Arrhythmias and cardiac MRI associations in patients with established cardiac dystrophinopathy.

AIMS: Some patients with cardiac dystrophinopathy die suddenly. Whether such deaths are preventable by specific antiarrhythmic management or simply indicate heart failure overwhelming medical therapies is uncertain. The aim of this prospective, cohort study was to describe the occurrence and nature of cardiac arrhythmias recorded during prolonged continuous ECG rhythm surveillance in patients with established cardiac dystrophinopathy and relate them to abnormalities on cardiac MRI. METHODS AND RESULTS: A cohort of 10 patients (36.3 years; 3 female) with LVEF<40% due to Duchenne (3) or Becker muscular (4) dystrophy or Duchenne muscular dystrophy-gene carrying effects in females (3) were recruited, had cardiac MRI, ECG signal-averaging and ECG loop-recorder implants. All were on standard of care heart medications and none had prior history of arrhythmias.No deaths or brady arrhythmias occurred during median follow-up 30 months (range 13-35). Self-limiting episodes of asymptomatic tachyarrhythmia (range 1-29) were confirmed in 8 (80%) patients (ventricular only 2; ventricular and atrial 6). Higher ventricular arrhythmia burden correlated with extent of myocardial fibrosis (extracellular volume%, p=0.029; native T1, p=0.49; late gadolinium enhancement, p=0.49), but not with LVEF% (p=1.0) on MRI and atrial arrhythmias with left atrial dilatation. Features of VT episodes suggested various underlying arrhythmia mechanisms. CONCLUSIONS: The overall prevalence of arrhythmias was low. Even in such a small sample size, higher arrhythmia counts occurred in those with larger scar burden and greater ventricular volume, suggesting key roles for myocardial stretch as well as disease progression in arrhythmogenesis. These features overlap with the stage of left ventricular dysfunction when heart failure also becomes overt. The findings of this pilot study should help inform the design of a definitive study of specific antiarrhythmic management in dystrophinopathy. TRIAL REGISTRATION NUMBER: ISRCTN15622536.

Durable ventricular assist device in Spain (2007-2020). First report of the REGALAD registry.

INTRODUCTION AND OBJECTIVES: This report presents the clinical characteristics, outcomes and complications of all consecutive patients implanted with a long-term mechanical circulatory support device in Spain between 2007 and 2020. METHODS: Analysis of the Spanish Registry of durable ventricular assist devices (REGALAD) including data form Spanish centers with a mechanical circulatory support program. RESULTS: During the study period, 263 ventricular assist devices were implanted in 22 hospitals. The implanted device was an isolated continuous-flow left ventricular assist device in 182 patients (69%), a pulsatile-flow device (58 isolated left ventricular and 21 biventricular) in 79 (30%), and a total artificial heart in 2 patients (1%). The strategy of the implant was as bridge to heart transplant in 78 patients (30%), bridge to candidacy in 110 (42%), bridge to recovery in 3 (1%) and destination therapy in 72 patients (27%). Overall survival at 6, 12 and 24 months was 79%, 74% and 69%, respectively, and was better in continuous-flow left ventricular assist devices (84%, 80%, and 75%). The main adverse events related to this therapy were infections (37% of patients), bleeding (35%), neurological (29%), and device malfunction (17%). CONCLUSIONS: Durable ventricular assist devices have emerged in Spain in the last few years as a useful therapy for patients with advanced heart failure. As in other international registries, the current trend is to use continuous-flow intracorporeal left ventricular devices, which are associated with better results. Adverse events continue to be frequent and severe.

Ventricular assist devices in transposition and failing systemic right ventricle: role of tricuspid valve replacement.

OBJECTIVES: Ventricular assist device (VAD) for systemic right ventricular (RV) failure patients post-atrial switch, for transposition of the great arteries (TGA), and those with congenitally corrected TGA has proven useful to reduce transpulmonary gradient and bridge-to-transplantation. The purpose of this study is to describe our experience of VAD in systemic RV failure and our move towards concomitant tricuspid valve replacement (TVR). METHODS: This is a single-centre retrospective study of consecutive adult patients receiving HeartWare VAD for systemic RV failure between 2010 and 2019. From 2017, concomitant TVR was performed routinely. Demographic, clinical variables and echocardiographic and haemodynamic measurements pre- and post-VAD implantation were recorded. Complications on support, heart transplantation and survival rates were described. RESULTS: Eighteen patients underwent VAD implantation. Moderate or severe systemic tricuspid regurgitation was present in 83.3% of patients, and subpulmonic left ventricular impairment in 88.9%. One-year survival was 72.2%. VAD implantation was technically feasible and successful in all but one. Post-VAD, transpulmonary gradient fell from 16 (15-22) to 10 (7-13) mmHg (P = 0.01). Patients with TVR (n = 6) also demonstrated a reduction in mean pulmonary and wedge pressures. Furthermore, subpulmonic left ventricular end-diastolic dimension (44.3 vs 39.6 mm; P = 0.03) and function improved in this group. After 1 year of support, 72.2% of patients were suitable for transplantation. CONCLUSIONS: VAD is an effective strategy as bridge-to-candidacy and bridge-to-transplantation in patients with end-stage systemic RV failure. Concomitant TVR at the time of implant is associated with better early haemodynamic and echocardiographic results post-VAD.

Does infection predispose to thrombosis during long-term ventricular assist device support?

BACKGROUND: Infections and thrombotic events remain life-threatening complications in patients with ventricular assist devices (VAD). METHODS: We describe the relationship between both events in our cohort of patients (n = 220) supported with the HeartWare VAD (HVAD). This is a retrospective analysis of patients undergoing HVAD implantation between July 2009 and March 2019 at the Freeman Hospital, Newcastle upon Tyne, United Kingdom. RESULTS: Infection was the most common adverse event in HVAD patients, with 125 patients (56.8%) experiencing ≥ one infection (n = 168, 0.33 event per person year (EPPY)), followed by pump thrombosis (PT) in 61 patients (27.7%, 0.16 EPPY). VAD-specific infections were the largest group of infections. Of the 125 patients who had an infection, 66 (53%) had a thrombotic event. Both thrombotic events and infections were related to the duration of support, though there was only limited evidence that infections predispose to thrombosis. Those with higher than median levels of C-reactive protein during the infection were more likely to have an ischaemic stroke (IS) (34.5% vs 16.7%, p = .03), though not PT or a combined thrombotic event (CTE: first PT or IS). However, in multivariate analysis, there was no significant effect of infection predisposing to CTE. CONCLUSIONS: Infection and thrombotic events are significant adverse events related to the duration of support in patients receiving HVADs. Infections do not clearly predispose to thrombotic events.

Remote heart failure management using the HeartLogic algorithm. RE-HEART registry.

INTRODUCTION AND OBJECTIVES: HeartLogic is a multiparametric algorithm incorporated into implantable cardioverter-defibrillators (ICD). The associated alerts predict impending heart failure (HF) decompensations. Our objective was to analyze the association between alerts and clinical events and to describe the implementation of a protocol for remote management in a multicenter registry. METHODS: We evaluated study phase 1 (the investigators were blinded to the alert state) and phases 2 and 3 (after HeartLogic activation, managed as per local practice and with a standardized protocol, respectively). RESULTS: We included 288 patients from 15 centers. In phase 1, the median observation period was 10 months and there were 73 alerts (0.72 alerts/patient-y), with 8 hospitalizations and 2 emergency room admissions for HF (0.10 events/patient-y). There were no HF hospitalizations outside the alert period. In the active phases, the median follow-up was 16 (95%CI, 15-22) months and there were 277 alerts (0.89 alerts/patient-y); 33 were associated with HF hospitalizations or HF death (n=6), 46 with minor decompensations, and 78 with other events. The unexplained alert rate was 0.39 alerts/patient-y. Outside the alert state, there was only 1 HF hospitalization and 1 minor HF decompensation. Most alerts (82% in phase 2 and 81% in phase 3; P=.861) were remotely managed. The median NT-proBNP value was higher within than outside the alert state (7378 vs 1210 pg/mL; P <.001). CONCLUSIONS: The HeartLogic index was frequently associated with HF-related events and other clinically relevant situations, with a low rate of unexplained events. A standardized protocol allowed alerts to be safely and remotely detected and appropriate action to be taken on them.

Using existing technology better: Improving outcomes with the HeartWare left ventricular assist device.

BACKGROUND: The HeartWare left ventricular assist device has been in use for over 12 years. We sought to determine how outcomes at our centre have improved over time. METHODS: Review of electronic hospital records at the Freeman Hospital, Newcastle upon Tyne, United Kingdom. RESULTS: A total of 255 first time adult implants were divided into 2 eras: Era 1: 2009-2015 (N = 154) and Era 2: 2016-2020 (N = 101). We prospectively aimed to avoid higher risk Intermacs Classifications in Era 2, which resulted in significant changes in Intermacs class to lower risk in Era 2 (P < 0.001). There was a significant improvement in survival in Era 2, with 1 year survival increasing from 70 to 80% (P < 0.05). This was particularly associated with lower 30 day mortality in Era 2 (1.7 ± 2.3 vs 15.5 ± 7%, P < 0.005). This was associated with better right ventricular function in Era 2, and there was a trend to more temporary right ventricular assist devices used in Era 2 (28 ± 13 vs 12 ± 14%, P = 0.06). Deaths from intracranial haemorrhage, sepsis and right heart failure were unchanged between eras, though there was a trend towards less deaths in Era 2 from combined thromboses deaths (stroke and device thrombosis; 3.3 ± 5.4 vs 11.1 ± 7.4%, P = 0.07). CONCLUSIONS: Better patient selection in association with more use of temporary right ventricular assist support has resulted in a significant improvement in survival. Intracranial haemorrhage, sepsis and right heart failure remain significant problems.

Markers of Right Ventricular Dysfunction Predict Maximal Exercise Capacity After Left Ventricular Assist Device Implantation.

Although left ventricular assist device (LVAD) improves functional capacity, on average LVAD patients are unable to achieve the aerobic capacity of normal healthy subjects or mild heart failure patients. The aim of this study was to examine if markers of right ventricular (RV) function influence maximal exercise capacity. This was a single-center prospective study that enrolled 20 consecutive HeartWare ventricular assist device patients who were admitted at the Freeman Hospital (Newcastle upon Tyne, United Kingdom) for a heart transplant assessment from August 2017 to October 2018. Mean peak oxygen consumption (Peak VO2) was 14.0 ± 5.0 ml/kg/min, and mean peak age and gender-adjusted percent predicted oxygen consumption (%VO2) was 40.0% ± 11.5%. Patients were subdivided into two groups based on the median peak VO2, so each group consisted of 10 patients (50%). Right-sided and pulmonary pressures were consistently higher in the group with poorer exercise tolerance. Patients with poor exercise tolerance (peak VO2 below the median) had higher right atrial pressures at rest (10.6 ± 6.4 vs. 4.3 mmHg ± 3.2; p = 0.02) and the increase with passive leg raising was significantly greater than those with preserved exercise tolerance (peak VO2 above the median). Patients with poor functional capacity also had greater RV dimensions (4.4 cm ± 0.5 vs. 3.7 cm ± 0.5; p = 0.02) and a higher incidence of significant tricuspid regurgitation (moderate or severe tricuspid regurgitation in five patients in the poor exercise capacity group vs. none in the preserved exercise capacity group; p = 0.03). In conclusion, echocardiographic and hemodynamic markers of RV dysfunction discriminate between preserved and nonpreserved exercise capacity in HeartWare ventricular assist device patients.

Dímero D y alteraciones del ventrículo derecho como factores pronósticos en pacientes críticos con COVID-19 / D-dimer and right ventricular abnormalities as prognostic factors in critically ill COVID-19 patients

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Neutrophil to Lymphocyte Ratio Is Related to Thrombotic Complications and Survival in Continuous Flow Left Ventricular Assist Devices.

Left ventricular assist devices (LVADs) have become an established treatment for advanced heart failure, although with long-term support these patients are potentially exposed to serious complications. Our purpose was to assess the role of the neutrophil to lymphocyte ratio (NLR) in LVAD complications and to evaluate if higher values of NLR after 4-6 months on LVAD support (NLR 4_6m) are associated with worse prognosis. All consecutive patients who received a HeartWare LVAD (N = 188, age 50 ± 13 years), as bridge to transplant from December 2009 to January 2018 were included. Neutrophil to lymphocyte ratio was recorded pre-LVAD, post-LVAD, after 4-6 months on support and in case of a first adverse event to occur after the 4-6 months NLR was recorded. Median NLR values were pre-LVAD 4.26 (interquartile range [IQR], 3.1-6.9), at 1 day postoperative 11.6 (IQR, 8.3-16.6), and NLR 4_6m 4.4 (IQR, 3.0-6.4) (p < 0.001). Neutrophil to lymphocyte ratio increased significantly when patients had an infection, stroke, or pump thrombosis, as compared with the NLR 4_6m (all p < 0.05). Patients with NLR 4_6m ≥ median had higher rates of stroke and mortality. Survival time was shorter among patients with NLR 4_6m ≥ 4.4 (log-rank test p = 0.006). Neutrophil to lymphocyte ratio 4_6m was found to be predictive of increased mortality (area under the curve of 0.62, p = 0.007). After multivariate analysis, NLR 4_6m remained independently associated with increased mortality (hazard ratio [HR] 1.67; 95% confidence interval [CI], 1.03-2.7; p = 0.037). Neutrophil to lymphocyte ratio 4_6m values significantly increase in association with adverse events on LVAD support and are independently associated with mortality. This association suggests presence of inflammation adversely affects LVAD outcomes.

Effect of Preoperative Tricuspid and/or Mitral Regurgitation on Development of Late Right-Sided Heart Failure After Insertion of the HeartWare Left Ventricular Assist Device.

Right-sided heart failure (RHF) after left ventricular assist device implantation is a significant cause of morbidity and mortality. Although multiple predictors of early RHF have been described, information on late RHF is scarce. The aim of this study was to identify predictors of late RHF in left ventricular assist device patients. A retrospective analysis of all adult patients who underwent HeartWare-ventricular assist device implantation as a bridge to transplantation in a single-centre was performed. Late RHF was defined as RHF requiring rehospitalization after 30 days of implantation. A total of 16 (10.3%) patients from 156 implantations developed late RHF. Median time to late RHF onset was 182.5 (interquartile range 105 to 618) days. Patients developing late RHF were older at surgery. A significantly higher rate of moderate or severe tricuspid regurgitation before implantation was found in patients presenting with late RHF (81.2% vs 33.5%; p <0.001). Several echocardiographic parameters at discharge postimplant, such as significant mitral regurgitation, demonstrated a strong association with late RHF. A multivariate Cox regression analysis revealed that significant preoperative tricuspid regurgitation was the strongest predictor of late RHF (hazard ratio 5.50, 95% confidence interval [1.34 to 22.58]; p = 0.02). Significant mitral regurgitation postimplantation and older age also significantly predicted late RHF. In conclusion, preoperative significant tricuspid regurgitation and mitral regurgitation after implantation predict the occurrence of late RHF.

Long term clinical outcomes in survivors after out-of-hospital cardiac arrest.

INTRODUCTION AND OBJECTIVES: Information regarding long-term outcomes in patients surviving out-of-hospital cardiac arrest (OHCA) is scarce. Our aim was to study the long-term clinical outcomes of a large cohort of OHCA patients surviving until hospital discharge and to identify predictors of mortality and cardiovascular events. METHODS: Consecutive OHCA patients admitted in the Acute Cardiac Care Unit who survived at least until hospital discharge between 2007 and 2019 were included. All received therapeutic hypothermia according to the local protocol. Pre- and intra-hospital clinical and analytical variables were analyzed, as well as the clinically relevant events during follow-up. RESULTS: A total of 201 patients were included, with a mean age of 57.6 ± 14.2 years, 168 (83.6%) were male. Thirty-six (17.9%) died during a median follow-up of 40.3 months (18.9-69.1), the most frequent causes of death being cardiovascular and neurological, followed by cancer. We calculated a predictive model for mortality during follow-up using Cox regression that included the following variables: poor neurological outcome [HR 3.503 (1.578-7.777)], non-shockable rhythm [HR 2.926 (1.390-6.163)], time to onset of CPR [HR 1.063 (0.997-1.134)], older age [1.036 (1.008-1.064)) and worse ejection fraction at discharge [1.033 (1.009-1.058)]. CONCLUSIONS: Even though few patients experience recurrent cardiac arrest events, survivors after OHCA face high morbidity and mortality during long-term follow-up. Therefore, they may benefit from multidisciplinary teams providing an integral management and ensuring continuity of care.

Initial conservative management strategy of HeartWare left ventricular assist device thrombosis with intravenous heparin or bivalirudin.

INTRODUCTION AND OBJECTIVES: Pump thrombosis is a serious left ventricular assist device complication, though there are no guidelines regarding its treatment. The main aim of this study was to describe a strategy of intravenous anticoagulation as the initial treatment in these patients and then to compare intravenous heparin with bivalirudin. METHODS: All consecutive patients who received a HeartWare left ventricular assist device from July 2009 to March 2019 were retrospectively analysed. Patients developing a pump thrombosis were selected, and treatment, outcomes and complications were recorded. RESULTS: During this period of time (116 months), 220 patients underwent HeartWare left ventricular assist device implantation and 57 developed pump thrombosis, with an incidence rate of first pump thrombosis of 0.17 events per patient-year of support (incidence rate of all episodes of pump thrombosis: 0.30 events per patient-year of support). All the patients were initially treated medically, predominantly with either intravenous heparin (n = 26) or bivalirudin (n = 16). Patients treated with bivalirudin during the first pump thrombosis episode had less subsequent re-thrombosis episodes (18.7% vs 57.7%, p < 0.05). In addition, percentage time in therapeutic range was greater for bivalirudin compared with heparin (68.5% ± 16.9% vs 37.4% ± 31.0%, p < 0.01). During the first pump thrombosis episode, 26.3% of the patients needed surgery (left ventricular assist device exchange (n = 8), transplant (n = 6) or decommissioning (n = 1)). The overall survival at 1 year was 61.4%, and there was no significant difference in survival. CONCLUSION: Left ventricular assist device thrombosis is a serious life-threatening complication; hence, we propose an initial conservative management of pump thrombosis with enhanced intravenous anticoagulation with either intravenous heparin or bivalirudin, with surgery reserved for refractory cases.

Dataset regarding baseline and follow-up characteristics of out-of-hospital cardiac arrest patients focused on neurological outcomes.

This data article contains the data related to the research article entitled "Long-term neurological outcomes in out-of-hospital cardiac arrest patients treated with targeted-temperature management" (Caro-Codón et al., 2018). In this dataset, we report details regarding the flow chart of the included patients and the specific exclusion criteria. We also include information on the difference between the patients who attended the structured personal interview (and therefore were finally included in the study) and those who did not attend. Neuropsychiatric and functional data before and after cardiac arrest are also reported. Finally, we list all the "de novo" focal neurological deficits identified after cardiac arrest in the related population.

Long-term neurological outcomes in out-of-hospital cardiac arrest patients treated with targeted-temperature management.

BACKGROUND: This study aimed to assess long-term cognitive and functional outcomes in out-of-hospital cardiac arrest (OHCA) patients treated with targeted-temperature management, investigate the existence of prognostic factors that could be assessed during initial admission and evaluate the usefulness of classic neurological scales in this clinical scenario. METHODS: Patients admitted due to OHCA from August 2007 to November 2015 and surviving at least one year were included. Each patient completed a structured interview focused on the collection of clinical, social and demographic data. All available information in clinical records was reviewed and a battery of neurocognitive and psychometric tests was performed. RESULTS: Seventy-nine patients were finally included in the analysis. Forty-three patients (54.4%) scored below the usual cut-off points for the diagnosis of mild cognitive impairment, even though most of these deficits went unnoticed when patients were assessed using CPC and modified Rankin scale. Nineteen (24%) developed certain degree of impairment in their attention capacity and executive functions. A significant proportion developed new memory-related disorders (43%), depressive symptoms (17.7%), aggressive/uninhibited behavior (12.7%) and emotional lability (8.9%). A greater number of weekly hours of intellectual activity and a qualified job were independent protective factors for the development of cognitive impairment. However, being older at the time of the cardiac arrest was identified as a poor prognostic factor. CONCLUSIONS: There is a high prevalence of long-term cognitive deficits and functional limitations in OHCA survivors. Most commonly used clinical scales in clinical practice are crude and lack sensitivity to detect most of these deficits.

Clinical outcomes in myocardial infarction and multivessel disease after a cardiac rehabilitation programme: Partial versus complete revascularization.

BACKGROUND: Current guideline recommendations encourage culprit vessel only percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. However, recent studies have shown a better clinical outcome in patients who receive multivessel PCI. AIM: To measure and compare clinical outcomes between partial revascularization (PR) versus complete revascularization (CR) in patients with STEMI and multivessel disease who underwent a cardiac rehabilitation programme. METHODS: We retrospectively reviewed the medical records of 282 patients with STEMI and multivessel disease who received PR or CR and were subsequently enrolled in a cardiac rehabilitation programme between July 2006 and November 2013 at La Paz University Hospital. The incidences of cardiovascular events, new PCI, hospital admissions for cardiovascular reasons and mortality were compared between the PR and CR groups. RESULTS: Overall, 143 patients received PR and 139 received CR. Baseline characteristics were similar in both groups, except for mean age (59.3 vs. 56.7 years; P=0.02), diabetes mellitus prevalence (34.3% vs. 20.1%; P=0.01) and number of arteries with stenosis (2.6 vs. 2.3; P=0.001). During the mean follow-up of 48.0±25.9 months, a cardiovascular event occurred in 23 (16.1%) PR patients and 20 (14.4%) CR patients, with no statistically significant differences in the early (hazard ratio: 0.61, 95% confidence interval: 0.19-1.89) or late (hazard ratio: 1.40, 95% confidence interval: 0.62-3.14) follow-up periods. Cox regression, adjusted for age, sex, presence of diabetes mellitus and number of affected coronary vessels, showed no difference in new cardiovascular event risk. CONCLUSIONS: There were no statistical differences in clinical outcomes between PR and CR among patients who received cardiac rehabilitation.

Sources of perceived sociocultural pressure on physical self-concept / Fuentes de la presión sociocultural percibida sobre el autoconcepto físico

The aim of this study is to analyze the four-factor structure (advertising, information, family environment and friendship setting) of the Cuestionario de Influjos Socioculturales sobre el Autoconcepto Físico (CIAF) [Sociocultural Influences on Physical Self-concept Questionnaire] and its invariance in relation to sex, age and physical activity. Method: Participants were 579 students (339 men and 240 women) aged between 12 and 23, divided into three groups (137 under 14 years, 338 aged between 15 and 18 and 104 over 18 years). All completed the CIAF. Results: Both the confirmatory factor analyses and the factor invariance tests support the four-factor structure of the CIAF and, therefore, the identification of four different types of sociocultural perceived influence. Conclusions: These results allow us to apply the abundant data found by previous studies on sociocultural pressure on body image to our understanding of physical selfconcept (AU)

Antecedentes: el objetivo de este trabajo es estudiar la estructura tetrafactorial (publicidad, información, entorno familiar y entorno de las amistades) del Cuestionario de Influjos Socioculturales sobre el Autoconcepto Físico (CIAF) y su invarianza en función del sexo, edad y de la actividad física. Método: participaron en la investigación un total de 579 estudiantes (339 hombres y 240 mujeres), de entre 12 y 23 años de edad, divididos en tres grupos (137 menores de 14 años, 338 de entre 15 y 18 años y 104 mayores de 18 años), quienes cumplimentaron el Cuestionario de Influjos Socioculturales sobre el Autoconcepto Físico (CIAF). Resultados: tanto los análisis factoriales confirmatorios como las pruebas de invarianza factorial refrendan la estructura tetrafactorial del CIAF y por tanto la diferenciación de cuatro tipos de influjos socioculturales autopercibidos. Conclusiones: estos resultados permiten aproximar a la comprensión del autoconcepto físico la abundante información previa acerca de la presión sociocultural sobre la imagen corporal (AU)

Sources of perceived sociocultural pressure on physical self-concept.

BACKGROUND: The aim of this study is to analyze the four-factor structure (advertising, information, family environment and friendship setting) of the Cuestionario de Influjos Socioculturales sobre el Autoconcepto Físico (CIAF) [Sociocultural Influences on Physical Self-concept Questionnaire] and its invariance in relation to sex, age and physical activity. METHOD: Participants were 579 students (339 men and 240 women) aged between 12 and 23, divided into three groups (137 under 14 years, 338 aged between 15 and 18 and 104 over 18 years). All completed the CIAF. RESULTS: Both the confirmatory factor analyses and the factor invariance tests support the four-factor structure of the CIAF and, therefore, the identification of four different types of sociocultural perceived influence. CONCLUSIONS: These results allow us to apply the abundant data found by previous studies on sociocultural pressure on body image to our understanding of physical self-concept.

Activation of the BRCA1/Chk1/p53/p21(Cip1/Waf1) pathway by nitric oxide and cell cycle arrest in human neuroblastoma NB69 cells.

Nitric oxide (NO) works as a bi-modal effector of cell proliferation, inducing either the increase or decrease of cell growth when cells are exposed, respectively, to low or high NO concentrations. To get further insight into the action of NO, we tested the effect of short- and long-lived NO donors on the control of the cell cycle in human neuroblastoma NB69 cells. We demonstrated that long-time exposure of cells to NO not only decreased the expression and/or the phosphorylation of elements involved in the control of the G(1)/S transition, such as the transcriptional repressor pRb and cyclin D1, but also down-regulated systems controlling the S and G(2)/M phases, such as the phosphorylation of Cdk1(cdc2) and the expression of cyclins A and B1. Increasing concentrations of NO also induced a biphasic effect on the expression of cyclins D1, A and B1, while this effect was less pronounced for cyclin E expression, but the levels of mRNAs of those cyclins changed in a distinct and complex manner. NO also changed the phosphorylation pattern of cyclin E and decreased the levels of phospho-cyclins D1 and B1. Moreover, NO decreased the expression of the Cdk inhibitors p16(Ink4a) and p19(Ink4d), without affecting p27(Kip1). In contrast, NO induced a biphasic effect on p21(Cip1/Waf1) expression. The BRCA1/Chk1/p53 pathway mediated the upregulation of p21(Cip1/Waf1). We also demonstrated that the NO-mediated up-regulation of p21(Cip1/Waf1) was inversely correlated with the activation status of the p38MAPK pathway.