Maturation of human pluripotent stem cell derived cardiomyocytes in vitro and in vivo.

Human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) represent an inexhaustible cell source for in vitro disease modeling, drug discovery and toxicity screening, and potential therapeutic applications. However, currently available differentiation protocols yield populations of hPSC-CMs with an immature phenotype similar to cardiomyocytes in the early fetal heart. In this review, we consider the developmental processes and signaling cues involved in normal human cardiac maturation, as well as how these insights might be applied to the specific maturation of hPSC-CMs. We summarize the state-of-the-art and relative merits of reported hPSC-CM maturation strategies including prolonged duration in culture, metabolic manipulation, treatment with soluble or substrate-based cues, and tissue engineering approaches. Finally, we review the evidence that hPSC-CMs mature after implantation in injured hearts as such in vivo remodeling will likely affect the safety and efficacy of a potential hPSC-based cardiac therapy.

In Vitro Matured Human Pluripotent Stem Cell-Derived Cardiomyocytes Form Grafts With Enhanced Structure and Function in Injured Hearts.

BACKGROUND: Human pluripotent stem cell (hPSC)-derived cardiomyocytes (hPSC-CMs) have tremendous promise for application in cardiac regeneration, but their translational potential is limited by an immature phenotype. We hypothesized that large-scale manufacturing of mature hPSC-CMs could be achieved through culture on polydimethylsiloxane (PDMS)-lined roller bottles and that the transplantation of these cells would mediate better structural and functional outcomes than with conventional immature hPSC-CM populations. METHODS: We comprehensively phenotyped hPSC-CMs after in vitro maturation for 20 and 40 days on either PDMS or standard tissue culture plastic substrates. All hPSC-CMs were generated from a transgenic hPSC line that stably expressed a voltage-sensitive fluorescent reporter to facilitate in vitro and in vivo electrophysiological studies, and cardiomyocyte populations were also analyzed in vitro by immunocytochemistry, ultrastructure and fluorescent calcium imaging, and bulk and single-cell transcriptomics. We next compared outcomes after the transplantation of these populations into a guinea pig model of myocardial infarction using end points including histology, optical mapping of graft- and host-derived action potentials, echocardiography, and telemetric electrocardiographic monitoring. RESULTS: We demonstrated the economic generation of >1×108 mature hPSC-CMs per PDMS-lined roller bottle. Compared with their counterparts generated on tissue culture plastic substrates, PDMS-matured hPSC-CMs exhibited increased cardiac gene expression and more mature structural and functional properties in vitro. More important, intracardiac grafts formed with PDMS-matured myocytes showed greatly enhanced structure and alignment, better host-graft electromechanical integration, less proarrhythmic behavior, and greater beneficial effects on contractile function. CONCLUSIONS: We describe practical methods for the scaled generation of mature hPSC-CMs and provide the first evidence that the transplantation of more mature cardiomyocytes yields better outcomes in vivo.

Evolution After Anti-TNF Discontinuation in Patients With Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study.

OBJECTIVES: The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed. METHODS: This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included. RESULTS: A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn's disease and ulcerative colitis patients, respectively. In both Crohn's disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn's disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe. CONCLUSIONS: The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.

Quantum dot interactions and flow effects in angiogenic zebrafish (Danio rerio) vessels and human endothelial cells.

Nanoparticle (NP) interactions with biological tissues are affected by the size, shape and surface chemistry of the NPs. Here we use in vivo (zebrafish) and in vitro (HUVEC) models to investigate association of quantum dots (QDs) with endothelial cells and the effect of fluid flow. After injection into the developing zebrafish, circulating QDs associate with endothelium and penetrate surrounding tissue parenchyma over time. Amino-functionalized QDs cluster, interact with cells, and clear more rapidly than carboxy-functionalized QDs in vivo, highlighting charge influences. QDs show stronger accumulation in slow-flowing, small caliber venous vessels than in fast-flowing high caliber arterial vessels. Parallel-plate flow experiments with HUVEC support these findings, showing reduced QD-EC association with increasing flow. In vivo, flow arrest after nanoparticle injection still results in venous accumulation at 18 h. Overall our results suggest that both QD charge and blood flow modulate particle-endothelial cell interactions.

MICA*A4 protects against ulcerative colitis, whereas MICA*A5.1 is associated with abscess formation and age of onset.

Ulcerative colitis (UC) is one of the two major forms of inflammatory bowel disease, the aetiology of which remains unknown. Several studies have demonstrated the genetic basis of disease, identifying more than 130 susceptibility loci. The major histocompatibility complex class I chain-related gene A (MICA) is a useful candidate to be involved in UC pathogenesis, because it could be important in recognizing the integrity of the epithelial cell and its response to stress. The aim of this study was to analyse the relationship between polymorphisms in the transmembrane domain of MICA and susceptibility to develop UC. A total of 340 patients with UC and 636 healthy controls were genotyped for MICA transmembrane polymorphism using a polymerase chain reaction (PCR) combined with fluorescent technology. Different MICA alleles were determined depending on the PCR product size. The allele MICA*A4 was less frequent in patients than in controls (P = 0·003; OR = 0·643), and this protective role is higher when it forms haplotype with B*27 (P = 0·002; OR = 0·294). The haplotype HLA-B*52/MICA*A6 was also associated with UC [P = 0·001; odds ratio (OR) = 2·914]. No other alleles, genotypes or haplotypes were related with UC risk. Moreover, MICA*A5.1 is associated independently with abscesses (P = 0·002; OR = 3·096) and its frequency is lower in patients diagnosed between ages 17 and 40 years (P = 0·007; OR = 0·633), meaning an extreme age on onset. No association with location, extra-intestinal manifestations or need for surgery was found.

Decatropis bicolor (Zucc.) Radlk essential oil induces apoptosis of the MDA-MB-231 breast cancer cell line.

BACKGROUND: Decatropis bicolor (Zucc.)Radlk is a plant that has been traditionally used for the treatment of breast cancer in some communities of Mexico. So, the aim of this study was to determine the cytotoxic and apoptotic effect of the essential oil of Decatropis bicolor against breast cancer cell line, MDA-MB-231. METHODS: The essential oil obtained from hydrodestillation of leaves of Decatropis bicolor was studied for its biological activity against breast cancer cells MDA-MB-231 by MTT assay, Hematoxylin-eosin stain, Annexin V-FITC, TUNEL and western blot assays and for its chemical composition by GC-MS. RESULTS: The results showed a relevant cytotoxic effect of the essential oil towards MDA-MB-231 cells in a dose- and time- dependent manner, with an IC50 of 53.81 ± 1.691 µg/ml but not in the epithelial mammary cell line MCF10A (207.51 ± 3.26 µg/ml). Morphological examination displayed apoptotic characteristics in the treated cells like cell size reduction, membrane blebbing and apoptotic bodies. In addition, the apoptotic rate significantly increased as well as DNA fragmentation and western blot analysis revealed that the essential oil induced apoptosis in the MDA-MB-231 cells via intrinsic pathways due to the activation of Bax, caspases 9 and 3. Phytochemical analysis of the Decatropis bicolor essential oil showed the presence of twenty-three compounds. Major components of the oil were 1,5-cyclooctadiene,3-(methyl-2)propenyl (18.38 %), ß-terpineol (8.16 %) and 1-(3-methyl-cyclopent-2-enyl)-cyclohexene (6.12 %). CONCLUSIONS: This study suggests that essential oil of Decatropis bicolor has a potential cytotoxic and antitumoral effect against breast cancer cells, with the presence of potential bioactive compounds. Our results contribute to the validation of the anticancer activity of the plant in Mexican traditional medicine.

[Vulvar squamous cell carcinoma in young women with HPV negative]. / Carcinoma epidermoide de vulva en mujer joven con VPH negative.

BACKGROUND: The vulvar cancer is the fourth more frequent neoplasia after the endometrial, cervix and ovarian cancer. Normally, it has been related to old women of ages from 70 to 80 years old. Rarely, it has been detected cases in adult or young women. However, its incidence has been increased in the last years and in more early years. It is for this change in the incidence and its appearance in early years why a possible etiology has been looked for, opening different hypothesis that go from that related to the HPV to those that study an inflammatory chronic process as the basis for the carcinogenesis. CLINICAL CASE: In this article, it has been presented the case of a woman who is 34 years old with negative VPH that made her debut with epidermoid carcinoma of the vulva moderately different and on purpose of the case, we do a revision of the literature existent. CONCLUSIONS: Vulvar cancer diagnosed in young women as in older, but with different trends, risk factors and natural history. The case reported here escapes the theories studied so far so needed new lines of inquiry to investigate this form of presentation young woman, without HPV infection.

Safety of thiopurines and anti-TNF-α drugs during pregnancy in patients with inflammatory bowel disease.

OBJECTIVES: The safety of thiopurines and anti-tumor necrosis factor-α (TNF-α) drugs during pregnancy remains controversial, as the experience with these drugs in this situation is limited. Our aim is to assess the safety of thiopurines and anti-TNF-α drugs for the treatment of inflammatory bowel disease (IBD) during pregnancy. METHODS: Retrospective, multicenter study in IBD patients. Pregnancies were classified according to the therapeutic regimens during pregnancy or during the 3 months before the conception: non-exposed group, pregnancies exposed to thiopurines alone (group A), and pregnancies exposed to anti-TNF-α drugs (group B). An unfavorable Global Pregnancy Outcome (GPO) was considered if pregnancy developed with obstetric complications in the mother and in the newborn. RESULTS: A total of 187 pregnancies in the group A, 66 pregnancies in the group B, and 318 pregnancies in the non-exposed group were included. The rate of unfavorable GPO was different among the three groups (31.8% in non-exposed group, 21.9% in group A, and 34.8% in group B), being lower in pregnancies under thiopurines than among non-exposed (P = 0.01). The rate of pregnancy complications was similar among the three groups (27.7% in non-exposed, 20.9% in group A, and 30.3% in group B). The rate of neonatal complications was different among the three groups (23.3% in non-exposed group, 13.9% in group A, and 21.2% in group B), being lower in pregnancies under thiopurines than among non-exposed (P = 0.01). In the multivariate analysis, the treatment with thiopurines (odds ratio = 0.6; 95% confidence interval = 0.4-0.9, P = 0.02) was the only predictor of favorable GPO, whereas maternal age >35 years at conception was the only predictor of unfavorable GPO. The treatment with anti-TNF-α drugs was not associated with an unfavorable GPO. CONCLUSION: The treatment with thiopurines and anti-TNF-α drugs does not seem to increase the risk of complications during pregnancy and does seem to be safe for the newborn.

Lack of association of ACP1 gene with inflammatory bowel disease: a case-control study.

The red cell acid phosphatease (ACP1) gene, which encodes a low molecular weight phosphotyrosine phosphatase (LMW-PTP), has been suggested as a common genetic factor of autoimmunity. In the present study, we aimed to investigate the possible influence of ACP1 polymorphisms in the susceptibility of inflammatory bowel disease (IBD). A total of 1271 IBD Spanish patients [720 Crohn's disease (CD) and 551 ulcerative colitis (UC)] and 1877 healthy subjects were included. Four single-nucleotide polymorphisms (SNPs), rs10167992, rs11553742, rs7576247 and rs3828329, were genotyped using TaqMan SNP genotyping assays. Common ACP1 alleles (i.e. ACP1*A, ACP1*B and ACP1*C) were determined by two of these SNPs. After the analysis, no evidence of association of the ACP1 genetic variants was found with CD or UC. Therefore, our results suggest that the ACP1 gene may not play a relevant role in the development of IBD.

New support roller profile design for railway wheel re-profiling process by under-floor lathes with a single cutting tool.

The wheel re-profiling is an important part of railway wheelset maintenance. Researchers and railway operators have been very concerned about how to minimize the loss of time during wheel re-profiling without decreasing safety. Avoiding wheelset disassembly means considerable time savings, while reducing wheel damage during operation. Underfloor wheel lathes are the most appropriate tool to achieve this double objective, and therefore the most used nowadays. Multi-cut tool lathes have the disadvantage of being extremely expensive. On the other hand, with single tool lathes, re-profiling is not smooth or safe enough when current convex profile support rollers are used. It is well known by the companies that during reprofiling the wheel suffers impacts/damaged. In this article, a methodology to optimize the profile of the support rollers used in underfloor single tool lathes for railway wheel re-profiling is proposed. This novel profile design will minimize damage and increase the safety of such lathes, since it proposes a greater smoothness in the process. Simulations of re-profiling process have been carried out by the finite element method showing that the designed roller profile reduces drastically the impact/damage during the operation. The impact generated between the re-profiling wheel and the rollers is avoided. Profile-optimized support rollers have been used in a real underfloor wheel lathe, showing good results.

Association of Toll-like receptor 10 and susceptibility to Crohn's disease independent of NOD2.

Impaired innate inflammatory response has a key role in the Crohn's disease (CD) pathogenesis. The aim of this study was to investigate the possible role of the TLR10-TLR1-TLR6 gene cluster in CD susceptibility. A total of 508 CD patients (284, cohort 1 and 224, cohort 2) and 576 controls were included. TLR10-TLR1-TLR6 cluster single-nucleotide polymorphisms genotyping, NOD2 mutations and TLR10 mRNA quantification were performed using TaqMan assays. Nucleotide-binding oligomerization domain containing 2 (NOD2) and Toll-like receptor (TLR) loci interaction was analyzed by logistic regression and multifactor-dimensionality reduction (MDR). Entropy-based analysis was used to interpret combination effects. One TLR10 haplotype (TLR10(GGGG)) was found associated with CD susceptibility in both cohorts, individuals with two copies had approximately twofold more risk of CD susceptibility than individuals having no copies (odds ratio=1.89, P-value=0.0002). No differences in the mRNA levels were observed among the genotypes. The strongest model for predicting CD risk according to the MDR analysis was a two-locus model including NOD2 mutations and TLR10(GGGG) haplotype (P(c)<0.0001). The interaction gain attributed to the combination of both genes was negative (IG=-2.36%), indicating redundancy or independent effects. Our results support association of the TLR10 gene with CD susceptibility. The effect of TLR10 would be independent of NOD2, suggesting different signaling pathways for both genes.

Differentiation of Candida parapsilosis, C. orthopsilosis, and C. metapsilosis by specific PCR amplification of the RPS0 intron.

Although Candida parapsilosis is the most prevalent among the 3 species of the *psilosis group, studies applying DNA-based diagnostic techniques with isolates previously identified as C. parapsilosis have revealed that both C. orthopsilosis and C. metapsilosis account for 0-10% of all these isolates, depending on the geographical area. Differences in the degrees of antifungal susceptibility and virulence have been found, so a more precise identification is required. In a first approach, we reidentified 38 randomly chosen clinical isolates, previously identified as C. parapsilosis, using the RPO2 (CA2) RAPD marker. Among them, we reclassified 4 as C. metapsilosis and 5 as C. orthopsilosis. We previously developed a method to identify different pathogen yeast species, including C. parapsilosis, based on the amplification of the RPS0 gene intron. In this work, we extend this approach to the new *psilosis species by partially sequencing their RPS0 gene, including the intron sequence. Based on intron sequences, we designed specific primers capable of identifying C. orthopsilosis and C. metapsilosis species, and we reidentified species among the initial isolates. These new primers have allowed a specific and rapid identification of C. orthopsilosis and C. metapsilosis.

The removal of the trivalent chromium from the leather tannery wastewater: the optimisation of the electro-coagulation process parameters.

The capacity of the electro-coagulation (EC) process for the treatment of the wastewater containing Cr3+, resulting from a leather tannery industry placed in Medellin (Colombia), was evaluated. In order to assess the effect of some parameters, such as: the electrode type (Al and/or Fe), the distance between electrodes, the current density, the stirring velocity, and the initial Cr3+ concentration on its efficiency of removal (%RCr+3), a multifactorial experimental design was used. The %RCr3+ was defined as the response variable for the statistical analysis. In order to optimise the operational values for the chosen parameters, the response surface method (RSM) was applied. Additionally, the Biological Oxygen Demand (BOD5), the Chemical Oxygen Demand (COD), and the Total Organic Carbon (TOC) were monitored during the EC process. The electrodes made of aluminium appeared to be the most effective in the chromium removal from the wastewater under study. At pH equal to 4.52 and at 28°C, the optimal conditions of Cr3+ removal using the EC process were found, as follows: the initial Cr3+ concentration=3,596 mg/L, the electrode gap=0.5 cm, the stirring velocity=382.3 rpm, and the current density=57.87 mA/cm2. At those conditions, it was possible to reach 99.76% of Cr3+ removal, and 64% and 61% of mineralisation (TOC) and COD removal, respectively. A kinetic analysis was performed in order to verify the response capacity of the EC process at optimised parameter values.

Betaine increases net portal absorption of volatile fatty acids in Iberian pigs.

Betaine is an osmolyte with the potential to increase volatile fatty acids (VFAs) production and hence improve intestinal health.The present study investigated how betaine affects portal and arterial concentrations and net portal absorption (NPA) of VFA in growing Iberian pigs. Eight 30 kg BW Iberian growing barrows with indwelling catheters in portal vein, ileal vein and carotid artery were randomly assigned to a control diet or a diet supplemented with 0.5% betaine. Para-aminohippuric acid was infused into the ileal vein as a marker to determine portal blood flow using the dilution method. Blood samples were simultaneously taken from the carotid artery and portal vein at -60, 60, 120, 180, 240, 300 and 360 min after feeding 1 200 g of the diet. The NPA of VFA (acetate, propionate, butyrate, valerate, isobutyrate and caproate) was determined by multiplying the porto-arterial plasma concentration differences by portal plasma flow. Betaine increased NPA of acetate (1.44 fold; P < 0.001) and total VFA (0.55 fold; P < 0.001) while decreased NPA of propionate (-0.38 fold; P < 0.05) and valerate (-1.46 fold; P < 0.05) compared with control pigs. Estimated heat production potentially derived from NPA of VFA accounted for 0.20-0.27 of metabolizable energy for maintenance. Acetate and propionate accounted for most of the total VFA estimated heat production (0.83-0.89). Regarding bacterial communities, betaine apparently did not change the DNA abundance of fecal total bacteria, Lactobacillus, Bifidobacterium, Enterobacteriaceae, Bacteroides and the Clostridium clusters I, IV and XIV. In conclusion, betaine increased portal appearance and NPA of VFA, contributing to cover maintenance energy requirements.

[Blood glucose control and cardiovascular risk factors in type 2 diabetic patients with cardiovascular disease in Spain, and its treatment pattern, according to gender: CODICE study]. / Control glucémico y de los factores de riesgo cardiovascular en los pacientes con diabetes tipo 2 con enfermedad cardiovascular en España, y su patrón de tratamiento, en función del género: Estudio CODICE.

INTRODUCTION AND OBJECTIVES: With the implementation of the Strategy of Health Promotion and Prevention in Spain, the scenario reflected in previous studies of low control of cardiovascular risk factors (CVRF) in patients with type 2 diabetes (DM2) and cardiovascular disease (CVD) can be modified. This study intends to determine the level of blood glucose control and other CVRF in patients with DM2 and CVD currently seen in clinics in Spain, as well as the pattern of antidiabetic treatment, and differences according to gender. MATERIALS AND METHODS: An epidemiological, observational, cross-sectional, nationwide study was conducted in patients of both genders diagnosed with DM2 and established CVD. RESULTS: The study included 3,143 patients with a mean age 69.0±10 years. The mean HbA1c was 7.4±1.1% in females vs 7.3±1.2% in males (P<.05) and systolic blood pressure was 137±15.0mmHg in females vs 135.6±14.7mmHg in males (P<.05). The mean LDL-cholesterol was 101.5±38.1mg/dl in females vs 91.1±37.5mg/dl in males; P<.001) and the mean body mass index (30.7±5.4kg/m2 in females vs 29.6±4.5kg/m2 in males; P<.001). The most used treatments were metformin (68.1%) and/or DPP4 inhibitors (53.7%), with no differences between genders. CONCLUSIONS: The level of blood glucose control of DM2 patients with CVD in Spain can be improved. The treatment profile does not conform to the recommendations of clinical practice guidelines in general. The differences in the control of CVRF are worse in women for lipids and obesity.

[ESCRYTO study. Diabetes without cardiovascular disease and level of control]. / Estudio ESCRYTO. Diabetes sin enfermedad cardiovascular y grado de control.

BACKGROUND AND OBJECTIVES: Diabetes is a significant risk factor for the development of cardiovascular disease, which is the main cause of death. The purpose of this study was to determine the level of glycaemic control in patients with type 2 diabetes without cardiovascular disease in Spain. The data used includes the most recent determination of glycosylated haemoglobin, as well as the pattern of antidiabetic treatment, the incidence of episodes of severe hypoglycaemia in the last 6 months, and the level of control of cardiovascular risk factors, and gender. PATIENTS AND METHODS: A national, multicentre, and cross-sectional epidemiological study in which 800 doctors associated with the GDPS network participated. RESULTS: Of the total of 1,059 patients, 57% male, with a mean age of 62.7 years in men vs. 65.2 in women (P<.001). The mean onset of diabetes was 9.4±7.5 years. The mean HbA1C was 7.0% in men vs. 7.1% in women (P=.039), with the control objective of <7% being observed in 47.2%. There were 65% patients on treatment with metformin, and 62.4% on DPP-4 inhibitors, and basal insulin: 14.2%. Incidence of severe hypoglycemias in the last 6 months was 1.9%. The women had worse glycaemic control, total cholesterol, LDL cholesterol, abdominal obesity, and glomerular filtration levels. CONCLUSIONS: The glycaemic control is worse in women even if adjusted for age and time of onset of diabetes (P=.043), and for the number of hypoglycaemic agents (P=.015). The level of control is also worse in women for dyslipidaemia, abdominal obesity, and glomerular filtration. A preventive strategy promoted from Primary care on healthy lifestyles and controlling all vascular risk factors is essential.

Association of ATG16L1 and IRGM genes polymorphisms with inflammatory bowel disease: a meta-analysis approach.

The aim of this study was to determine the role of the ATG16L1 (rs2241880) and IRGM (rs13361189 and rs4958847) genes polymorphism in Crohn's disease (CD) and ulcerative colitis (UC). Our study included 557 CD and 425 UC patients and 672 ethnically matched Spanish controls and a meta-analysis with the data published to date. The polymorphisms were genotyped using predesigned TaqMan single nucleotide polymorphism genotyping assays. There was a statistically significant difference in the distribution of the ATG16L1 rs2241880 G allele between CD patients and controls in the Spanish population: P=6.5 x 10(-9), odds ratio (OR)=1.62. Although no differences were observed between UC patients and controls in the Spanish cohort, a meta-analysis demonstrated that the ATG16L1 G allele increase significantly risk for UC (P=0.0003, pooled OR=1.08). In addition, our meta-analysis data showed that IRGM rs13361189 and rs4958847 polymorphisms were associated with CD (rs13361189 C allele P=1.07 x 10(-19), pooled OR=1.34; rs4958847 A allele P=2.78 x 10(-17), pooled OR=1.31) and UC (rs13361189 P=0.0069, pooled OR=1.16; rs4958847 P=0.014, pooled OR=1.13). In conclusion, our results confirm the ATG16L1 rs2241880 and IRGM rs13361189 and rs4958847 polymorphisms as important markers for CD susceptibility and indicate that these variants are also associated with UC.

Imaging with extended focal depth by means of the refractive light sword optical element.

The paper presents first experiments with a refractive light sword optical element (LSOE). A refractive version of the LSOE was prepared in photoresist by gray scale photolithography. Then we examined chromatic aberrations of the produced element and compared them with those corresponding to two different lenses. For this purpose we performed two experiments, the first one where white light illumination was used and the latter one by the help of monochromatic illumination with three different wavelengths. The obtained results lead to the conclusion that the refractive LSOE does not exhibit significant chromatic aberrations and can be successfully used for imaging with extended depth of focus in polychromatic illumination.