Age-associated anatomical and physiological alterations in Caenorhabditis elegans.

Since its introduction by Sydney Brenner, Caenorhabditis elegans has become a widely studied organism. Given its highly significant properties, including transparency, short lifespan, self-fertilization, high reproductive yield and ease in manipulation and genetic modifications, the nematode has contributed to the elucidation of several fundamental aspects of biology, such as development and ageing. Moreover, it has been extensively used as a platform for the modelling of ageing-associated human disorders, especially those related to neurodegeneration. The use of C. elegans for such purposes requires, and at the same time promotes the investigation of its normal ageing process. In this review we aim to summarize the major organismal alterations during normal worm ageing, in terms of morphology and functionality.

P-wave duration and interatrial block as predictors of new-onset atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: Early detection of atrial fibrillation (AF) could improve patient outcomes. P-wave duration (PWD) and interatrial block (IAB) are known predictors of new-onset AF and could improve selection for AF screening. This meta-analysis reviews the published evidence and offers practical implications. METHODS: Publication databases were systematically searched, and studies reporting PWD and/or morphology at baseline and new-onset AF during follow-up were included. IAB was defined as partial (pIAB) if PWD≥120 ms or advanced (aIAB) if the P-wave was biphasic in the inferior leads. After quality assessment and data extraction, random-effects analysis calculated odds ratio (OR) and confidence intervals (CI). Subgroup analysis was performed for those with implantable devices (continuous monitoring). RESULTS: Among 16,830 patients (13 studies, mean 66 years old), 2,521 (15%) had new-onset AF over a median of 44 months. New-onset AF was associated with a longer PWD (mean pooled difference: 11.5 ms, 13 studies, p < 0.001). The OR for new-onset AF was 2.05 (95% CI: 1.3-3.2) for pIAB (5 studies, p = 0.002) and 3.9 (95% CI: 2.6-5.8) for aIAB (7 studies, p < 0.001). Patients with pIAB and devices had higher AF-detection risk (OR: 2.33, p < 0.001) than those without devices (OR: 1.36, p = 0.56). Patients with aIAB had similarly high risk regardless of device presence. There was significant heterogeneity but no publication bias. CONCLUSION: Interatrial block is an independent predictor of new-onset AF. The association is stronger for patients with implantable devices (close monitoring). Thus, PWD and IAB could be used as selection criteria for intensive screening, follow-up or interventions.

Perfusion parameters analysis of the vertebral bone marrow in patients with Ph¹â» chronic myeloproliferative neoplasms (Ph(neg) MPN): a dynamic contrast-enhanced MRI (DCE-MRI) study.

PURPOSE: To evaluate perfusion parameters of the vertebral bone marrow in patients with Philadelphia negative chronic myeloproliferative neoplasms (Ph(neg) MPN) using dynamic contrast-enhanced MRI (DCE-MRI). MATERIALS AND METHODS: The study enrolled 24 patients with Ph(neg) MPN: 12 patients with myelofibrosis (Group A), 6 with essential thrombocythemia (ET), and 6 with polycythemia vera (PV) (Group B) who underwent DCE-MRI of the lumbosacral spine. Twelve normal individuals served as control group (Group C). Wash-in (WIN), wash-out (WOUT), maximum contrast-enhancement (CE max), time-to-peak (TTPK), time-to-maximum slope (TMSP), and the WIN/TMSP ratio (WTSP) were calculated. RESULTS: WIN, CE(max) , and WTSP parameters were higher in Group A than in Group C (P < 0.05). These parameters were significant (P < 0.0001) in discriminating patients with myelofibrosis from normal individuals with sensitivities 74.14%, 87.93%, 74.14%, and specificities 91.07%, 83.93%, 91.07%, respectively. WIN, WOUT, CE(max) , and WTSP parameters were higher in Group A than in Group B (P < 0.05). Group B exhibited no differences in perfusion parameters as compared with Group C with the exception of WOUT. CONCLUSION: Patients with myelofibrosis exhibited increased perfusion parameters in vertebral bone marrow, which could be consisted with increased vascularity, probably related to neoangiogenesis as opposed to ET or PV patients showing no increased perfusion. DCE-MRI may be of value in discriminating subgroups of Ph(neg) MPN patients and in indicating those progressing to myelofibrosis.

Leukocyte activation after coronary stenting in patients during the subacute phase of a previous ST-elevation myocardial infarction.

OBJECTIVE: To study leukocyte activation after percutaneous coronary intervention in patients with previous ST elevation myocardial infarction. METHODS: Neutrophil and monocyte activation (by flow cytometric assessment of the surface expression of CD11b and CD62L adhesion molecules) was assessed in 39 patients during the subacute period of a previous ST elevation myocardial infarction initially treated with fibrinolytic agents, before and after diagnostic coronary angiography (coronary angiography control phase) as well as before and after stent implantation (percutaneous coronary intervention phase). Simultaneous evaluation of C-reactive protein (C-reactive protein immonoturbidimetry) and plasma cytokine levels (interleukins-1, -6, -10 and tumor necrosis alpha by immunoassay) was also performed. To track the earliest detectable change in the first few minutes after stent deployment, all measurements were performed before and 60 min after the procedures. RESULTS: CD11b expression increased 1 h after stent deployment in neutrophils (P<0.0001) and monocytes (P<0.0001). A comparable increase, however, was also observed after coronary angiography (neutrophils, P=0.03; monocytes, P=0.01), although the increase of CD11b expression was greater after percutaneous coronary intervention on both neutrophils (90 vs. 40%, P=0.014) and monocytes (65 vs. 33%, P=0.04). CD62L expression decreased significantly after percutaneous coronary intervention (neutrophils, P=0.01; monocytes, P=0.006), but remained unchanged after coronary angiography. Plasma cytokine and C-reactive protein concentrations did not change after the procedures. CONCLUSION: CD62L appears to be a specific and reliable early cellular biomarker of leukocyte activation after percutaneous coronary intervention, when this procedure is performed in patients with previous ST elevation myocardial infarction. Whether this marker represents also a potential predictor of future events and/or restenosis in this group of patients remains to be defined.

Amifostine stimulates the formation of hematopoietic bone marrow progenitors from B-cell chronic lymphocytic leukemia.

Amifostine is a phosphorylated aminothiol that not only protects hematopoietic progenitor cells from chemotherapy and radiotherapy, but also stimulates normal hematopoiesis. The effect of amifostine on the in vitro growth of hematopoietic progenitors derived from B-cell chronic lymphocytic leukemia(B-CLL) was investigated. The colony-forming units (CFU)-granulocyte macrophage (CFU-GM), the burst-forming units-erythroid (BFU-E) and the CFU-granulocyte erythroid macrophage megakaryocytes (CFU-GEMM) increased 38, 20 and 100%, respectively, after the incubation with amifostine. There was no statistical difference in the in vitro progenitor growth of patients grouped according to their disease stage, bone marrow lymphocytic infiltration or therapy. Our data indicate that apart from cytoprotection the parallel use of amifostine and chemotherapy in patients with B-CLL could enhance bone marrow recovery.