The F-actin cytoskeleton in syncytia from non-clonal progenitor cells

The actin cytoskeleton of plant syncytia (a multinucleate cell arising through fusion) is poorly known: to date, there have only been reports about F-actin organization in plant syncytia induced by parasitic nematodes. To broaden knowledge regarding this issue, we analyzed F-actin organization in special heterokaryotic Utricularia syncytia, which arise from maternal sporophytic tissues and endosperm haustoria. In contrast to plant syncytia induced by parasitic nematodes, the syncytia of Utricularia have an extensive F-actin network. Abundant F-actin cytoskeleton occurs both in the region where cell walls are digested and the protoplast of nutritive tissue cells fuse with the syncytium and also near a giant amoeboid in the shape nuclei in the central part of the syncytium. An explanation for the presence of an extensive F-actin network and especially F-actin bundles in the syncytia is probably that it is involved in the movement of nuclei and other organelles and also the transport of nutrients in these physiological activity organs which are necessary for the development of embryos in these unique carnivorous plants. We observed that in Utricularia nutritive tissue cells, actin forms a randomly arranged network of F-actin, and later in syncytium, two patterns of F-actin were observed, one characteristic for nutritive cells and second—actin bundles—characteristic for haustoria and suspensors, thus syncytia inherit their F-actin patterns from their progenitors

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Penetrating injury to the head: case reviews

Penetrating injury to the head is considered a form of severe traumatic brain injury. Although uncommon, most neurosurgical centres would have experienced treating patients with such an injury. Despite the presence of well written guidelines for managing these cases, surgical treatment requires an individualized approach tailored to the situation at hand. We describe a collection of three cases of non-missile penetrating head injury which were managed in two main Neurosurgical centres within Malaysia and the unique management approaches for each of these cases

Time-Course of Hypothalamic-Pituitary-Adrenal Axis Activity and Inflammation in Juvenile Rat Brain After Cranial Irradiation

Recent studies reported that exposure of juvenile rats to cranial irradiation affects hypothalamic-pituitary-adrenal (HPA) axis stability, leading to its activation along with radiation-induced inflammation. In the present study, we hypothesized whether inflammatory reaction in the CNS could be a mediator of HPA axis response to cranial irradiation (CI). Therefore, we analyzed time-course changes of serum corticosterone level, as well IL-1 beta and TNF-alpha level in the serum and hypothalamus of juvenile rats after CI. Protein and gene expression of the glucocorticoid receptor (GR) and nuclear factor kappaB (NF kappa B) were examined in the hippocampus within 24 h postirradiation interval. Cranial irradiation led to rapid induction of both GR and NF kappa B mRNA and protein in the hippocampus at 1 h. The increment in NF kappa B protein persisted for 2 h, therefore NF kappa B/GR protein ratio was turned in favor of NF kappa B. Central inflammation was characterized by increased IL-1 beta in the hypothalamus, with maximum levels at 2 and 4 h after irradiation, while both IL-1 beta and TNF-alpha were undetectable in the serum. Enhanced hypothalamic IL-1 beta probably induced the relocation of hippocampal NF kappa B to the nucleus and decreased NF kappa B mRNA at 6 h, indicating promotion of inflammation in the key tissue for HPA axis regulation. Concomitant increase of corticosterone level and enhanced GR nuclear translocation in the hippocampus at 6 h might represent a compensatory mechanism for observed inflammation. Our results indicate that acute radiation response is characterized by increased central inflammation and concomitant HPA axis activation, most likely having a role in protection of the organism from overwhelming inflammatory reaction.Ministry of Education and Science of the Republic of Serbia [173044