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001; adjusted p-values). Similarly, in shift workers, mood and well-being levels were significantly reduced throughout days of misalignment, as compared to circadian alignment (interaction of "circadian alignment condition" vs. "day", mood p = 0.002; well-being p = 0.002; adjusted p-values). Our findings indicate that circadian misalignment is an important biological component for mood vulnerability, and that individuals who engage in shift work are susceptible to its deleterious mood effects.Transport networks are becoming increasingly large and interconnected. This interconnectivity is a key enabler of accessibility; on the other hand, it results in vulnerability, i.e. reduced performance, in case any specific part is subject to disruptions. We analyse how railway systems are vulnerable to delay, and how delays propagate in railway networks, studying real-life delay propagation phenomena on empirical data, determining real-life impact and delay propagation for the uncommon case of railway disruptions. We take a unique approach by looking at the same system, in two different operating conditions, to disentangle processes and dynamics that are normally present and co-occurring in railway operations. We exploit the unique chance to observe a systematic change in railway operations conditions, without a correspondent system change of infrastructure or timetable, coming from the occurrence of the large-scale disruption at Rastatt, Germany, in 2017. We define new statistical methods able to detect weak signals in the noisy dataset of recorded punctuality for passenger traffic in Switzerland, in the disrupted and undisrupted state, along a period of 1 year. We determine how delay propagation changed, and quantify the heterogeneous, large-scale cascading effects of the Rastatt disruption towards the Swiss network, hundreds of kilometers away. Operational measures of transport performance (i.e. punctuality and delays), while globally being very decreased, had a statistically relevant positive increase (though very geographically heterogeneous) on the Swiss passenger traffic during the disruption period. We identify two factors for this (1) the reduced delay propagation at an international scale; and (2) to a minor extent, rerouted railway freight traffic; which show to combine linearly in the observed outcomes.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Melicoccus bijugatus Jacq (Mb) has been reported to have cardiovascular modulatory effects. In this study, we evaluated the antihypertensive effects and mechanism of action of Mb on NG-Nitro-L-arginine Methyl Ester (L-NAME) and Deoxycorticosterone Acetate (DOCA) rat models. Aqueous extract of Mb fruit (100 mg/kg) was administered for 6 weeks to rats by gavage and blood pressure was recorded. Effects of the extract on vascular reactivity was evaluated using isolated organ baths, and tissues were collected for biochemical and histological analysis. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were significantly (P less then 0.05) reduced with extract (100 mg/kg) administration and treatment compared to the hypertensive models. Mb (100 µg/mL) reduced the vascular contractility induced by phenylephrine (PE), and caused a dose-dependent relaxation of PE-induced contraction of aortic vascular rings. The vasorelaxation properties seemed to be endothelium dependent, as well as nitric oxide (NO) and guanylyl cyclase, but not prostaglandin dependent. Histomicrograph of transverse sections of the ventricles from the Mb group did not show abnormalities. The extract significantly (P less then 0.05) reduced an L-NAME induced elevation of cardiac output and Creatine Kinase Muscle-Brain (CKMB), but had no significant impact on the activities of arylamine N-acetyltransferase. In conclusion, Mb significantly decreased blood pressure in hypertensive models. The extract possesses the ability to induce endothelium dependent vasodilation, which is dependent on guanylyl cyclase but not prostaglandins.Human taste perception is associated with the papillae on the tongue as they contain a large proportion of chemoreceptors for basic tastes and other chemosensation. Especially the density of fungiform papillae (FP) is considered as an index for responsiveness to oral chemosensory stimuli. The standard procedure for FP counting involves visual identification and manual counting of specific parts of the tongue by trained operators. This is a tedious task and automated image analysis methods are desirable. In this paper a machine learning image processing method based on a convolutional neural network is presented. This automated method was compared with three standard manual FP counting procedures using tongue pictures from 132 subjects. Automated FP counts, within the selected areas and the whole tongue, significantly correlated with the manual counting methods (all ρs ≥ 0.76). When comparing the images for gender and PROP status, the density of FP predicted from automated analysis was in good agreement with data from the manual counting methods, especially in the case of gender. Moreover, the present results reinforce the idea that caution should be applied in considering the relationship between FP density and PROP responsiveness since this relationship can be an oversimplification of the complexity of phenomena arising at the central and peripherical levels. Indeed, no significant correlations were found between FP and PROP bitterness ratings using the automated method for selected areas or the whole tongue. Besides providing estimates of the number of FP, the machine learning approach used a tongue coordinate system that normalizes the size and shape of an individual tongue and generated a heat map of the FP position and normalized area they cover. The present study demonstrated that the machine learning approach could provide similar estimates of FP on the tongue as compared to manual counting methods and provide estimates of more difficult-to-measure parameters, such as the papillae's areas and shape.Chronic rhinosinusitis (CRS) occurs in >10% of the adult population in Europe and the USA and can be differentiated into CRS without nasal polyps and CRS with nasal polyps (CRSwNP). Both phenotypes are characterized by a high disease burden and an overlapping spectrum of symptoms, with facial pain and loss of smell being the most differentiating. Great progress has been made in the understanding of CRS pathophysiology from the epithelium and epithelial-mesenchymal transition to innate and adaptive immunity pathways and, finally, on the role of eosinophils and Staphylococcus aureus in the persistence of disease. Although clinical manifestations and diagnostic tools (including nasal endoscopy and imaging) have undergone major changes over the past few years, management (including pharmacotherapy, surgery and biologics) has experienced enormous progress based on the growing knowledge of key mediators in severe CRSwNP. The introduction of endotyping has led to a differentiation of 'tailored' surgical approaches, focusing on the mucosal concept in those with severe CRSwNP and on the identification of patients eligible for extended surgery and possibly biologics in the future.An amendment to this paper has been published and can be accessed via a link at the top of the paper.The selected A. tricolor accessions contained abundant color attributes, betacyanin, carotenoids, betalains, betaxanthins, and antioxidants potentiality that varied in terms of genotypes. For the first time, we identified 4 betacyanins, and 5 carotenoid compounds in A. tricolor genotypes. The genotype VA14 and VA16 had abundant color attributes, betacyanin such as amaranthine, iso-amaranthine, betanin, iso-betanin, and antioxidants potentiality. These two genotypes having an excellent source of color attributes, betacyanins, betalains, betaxanthins, and antioxidants potentiality could be used as potent antioxidant varieties. The genotype VA11 and VA16 had abundant carotenoid components, such as zeaxanthin, lutein, violaxanthin, neoxanthin, total xanthophylls, and beta-carotene. The genotype VA11 and VA16 had abundant carotenoid components that could be used as carotenoid enrich varieties. It revealed from the correlation study that pigment profiles of A. tricolor genotypes exhibited high quenching capacity of radicals. These accessions have high antioxidant potentials and great opportunity to make drinks, preservatives, and colorant of food products to feed the community deficient in antioxidants. The identified components of betacyanins and carotenoids in A. tricolor require comprehensive pharmacological study. The baseline data on color attributes, betacyanins profile, carotenoids profile, betaxanthins, betalains and antioxidant potentiality obtained in the present study could contribute to pharmacologists for evaluating these components scientifically in A. tricolor.Although PEGylated filgrastim-induced aortitis is very rare and unknown clinically, some cases were reported and increasing, especially in breast cancer patients. The present study investigated the prevalence, clinical features and treatment of aortitis induced by PEGylated filgrastim in patients with breast cancer. A total of 2068 consecutive patients who underwent neoadjuvant/adjuvant chemotherapy with PEGylated filgrastim for breast cancer were enrolled. From the medical record, clinical, laboratory, medication, and imaging evaluation findings were collected. PEGylated filgrastim-induced aortitis was established in 0.3% of the study population. Common clinical presentations included extremely high fever and chest/back pain with high levels of inflammatory markers without any signs of infection. Contrast-enhanced computed tomography scans revealed typical enhancing wall thickening and periaortic soft tissue infiltration at various levels of aorta. All patients improved rapidly after treatment with modest doses of prednisolone (0.5 mg/kg/day) without any complications. Clinicians should be aware of aortitis as a possible complication of granulocyte-colony stimulating factor therapy, especially PEGylated filgrastim, given the frequent misdiagnoses in neutropenic patients undergoing chemotherapy.Preterm prelabor rupture of membranes (PPROM) is the most frequent complication of fetal surgery. Strategies to seal the membrane defect created by fetoscopy aiming to reduce the occurrence of PPROM have been attempted with little success. The objective of this study was to evaluate the ex-vivo mechanical sealing properties and toxicity of four different bioadhesives integrated in semi-rigid patches for fetal membranes. We performed and ex-vivo study using term human fetal membranes to compare the four integrated patches composed of silicone or silicone-polyurethane combined with dopaminated-hyaluronic acid or hydroxypropyl methylcellulose (HPMC). For mechanical sealing properties, membranes were mounted in a multiaxial inflation device with saline, perforated and sealed with the 4 combinations. We measured bursting pressure and maximum pressure free of leakage (n = 8). For toxicity, an organ culture of membranes sealed with the patches was used to measure pyknotic index (PI) and lactate dehydrogenase (LDH) concentration (n = 5).
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