Ultralarge Free-Standing Imine-Based Covalent Organic Framework Membranes Fabricated via Compression

Demand continues for processing methods to shape covalent organic frameworks (COFs) into macroscopic objects that are needed for their practical applications. Herein, a simple compression method to prepare large-scale, free-standing homogeneous and porous imine-based COF-membranes with dimensions in the centimeter range and excellent mechanical properties is reported. This method entails the compression of imine-based COF-aerogels, which undergo a morphological change from an elastic to plastic material. The COF-membranes fabricated upon compression show good performances for the separation of gas mixtures of industrial interest, N2/CO2 and CH4/CO2. It is believed that the new procedure paves the way to a broader range of COF-membranes

The K153R Polymorphism in the Myostatin Gene and Muscle Power Phenotypes in Young, Non-Athletic Men

The Lys(K)153Arg(R) polymorphism in exon 2 (rs1805086, 2379 A>G replacement) of the myostatin (MSTN) gene is a candidate to influence skeletal muscle phenotypes. We examined the association between the MSTN K153R polymorphism and ‘explosive’ leg power, assessed during sprint (30 m) and stationary jumping tests [squat (SJ) and counter-movement jumps (CMJ)] in non-athletic young adults (University students) [n = 281 (214 men); age: 21–32 years]. We also genotyped the MSTN exonic variants E164K (rs35781413), I225T, and P198A, yet no subject carried any of these variant MSTN alleles. As for the K153R polymorphism, we found only one woman with the KR genotype; thus, we presented the results only for men. The results of a one-way ANCOVA (with age, weight and height entered as covariates) showed that men with the KR genotype (n = 15) had a worse performance in vertical jumps compared with those with the KK genotype [SJ: vertical displacement of center of gravity (CG) of 35.17±1.42 vs. 39.06±0.39 cm, respectively, P = 0.009; CMJ: vertical displacement of CG of 36.44±1.50 vs. 40.63±0.41 cm, respectively, P = 0.008]. The results persisted after adjusting for multiple comparisons according to Bonferroni. Performance in 30 m sprint tests did however not differ by K153R genotypes. In summary, the MSTN K153R polymorphism is associated with the ability to produce ‘peak’ power during muscle contractions, as assessed with vertical jump tests, in young non-athletic men. Although more research is still needed, this genetic variation is among the numerous candidates to explain, alone or in combination with other polymorphisms, individual variations in muscle phenotypes

‘Smoking Genes’: A Genetic Association Study

Some controversy exists on the specific genetic variants that are associated with nicotine dependence and smoking-related phenotypes. The purpose of this study was to analyse the association of smoking status and smoking-related phenotypes (included nicotine dependence) with 17 candidate genetic variants: CYP2A6*1×2, CYP2A6*2 (1799T>A) [rs1801272], CYP2A6*9 (−48T>G) [rs28399433], CYP2A6*12, CYP2A13*2 (3375C>T) [rs8192789], CYP2A13*3 (7520C>G), CYP2A13*4 (579G>A), CYP2A13*7 (578C>T) [rs72552266], CYP2B6*4 (785A>G), CYP2B6*9 (516G>T), CHRNA3 546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2-ANKK1 2137G>A (Taq1A) [rs1800497], 5HTT LPR, HTR2A −1438A>G [rs6311] and OPRM1 118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms in a cohort of Spanish smokers (cases, N = 126) and ethnically matched never smokers (controls, N = 80). The results showed significant between-group differences for CYP2A6*2 and CYP2A6*12 (both P<0.001). Compared with carriers of variant alleles, the odds ratio (OR) for being a non-smoker in individuals with the wild-type genotype of CYP2A6*12 and DRD2-ANKK1 2137G>A (Taq1A) polymorphisms was 3.60 (95%CI: 1.75, 7.44) and 2.63 (95%CI: 1.41, 4.89) respectively. Compared with the wild-type genotype, the OR for being a non-smoker in carriers of the minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65). We found a significant genotype effect (all P≤0.017) for the following smoking-related phenotypes: (i) cigarettes smoked per day and CYP2A13*3; (ii) pack years smoked and CYP2A6*2, CYP2A6*1×2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A); (iii) nicotine dependence (assessed with the Fagestrom test) and CYP2A6*9. Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms) are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5), serotoninergic (HTR2A), opioid (OPRM1) or cannabinoid receptors (CNR1)

Follow-up in healthy schoolchildren and in adolescents with DOWN syndrome: psycho-environmental and genetic determinants of physical activity and its impact on fitness, cardiovascular diseases, inflammatory biomarkers and mental health; the UP&DOWN Study

[Background] An objective diagnosis of sedentary behaviour as well as of the physical activity and fitness levels in youth and to better understand how lifestyle is associated with cardiovascular disease risk factors and other phenotypes is of clinical and public health interest, and might be informative for developing intervention studies focused on the promotion of physical activity in these population. The aim of this methodological paper is to describe the design and assessment in the UP&DOWN study. [Methods/Design] The UP&DOWN study is a multi-center follow-up design where 2225 Spanish primary and secondary schoolchildren from Cadiz and Madrid, respectively, as well as 110 Spanish adolescents with Down syndrome from Madrid and Toledo were recruited to be assessed. Nine main measurement categories are assessed: i) socio-demographic and early determinants; ii) environmental determinants; iii) physical activity and sedentary behaviour; iv) health-related fitness; v) blood pressure and resting heart rate; vi) mental health; vii) dietary patterns; viii) blood samples; and ix) genetic analysis. During the 3-yr follow-up study, socio-demographic and early determinants, and genetic analysis are only assessed in the first year. Blood sampling is assessed in the first year and the third year (2nd follow-up), and all the other measurements are assessed every year. [Discussion] The findings of the UP&DOWN study may help the Health Information Systems and policy makers to identify the target population for primary prevention and health promotion policies, and to develop and test preventive strategies. Moreover, these data will allow following the trends at population level, as well as to modify/adapt/create new evidence-based physical activity guidelines at national level. The findings will also serve as a scientific platform for interventional studies.This study was supported by the DEP 2010-21662-C04-00 (DEP 2010-21662-C04-01, DEP 2010-21662-C04-02, DEP 2010-21662-C04-03, DEP 2010-21662-C04-04) RYC-2010-05957 grants from the National Plan for Research, Development and Innovation (R + D + i) MICINN

Influence of ACE Gene I/D Polymorphism on Cardiometabolic Risk, Maximal Fat Oxidation, Cardiorespiratory Fitness, Diet and Physical Activity in Young Adults

There is controversy about the relationship between ACE I/D polymorphism and health. Seventy-four healthy adults (n = 28 women; 22.5 +/- 4.2 years) participated in this cross-sectional study aimed at determining the influence of ACE I/D polymorphism, ascertained by polymerase chain reaction, on cardiometabolic risk (i.e., waist circumference, body fat, blood pressure (BP), glucose, triglycerides, and inflammatory markers), maximal fat oxidation (MFO), cardiorespiratory fitness (maximal oxygen uptake), physical activity and diet. Our results showed differences by ACE I/D polymorphism in systolic BP (DD: 116.4 +/- 11.8 mmHg; ID: 116.7 +/- 6.3 mmHg; II: 109.4 +/- 12.3 mmHg, p = 0.035) and body fat (DD: 27.3 +/- 10.8%; ID: 22.6 +/- 9.7%; II: 19.3 +/- 7.1%, p = 0.030). Interestingly, a genotype*sex interaction in relativized MFO by lean mass (p = 0.048) was found. The DD polymorphism had higher MFO values than ID/II polymorphisms in men (8.4 +/- 3.0 vs. 6.5 +/- 2.9 mg/kg/min), while the ID/II polymorphisms showed higher R-MFO values than DD polymorphism in women (6.6 +/- 2.3 vs. 7.6 +/- 2.6 mg/kg/min). In conclusion, ACE I/D polymorphism is apparently associated with adiposity and BP, where a protective effect can be attributed to the II genotype, but not with cardiorespiratory fitness, diet and physical activity. Moreover, our study highlighted that there is a sexual dimorphism in the influence of ACE I/D gene polymorphism on MFO

A Novel, Single Algorithm Approach to Predict Acenocoumarol Dose Based on CYP2C9 and VKORC1 Allele Variants

The identification of CYP2C9 and VKORC1 genes has strongly stimulated the research on pharmacogenetics of coumarins in the last decade. We assessed the combined influence of CYP2C9 *2 and *3, and VKORC1 c.-1639G>A, 497C>G, and 1173C>T variants, on acenocoumarol dosage using a novel algorithm approach, in 193 outpatients who had achieved stable anticoagulation. We constructed an “acenocoumarol-dose genotype score” (AGS, maximum score = 100) based on the number of alleles associated with higher acenocoumarol dosage carried by each subject for each polymorphism. The mean AGS was higher in the high-dose (>28mg/week) compared with the low-dose (<7mg/week) group (mean(SEM) of 84.1±3.4 vs. 62.2±4.8, P = 0.008). An AGS>70 was associated with an increased odds ratio (OR) of requiring high acenocoumarol dosage (OR: 3.347; 95%CI: 1.112–10.075; P = 0.032). In summary, although more research is necessary in other patient cohorts, and this algorithm should be replicated in an independent sample, our data suggest that the AGS algorithm could be used to help discriminating patients requiring high acenocoumarol doses to achieve stable anti-coagulation

Impact of late presentation of HIV infection on short-, mid- and long-term mortality and causes of death in a multicenter national cohort: 2004–2013

SummaryObjectivesTo analyze the impact of late presentation (LP) on overall mortality and causes of death and describe LP trends and risk factors (2004–2013).MethodsCox models and logistic regression were used to analyze data from a nation-wide cohort in Spain. LP is defined as being diagnosed when CD4 < 350 cells/ml or AIDS.ResultsOf 7165 new HIV diagnoses, 46.9% (CI95%:45.7–48.0) were LP, 240 patients died.First-year mortality was the highest (aHRLP.vs.nLP = 10.3[CI95%:5.5–19.3]); between 1 and 4 years post-diagnosis, aHRLP.vs.nLP = 1.9(1.2–3.0); and >4 years, aHRLP.vs.nLP = 1.5(0.7–3.1).First-year's main cause of death was HIV/AIDS (73%); and malignancies among those surviving >4 years (32%). HIV/AIDS-related deaths were more likely in LP (59.2% vs. 25.0%; p < 0.001). LP declined from 55.9% (2004–05) to 39.4% (2012–13), and reduced in 46.1% in men who have sex with men (MSM) and 37.6% in heterosexual men, but increased in 22.6% in heterosexual women.Factors associated with LP: sex (ORMEN.vs.WOMEN = 1.4[1.2–1.7]); age (OR31–40.vs.<30 = 1.6[1.4–1.8], OR41–50.vs.<30 = 2.2[1.8–2.6], OR>50.vs.<30 = 3.6[2.9–4.4]); behavior (ORInjectedDrugUse.vs.MSM = 2.8[2.0–3.8]; ORHeterosexual.vs.MSM = 2.2[1.7–3.0]); education (ORPrimaryEducation.vs.University = 1.5[1.1–2.0], ORLowerSecondary.vs.University = 1.3[1.1–1.5]); and geographical origin (ORSub-Saharan.vs.Spain = 1.6[1.3–2.0], ORLatin-American.vs.Spain = 1.4[1.2–1.8]).ConclusionsLP is associated with higher mortality, especially short-term- and HIV/AIDS-related mortality. Mid-term-, but not long-term mortality, remained also higher in LP than nLP. LP decreased in MSM and heterosexual men, not in heterosexual women. The groups most affected by LP are low educated, non-Spanish and heterosexual women

APICAMPUS, a project on Urban beekeeping developed at the University of Malaga

Urban beekeeping has ourished in the last years, with many institutions interested in creating colonies on their roofs. Bees and other animal pollinators contribute to increase food production, making bees essential for agriculture and plant life, in general. And, as bee populations decline, the need for secondary sources of pollinators for agricultural production grows. The Vice-rectorate of Smart-Campus of the University of Malaga focuses on two fundamen tal aspects: understanding the UMA campus as a Smart City in itself and marking new lines of action at the academic level that will make the UMA an international benchmark in Sustainability. Framed in the program above mentioned, APICAMPUS is a pilot and interdisciplinary project that involves researchers and students belonging to 4 departments of 2 university faculties together with Bee Garden Malaga, a multi-disciplinary environmental company with thematic areas on beekeeping. The project aims to promote the development of beekeeping in urban environments, raising awareness about the importance of the bees as pollinating insects, as well as the use of the beehive products. For the above mentioned, two beehives Langstroth type, were installed at the roof of the Faculty of Science, a traditional wooden one, and another made of polystyrene. The main interest of this project lies in the monitoring of the hives by means of temperature and humidity sensors, electronic scales for weight control, video cameras located inside and outside of them, together with the use of bee-marking systems. Additionally, analysis for characterizing and study the origin and the properties of the beehive products will be carried out, as well as field monitoring to highlight the situation of pollinators at the University Campus of Teatinos. Although the samplings have barely begun, this communication intends to be the offcial presentation of the project APICAMPUS to the scientific community.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Are ‘Endurance’ Alleles ‘Survival’ Alleles? Insights from the ACTN3 R577X Polymorphism

Exercise phenotypes have played a key role for ensuring survival over human evolution. We speculated that some genetic variants that influence exercise phenotypes could be associated with exceptional survival (i.e. reaching ≥100years of age). Owing to its effects on muscle structure/function, a potential candidate is the Arg(R)577Ter(X) polymorphism (rs1815739) in ACTN3, the structural gene encoding the skeletal muscle protein α-actinin-3. We compared the ACTN3 R577X genotype/allele frequencies between the following groups of ethnically-matched (Spanish) individuals: centenarians (cases, n = 64; 57 female; age range: 100–108 years), young healthy controls (n = 283, 67 females, 216 males; 21±2 years), and humans who are at the two end-points of exercise capacity phenotypes, i.e. muscle endurance (50 male professional road cyclists) and muscle power (63 male jumpers/sprinters). Although there were no differences in genotype/allele frequencies between centenarians (RR:28.8%; RX:47.5%; XX:23.7%), and controls (RR:31.8%; RX:49.8%; XX:18.4%) or endurance athletes (RR:28.0%; RX:46%; XX:26.0%), we observed a significantly higher frequency of the X allele (P = 0.019) and XX genotype (P = 0.011) in centenarians compared with power athletes (RR:47.6%; RX:36.5%;XX:15.9%). Notably, the frequency of the null XX (α-actinin-3 deficient) genotype in centenarians was the highest ever reported in non-athletic Caucasian populations. In conclusion, despite there were no significant differences with the younger, control population, overall the ACTN3 genotype of centenarians resembles that of world-class elite endurance athletes and differs from that of elite power athletes. Our preliminary data would suggest a certain ‘survival’ advantage brought about by α-actinin-3 deficiency and the ‘endurance’/oxidative muscle phenotype that is commonly associated with this condition

Golimumab in refractory uveitis related to spondyloarthritis. Multicenter study of 15 patients

Objective: To assess the efficacy of golimumab (GLM) in refractory uveitis associated to spondyloarthritis (SpA). Methods: Multicenter study of SpA-related uveitis refractory to at least one immunosuppressive drug. The main outcome variables were degree of anterior and posterior chamber inflammation, visual acuity, and macular thickness. Results: Fifteen patients (13 men/2 women; 18 affected eyes; mean age 39±6 years) were evaluated. The underlying SpA subtypes were ankylosing spondylitis (n=8), psoriatic arthritis (n=6) and non-radiographic axial SpA (n=1). The ocular involvement patterns were recurrent anterior uveitis in 8 patients and chronic anterior uveitis in 7. Before GLM they have received methotrexate (n=13), sulfasalazine (n=6), pulses of methylprednisolone (n=4), azathioprine (n=3), leflunomide (n=2) and cyclosporine (n=1). Ten of them had also been treated with TNF-? blockers; etanercept (n=7), adalimumab (n=7), infliximab (n=6), and certolizumab (n=1). GLM was given at the standard dose (50 mg/sc/monthly) as monotherapy (n=7) or in combination with conventional immunosuppressive drugs (n=8), mainly methotrexate. Most patients had rapid and progressive improvement of intraocular inflammation parameters. The median number of cells in the anterior chamber at 2 years (0 [0-0]) was significantly reduced compared to baseline findings (1 [0-3]); p=0.04). The mean best corrected visual acuity value also improved (0.84±0.3 at 2 years versus 0.62±0.3 at baseline; p=0.03). Only minor side effects were observed after a mean follow-up of 23±7 months. Conclusions: Our results indicate that GLM may be a useful therapeutic option in refractory SpA-related uveitis