Correlation between high-risk HPV infection and p16/Ki-67 abnormalities in Pap samples in a South Eastern Europe cohort.

Cervical cancer (CC) is the fourth most common cause of cancer-related deaths amongst women worldwide. CC represents a major global healthcare issue, and Romania ranks the worst in mortality rates amongst EU countries. However, the early detection of CC can be lifesaving. To understand the testing process undergone by women in Romania, we performed a retrospective study, and investigated a cohort of 83 785 cervical cases from Romanian women aged 15-70, obtained in private-based opportunistic screening. We examined the correlation between Pap smear results, human papilloma virus (HPV) genotyping, and the expression of cell cycle markers p16 and Ki-67. Analysis of Pap results revealed approximately 10% abnormal cases, of which high-grade squamous intraepithelial lesions constituted 4.9%. HPV genotyping of 12 185 cases with available Pap results unveiled a range of high-risk HPV (hrHPV) types associated with cervical abnormalities. Notably, 26% of hrHPV-positive cases showed no observable abnormalities. In a subset of cases with abnormal Pap and a type of hrHPV, P16/Ki-67 double-staining was also positive. This study suggests the importance of an integrated diagnostic algorithm that should consider the HPV genotype, Pap smear, and p16/Ki-67 staining. This algorithm should enhance the CC screening accuracy and its management strategies, particularly in those regions with a high disease burden, such as Romania.

Dynamic Involvement of Telocytes in Modulating Multiple Signaling Pathways in Cardiac Cytoarchitecture.

Cardiac interstitium is a complex and dynamic environment, vital for normal cardiac structure and function. Telocytes are active cellular players in regulating main events that feature myocardial homeostasis and orchestrating its involvement in heart pathology. Despite the great amount of data suggesting (microscopically, proteomically, genetically, etc.) the implications of telocytes in the different physiological and reparatory/regenerative processes of the heart, understanding their involvement in realizing the heart's mature cytoarchitecture is still at its dawn. Our scrutiny of the recent literature gave clearer insights into the implications of telocytes in the WNT signaling pathway, but also TGFB and PI3K/AKT pathways that, inter alia, conduct cardiomyocytes differentiation, maturation and final integration into heart adult architecture. These data also strengthen evidence for telocytes as promising candidates for cellular therapies in various heart pathologies.

Areas of Cartilaginous and Osseous Metaplasia After Experimental Myocardial Infarction in Rats.

The presence of hyaline cartilage has been previously documented in heart tissue of different vertebrates, ranging from birds to superior mammals. However, there is scarce published data regarding the appearance of focal deposits of hyaline-like cartilage within the hearts of laboratory rats. Few mechanisms that could trigger the appearance of this type of cartilage in heart were hypothesized (e.g., mechanical stress, ageing). Using different microscopy techniques this report confirms the presence of hyaline cartilage and bone in Wistar rats, which underwent left anterior coronary artery ligation for experimental myocardial infarction. The presented (ultra)structural evidence of focal chondroid metaplasia in the papillary muscles and close to the insertion point in the ventricular mass of the infarcted heart suggests a structural adaptation of cardiac myocardium to the newly acquired kinetics of left ventricular wall, after experimental myocardial infarction. Specific cartilaginous matrix proteins are known to mediate cardiac extracellular matrix remodeling, and this study provides evidence of a complete transition to a cartilaginous pattern in postinfarcted heart, which may nonetheless constitute a supplemental risk factor of a further heart failure condition. Moreover, for heart focal chondrogenesis, we also presume the involvement of the cellular and molecular inflammatory milieu that dominates the first 24 hr border zone landscape of the experimental myocardial infarction lesion. Anat Rec, 302:947-953, 2019. © 2018 Wiley Periodicals, Inc.

Telocytes - a Hope for Cardiac Repair after Myocardial Infarction.

Cardiovascular diseases, particularly myocardial infarction, remain the leading cause of morbidity and mortality worldwide, even though pharmacological and interventional therapies improved significantly in the last years. Moreover, despite encouraging results of cell - based therapies in experimental myocardial infarction models, clinical trials showed inconsistent and modest efficiency. Therefore the next step should be the revealing of a new cell type, capable of regenerating the damaged myocardium. Telocytes (TCs), a relatively new type of interstitial cells, were described few years ago and are credited with important roles in regenerative therapies. In this paper we review their most important characteristics and functions, showing the evidences of their potential role in cardiac repair and regeneration. Our research leads to the conclusion that TCs might be a novel target for therapeutic strategies in myocardial infarction.

New Echocardiographic Protocol for the Assessment of Experimental Myocardial Infarction in Rats.

BACKGROUND: The rat infarct model was used extensively to study the pathophysiology of myocardial infarction and to evaluate different therapies. Transthoracic echocardiography is used in rats in order to assess cardiac anatomy and function, being a safe and reliable non-invasive technique. However, studies combining conventional with new echo techniques, such as tissue Doppler imaging (TDI) and speckletracking echocardiography (STE), are lacking. OBJECTIVES: To validate a protocol using the available conventional and new echocardiographic techniques (TDI and STE) for a comprehensive assessment of cardiac remodelling and function, after myocardial infarction in rats. METHODS: Ten Wistar (W) and five Sprague Dawley (SD) male rats (aged 21±2 weeks, mean weight 355±43 g) were evaluated by echocardiography, before and 24 hours post-ligation of the left coronary artery, with previous anaesthesia. Left ventricular (LV) structure was assessed by end-diastolic and endsystolic anterior wall thickness and LV diameters (from the SAX view), while LV function by fractional shortening (FS) and ejection fraction (EF) (by area-length formula), septal mitral annular plane systolic excursion (MAPSE), cardiac output (CO), myocardial performance index (MPI), septal mitral annular systolic velocity (S', by TDI), and global circumferential and radial systolic strain (GCS, GRS) and strain rate (GCSr, GRSr) by STE, from the SAX view at the level of papillary muscles. RESULTS: Feasibility of measuring the above mentioned parameters was 100%. Twenty-four hours after myocardial infarction, rats had lower heart rate (373±44 vs. 351±32 bpm, p<0.05) and thinner LV anterior wall, while LV diameters and volumes were significantly higher. FS (54±7 vs. 33±9%), EF (72±9vs. 47±10%), septal MAPSE (2.02±0.17 vs. 1.44±0.22 mm), CO (76±15 vs. 48±12 ml/min), MPI (0.33±0.11 vs. 0.50±0.14), S' (5.58±1.20 vs. 3.84±1.06 cm/s), and LV strain and strain rate (GCS: -23.52±2.44 vs. -13.33±1.51% and GRS: 50.45±13.11 vs. 17.27±5.2%, GCSr: -8.42±0.85 vs. -4.68±0.53; and GRSr: 11.93±2.39 vs. 4.89±1.18 1/s) were significantly lower, all p<0.01. CONCLUSIONS: Our echocardiographic protocol of experimental myocardial infarction in rats is feasible. The impact of myocardial infarction in rats could be more extensively assessed using a comprehensive echocardiographic protocol of conventional and specific myocardial parameters, measured by TDI and STE, in order to quantify better the LV structure and function. Therefore, we suggest that this protocol may be used in order to assess the effect of different regenerative therapies in experimental myocardial infarction in rats.