Delayed Suspicion, Treatment and Isolation of Tuberculosis Patients in Pulmonology/Infectious Diseases and Non-Pulmonology/Infectious Diseases Wards

Background/PurposeDelayed diagnosis and isolation increases the risk of nosocomial transmission of tuberculosis (TB). To assess the risk of delayed management of TB, we analyzed the risk factors of prolonged delay in isolation of smear-positive TB patients in pulmonology/infectious diseases and other wards in a tertiary teaching hospital.MethodsWe enrolled smear-positive TB patients aged > 16 years with delayed respiratory isolation following hospitalization. Medical records were reviewed retrospectively. Time intervals between admission, order of sputum acid-fast staining, initiation of anti-tuberculous treatment and isolation were compared between pulmonology/infectious diseases wards (PIWs) and other wards. Risk factors were analyzed in patients with prolonged isolation delay of > 7 days in individual groups.ResultsIsolation was delayed in 191 (73.7%) of 259 hospitalized smear-positive TB patients. Median suspicion, treatment and isolation delays were 0, 3 and 4 days in PIWs and 1, 5 and 7 days in other wards. For patients admitted to non-PIWs, atypical chest radiographs, symptoms without dyspnea or not being admitted from the emergency department (ED) were risk factors for prolonged isolation delay exceeding 7 days. The only risk factor for delayed isolation in patients admitted to PIWs was age ≥ 70 years.ConclusionDelays in suspicion, treatment and isolation of TB patients were longer in non-PIWs. Clinicians should be alert to those admitted to non-PIWs with atypical chest radiographs, atypical symptoms, or not admitted from the ED

A Two-Degree-Of-Freedom Time-Optimal Solution for Hard Disk Drive Servo Problems

This paper deals with the hard disk drive (HDD) servo problems. A novel discrete time-optimal control solution is proposed in a two-degree-of-freedom (2DOF) structure, employing both the feedback and feedforward controllers. The time-optimal feedback controller, derived from a simple, double integral plant model, shows remarkable robustness and disturbance rejection in the presence of resonant modes, measurement noises and position and torque disturbances. It eliminates the needs for two separate controllers for track-seeking and track-following operations. The proposed feedforward controller in this 2DOF structure proves to be quite beneficial in reducing the seek time. It also allows the feedback controller to be tuned more aggressively, which helps to improve the quality of track following. The proposed control scheme offers a novel basic control structure for HDD servo, upon which numerous further improvements can be made. It is successfully tested in simulation on an industrial 13.0-kTPI HDD

Construction of an Artificial MicroRNA Expression Vector for Simultaneous Inhibition of Multiple Genes in Mammalian Cells

Recently, artificial microRNA (amiRNA) has become a promising RNA interference (RNAi) technology. Here, we describe a flexible and reliable method for constructing both single- and multi-amiRNA expression vectors. Two universal primers, together with two specific primers carrying the encoding sequence of amiRNA were designed and utilized to synthesize the functional amiRNA cassette through a one-step PCR. With appropriate restriction sites, the synthesized amiRNA cassettes can be cloned into any site of different destination vectors. Using the method, we constructed both single- and multi-amiRNA expression vectors to target three reporter genes, which code firefly luciferase (Fluc), enhanced green fluorescent protein (EGFP) and β-galactosidase (LacZ), respectively. The expressions of three genes were all specifically inhibited by either the corresponding single- or the multi-amiRNA expression vector in 293T cells. And the RNAi efficiency of each amiRNA produced by both single- and multi-amiRNA expression vectors was comparable

Transient Global Amnesia Linked to Impairment of Brain Venous Drainage: An Ultrasound Investigation

Background: Previous neuroimaging and ultrasound studies suggested that compression and stenosis of the internal jugular vein (IJV) in patients with transient global amnesia (TGA) may impair IJV drainage, while a patent IJV releases intracranial pressure caused by the Valsalva maneuver (VM).Methods: Seventy-nine TGA patients with complete ultrasound examination data during admission were recruited prospectively to evaluate IJV drainage, which included the time-averaged mean velocity, and the cross-sectional lumen area of the IJV at the vein's middle (J2) and distal (J3) segments and the cross-sectional area during a 10-s VM to test for any retrograde or anti-grade flow. Forty-five TGA patients and 45 age- and sex-matched control subjects underwent complete contrast-enhanced magnetic resonance (MR) venous studies, which included time-resolved imaging of contrast kinetics, contrast-enhanced axial T1-weighted MR imaging, and phase-contrast-based non-contrast enhanced magnetic resonance venography (MRV).Results: In those subjects with complete MRV studies, the flow volumes exhibited at both the J2 and J3 segments of the left IJV and left vertebral vein (VV) were significantly lower in the TGA patients than in the control subjects. Although there was no significant difference in the flow volume of right IJV, the total of bilateral IJV, and VV flow volumes was still significantly lower in the TGA patients. As compared with the control subjects, the TGA patients exhibited significantly higher prevalence of completely blocked right IJV drainage at the J3 segment during the VM, but non-significantly higher for the left IJV at the J3 segment and for the right IJV at the J2 segment.Conclusion: Our results confirmed that the total venous flow decreases in the IJVs and VVs of the patients with TGA. This is consistent with the findings of previous MR imaging studies that have reported about compression and stenosis of the draining veins. We also found that IJV drainage is relatively compromised during the VM in the patients with TGA

Suppressive Effect on Lipopolysaccharide-Induced Proinflammatory Mediators by Citrus aurantium L. in Macrophage RAW 264.7 Cells via NF-κB Signal Pathway

Citrus fruits have been used as an edible fruit and a traditional medicine since ancient times. In particular, the peels of immature citrus fruits are used widely in traditional herbal medicine in Korea, as they are believed to contain bioactive components exerting anti-inflammatory activity. This study examined whether the crude methanol extract of Citrus aurantium L. (CME) has a suppressive effect on inducible enzymes and proinflammatory cytokines by inhibiting the NF-κB pathway in LPS-stimulated macrophage RAW 264.7 cells. The cells were pretreated with the indicated concentrations of CME (5, 10, 20, and 50 μg/mL) and then treated with LPS (1 μg/mL). The results showed that CME (10, 20, and 50 μg/mL) inhibited the LPS- (1 μg/mL) induced mRNA and protein expression of iNOS in macrophage Raw 264.7 cells. In addition, the expression of COX-2 was inhibited at the mRNA and protein levels by CME in a dose-dependent manner. The mRNA expression of proinflammatory cytokines, such as TNF-α and IL-6, were markedly reduced by CME (10, 20, and 50 μg/mL). Moreover, CME clearly suppressed the nuclear translocation of the NF-κB p65 subunits, which was correlated with its inhibitory effect on I-κB phosphorylation. These results suggest that CME has anti-inflammatory properties by modulating the expression of COX-2, iNOS, and proinflammatory cytokines, such as TNF-α and IL-6, in macrophage RAW 264.7 cells via the NF-κB pathway

Enhanced Plant-Derived Vesicles for Nucleotide Delivery for Cancer Therapy

Small RNAs (microRNAs [miRNAs] or small interfering RNAs [siRNAs]) are effective tools for cancer therapy, but many of the existing carriers for their delivery are limited by low bioavailability, insufficient loading, impaired transport across biological barriers, and low delivery into the tumor microenvironment. Extracellular vesicle (EV)-based communication in mammalian and plant systems is important for many physiological and pathological processes, and EVs show promise as carriers for RNA interference molecules. However, some fundamental issues limit their use, such as insufficient cargo loading and low potential for scaling production. Plant-derived vesicles (PDVs) are membrane-coated vesicles released in the apoplastic fluid of plants that contain biomolecules that play a role in several biological mechanisms. Here, we developed an alternative approach to deliver miRNA for cancer therapy using PDVs. We isolated vesicles from watermelon and formulated a hybrid, exosomal, polymeric system in which PDVs were combined with a dendrimer bound to miRNA146 mimic. Third generation PAMAM was chosen due to its high branching structure and versatility for loading molecules of interest. We performed several in vivo experiments to demonstrate the therapeutic efficacy of our compound and explored in vitro biological mechanisms underlying the anti-tumor effects of miRNA146, which are mostly related to its anti-angiogenic activity

Polar Constituents and Biological Activity of the Berry-Like Fruits from Hypericum androsaemum L

open14noHypericum androsaemum, also known as Tutsan, is a small evergreen shrub common in the Mediterranean basin where it is traditionally used as diuretic and hepatoprotective herbal drug. This plant possesses the peculiarity to produce fleshy and berry-like fruits that ripen from red to shiny black. In the present work, the chemical constituents of methanolic extracts and infusions of red and black fruits were analyzed by HPLC, and correlated with their antioxidant properties which were evaluated by the DPPH, β-Carotene/linoleic acid, and hypochlorous acid tests. In addition, the red pigment of the fruit was isolated by column chromatography and structurally elucidated by NMR. Results showed that H. androsaemum fruits contain high amounts of shikimic and chlorogenic acids, while their color was given by a tetraoxygenated-type xanthone, reported for the first time in Hypericum species. The red berries infusion gave the highest content of total phenolic compounds, DPPH, and hypochlorous acid scavenging activity, and β-carotene bleaching. Cytotoxicity of the berries extracts on three human tumor cell lines (malignant melanoma, breast adenocarcinoma, and colon carcinoma) was evaluated by MTT assay, and relevant inhibition on colon carcinoma cells (IC50 value of 8.4 μg/mL) was found. Finally, the effects of red berries extract on the immune system were evaluated by peripheral blood mononuclear cell (PBMC) proliferation assay that revealed a strong stimulation on lymphocytes at low doses (0.4-6 μg/mL).openCaprioli, Giovanni; Alunno, Alessia; Beghelli, Daniela; Bianco, Armandodoriano; Bramucci, Massimo; Frezza, Claudio; Iannarelli, Romilde; Papa, Fabrizio; Quassinti, Luana; Sagratini, Gianni; Tirillini, Bruno; Venditti, Alessandro; Vittori, Sauro; Maggi, FilippoCaprioli, Giovanni; Alunno, Alessia; Beghelli, Daniela; Bianco, Armandodoriano; Bramucci, Massimo; Frezza, Claudio; Iannarelli, Romilde; Papa, Fabrizio; Quassinti, Luana; Sagratini, Gianni; Tirillini, Bruno; Venditti, Alessandro; Vittori, Sauro; Maggi, Filipp

Chalcogenide Glass-on-Graphene Photonics

Two-dimensional (2-D) materials are of tremendous interest to integrated photonics given their singular optical characteristics spanning light emission, modulation, saturable absorption, and nonlinear optics. To harness their optical properties, these atomically thin materials are usually attached onto prefabricated devices via a transfer process. In this paper, we present a new route for 2-D material integration with planar photonics. Central to this approach is the use of chalcogenide glass, a multifunctional material which can be directly deposited and patterned on a wide variety of 2-D materials and can simultaneously function as the light guiding medium, a gate dielectric, and a passivation layer for 2-D materials. Besides claiming improved fabrication yield and throughput compared to the traditional transfer process, our technique also enables unconventional multilayer device geometries optimally designed for enhancing light-matter interactions in the 2-D layers. Capitalizing on this facile integration method, we demonstrate a series of high-performance glass-on-graphene devices including ultra-broadband on-chip polarizers, energy-efficient thermo-optic switches, as well as graphene-based mid-infrared (mid-IR) waveguide-integrated photodetectors and modulators

Methodology based on genetic heuristics for in-vivo characterizing the patient-specific biomechanical behavior of the breast tissues

[EN] This paper presents a novel methodology to in-vivo estimate the elastic constants of a constitutive model proposed to characterize the mechanical behavior of the breast tissues. An iterative search algorithm based on genetic heuristics was constructed to in-vivo estimate these parameters using only medical images, thus avoiding invasive measurements of the mechanical response of the breast tissues. For the first time, a combination of overlap and distance coefficients were used for the evaluation of the similar- ity between a deformed MRI of the breast and a simulation of that deformation. The methodology was validated using breast software phantoms for virtual clinical trials, compressed to mimic MRI-guided biopsies. The biomechanical model chosen to characterize the breast tissues was an anisotropic neo-Hookean hyperelastic model. Results from this analysis showed that the algorithm is able to find the elastic constants of the constitutive equations of the proposed model with a mean relative error of about 10%. Furthermore, the overlap between the reference deformation and the simulated deformation was of around 95% showing the good performance of the proposed methodology. This methodology can be easily extended to characterize the real biomechanical behavior of the breast tissues, which means a great novelty in the field of the simulation of the breast behavior for applications such as surgical planing, surgical guidance or cancer diagnosis. This reveals the impact and relevance of the presented work.This project has been funded by MECD (reference AP2009-2414) and US National Institutes of Health (R01 Grant #CA154444), and the US National Science Foundation (III Grant #0916690). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, and NSF. The authors of this manuscript have no conflict of interest with the presented workLago, MA.; Rupérez Moreno, MJ.; Martínez Martínez, F.; Martinez-Sanchis, S.; Bakic, P.; Monserrat, C. (2015). Methodology based on genetic heuristics for in-vivo characterizing the patient-specific biomechanical behavior of the breast tissues. Expert Systems with Applications. 42(21):7942-7950. https://doi.org/10.1016/j.eswa.2015.05.058S79427950422

Transcatheter Arterial Embolization Therapy for a Massive Polycystic Liver in Autosomal Dominant Polycystic Kidney Disease Patients

Polycystic liver is the most common extra-renal manifestation associated with autosomal dominant polycystic kidney disease (ADPKD), comprising up to 80% of all features. Patients with polycystic liver often suffer from abdominal discomfort, dyspepsia, or dyspnea; however, there have been few ways to relieve their symptoms effectively and safely. Therefore, we tried transcatheter arterial embolization (TAE), which has been used in treating hepatocellular carcinoma. We enrolled four patients with ADPKD in Seoul National University Hospital, suffering from enlarged polycystic liver. We embolized the hepatic arteries supplying the dominant hepatic segments replaced by cysts using polyvinyl alcohol particles and micro-coils. The patients were evaluated 12 months after embolization for the change in both liver and cyst volumes. Among four patients, one patient was lost in follow up and 3 patients were included in the analysis. Both liver (33%; 10%) and cyst volume (47.7%; 11.4%) substantially decreased in two patients. Common adverse events were fever, epigastric pain, nausea, and vomiting. We suggest that TAE is effective and safe in treating symptomatic polycystic liver in selected ADPKD patients