Observation of room-temperature polar skyrmions.

Complex topological configurations are fertile ground for exploring emergent phenomena and exotic phases in condensed-matter physics. For example, the recent discovery of polarization vortices and their associated complex-phase coexistence and response under applied electric fields in superlattices of (PbTiO3)n/(SrTiO3)n suggests the presence of a complex, multi-dimensional system capable of interesting physical responses, such as chirality, negative capacitance and large piezo-electric responses1-3. Here, by varying epitaxial constraints, we discover room-temperature polar-skyrmion bubbles in a lead titanate layer confined by strontium titanate layers, which are imaged by atomic-resolution scanning transmission electron microscopy. Phase-field modelling and second-principles calculations reveal that the polar-skyrmion bubbles have a skyrmion number of +1, and resonant soft-X-ray diffraction experiments show circular dichroism, confirming chirality. Such nanometre-scale polar-skyrmion bubbles are the electric analogues of magnetic skyrmions, and could contribute to the advancement of ferroelectrics towards functionalities incorporating emergent chirality and electrically controllable negative capacitance.

Local negative permittivity and topological phase transition in polar skyrmions.

Topological solitons such as magnetic skyrmions have drawn attention as stable quasi-particle-like objects. The recent discovery of polar vortices and skyrmions in ferroelectric oxide superlattices has opened up new vistas to explore topology, emergent phenomena and approaches for manipulating such features with electric fields. Using macroscopic dielectric measurements, coupled with direct scanning convergent beam electron diffraction imaging on the atomic scale, theoretical phase-field simulations and second-principles calculations, we demonstrate that polar skyrmions in (PbTiO3)n/(SrTiO3)n superlattices are distinguished by a sheath of negative permittivity at the periphery of each skyrmion. This enhances the effective dielectric permittivity compared with the individual SrTiO3 and PbTiO3 layers. Moreover, the response of these topologically protected structures to electric field and temperature shows a reversible phase transition from the skyrmion state to a trivial uniform ferroelectric state, accompanied by large tunability of the dielectric permittivity. Pulsed switching measurements show a time-dependent evolution and recovery of the skyrmion state (and macroscopic dielectric response). The interrelationship between topological and dielectric properties presents an opportunity to simultaneously manipulate both by a single, and easily controlled, stimulus, the applied electric field.

Optical creation of a supercrystal with three-dimensional nanoscale periodicity.

Stimulation with ultrafast light pulses can realize and manipulate states of matter with emergent structural, electronic and magnetic phenomena. However, these non-equilibrium phases are often transient and the challenge is to stabilize them as persistent states. Here, we show that atomic-scale PbTiO3/SrTiO3 superlattices, counterpoising strain and polarization states in alternate layers, are converted by sub-picosecond optical pulses to a supercrystal phase. This phase persists indefinitely under ambient conditions, has not been created via equilibrium routes, and can be erased by heating. X-ray scattering and microscopy show this unusual phase consists of a coherent three-dimensional structure with polar, strain and charge-ordering periodicities of up to 30 nm. By adjusting only dielectric properties, the phase-field model describes this emergent phase as a photo-induced charge-stabilized supercrystal formed from a two-phase equilibrium state. Our results demonstrate opportunities for light-activated pathways to thermally inaccessible and emergent metastable states.

Technical performance of colonoscopy -- multicenter study in university and non-university centers of Romania.

UNLABELLED: The aim of the paper was to evaluate the national availability of colonoscopy and the quality parameters of this procedure in our country. MATERIAL AND METHOD: During a 6 months period (01.07- 31.12.2009), we performed a prospective multicenter study in which 76 centers were invited to respond to a questionnaire regarding colonoscopy, 39 centers agreeing to participate. We assessed: the number of colonoscopies, the number of total colonoscopies and the causes of incomplete colonoscopies. RESULTS: During the study period, 16,083 colonoscopies were performed, 12,294 (76.4%) of them total colonoscopies. In 1,191 cases, stenosis was the cause of incomplete colonoscopy. If we consider this an objective reason for an incomplete colonoscopy, there were 12,294 total colonoscopies (82.4%). Comparing university centers with non-university ones, the proportion of total colonoscopies was 10,400/12,475 (83.4%) vs. 1,894/2,417 (78.4%) (p less then 0.0001). However, comparing the present study with previous ones, performed in 2003 and 2007, the proportion of total colonoscopies increased from 70.5% to 76.9% and 82.4% respectively (2003 vs. 2007 p less then 0.0001; 2007 vs. 2009 p less then 0.0001), while the quality difference between university and non-university hospitals persisted. CONCLUSIONS: the quality of colonoscopy in Romania increased in the last 5 years, while the quality difference between university and non-university hospitals persisted.

Retraction Notice to: Stem cell and colorectal carcinogenesis.

[This retracts the article on p. 6 in vol. 9, PMID: 27713769.].

Isospin character of the pygmy dipole resonance in 124Sn.

The pygmy dipole resonance has been studied in the proton-magic nucleus 124Sn with the (α, α'γ) coincidence method at Eα=136 MeV. The comparison with results of photon-scattering experiments reveals a splitting into two components with different structure: one group of states which is excited in (α, α'γ) as well as in (γ, γ') reactions and a group of states at higher energies which is only excited in (γ, γ') reactions. Calculations with the self-consistent relativistic quasiparticle time-blocking approximation and the quasiparticle phonon model are in qualitative agreement with the experimental results and predict a low-lying isoscalar component dominated by neutron-skin oscillations and a higher-lying more isovector component on the tail of the giant dipole resonance.

Stem cells and colorectal carcinogenesis.

Colorectal cancer represents an important cause of mortality and morbidity. Unfortunately, the physiopathology is still under study. There are theories about carcinogenesis and it is known that not only a single factor is responsible for the development of a tumor, but several conditions. Stem cells are a promising target for the treatment of colorectal cancer, along with the environment that has an important role. It has been postulated that mutations within the adult colonic stem cells may induce neoplastic changes. This theory is based on the observation that within a colon cancer, less than 1% of the neoplastic cells have the ability to regenerate the tumor and therefore they are responsible for recurrence. It is important to know that a new way of treatment needs to be found, since these cells are resistant to chemotherapy and radiotherapy.

Colorectal Chemoprevention.

With over 1 million cases diagnosed worldwide each year - incidence which seems to rise with the progressive westernization of lifestyles in Asian and African populations - colorectal cancer is the third most commonly diagnosed cancer in both men and women. Colorectal neoplasms and/or pre-neoplasms can be prevented by interfering with the various steps of oncogenesis, which begins with uncontrolled epithelial cell replication, continues with the formation of adenomas and eventually evolves into malignancy. The knowledge described herein will help to reduce and prevent this malignancy, which is one of the most frequent neoplasms in some developed countries. Genetics, experimental and epidemiologic studies suggest that colorectal cancer results from complex interactions between inherited susceptibility and environmental factors. Primary prevention involves the identification of genetic, biologic, and environmental factors that are etiologic or pathogenic in the development of cancer, and subsequent complete or significant interference with their effects on carcinogenesis.

Biomarkers in Rheumatoid Arthritis, what is new?

UNLABELLED: Rheumatoid arthritis (RA) is a chronic inflammatory disease with autoimmune pathogenesis. It affects mainly small joints (of the hands and feet) and has many systemic manifestations. Studying biomarkers in rheumatology intensely appeared from the need to understand the mechanisms underlying some rheumatic diseases. Discovering new biomarkers with key roles in various stages of evolution, remains a subject of interest for RA. Currently, according to the EULAR 2010 criteria, the rheumatoid factor (RF) and the anti-cyclic citrullinated peptide (anti-CCP) are used for RA diagnosis. Since 2010, new biomarkers were discovered and proved useful in identifying RA in early stages. For a more rigorous management of these cases, one of the key steps in the evolution of patients with RA is to recognize and distinguish the more aggressive forms of the disease through prognostic biomarkers. "Treat to target" recommends the use of 3 composite scores to monitor the evolution of the disease: disease activity score (DAS 28), simple disease activity index (SDAI) and clinical disease activity index (CDAI), but, a new test was developed which better monitors the disease activity. The introduction of biological therapies has revolutionized the treatment of RA. Despite these advances, 20-40% of the patients are declared nonresponders to at least one of the therapies. The patient exposure to the potential side effects and high costs requires the discovery of a biomarker that could identify those who can benefit from the pretreatment of a certain therapy. ABBREVIATIONS: RA = rheumatoid arthritis, RF = rheumatoid factor, DAS 28 = disease activity score, SDAI = simple disease activity index, CDAI = clinical disease activity index, ACR = American College of Rheumatology, EULAR = European League against Rheumatism, anti-CCP = antibodies against cyclic citrullinated proteins, anti-MCV = mutated citrullinated vimentin antibodies, anti-CarP = antibodies against carbamylated proteins, MBDA = multi biomarker disease activity test, COMP = cartilage oligomeric matrix protein, ADAs = antidrug antibodies, CDA = clinical disease activity index, SDAI = simplified disease activity index, ESR = erythrocyte sedimentation rate, CRP = C reactive protein, SAA = serum amyloid A, VCAM-1 = vascular cell adhesion molecule-1, IL-6 = interleukin-6, TNF-R1 = tumor necrosis factor receptor 1, EGF = epidermal growth factor, VEGF-A = vascular endothelial growth factor A.

The efficiency of biologic therapy in a group of patients with rheumatoid arthritis.

OBJECTIVES: The following study aims to evaluate the monotherapy with biologic agents: Infliximab (IFX), Etanercept (ETA), Adalimumab (ADA) and Rituximab (RTX) in patients diagnosed with rheumatoid arthritis (RA). METHODS: To achieve these objectives, the database of "Dr. I. Cantacuzino" Clinical Hospital, Department of Internal Medicine and Rheumatology, was used. The study was retrospective and descriptive, covering 168 patients with RA, followed for 12 months, from January 2012 to January 2013. Admission criteria for the study were the following: patients diagnosed with RA according to ACR 1987/ EULAR 2010 criteria, disease activity score (DAS 28)> 5.1, positive inflammation tests, presence of RA refractory to classic remitting treatment administered at least 6 months prior to the initiation of biological therapy, on patients treated with RTX. They were considered non-responders after 6 months of treatment with anti tumor necrosis factor alpha (anti-TNF) and decided to switch agents with anti CD-20. RESULTS: Comparing values between any two points in time (baseline - 6 months -12 months) for any type of therapy, there were significant decreases in the values of erythrocyte sedimentation rate (ESR), reactive C protein (CRP) and disease activity score (DAS 28). There were no significant differences between therapies regarding ESR at 6 months (p = 0.070, ANOVA) and 12 months (p = 0.375, Kruskal-Wallis), significant differences were regarding CRP at 6 and 12 months (p = 0.000, Kruskal-Wallis) and DAS 28 at 6 months (p = 0.000, Kruskal- Wallis) and 12 months (p = 0.018, Kruskal-Wallis). CONCLUSION: All 4 therapies have proven efficient, prognostic markers decreasing gradually at 6 and 12 months.

Apoptosis in colorectal cancer.

Apoptosis is an inborn process that has been preserved during evolution; it allows the cells to systematically inactivate, destroy and dispose of their own components thus leading to their death. This programme can be activated by both intra and extracellular mechanisms. The intracellular components involve a genetically defined development programme while the extracellular aspects regard endogenous proteins, cytokines and hormones as well as xenobiotics, radiations, oxidative stress and hypoxia. The ability of a cell to enter apoptosis as a response to a "death" signal depends on its proliferative status, the position in the cell cycle and also on the controlled expression of those genes that have the capacity of promoting and inhibiting cell death. The fine regulation of these parameters needs to be maintained in order to ensure the physiological environment required for the induction of apoptosis. Any malfunction in any of the steps of controlled cellular death can lead to dysfunctions and, as a consequence, to different pathological conditions. The importance of apoptosis lies in its active nature and in the potential of controlling biological systems.

Cardiovascular disease risk scores in the current practice: which to use in rheumatoid arthritis?

Cardiovascular disease (CVD) is the highest prevalence disease in the general population (GP) and it accounts for 20 million deaths worldwide each year. Its prevalence is even higher in rheumatoid arthritis. Early detection of subclinical disease is critical and the use of cardiovascular risk prediction models and calculators is widely spread. The impact of such techniques in the GP was previously studied. Despite their common background and similarities, some disagreement exists between most scores and their importance in special high-risk populations like rheumatoid arthritis (RA), having a low level of evidence. The current article aims to single out those predictive models (models) that could be most useful in the care of rheumatoid arthritis patients.

Utility of different cardiovascular disease prediction models in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis comes with a 30% higher probability for cardiovascular disease than the general population. Current guidelines advocate for early and aggressive primary prevention and treatment of risk factors in high-risk populations but this excess risk is under-addressed in RA in real life. This is mainly due to difficulties met in the correct risk evaluation. This study aims to underline the differences in results of the main cardiovascular risk screening models in the real life rheumatoid arthritis population. METHODS: In a cross-sectional study, patients addressed to a tertiary care center in Romania for an biannual follow-up of rheumatoid arthritis and the ones who were considered free of any cardiovascular disease were assessed for subclinical atherosclerosis. Clinical, biological and carotidal ultrasound evaluations were performed. A number of cardiovascular disease prediction scores were performed and differences between tests were noted in regard to subclinical atherosclerosis as defined by the existence of carotid intima media thickness over 0,9 mm or carotid plaque. RESULTS: In a population of 29 Romanian rheumatoid arthritis patients free of cardiovascular disease, the performance of Framingham Risk Score, HeartSCORE, ARIC cardiovascular disease prediction score, Reynolds Risk Score, PROCAM risk score and Qrisk2 score were compared. All the scores under-diagnosed subclinical atherosclerosis. With an AUROC of 0,792, the SCORE model was the only one that could partially stratify patients in low, intermediate and high-risk categories. The use of the EULAR recommended modifier did not help to reclassify patients. CONCLUSION: The only score that showed a statistically significant prediction capacity for subclinical atherosclerosis in a Romanian rheumatoid arthritis population was SCORE. The additional calibration or the use of imaging techniques in CVD risk prediction for the intermediate risk category might be warranted.

Malignancy and mortality of colorectal polyps.

OBJECTIVES: To evaluate the rate of morbidity and mortality associated with colorectal polyps after the next 8-years period of endoscopic polypectomy, in a high risk managed care population. MATERIAL AND METHOD: Cohorts of 77 subjects with benign neoplasms were identified with a colonoscopy in 1999. Three groups of subjects: benign neoplasms with polypectomy, benign neoplasms without polypectomy, and no neoplasms were evaluated. Five years recurrence rates (1999-2004) of benign or new malignant colorectal neoplasms were identified: for the benign determined for the baseline benign neoplasms with polypectomy and no neoplasm groups neoplasm without polypectomy, only rates for malignancy were observed. Malignancy was evaluated with immunohistochemical p53 (tumor protein 53) and PCNA (Proliferating Cell Nuclear Antigen) staining pattern. Over the next 8 years 2004-2012 were evaluated the mortality and the recurrence rate of the benign polyps. RESULTS: 77 subjects were enrolled in our study; 71.4% were diagnosed with benign and 2.5% with malignant neoplasms. The 5-years cumulative incidence rates of malignant colorectal neoplasms in the no neoplasm (n = 20) and benign neoplasm groups (n = 55) were (n = 1) 5% and ( n = 10) 18.1%, respectively (p < 0.005). A lower 5-years malignancy rate was observed in benign neoplasms group with polypectomy (12%) compared to the benign neoplasm group without polypectomy (33.3%) (p < 0.05). The 8-years mortality rate was compared into benign recurrent polyps group and into malign group: the lower 8-years mortality rate was observed into benign polyp no neoplasm group (0%) and into benign recurrent polyps group (40%); the highest rate was observed into neoplasm group (100%). CONCLUSIONS: The high recurrence rate of benign colorectal neoplasms and a higher incidence of colorectal cancer in subjects at high risk-history of benign colorectal neoplasm-highlight a healthcare opportunity for surveillance and/or interventions to reduce the morbidity associated with colorectal neoplasms.

Albuminuria--marker of progressive renal disease.

The presence of albuminuria has long been recognized as an adverse prognostic feature in patients with renal disease: the patients with appreciable albuminuria are much more likely to develop tubulointerstitial scarring and fibrosis and progress to end-stage renal failure. For many years, it was thought that excess albuminuria was simply a marker of a more severe renal disease, which was more likely to progress as a result of this severity rather than as a result of the albuminuria itself. This conviction was strengthened by the general assumption that albumin was a benign or inert molecule serving primarily to exert oncotic pressure and act as a carrier within the circulation. More recently, this view has been challenged with the accumulation of evidence suggesting that albumin is able to influence the function of cells with which it makes contact in the manner of a signalling molecule.

Trends of rheumatoid arthritis monitorization in Romania.

BACKGROUND: rheumatoid arthritis (RA) is associated with the loss of overall functionality, which leads to substantial economic losses. Second line agents used in RA treatment require careful monitorization in terms of efficiency and tolerability. OBJECTIVE: trends, predictive factors and characteristics of clinical, biological and radiological RA monitorization in a cross sectional observational cohort study, conducted on over 206 patients in Romania, with a 12 months follow up (December 2007 - December 2008). METHOD: Cases were recruited from the south-west region of the country, covering a geographical area of 23 counties. Patients were invited to complete three sets of interviews (collected by post) in a consent letter, containing self reported questionnaires, at 6 months intervals: an original questionnaire (which included quantitative self reported of pain, disease activity and fatigue on visual analogue scale-VAS), Health Assessment Questionnaire-HAQ-Disability and Discomfort Scales and EUROQOL EQ-5D, validated in Romanian (obtaining a user agreement by authors of the original version). RESULTS: analysis was carried out in SPSS 10. The cohort enrolled 206 patients, with the average age of 54.90 +/- 12.67 years, 66% urban, 86.4% women, 29.1% professionally active, 48.5% graduates of primary education. The average disease duration after diagnosis of RA was of 9.40 +/- 8.87 years. The duration of the treatment reported at baseline was of 2.70 +/- 2.64 years. Most patients followed a program of monthly monitoring at a general practitioner (GP) (41.7% at baseline and 37.1% to 12 months). Visits to the rheumatologist followed a monthly regimen (32.3% at baseline and 31.7% to 12 months) or a 2 months interval (19.4% at baseline and 29.6% to 12 months, p = 0.000). Biological monitoring was quarterly (39.6% and 53.2% at 12 months; p = 0.000) or at 2 months interval (26.2% at baseline and 16.7% to 12 months, p = 0.000). X-ray monitoring lacked in over half the cases in a year of disease progression (63.3% at 6 months and 62.2% at 12 months), although it sums between 1 and 3 radiographs to one third of the cases (36.8%), CONCLUSION: generally, in our country, there is a lack of aggregation in the dispensarization algorithm of patients with RA; consequently, the decision is awarded to the human factor. Under these circumstances, some patients are over evaluated. Promoting a dispensarization guide for RA patients could induce benefits both clinically and economically. Therefore, we submit a proposal of recommendations as a guideline for clinical, biological and radiological monitoring, according to the phase and stage of RA.

Rheumatoid arthritis: travelling biological era a Romanian X-ray population.

BACKGROUND: Rheumatoid arthritis (RA) is associated with loss of overall functionality of the locomotion system and it is connected with substantial economic losses. OBJECTIVE: To describe the clinical characteristics and healthcare resource utilization characteristics and to analyze the correlations in a cross-sectional sample of 206 patients in Romania. METHOD: RA cases have been enrolled from southern and western part of the country, covering a surface of 23 counties. RESULTS: Particularly in the literature data, Romanian RA patients become work disabled at 5.65 +/- 5.99 years old after the diagnosis. At cohort level, retirement in the first year after RA diagnosis is of 22.9%. From those, 13% were treated with biologic DMARDs; those on non-biologic DMARDs were 28.6%. In oral therapy group the most prescribed drug is lefunomide (61.2%). RA has an important impact on pain, function and utility, influenced by social factors. Patients' follow up is often based on hospitalization. CONCLUSION: Currently, when the clinician may choose for one certain therapy or another, the social influence is still overwhelming at all the evaluation levels in RA patients, as well as at economic impact.

Epidemiology of ocular involvement in autoimmune diseases.

UNLABELLED: The main objective of this study was to identify the prevalence of ocular manifestations in Romanian rheumatic patients admitted in a specialized rheumatology clinic since January 2006 till June 2007. The secondary outcome was the occurrence of adverse visual events associated with systemic therapy. METHODS: Information regarding rheumatic and ocular diseases was extracted from medical records system available in "I. Cantacuzino" Clinical Hospital in Bucharest. The prevalence of ocular involvement reported passively by rheumatologists (retrospective descriptive study of 375 different cases of rheumatic patients) was compared with the literature data. RESULTS: There were 29 cases of ocular manifestations. Ocular manifestation included keratoconjunctivitis sicca (KCS), anterior uveitis, conjunctivitis, retinal vasculitis and optic neuritis. Complications clearly related to steroid therapy were cataracts and glaucoma. One case with typical "bull's eye" maculopathy due to Hydroxychloroquine treatment was detected. CONCLUSIONS: The main conclusion of our study is that the rheumatic patients need to be referred to an ophthalmologist for a precocious diagnosis of ocular involvement and an optimal treatment of eye manifestations.

A clinical approach in regression of glomerulosclerosis.

The role of the renin angiotensin system (RAS) in hypertension and end organ damage has long been recognized. Angiotensin 1 converting enzyme inhibitors (ACEI) are superior to other antihypertensive agents in protecting the kidney against progressive deterioration, even in normotensive persons. Like ACEI, angiotensin II type 1 receptor antagonists (AT1RA) ameliorate or even reverse glomerulosclerosis in rat animal models. These findings suggest that Angiotensin II (Ang II) has nonhemodynamic effects in progressive renal disease. The RAS is now recognized to be linked to induction of plasminogen activator-inhibitor-1 (PAI-1), possibly via the AT4 receptor, thus promoting both thrombosis and fibrosis. Interactions of the RAS with aldosterone and bradykinin may have an impact on both blood pressure and tissue injury. The beneficial effect on renal fibrosis of inhibiting the RAS likely reflects the central role that angiotensin has in regulating renal function and structure by its various actions. This article explores the interaction of the renin angiotensin aldosterone system with PAI-1, and the potential significance of these interactions in the pathogenesis of progressive renal disease and remodeling of renal sclerosis.