Impact of Routine Fractional Flow Reserve Evaluation During Coronary Angiography on Management Strategy and Clinical Outcome: One-Year Results of the POST-IT.

Penetration of fractional flow reserve (FFR) in clinical practice varies extensively, and the applicability of results from randomized trials is understudied. We describe the extent to which the information gained from routine FFR affects patient management strategy and clinical outcome. METHODS AND RESULTS: Nonselected patients undergoing coronary angiography, in which at least 1 lesion was interrogated by FFR, were prospectively enrolled in a multicenter registry. FFR-driven change in management strategy (medical therapy, revascularization, or additional stress imaging) was assessed per-lesion and per-patient, and the agreement between final and initial strategies was recorded. Cardiovascular death, myocardial infarction, or unplanned revascularization (MACE) at 1 year was recorded. A total of 1293 lesions were evaluated in 918 patients (mean FFR, 0.81±0.1). Management plan changed in 406 patients (44.2%) and 584 lesions (45.2%). One-year MACE was 6.9%; patients in whom all lesions were deferred had a lower MACE rate (5.3%) than those with at least 1 lesion revascularized (7.3%) or left untreated despite FFR≤0.80 (13.6%; log-rank P=0.014). At the lesion level, deferral of those with an FFR≤0.80 was associated with a 3.1-fold increase in the hazard of cardiovascular death/myocardial infarction/target lesion revascularization (P=0.012). Independent predictors of target lesion revascularization in the deferred lesions were proximal location of the lesion, B2/C type and FFR. CONCLUSIONS: Routine FFR assessment of coronary lesions safely changes management strategy in almost half of the cases. Also, it accurately identifies patients and lesions with a low likelihood of events, in which revascularization can be safely deferred, as opposed to those at high risk when ischemic lesions are left untreated, thus confirming results from randomized trials.

Classification and clinical behavior of blastic plasmacytoid dendritic cell neoplasms according to their maturation-associated immunophenotypic profile

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare subtype of leukemia/lymphoma, whose diagnosis can be difficult to achieve due to its clinical and biological heterogeneity, as well as its overlapping features with other hematologic malignancies. In this study we investigated whether the association between the maturational stage of tumor cells and the clinico-biological and prognostic features of the disease, based on the analysis of 46 BPDCN cases classified into three maturation-associated subgroups on immunophenotypic grounds. Our results show that blasts from cases with an immature plasmacytoid dendritic cell (pDC) phenotype exhibit an uncommon CD56- phenotype, coexisting with CD34+ non-pDC tumor cells, typically in the absence of extramedullary (e.g. skin) disease at presentation. Conversely, patients with a more mature blast cell phenotype more frequently displayed skin/extramedullary involvement and spread into secondary lymphoid tissues. Despite the dismal outcome, acute lymphoblastic leukemia-type therapy (with central nervous system prophylaxis) and/or allogeneic stem cell transplantation appeared to be the only effective therapies. Overall, our findings indicate that the maturational profile of pDC blasts in BPDCN is highly heterogeneous and translates into a wide clinical spectrum -from acute leukemia to mature lymphoma-like behavior-, which may also lead to variable diagnosis and treatment.

Neurobiology and clinical implications of lucid dreaming

Several lines of evidence converge to the idea that rapid eye movement sleep (REMS) is a good model to foster our understanding of psychosis. Both REMS and psychosis course with internally generated perceptions and lack of rational judgment, which is attributed to a hyperlimbic activity along with hypofrontality. Interestingly, some individuals can become aware of dreaming during REMS, a particular experience known as lucid dreaming (LD), whose neurobiological basis is still controversial. Since the frontal lobe plays a role in self-consciousness, working memory and attention, here we hypothesize that LD is associated with increased frontal activity during REMS. A possible way to test this hypothesis is to check whether transcranial magnetic or electric stimulation of the frontal region during REMS triggers LD. We further suggest that psychosis and LD are opposite phenomena: LD as a physiological awakening while dreaming due to frontal activity, and psychosis as a pathological intrusion of dream features during wake state due to hypofrontality. We further suggest that LD research may have three main clinical implications. First, LD could be important to the study of consciousness, including its pathologies and other altered states. Second, LD could be used as a therapy for recurrent nightmares, a common symptom of depression and post-traumatic stress disorder. Finally, LD may allow for motor imagery during dreaming with possible improvement of physical rehabilitation. In all, we believe that LD research may clarify multiple aspects of brain functioning in its physiological, altered and pathological states.

The development and field test of a Mealtime Interaction Clinical Observation Tool: a pilot study and clinical research portfolio

Objective: The purpose of this study was to develop and test psychometric properties of a Mealtime Interaction Clinical Observation Tool (MICOT) that could be used to facilitate assessment and behavioural intervention in childhood feeding difficulties. Methods: Thematic analysis of four focus groups with feeding and behaviour experts identified the content and structure of the MICOT. Following refinement, inter-rater reliability was tested between three healthcare professionals. Results: Six themes were identified for the MICOT, which utilises a traffic-light system to identify areas of strength and areas for intervention. Despite poor inter-rater reliability, for which a number of reasons are postulated, some correlation between psychologists’ ratings was evident. Healthcare professionals liked the tool and reported that it could have good clinical utility. Conclusion: The study provides a promising first version of a clinical observation tool that facilitates assessment and behavioural intervention in childhood feeding difficulties.

Parents’ experiences during the transition from childhood to adolescence with Type 1 Diabetes: Parent-child relationships and support received during this time and clinical research portfolio

Background: Type 1 Diabetes (T1D) management often worsens as children become adolescents. This can be a difficult time for parents as they hand over responsibility of diabetes management to their adolescent. Objectives: To look at the experiences of parents with a child with T1D as they move to adolescence and take more responsibility for their diabetes management. To find out about parents’ experience of support during this transition. Subjects: Three parents of adolescents with T1D. Participants were recruited from the NHS Highland Paediatric Diabetes Service. Methods: Participants took part in a one-to-one semi-structured interview with a researcher. Interpretative Phenomenological Analysis was used to analyse the interviews and find common themes across the interviews. Results: Participants experienced worry throughout their child’s transition to adolescence. They found it difficult to let their child take responsibility for their diabetes but acknowledged that their involvement caused tensions with their adolescent. Participants’ experience was that there were a number of practical adjustments to be made with a diagnosis of T1D and educating the network around their child was important. The participants reported that the diagnosis of T1D had an impact on the whole family and not just the child with the diagnosis. The parents felt well supported medically but said that the amount of time before their first clinic appointment felt too long. All participants had concerns about their adolescent moving to the adult diabetic service. Conclusions: Participants experienced worry relating to aspects of their adolescents T1D that they could not control, but were aware of the tensions caused by trying to keep elements of control. Areas of future research were identified.

Attachment Style, Therapeutic Alliance and Recovery in forensic mental health: the A-STAR study and clinical research portfolio

Background: Research suggests that forensic mental health services and staff can play an important role in the recognition and intervention with attachment-related behaviours to promote engagement and recovery. There is a lack of literature exploring whether the attachment needs of forensic service-users are recognised and, associations between attachment style and factors predictive of recovery. Aims: This study aimed to examine the extent to which service-users and keyworkers agree about service-users’ attachment and to identify whether attachment was associated with service attachment, working alliance, ward climate and recovery. Methods: Twenty-two service-users from low and medium secure forensic services, completed questionnaire measures of their attachment style, service attachment, working alliance, ward climate and experiences of recovery. Nineteen keyworkers completed measures of the service-users attachment style and working alliance. Results: There was strong agreement between service-users and staff for attachment anxiety (ICC=0.71) but poor agreement for attachment avoidance (ICC=0.39). Service attachment was associated with more positive perceptions of staff support (r=0.49) and avoidant attachment was associated with lower ratings of recovery (r=-0.51). Correlations between attachment style and service attachment, working alliance and ward climate were small and non-significant. Conclusions: A focus on staff training to support recognition of the nature and impact of avoidant attachment styles is indicated. The findings suggest that interventions to enhance staff - service-user relationships may be important for service attachment and indeed promotion of a recovery focused orientation amongst service-users high in avoidant attachment may improve wellbeing and outcomes.

A preliminary examination of the relationship between compulsive exercise and shame in individuals with an eating disorder: and clinical research portfolio

Objective: To explore the relationship between compulsive exercise and shame in a clinical sample of eating disorder patients. Method: In a cross-sectional study, individuals with an eating disorder (n=21) completed self-report measures of compulsive exercise, internal shame, external shame, bodily shame, anxiety and depression. Results: Internal shame was moderately associated with compulsive exercise (r=.496, p<.05). No further variables were significantly related to compulsive exercise. Individuals with Anorexia-Nervosa and Bulimia-Nervosa did not significantly differ on any of the study variables. Discussion: Hypotheses regarding the possible nature of the relationship between compulsive exercise and shame are suggested. For instance, that compulsive exercise may serve a role in the regulation of internal shame. That compulsive exercise may act as a compensatory behaviour and be a consequence of high levels of shame. Or that internal shame may result as a response to negative perceptions of one’s exercise habits. The results are discussed in line with current literature.

Molecular and biochemical mechanisms involved in the toxicity of a marine cyanobacteria compound on cancer cell lines

In recent years marine biotechnology has revealed a crucial role in the future of bioindustry. Among the many marine resources, cyanobacteria have shown great potential in the production of bioactive compounds with diverse applicability. The pharmacological potential of these organisms has been one of the most explored areas in particular its antibacterial, antifungal and anticancer potential. This work was based on the assessment of potential anticancer compound E13010 F 5.4 isolated from marine cyanobacteria strain Synechocystis salina LEGE 06099. Thus the aim of this work was to explore molecular and biochemical mechanisms underlying the bioactivity detected in human cancer cells, specifically in lines RKO colon carcinoma and HT-29. The isolation of the compound was performed from biomass obtained by large-scale culture. To obtain the compound fractionation was carried and confirmation and isolation performed by Nuclear Magnetic Resonance (NMR), Thin Layer Chromatography (TLC) and High-Performance Liquid Chromatography (HPLC). Cell viability assays were performed based on reduction of 3- (4,5-dimetiltiaziol-2-yl) -2,5-diphenyltetrazolium bromide (MTT) to assess the cytotoxic potential of the compound. From the battery of cell lines RKO (colon carcinoma), HT-29 (colorectal adenocarcinoma), MG-63 (osteosarcoma) and T47D (breast carcinoma) the cell lines RKO and HT-29 were selected for elucidation of mechanisms of cytotoxicity. For the elucidation of the mechanisms involved in cytotoxicity the cell lines RKO and HT29 were exposed to the compound. A genomic approach based in the mRNA expression of genes involved in apoptosis and cell cycle by Real-Time PCR and a proteomic approach based on the separation of proteins by two-dimensional electrophoresis (2DGE) was performed. For mRNA expression were selected the genes RPL8, HPRT1, VDAC, SHMT2, CCNE, CCNB1, P21CIP, BCL-2 and BAD and for proteomics isoelectric focussing between 3 – 10 and molecular weight of 19 – 117 kDa separated by polyacrylamide gels (2DGE). The MTT results confirmed the reduction of the cell viability. The RT-PCR results for the expression of genes studied were not yet fully elucidative. For the cell line RKO there was a significant reduction in the expression of the gene P21CIP, and a tendency for reduction in the BAD gene expression and for increased expression of gene CCNB1, pointing to an effort for cell proliferation. In HT-29 cell line, there was a tendency for increase in the expression of P21CIP and BAD, which may explain the reduction in cell viability. The 2DGE results indicate proteomic patterns with differentially altered spots in the treated and control cells with both qualitative and quantitative differences, and differences in response between the RKO and HT-29 cell lines.

Behçet's syndrome: literature review and clinical case report

Behçet's disease (BD) is a multi-systemic vascular disorder characterized by oral and genital ulcers, as well as cutaneous, ocular, arthritic, vascular, central nervous system and gastrointestinal involvement. It usually affects young adults, and its pathological origin is unknown. The case of a 47-year-old woman with recurrent ulcers in the oral cavity is presented. She linked the pain with sitting and during the sexual act, with vaginal and oral cavity pain, due to the lesions present at those sites, as well as swelling and pain in the knees, making walk painful. The patient was kept under observation and underwent multidisciplinary treatment with prescription of topical and systemic drugs to improve quality of life. Dentists should be aware of BD and the need of multidisciplinary treatment to increase the patient's quality of life.

Molecular and serological detection of occult hepatitis B virus among healthy hepatitis B surface antigen-negative blood donors in Malaysia.

Background: Occult hepatitis B infections are becoming a major global threat, but the available data on its prevalence in various parts of the world are often divergent. Objective: This study aimed to detect occult hepatitis B virus in hepatitis B surface antigen-negative serum using anti-HBc as a marker of previous infection. Patient and Methods: A total of 1000 randomly selected hepatitis B surface antigen-negative sera from blood donors were tested for hepatitis B core antibody and hepatitis B surface antibody using an ELISA and nested polymerase chain reaction was done using primers specific to the surface gene (S-gene). Results: Of the 1000 samples 55 (5.5%) were found to be reactive, of which 87.3% (48/55) were positive for hepatitis B surface antibody, indicating immunity as a result of previous infection however, that does not exclude active infection with escaped mutant HBV. Nested PCR results showed the presence of hepatitis B viral DNA in all the 55 samples that were positive for core protein, which is in agreement with the hepatitis B surface antibody result. Conclusion: This study reveals the 5.5% prevalence of occult hepatitis B among Malaysian blood donors as well as the reliability of using hepatitis B core antibody in screening for occult hepatitis B infection in low endemic, low socioeconomic settings.

A study of the effect of molecular and aerosol conditions in the atmosphere on air fluorescence measurements at the Pierre Auger Observatory

The air fluorescence detector of the Pierre Auger Observatory is designed to perforin calorimetric measurements of extensive air showers created by Cosmic rays of above 10(18) eV. To correct these measurements for the effects introduced by atmospheric fluctuations, the Observatory contains a group Of monitoring instruments to record atmospheric conditions across the detector site, ail area exceeding 3000 km(2). The atmospheric data are used extensively in the reconstruction of air showers, and are particularly important for the correct determination of shower energies and the depths of shower maxima. This paper contains a summary of the molecular and aerosol conditions measured at the Pierre Auger Observatory since the start of regular operations in 2004, and includes a discussion of the impact of these measurements oil air shower reconstructions. Between 10(18) and 10(20) eV, the systematic Uncertainties due to all atmospheric effects increase from 4% to 8% in measurements of shower energy, and 4 g cm(-2) to 8 g cm(-2) in measurements of the shower maximum. (C) 2010 Elsevier B.V. All rights reserved.

Shaping the Dicot Fruit: Molecular and Genomic Approaches to Fruit Development

The fruit is one of the most complex and important structures produced by flowering plants, and understanding the development and maturation process of fruits in different angiosperm species with diverse fruit structures is of immense interest. In the work presented here, molecular genetics and genomic analysis are used to explore the processes that form the fruit in two species: The model organism Arabidopsis and the diploid strawberry Fragaria vesca. One important basic question concerns the molecular genetic basis of fruit patterning. A long-standing model of Arabidopsis fruit (the gynoecium) patterning holds that auxin produced at the apex diffuses downward, forming a gradient that provides apical-basal positional information to specify different tissue types along the gynoecium’s length. The proposed gradient, however, has never been observed and the model appears inconsistent with a number of observations. I present a new, alternative model, wherein auxin acts to establish the adaxial-abaxial domains of the carpel primordia, which then ensures proper development of the final gynoecium. A second project utilizes genomics to identify genes that regulate fruit color by analyzing the genome sequences of Fragaria vesca, a species of wild strawberry. Shared and distinct SNPs among three F. vesca accessions were identified, providing a foundation for locating candidate mutations underlying phenotypic variations among different F. vesca accessions. Through systematic analysis of relevant SNP variants, a candidate SNP in FveMYB10 was identified that may underlie the fruit color in the yellow-fruited accessions, which was subsequently confirmed by functional assays. Our lab has previously generated extensive RNA-sequencing data that depict genome-scale gene expression profiles in F. vesca fruit and flower tissues at different developmental stages. To enhance the accessibility of this dataset, the web-based eFP software was adapted for this dataset, allowing visualization of gene expression in any tissues by user-initiated queries. Together, this thesis work proposes a well-supported new model of fruit patterning in Arabidopsis and provides further resources for F. vesca, including genome-wide variant lists and the ability to visualize gene expression. This work will facilitate future work linking traits of economic importance to specific genes and gaining novel insights into fruit patterning and development.

Factor structure of the General Health Questionnaire-28 (GHQ-28) from infertile women attending the Yazd Research and Clinical Center for Infertility

Background: Nowadays, infertility problems have become a social concern, and are associated with multiple psychological and social problems. Also, it affects the interpersonal communication between the individual, familial, and social characteristics. Since women are exposed to stressors of physical, mental, social factors, and treatment of infertility, providing a psychometric screening tool is necessary for disorders of this group. Objective: The aim of this study was to determine the factor structure of the general health questionnaire-28 to discover mental disorders in infertile women. Materials and Methods: In this study, 220 infertile women undergoing treatment of infertility were selected from the Yazd Research and Clinical Center for Infertility with convenience sampling in 2011. After completing the general health questionnaire by the project manager, validity and, reliability of the questionnaire were calculated by confirmatory factor structure and Cronbach's alpha, respectively. Results: Four factors, including anxiety and insomnia, social dysfunction, depression, and physical symptoms were extracted from the factor structure. 50.12% of the total variance was explained by four factors. The reliability coefficient of the questionnaire was obtained 0.90. Conclusion: Analysis of the factor structure and reliability of General Health Questionnaire-28 showed that it is suitable as a screening instrument for assessing general health of infertile women.