Gender difference in the impact of coexisting diabetes mellitus on long-term clinical outcome in people with heart failure: a report from the Korean Heart Failure Registry.

AIM: Few data are available on the gender-related differences in the prognostic impact of diabetes in people with heart failure. This study was performed to investigate whether there is a gender difference in the association between diabetes and long-term clinical outcomes in people hospitalized for heart failure. METHODS: A total of 3162 people hospitalized with heart failure (aged 67.4 ± 14.1 years, 50.4% females) from the data set of the nationwide registry were analysed. The primary endpoint was a composite of all-cause mortality and heart failure readmission. RESULTS: People with diabetes (30.5% for males vs. 31.1% for females, P = 0.740) were older and had more unfavourable risk factors and laboratory findings than those without diabetes in both genders. During a median follow-up period of 549 days, there were 1418 cases of composite events (44.8%). In univariable analysis, the coexistence of diabetes was significantly associated with a higher incidence of composite events in both genders (P < 0.05 each for males and females). In multivariable analysis, the prognostic impact of diabetes on the development of composite events remained significant in females even after controlling for potential confounders (hazard ratio 1.43, 95% confidence intervals 1.12-1.84; P = 0.004). However, an independent association between diabetes and composite events was not seen in males in the same multivariable analysis (P > 0.05). CONCLUSIONS: In people with heart failure, the impact of diabetes on long-term mortality and heart failure readmission seems to be stronger in females than in males. More careful and intensive management is needed especially in females with heart failure and diabetes.

Kondo Resonance of a Co Atom Exchange Coupled to a Ferromagnetic Tip.

The Kondo effect of a Co atom on Cu(100) was investigated with a low-temperature scanning tunneling microscope using a monoatomically sharp nickel tip. Upon a tip-Co contact, the differential conductance spectra exhibit a spin-split asymmetric Kondo resonance. The computed ab initio value of the exchange coupling is too small to suppress the Kondo effect, but sufficiently large to produce the splitting observed. A quantitative analysis of the line shape using the numerical renormalization group technique indicates that the junction spin polarization is weak.

Conductance-driven change of the Kondo effect in a single cobalt atom.

A low-temperature scanning tunneling microscope is employed to build a junction comprising a Co atom bridging a copper-coated tip and a Cu(100) surface. An Abrikosov-Suhl-Kondo resonance is evidenced in the differential conductance and its width is shown to vary exponentially with the ballistic conductance for all tips employed. Using a theoretical description based on the Anderson model, we show that the Kondo effect and the total conductance are related through the atomic relaxations affecting the environment of the Co atom.

Engineering negative differential conductance with the Cu(111) surface state.

Low-temperature scanning tunneling microscopy and spectroscopy are employed to investigate electron tunneling from a C60-terminated tip into a Cu(111) surface. Tunneling between a C60 orbital and the Shockley surface states of copper is shown to produce negative differential conductance (NDC) contrary to conventional expectations. NDC can be tuned through barrier thickness or C60 orientation up to complete extinction. The orientation dependence of NDC is a result of a symmetry matching between the molecular tip and the surface states.

Multiphase CT Angiography: A Useful Technique in Acute Stroke Imaging-Collaterals and Beyond.

Multiphase CTA offers several important advantages over the traditional single-phase CTA technique in acute ischemic stroke, including improved detection of large-vessel occlusion, improved characterization of collateral status, improved tolerance of patient motion and poor hemodynamics, and higher interrater reliability. These benefits are gleaned at little additional cost in terms of time, risk to the patient, and capital expense. Existing data suggest that there are important benefits to using multiphase CTA in lieu of single-phase CTA in the initial vessel assessment of patients with acute stroke.

Vibron-assisted spin excitation in a magnetically anisotropic molecule.

The electrical control and readout of molecular spin states are key for high-density storage. Expectations are that electrically-driven spin and vibrational excitations in a molecule should give rise to new conductance features in the presence of magnetic anisotropy, offering alternative routes to study and, ultimately, manipulate molecular magnetism. Here, we use inelastic electron tunneling spectroscopy to promote and detect the excited spin states of a prototypical molecule with magnetic anisotropy. We demonstrate the existence of a vibron-assisted spin excitation that can exceed in energy and in amplitude a simple excitation among spin states. This excitation, which can be quenched by structural changes in the magnetic molecule, is explained using first-principles calculations that include dynamical electronic correlations.

Overexpression of the rat sarcoplasmic reticulum Ca2+ ATPase gene in the heart of transgenic mice accelerates calcium transients and cardiac relaxation.

The Ca2+ ATPase of the sarcoplasmic reticulum (SERCA2) plays a dominant role in lowering cytoplasmic calcium levels during cardiac relaxation and reduction of its activity has been linked to delayed diastolic relaxation in hypothyroid and failing hearts. To determine the contractile alterations resulting from increased SERCA2 expression, we generated transgenic mice overexpressing a rat SERCA2 transgene. Characterization of a heterozygous transgenic mouse line (CJ5) showed that the amount of SERCA2 mRNA and protein increased 2. 6-fold and 1.2-fold, respectively, relative to control mice. Determination of the relative synthesis rate of SERCA2 protein showed an 82% increase. The mRNA levels of some of the other genes involved in calcium handling, such as the ryanodine receptor and calsequestrin, remained unchanged, but the mRNA levels of phospholamban and Na+/Ca2+ exchanger increased 1.4-fold and 1.8-fold, respectively. The increase in phospholamban or Na+/Ca2+ exchanger mRNAs did not, however, result in changes in protein levels. Functional analysis of calcium handling and contractile parameters in isolated cardiac myocytes indicated that the intracellular calcium decline (t1/2) and myocyte relengthening (t1/2) were accelerated by 23 and 22%, respectively. In addition, the rate of myocyte shortening was also significantly faster. In isolated papillary muscle from SERCA2 transgenic mice, the time to half maximum postrest potentiation was significantly shorter than in negative littermates. Furthermore, cardiac function measured in vivo, demonstrated significantly accelerated contraction and relaxation in SERCA2 transgenic mice that were further augmented in both groups with isoproterenol administration. Similar results were obtained for the contractile performance of myocytes isolated from a separate line (CJ2) of homozygous SERCA2 transgenic mice. Our findings suggest, for the first time, that increased SERCA2 expression is feasible in vivo and results in enhanced calcium transients, myocardial contractility, and relaxation that may have further therapeutic implications.

Acute heart failure and cardiogenic shock: a multidisciplinary practical guidance.

PURPOSE: Acute heart failure (AHF) causes high burden of mortality, morbidity, and repeated hospitalizations worldwide. This guidance paper describes the tailored treatment approaches of different clinical scenarios of AHF and CS, focusing on the needs of professionals working in intensive care settings. RESULTS: Tissue congestion and hypoperfusion are the two leading mechanisms of end-organ injury and dysfunction, which are associated with worse outcome in AHF. Diagnosis of AHF is based on clinical assessment, measurement of natriuretic peptides, and imaging modalities. Simultaneously, emphasis should be given in rapidly identifying the underlying trigger of AHF and assessing severity of AHF, as well as in recognizing end-organ injuries. Early initiation of effective treatment is associated with superior outcomes. Oxygen, diuretics, and vasodilators are the key therapies for the initial treatment of AHF. In case of respiratory distress, non-invasive ventilation with pressure support should be promptly started. In patients with severe forms of AHF with cardiogenic shock (CS), inotropes are recommended to achieve hemodynamic stability and restore tissue perfusion. In refractory CS, when hemodynamic stabilization is not achieved, the use of mechanical support with assist devices should be considered early, before the development of irreversible end-organ injuries. CONCLUSION: A multidisciplinary approach along the entire patient journey from pre-hospital care to hospital discharge is needed to ensure early recognition, risk stratification, and the benefit of available therapies. Medical management should be planned according to the underlying mechanisms of various clinical scenarios of AHF.

Modification to the accelerator of the NBI-1B ion source for improving the injection efficiency.

Minimizing power loss of a neutral beam imposes modification of the accelerator of the ion source for further improvement of the beam optics. The beam optics can be improved by focusing beamlets. The injection efficiencies by the steering of ion beamlets are investigated numerically to find the optimum modification of the accelerator design of the NBI-1B ion source. The beam power loss was reduced by aperture displacement of three edge beamlets arrays considering power loadings on the beamline components. Successful testing and operation of the ion source at 60 keV/84% of injection efficiency led to the possibility of enhancing the system capability to a 2.4 MW power level at 100 keV/1.9 µP.

Renal denervation for treatment of uncontrolled hypertension in an Asian population: results from the Global SYMPLICITY Registry in South Korea (GSR Korea).

Reports detailing the response of hypertensive patients to renal denervation (RDN) in Asian patients are limited. We evaluated 6- and 12-month outcomes after RDN in an Asian population and compared outcomes to a primarily Caucasian population. The Global SYMPLICITY Registry (GSR) is a prospective, all-comer, worldwide registry that evaluates the safety and effectiveness of RDN and includes the Korean registry substudy (GSR Korea) and a Caucasian subset (GSR Caucasian). Given differences in baseline characteristics among GSR Korea (n=93) as compared with GSR Caucasian (n=169) patients, including lower baseline office systolic blood pressure (SBP), lower body mass index and differences in medications, propensity score adjustment was performed when comparing the change in SBP between subsets. The 6- and 12-month change in SBP in GSR Korea was -19.4±17.2 and -27.2±18.1 mm Hg, respectively (P<0.001 for both vs baseline). GSR Caucasian had a SBP change similar to GSR Korea at 6 months (-20.9±21.4 mm Hg, unadjusted P=0.547, adjusted P=0.998), whereas at 12 months the change was significantly less pronounced (-20.1±23.9 mm Hg, unadjusted P=0.004, adjusted P=0.002). There were no protocol-defined procedure-related adverse events and no chronic adverse events associated with the device in an Asian population. RDN provided a significant reduction in 6- and 12-month office SBP among Asian patients, with a favorable safety profile. The 12-month SBP reduction was larger than that observed in Caucasian patients.

Incorrect base insertion and prematurely terminated transcripts during T7 RNA polymerase transcription elongation past benzo[a]pyrenediol epoxide-modified DNA.

DNA replication and transcription are affected adversely by the presence of bulky adducts that are generated by the covalent binding of a variety of metabolically activated environmental pollutants to cellular DNA. When these lesions are not cleared by cellular repair enzymes prior to replication, mutations and ultimately tumor initiation can occur. Transcription and DNA repair appear to be intimately connected, since certain adducts are more efficiently removed from the transcribed strands of active loci than from non-transcribed strands and other quiescent domains in the genome. The mechanism by which RNA polymerases deal with bulky adducts during DNA transcription is therefore of great interest. The availability of site-specifically modified and stereochemically defined oligodeoxyribonucleotides derived from the covalent reaction of 7r, 8t-dihydroxy-9, 10t-epoxy- 7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) with guanine residues prompted us to study the efficiencies of transcription past these lesions using bacteriophage T7 RNA polymerase. We show here that T7 RNA polymerase can bypass such lesions in a DNA template, providing that a cytosine residue is incorporated opposite anti-BPDE-modified guanine. However, when an incorrect base (most frequently a purine) is inserted opposite the modified site, the RNA polymerase stalls, and the complex dissociates, resulting in a truncated transcript. The ability of the T7 RNA polymerase to discriminate between a correct and an incorrect inserted base and, accordingly, to continue or terminate transcription, might constitute an important mechanism that ensures the fidelity of transcription past a modified base present on the transcribed strand of the DNA template.

The characterization of Gardnerella vaginalis DNA using non-radioactive DNA probes.

DNA restriction profiles of various Gardnerella vaginalis isolates, generated by BamHI, EcoRI, PstI and other restriction enzymes, varied considerably. Only a few DNA fragments were identified as common in ethidium bromide fluorescence profile and Southern-blot hybridization patterns (employing a digoxigenin-labelled G. vaginalis DNA probe and an enzyme-linked immunoassay detection method). While the efficiencies of Southern-blot hybridization appeared inconsistent, in dot-blot assays, DNA from each isolate hybridized readily, enabling the detection of at least 10 ng DNA. A 5.7-kb DNA fragment from G. vaginalis ATCC 14018 genomic library, cloned in the BamHI site of pBR322, could replace the total genomic DNA probe. This specific DNA fragment was present in different sizes in 12 analysed G. vaginalis strains, describing a restriction fragment length polymorphism. In control studies, none of the DNA from bacteria other than G. vaginalis (including some genitourinary tract residents) hybridized with the G. vaginalis total or specific DNA probes. Non-radioactive G. vaginalis DNA probes can thus form the basis of a useful detection method for further studies of this organism.

Adenosquamous carcinoma of the cervix: prognosis in stage IB.

The outcome of women with adenosquamous carcinoma of the cervix has been a controversial issue. To assess the prognostic significance of this cell type, the medical records of 29 patients with stage IB primary adenosquamous carcinoma of the cervix were reviewed. Twenty-six had cervical tumors measuring 3 cm or less. With a median follow-up of 60 months, the overall disease-free 5-year survival was 85%. Pelvic lymph node metastases were found in three of 19 patients (16%) with stage IB, and periaortic lymph nodes were negative in eight. A log-likelihood chi 2 test comparing lymphatic spread, recurrence rate, and 5-year disease-free survival in patients with stage IB disease and tumors less than 3 cm versus a similar group of 58 patients with pure squamous cell carcinoma of equivalent stage and comparable size treated during the same time disclosed no significant differences in any of the indicators analyzed. We conclude that stage IB adenosquamous carcinoma of the cervix does not differ in its metastatic potential or outcome from the more common pure squamous cell carcinoma.

A hybrid artificial neural network as a software sensor for optimal control of a wastewater treatment process.

For control and automation of biological treatment processes, lack of reliable on-line sensors to measure water quality parameters is one of the most important problems to overcome. Many parameters cannot be measured directly with on-line sensors. The accuracy of existing hardware sensors is also not sufficient and maintenance problems such as electrode fouling often cause trouble. This paper deals with the development of software sensor techniques that estimate the target water quality parameter from other parameters using the correlation between water quality parameters. We focus our attention on the preprocessing of noisy data and the selection of the best model feasible to the situation. Problems of existing approaches are also discussed. We propose a hybrid neural network as a software sensor inferring wastewater quality parameter. Multivariate regression, artificial neural networks (ANN), and a hybrid technique that combines principal component analysis as a preprocessing stage are applied to data from industrial wastewater processes. The hybrid ANN technique shows an enhancement of prediction capability and reduces the overfitting problem of neural networks. The result shows that the hybrid ANN technique can be used to extract information from noisy data and to describe the nonlinearity of complex wastewater treatment processes.

Effect of corticosteroid treatment on salicylate ototoxicity.

Our previous studies showed that salicylate ototoxicity is associated with decreased levels of prostaglandins (PGs) and elevated levels of leukotrienes (LTs) in the perilymph. The purpose of this study was to determine whether or not pretreatment with corticosteroid, which suppresses both PGs and LTs in arachidonic acid metabolism, prevents salicylate ototoxicity. Salicylate ototoxicity was induced in chinchillas with or without treatment with dexamethasone. Hearing thresholds were measured by auditory brain stem response, and perilymph samples were assayed by high-performance liquid chromatography. Dexamethasone pretreatment, given by either systemic or local round window membrane application, partially prevented salicylate-induced hearing loss. Prevention of salicylate ototoxicity by dexamethasone seems to be correlated with increased PG levels and decreased LT levels in the perilymph. This is another piece of evidence that salicylate ototoxicity may be mediated by abnormal arachidonic acid metabolism in the inner ear.

Estrogen affects vascular tone differently according to vasoactive substances in ovariectomized Sprague-Dawley rat.

The favorable effects of estrogen on cardiovascular diseases can be explained by several mechanisms such as changes in serum lipid profiles and thrombogenecity. Estrogen also affects the vascular tone, but there has been no report in which the effect of estrogen was tested comprehensively for several vasoactive substances, especially after long-term administration. Two weeks after bilateral ovariectomy in 8-week old female Sprague-Dawley rats, placebo or 17 beta-estradiol (E2) pellets (0.5 mg; released over 3 weeks) were implanted subcutaneously. Two weeks after pellet implantation, organ chamber experiments were performed using aortae. Compared with control, E2-treated vessels showed impaired endothelium-dependent relaxation to acetylcholine. E2 enhanced the contraction to norepinephrine and U46619 and had no effect on endothelin-1-induced contraction. In contrast, the contraction to angiotensin (AT)-II was inhibited by E2. Northern blot analysis for AT1 receptor expression using cultured aortic smooth muscle cells showed no difference between control and E2-treated cells, suggesting that AT1 receptor downregulation is not the likely mechanism. These results suggest that E2 affects the vascular tone variably according to vasoactive substances.

Cisplatin based combination chemotherapy in the treatment of stage III ovarian epithelial tumors of low malignant potential.

Eleven patients diagnosed with Stage III epithelial ovarian tumors of low malignant potential were treated with a combination of cisplatin and cyslophosphamide with or without doxorubicin following primary cytoreductive surgery. Residual disease after initial cytoreduction was macroscopic in nine patients and not observable in two. Eight of the nine patients with macroscopic residual were assessed by second look laparotomy (one refused the procedure), seven showed tumor and one was found to be a complete responder. Of the two patients with no residual disease, one refused second look operation and one had a negative second look. Our findings plus those of other authors suggest that cisplatin based combination chemotherapy is of limited value in the treatment of metastatic ovarian epithelial tumors of low malignant potential.