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ObjectivesTo estimate population sodium and potassium intakes and explore knowledge, attitudes and behaviour (KAB) towards the use of salt in adults in the Sultanate of Oman.DesignNational cross-sectional population-based survey.SettingProportional random samples, representative of Omani adults (18 years or older), were obtained from all governorates of the Sultanate of Oman.ParticipantsFive hundred and sixty-nine (193 men, 376 women; 18 years or older) were included in the analysis (response rate 57%). Mean age was 39.4 years (SD 13.1). Participants attended a screening including demographic, anthropometric and physical measurements.Primary and secondary outcome measuresWe assessed dietary sodium, potassium and creatinine by 24-hour urinary sodium (UNa), potassium (UK) and creatinine (UCr) excretions. We collected KAB by a questionnaire on an electronic tablet.ResultsMean UNa was 144.3 (78.8) mmol/day, equivalent to 9.0 g of salt/day and potassium excretion 52.6 (32.6) mmol/day, equivalent to 2.36 g/day, after adjusting for non-urinary losses. Men ate significantly more sodium and potassium than women. Only 22% of the sample had a salt intake below the WHO recommended target of 5 g/day and less than 10% met WHO targets for potassium excretion (>90 mmol/day). While 89.1% of those interviewed knew that consuming too much salt could cause serious health problems and only 6.9% felt they were using too much added salt, one in two participants used always or often salt, salty seasonings or salty sauces in cooking or when preparing food at home.ConclusionsIn the Sultanate of Oman, salt consumption is higher and potassium consumption lower than recommended by WHO, both in men and in women. The present data provide, for the first time, evidence to support a national programme of population salt reduction to prevent the increasing burden of cardiovascular disease in the area.

Background and aims To systematically review the latest evidence on established and emerging nutrition-related risk factors for incidence of and mortality from total, ischemic and haemorrhagic strokes. The present review was conducted in the framework of the work carried out through 2015 and 2016 for the preparation of the Italian Guidelines for the Prevention and Treatment of Stroke, 8th Edition, by ISO-SPREAD (Italian Stroke Organization and the Stroke Prevention and Educational Awareness Diffusion). Methods and results Systematic review of articles focused on primary prevention of stroke published between January 2013 to May 2016 through an extensive search of the literature using MEDLINE/PUBMED, EMBASE and the Cochrane Library. Articles were ranked according to the SIGN methodology while the GRADE system was used to establish the strength of recommendations. As a result of our literature search, we examined 87 meta-analyses overall (mainly of prospective studies), a few isolated more recent prospective studies not included in the meta-analyses, and a smaller number of available randomized controlled trials and case–control studies. Based on the analysis of the above articles, 36 Syntheses of the available evidence and 36 Recommendations were eventually prepared. The present document was developed by organizing the available evidence into three individual areas (nutrients, food groups and dietary patterns) to provide a systematic and user-friendly overview of the available evidence on the relationship between nutrition and primary prevention of stroke. Yet analysis of foods and food patterns allowed translating the information about nutrients in a tool more amenable to use in daily life also in the light of the argument that people eat foods rather than nutrients. Conclusions The present literature review and dietary recommendations provide healthcare professionals and all interested readers with a useful overview for the reduction of the risk of total, ischemic and haemorrhagic stroke through dietary modifications.

Acoustic noise assessment is a crucial problem in areas in which transportation means, such as motorway, railway, airport, etc., are present. Dwelled areas, in fact, represent a sensible point, that is affected by several externalities, among which, acoustic noise is very important. In this paper, the techniques known as Time Series Analysis (TSA), are used to analyze datasets of noise level produced by transport systems. This approach is based on the analysis of trend and seasonality of the series, and on the implementation of a function of the time that can provide predictions for future time periods. According to the choice and to the input of each model, the forecast horizon can vary from few days further to any time period in the future. Two techniques will be presented: one is based on a Deterministic Decomposition (DD-TSA), able to predict at any future time period; the second is based on a stochastic approach, and adopt the so called SARIMA (Seasonal AutoRegressive Integrated Moving Average) models, to provide prediction on a short time range. Both techniques will be applied to a road traffic noise dataset and to an airport noise levels time series. Results will show that the typology of transportation system does not affect the prediction performances of both the DD-TSA and the SARIMA techniques, even though the time basis of the data is different, being daily for traffic noise and hourly for airport.

Objective:In Moldova, cardiovascular disease is the main cause of morbidity and mortality. High blood pressure is the leading risk factor for the CVD burden. It is common habit in Moldova to add salt to food at the table and when cooking and to eat processed food. The aim was to measure population s

Objective:Hypertension in young adults is a steadily increasing phenomenon. Increased arterial stiffness is possibly involved in its pathophysiology and may predict its development. Socio-economic and lifestyle risk factors may play a major role in early vascular aging in young adults. Thus, the aim

Objective:Excess salt (sodium chloride) and inadequate potassium intakes are responsible for high blood pressure in populations and they are associated with higher cardiovascular disease (CVD). In Montenegro, CVD is the leading cause of death and disability. Moreover, there is no survey that has dir

We have deposited TiAlN films by using the reactive laser ablation technique. TiAl targets were ablated in low-pressure N2 (0.1–10 Pa) atmosphere by 2×104 XeCl excimer laser pulses at the repetition rate of 10 Hz. The laser fluence at the target was set at 6 J/cm2, corresponding to a power density of 0.2 GW/cm2. The films were deposited on Si substrates at room temperature, placed at 40 mm from the target. Their characteristics were investigated by many different techniques. Scanning electron micrographs show that surfaces are plane without cracks or corrugations. From Rutherford backscattering spectra it results that the thickness vary from ∼100 nm for films deposited at 0.1–0.5 Pa to 50 nm for the film deposited at 10 Pa. The mean composition is close to TiAlN for the film deposited at 0.1 Pa and close to TiAlN2 for the film deposited at 0.5 Pa. X-Ray diffraction analysis points to an amorphous structure of the film deposited at the lowest pressure (0.1 Pa), while peaks of fcc TiN and hexagonal Ti3Al2N2 appear in the spectra of the films deposited at higher N2 pressures. The complex chemical bonding of the top surface layer of the films was studied by X-ray photoelectron spectroscopy.

In this work, we report on a structural and compositional characterization of B-C-N thin films deposited by laser reactive ablation of a B4C target, in low-pressure (5 Pa) nitrogen atmosphere. For target ablation, a KrF excimer laser (lambda = 248 nm, tau = 20 ns) has been used, at the fluences of 6 and 12 J/cm(2). Films have been deposited on silicon (100) substrates at room temperature. Scanning electron miroscopy (SEM), Auger electron spectroscopy (AES), X-ray photoelectron spectroscopy (XPS), time-of-night secondary ion mass spectrometry (ToF-SIMS), and Fourier transform-infrared spectroscopy (FT-IR) characterization techniques were used to analyze the composition and the structure of the deposited films. The film results to be a mixture of sp(2)/sp(3) BN and sp(2)/sp(3) nitrogenated C phases. The concentration of the different BN phases depends on the used laser fluence for the deposition of the film.

Background: Both short and long duration of habitual sleep are associated with adverse health outcomes. Objective: To assess the population longitudinal evidence of a relationship between duration of sleep and morbidity and mortality from coronary heart disease (CHD), stroke and total cardiovascular disease (CVD), and to obtain estimates of risk. Methods and Results: We performed a systematic search of publications using MEDLINE (1966–2009), EMBASE (from 1980), the Cochrane Library and manual searches without language restrictions. Studies were included if they were prospective, follow up >3 years, had duration of sleep at baseline and cases of fatal and non-fatal CHD, stroke or total CVD assessed prospectively. Relative risks (RR) and 95% C.I. were extracted and pooled using a random effect model. Sensitivity analysis was performed, heterogeneity and publication bias were also assessed. Overall, 15 studies provided 24 independent cohort samples, including 474,866 male and female participants (follow-up range 6.9 to 25 years), and 16,502 fatal and non-fatal events (3,753 for CHD, 3,163 for stroke and 9,586 for total CVD). Sleep duration was assessed by questionnaire, death through certification and non-fatal events event registers. In the pooled analyses, short duration of sleep was associated with a greater risk of developing or dying of CHD (RR: 1.48; 95% CI 1.22 to 1.80; p Conclusion: Both short and long duration of sleep are significant predictors of cardiovascular outcomes in prospective population studies.

Background:Increasing evidence suggests an association between both short and long duration of habitual sleep with adverse health outcomes.Objectives:To assess whether the population longitudinal evidence supports the presence of a relationship between duration of sleep and all-cause mortality, to i

BLOOD COAGULATION AND PLATELET AGGREGATION IN A GROUP OF CHILDREN WITH CONGENITAL HYPOTHYROIDISM 165

Functional results of resection arthroplasty are currently considered poor. In 104 hip prosthesis removals after either septic or aseptic loosening, pain, walking, joint motility, life style, and patient's opinion were evaluated. A satisfactory result was recorded in 72% of cases. Prognosis is poorer in patients who are young, have septic loosening, and have poor residual mobility. Resection arthroplasty should be considered a salvage procedure in cases of septic loosening and/or bone stock deficiency after a failed total hip arthroplasty.

Endoscopic restoration of a totally obstructed ureteroileal anastomosis was accomplished in 3 patients. The combined use of rigid endoscopy of the ileal conduit and flexible nephroureteroscopy provided full visualization of the blind-ending segments and allowed location of the shortest segment between the lumina. A guide wire was passed through intervening tissue with fluoroscopic monitoring to re-establish internal drainage. This technique offers an alternative to laparotomy and reimplantation in selected cases of ureteroileal stricture.

Forty patients with stage O papillary transitional cell carcinoma of the bladder were tested for the presence or absence of ABH blood group substances. Of 25 tumors with antigens 21 (84 per cent) remained stage 0, with a mean followup of 13.3 years. Of 15 tumors devoid of blood group substances 11 (73.3 per cent) progressed to stage B or greater in a mean of 4.3 years. Patients without antigens whose tumor remained stage O were followed for a mean of 10 years. Two patients with initially positive tumors subsequently showed loss of antigens and invasion. In 7 of 8 patients the benign epithelium showed a greater concentration of blood group substances than did the corresponding tumor. The presence or absence of blood group substances can be used to predict the biological behavior of stage O transitional cell carcinoma.

We report a case of acute renal failure secondary to left ureteral obstruction by a gravid uterus. Marked atrophy of the right kidney and lower pole of the left kidney had been documented before pregnancy. Radiographic, laboratory and operative evidence of the diagnosis is offered.

We compared the method of indirect immunofluorescence (IIF) with that of specific red blood cell adherence (SRCA) for detecting ABH blood group substance (BGS) on stage O papillary transitional cell carcinoma (TCC) of the bladder. In evaluating BGS “positivity” or “negativity” both methods gave identical results. The IIF is somewhat easier to perform and less subjective in interpretation while the SRCA method needs only a conventional light microscope and the slides themselves are permanent “records”. In cases of questionable reactivity with the SRCA, the IIF was a helpful adjunct. The IIF method is a viable option to the SRCA method when studying TCC for BGS.

Introduction Serum uric acid (SUA) has been depicted as a contributory causal factor in metabolic syndrome (MS), which in turn, portends unfavourable prognosis. Aim We assessed the prognostic role of SUA in patients with and without MS. Methods We used data from the multicentre Uric Acid Right for Heart Health study and considered cardiovascular mortality (CVM) as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. Results A total of 9589 subjects (median age 58.5 years, 45% males) were included in the analysis, and 5100 (53%) patients had a final diagnosis of MS. After a median follow-up of 142 months, we observed 558 events. Using a previously validated cardiovascular SUA cut-off to predict CVM (> 5.1 mg/dL in women and 5.6 mg/dL in men), elevated SUA levels were significantly associated to a worse outcome in patients with and without MS (all p p = 0.004). Cox regression analyses identified an independent association between SUA and CVM (Hazard Ratio: 1.79 [95% CI, 1.15–2.79]; p p Conclusion Increasing SUA levels are associated with a higher CVM risk irrespective of the presence of MS: a cardiovascular SUA threshold may improve risk stratification. Graphic abstract

Aims Whether the association between uric acid (UA) and cardiovascular disease is influenced by some facilitating factors is unclear. The aim of this study was to investigate whether the risk of cardiovascular mortality (CVM) associated with elevated UA was modulated by the level of resting heart rate (HR). Methods and results Multivariable Cox analyses were made in 19 128 participants from the multicentre Uric acid Right for heArt Health study. During a median follow-up of 11.2 years, there were 1381 cases of CVM. In multivariable Cox models both UA and HR, either considered as continuous or categorical variables were independent predictors of CVM both improving risk discrimination (P ≤ 0.003) and reclassification (P Conclusion This data suggest that the contribution of UA to determining CVM is modulated by the level of HR supporting the hypothesis that activation of the sympathetic nervous system facilitates the action of UA as a cardiovascular risk factor.

Serum uric acid (SUA) levels discriminating across the different strata of cardiovascular risk is still unknown. By utilizing a large population-based database, we assessed the threshold of SUA that increases the risk of total mortality and cardiovascular mortality (CVM). The URRAH study (Uric Acid Right for Heart Health) is a multicentre retrospective, observational study, which collected data from several large population-based longitudinal studies in Italy and subjects recruited in the hypertension clinics of the Italian Society of Hypertension. Total mortality was defined as mortality for any cause, CVM as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. A total of 22 714 subjects were included in the analysis. Multivariate Cox regression analyses identified an independent association between SUA and total mortality (hazard ratio, 1.53 [95% CI, 1.21–1.93]) or CVM (hazard ratio, 2.08 [95% CI, 1.146–2.97]; P P

Background/objectives: The aim of the present study was to validate a short questionnaire on habitual dietary salt intake, to quickly and easily identify individuals whose salt consumption exceeds recommended levels. Subjects/methods: A total of 1131 hypertensive subjects participating in the MINISAL-SIIA study were included in the analysis. Anthropometric indexes, blood pressure, and 24-h urinary sodium excretion (NaU) were measured. A fixed-sequence questionnaire on dietary salt intake was administered. Results: NaU was significantly associated with scores, with a linear association across categories (p for trend 85 mmol/day) and “very high NaU” (NaU > 170 mmol/day) was 86 and 35%, respectively. The score of the questionnaire had a significant ability to detect both “high NaU”—with a specificity of 95% at the score of 10 points—and “very high NaU”—with a specificity of 99.6% at score of 13 points. Conclusions: The main results of the study indicates that a higher score of this short questionnaire is distinctive of habitual high salt consumption in hypertensive patients.

Rationale : The sympathetic nervous system plays a fundamental role in the regulation of myocardial function. During chronic pressure overload, overactivation of the sympathetic nervous system induces the release of catecholamines, which activate β-adrenergic receptors in cardiomyocytes and lead to increased heart rate and cardiac contractility. However, chronic stimulation of β-adrenergic receptors leads to impaired cardiac function, and β-blockers are widely used as therapeutic agents for the treatment of cardiac disease. MicroRNA-133 (miR-133) is highly expressed in the myocardium and is involved in controlling cardiac function through regulation of messenger RNA translation/stability. Objective : To determine whether miR-133 affects β-adrenergic receptor signaling during progression to heart failure. Methods and Results : Based on bioinformatic analysis, β 1 -adrenergic receptor (β 1 AR) and other components of the β 1 AR signal transduction cascade, including adenylate cyclase VI and the catalytic subunit of the cAMP-dependent protein kinase A, were predicted as direct targets of miR-133 and subsequently validated by experimental studies. Consistently, cAMP accumulation and activation of downstream targets were repressed by miR-133 overexpression in both neonatal and adult cardiomyocytes following selective β 1 AR stimulation. Furthermore, gain-of-function and loss-of-function studies of miR-133 revealed its role in counteracting the deleterious apoptotic effects caused by chronic β 1 AR stimulation. This was confirmed in vivo using a novel cardiac-specific TetON-miR-133 inducible transgenic mouse model. When subjected to transaortic constriction, TetON-miR-133 inducible transgenic mice maintained cardiac performance and showed attenuated apoptosis and reduced fibrosis compared with control mice. Conclusions : miR-133 controls multiple components of the β 1 AR transduction cascade and is cardioprotective during heart failure.

Abstract 575 Incorporation of the tyrosine kinase inhibitor (TKI) imatinib in the frontline treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) patients (pts) has significantly improved the anti-leukemic efficacy of induction therapy. In contrast to chronic myeloid leukemia (CML), however, responses are short-lived and relapse is frequently associated with the selection of Bcr-Abl kinase domain (KD) mutations, fostered by the high genetic instability of Ph+ ALL cells. The advent of the 2nd-generation TKIs dasatinib and nilotinib has brought additional treatment options both for newly diagnosed and for imatinib-resistant pts. To analyze the changes they have brought in mutation frequency and type, we have reviewed the database recording the results of BCR-ABL KD mutation analyses done in our laboratory from January 2004 to June 2011. Overall, 781 tests on 258 Ph+ ALL pts (number of tests per pt, range: 1–15) were performed by denaturing high-performance liquid chromatography (D-HPLC) followed by direct sequencing of D-HPLC-positive cases. One hundred and fourty-three pts were analyzed because of imatinib resistance. One hundred and one out of 143 (71%) pts scored positive for one or more KD mutations. Similarly to what is know to occur in CML, hematologic and cytogenetic resistance were by far more frequently associated with mutations than molecular resistance (Bcr-Abl transcript increase as assessed by RT-Q-PCR). Overall, mutations at thirteen residues were detected. In contrast to what can be observed in CML, three mutations were by far the most frequent, accounting for almost 75% of the mutated cases: T315I (n=38 pts, 37%), E255K/V (n=19 pts, 18%) and Y253H (n=19 pts, 18%). The other mutations were, in order of frequency: F359V/I, M244V, M351T, F317L, G250E, Q252H, L387M, D276G, L248R, E279K. Nine out of 103 (9%) pts had two mutations, in the same (2 pts) or in different (7 pts) subclones. In 84 pts who were analyzed because they were reported to have developed resistance to dasatinib (n=72) or nilotinib (n=12) as 2nd- or 3rd-line TKIs, 65 (77%) had newly acquired mutations (57/72 dasatinib-resistant pts and 8/12 nilotinib-resistant pts). The most frequent newly acquired mutation in this setting was the T315I, detected in 35/57 (61%) cases acquiring mutations on dasatinib and in 2/8 cases acquiring mutations on nilotinib. Other recurrent newly acquired mutations were F317L, V299L, T315A in dasatinib-resistant pts and Y253H and E255K in nilotinib-resistant pts. Thirty out of 65 pts (46%) were positive for multiple mutations (2 to 4 mutations, in the same or in different subclones or both) that emerged under the same TKI in 11 cases (37%) and accumulated as a consequence of multiple lines of TKI therapy in the remaining 19 (63%) cases. Mutation analysis was also performed in 15 resistant pts enrolled in a clinical trial of dasatinib as first-line treatment for Ph+ ALL. Twelve pts were positive for mutations; 11/12 had a T315I. Sixty-one pts were analyzed at the time of diagnosis in order to assess whether TKI-resistant mutations could already be detectable. Only two pts (3%) were positive for mutations: one patient had an F311L that disappeared after one month of nilotinib treatment; an additional patient was positive only by D-HPLC, but not by the less sensitive direct sequencing – most likely for the T315I mutation that shortly after the start of dasatinib treatment outgrew and led to resistance. Taking advantage of the recent availability of a next-generation sequencing platform (Roche 454), allowing high sensitivity (0.01%) mutation scanning of the KD, samples collected at the time of diagnosis and during follow-up from selected Ph+ ALL cases who developed mutations and resistance to TKI therapy were retrospectively analyzed – but the mutations were not always already detectable at diagnosis. In conclusion: a) although 2nd generation TKIs may ensure a more rapid debulking of the neoplastic clone and have much fewer insensitive mutations, long-term disease control remains a problem and the T315I becomes an even tougher enemy; b) the clinical usefulness of mutation screening of Ph+ ALL pts at diagnosis before TKI start, even with highly sensitive approaches is low – not all mutations pre-exist since genetic instability remains high and fosters mutational events anytime during treatment. Supported by PRIN, FIRB, AIL and AIRC. Disclosures: Soverini: ARIAD: Consultancy; Novartis: Consultancy; Bristol-Myers Squibb: Consultancy. Luppi:CELGENE CORPORATION: Research Funding. Foà:Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees. Baccarani:Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Martinelli:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy.

In Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) patients (pts) treated with tyrosine kinase inhibitors (TKIs), responses are generally short-lived and relapse is most often accompanied by selection of point mutations in the Bcr-Abl kinase domain (KD). In order to assess whether mutations are already present at the time of diagnosis, we analyzed RNA samples from 13 pts with newly diagnosed Ph+ ALL enrolled on the GIMEMA LAL1205 protocol – designed to assess activity, safety and tolerability of dasatinib monotherapy as first-line treatment for adult Ph+ ALL. The pts investigated (males/ females: 6/7; median age: 56 years, range 30–73) included 6 pts who subsequently relapsed with dasatinib-resistant mutations, 2 pts who relapsed without evidence of mutations as assessed by direct sequencing and 5 pts in persistent remission. Screening for low level mutations was performed by cloning the entire Bcr-Abl KD (amino acid 206 through 524) in a bacterial vector and sequencing 150 to 200 independent clones for each pt. All pts, irrespective of their subsequent response to dasatinib, had evidence of aberrant KD sequences due to point mutations (13/13 pts), small insertions (2/13 pts) or small deletions (1/13 pts). Two to five point mutations were detectable for each pt. In some cases, multiple mutations could be found to co-exist in the same cloned fragment. A total of 45 different point mutations (including 18 silent mutations, 4 nonsense mutations and 23 missense mutations) were observed. Base substitutions were scattered all over the KD and there were no mutation hotspots. Thirty-nine out of 45 (87%) mutations were transitions: G>A (n=14), A>G (n=10), C>T (n=9), T>C (n=6). Such a high prevalence of transitions (which normally occur 1.4 times more frequently than transversions) suggests that a specific mechanism generating mutations is predominant. Activation-induced cytidine deaminase (AID) has been recently shown to be aberrantly expressed in a proportion of Ph+ ALLs and has been implicated in the development of at least some Bcr-Abl mutations; correlation with AID expression will be presented. Mutations were detected in no more than three independent clones, suggesting that they were present at low levels. Mutations detected in less than two clones were considered only if independently validated by a specifically designed ASO-PCR assay run on the original cDNA sample. The majority of point mutations detected have never been reported in association with TKI resistance. However, three pts were found to harbor known imatinib- or dasatinib-resistant mutations, including two T315I mutations that were later on selected and led to relapse. This supports the theory that mutations randomly arise as a consequence of a high genetic instability and very few of them will confer a growth advantage under the selective pressure of TKIs. Six samples from newly diagnosed chronic phase CML (CP-CML) pts were screened for comparison with the same cloning approach, including 2 pts who later progressed with evidence of KD mutations after 3 and 6 months from the start of imatinib, respectively, and 4 pts who achieved a stable molecular response on imatinib. Both pts who experienced early relapse on imatinib had low level mutations detectable at the time of diagnosis, whereas none of the clones from CP-CML imatinib responders had evidence of KD mutations. The results herein presented support the concept that Ph+ ALL cells have a particularly high genomic instability that allows early escape from TKI inhibitor therapy. Only a fraction of CML cases share this feature. Our data highlight the importance of understanding the mechanism(s) responsible for this ‘mutator’ phenotype, as well as how to interfere therapeutically with it.