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Patients with type 2 diabetes (T2D) are threatened by excessive cardiovascular morbidity and mortality. While accelerated arterial stiffening may represent a critical mechanistic factor driving cardiovascular risk in T2D, specific therapies to contain the underlying diabetic arterial remodeling have been elusive. The present translational study investigates the role of microRNA-29b (miR-29b) as a driver and therapeutic target of diabetic aortic remodeling and stiffening. Using a murine model (db/db mice), as well as human aortic tissue samples, we find that diabetic aortic remodeling and stiffening is associated with medial fibrosis, as well as fragmentation of aortic elastic layers. miR-29b is significantly downregulated in T2D and miR-29b repression is sufficient to induce both aortic medial fibrosis and elastin breakdown through upregulation of its direct target genes COL1A1 and MMP2 thereby increasing aortic stiffness. Moreover, antioxidant treatment restores aortic miR-29b levels and counteracts diabetic aortic remodeling. Concluding, we identify miR-29b as a comprehensive—and therefore powerful—regulator of aortic remodeling and stiffening in T2D that moreover qualifies as a (redox-sensitive) target for therapeutic intervention., Graphical Abstract, Stiffening of large arteries represents a significant complication in patients with diabetes mellitus resulting in high blood pressure levels and widespread organ damage (in particular in heart, brain, and kidneys). In this study we identify microRNA-29b as a comprehensive regulator and potential therapeutical target of diabetic arterial remodeling and stiffening.

Purpose To determine the operative time and complication rates of resident phacoemulsification surgeries at different time points in training. Methods Retrospective cross-sectional study at the Department of Ophthalmology of the Philippine General Hospital. All resident-performed elective adult phacoemulsification surgeries from January 1, 2014, to December 31, 2018, were included, while operations with planned anterior or posterior procedures were excluded. Cases were arranged chronologically and divided into time points with 25 cases each. Operative time and complication rates were computed for each time point. As defined by the ICO Ophthalmology Surgical Competency Assessment Rubric (OSCAR), 30 minutes was used to gauge competency based on operative time, while complications were compared to published rates for residents. Results for the first 50 cases, the minimum number required by graduation, were also compared with succeeding cases. Results A total of 4635 cases were included. Residents performed an average of 115.9 ± 30.4 cases, with no significant difference among residents (F(4,35)=2.64, p=0.12). Overall complication rate was 6% (n=276), similar to those reported internationally. Both median operative time and complication rates decreased significantly for every time point in training (p

Purpose Operating room processes must be efficient to boost profitability and minimize cost while retaining surgical care quality. This study aims to assess operating room efficiency for resident-performed elective phacoemulsification surgeries done under local anesthesia by measuring different key performance indicators and comparing this with international benchmark data. Patients and Methods This is a prospective cross-sectional study done in the Department of Ophthalmology of the Philippine General Hospital, the National University Hospital. The operating room milestones were noted and recorded by a single third-party observer in randomly selected operating rooms from April to June 2019. Results Fifty-six phacoemulsification cases in randomly selected rooms fulfilling both inclusion and exclusion criteria were observed. None of the cases started on or before the scheduled 6:30 a.m. cutting time, with an average of 34 (SD 8.53) minutes late. Entry lag was above the median, while exit lag and turnover time were above the 95th percentile compared to benchmarking data. Segment analysis also showed an increased entry lag (35.11% vs 21.5%), significantly higher than benchmarks (t: 10.99, df: 55, p

Purpose: Many rare ovarian cancer subtypes, such as small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT), have poor prognosis due to their aggressive nature and resistance to standard platinum- and taxane-based chemotherapy. The development of effective therapeutics has been hindered by the rarity of such tumors. We sought to identify targetable vulnerabilities in rare ovarian cancer subtypes. Experimental Design: We compared the global proteomic landscape of six cases each of endometrioid ovarian cancer (ENOC), clear cell ovarian cancer (CCOC), and SCCOHT to the most common subtype, high-grade serous ovarian cancer (HGSC), to identify potential therapeutic targets. IHC of tissue microarrays was used as validation of arginosuccinate synthase (ASS1) deficiency. The efficacy of arginine-depriving therapeutic ADI-PEG20 was assessed in vitro using cell lines and patient-derived xenograft mouse models representing SCCOHT. Results: Global proteomic analysis identified low ASS1 expression in ENOC, CCOC, and SCCOHT compared with HGSC. Low ASS1 levels were validated through IHC in large patient cohorts. The lowest levels of ASS1 were observed in SCCOHT, where ASS1 was absent in 12 of 31 cases, and expressed in less than 5% of the tumor cells in 9 of 31 cases. ASS1-deficient ovarian cancer cells were sensitive to ADI-PEG20 treatment regardless of subtype in vitro. Furthermore, in two cell line mouse xenograft models and one patient-derived mouse xenograft model of SCCOHT, once-a-week treatment with ADI-PEG20 (30 mg/kg and 15 mg/kg) inhibited tumor growth in vivo. Conclusions: Preclinical in vitro and in vivo studies identified ADI-PEG20 as a potential therapy for patients with rare ovarian cancers, including SCCOHT.

Stroke remains one of the most common causes of death and disability worldwide. Several preclinical studies demonstrated that the brain can be effectively protected against ischaemic stroke by two seemingly distinct treatments: remote ischaemic conditioning (RIC), involving cycles of ischaemia/reperfusion applied to a peripheral organ or tissue, or by systemic administration of glucagon-like-peptide-1 (GLP-1) receptor (GLP-1R) agonists. The mechanisms underlying RIC- and GLP-1-induced neuroprotection are not completely understood. In this study, we tested the hypothesis that GLP-1 mediates neuroprotection induced by RIC and investigated the effect of GLP-1R activation on cerebral blood vessels, as a potential mechanism of GLP-1-induced protection against ischaemic stroke. A rat model of ischaemic stroke (90 min of middle cerebral artery occlusion followed by 24-h reperfusion) was used. RIC was induced by 4 cycles of 5 min left hind limb ischaemia interleaved with 5-min reperfusion periods. RIC markedly (by ~ 80%) reduced the cerebral infarct size and improved the neurological score. The neuroprotection established by RIC was abolished by systemic blockade of GLP-1R with a specific antagonist Exendin(9–39). In the cerebral cortex of GLP-1R reporter mice, ~ 70% of cortical arterioles displayed GLP-1R expression. In acute brain slices of the rat cerebral cortex, activation of GLP-1R with an agonist Exendin-4 had a strong dilatory effect on cortical arterioles and effectively reversed arteriolar constrictions induced by metabolite lactate or oxygen and glucose deprivation, as an ex vivo model of ischaemic stroke. In anaesthetised rats, Exendin-4 induced lasting increases in brain tissue PO2, indicative of increased cerebral blood flow. These results demonstrate that neuroprotection against ischaemic stroke established by remote ischaemic conditioning is mediated by a mechanism involving GLP-1R signalling. Potent dilatory effect of GLP-1R activation on cortical arterioles suggests that the neuroprotection in this model is mediated via modulation of cerebral blood flow and improved brain perfusion.

OBJECTIVESPatients with a bicuspid aortic valve (BAV) have an increased risk for developing thoracic aortic aneurysm, which is characterized by the destruction of the elastic media of the aortic wall. Several important enzymes have been characterized to play key roles in extracellular matrix homeostasis, namely matrix metalloproteinases (MMPs). In this study, we investigated MMP-2 levels and their epigenetic regulation via the miR-29 family.METHODSAortic tissue samples from 58 patients were collected during cardiac surgery, of which 30 presented with a BAV and 28 with a tricuspid aortic valve. Polymerase chain reaction, western blot analysis and immunohistochemistry were performed to analyse MMP-2. In addition, enzyme-linked immunosorbent assay measurements were carried out to investigate both MMP-2 and tissue inhibitor of metalloproteinase-2 levels. To examine the epigenetic regulation of aortic extracellular matrix homeostasis, we furthermore studied the expression levels of miR-29 via qRT-PCR.RESULTSPatients with a BAV were significantly younger at the time of surgery, presented significantly less frequently with arterial hypertension and displayed more often with an additional valvular disease. On a molecular level, we found that MMP-2 is increased on gene and protein level in BAV patients. Tissue inhibitor of metalloproteinase-2 levels do not differ between the groups. Interestingly, we also found that only miR-29A is significantly downregulated in BAVs.CONCLUSIONSOur findings highlight the importance of MMP-2 in the context of extracellular matrix destruction in BAV patients. We present new evidence that miR-29A is a crucial epigenetic regulator of these pathomechanistic processes and might hold promise for future translational research.

Aging has a significant impact not only on every single individual but on society as a whole. Today, people throughout the world exhibit an extended lifespan. Therefore, it becomes increasingly important to develop novel concepts that encourage a modern understanding of the aging process. The concept of healthy aging shifts the perception of aging as a burden towards aging as an opportunity for an extended healthy phase in later life. Morbidity and mortality in the elderly population are greatly defined by a raise in the incidence and prevalence of cardiovascular diseases. Consequently, it is critical to identify risk factors and underlying mechanisms that render the aging (cardio)vascular system prone to disease. In this review, we focus on structural mechanisms of arterial stiffening as a major manifestation of vascular aging and its functional implications for the concept of healthy aging.

Background and study aims Detection of polyps during colonoscopy is essential for screening colorectal cancer and computer-aided-diagnosis (CAD) could be helpful for this objective. The goal of this study was to assess the efficacy of CAD in detection of polyps in video colonoscopy by using three methods we have proposed and applied for diagnosis of polyps in wireless capsule colonoscopy. Patients and methods Forty-two patients were included in the study, each one bearing one polyp. A dataset was generated with a total of 1680 polyp instances and 1360 frames of normal mucosa. We used three methods, that are all binary classifiers, labelling a frame as either containing a polyp or not. Two of the methods (Methods 1 and 2) are threshold-based and address the problem of polyp detection (i. e. separation between normal mucosa frames and polyp frames) and the problem of polyp localization (i. e. the ability to locate the polyp in a frame). The third method (Method 3) belongs to the class of machine learning methods and only addresses the polyp detection problem. The mathematical techniques underlying these three methods rely on appropriate fusion of information about the shape, color and texture content of the objects presented in the medical images. Results Regarding polyp localization, the best method is Method 1 with a sensitivity of 71.8 %. Comparing the performance of the three methods in the detection of polyps, independently of the precision in the location of the lesions, Method 3 stands out, achieving a sensitivity of 99.7 %, an accuracy of 91.1 %, and a specificity of 84.9 %. Conclusion CAD, using the three studied methods, showed good accuracy in the detection of polyps with white light colonoscopy.

New technologies have greatly shaped the scientific and medical landscape within the last years. The unprecedented expansion of data and information on RNA biology has led to the discovery of new RNA classes with unique functions and unexpected modifications. Today, the biggest challenge is to transfer the large number of findings in basic RNA biology into corresponding clinical RNA-based therapeutics. Lately, this research begins to yield positive outcomes. RNA drugs advance to the final phases of clinical trials or even receive FDA approval. Furthermore, the introduction of the RNA-guided gene-editing technology CRISPR and advances in the delivery of messenger RNAs have triggered a major progression in the field of RNA-therapeutics. Especially short interfering RNAs and antisense oligonucleotides are promising examples for novel categories of therapeutics. However, several issues need to be addressed including intracellular delivery, toxicity, and immune responses before utilizing RNAs in a clinical setting. In this review, we provide an overview on opportunities and challenges for clinical translation of RNA-based therapeutics, with an emphasis on advances in novel delivery technologies and abdominal aortic aneurysm disease where non-coding RNAs have been shown to play a crucial regulatory role.

Altered host-intestinal microbiota interactions are increasingly implicated in the metabolic benefits of Roux-en-Y gastric bypass (RYGB) surgery. We previously found, however, that RYGB-associated ileal microbiota can paradoxically impair host glycemic control when transferred to germ-free mice. Here we present complementary evidence suggesting that this could be due to the heightened development of systemic endotoxemia. Consistently, application of ileal content from RYGB-treated compared with sham-operated rats onto Caco-2 cell monolayers compromised barrier function and decreased expression of the barrier-stabilizing proteins claudin-4 and desmoglein-2. Our findings raise the possibility that RYGB-associated ileal microbiota produce and release soluble metabolites which locally increase intestinal permeability to promote systemic endotoxemia-induced insulin resistance, with potential implications for the treatment of RYGB patients who eventually relapse onto type 2 diabetes.

Objective. To determine operating room efficiency for elective ophthalmologic surgeries requiring general anesthesia in a public tertiary institution based on standard efficiency parameters. Methods. Prospective observational cross-sectional study of randomly selected elective cases requiring general anesthesia from April 2019 to June 2019 in the Department of Ophthalmology of the Philippine General Hospital. A single third-party observer recorded operating room milestones from which efficiency parameters were determined and compared with local and international guidelines and efficiency benchmarks. Results. A total of fifty cases from the Retina, Plastic, Orbit, Glaucoma, and Motility services were observed. None started on the specified start time of 6:30 a.m., with surgeries starting an average of 52 ± 11.90 minutes after. Across subspecialties, median surgical preparation time was statistically significant (χ2: 12.01, p: 0.02), with the Retina and Orbit services having the most extended duration. Across age groups, pediatric cases had lower mean anesthesia preparation times (t: 2.15, df: 48, p: 0.04) and median trans-out lag times (χ2: 4.56, p: 0.03) than adults. Overall, more than 60% of cases reached targets for induction and surgical lag time. Turnaround for adult and pediatric patients was 75 ± 22.77 minutes and 71 ± 14.91 minutes, respectively. Benchmarking analysis showed that the first case on time, entry lag, and exit lag were below the 50th percentile while the room turnover time was above the 95th percentile. Conclusion. Ensuring efficiency requires a multidisciplinary team approach. This research can guide administrators in determining interventions to increase operating room efficiency.

Wireless Capsule Endoscopy (WCE) is a non-invasive medical procedure devised for painless in vivo inspection of the gastrointestinal (GI) tract. It is especially valuable for the examination of the small intestine since it is difficult to reach by traditional endoscopic procedures. The setup includes a camera with an embedded light source and a circuit capable of acquiring and transmitting the video. The main challenge of this technology is the identification of the position and trajectory of the capsule as it travels through the GI tract, which is particularly relevant during the detection of anomalies in the tissue. Given only the information provided by the recorded images, it is possible to estimate the 3D motion of the camera capsule and provide a full trajectory reconstruction. A critical yet difficult step in this process is the image registration between sequential frames. Therefore, being able to determine accurate correspondences between points, regions or features in two consecutive frames is crucial for the computation of the relative rotation and translation of the capsule. This paper comprises a comparative assessment of methodologies to address this problem with a porcine colon dataset obtained with our experimental setup.

Petroleum is a very complex and diverse organic mixture. Its composition depends on reservoir location and in situ conditions and changes once crude oil is spilled into the environment, making the characteristics associated with every spill unique. Polycyclic aromatic hydrocarbons (PAHs) are common components of the crude oil and constitute a group of persistent organic pollutants. Due to their highly hydrophobic, and their low solubility tend to accumulate in soil and sediment. The process by which oil is sourced and made available for use is referred to as the oil supply chain and involves three parts: (1) upstream, (2) midstream and (3) downstream activities. As consequence from oil supply chain activities, crude oils are subjected to biodeterioration, acidification and souring, and oil spills are frequently reported affecting not only the environment, but also the economy and human resources. Different bioremediation techniques based on microbial metabolism, such as natural attenuation, bioaugmentation, biostimulation are promising approaches to minimize the environmental impact of oil spills. The rate and efficiency of this process depend on multiple factors, like pH, oxygen content, temperature, availability and concentration of the pollutants and diversity and structure of the microbial community present in the affected (contaminated) area. Emerging approaches, such as (meta-)taxonomics and (meta-)genomics bring new insights into the molecular mechanisms of PAH microbial degradation at both single species and community levels in oil reservoirs and groundwater/seawater spills. We have scrutinized the microbiological aspects of biodegradation of PAHs naturally occurring in oil upstream activities (exploration and production), and crude oil and/or by-products spills in midstream (transport and storage) and downstream (refining and distribution) activities. This work addresses PAH biodegradation in different stages of oil supply chain affecting diverse environments (groundwater, seawater, oil reservoir) focusing on genes and pathways as well as key players involved in this process. In depth understanding of the biodegradation process will provide/improve knowledge for optimizing and monitoring bioremediation in oil spills cases and/or to impair the degradation in reservoirs avoiding deterioration of crude oil quality.

Astrocytes provide neurons with essential metabolic and structural support, modulate neuronal circuit activity and may also function as versatile surveyors of brain milieu, tuned to sense conditions of potential metabolic insufficiency. Here we show that astrocytes detect falling cerebral perfusion pressure and activate CNS autonomic sympathetic control circuits to increase systemic arterial blood pressure and heart rate with the purpose of maintaining brain blood flow and oxygen delivery. Studies conducted in experimental animals (laboratory rats) show that astrocytes respond to acute decreases in brain perfusion with elevations in intracellular [Ca2+]. Blockade of Ca2+-dependent signaling mechanisms in populations of astrocytes that reside alongside CNS sympathetic control circuits prevents compensatory increases in sympathetic nerve activity, heart rate and arterial blood pressure induced by reductions in cerebral perfusion. These data suggest that astrocytes function as intracranial baroreceptors and play an important role in homeostatic control of arterial blood pressure and brain blood flow., The brain receives 20% of cardiac output, but in accord with the current knowledge lacks a specialized sensor of its own blood flow. Here, the authors show that brain astrocytes detect drops in perfusion and trigger compensatory increases in arterial pressure and heart rate to preserve brain blood flow and oxygen delivery.

A custom head-mounted system to track smooth eye movements for control of a mouse cursor is implemented and evaluated. The system comprises a head-mounted infrared camera, an infrared light source, and a computer. Software-based image processing techniques, implemented in Microsoft Visual Studio, OpenCV, and Pupil, detect the pupil position and direction of pupil movement in near real-time. The identified direction is used to determine the desired positioning of the cursor, and the cursor moves towards the target. Two users participated in three tests to quantify the differences between incremental tracking of smooth eye movement resulting from the Vestibulo-ocular Reflex versus step-change tracking of saccadic eye movement. Tracking smooth eye movements was four times more accurate than tracking saccadic eye movements, with an average position resolution of 0.80 cm away from the target. In contrast, tracking saccadic eye movements was measured with an average position resolution of 3.21 cm. Using the incremental tracking of smooth eye movements, the user was able to place the cursor within a target as small as a 9 x 9 pixel square 90 % of the time. However, when using the step change tracking of saccadic eye movements, the user was unable to position the cursor within the 9 x 9 pixel target. The average time for the incremental tracking of smooth eye movements to track a target was 6.45 s, whereas for the step change tracking of saccadic eye movements, it was 2.61 s., Comment: 16 pages, 4 figures, 2 tables

Objective— There are currently no effective treatments for the prevention of dementia associated with vascular cognitive impairment. MicroRNAs regulate gene expression at the post-transcriptional level and play key roles in vascular disorders. TNFα (tumor necrosis factor-α) regulates blood–brain barrier breakdown through modification of cerebral tight junctions. Here, we sought key TNFα-responsive microRNAs that might influence blood–brain barrier breakdown via cerebral tight junction disruption in vascular cognitive impairment. Approach and Results— Using a mouse model of vascular cognitive impairment, chronic cerebral hypoperfusion within the white matter was induced with bilateral common carotid artery stenosis (BCAS) surgery. TNFα gene expression was increased in white matter post-BCAS surgery, and TNFα stimulation decreased claudin-5, ZO-1 (tight-junction protein 1), and occludin gene expression in murine brain endothelial cells. In silico analysis predicted 8 candidate microRNAs as regulators of claudin-5, ZO-1, and occludin gene expression. Of these, only miR-501-3p was upregulated by TNFα in vitro and was upregulated in the white matter after BCAS surgery. Further, miR-501-3p directly bound to the 3′-untranslated region of human ZO-1 and downregulated transendothelial electric resistance. In vivo administration of a locked nucleic acid –modified antisense oligonucleotide versus miR-501-3p suppressed BCAS-induced reduction of ZO-1 gene expression and blood–brain barrier disruption within the white matter and significantly ameliorated working memory deficits after BCAS surgery. Conclusions— We here provide the first evidence that the TNFα–miR-501-3p–ZO-1 axis plays an important role in the pathogenesis of cerebral hypoperfusion–induced working memory deficits and white matter lesions, as a result of blood–brain barrier breakdown via tight junction disruption. Therapeutic manipulation of miR-501-3p holds promise for limiting vascular cognitive impairment progression.

Wireless capsule endoscope (WCE) enables the visualization of the interior of the gastrointestinal (GI) tract. In particular it is very important for the examination of regions in the small bowel that cannot be reached by conventional endoscopy techniques. However, when an abnormality is found in WCE images of the small bowel, it is unknown how far is this abnormality from an anatomical reference point. The primary objective of the present paper is to give a contribution to WCE localization, using image-based methods. The main focus of this work is on the description of a hybrid multiscale affine and elastic image registration approach, its experimental application on WCE videos, and comparison with a multiscale affine registration. The proposed approach intends to track the WCE motion, by using the successive WCE frames that image the walls of the elastic small intestine. It includes registrations that capture both rigid-like and non-rigid deformations, due respectively to the rigid-like WCE movement and the elastic deformation of the small intestine originated by the GI peristaltic movement. Furthermore, the proposed approach enables the extraction of two parameters (scale and rotation) from which the relative displacement and orientation of the WCE inside the GI tract can be derived, via projective geometry. Under this approach an indicator of the WCE speed can be inferred, which can be clinically useful for video interpretation. The results of the experimental tests with real WCE video frames show the good performance of the proposed approach, when elastic deformations of the small intestine are involved in successive frames, and its superiority with respect to a multiscale affine image registration, which accounts for rigid-like deformations only and discards elastic deformations.

Background Bicuspid aortic valve (BAV), the most frequent congenital cardiac abnormality, is associated with a higher risk for ascending aortic aneurysms and aorta-related complications (ie, dissection and rupture). The aim of this study was to quantify granular media calcinosis (GMC) in the ascending aortic wall of patients with BAV. Methods We analyzed samples of the ascending aorta from patients with BAV (n = 54) and patients with tricuspid aortic valve (TAV) (n = 33) who underwent aortic repair, regarding medial thickness and diameter expansion. Additionally, the convexity and concavity of the samples were stained for GMC and elastin fragmentation. Results The quantitative analysis revealed a significantly higher extent of GMC in patients with BAV at the aortic convexity and concavity compared with patients with TAV, independent of aortic diameter. Additionally, GMC increased with enlargement of the aortic diameter in patients with BAV. Furthermore, we found a significantly reduced total medial thickness in patients with BAV compared with patients with TAV. Conclusions Our findings highlight GMC as a prominent feature of bicuspid aortopathy.

We present results concerning the validation of a novel approach for wireless capsule endoscope localization, using as ground truth a simulated biological/mechanical environment experiment. The approach relies essentially on image-based methods. It involves a hybrid multi-scale affine and elastic image registration procedure which is afterwards appropriately complemented with calibration and visual odometry techniques. The capsule was fixed at the extremity of a robotic arm and moved along a part of an ex-vivo mammalian bowel. The first validation results indicate a good correlation between the ground truth velocity and distance traveled by the capsule and the velocity and distance given by the proposed approach.

Colon cancer prevention, diagnosis, and prognosis are directly related to the identification of colonic polyps, in colonoscopy video sequences. In addition, diagnosing colon cancer in the early stages improves significantly the chance of surviving and effective treatment. Due to the large number of images that come from colonoscopy, the identification of polyps needs to be automated for effciency. In this paper, we propose a strategy for automatic polyp recognition, based on a recent multi-objective anomaly detection concept, which itself is based on Pareto Depth Analysis (PDA). Clinically, in medical images, polyps are diagnosed based on a few criteria, such as texture, shape and color. Few works use multi-criteria classification in a systematic way for polyp detection. In the present paper we use a PDA approach, to act as a binary classifier for the identification of colonic polyps. The results obtained in a medical dataset, of conventional colonoscopy images, consisting of short videos from 34 different patients, and 34 different polyps, with a total of 1360 different polyp frames, confirm that the proposed method clearly outperforms the single performance of each criterion.

Currently, a number of studies focus on the study and design of new healthcare technologies to improve elderly health and quality of life. Taking advantage of the popularity, portability, and inherent technology of smartphones, we present an emergency application for smartphones, designated as knock-to-panic (KTP). This innovative and novel system enables users to simply hit their devices in order to send an alarm signal to an emergency service. This application is a complete and autonomous emergency system, and can provide an economic, reliable, and unobtrusive method for elderly monitoring or safety protection. Moreover, the simple and fast activation of KTP makes it a viable and potentially superior alternative to traditional ambient assisted living emergency calls. Furthermore, KTP can be further extended to the general population as well and not just be limited for elderly persons. The proposed method is a threshold-based algorithm and is designed to require a low battery power consumption. The evaluation of the performance of the algorithm in collected data indicates that both sensitivity and specificity are above 90%.

This paper describes a novel method for fast colonic polyp detection in colonoscopy images. Firstly, polyp detection is formulated as a similarity-based anomaly detection method, which formally involves non-dominated sorting based on multiple objectives. The chosen objectives rely on the main physical and visible differences, observed in colonoscopy images, between regions containing colonic polyps and the surrounding normal mucosa. These differences are defined primarily according to the contrast in shape, texture, and color. Secondly, as non-dominated sorting is of combinatorial nature and is costly to compute, it is replaced by a fast algorithm that approximates the sorting in the continuum limit. The fast algorithm involves numerical solutions to a particular Hamilton–Jacobi equation. The proposed similarity-based anomaly detection is thus reformulated into a fast polyp detection method. Several experiments were conducted with a proprietary medical data set, containing 1640 instances of 41 different polyps. The results show that the proposed Hamilton–Jacobi approach to non-dominated sorting speeds up the non-dominated sorting procedure, by more than 500%, and, when compared with other existing methods, it is also faster without lost of accuracy. Moreover, the tests conducted for streaming data, reveal an outstanding performance, in terms of sensitivity and specificity, as well as, a fast auto-adaptability, which demonstrate the power of the proposed approach towards a real-time and automatic detection, undoubtedly beneficial for clinical practice.

Aim: Arterial stiffness is a significant risk factor for many cardiovascular diseases, including abdominal aortic aneurysms (AAA). Nicotine, the major active ingredient of e-cigarettes and tobacco smoke, induces acute vasomotor effects that may temporarily increase arterial stiffness. Here, we investigated the effects of long-term nicotine exposure on structural aortic stiffness. Methods: Mice (C57BL/6) were infused with nicotine for 40 days (20 mg/kg/day). Arterial stiffness of the thoracic (TS) and abdominal (AS) aortic segments was analyzed using ultrasound (PWV, pulse wave velocity) and ex vivo pressure myograph measurements. For mechanistic studies, aortic matrix-metalloproteinase (MMP) expression and activity as well as medial elastin architecture were analyzed. Results: Global aortic stiffness increased with nicotine. In particular, local stiffening of the abdominal segment occurred after 10 days, while thoracic aortic stiffness was only increased after 40 days, resulting in aortic stiffness segmentation. Mechanistically, nicotine exposure enhanced expression of MMP-2/-9 and elastolytic activity in both aortic segments. Elastin degradation occurred in both segments; however, basal elastin levels were higher in the thoracic aorta. Finally, MMP-inhibition significantly reduced nicotine-induced MMP activity, elastin destruction, and aortic stiffening. Conclusion: Chronic nicotine exposure induces aortic MMP expression and structural aortic damage (elastin fragmentation), irreversibly increasing aortic stiffness. This process predominantly affects the abdominal aortic segment, presumably due in part to a lower basal elastin content. This novel phenomenon may help to explain the role of nicotine as a major risk factor for AAA formation and has health implications for ECIGs and other modes of nicotine delivery.

Objective— Recruitment of immunologic competent cells to the vessel wall is a crucial step in formation of abdominal aortic aneurysms (AAA). Innate immunity effectors (eg, macrophages), as well as mediators of adaptive immunity (eg, T cells), orchestrate a local vascular inflammatory response. IL-10 (interleukin-10) is an immune-regulatory cytokine with a crucial role in suppression of inflammatory processes. We hypothesized that an increase in systemic IL-10-levels would mitigate AAA progression. Approach and Results— Using a single intravenous injection protocol, we transfected an IL-10 transcribing nonimmunogenic minicircle vector into the Ang II (angiotensin II)-ApoE −/− infusion mouse model of AAA. IL-10 minicircle transfection significantly reduced average aortic diameter measured via ultrasound at day 28 from 166.1±10.8% (control) to 131.0±5.8% (IL-10 transfected). Rates of dissecting AAA were reduced by IL-10 treatment, with an increase in freedom from dissecting AAA from 21.5% to 62.3%. Using flow cytometry of aortic tissue from minicircle IL-10-treated animals, we found a significantly higher percentage of CD4 + /CD25 + /Foxp3 (forkhead box P3) + regulatory T cells, with fewer CD8 + /GZMB + (granzyme B) cytotoxic T cells. Furthermore, isolated aortic macrophages produced less TNF-α (tumor necrosis factor-α), more IL-10, and were more likely to be MRC1 (mannose receptor, C type 1)–positive alternatively activated macrophages. These results concurred with gene expression analysis of lipopolysaccharide-stimulated and Ang II-primed human peripheral blood mononuclear cells. Conclusions— Taken together, we provide an effective gene therapy approach to AAA in mice by enhancing antiinflammatory and dampening proinflammatory pathways through minicircle-induced augmentation of systemic IL-10 expression.

Background: Aortic atherosclerosis and dissection cause significant morbidity and mortality. Although atherosclerosis is associated with aortic dissection, points of interaction are unclear. Regulator-of-G-protein signaling 5 (RGS5) is still insufficiently characterized regarding its role in aortic atherosclerosis and dissection. Objectives: We investigated Rgs5-deficiencie’s effects on aortic atherosclerosis and dissection. Methods: ApoE -/- Rgs5 GFP/GFP double knockout mice (rraa, n=15) and WT littermates (RRaa, n=17) were fed a cholesterol-rich diet for 14weeks. Plaque size, plaque morphology (composition and a validated vulnerability score based on Stary criteria), macrophage phenotype and aortic dissection were evaluated. Results: rraa mice displayed more aortic dissections (5/15) compared to WT (0/17; p2 -test). Surprisingly, rraa showed significantly smaller (rraa plaque size 190 657 μm 2 ± 93184 vs. control 398 279 μm 2 ± 153339) and less complicated plaques (5 of 15 mice with >2 vulnerability features) compared to RRaa (14 of 15 with >2 vulnerability features, p+ -myeloid cells revealed increased proportions of macrophages staining positive for pro-inflammatory markers (Cd86/Cd45: 24.71 area% ± 3.75 for RRaa; 60.95 area% ± 5.909, for rraa and iNOS/Cd45: 37.22 area% ± 6.37, for RRaa; 73.99 area% ± 3.997 for rraa, p Conclusions: rraa mice are more prone to aortic dissection despite smaller and less complex plaques with reduced anti-inflammatory but increased numbers of pro-inflammatory macrophages. We hypothesize that pro-inflammatory macrophage polarization along with evasion of anti-inflammatory macrophages in rraa mice could be causative for higher dissection numbers. Our data warrant further studies into the diverging pathomechanistic roles of Rgs5 in aortic dissection and atherosclerosis.

Background: Arterial stiffness is part of arterial aging and strongly associated with increased risk for cardiovascular events. Unfortunately, until today there is no treatment available effectively counteracting arterial stiffening. One key feature of arterial stiffening is elastin fragmentation. Breakdown of elastin is mediated by matrix metalloproteinases (MMPs), in particular MMP-2 and MMP-9 play a pivotal role in this process. Non-coding micro RNAs (miRs) were found to effectively regulate gene expression, consequentially representing potential therapeutic targets. We hypothesize that miR146a inhibits MMP-2 and MMP-9, thus leading to decreased elastin fragmentation in the vascular extracellular matrix. Methods and Results: RNA Sequencing found miR146a to be upregulated in a stiffness-dependent manner in vitro and in an age dependent manner in vivo . Since both MMP-2 and MMP-9 are predicted targets of miR146a, we transfected aortic smooth muscle cells with constructs either increasing (mimicking construct) or decreasing (inhibitory anti-sense construct) effective miR146a levels and evaluated the effect on MMP-2 and MMP-9 expression and activity in vitro . qRT-PCR analysis demonstrated significantly de-repressed MMP-2 and MMP-9 levels upon transfection with inhibitor constructs, while mimic constructs further repressed the expression of MMP-2 and MMP-9. Overall MMP activity was significantly altered accordingly after transfection with the respective constructs as determined by a fluorimetric MMP Activity Assay. MMP-2 activity could be specifically assessed using Zymography. After transfection with miR146a inhibitor, both active MMP-2 as well as pro-MMP-2 activity were found to be significantly increased. Conclusion: Our study provides first evidence that miR146a reduces the levels and activity of MMP-2 and MMP-9 in vascular smooth muscle cells. We conclude that miR146a might have protective function on the integrity of the elastin network in the arterial media. We therefore consider miR146a a potential drug target in the context of elastin fragmentation and arterial stiffness, thus potentially alleviating the development of aortic aneurysm.

Background: Arterial stiffness, which may develop due to vascular calcification, is a significant pathophysiological factor associated with arterial aging or diseases such as type-2 diabetes or end stage renal disease. With no effective therapy clinically available to date, molecular and epigenetic mechanisms of ectopic calcification in conduit arteries are receiving increasing attention to identify targets for therapeutical interference. Here we show that miR-146a may serve as a therapeutic candidate to counteract vascular calcification. Methods: Ectopic calcification was assessed in human aortic smooth muscle cells (AoSMCs) using Alizarin red and Von kossa stainings. The total calcium content in hydroxyapatite crystals was assessed using QuantiChrom TM calcium assay kit. The mRNA expression levels of BMP2, MSX2 and SORT1 were assessed by TaqMan real-time PCR. Results: The endogenous expression of miR-146a was significantly decreased and simultaneously ectopic calcium deposition was significantly increased in AoSMCs exposed to osteogenic stimulation. However, overexpression of miR-146a in AoSMCs cultured in vitro reduced the ectopic calcium deposits. Simultaneously, mRNA expression levels of osteogenic markers and drivers of calcification, such as BMP2, MSX2 and SORT1 - all predicted miR-146a target genes - were significantly reduced. Conversely, significantly increased calcium deposits were observed when miR-146a was inhibited in these cells in similar culture conditions with upregulated BMP2, MSX2 and SORT1 mRNA expression levels. Conclusion: The results suggest that miR-146a may serve as a modulator of AoSMC calcification and miR-146a supplementation may qualify as a therapeutic intervention to counteract vascular calcification due to aging, type-2 diabetes or end stage renal disease.

Background Context The optimal method for surgical treatment of early onset scoliosis is currently unknown. Although the aim of growth-friendly systems is to reduce the curve and maintain growth, there is no consensus on how to measure spinal growth during and after the treatment. Different measurements of different segments (T1–S1, T1–T12, instrumented length) are used for different time points to evaluate growth. The aim of this review is to assess what measurements are used and to compare the growth-friendly systems based on spinal growth during treatment. Methods The electronic MEDLINE, EMBASE, and Cochrane databases were systematically searched for original articles that reported growth for traditional growing rods (TGR), vertical expandable prosthetic titanium rib expansion technique (VEPTR), Shilla, magnetically controlled growing rods (MCGR), and Luque-trolley systems. All measurements were recorded, and weighted averages calculated in centimeter per year were compared. Results We included 52 studies (26 TGR, 12 MCGR, 6 VEPTR, 4 Luque trolley, 1 Shilla, and 3 mixed). Often only one segment was reported (T1–S1 length in 22 studies, T1–T12 length in two studies, and instrumented length in five studies). The remaining 22 studies reported T1–S1 length in combination with T1–T12 length (15 studies) or instrumented length (eight studies). Spinalgrowth achieved by initial correction only was a considerable 3.9 cm (based on 34 studies) as well as the spinal growth achieved by the final fusion surgery (2.3 cm in four studies). To specifically assess growth achieved with the system, length gain after initial surgery and before final fusion in growth system graduates was considered. Only four TGR studies reported on this “true” spinal growth with 0.6 and 0.3 cm/y in the T1–S1 and T1–T12 segment, respectively. Conclusions Reporting on spinal growth is currently inadequate and does not allow a good comparison of different techniques. However, all systems often report growth similar to Dimeglio's T1–S1 spinal growth of 1 cm/y. It should be recognized though that a considerable portion of the reported spinal growth is the result of the initial and final surgical correction and not due to the growth-friendly implant.

Agriculture is the primary economic activity for between 50 and 90 percent of the population in Sub-Saharan African countries. Ninety five percent of the food that is produced in Sub-Saharan Africa is grown through rain-fed agriculture. This implies that the region will suffer most from climate change due to its dependence on rain-fed agriculture. Vulnerability to climate change will be especially significant among the resource poor smallholder farmers in African countries whose livelihoods depend on rain-fed agriculture in marginal areas. African agriculture is characterized by variations in farming systems with about 90% of the farming occurring in integrated systems. In these mixed farming systems, the food security challenge may require an integrated approach to match the existing systems. A rainbow evolution which emphasizes the need for diversified systems may be the best practice in raising agricultural productivity. A multidisciplinary approach based on the theory of embededdness whereby farmers, researchers, extension institutions, and political institutions work together can further raise agriculture production and improve food security. Social networks in communities of farmers provide channels for identifying problems and farmers? knowledge integrated with that of research and extension can provide sustainable solutions for food production in smallholder farming systems in Africa.?

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among patients with diabetes mellitus (DM). DM can lead to multiple cardiovascular complications, including coronary artery disease (CAD), cardiac hypertrophy, and heart failure (HF). HF represents one of the most common causes of death in patients with DM and results from DM-induced CAD and diabetic cardiomyopathy. Oxidative stress is closely associated with the pathogenesis of DM and results from overproduction of reactive oxygen species (ROS). ROS overproduction is associated with hyperglycemia and metabolic disorders, such as impaired antioxidant function in conjunction with impaired antioxidant activity. Long-term exposure to oxidative stress in DM induces chronic inflammation and fibrosis in a range of tissues, leading to formation and progression of disease states in these tissues. Indeed, markers for oxidative stress are overexpressed in patients with DM, suggesting that increased ROS may be primarily responsible for the development of diabetic complications. Therefore, an understanding of the pathophysiological mechanisms mediated by oxidative stress is crucial to the prevention and treatment of diabetes-induced CVD. The current review focuses on the relationship between diabetes-induced CVD and oxidative stress, while highlighting the latest insights into this relationship from findings on diabetic heart and vascular disease.

In the last two decades, we have seen an amazing development of image processing techniques targeted for medical applications. We propose multi-GPU-based parallel real-time algorithms for segmentation and shape-based object detection, aiming at accelerating two medical image processing methods: automated blood detection in wireless capsule endoscopy (WCE) images and automated bright lesion detection in retinal fundus images. In the former method we identified segmentation and object detection as being responsible for consuming most of the global processing time. While in the latter, as segmentation was not used, shape-based object detection was the compute-intensive task identified. Experimental results show that the accelerated method running on multi-GPU systems for blood detection in WCE images is on average 265 times faster than the original CPU version and is able to process 344 frames per second. By applying the multi-GPU framework for bright lesion detection in fundus images we are able to process 62 frames per second with a speedup average 667 times faster than the equivalent CPU version.

miRNAs are potential regulators of carotid artery stenosis and concordant vulnerable atherosclerotic plaques. Hence, we analyzed miRNA expression in laser captured micro-dissected fibrous caps of either ruptured or stable plaques (n = 10 each), discovering that miR-21 was significantly downregulated in unstable lesions. To functionally evaluate miR-21 in plaque vulnerability, miR-21 and miR-21/apolipoprotein-E double-deficient mice (Apoe−/−miR-21−/−) were assessed. miR-21−/− mice lacked sufficient smooth muscle cell proliferation in response to carotid ligation injury. When exposing Apoe−/−miR-21−/− mice to an inducible plaque rupture model, they presented with more atherothrombotic events (93%) compared with miR-21+/+Apoe−/− mice (57%). We discovered that smooth muscle cell fate in experimentally induced advanced lesions is steered via a REST-miR-21-REST feedback signaling pathway. Furthermore, Apoe−/−miR-21−/− mice presented with more pronounced atherosclerotic lesions, greater foam cell formation, and substantially higher levels of arterial macrophage infiltration. Local delivery of a miR-21 mimic using ultrasound-targeted microbubbles into carotid plaques rescued the vulnerable plaque rupture phenotype. In the present study, we identify miR-21 as a key modulator of pathologic processes in advanced atherosclerosis. Targeted, lesion site-specific overexpression of miR-21 can stabilize vulnerable plaques.

The 22q11.2 Deletion Syndrome (22q11.2DS) is the most common microdeletion syndrome with an estimated prevalence of 1:4,000 live births. 22q11.2DS is known to have wide phenotypic variability, including orthopaedic manifestations. The purpose of this systematic review is to increase the awareness of orthopaedic manifestations associated with 22q11.2DS. This systematic review was performed according to the PRISMA Guidelines. Original epidemiological studies on the prevalence of orthopaedic manifestations within 22q11.2DS were systematically searched for in PubMed and EMBASE. The included articles were scored according to a risk-of-bias tool, a best-evidence synthesis was performed and the prevalence data was extracted. Sixty-nine published manuscripts described 58 orthopaedic manifestations in a total of 6,055 patients. The prevalence of at least one cervical or occipital anomaly is 90.5-100% (strong evidence). Fourteen studies (n = 2,264) revealed moderate evidence for a wide scoliosis prevalence of 0.6-60%. Two studies demonstrated that 5-6.4% of all 22q11.2DS patients required surgical scoliosis correction. Fifteen studies (n = 2,115) reported a 1.1-13.3% prevalence of clubfoot with moderate evidence. Other reported orthopaedic manifestations are patellar dislocation (10-20%), juvenile rheumatic arthritis (3.75%), impaired growth and skeletal anomalies like polydactyly (1.0-3.7%), syndactyly (11-11.8%), butterfly vertebrae (11.1%) and 13 ribs (2-19%). Orthopaedic findings are important manifestations of the 22q11.2DS, both in bringing patients to diagnostic attention and in requiring surveillance and appropriate intervention. Data on these manifestations are scattered and incomprehensive. Routinely screening for cervical anomalies, scoliosis, and upper and lower limb malformations is recommended in this vulnerable group of patients.

In the search for markers and modulators of vascular disease, miRNAs have emerged as potent therapeutic targets. We investigated miRNAs of clinical interest in patients with unstable carotid stenosis at risk of stroke. Utilizing patient material from the Biobank of Karolinska Endarterectomies (BiKE), we profiled miRNA expression in symptomatic versus asymptomatic patients with high-grade carotid artery stenosis. A PCR-based miRNA of plasma, sampled at the carotid lesion site, identified eight deregulated miRNAs (miR-15b, -29c, -30c/d, -150, -191, -210 and -500). miR-210 was the most significantly downregulated miRNA in local plasma material. Laser-capture microdissection as well as in situ hybridization revealed a distinct localization of miR-210 in the fibrous caps of atherosclerotic lesions and showed reduced miR-210 expression in the unstable fibrous cap. We confirmed that miR-210 directly targets the tumor suppressor gene adenomatous polyposis coli (APC), thereby affecting Wnt signaling and regulating vascular smooth muscle cell survival, as well as differentiation, in advanced atherosclerotic lesions. Substantial changes in arterial miR-210 were detectable in two rodent models of vascular remodeling and plaque rupture. Modulating miR-210 in vitro and in vivo improved fibrous cap stability with implications for vascular disease. We discovered that an unstable carotid plaque at risk of stroke is characterized by low expression of miR-210. miR-210 contributes to stabilizing carotid plaques through inhibition of APC, ensuring vascular smooth muscle cell survival. We present local delivery of miR-210 as a therapeutic approach for prevention of atherothrombotic disease.

Background: Abdominal aortic aneurysm (AAA) is defined as a permanent dilation of the abdominal aorta that is highly lethal in case of rupture. Current therapeutic approaches are limited to open surgery or stent-based endovascular aortic repair (EVAR) to exclude large sized AAA (>5.5 cm) from the circulation. However, to date there is no effective therapy to prevent small AAA formation and progression. Nonetheless, options for small AAA disease are highly desirable as even small AAA may rupture and app. 70% of all small AAA will grow and eventually require surgical repair. Objective: Building on our previous experimental research findings we present a novel therapeutic approach for early AAA intervention. Methods and Results: Our recent biomechanical studies in a murine model of AAA development (elastase model) as well as in human aortae indicate that early AAA growth is critically driven by a stiffness gradient between a stiff AAA segment and the adjacent more compliant aorta. As a promising therapeutic intervention, we found that stiffening of the AAA-adjacent aorta (by external glue application) was sufficient to stop murine AAA formation. In a translational approach we now aim to develop an intravascular stent prototype that is deployed in the neck region of a developing AAA to increase the mechanical stiffness of the AAA-adjacent aorta. We hypothesize that this intervention will decrease the aortic stiffness gradient towards the AAA segment – thereby preventing further AAA growth. Stent prototypes with varying designs will be tested in a pig model of AAA disease that closely resembles the human anatomic situation. Conclusion: This project demonstrates a highly promising opportunity to directly translate novel pathomechanistic insights into AAA pathobiology from bench to bedside application and stop early AAA progression in humans.

Background Context Radiation exposure remains a big concern in adolescent idiopathic scoliosis (AIS). Ultrasound imaging of the spine could significantly reduce or possibly even eliminate this radiation hazard. The spinous processes (SPs) and transverse processes (TPs) were used to measure the coronal deformity. Both landmarks provided reliable information on the severity of the curve as related to the traditional Cobb angle. However, it remained unclear which coronal ultrasound angle is the most appropriate method to measure the curve severity. Purpose The objective of this study was to test the reliability and the validity of several ultrasound angle measurements in the coronal plane as compared with the radiographic coronal Cobb angle in patients with AIS. Study Design/Setting This is a cross-sectional study. Patient Sample The study included 33 patients with AIS, both male and female (Cobb angle range: 3°–90°, primary and secondary curves), who underwent posterior-anterior radiography of the spine. Outcome Measures The outcome measures were the reliability (intraclass correlation coefficients [ICCs] for the intra- and interobserver variabilities) and the validity (linear regression analysis and Bland-Altman method, including the mean absolute difference [MAD]) of different ultrasound measurements. Materials and Methods The patients were scanned using a dedicated ultrasound machine (Scolioscan, Telefield Medical Imaging Ltd, Hong Kong). The reliability and the validity were tested for three coronal ultrasound angles: an automatic and manual SP angle and a manual TP angle as compared with the radiographic coronal main thoracic or (thoraco)lumbar Cobb angles. Results The ICC showed very reliable measurements of all ultrasound methods (ICC ≥0.84). The ultrasound angles were 15%–37% smaller as compared with the Cobb angles; however, excellent linear correlations were seen between all ultrasound angles and the Cobb angle (thoracic: R2≥0.987 and (thoraco)lumbar R2≥0.970), and the Bland-Altman plot showed a good agreement between all ultrasound angles and the Cobb angle. The MADs of the ultrasound angles, corrected using the linear regression equation, and the Cobb angles showed no significant difference between the different ultrasound angles (MAD: automatic SP angle 4.9°±3.2°, manual SP angle 4.5°±3.1°, and manual TP angle 4.7°±3.6°; p≥.388). Conclusions Coronal ultrasound angles are based on different landmarks than the traditional Cobb angle measurement and cannot represent the same angle values. In this study, we found excellent correlations between the ultrasound and Cobb measurements, without differences in the reliability and validity between the ultrasound angles based on the SPs and TPs. Therefore, the severity of the deformity in patients with AIS can be assessed by ultrasound imaging, avoiding hazardous ionizing radiation and enabling more individualized patient care. It also opens possibilities for screening.

In a previous work we have shown that the curve representing the dissimilarity measure between consecutive frames of a wireless capsule endoscopic video of the small bowel, obtained by means of an image registration method, can be regarded as a rough indicator of the speed of the capsule, and simultaneously, it is also a valuable auxiliary medical tool. In effect, this curve enables a global and fast interpretation of the video, in the sense that it clearly divides the video frames into two main categories: consecutive frames with similar content, which correspond to low values in the curve, and consecutive frames displaying abrupt changes in the image content, which are depicted by peaks, i.e. high values, in the curve. As the main goal of a wireless capsule video examination consists in searching for abnormal features in the images, the purpose of the present work is to analyse whether this curve can also be used to search, quickly, for abnormalities. The experiments performed focus on bleeding identification in small bowel images.

In 1949, the first commercial fracturing treatment was performed by Stanolind Oil and Gas Company (Pan American Energy at present) for increasing well productivity. That is how the most outstanding well stimulation procedures that industry ever known began. Since this technique was spread wide world, many natural polymers such as guar, modified guar, xanthan gums, and also modified cellulose, among others, were used as gelant agents.

Background Takotsubo syndrome (TTS) is characterized by an acute left ventricular dysfunction and is associated with life-threating complications in the acute phase. The underlying disease mechanism in TTS is still unknown. A genetic basis has been suggested to be involved in the pathogenesis. Objectives The aims of the study were to establish an in vitro induced pluripotent stem cell (iPSC) model of TTS, to test the hypothesis of altered β-adrenergic signaling in TTS iPSC-cardiomyocytes (CMs), and to explore whether genetic susceptibility underlies the pathophysiology of TTS. Methods Somatic cells of patients with TTS and control subjects were reprogrammed to iPSCs and differentiated into CMs. Three-month-old CMs were subjected to catecholamine stimulation to simulate neurohumoral overstimulation. We investigated β-adrenergic signaling and TTS cardiomyocyte function. Results Enhanced β-adrenergic signaling in TTS-iPSC-CMs under catecholamine-induced stress increased expression of the cardiac stress marker NR4A1; cyclic adenosine monophosphate levels; and cyclic adenosine monophosphate–dependent protein kinase A–mediated hyperphosphorylation of RYR2-S2808, PLN-S16, TNI-S23/24, and Cav1.2-S1928, and leads to a reduced calcium time to transient 50% decay. These cellular catecholamine-dependent responses were mainly mediated by β1-adrenoceptor signaling in TTS. Engineered heart muscles from TTS-iPSC-CMs showed an impaired force of contraction and a higher sensitivity to isoprenaline-stimulated inotropy compared with control subjects. In addition, altered electrical activity and increased lipid accumulation were detected in catecholamine-treated TTS-iPSC-CMs, and were confirmed by differentially expressed lipid transporters CD36 and CPT1C. Furthermore, we uncovered genetic variants in different key regulators of cardiac function. Conclusions Enhanced β-adrenergic signaling and higher sensitivity to catecholamine-induced toxicity were identified as mechanisms associated with the TTS phenotype. (International Takotsubo Registry [InterTAK Registry] [InterTAK]; NCT01947621)

Colorectal polyps are important precursors to colon cancer, a major health problem. Colon capsule endoscopy (CCE) is a safe and minimally invasive examination procedure, in which the images of the intestine are obtained via digital cameras on board of a small capsule ingested by a patient. The video sequence is then analyzed for the presence of polyps. We propose an algorithm that relieves the labor of a human operator analyzing the frames in the video sequence. The algorithm acts as a binary classifier, which labels the frame as either containing polyps or not, based on the geometrical analysis and the texture content of the frame. The geometrical analysis is based on a segmentation of an image with the help of a mid-pass filter. The features extracted by the segmentation procedure are classified according to an assumption that the polyps are characterized as protrusions that are mostly round in shape. Thus, we use a best fit ball radius as a decision parameter of a binary classifier. We present a statistical study of the performance of our approach on a data set containing over 18,900 frames from the endoscopic video sequences of five adult patients. The algorithm demonstrates a solid performance, achieving 47% sensitivity per frame and over 81% sensitivity per polyp at a specificity level of 90%. On average, with a video sequence length of 3747 frames, only 367 false positive frames need to be inspected by a human operator., 16 pages, 9 figures, 4 tables

Colorectal cancer (CRC) is one of the most common cancers worldwide and after a certain age (≥50) regular colonoscopy examination for CRC screening is highly recommended. One of the most prominent precursors of CRC are abnormal growths known as polyps. If a polyp is detected during colonoscopy examination the endoscopist needs to decide whether the polyp should be discarded, removed, or biopsied for further examination. However, the last two options involve some risks for the patient, while not all the polyps are precancerous. On the other hand, discarding a polyp has the risk of failing to detect CRC. We propose an automatic and unsupervised method for the segmentation of colonic polyps for in vivo Narrow-Band-Imaging (NBI) data. Polyp segmentation is a crucial step towards an automatic real-time polyp classification system, that could help the endoscopist in the diagnosis of CRC. The proposed method is a histogram based two-phase segmentation model, involving the Wasserstein distance. These histograms incorporate fused information about suitable image descriptors, namely semi-local texture, geometry and color. To test the proposed segmentation methodology we use a dataset consisting of 86 NBI polyp frames: the 83% sensitivity, 95% specificity, and 93% accuracy suggest a better performance compared to the results obtained with other methods.

Wireless capsule endoscopy (WCE) has revolutionised the diagnosis and treatment of gastrointestinal tract, especially the small intestine where traditional endoscopies cannot reach. However, this new technology leads to the inspection of a large number of images, which is a time-consuming process and also too hard by naked eyes for doctors. In this paper, we propose a new computerised method for bleeding detection in WCE images. We use the second component of CIE Lab colour space together with appropriate segmentation and enhancement techniques, involving an adaptive anisotropic diffusion (alike Perona–Malik diffusion). As a result of this procedure, it is possible to devise four functions to discriminate between bleeding and normal regions in WCE images. These four bleeding detectors rely on the eigenvalues of the Hessian and on the Laplacian of the modified enhanced image. Multiscale image analysis approach is also involved in the definition of these detectors for handling the maximum and minimum sizes ...

Background: Accelerated arterial stiffening is a complication of diabetes mellitus and associated with the development of hypertension. Arterial stiffening results from extensive extracellular matrix remodeling (elastin breakdown, collagen accumulation). MicroRNA miR-29b directly regulates the expression of genes governing fibrosis (such as COL1A1, COL3A1) and elastin breakdown ( MMP2, MMP9 ). However, its impact on aortic stiffness is unclear. Objective: This study was designed to investigate the role of miR-29b as potential mediator of diabetic aortic stiffening. Methods and Results: Serial ex vivo mechanical testing of the thoracic aorta and volume-pressure recording (VPR) based tail-cuff blood pressure measurements revealed that aortic stiffening precedes blood (pulse) pressure elevations in diabetic db/db mice. Vascular stiffening was accompanied by increased elastin fragmentation and collagen deposition (EvG and Picrosirius Red staining). qRT-PCR, in-situ hybridization and immunohistochemistry revealed decreased expression of miR-29b and de-repression of target genes ( Col1A1, COL3A1, MMP2, MMP9 ) in db/db mice compared to controls. Investigating the mechanistic significance of miR-29b for arterial stiffening, forced downregulation of miR-29b (via systemic LNA-miR-29b inhibitor application) results in enhanced elastin fragmentation, increased medial collagen deposition, aortic stiffness and augmented pulse pressure. Conclusions: In conclusion this study identifies miR-29b as a regulator and potential therapeutic target of diabetic aortic stiffening.