Reduced systemic vascular resistance is the underlying hemodynamic mechanism in nitrate-stimulated vasovagal syncope during head-up tilt-table test

AbstractBackgroundNitroglycerin (NTG) challenge during head-up tilt-table testing (HUTT) is often utilized to determine the etiology of unexplained vascular syncope. However, conflicting results concerning nitrate-induced hemodynamic changes during HUTT have been reported. The purpose of this study was to assess the determinants of presyncopal symptoms during NTG-stimulated HUTT.MethodsWe evaluated 40 patients with suspected vasovagal syncope. Beat-to-beat changes in blood pressure, heart rate (HR), cardiac index (CI), and systemic vascular resistance (SVR) during HUTT were measured with thoracic impedance cardiography and a plethysmographic finger arterial pressure monitoring device.ResultsNone of the 40 patients complained of presyncopal symptoms during passive HUTT. However, after the administration of NTG 28 patients showed presyncopal symptoms (NTG+ group) and the remaining 12 patients did not (NTG– group). HR, CI, and the stroke index did not significantly differ between the two groups, whereas mean arterial pressure and SVR were significantly lower in the NTG+ group.ConclusionsPresyncopal symptoms during NTG-stimulated HUTT are SVR mediated, not cardiac output mediated. This study challenges the conventional idea of a decrease in cardiac output mediated by NTG as the overriding cause of presyncopal symptoms during HUTT

Retinoid production using metabolically engineered Escherichia coli with a two-phase culture system

<p>Abstract</p> <p>Background</p> <p>Retinoids are lipophilic isoprenoids composed of a cyclic group and a linear chain with a hydrophilic end group. These compounds include retinol, retinal, retinoic acid, retinyl esters, and various derivatives of these structures. Retinoids are used as cosmetic agents and effective pharmaceuticals for skin diseases. Retinal, an immediate precursor of retinoids, is derived by β-carotene 15,15'-mono(di)oxygenase (BCM(D)O) from β-carotene, which is synthesized from the isoprenoid building blocks isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Retinoids are chemically unstable and biologically degraded via retinoic acid. Although extensive studies have been performed on the microbial production of carotenoids, retinoid production using microbial metabolic engineering has not been reported. Here, we report retinoid production using engineered <it>Escherichia coli </it>that express exogenous BCM(D)O and the mevalonate (MVA) pathway for the building blocks synthesis in combination with a two-phase culture system using a dodecane overlay.</p> <p>Results</p> <p>Among the BCM(D)O tested in <it>E. coli</it>, the synthetic retinoid synthesis protein (SR), based on bacteriorhodopsin-related protein-like homolog (Blh) of the uncultured marine bacteria 66A03, showed the highest β-carotene cleavage activity with no residual intracellular β-carotene. By introducing the exogenous MVA pathway, 8.7 mg/L of retinal was produced, which is 4-fold higher production than that of augmenting the MEP pathway (<it>dxs </it>overexpression). There was a large gap between retinal production and β-carotene consumption using the exogenous MVA pathway; therefore, the retinal derivatives were analyzed. The derivatives, except for retinoic acid, that formed were identified, and the levels of retinal, retinol, and retinyl acetate were measured. Amounts as high as 95 mg/L retinoids were obtained from engineered <it>E. coli </it>DH5α harboring the synthetic <it>SR </it>gene and the exogenous MVA pathway in addition to <it>dxs </it>overexpression, which were cultured at 29°C for 72 hours with 2YT medium containing 2.0% (w/v) glycerol as the main carbon source. However, a significant level of intracellular degradation of the retinoids was also observed in the culture. To prevent degradation of the intracellular retinoids through <it>in situ </it>extraction from the cells, a two-phase culture system with dodecane was used. The highest level of retinoid production (136 mg/L) was obtained after 72 hours with 5 mL of dodecane overlaid on a 5 mL culture.</p> <p>Conclusions</p> <p>In this study, we successfully produced 136 mg/L retinoids, which were composed of 67 mg/L retinal, 54 mg/L retinol, and 15 mg/L retinyl acetate, using a two-phase culture system with dodecane, which produced 68-fold more retinoids than the initial level of production (2.2 mg/L). Our results demonstrate the potential use of <it>E. coli </it>as a promising microbial cell factory for retinoid production.</p

Parenchymal Neurocutaneous Melanosis in Association with Intraventricular Dermoid and Dandy-Walker Variant: A Case Report

Neurocutaneous melanosis (NCM) is a rare congenital disease that is characterized by the presence of large or multiple congenital melanocytic nevi and melanotic lesions of the central nervous system. We report here on the CT and MR imaging findings of an unusual case of NCM that was associated with intraventricular dermoid and Dandy-Walker malformation

Primary Acinic Cell Carcinoma of the Breast: A Case Report with an Immunohistochemical and Ultrastructural Studies

Acinic cell carcinoma (ACC) of the breast is extremely rare and is characterized by widespread acinar cell-like differentiation. We report of a 39-year-old woman presented with a palpable breast mass with significant morphological, immunohistochemical and ultrastructural findings. Histologically, ACC showed a diffuse glandular infiltrative pattern, with small acinar or glandular structures mixed with solid nests. Neoplastic cells were monotonous proliferation of cells with a granular or clear cytoplasm, resembling acinar cells of the salivary glands or Paneth cells. Both glandular and solid tumor cell populations were strongly positive for lysozyme and α-1-antitrypsin

Clinical Outcomes and Prognostic Factors of Up-Front Autologous Stem Cell Transplantation in Patients with Extranodal Natural Killer/T Cell Lymphoma

AbstractLimited data exist on up-front autologous stem cell transplantation (ASCT) in extranodal natural killer/T cell lymphoma (ENKTL). Sixty-two patients (43 men and 19 women) with newly diagnosed ENKTL who underwent up-front ASCT after primary therapy were identified. Poor-risk characteristics included advanced stage (50%), high-intermediate to high-risk International Prognostic Index (25.8%), and group 3 to 4 of NK/T Cell Lymphoma Prognostic Index (NKPI, 67.7%). Pretransplant responses included complete remission in 61.3% and partial remission in 38.7% of patients, and final post-transplantation response included complete remission in 78.3%. Early progression occurred in 12.9%. At a median follow-up of 43.3 months (range, 3.7 to 114.6), 3-year progression-free survival (PFS) was 52.4% and 3-year overall survival (OS) was 60.0%. Patients with limited disease had significantly better 3-year PFS (64.5% versus 40.1%, P = .017) and OS (67.6% versus 52.3%, P = .048) than those with advanced disease. Multivariate analysis showed NKPI and pretransplant response were independent prognostic factors influencing survival, particularly NKPI in limited disease and pretransplant response in advanced disease. Radiotherapy was an independent factor for reduced progression and survival in patients with limited disease, but anthracycline-based chemotherapy was a poor prognostic factor for progression in patients with advanced disease. Up-front ASCT is an active treatment in ENKTL patients responding to primary therapy

Effects of Posture and Acute Sleep Deprivation on Heart Rate Variability

PURPOSE: In our previous study to investigate autonomic nervous system (ANS) activity due to radio frequency (RF) radiation using heart rate variability (HRV), drowsiness was observed in approximately half of all subjects. Therefore, the usage of HRV with unwanted drowsiness could falsely indicate the effects of RF radiation by mobile phones on the ANS. The objective of this study was to determine which posture is appropriate for accurate HRV analysis for provocation study. MATERIALS AND METHODS: A total of 52 healthy subjects (25 males and 27 females) participated in this experiment. We measured the number of times a subject showed drowsiness or sleep deprivation due to awakening, and analyzed HRV six times over 30 minutes in sitting and recumbent postures, using power spectrum. RESULTS: We employed the ratio of low frequency power to high frequency power (LFP/HFP) to analyze the changes in the ANS. The number of sleep deprivation occurrences in the sitting posture was significantly less than that in the recumbent posture (p<0.01), resulting in smaller increase of LFP/HFP. Although LFP/HFP of the two postures varied with time without any provocation, it was more stable in sitting than in recumbent postures. CONCLUSION: A sitting posture is preferable to a recumbent posture for analyzing HRV, because of decreased drowsiness and sleep deprivation, thereby decreasing variation of LFP/HFP during experiment. Considering the drowsiness, it is also recommended that any experiment should be completed within 15 minutes, if possible.ope

Paenibacillus yonginensis DCY84T induces changes in Arabidopsis thaliana gene expression against aluminum, drought, and salt stress

Current agricultural production methods, for example the improper use of chemical fertilizers and pesticides, create many health and environmental problems. Use of plant growth-promoting bacteria (PGPB) for agricultural benefits is increasing worldwide and also appears to be a trend for the future. There is possibility to develop microbial inoculants for use in agricultural biotechnology, based on these beneficial plant–microbe interactions. For this study, ten bacterial strains were isolated from Yongin forest soil for which in vitro plant-growth promoting trait screenings, such as indole acetic acid (IAA) production, a phosphate solubilization test, and a siderophore production test were used to select two PGPB candidates. Arabidopsis thaliana plants were inoculated with Paenibacillus yonginensis DCY84T and Micrococcus yunnanensis PGPB7. Salt stress, drought stress and heavy metal (aluminum) stress challenges indicated that P. yonginensis DCY84T-inoculated plants were more resistant than control plants. AtRSA1, AtVQ9 and AtWRKY8 were used as the salinity responsive genes. The AtERD15, AtRAB18, and AtLT178 were selected to check A. thaliana responses to drought stress. Aluminum stress response was checked using AtAIP, AtALS3 and AtALMT1. The qRT-PCR results indicated that P. yonginensis DCY84T can promote plant tolerance against salt, drought, and aluminum stress. P. yonginensis DCY84T also showed positive results during in vitro compatibility testing and virulence assay against X. oryzae pv. oryzae Philippine race 6 (PXO99). Better germination rates and growth parameters were also recorded for the P. yonginensis DCY84T Chuchung cultivar rice seed which was grown on coastal soil collected from Suncheon. Based on these results, P. yonginensis DCY84T can be used as a promising PGPB isolate for crop improvement