1,721,014 research outputs found
TITIN DOWNREGULATION AFFECTS CARDIOMYOCYTES PROLIFERATION
Full text linkA recent investigation, focused on the potential of specific miRNAs to augment CM proliferation, has unveiled that this phenomenon arises from the cumulative impact on multiple mRNA targets within the cells (4). This comprehensive analysis of genes downregulated by these miRNAs has demonstrated a noteworthy enrichment in genes associated with categories such as 'skeletal and muscular system development and function' and 'cellular assembly and organization.' Among these genes is TTN, a pivotal player. Notably, targeted downregulation of these genes has the potential to independently induce CM proliferation.
In humans, it is well-established that TTNtv represent a preeminent genetic ethology of DCM, with their pathogenicity primarily attributed to haploinsufficiency mechanisms(75). The aim of this study is to probe the repercussions of reducing TTN levels, particularly with regard to cardiac myocyte turnover and proliferative dynamics, and if these replicative abnormalities could be a causative association with TTNtv-DCM.
To induce a targeted reduction in TTN expression, we have employed a precise strategy involving the administration of TTN-specific siRNA/shRNA respectively in vitro and in vivo models. This approach enabled us to comprehensively evaluate cardiac phenotypic alterations, conduct an in-depth examination of CM structural changes, and explore the proliferative capacities of the cells under regulated TTN downregulation.A recent investigation, focused on the potential of specific miRNAs to augment CM proliferation, has unveiled that this phenomenon arises from the cumulative impact on multiple mRNA targets within the cells (4). This comprehensive analysis of genes downregulated by these miRNAs has demonstrated a noteworthy enrichment in genes associated with categories such as 'skeletal and muscular system development and function' and 'cellular assembly and organization.' Among these genes is TTN, a pivotal player. Notably, targeted downregulation of these genes has the potential to independently induce CM proliferation.
In humans, it is well-established that TTNtv represent a preeminent genetic ethology of DCM, with their pathogenicity primarily attributed to haploinsufficiency mechanisms(75). The aim of this study is to probe the repercussions of reducing TTN levels, particularly with regard to cardiac myocyte turnover and proliferative dynamics, and if these replicative abnormalities could be a causative association with TTNtv-DCM.
To induce a targeted reduction in TTN expression, we have employed a precise strategy involving the administration of TTN-specific siRNA/shRNA respectively in vitro and in vivo models. This approach enabled us to comprehensively evaluate cardiac phenotypic alterations, conduct an in-depth examination of CM structural changes, and explore the proliferative capacities of the cells under regulated TTN downregulation
Subclinical systolic dysfunction in genotype-positive phenotype-negative relatives of dilated cardiomyopathy patients: A systematic review and meta-analysis
Full text linkThe absence of left ventricular (LV) dilatation and systolic dysfunction, as assessed by LV ejection fraction (LVEF), in family members of genetically confirmed dilated cardiomyopathy (DCM) patients, carrying pathogenic (P) or likely pathogenic (LP) familial gene variants categorizes them as a subgroup called genotype-positive phenotype-negative (GEN+ PHEN−). Identifying GEN+ PHEN− who are at the highest risk of developing the disease throughout their lifetime is crucial
Reply to the letter regarding the article 'Subclinical systolic dysfunction in genotype-positive phenotype-negative relatives of dilated cardiomyopathy patients: A systematic review and meta-analysis'
Full text linkWe would like to express our gratitude to Dr. Albulushi and colleagues for their interest in our work and for raising insightful questions that allow us to clarify certain concepts
The contribution of cardiopulmonary exercise testing in the familial screening for dilated and non-dilated left ventricular cardiomyopathies: case series
Full text linkBackground: The importance of family screening in relatives of patients affected by cardiomyopathies is highlighted in the international guidelines. Although electrocardiogram (ECG) and echocardiogram represent cornerstones of family screening, they may not always be sufficient to detect subtle abnormalities, especially in genotype-positive/phenotype-negative relatives. The role of cardiopulmonary exercise testing (CPET) in providing additional clinical information during family screening, remains to be fully elucidated.
Case summary: Ten asymptomatic genotype-positive/phenotype-negative first-degree relatives of probands affected by dilated cardiomyopathy (DCM) and non-dilated left ventricular cardiomyopathy (NDLVC) were evaluated in the context of family screening. Cardiopulmonary exercise testing was integrated into the initial diagnostic evaluation. Two out of 10 relatives showed an abnormal CPET, with alteration in O2 kinetic.
Discussion: Family screening in relatives of DCM and NDLVC patients, particularly in genotype-positive/phenotype-negative subjects, remains challenging due to difficulties in assessing the subtle abnormalities that may represent an initial clinical manifestation of the disease and support early treatment initiation. A more accurate and comprehensive familial screening may be achieved by integrating ECG and echocardiogram-the current first-line assessments-with data from additional tools, such as global longitudinal strain on echocardiogram, cardiac magnetic resonance, Holter ECG, and CPET
Effects of oral immunonutrition on histological changes of inflammatory infiltration of the tumor microenvironment among patients with a new diagnosis of gastric cancer
No full textObjectives: We assessed the effects of oral immunonutrition (OI) on the inflammatory infiltration of the tumor microenvironment (TME) of patients undergoing surgery for gastric cancer. Methods: We analyzed patients at the time of their first gastric cancer diagnosis. We collected surgical tissue specimens (stomach), and performed an immunohistochemical analysis to evaluate the inflammatory infiltration of the TME. Patients receiving OI were compared with patients receiving standard oral nutritional supplements and no nutritional support. Results: We enrolled 12 patients with gastric cancer in the study. The median body weight loss was 5.6%. Four patients received OI, five patients received standard nutritional supplement, and three patients received no nutritional supplementation. No difference in age, body mass index (BMI), and body weight loss was observed between the three groups. The OI group showed a tendency of increased number of T-lymphocyte cluster of differentiation (CD) 8+ compared with the other groups, as well as the number of CD83+ and CD68+. The absence of F4/80+ cells was documented only in the TME of the OI group, where a linear positive correlation was present between lymphocytes CD4+ and CD8+ (R = 0.48), and between CD4+ and CD83+ (R = 0.89), although not statistically significant. In the OI group, we observed a positive correlation (not significant) between the number of lymphocytes CD8+ and macrophages CD68+ (R = 0.70; P = 0.30). A strong significant correlation was documented between CD68+ and CD40+ (R = 0.99; P = 0.01), but this correlation did not reach the significance among the patients of the other two groups (R = 0.60; P = 0.116). Conclusions: The administration of OI in patients with gastric cancer might determine changes in inflammatory patterns of the TME
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Left bundle branch block in dilated cardiomyopathy with intermediate left ventricular dysfunction: clinical phenotyping and outcome correlates
No full textBACKGROUND:
Left bundle branch block (LBBB) negatively affects prognosis in heart failure patients with a reduced left ventricular ejection fraction (LVEF). Less is known about the prognostic role of LBBB in dilated cardiomyopathy (DCM) with intermediate LVEF (between 36% and 50%). We sought to assess the role of LBBB in optimally treated DCM patients with mildly to moderately reduced LVEF and to determine the possible variables associated with subsequent LVEF reduction.
METHODS:
We retrospectively analyzed DCM patients with LVEF >35% after 3-to-9 months of optimal medical treatment (OMT) consecutively evaluated from 1990 to 2010. All-cause mortality or heart transplantation (D/HTx) and sudden cardiac death (SCD) or major ventricular arrhythmias (MVA) were considered as outcome measures. LVEF deterioration during follow-up was also considered.
RESULTS:
Among 280 (49%) patients that met the study criteria, 76 had LBBB (27%). During a mean follow-up of 151 months, the rates of D/HTx and SCD/MVA were similar between LBBB and not LBBB patients (p value = 0.52 and p = 0.39, respectively). Twenty-six out of 76 (34%) patients with LBBB experienced LVEF deterioration below 36%. The persistence of moderate-severe mitral regurgitation (MR), left atrial end-systolic area index and LV end-diastolic volume index emerged as independent predictors of LVEF deterioration and were associated with an increased risk of D/HTx during follow-up.
CONCLUSIONS:
LBBB does not affect mortality in DCM patients with intermediate LVEF after OMT. However, among these patients those with persistent significant MR, left atrial and LV remodeling carries a higher risk of LVEF deterioration during follow-up
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