Asteroid impact: the potential of astrocytes to modulate human neural networks within organoids.

Astrocytes are a vital cellular component of the central nervous system that impact neuronal function in both healthy and pathological states. This includes intercellular signals to neurons and non-neuronal cells during development, maturation, and aging that can modulate neural network formation, plasticity, and maintenance. Recently, human pluripotent stem cell-derived neural aggregate cultures, known as neurospheres or organoids, have emerged as improved experimental platforms for basic and pre-clinical neuroscience compared to traditional approaches. Here, we summarize the potential capability of using organoids to further understand the mechanistic role of astrocytes upon neural networks, including the production of extracellular matrix components and reactive signaling cues. Additionally, we discuss the application of organoid models to investigate the astrocyte-dependent aspects of neuropathological diseases and to test astrocyte-inspired technologies. We examine the shortcomings of organoid-based experimental platforms and plausible improvements made possible by cutting-edge neuroengineering technologies. These advancements are expected to enable the development of improved diagnostic strategies and high-throughput translational applications regarding neuroregeneration.

[Profile of drug use in adolescents. Protective factors]. / Perfil de consumo de drogas en adolescentes. Factores protectores.

OBJECTIVE: To determine the patterns of drug use in an adolescent population and to analyse the role of personal and social protective factors in alcohol consumption. MATERIAL AND METHODS: A descriptive cross-sectional study was carried out in five secondary schools in the city of Cuenca (Spain) in the period 2015-2016. The groups were randomly selected (3rd - 4th GCSE and 1st - 2nd GCE), with a total of 844 students giving their consent. A self-administered questionnaire was used, which included sociodemographic variables, consumption data, CD-RISC 10 scale to evaluate resilience, and KIDSCREEN-52 questionnaire to measure individual and social aspects associated with health-related quality of life in adolescents. Descriptive bivariate and multivariate analyses were performed. RESULTS: Just over half (55.7%) of the pupils selected were girls, and the mean age was 16.3±1.01 years. The pupils began consumption when they became 13-14 years old. The percentages of habitual consumption were 70.9% for alcohol, 26.4% for tobacco, and 14.2% for cannabis. Multiple drug use was also found in 35%. The regression model for alcohol showed that non-consumers showed better values in emotional moods, self-perception, relationships with their parents, and their school environment. CONCLUSIONS: Adolescents start using drugs, especially cannabis, at an earlier age. Availability and the perception of low-risk make alcohol the most widespread drug. Actions aimed at fostering emotional well-being and family support provides security for adolescents, as well as the resources that help them overcome the pressures of the group.

Anogenital distance and reproductive parameters in young men.

The purpose of this study was to assess the relationship between anogenital distance (AGD) measures and semen quality and serum reproductive hormone levels in Caucasian young men from southern Spain. Two variants of AGD [from the anus to the posterior base of the scrotum (AGD(AS)) and to the cephalad insertion of the penis (AGD(AP))] were assessed in 215 university students. Semen parameters (semen volume, sperm concentration, total sperm counts, motility and morphology) and serum reproductive hormones (follicle stimulating hormone, luteinising hormone, inhibin B, testosterone, calculated free testosterone, oestradiol and sex hormone-binding globulin) were also determined. Associations between AGD measures and the semen quality and reproductive hormone levels were tested using multiple regression analyses. Overall, median sperm concentration was 44.0 × 10(6) ml(-1) (5th-95th percentiles: 8.9-129 × 10(6 ) ml(-1)), median total sperm count was 121 × 10(6) (18.0-400 × 10(6)), and mean (SD) testosterone level was 21.7 nmol/l (6.9). Mean (SD) AGD(AS) and AGD(AP) measures were 48.3 mm (11.6) and 128 mm (12.0) respectively. In the multivariable analysis, AGD measures were not associated with any semen parameters or any of the reproductive hormone levels, which is in contrast to results of studies of US young men or infertile men. Further research is warranted to confirm these findings.

Acute phase protein concentrations in retired racing Greyhounds.

BACKGROUND: Retired racing Greyhounds are popular as pets. Greyhounds have several differences in physiological values compared with other breeds, including lower serum alpha- and beta-globulin concentrations. We hypothesized that lower acute phase protein (APP) concentrations could contribute to lower alpha- and beta-globulin concentrations in this breed. OBJECTIVES: The purpose of this study was to compare serum concentrations of several APPs in Greyhounds with those of other dog breeds. METHODS: We measured the serum concentrations of C-reactive protein (CRP), haptoglobin (Hp), acid-soluble glycoprotein (ASG), ceruloplasmin (CP), and serum amyloid A (SAA) in 15 clinically healthy retired racing Greyhounds and 11 age- and gender-matched healthy nonGreyhound controls using previously validated methods. Results were compared by Student's t-tests. RESULTS: The concentration of Hp by both colorimetric and immunoturbidimetric methods was significantly lower in Greyhounds than in nonGreyhound dogs (P=.0009 and .019, respectively). The concentration of ASG was also significantly (P=.007) lower in Greyhounds, but CRP and CP concentrations were not significantly different between groups. SAA concentration was below the detection limit of the method in all dogs. CONCLUSIONS: The low serum concentrations of Hp and ASG should be taken into consideration when interpreting APP results in Greyhounds. Because both Hp and some ASG migrate in the alpha-globulin fraction, these results may explain the low alpha-globulin concentrations in Greyhounds.

C-reactive protein measurements in meat juice of pigs.

A time-resolved immunofluorometric assay was evaluated for measurement of C-reactive protein in meat juice from diaphragmatic muscle collected from slaughtered pigs. Analytical and clinical validation of the method was performed by using meat juice samples, obtained by freezing and thawing muscle pieces. The intra- and inter-assay coefficients of variation ranged from 2.2-5.8% to 7.9-14.3%, respectively. The limit of detection was 0.00038 microg/ml. The method measured the CRP concentrations in a linear manner with a good accuracy (r=0.99). CRP concentrations in serum were highly correlated with those in diaphragmatic meat juice (r=0.90; p<0.001). CRP concentrations were significantly higher in clinically affected pigs compared to non-diseased pigs. The assay described here provides a sensitive method for measuring CRP concentrations in meat juice, which can represent a suitable alternative to serum or blood samples and simplifies the process of sampling collection at slaughter.

Randomized trial of weight-loss-diets for young adults varying in fish and fish oil content.

OBJECTIVE: To investigate the effect of including seafood and fish oils, as part of an energy-restricted diet, on weight loss in young overweight adults. DESIGN: Randomized controlled trial of energy-restricted diet varying in fish and fish oil content was followed for 8 weeks. Subjects were randomized to one of four groups: (1) control (sunflower oil capsules, no seafood); (2) lean fish (3 x 150 g portions of cod/week); (3) fatty fish (3 x 150 g portions of salmon/week); (4) fish oil (DHA/EPA capsules, no seafood). The macronutrient composition of the diets was similar between the groups and the capsule groups, were single-blinded. SUBJECTS: A total of 324 men and women aged 20-40 years, BMI 27.5-32.5 kg/m(2) from Iceland, Spain and Ireland. MEASUREMENTS: Anthropometric data were collected at baseline, midpoint and endpoint. Confounding factors were accounted for, with linear models, for repeated measures with two-way interactions. The most important interactions for weight loss were (diet x energy intake), (gender x diet) and (gender x initial-weight). RESULTS: An average man in the study (95 kg at baseline receiving 1600 kcal/day) was estimated to lose 3.55 kg (95% CI, 3.14-3.97) (1); 4.35 kg (95% CI, 3.94-4.75) (2); 4.50 kg (95% CI, 4.13-4.87) (3) and 4.96 kg (95% CI, 4.53-5.40) on diet (4) in 4 weeks, from baseline to midpoint. The weight-loss from midpoint to endpoint was 0.45 (0.41-0.49) times the observed weight loss from baseline to midpoint. The diets did not differ in their effect on weight loss in women. Changes in measures of body composition were in line with changes in body weight. CONCLUSION: In young, overweight men, the inclusion of either lean or fatty fish, or fish oil as part of an energy-restricted diet resulted in approximately 1 kg more weight loss after 4 weeks, than did a similar diet without seafood or supplement of marine origin. The addition of seafood to a nutritionally balanced energy-restricted diet may boost weight loss.

Influencia de los cambios en la dieta sobre el perfil lipídico y los niveles de apoproteinas A-1 y B / Influence of changes in the diet on the lipid profile and levels of apolipoproteins A-1 and B

Objetivos. El objetivo del presente trabajo es conocer la influencia que las modificaciones importantes en la dieta tipo mediterráneo, propia de nuestro medio, pueden tener sobre los lípidos plasmáticos y niveles de lipoproteínas. Material y métodos.- Se han de diferenciar los sujetos en función del sexo y se estudiará la influencia de las dietas especialmente abundantes en vegetales (dietas vegetarianas), en productos ricos en grasas saturadas y colesterol (dieta rica en carne y productos de origen animal) o abundantes en ácidos grasos de la serie n-3 (dieta rica en pescados y otros productos marinos). Resultados y conclusiones.- Los sujetos ovolactovegetarianos no muestran diferencias en cuanto a perfil lipídico, niveles de apo A1 y B o índices de riesgo con respecto a los sujetos que ingieren una dieta convencional de tipo mediterráneo (dieta mixta variada), mientras que los sujetos lactovegetarianos presentan niveles más bajos tanto de apo B como de apo A1 , por lo que su índice de riesgo apo B/apo A1 no es mucho más favorable. Los sujetos que ingieren una dieta abundante en carne y productos derivados, presentan niveles más altos de apo B, colesterol total y triglicéridos, así como peores índices de riesgo. Por último los sujetos con una dieta abundante rica en pescado apenas si modifican el perfil lipídico o niveles de apo A1 o apo B en relación con los sujetos que siguen una dieta mixta (AU)

Aim The aim of the study was to know the possible influence that important changes in the Mediterranean diet of our environment have on plasma lipid and lipoproteins levels. Material and methods.- Subjects were divided according to sex, and the influence of diets specially rich in vegetables (vegetarian diets), saturated fats and cholesterol (diets rich in meat and animal product), or n-3 fatty acids (diets rich in fish and other seafood products) was studied. Results. Conclusions.- According to our results, no differences were found in the lipid profile, apo A1 and B levels or risk indexes between ovolactovegetarians and subjects consuming the traditional Mediterranean diet (mixed diet); whereas lactovegetarians presented lower levels of apo B and apo A1 so that their risk index apo B/apo A1 was not much more favourable. Subjects consuming a diet rich in meat and derived products showed higher levels of apo B, total cholesterol and triglycerides, as well as, risk indexes less favourable. Finally, subjects following an affluent diet rich in fish did not almost modify their lipid profile or levels of apo A1, or apo B compared to those consuming a mixed diet (AU)

A time-resolved immunofluorometric assay for porcine C-reactive protein quantification in whole blood.

A time-resolved immunofluorometric assay (TR-IFMA) for C-reactive protein (CRP) determination in whole blood of pigs was developed and validated. CRP was isolated from porcine acute-phase serum by affinity chromatography on agarose, coupled with phosphorylethanolamine and polyclonal antibodies to porcine CRP were purified from antiserum raised in sheep immunized with porcine CRP. Intra- and inter-assay coefficients of variation (CVs) were in the range 3.13-7.19% and 7.06-15.66%, respectively, showing good precision. The assay measured the CRP values in a proportional and linear manner (r=0.99); additionally, CRP concentrations measured in whole blood by the present TR-IFMA and in serum by an established immunoturbidimetric assay were highly correlated (R(2)=0.97). The limit of detection of the method was 0.0028 mg/L. Significantly lower CRP concentrations were observed after 7 days of sample storage at 4 degrees C. The injection of turpentine oil caused a significant increase in CRP concentrations and significantly higher CRP concentrations were observed in pigs with pathological processes compared to healthy animals.

Analytical validation of commercially available methods for acute phase proteins quantification in pigs.

The aim of this study was to validate commercially available methods for porcine haptoglobin (Hp), C-reactive protein (CRP), serum amyloid A (SAA) and major acute phase protein (Pig-MAP) determinations. Intra and inter assay coefficients of variation (CVs) were lower than 20% in all cases with exception of inter assay CVs for CRP and Pig-MAP assays with samples of low acute phase proteins concentration, and for SAA assay at any acute phase proteins concentration. All methods showed good linearity and detection limits were low enough to detect APPs levels in healthy animals. Hp and SAA were very affected by haemolysis. Lipaemia influenced mainly on SAA determination. Over 15-fold increase was observed in CRP and SAA concentrations after artificially induced inflammation by a single subcutaneous dose of turpentine, whereas Hp and Pig-MAP increased less than 5-fold.

Porcine acute phase protein concentrations in different diseases in field conditions.

Five acute phase proteins (APPs) [C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), pig-MAP and albumin] were measured in pigs with naturally occurring infections by porcine reproductive and respiratory syndrome virus (PRRSV), Aujeszky's disease virus (ADV), porcine circovirus type 2 (PCV2) and Mycoplasma hyopneumoniae, and in animals with tail and ear bites, arthritis and other acute inflammatory processes. Healthy specific pathogen-free (SPF) pigs were used as controls. In PRRSV-infected pigs, all APPs with the exception of pig-MAP exhibited significant changes compared with controls. In animals affected with ADV only Hp presented changes of statistical significance, whereas pigs with PCV2 showed marked modifications in all APPs tested. Animals affected with Mycoplasmosis showed concentrations of all positive APPs significantly above levels obtained in SPF pigs, though albumin concentrations did not differ from controls. Finally, all APPs studied showed substantial changes in pigs with acute inflammation. The results indicated that an acute phase response was developed in the different diseases studied, this response being higher in animals with clinical signs and concurrent bacterial processes. Haptoglobin would be the APP that better reflects pathological states; however, to get more complete and valuable information it might be advisable to perform APPs profiles including another APP, such as CRP or SAA.

Reducción en el consumo del tabaco como paso previo a la cesación. Concepto. Razones que lo explican / Reduction in consumption of tobacco as previous step to stopping smoking. Concept. Reasons that explain it

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Concentrations of C-reactive protein in effusions in dogs.

The concentration of C-reactive protein (CRP) was measured in effusions from 50 dogs to assess the potential for measuring this protein to differentiate body cavity fluids. The effusions were classified as either transudates, modified transudates or exudates according to their total protein concentration, total nucleated cell count, cytological findings and aetiology, and the concentration of CRP was determined by a time-resolved immunofluorometric assay. There were significant differences between the concentrations of CRP in the three types of effusion; the highest concentrations were observed in the exudates (4.47 to 54.59 microg/ml), the lowest were in the transudates (0.0094 to 7.87 microg/ml), and the modified transudates contained intermediate concentrations of CRP (0.045 to 10.78 microg/ml). A cut-off value of 4 microg/ml had a sensitivity of 100 per cent and a specificity of 94.4 per cent for differentiating transudates from exudates, and a cut-off value of 11 microg/ml had a sensitivity of 88.2 per cent and a specificity of 100 per cent for distinguishing modified transudates from exudates. However, a cut-off value of 1 microg/ml had a lower sensitivity (80 per cent) and an unacceptably low specificity (66.7 per cent) for differentiating transudates from modified transudates.

Analytical and clinical validation of a time-resolved immunofluorometric assay (TR-IFMA) for canine C-reactive protein in serum.

A time-resolved immunofluorometric assay (TR-IFMA) was developed for the determination of C-reactive protein (CRP) in canine serum. CRP was isolated from canine acute-phase serum by affinity chromatography on agarose coupled with phosphorylethanolamine. This isolated dog CRP was used as standard to calibrate the assay. Intra-assay and inter-assay coefficients of variation were in the ranges 5.3-7.1% and 4.8-13.3%, respectively. Accuracy, evaluated by adding 2 and 10 microg/ml of CRP to serum samples, provided recoveries of 99.9% and 106.8%. High correlation was found between CRP measurements by TR-IFMA and a by commercial enzyme-linked immunosorbent assay (R2 = 0.98). The limit of detection for the TR-IFMA method was 0.000067 microg/ml and the measurement of CRP in serial dilutions of acute-phase dog sera generated curves with the same slope as the one constructed with purified CRP. The TR-IFMA provides a precise, accurate and highly sensitive assay for CRP determination in dog samples. CRP levels in dogs with different diseases ranged between 10.2 and 210.7 microg/ml and were significantly higher than those observed in healthy dogs (< 7.1 microg/ml).

Different dietary strategies for weight loss in obesity: role of energy and macronutrient content.

Obesity is a chronic disorder caused by an imbalance of the energy metabolism with high associated burdens. Therefore, huge efforts are being currently devoted in studying new types of hypoenergetic diets and their composition, in order to characterise more specific, long-lasting and safe slimming protocols. A number of investigations are trying to determine the specific influence of the macronutrient distribution in energy-restricted diets on the management of excessive body weight. In this context, very-low-energy diets supplying between 1670 and 3350 kJ (400 and 800 kcal)/d have been beneficial in short-term treatments causing a weight loss of 300-500 g/d. Such strategies place more emphasis on energy restriction than on the macronutrient composition of the diet prescription. Weight loss produced by either low-carbohydrate or low-fat moderately energy-restricted diets ranges from 0.5 to 1.0 kg/week, while diets with high or moderately high protein content have also been applied in weight-reducing programmes by inducing losses of 0.2-0.4 kg/week. Other factors that determine weight loss by dieting are sex, age, initial body weight, race, genetics, regional fat deposition, etc, which must be taken into account to explain the variability in the outcomes of different low-energy diets. Therefore, more research is needed about the impact of diets with different fuel substrates and foods on the characteristics of the weight-loss process.

Postprandial insulin response and mitochondrial oxidation in obese men nutritionally treated to lose weight.

Obesity, hyperglycemia, and insulin resistance have been associated to an oxidative mitochondrial dysfunction. The aim of this research was to evaluate the relation between carbohydrate metabolism and mitochondrial oxidation, as affected by the weight status and the weight loss induced by a calorie-restricted diet. Lean control men (BMI<25 kg/m2, n = 6) and obese men (BMI>30 kg/m2, n = 14), who were characterized as insulin resistant (n = 6) or insulin sensitive (n = 8) based on HOMA index values, participated in the trial. Plasma insulin levels and mitochondrial oxidation estimated by the 2-keto(1-13C)isocaproate breath test, were measured after ingestion of a test meal during 3 h. Obese subjects repeated the breath test protocol after a 10-week caloric restriction diet to lose weight. Postprandial insulin secretion tended to be marginally higher (P = 0.059) in both obese groups than in controls, while the rate of postprandial mitochondrial oxidation was markedly decreased (P = 0.019) in the obese subjects as compared with lean individuals. The nutritionally induced weight loss produced a rise in the postprandial oxidative process in volunteers initially considered as insulin resistant (P = 0.036), while no statistical differences in the insulin-sensitive obese (P = 0.241) were found. Interestingly, the percentage of oxidized tracer was inversely related to postprandial insulin secretion (r = -0.56; P = 0.001). In conclusion, these results support the hypothetized relation between carbohydrate metabolism and mitochondrial oxidation at a postprandial state in obese subjects, raising interest about mitochondria stimulation as a target in the therapy of obesity.

Inflammation and conjugated linoleic acid: mechanisms of action and implications for human health.

Data from a number of studies and trials have shown that different conjugated linoleic acids (CLA's) may produce beneficial effects on cancer, atherosclerosis, hypertension, diabetes and changes in body composition. Despite the increasing knowledge about CLA's implications on health, the mechanism of action of these fatty acids is not completely understood. Moreover, human studies indicate that some of these beneficial effects are considerably less evident than anticipated from mice studies, while the efficacy and safety of dietary supplements containing CLA have been questioned in some intervention trials. Recently, it has been suggested that the anti-carcinogenic and anti-atherosclerosis effects of CLA's stem from its anti-inflammatory properties. Because inflammatory responses are associated with the pathophysiology of many diseases, including obesity and the metabolic syndrome, the investigation in this area is of growing interest in recent years.

[Role of IL-6 and its -174G>C polymorphism in weight management and in the metabolic comorbidities associated with obesity]. / Implicación de la IL-6 y su polimorfismo -174G>C en el control del peso corporal y en las complicaciones metabólicas asociadas a la obesidad.

Obesity and its comorbidities have been associated with a low grade proinflammatory state, in which the adipose tissue seems to be involved. In fact, this tissue produces different proinflammatory cytokines, such as IL-6 and others. High circulating concentrations of IL-6 have been related to high body mass index, to diabetes mellitus type 2, to lipid abnormalities and to high blood pressure. There are some studies, which reported a relationship between IL-6 and energy metabolism, so this cytokine and its -174G>C gene polymorphism could be factors involved in the development of obesity. Different studies have associated the G allele of the IL-6 gene with obesity, with insulin resistance and with different cardiovascular risk factors. However, other published reports have associated the C allele of this gene to these metabolic disturbances and pathologies. This paper reviews recently published evidences about IL-6 and its physiopathological involvement in obesity and comorbidities, with emphasis on the role of the -174G>C polymorphism in the aetiology of these disturbances, in which obesity is a major risk factor.

Daily ingestion of fermented milk containing Lactobacillus casei DN114001 improves innate-defense capacity in healthy middle-aged people.

Different lactic acid bacteria have often been administered as a dietary means to enhance immune system activity. Based on this statement, the aim of the current work was to test the effects of a Lactobacillus casei DN114001 fermented milk consumption on the immune response capacity in middle-age volunteers. Forty-five healthy volunteers, 24 women and 21 men (aged: 51-58 years), were randomized into two groups to receive three cups per day of a L. casei DN114001 (10(8)-10(10) ufc/g) fermented milk (n = 23), or placebo (n = 22), during an 8-week period. Measurements were performed before (day 0), and after the nutritional intervention (day 56). After the trial, no changes in immune cell proportions were detected, but the probiotic-treated group increased oxidative burst capacity of monocytes (probiotic group: p = 0.029; placebo group: p = 0.625), as well as NK cells tumoricidal activity (probiotic group: p = 0.023; placebo group: p = 0.125). Results showed that daily intake of fermented milk containing Lactobacillus casei DN114001 could have a positive effect in modulating the innate immune defense in healthy-middle-age people.

Cortisol and free thyroxine determination by time-resolved fluorometry in canine serum.

Validation for canine serum of 2 commercially available time-resolved fluoroimmunoassays (TR-FIAs) designed for analysis of cortisol and free thyroxine (fT4) in human serum was carried out. Included was the study of interference by hemolysis, lipemia, and bilirubinemia. With the dissociation enhancement lanthanide fluoroimmunoassay kits, the intra-assay coefficient of variation (CV) ranged from 6.4% to 8.7% for cortisol and from 5.3% to 9.8% for fT4; the interassay CVs ranged from 5.8% to 10.8% and from 3.9% to 14.1%, respectively. Accuracy was evaluated by comparing cortisol and fT4 results obtained with TR-FIA and those obtained with a validated enzyme-linked immunosorbent assay (ELISA) and an equilibrium dialysis (ED) assay, respectively. The regression equations obtained were y = 0.57x + 1.18 (r2 = 0.90) for cortisol and y = 0.87x + 0.82 (r2 = 0.93) for fT4. The limits of detection for cortisol and fT4 were 4.84 nmol/L and 2.68 pmol/L, respectively. The results of adrenocorticotropin-stimulation and dexamethasone-suppression tests were similar to those published previously; likewise, serial dilution of a canine serum sample with a high cortisol content demonstrated that the TR-FIA was immunologically specific. Serial dilution of a serum sample with a high fT4 concentration showed a methodologic bias, a dependence on serum binding capacity, which indicates that the results obtained with this method should be interpreted with caution. Finally, hemolysis and lipemia significantly interfered with cortisol and fT4 measurements, whereas bilirubinemia did not affect the results.

Infección por "Mycoplasma pneumoniae" / "Mycoplasma pneumoniae" infection

Presentarnos un caso de neumonía por Mycoplasma pneumoniae en un paciente de seis años de edad. La sospecha diagnóstica se basó en la clínica y en las pruebas de imagen, confirmándose posteriormente con la serología. El propósito de este artículo es destacar que, dentro de la variabilidad de presentación radiológica de la neumonía por micoplasma, existe un patrón radiológico característico que debe orientar el diagnóstico hacia dicha entidad (AU)