. The results showed that inactivation of frpA completely disables piscibactin utilization, and the original phenotype could be restored by gene complementation, confirming that FrpA is the OMT that mediates ferri-Pcb uptake. Additionally, the ability of several Pcb thiazole analogues, with different configurations at positions 9, 10, and 13, to be internalized through FrpA, was evaluated measuring their ability to promote growth under iron deficiency of several indicator strains. The results showed that while those analogues with a thiazole ring maintain almost the same activity as Pcb, the maintenance of the hydroxyl group present in natural piscibactin configuration at position C-13 is crucial for Fe3+ chelation and, in consequence, for the recognition of the ferri-siderophore by the cognate OMT. All these findings allowed us to propose a Pcb analogue as a good candidate to vectorize antimicrobial compounds, through the Trojan horse strategy, to develop novel compounds against bacterial fish diseases.

Asociación del nivel socioeconómico y educacional en los egresos por cáncer de mama en Chile durante los años 2001 al 2016 / Association of the socioeconomic and educational level in the breast cancer hospital outbreaks in Chile during the years 2001 to 2016

Introducción: El cáncer de mama constituye la primera causa de muerte en los cánceres en Chile según Globocan 2018. Dentro de los factores que explican esta alta mortalidad encontramos una baja tasa de detección y de realización de mamografías en los niveles socioeconómicos altos. Es por esto que comprender las causas de defunción y los factores que afectan en la mortalidad y letalidad por cáncer de mama en los últimos 17 años nos permitirá enfocar las políticas públicas de los próximos 50 años. Los objetivos generales de este trabajo fueron caracterizar los egresos hospitalarios en los pacientes por cáncer de mama según la edad, el sexo, la previsión, el nivel socioeconómico y educacional en Chile durante los años 2001 al 2016 y calcular la mortalidad y letalidad específica en estas mismas variables durante los años 2001 a 2016. El objetivo específico es asociar las variables socioeconómicas y educacionales, estimando los Odd's ratios de las variables en los egresos hospitalarios por cáncer de mama en Chile durante los años 2001 al 2016. Materiales y Métodos: Estudio de cohorte longitudinal retrospectivo en 81,072 egresos hospitalarios y 20,220 defunciones obtenidas de la página DEIS MINSAL, años 2001-2016. Para el análisis univariado se efectuó una regresión de ajuste de tasas Prais-weinstein según edad y sexo según modelo OMS de ajuste de tasas. Para las variables de tipo discreta se describieron mediante porcentajes y tasas y para las variables de tipo continua se utilizó mediana y desviación estándar. Se efectuó un test de smirnov-kolmolgorov para determinar el tipo de distribución y de normalidad de las muestras. Para las variables de tipo dicotómica se utilizó un modelo de regresión logística binaria para describir estas variables y determinar la posible asociación entre el nivel socioeconómico y educacional de las pacientes diagnosticadas por cáncer de mama. Resultados: Murieron 1,88 veces más personas de nivel socioeconómico alto con un IC entre 1,83- 1,94 con respecto a la población de nivel socioeconómico bajo. En cambio, las personas con un mayor nivel educacional murieron 0,5 veces menos según la regresión realizada respecto al bajo nivel educacional con un IC entre 0,47- 0,52, pero a menor nivel educacional aumentó 20 veces la mortalidad, constituyendo una causa inversa. Respecto al sexo las mujeres murieron 2,08 veces más que los hombres. Para el nivel socioeconómico alto en relación al bajo un OR [1.88 (1.83 a 1,94)], p<0,0001], para el nivel educacional alto en relación al bajo fue a favor del mayor nivel educacional con OR [0,5 (0,47 - 0,52)] y en cuanto a la comparación de sexos un OR [1,04 (1,03-2,17), p=0,039]. Es decir, la diferencia entre mortalidad que hubo fue significativa para todos los intervalos tanto para sexo, nivel educacional como para nivel socioeconómico. Se encontró una constante de 0,013 de mortalidad basal, es decir, todos tienen 1,3% de riesgo de morir por cáncer de mama independiente del nivel socioeconómico, educacional y del sexo. Conclusión: Existen diferencias estadísticamente significativas respecto a la mortalidad entre los niveles socioeconómicos altos y bajos y también en nivel educacional, sin embargo, al realizar los métodos de regresión se obtuvo una mayor mortalidad y mayor riesgo de morir por cáncer de mama en los niveles socioeconómicos más altos asociados a, probablemente, la menor cantidad de tamizajes y realización de mamografías en este estrato. A partir del año 2008 se observó un incremento a los niveles originales observados al inicio del segundo milenio incrementando las diferencias existentes en los índices de desigualdad tanto por nivel educacional como por nivel socioeconómico incrementando en 20 veces respecto al nivel educacional, y 1.88 respecto al nivel socioeconómico.

Introduction: Breast cancer is the leading cause of death in cancers in Chile according to Globocan 2018. Among the factors that explain this high mortality, we find a low rate of detection and performance of mammograms in high socioeconomic levels. This is why understanding the causes of death and the factors that affect mortality and fatality from breast cancer in the last 17 years will allow us to focus on public policies for the next 50 years Materials and Methods: Retrospective longitudinal cohort study in 79,996 hospital discharges and 20,220 deaths obtained from the DEIS MINSAL page, years 2001 -2016. For the univariate analysis, a Prais-Weinstein rate adjustment regression was performed according to age and sex according to the WHO rate adjustment model. For discrete type variables, they were described by percentages and rates, and median and standard deviation were used for continuous type variables. A smirnov-kolmolgorov test was performed to determine the type of distribution and normality of the samples. For dichotomous variables, a binary logistic regression model was used to describe these variables and determine the possible association between the socioeconomic and educational level of the patients diagnosed with breast cancer. Abstract: In this observational, longitudinal and retrospective study with 101.292 patients that includes men and women of all ages with diagnosis of breast cancer all along Chile, we´ll analyze the impact of socioeconomic level, evaluated through educational level and money income, into the prevalence, mortality and lethality of breast cancer in the years 2001 to 2016. Results: People with a high socioeconomic level died 1.88 times more, with a CI between 1.83 and 1.94, than those with a low socioeconomic level. On the other hand, people with a higher educational level died 0.5 times less according to the regression carried out with respect to the low educational level with a CI between 0.47 and 0.52, but the lower the educational level the mortality increased 20 times, constituting an inverse cause. Regarding sex, women died 2.08 times more than men. For the high socioeconomic level in relation to the low one an OR [1.88 (1.83 to 1.94)], p<0.0001], for the high educational level in relation to the low one it was in favor of the higher educational level with OR [0.5 (0.47 - 0.52)] and as for the comparison of sexes an OR [1.04 (1.03-2.17), p=0.039]. In other words, the difference between mortality was significant for all the intervals for sex, educational level and socioeconomic level. A constant baseline mortality of 0.013 was found, i.e., everyone has a 1.3% risk of dying from breast cancer regardless of socioeconomic level, educational level and sex. Conclusions: There are statistically significant differences in mortality between high and low socioeconomic levels and also in educational level; however, when regression methods were used, a higher mortality and higher risk of dying from breast cancer was obtained in the higher socioeconomic levels, probably associated with the lower number of screenings and mammograms performed in this stratum. As of 2008, an increase to the original levels observed at the beginning of the second millennium was observed, increasing the existing differences in the inequality indexes both by educational level and socioeconomic level, increasing by 20 times with respect to educational level, and 1.88 times with respect to socioeconomic level.

Non-invasive and reliable assessment of compartment elasticity by pressure related ultrasound: An in-vitro study.

PURPOSE: The development of acute compartment syndrome is a serious threat to trauma patients. The clinical assessment alone is not reliable enough to determine the need for fasciotomy in many cases. The Physician´s assessment of the elasticity of the muscle compartment might be particularly important to objectively evaluate the pressure in this enclosed space. The purpose of this study was to determine the observer´s reproducibility, of compartment elasticity measurements by a novel ultrasonic approach. METHODS: Increasing intra-compartmental pressures (ICP) were simulated in a water filled in-vitro model. Pressure related ultrasound was used to determine the relative elasticity (RE) of soft tissue compartments. A pressure transducing probe head was combined with the ultrasonic probe to obtain cross section views of the simulated compartment and to detect the amount of applied pressure by the observer. In this model, the compartment depth without compression (P0) was set to be 100%. Changes of the compartment depth due to a probe pressure of 80 mmHg (P80) were correlated to P0 and an elasticity quotient as a value for RE (%) was calculated. Twelve blinded observers performed measurements for RE determination (%) under three pressure conditions. Reproducibility was calculated using intraclass correlation coefficient (ICC). RESULTS: Measurements (n = 432) revealed that the RE (%) in the control group was 17,06% (SD+/-2,13), whereas the RE of the group ICP30 significantly decreased to 12,66% (SD+/- 1,19) (p<0,001). The ICP50 group revealed a further significant decrease to 8,43% (SD+/- 0,67) (p<0,001). Repeated measurement of RE and ICP showed a high level of correlation (spearman correlation coefficient: roh=0,922). A RE <14% resulted in a sensitivity of 96% and a specificity of 90,3% for diagnosis of an ICP >30 mmHg. ICCinter was 0,986; 95%, CI: 0,977-0,992 (p<0,001). DISCUSSION: The presented ultrasound-based approach reliably assesses the elasticity in a simulated compartment model. In this pioneer study investigating the inter- and intra-observer reproducibility, this method of measurement appears to be of low cost in addition to being an easy and secure approach that may have the potential to substitute invasive measurement. Further investigations are required to improve its feasibility and to confirm the reliability under clinical conditions.

Convergent Total Synthesis of the Siderophore Piscibactin as Its Ga3+ Complex.

The siderophore piscibactin is a key virulence factor involved in the iron uptake of pathogenic bacteria Photobacterium damselae subsp. piscicida and Vibrio anguillarum, responsible for the fish diseases photobacterioisis (pasteurellosis) and vibriosis, respectively. A convergent total synthesis of its Ga3+ complex using l-/d-cysteine as chiral agents and Meldrum's acid is described. A Staudinger reduction/Aza-Wittig process in the synthesis of the acid-sensitive ß-hydroxy-2,4-disubstituted thiazoline moiety and the convenient protecting groups was a key step in this synthesis.

The use of a bed with an insulating system of electromagnetic fields improves immune function, redox and inflammatory states, and decrease the rate of aging.

BACKGROUND: The immune system, as a homeostatic system, is an excellent marker of health and has also been proposed as an indicator of the rate of aging. The base of the age-related changes in the immune system, "immunosenescence", is oxidative-inflammatory stress. Studies have shown that long-term exposure to electromagnetic fields (EMFs) produced by technology causes inhibitory effects on the immune response and increases oxidation. The aim of the present study was to investigate the effects of resting on an EMF-insulated system on several immune functions, the oxidative-inflammatory state and subsequently the rate of aging (biological age). METHODS: Several immune functions, in peripheral blood neutrophils and mononuclear cells, of 31 volunteers were analyzed before and after 2 months of using a bed with the patented HOGO system, which insulated participants against EMFs. Several oxidative and inflammatory parameters, in whole blood cells, were also studied. The biological age was calculated using a mathematical formula, which was based on several immune function parameters. A placebo group of 11 people using beds without that property were used as a control. RESULTS: The results showed a significant improvement of immune functions and antioxidant and anti-inflammatory defenses after using the HOGO system for 2 months. In addition, a decrease in oxidants and pro-inflammatory compounds, a lowering of oxidative damage in lipids and in DNA as well as a reduction of calculated biological age was also observed. The placebo group did not show any changes. CONCLUSIONS: In conclusion, 2 months of resting on a bed insulated from EMFs demonstrates improvement in immune function, oxidative-inflammatory state and biological age.

Impact of bariatric surgery on subclinical atherosclerosis in patients with morbid obesity.

BACKGROUND: The main cause of death in obese individuals is cardiovascular disease precipitated by atherosclerosis. Endothelial dysfunction and inflammation are considered early events in the development of the disease. OBJECTIVES: The aim of this study was to identify biomarkers of subclinical atherosclerosis in patients with morbid obesity by comparing clinical, vascular, and biochemical parameters indicative of endothelial dysfunction in patients with and without atheromatous plaque and monitoring changes after bariatric surgery. SETTINGS: Multicenter collaboration between Biochemistry and Biomedicine Department in Barcelona University and University Hospital Arnau de Vilanova in Lleida. METHODS: Plasma samples from 66 patients with morbid obesity were obtained before bariatric surgery and at 6 and 12 months after. Patients were divided into 2 groups based on the presence of atheromatous plaque. We used contrast-enhanced carotid ultrasound, enzyme-linked immunosorbent assay, Griess, and EndoPAT-2000 methods. RESULTS: Patients with plaque showed the worst profile of cardiovascular risk factors. Carotid intima-media thickness and plasminogen activator inhibitor-1 were higher in plaque group (P < .0001). After bariatric surgery, vasa vasorum, oxidized low-density lipoprotein, and plasminogen activator inhibitor-1 decreased (P < .0001 in all cases). CONCLUSIONS: Obesity promotes atherogenesis, leading to vascular endothelial damage. Bariatric surgery reduces cardiovascular risk and the prognosis is better for patients without plaque. The increase in plasminogen activator inhibitor-1, carotid intima-media thickness, and vasa vasorum proliferation might be the first alterations in the atheromatous process in obesity and could serve as good biomarkers of subclinical atherosclerosis.

The ratio of prematurely aging to non-prematurely aging mice cohabiting, conditions their behavior, immunity and lifespan.

Adult prematurely aging mice (PAM) show behavioral deterioration, premature immunosenescence and increased oxidative stress, impairments that are associated with their shorter lifespan, compared to the corresponding exceptional non-prematurely aging mice (ENPAM). When PAM live in a predominantly ENPAM environment (2/5, respectively) they exhibit an improvement of immunity and redox state in their spleen and thymus leukocytes, and an increased lifespan. Nevertheless, it is unknown if other PAM/ENPAM ratios could affect behavioral and peritoneal leukocyte functions of PAM and change their lifespan. ENPAM and PAM were divided into the following groups: C-ENPAM (8 ENPAM in the cage); C-PAM (8 PAM in the cage); ENPAM>50% and PAM<50% (5 ENPAM/2 PAM in each cage); ENPAM = 50% and PAM = 50% (4 ENPAM/4 PAM in each cage), and PAM>50% and ENPAM<50% (5 PAM/2 ENPAM in each cage). After two months, mice were submitted to a battery of behavioral tests. Several functions and oxidative stress parameters were then assessed in their peritoneal leukocytes. Animals were maintained in these conditions to analyze their lifespan. The results showed that PAM>50%, PAM = 50% and PAM<50% exhibited better behavioral responses, immunity and redox states in their peritoneal leukocytes than C-PAM. This improvement was higher when the number of ENPAM in the cage was increased, with most of the parameters in PAM<50% reaching similar values to those in C-ENPAM, and an increased lifespan. However, ENPAM that cohabited with PAM showed, in general, an impairment of parameters studied. In conclusion, the PAM/ENPAM cohabitation ratio is relevant to behavior and immunity.

Biocompatible iron(iii) carboxylate metal-organic frameworks as promising RNA nanocarriers.

Despite the great interest in RNA therapeutics, the development of a successful gene delivery process is still a major challenge. We propose an efficient nucleic acid entrapment into the mesopores of biocompatible nanoscaled metal-organic frameworks. Their rapid cellular uptake together with RNA protection and release led to a relevant in vitro gene activity.

Effect of forage type in the ovine diet on the nutritional profile of sheep milk cheese fat.

The high nutritional value of sheep milk can be advantageous in the manufacture of cheese, and fat plays an important role in sheep cheese properties. The aim of this study was to investigate the effect of feeding common hay or silage diets used in commercial farms on the nutritional value of sheep cheese fat. We also monitored the effect of cheese ripening period on the fatty acid profile. Cheeses were produced from milk of sheep fed hay and silage diets from 8 farms, on 4 separate occasions (February, May, August, and November) over a 1-yr period. Eighty-four individual fatty acids were determined and identified by gas chromatography. Ripening time (100 and 180 d) significantly reduced moisture, acidity, and water activity of cheeses but did not affect the fatty acid content. However, hay feeding, compared with silage feeding, led to cheeses with 1.5- and 1.3-fold higher contents of vaccenic acid and conjugated linoleic acid, without detrimental changes in saturated and n-3 (omega-3) fatty acid composition. Hay forages could be a low-cost alternative for producing cheese with a fatty acid profile suitable for human health, which is an aspect of great interest to the food industry.

Non-invasive measurement of muscle compartment elasticity in lower limbs to determine acute compartment syndrome: Clinical results with pressure related ultrasound.

PURPOSE: Close monitoring of patients at risk to develop an acute compartment syndrome (ACS) is well known to be essential. There is a relevant risk that clinical assessment alone is not reliable enough. Reliable assessment of the elasticity of the muscle compartment might represent a helpful tool to assess the pressure in this enclosed space. Therefore, the purpose of this study was to determine the feasibility of muscle elasticity measurements by a non-invasive device. METHODS: In a prospective study, patients with elevated intra-compartmental pressure (ICP) were included. An ultrasound-based measurement approach was used to determine the relative elasticity (RE) of both, the affected and unaffected limb. A pressure transducing ultrasonic probe head was combined with the probe to obtain cross section views of the anterior tibial compartment and to detect the observer´s amount of pressure applied on the limb surface. The compartment depth without compression (P0) corresponds to 100%. The difference to the compartment depth with a probe pressure of 80mmHg (P80) on the limb (delta) related to P0 resulted in a value of relative elasticity (%). These values were compared with the invasive needle measurement (mmHg) regarding their intra-individual difference and correlation of the compartmental pressure. RESULTS: In six trauma patients the relative elasticity in their paired limbs showed a significant difference. The RE in the healthy compartments revealed a level of 17.95% (SD+/-5,4), whereas the RE of the affected limbs significantly decreased to a mean of 5,14% (SD+/-2,1) (p < 0,0001). The average values of the repetitively measured RE and the ICP showed a high level of correlation (spearman correlation coefficient: roh = 0,929). The RE less than 10,5% of the anterior tibial compartment had a sensitivity of 95,8% and a specificity of 87,5% to an appropriate diagnosis of ACS. DISCUSSION: The presented study appears to represent a promising approach to reliably assess the pressure in a muscle compartment. In this first clinical study, our measurement method represents a low cost, easy and secure approach that has the potential to substitute invasive measurement. Further investigations and development in lager cohorts are required to improve its practicality and to confirm the reliability.