Critical Care of Acute Heart Failure

Acute heart failure is a life-threatening medical condition. Improving acute heart failure care is important. Early diagnosis and evaluating the etiology are important in acute heart failure. Patients with suspected acute heart failure should have a diagnostic workup, and appropriate pharmacological and nonpharmacological management should be started promptly and in parallel. Diagnosis of acute heart failure should be based on history and symptoms. The physical examination typically presents with some combination of increased congestion and decreased peripheral perfusion, further confirmed by electrocardiogram, chest radiograph, biomarkers, and echocardiogram. The first step in the management of a patient is to address life-threatening issues. Patients with respiratory failure or cardiogenic shock should be treated soon. The next step is the identification of precipitants that needs urgent management. Evidence-based medication to reduce morbidity and mortality for patients with heart failure includes an angiotensin converting enzyme inhibitor, angiotensin receptor blocker, or angiotensin receptor-neprilysin inhibitor; a beta blocker; and a mineralocorticoid receptor antagonist. During an acute heart failure episode, management of these agents depends upon whether the patient has contraindications to therapy such as hemodynamic instability or acute kidney injury. Once the patient is stable, therapies are carefully initiated, reinitiated, or titrated with appropriate follow-up

Retraction and Generalized Extension of Computing with Words

Fuzzy automata, whose input alphabet is a set of numbers or symbols, are a formal model of computing with values. Motivated by Zadeh's paradigm of computing with words rather than numbers, Ying proposed a kind of fuzzy automata, whose input alphabet consists of all fuzzy subsets of a set of symbols, as a formal model of computing with all words. In this paper, we introduce a somewhat general formal model of computing with (some special) words. The new features of the model are that the input alphabet only comprises some (not necessarily all) fuzzy subsets of a set of symbols and the fuzzy transition function can be specified arbitrarily. By employing the methodology of fuzzy control, we establish a retraction principle from computing with words to computing with values for handling crisp inputs and a generalized extension principle from computing with words to computing with all words for handling fuzzy inputs. These principles show that computing with values and computing with all words can be respectively implemented by computing with words. Some algebraic properties of retractions and generalized extensions are addressed as well.Comment: 13 double column pages; 3 figures; to be published in the IEEE Transactions on Fuzzy System

A multi-product FPR model with rework and an improved delivery policy

A multi-item finite production rate (FPR) model with rework and an improved delivery policy is examined in this paper. Unlike the classic FPR model whose purpose is to derive the most economic lot size for a single-product production system with perfect quality and a continuous issuing policy, this paper considers a production of multiple products on a single machine, rework of all nonconforming items produced, and a cost-reduction, multi-delivery policy. We extend the work of Chiu et al. [1] by incorporating an improved n+1 shipment policy into their model. According to such a policy, one extra delivery of finished items is made during vendor’s production uptime to satisfy product demands during the period of vendor’s uptime and rework time. When the rest of the production lot is quality assured and the rework has been finished as well, n fixed-quantity installments of finished items are delivered to customers. The objectives are to determine an optimal, common-production cycle time that minimizes the long-run average system cost per time unit, study the effects of rework and the improved delivery policy on the optimal production. Mathematical modelling and analysis is used to derive a closed-form, optimal, common-cycle time. Finally, practical usages of the obtained results are demonstrated by a numerical example

5-ALA mediated photodynamic therapy induces autophagic cell death via AMP-activated protein kinase

Photodynamic therapy (PDT) has been developed as an anticancer treatment, which is based on the tumor-specific accumulation of a photosensitizer that induces cell death after irradiation of light with a specific wavelength. Depending on the subcellular localization of the photosensitizer, PDT could trigger various signal transduction cascades and induce cell death such as apoptosis, autophagy, and necrosis. In this study, we report that both AMP-activated protein kinase (AMPK) and mitogen-activated protein kinase (MAPK) signaling cascades are activated following 5-aminolevulinic acid (ALA)-mediated PDT in both PC12 and CL1-0 cells. Although the activities of caspase-9 and -3 are elevated, the caspase inhibitor zVAD-fmk did not protect cells against ALA-PDT-induced cell death. Instead, autophagic cell death was found in PC12 and CL1-0 cells treated with ALA-PDT. Most importantly, we report here for the first time that it is the activation of AMPK, but not MAPKs that plays a crucial role in mediating autophagic cell death induced by ALA-PDT. This novel observation indicates that the AMPK pathway play an important role in ALA-PDT-induced autophagy

Sodium vanadate combined with l-ascorbic acid delays disease progression, enhances motor performance, and ameliorates muscle atrophy and weakness in mice with spinal muscular atrophy

BACKGROUND: Proximal spinal muscular atrophy (SMA), a neurodegenerative disorder that causes infant mortality, has no effective treatment. Sodium vanadate has shown potential for the treatment of SMA; however, vanadate-induced toxicity in vivo remains an obstacle for its clinical application. We evaluated the therapeutic potential of sodium vanadate combined with a vanadium detoxification agent, L-ascorbic acid, in a SMA mouse model. METHODS: Sodium vanadate (200 μM), L-ascorbic acid (400 μM), or sodium vanadate combined with L-ascorbic acid (combined treatment) were applied to motor neuron-like NSC34 cells and fibroblasts derived from a healthy donor and a type II SMA patient to evaluate the cellular viability and the efficacy of each treatment in vitro. For the in vivo studies, sodium vanadate (20 mg/kg once daily) and L-ascorbic acid (40 mg/kg once daily) alone or in combination were orally administered daily on postnatal days 1 to 30. Motor performance, pathological studies, and the effects of each treatment (vehicle, L-ascorbic acid, sodium vanadate, and combined treatment) were assessed and compared on postnatal days (PNDs) 30 and 90. The Kaplan-Meier method was used to evaluate the survival rate, with P < 0.05 indicating significance. For other studies, one-way analysis of variance (ANOVA) and Student's t test for paired variables were used to measure significant differences (P < 0.05) between values. RESULTS: Combined treatment protected cells against vanadate-induced cell death with decreasing B cell lymphoma 2-associated X protein (Bax) levels. A month of combined treatment in mice with late-onset SMA beginning on postnatal day 1 delayed disease progression, improved motor performance in adulthood, enhanced survival motor neuron (SMN) levels and motor neuron numbers, reduced muscle atrophy, and decreased Bax levels in the spinal cord. Most importantly, combined treatment preserved hepatic and renal function and substantially decreased vanadium accumulation in these organs. CONCLUSIONS: Combined treatment beginning at birth and continuing for 1 month conferred protection against neuromuscular damage in mice with milder types of SMA. Further, these mice exhibited enhanced motor performance in adulthood. Therefore, combined treatment could present a feasible treatment option for patients with late-onset SMA

High ERCC1 expression predicts cisplatin-based chemotherapy resistance and poor outcome in unresectable squamous cell carcinoma of head and neck in a betel-chewing area

<p>Abstract</p> <p>Background</p> <p>This study was to evaluate the effect of excision repair cross-complementation group 1(ERCC1) expression on response to cisplatin-based induction chemotherapy (IC) followed by concurrent chemoradiation (CCRT) in locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) patients.</p> <p>Methods</p> <p>Fifty-seven patients with locally advanced unresectable HNSCC who received cisplatin-based IC followed by CCRT from January 1, 2006 through January 1, 2008. Eligibility criteria included presence of biopsy-proven HNSCC without a prior history of chemotherapy or radiotherapy. Immunohistochemistry was used to assess ERCC1 expression in pretreatment biopsy specimens from paraffin blocks. Clinical parameters, including smoking, alcohol consumption and betel nuts chewing, were obtained from the medical records.</p> <p>Results</p> <p>The 12-month progression-free survival (PFS) and 2-year overall survival (OS) rates of fifty-seven patients were 61.1% and 61.0%, respectively. Among these patients, thirty-one patients had low ERCC1 expression and forty-one patients responded to IC followed by CCRT. Univariate analyses showed that patients with low expression of ERCC1 had a significantly higher 12-month PFS rates (73.3% vs. 42.3%, p < 0.001) and 2-year OS (74.2 vs. 44.4%, p = 0.023) rates. Multivariate analysis showed that for patients who did not chew betel nuts and had low expression of ERCC1 were independent predictors for prolonged survival.</p> <p>Conclusions</p> <p>Our study suggest that a high expression of ERCC1 predict a poor response and survival to cisplatin-based IC followed by CCRT in patients with locally advanced unresectable HNSCC in betel nut chewing area.</p

The microtubule-associated protein, EB1, links AIM2 inflammasomes with autophagy-dependent secretion

Inflammasomes are multi-protein complexes that regulate chronic inflammation-associated diseases by inducing interleukin-1 β (IL-1β) secretion. Numerous components involved in inflammasome activation have been identified, but the mechanisms of inflammasome-mediated IL-1β secretion have not yet been fully explored. Here, we demonstrate that end-binding protein 1 (EB1), which is required for activation of AIM2 inflammasome complex, links the AIM2 inflammasome to autophagy-dependent secretion. Imaging studies revealed that AIM2 inflammasomes colocalize with microtubule organizing centers and autophagosomes. Biochemical analyses showed that poly(dA-dT)-activated AIM2 inflammasomes induce autophagy and IL-1β secretion in an LC3-dependent fashion. Furthermore, depletion of EB1 decreases autophagic shedding and intracellular trafficking. Finally, we found that the 5′-AMP activated protein kinase may regulate this EB1-mediated autophagy-based inflammasome-induced secretion of IL-1β. These findings reveal a novel EB1-mediated pathway for the secretion of IL-1β

Single-crystalline δ-Ni2Si nanowires with excellent physical properties

[[abstract]]In this article, we report the synthesis of single-crystalline nickel silicide nanowires (NWs) via chemical vapor deposition method using NiCl2·6H2O as a single-source precursor. Various morphologies of δ-Ni2Si NWs were successfully acquired by controlling the growth conditions. The growth mechanism of the δ-Ni2Si NWs was thoroughly discussed and identified with microscopy studies. Field emission measurements show a low turn-on field (4.12 V/μm), and magnetic property measurements show a classic ferromagnetic characteristic, which demonstrates promising potential applications for field emitters, magnetic storage, and biological cell separation.[[notice]]補正完畢[[incitationindex]]SCI[[booktype]]電子版[[booktype]]紙