BackgroundAlthough cardiac injury has been reported in patients with various neurological conditions, few data report cardiac injury in patients with traumatic brain injury (TBI). The aim of this work is to report the incidence of cardiac injury in patients with TBI and its impact on patient outcome.MethodsA prospective observational study was conducted on a cohort of 50 patients with severe TBI. Only patients with isolated severe TBI defined as Glascow coma scale (GCS) < 8 were included in the study. Acute physiology and chronic health evaluation (APACHE) II score, GCS, hemodynamic data, serum Troponin I, electrocardiogram (ECG), and echocardiographic examination, and patients’ outcome were recorded. A neurogenic cardiac injury score (NCIS) was calculated for all patients (rising troponin = 1, abnormal echocardiography = 1, hypotension = 1). Univariate and multivariate analyses for risk factors for mortality were done for all risk factors.Results and discussionFifty patients were included; age was 31 ± 12, APACHE II was 21 ± 5, and male patients were 45 (90 %). Troponin I was elevated in 27 (54 %) patients, abnormal echocardiography and hypotension were documented in 14 (28 %) and 16 (32 %) patients, respectively. The in-hospital mortality was 36 %. Risk factors for mortality by univariate analysis were age, GCS, APACHE II score, serum troponin level, NCIS, and hypotension. However, in multivariate analysis, the only two independent risk factors for mortality were APACHE II score (OR = 1.25, 95 % confidence interval: 1.02–1.54, P = 0.03) and NCIS score (OR = 8.38, 95 % confidence interval: 1.44–48.74, P = 0.018).ConclusionsCardiac injury is common in patients with TBI and is associated with increased mortality. The association of high NCIS and poor outcome in these patients warrants a further larger study.
The therapeutic potential of Musashi (MSI) RNA-binding proteins, important stemness-associated gene expression regulators, remains insufficiently understood in breast cancer. This study identifies the interplay between MSI protein expression, stem cell characteristics, radioresistance, cell invasiveness and migration. MSI-1, MSI-2 and Notch pathway elements were investigated via quantitative polymerase chain reaction (qPCR) in 19 triple-negative breast cancer samples. Measurements were repeated in MDA-MB-231 cells after MSI-1 and -2 siRNA-mediated double knockdown, with further experiments performed after MSI silencing. Flow cytometry helped quantify expression of CD44 and leukemia inhibitory factor receptor (LIFR), changes in apoptosis and cell cycle progression. Proliferation and irradiation-induced effects were assessed using colony formation assays. Radiation-related proteins were investigated via Western blots. Finally, cell invasion assays and digital holographic microscopy for cell migration were performed. MSI proteins showed strong correlations with Notch pathway elements. MSI knockdown resulted in reduction of stem cell marker expression, cell cycle progression and proliferation, while increasing apoptosis. Cells were radiosensitized as radioresistance-conferring proteins were downregulated. However, MSI-silencing-mediated LIFR downregulation resulted in enhanced cell invasion and migration. We conclude that, while MSI knockdown results in several therapeutically desirable consequences, enhanced invasion and migration need to be counteracted before knockdown advantages can be fully exploited.
The trabeculae cranii are at first quite separate from each other, after few days their anterior two fifths are connected by a trabecular plate which is obliterated throughout development. The paired origin of the parachordal plate is not observed. The fused posterior orbital cartilages chondrify in the form of a wide short plate, traversed by the oculomotor and trochlear nerves. The basicranial fenestra and fenestra ovalis are formed by the degeneration of pre-existing cartilage. The cochlear portion is completely fused with the parachordal plate from the very beginning. The elements of the pterygoquadrate are fused together. The quadrate and Meckel's cartilage are in close contact from the very beginning. While the lower part of the interorbital septum is derived from the trabecula communis, its upper part is derived from the anterior orbital cartilages. The lateral parts of the fused posterior orbital cartilages give rise to most of the taeniae and pilae of the orbitotemporal region. There is only one commissure between the auditory capsule and parachordal plate. A cartilaginous connection between the distal portion of the columella auris and ceratohyal persists for some time. The parietotectal and paranasal cartilages are fused together from the very beginning. The processus paroticus originates from the columella auris.I n the fully formed stage the notochord is completely embedded in the occipital condyle. The union between the condyle and odontoid process persists. The auditory capsules and occipital arches contribute to the formation of the tectum synoticum plus posterius. The prefacial commissure and facial foramen lie i n front of the cochlear portion. The columella auris possesses a processus internus (connected with the quadrate), but the processus dorsalis has completely disappeared. The orbitotemporal region is quite complete. A medial fenestra is formed i n the planurn suprnseptale. A fenestra is observed in each of the interorbital and nasal septa. The lamina transversalis anterior is fused with the parietotectal cartilage. A complete zona annularis is present. The outer wall of the paranasal cartilage is perforated by a large fenestra lateralis. The parietotectal and paranasal cartilages and the posterior process of the lamina transversalis anterior contribute to the formation of the concha nasalis. There is a contact between the planurn antorbitale and nasal septum. The pterygoid process has disappeared. The common nium are deduced.
Aim: Design and synthesis of thienopyrimidine derivatives as dual EGFR and VEGFR-2 inhibitors. Material and methods: A series of novel 6,7,8,9-tetrahydro-5 H -cyclohepta[4,5]thieno[2,3- d ]pyrimidine derivatives with different substituents on C-4 position was synthesized and evaluated for their anticancer activity against MCF-7 cell line. EGFR, VEGFR-2 inhibitory assay, the cell cycle analysis and apoptosis induction ability of the most potent compound 5f were evaluated. Results: Most of the compounds showed moderate to significant anticancer activity. Compound 5f exhibited the most potent anticancer activity being 1.73- and 4.64-folds more potent than erlotinib and doxorubicin, respectively. Compound 5f showed potent EGFR inhibitory activity being 1.18-folds more potent than reference standard erlotinib and it also showed good VEGFR-2 inhibitory activity at the micromolar level with IC 50 value 1.23 µM. Compound 5f caused induction of cell cycle arrest at G2/M phase and accumulation of cells in pre-G1 phase. Compound 5f induced cellular apoptosis.
The fully formed chondrocranium of the Egyptian snake, Psammophis sihilaiis has been described in detail. The tectum syiioticum i s very broad and there is apparently no tectum posterius. The notochord is complctely embedded in the occipital condyle. The connection between the condyle and the odontoid process persists to the fully formed stagc. There is only one commissure, representing the anterior basicapsular commissure, connecting the auditory capsule to the basal plate. The fissura mctotica is continuous postero-dorsally with the fissura occipitocapsularis. The distal bent end of the shaft of the columella auris represents the processus dorsalis, and the nodule that separates from it and fuses with the quadrate is the intercalarc.The interorbital septum, orbitosphenoid cartilages, basitrabecular processes and planum supraseptale are coinpletely absent. The concha nasalis is of the simplified type, the active factor in its formation is the folding of the olfactory epithelium. Thc solum nasi is greatly reduced and comprises the floor of the cupola anterior, the composite lamina transversalis anterior, cartilago ectochoanalis, cartilago hypochoanalis and ectochoanal plate. The branchial arches are complctely absent. The pterygoquadrate is represented only by the quadrate cartilage. The ceratohyals are extremely long.In a previous paper, which is now in the press, the authors have studied the development of the chondrocranium of one of the Egyptian snakes which is Psammophis sibilans, up to a fairly late stage. Six selected successive stages, which demonstrated clearly the development of the chondrocranium, were described in detail. In the present paper, the morphology of the fully formed chondrocranium of Psammophis sihilans is dealt with. The most advanced stage (stage VI) described in the previous paper leads on conveniently to the stage (fully formed chondrocranium) described in the present work. A sufficient number of late embryos, up to ones which were about to hatch, were transversely sectioned, the technique used is the same described in the previous work. The age of the embryo, the chondrocranium of which is here reconstructed and fully described, was 44 days, its total body length was 157.8 mm. The osteocranium of a very late embryo of Psammophis sihilans will be studied in a third paper, which will soon be published.
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