Long-term supplementation with anthocyanin-rich or -poor Rubus idaeus berries does not influence microvascular architecture nor cognitive outcome in the APP/PS-1 mouse model of Alzheimer's disease.

Disruption of microvascular architecture is a common pathogenic mechanism in the progression of Alzheimer's disease (AD). Given the anti-angiogenic activity of berry (poly)phenols, we investigated whether long-term feeding of Rubus idaeus (raspberries) could ameliorate cerebral microvascular pathology and improve cognition in the APP/PS-1 mouse model of AD. Male C57Bl/6J mice (50 wild type, 50 APP/PS-1) aged 4-months were fed for 24-weeks, with a normal diet enriched with either 100 mg/day glucose (control diet) or supplemented with glucose and freeze-dried anthocyanin-rich (red) or -poor (yellow) raspberries (100 mg/day) and assessed/sampled post intervention. Cerebral microvascular architecture of wild-type mice was characterised by regularly spaced capillaries with uniform diameters, unlike APP/PS-1 transgenic mice which showed dysregulated microvascular architecture. Long-term feeding of raspberries demonstrated limited modulation of microbiota and no substantive effect on microvascular architecture or cognition in either mice model although changes were evident in endogenous cerebral and plasmatic metabolites.

Effects of Diet-Modulated Autologous Fecal Microbiota Transplantation on Weight Regain.

BACKGROUND & AIMS: We evaluated the efficacy and safety of diet-modulated autologous fecal microbiota transplantation (aFMT) for treatment of weight regain after the weight-loss phase. METHODS: In the DIRECT PLUS (Dietary Intervention Randomized Controlled Trial Polyphenols-Unprocessed) weight-loss trial (May 2017 through July 2018), abdominally obese or dyslipidemic participants in Israel were randomly assigned to healthy dietary guidelines, Mediterranean diet, and green-Mediterranean diet weight-loss groups. All groups received free gym membership and physical activity guidelines. Both isocaloric Mediterranean groups consumed 28 g/d walnuts (+440 mg/d polyphenols provided). The green-Mediterranean dieters also consumed green tea (3-4 cups/d) and a Wolffia globosa (Mankai strain, 100 g/d) green shake (+800 mg/d polyphenols provided). After 6 months (weight-loss phase), 90 eligible participants (mean age, 52 years; mean weight loss, 8.3 kg) provided a fecal sample that was processed into aFMT by frozen, opaque, and odorless capsules. The participants were then randomly assigned to groups that received 100 capsules containing their own fecal microbiota or placebo until month 14. The primary outcome was regain of the lost weight over the expected weight-regain phase (months 6-14). Secondary outcomes were gastrointestinal symptoms, waist circumference, glycemic status, and changes in the gut microbiome, as measured by metagenomic sequencing and 16s ribosomal RNA. We validated the results in a parallel in vivo study of mice specifically fed with Mankai compared with control chow diet. RESULTS: Of the 90 participants in the aFMT trial, 96% ingested at least 80 of 100 oral aFMT or placebo frozen capsules during the transplantation period. No aFMT-related adverse events or symptoms were observed. For the primary outcome, although no significant differences in weight regain were observed among the participants in the different lifestyle interventions during months 6-14 (aFMT, 30.4% vs placebo, 40.6%; P = .28), aFMT significantly attenuated weight regain in the green-Mediterranean group (aFMT, 17.1%, vs placebo, 50%; P = .02), but not in the dietary guidelines (P = .57) or Mediterranean diet (P = .64) groups (P for the interaction = .03). Accordingly, aFMT attenuated waist circumference gain (aFMT, 1.89 cm vs placebo, 5.05 cm; P = .01) and insulin rebound (aFMT, -1.46 ± 3.6 µIU/mL vs placebo, 1.64 ± 4.7 µIU/mL; P = .04) in the green-Mediterranean group but not in the dietary guidelines or Mediterranean diet (P for the interaction = .04 and .03, respectively). The green-Mediterranean diet was the only intervention to induce a significant change in microbiome composition during the weight-loss phase, and to prompt preservation of weight-loss-associated specific bacteria and microbial metabolic pathways (mainly microbial sugar transport) after the aFMT. In mice, Mankai-modulated aFMT in the weight-loss phase compared with control diet aFMT, significantly prevented weight regain and resulted in better glucose tolerance during a high-fat diet-induced regain phase (all, P < .05). CONCLUSIONS: Autologous FMT, collected during the weight-loss phase and administrated in the regain phase, might preserve weight loss and glycemic control, and is associated with specific microbiome signatures. A high-polyphenols, green plant-based or Mankai diet better optimizes the microbiome for an aFMT procedure. ClinicalTrials.gov number, NCT03020186.

Impact of wheat aleurone on biomarkers of cardiovascular disease, gut microbiota and metabolites in adults with high body mass index: a double-blind, placebo-controlled, randomized clinical trial.

PURPOSE: Aleurone is a cereal bran fraction containing a variety of beneficial nutrients including polyphenols, fibers, minerals and vitamins. Animal and human studies support the beneficial role of aleurone consumption in reducing cardiovascular disease (CVD) risk. Gut microbiota fiber fermentation, polyphenol metabolism and betaine/choline metabolism may in part contribute to the physiological effects of aleurone. As primary objective, this study evaluated whether wheat aleurone supplemented foods could modify plasma homocysteine. Secondary objectives included changes in CVD biomarkers, fecal microbiota composition and plasma/urine metabolite profiles. METHODS: A parallel double-blind, placebo-controlled and randomized trial was carried out in two groups of obese/overweight subjects, matched for age, BMI and gender, consuming foods supplemented with either aleurone (27 g/day) (AL, n = 34) or cellulose (placebo treatment, PL, n = 33) for 4 weeks. RESULTS: No significant changes in plasma homocysteine or other clinical markers were observed with either treatment. Dietary fiber intake increased after AL and PL, animal protein intake increased after PL treatment. We observed a significant increase in fecal Bifidobacterium spp with AL and Lactobacillus spp with both AL and PL, but overall fecal microbiota community structure changed little according to 16S rRNA metataxonomics. Metabolomics implicated microbial metabolism of aleurone polyphenols and revealed distinctive biomarkers of AL treatment, including alkylresorcinol, cinnamic, benzoic and ferulic acids, folic acid, fatty acids, benzoxazinoid and roasted aroma related metabolites. Correlation analysis highlighted bacterial genera potentially linked to urinary compounds derived from aleurone metabolism and clinical parameters. CONCLUSIONS: Aleurone has potential to modulate the gut microbial metabolic output and increase fecal bifidobacterial abundance. However, in this study, aleurone did not impact on plasma homocysteine or other CVD biomarkers. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT02067026) on the 17th February 2014.

Two apples a day modulate human:microbiome co-metabolic processing of polyphenols, tyrosine and tryptophan.

PURPOSE: Validated biomarkers of food intake (BFIs) have recently been suggested as a useful tool to assess adherence to dietary guidelines or compliance in human dietary interventions. Although many new candidate biomarkers have emerged in the last decades for different foods from metabolic profiling studies, the number of comprehensively validated biomarkers of food intake is limited. Apples are among the most frequently consumed fruits and a rich source of polyphenols and fibers, an important mediator for their health-protective properties. METHODS: Using an untargeted metabolomics approach, we aimed to identify biomarkers of long-term apple intake and explore how apples impact on the human plasma and urine metabolite profiles. Forty mildly hypercholesterolemic volunteers consumed two whole apples or a sugar and energy-matched control beverage, daily for 8 weeks in a randomized, controlled, crossover intervention study. The metabolome in plasma and urine samples was analyzed via untargeted metabolomics. RESULTS: We found 61 urine and 9 plasma metabolites being statistically significant after the whole apple intake compared to the control beverage, including several polyphenol metabolites that could be used as BFIs. Furthermore, we identified several endogenous indole and phenylacetyl-glutamine microbial metabolites significantly increasing in urine after apple consumption. The multiomic dataset allowed exploration of the correlations between metabolites modulated significantly by the dietary intervention and fecal microbiota species at genus level, showing interesting interactions between Granulicatella genus and phenyl-acetic acid metabolites. Phloretin glucuronide and phloretin glucuronide sulfate appeared promising biomarkers of apple intake; however, robustness, reliability and stability data are needed for full BFI validation. CONCLUSION: The identified apple BFIs can be used in future studies to assess compliance and to explore their health effects after apple intake. Moreover, the identification of polyphenol microbial metabolites suggests that apple consumption mediates significant gut microbial metabolic activity which should be further explored.

Dermatofluoroscopy Is Also for Redheads a Sensitive Method of Early Melanoma Detection.

BACKGROUND: Caucasians with red hair and fair skin have a remarkably increased risk of malignant melanoma compared to non-redhead Caucasians. OBJECTIVES: With the aim of a reliable melanoma diagnosis in redheads, the application of dermatofluoroscopy was analyzed in 16 patients with red hair. Most of them had been included in a clinical dermatofluoroscopy study for patients with the suspicion of melanoma. We examined whether the 25 lesions of the redheads showed the same characteristic melanin fluorescence spectra for dysplastic nevi and melanomas as those of non-redhead Caucasians or whether there was a different fluorescence pattern. This is important in view of the known significantly altered ratio of eumelanin to pheomelanin in the skin of redheads. METHODS: More than 8,000 spatially resolved fluorescence spectra of 25 pigmented lesions were measured and analysed. The spectra were excited by the stepwise absorption of two 800-nm photons (principle of dermatofluoroscopy). Furthermore, the fluorescence spectra of eumelanin and pheomelanin in hair samples were determined in the same way. RESULTS: The evaluation revealed that the melanin fluorescence spectra of dysplastic nevi and melanomas of redheads have the same spectral characteristics as those of non-redhead Caucasians. An accompanying result is that dermatofluoroscopy shows identical fluorescence spectra for eumelanin and pheomelanin. CONCLUSIONS: Dermatofluoroscopy proves to be a reliable diagnostic method also for redheads. Our results also explain our recent finding that there is a uniform fluorescence spectroscopic fingerprint for melanomas of all subtypes, which is of particular interest for hypomelanotic and apparently amelanotic melanomas containing pheomelanin.

Effects of woody biochar on dry thermophilic anaerobic digestion of organic fraction of municipal solid waste.

This study presents the results of semi-pilot scale anaerobic digestion tests conducted under dry thermophilic conditions with the addition of biochar (6% on fresh mass basis of inoculum), derived from an industrial gasification plant, for determining biogas and biomethane production from organic fraction of municipal solid waste. By using two types of inocula (from a full-scale dry anaerobic digestion plant and from lab-scale biomethanation tests), the obtained experimental results did not show significant increase in methane yield related to the presence of biochar (330.40 NL CH4 kgVS-1 using plant inoculum; 335.41 NL CH4 kgVS-1 using plant inoculum with biochar, 311.78 NL CH4 kgVS-1 using lab-inoculum and 366.43 NL CH4 kgVS-1 using lab-inoculum with biochar), but led to significant changes in the microbial community composition. These results are likely related with the specific biochar physical-chemical features and low adsorption potential. Resulting digestate quality was also investigated: biochar-enriched digestates were characterized by increased biological stability (809 ± 264 mg O2 kgVS-1 h-1 vs. 554 ± 76 mg O2 kgVS-1 h-1 for biochar-free and biochar-enriched digestates, respectively), lower heavy metals concentrations (with the exception of Cd), but higher polycyclic aromatic hydrocarbons content, with a reported maximum concentration of 8.9 mgPAH kgTS-1 for biochar-enriched digestate derived from AD test with lab-inoculum, which could trigger non-compliance with regulation limits for agricultural reuse of digestates. However, phytotoxicity assessments showed a decreased toxicity of biochar-containing digestates when compared to biochar-free digestates.

Strain-level microbial epidemiology and population genomics from shotgun metagenomics.

Identifying microbial strains and characterizing their functional potential is essential for pathogen discovery, epidemiology and population genomics. We present pangenome-based phylogenomic analysis (PanPhlAn; http://segatalab.cibio.unitn.it/tools/panphlan), a tool that uses metagenomic data to achieve strain-level microbial profiling resolution. PanPhlAn recognized outbreak strains, produced the largest strain-level population genomic study of human-associated bacteria and, in combination with metatranscriptomics, profiled the transcriptional activity of strains in complex communities.

A Diet Low in FODMAPs Reduces Symptoms in Patients With Irritable Bowel Syndrome and A Probiotic Restores Bifidobacterium Species: A Randomized Controlled Trial.

BACKGROUND & AIMS: Dietary restriction of fermentable carbohydrates (a low FODMAP diet) has been reported to reduce symptoms in some patients with irritable bowel syndrome (IBS). We performed a randomized, placebo-controlled study to determine its effects on symptoms and the fecal microbiota in patients with IBS. METHODS: We performed a 2×2 factorial trial of 104 patients with IBS (18-65 years old), based on the Rome III criteria, at 2 hospitals in the United Kingdom. Patients were randomly assigned (blinded) to groups given counselling to follow a sham diet or diet low in FODMAPs for 4 weeks, along with a placebo or multistrain probiotic formulation, resulting in 4 groups (27 receiving sham diet/placebo, 26 receiving sham diet/probiotic, 24 receiving low FODMAP diet /placebo, and 27 receiving low FODMAP diet/probiotic). The sham diet restricted a similar number of staple and non-staple foods as the low FODMAP diet; the diets had similar degrees of difficulty to follow. Dietary counselling was given to patients in all groups and data on foods eaten and compliance were collected. The incidence and severity of 15 gastrointestinal symptoms and overall symptoms were measured daily for 7 days before the study period; along with stool frequency and consistency. At baseline, global and individual symptoms were measured, along with generic and disease-specific health-related quality of life, using standard scoring systems. All data were collected again at 4 weeks, and patients answered questions about adequate symptom relief. Fecal samples were collected at baseline and after 4 weeks and analyzed by quantitative PCR and 16S rRNA sequencing. The co-primary endpoints were adequate relief of symptoms and stool Bifidobacterium species abundance at 4 weeks. RESULTS: There was no significant interaction between the interventions in adequate relief of symptoms (P = .52) or Bifidobacterium species (P = .68). In the intention-to-treat analysis, a higher proportion of patients in the low FODMAP diet had adequate symptom relief (57%) than in the sham diet group (38%), although the difference was not statistically significant (P = .051). In the per-protocol analysis, a significantly higher proportion of patients on the low FODMAP diet had adequate symptom relief (61%) than in the sham diet group (39%) (P = .042). Total mean IBS-Severity Scoring System score was significantly lower for patients on the low FODMAP diet (173 ± 95) than the sham diet (224 ± 89) (P = .001), but not different between those given probiotic (207 ± 98) or placebo (192 ± 93) (P = .721) Abundance of Bifidobacterium species was lower in fecal samples from patients on the low FODMAP diet (8.8 rRNA genes/g) than patients on the sham diet (9.2 rRNA genes/g) (P = .008), but higher in patients given probiotic (9.1 rRNA genes/g) than patients given placebo (8.8 rRNA genes/g) (P = .019). There was no effect of the low FODMAP diet on microbiota diversity in fecal samples. CONCLUSIONS: In a placebo-controlled study of patients with IBS, a low FODMAP diet associates with adequate symptom relief and significantly reduced symptom scores compared with placebo. It is not clear whether changes resulted from collective FODMAP restriction or removal of a single component, such as lactose. Co-administration of the multistrain probiotic increased numbers of Bifidobacterium species, compared with placebo, and might be given to restore these bacteria to patients on a low FODMAP diet. Trial registration no: ISRCTN02275221.

Printing sub-micron structures using Talbot mask-aligner lithography with a 193 nm CW laser light source.

A continuous improvement of resolution in mask-aligner lithography is sought after to meet the requirements of an ever decreasing minimum feature size in back-end processes. For periodic structures, utilizing the Talbot effect for lithography has emerged as a viable path. Here, by combining the Talbot effect with a continuous wave laser source emitting at 193 nm, we demonstrate successfully the fabrication of periodic arrays in silicon substrates with sub-micron feature sizes. The excellent coherence and the superior brilliance of this light source, compared to more traditional mercury lamps and excimer lasers as light source, enables the efficient beam shaping and a reduced minimum feature size at a fixed gap of 20 µm. We present a comprehensive study of proximity printing with this system, including simulations and selected experimental results of prints in up to the fourth Talbot plane. This printing technology can be used to manufacture optical metasurfaces, bio-sensor arrays, membranes, or microchannel plates.

Mask-aligner lithography using a continuous-wave diode laser frequency-quadrupled to 193 nm.

We present a mask-aligner lithographic system operated with a frequency-quadrupled continuous-wave diode laser emitting at 193 nm. For this purpose, a 772 nm diode laser is amplified by a tapered amplifier in the master-oscillator power-amplifier configuration. The emission wavelength is upconverted twice, using LBO and KBBF nonlinear crystals in second-harmonic generation enhancement cavities. An optical output power of 10 mW is achieved. As uniform exposure field illumination is crucial in mask-aligner lithography, beam shaping is realized with optical elements made from fused silica and CaF2 featuring a diffractive non-imaging homogenizer. A tandem setup of shaped random diffusers, one static and one rotating, is used to control speckle formation. We demonstrate first experimental soft contact and proximity prints for a field size of 1 cm2 with a standard binary photomask and proximity prints with a two-level phase mask, both printed into 120 nm layers of photoresist on unstructured silicon substrates.

Interference with ethylene perception at receptor level sheds light on auxin and transcriptional circuits associated with the climacteric ripening of apple fruit (Malus x domestica Borkh.).

Apple (Malus x domestica Borkh.) is a model species for studying the metabolic changes that occur at the onset of ripening in fruit crops, and the physiological mechanisms that are governed by the hormone ethylene. In this study, to dissect the climacteric interplay in apple, a multidisciplinary approach was employed. To this end, a comprehensive analysis of gene expression together with the investigation of several physiological entities (texture, volatilome and content of polyphenolic compounds) was performed throughout fruit development and ripening. The transcriptomic profiling was conducted with two microarray platforms: a dedicated custom array (iRIPE) and a whole genome array specifically enriched with ripening-related genes for apple (WGAA). The transcriptomic and phenotypic changes following the application of 1-methylcyclopropene (1-MCP), an ethylene inhibitor leading to important modifications in overall fruit physiology, were also highlighted. The integrative comparative network analysis showed both negative and positive correlations between ripening-related transcripts and the accumulation of specific metabolites or texture components. The ripening distortion caused by the inhibition of ethylene perception, in addition to affecting the ethylene pathway, stimulated the de-repression of auxin-related genes, transcription factors and photosynthetic genes. Overall, the comprehensive repertoire of results obtained here advances the elucidation of the multi-layered climacteric mechanism of fruit ripening, thus suggesting a possible transcriptional circuit governed by hormones and transcription factors.

Synthesis of Dicarba-closo-dodecaborane-1-carboxamides.

Amide bond formation is one of the most important chemical reactions. In peptide and organic chemistry, the application of amide coupling reagents is a routine strategy, but surprisingly not in carborane chemistry. Thus, we now report a fast, safe, and robust protocol to couple amines to m- and p-dicarba-closo-dodecaborane-1-carboxylic acids. The procedure comprises the activation of carboxylic acid with the coupling reagent (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)(dimethylamino)morpholinocarbenium hexafluorophosphate, extraction of the product using the hydrophobic nature of the cluster, and a straightforward chromatographic purification. The protocol allows access to a variety of carborane-organic hybrid molecules suitable for application in multiple areas.

Free-electron laser multiplex driven by a superconducting linear accelerator.

Free-electron lasers (FELs) generate femtosecond XUV and X-ray pulses at peak powers in the gigawatt range. The FEL user facility FLASH at DESY (Hamburg, Germany) is driven by a superconducting linear accelerator with up to 8000 pulses per second. Since 2014, two parallel undulator beamlines, FLASH1 and FLASH2, have been in operation. In addition to the main undulator, the FLASH1 beamline is equipped with an undulator section, sFLASH, dedicated to research and development of fully coherent extreme ultraviolet photon pulses using external seed lasers. In this contribution, the first simultaneous lasing of the three FELs at 13.4 nm, 20 nm and 38.8 nm is presented.

B-Cyanodicarba-closo-dodecaboranes: Facile Synthesis and Spectroscopic Features.

B-Cyanodicarba-closo-dodecaboranes are a poorly explored class of compounds due to their complex synthetic availability. Now, we report a fast, atom-efficient, and high-yielding synthesis. We obtained the cyano derivatives by reacting B-iododicarba-closo-dodecaboranes with copper(I) cyanide under both palladium catalysis and microwave irradiation. We successfully applied this method to 9-iodo-o-, 9-iodo-m-, and 2-iodo-p-dicarba-closo-dodecaborane, obtaining the corresponding cyanides up to 89% isolated yield. The facile synthesis and evaluation of their spectroscopic properties reported herein will pave the way to exploring the chemistry and application of B-cyanodicarba-closo-dodecaborane clusters in more detail.

A study of classroom acoustics and school teachers' noise exposure, voice load and speaking time during teaching, and the effects on vocal and mental fatigue development.

OBJECTIVES: The study investigated the noise exposure in a group of Danish school teachers. The aims were to investigate if noise posed a risk of impairment of hearing and to study the association between classroom acoustical conditions, noise exposure, vocal symptoms, and cognitive fatigue. METHODS: Background noise levels, vocal load and speaking time were measured on 35 teachers during actual classroom teaching. The classrooms were characterized acoustically by measurements of reverberation time. Before and after the workday, the teachers answered a questionnaire on fatigue symptoms and carried out two cognitive test tasks sensitive to mental fatigue. RESULTS: The average noise level during the lessons was 72 dB(A), but during indoor sports activities the average noise level increased 6.6 dB(A). Room reverberation time (range 0.39-0.83 s) had no significant effect on the noise level. The teachers were talking with a raised voice in 61% of the time, and the vocal load increased 0.65 dB(A) per dB(A) increase in the average lesson noise level. An increase in voice symptoms during the workday correlated significantly with individual average noise exposure, and a decrease in performance in the two-back test correlated significantly with individual average vocal load. CONCLUSIONS: Noise exposure in general classrooms posed no risk of noise-induced hearing impairment in school teachers. However, the results provide evidence for an association between noise exposure and vocal load and development of vocal symptoms and cognitive fatigue after work.

[Tailored surgery in the treatment of gastroesophageal cancer]. / Maßgeschneiderte Chirurgie in der Behandlung gastroösophagealer Tumoren.

The surgical options and particularly perioperative treatment, have significantly advanced in the case of gastroesophageal cancer. This progress enables a 5-year survival rate of nearly 50% to be achieved through curative multimodal treatment concepts for locally advanced cancer. Therefore, in tumor boards and surgical case discussions the question increasingly arises regarding the type of treatment that provides optimal oncological and functional outcomes for individual patients with pre-existing diseases. It is therefore essential to carefully assess whether organ-preserving treatment might also be considered in the future or in what way minimally invasive or robotic surgery can offer advantages. Simultaneously, the boundaries of surgical and oncological treatment are currently being shifted in order to enable curative forms of treatment for patients with pre-existing conditions or those with oligometastatic diseases. With the integration of artificial intelligence into decision-making processes, new possibilities for information processing are increasingly becoming available to incorporate even more data into making decisions in the future.

Heterosis manifestation during early Arabidopsis seedling development is characterized by intermediate gene expression and enhanced metabolic activity in the hybrids.

Heterosis-associated cellular and molecular processes were analyzed in seeds and seedlings of Arabidopsis thaliana accessions Col-0 and C24 and their heterotic hybrids. Microscopic examination revealed no advantages in terms of hybrid mature embryo organ sizes or cell numbers. Increased cotyledon sizes were detectable 4 days after sowing. Growth heterosis results from elevated cell sizes and numbers, and is well established at 10 days after sowing. The relative growth rates of hybrid seedlings were most enhanced between 3 and 4 days after sowing. Global metabolite profiling and targeted fatty acid analysis revealed maternal inheritance patterns for a large proportion of metabolites in the very early stages. During developmental progression, the distribution shifts to dominant, intermediate and heterotic patterns, with most changes occurring between 4 and 6 days after sowing. The highest incidence of heterotic patterns coincides with establishment of size differences at 4 days after sowing. In contrast, overall transcript patterns at 4, 6 and 10 days after sowing are characterized by intermediate to dominant patterns, with parental transcript levels showing the largest differences. Overall, the results suggest that, during early developmental stages, intermediate gene expression and higher metabolic activity in the hybrids compared to the parents lead to better resource efficiency, and therefore enhanced performance in the hybrids.

Detection of colon polyps by a novel, polymer pattern-based full blood test.

Numerous studies have shown that early screening for the presence of pre-cancerous colon polyps and their subsequent removal decreases the risk of developing colon cancer. Colonoscopy is currently the most effective screening method, but due to the invasive nature of the procedure many patients avoid forgo testing. Futhermore, the procedure itself requires perfect execution by the gastroenterologist. Against this backdrop, a non-invasive blood screening method for the detection of colon polyps that has higher sensitivity than current screening techniques would be beneficial in the early identification of patients at risk for colon cancer. A prospective, double-blinded, controlled clinical study was designed to demonstrate the diagnostic performance of Polyp Specific Polymer analysis, a novel laboratory methodology. The primary objective of this clinical trial was to estimate the diagnostic accuracy of the Polyp Specific Polymer analysis for colon polyps using colonoscopy and histological tests as the diagnostic accuracy standards. Secondary objectives of this trial included estimating positive and negative predictive values for colon polyps, investigating reliability, determining covariates influencing diagnostic accuracy and obtaining absolute and relative frequencies of valid test results.In patients undergoing screening colonoscopy and histology examination, a sensitivity of 72.4% and a specificity of 62.3% could be proven.These results indicate that using this improved screening method it is possible to effectively identify the highest-risk candidates for endoscopy, thereby advancing the goal of decreasing the incidence or mortality of colorectal cancer in the selected population. Moreover, this diagnostic tool has potential socio-economic implications, conserving healthcare resources by enabling higher patient selectivity for endoscopy and eventual transfer to curative prevention via polypectomy.By combining the best-established low-risk screening elements together with a validated, highly sensitive blood test as described in this study, a steadfast increase in the estimation of colorectal cancer-risk before colonoscopy can be expected.

Infarct-Related Artery as a Donor of Collaterals in ST-Segment-Elevation Myocardial Infarction With Concomitant Chronic Total Occlusion: Challenge of the Double-Jeopardy Thesis.

BACKGROUND In ST-segment-elevation myocardial infarction (STEMI), a concomitant chronic total occlusion (CTO) in a non-infarct-related artery (NIRA) is associated with adverse outcome. In the case of the infarct-related artery (IRA) as a donor vessel for collaterals to the CTO, the IRA occlusion may lead to an acute threat to both the immediate IRA and the collaterally supplied CTO area, which has been described as a double-jeopardy effect. METHODS AND RESULTS We investigated the role of preformed intercoronary collaterals to the CTO originating from either the IRA or NIRA. Data were obtained from 2 hospitals participating in the prospective FITT-STEMI (Feedback Intervention and Treatment Times in ST-Segment Elevation Myocardial Infarction) study. From a total cohort of 2102 patients with acute STEMI, 93 patients had single-vessel CTO in an NIRA and well-developed intercoronary collaterals to the CTO. In-hospital mortality differed significantly with respect to the origin of the collaterals. Mortality was 15.2% with collaterals originating from the NIRA, 29.4% with a collateral origin from the IRA proximal to the acute STEMI occlusion, and 3.3% with a collateral origin from the IRA distal to the acute occlusion (P=0.044). A multivariate regression model confirmed that a proximal collateral origin had a significant higher mortality compared with a branching in the distal position from the acute STEMI occlusion (P=0.027; odds ratio = 20.8 [95% CI, 1.4-304.1]). CONCLUSIONS In STEMI with CTO in an NIRA, a CTO collateralization from the IRA distal to the acute occlusion is associated with a better prognosis. This finding challenges the double-jeopardy assumption as the main cause of adverse outcome in STEMI with CTO in an NIRA. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT00794001.