A scaled explicitly correlated F12 correction to second-order Møller-Plesset perturbation theory.

An empirically scaled version of the explicitly correlated F12 correction to second-order Møller-Plesset perturbation theory (MP2-F12) is introduced. The scaling eliminates the need for many of the most costly terms of the F12 correction while reproducing the unscaled explicitly correlated F12 interaction energy correction to a high degree of accuracy. The method requires a single, basis set dependent scaling factor that is determined by fitting to a set of test molecules. We present factors for the cc-pVXZ-F12 (X = D, T, Q) basis set family obtained by minimizing interaction energies of the S66 set of small- to medium-sized molecular complexes and show that our new method can be applied to accurately describe a wide range of systems. Remarkably good explicitly correlated corrections to the interaction energy are obtained for the S22 and L7 test sets, with mean percentage errors for the double-zeta basis of 0.60% for the F12 correction to the interaction energy, 0.05% for the total electron correlation interaction energy, and 0.03% for the total interaction energy, respectively. Additionally, mean interaction energy errors introduced by our new approach are below 0.01 kcal mol-1 for each test set and are thus negligible for second-order perturbation theory based methods. The efficiency of the new method compared to the unscaled F12 correction is shown for all considered systems, with distinct speedups for medium- to large-sized structures.

Concentration of apelin inversely correlates with atrial fibrillation burden.

AIM: Asymptomatic atrial fibrillation (AF) detection and pulmonary veins isolation (PVI) outcome prediction remain challenging. Our aim was to study the association between apelin and paroxysmal AF in patients undergoing radiofrequency catheter PVI. METHODS: Sixty-three consecutive patients (55 ± 8years, 12 females) with paroxysmal AF without a structural heart disease and implanted ECG loop recorders undergoing PVI and healthy control group of 34 persons (41 ± 9.5years, 21 females) were included. Apelin plasmatic concentrations were measured before and three months after PVI. AF burden was continually assessed for three years. RESULTS: Apelin was significantly decreased in AF patients compared to the healthy controls (0.79 ± 0.09 vs 0.98 ± 0.06 ng/ml; p < 0.00001). Apelin plasmatic concentration of 0.89 ng/ml had 94 % specificity and 89 % sensitivity for AF prediction with the area under the curve (AUC) of 0.96. After propensity matching to sex, age and comorbidities, apelin concentration was significantly lower in AF group (0.78 ± 0.1 vs 0.99 ±0.06  ng/ml; p < 0.0001; AUC: 0.97). There was a significant inverse correlation between apelin concentration and AF burden both before and after PVI (Rho = ‒0.22; p = 0.05) and (Rho = ‒0.51; p = 0.006), respectively. There was no significant association between pre-PVI apelin and PVI long-term outcome. CONCLUSION: In patients without a structural heart disease apelin showed a significant specificity and sensitivity for AF prediction and inversely correlated with AF burden (Tab. 3, Fig. 3, Ref. 34).

Impact of UV-C Radiation Applied during Plant Growth on Pre- and Postharvest Disease Sensitivity and Fruit Quality of Strawberry.

Ultraviolet-C (UV-C) radiation is efficient in reducing the development of diseases in many species, including strawberry (Fragaria × ananassa). Several studies suggest that UV-C radiation is effective not only because of its disinfecting effect but also because it may stimulate plant defenses. In this study, the effect of preharvest UV-C radiation applied during strawberry cultivation on plant growth, fruit quality, and susceptibility to major fungal diseases such as gray mold, powdery mildew, and soft rot was evaluated. UV-C treatments had an impact on flowering initiation and fruit development. Flowering occurred earlier for UV-C-treated plants than for nontreated plants. At harvest, a larger amount of fruit was produced by treated plants despite their slight decrease in leaf area. UV-C treatment did not improve strawberry shelf life but did not alter the physical integrity of strawberry fruit. Natural infection of leaves to powdery mildew and of fruit to Rhizopus spp. strongly decreased in response to UV-C treatment.

Association of apelin and AF in patients with implanted loop recorders undergoing catheter ablation.

BACKGROUND: Previous studies showed an association between apelin and atrial fibrillation (AF). The aim of this study was to analyse the effect of pulmonary vein isolation (PVI) in patients with paroxysmal AF on plasmatic apelin concentrations. METHODS: Nine consecutive patients (aged from 43 to 69 years, 3 females and 6 males) with documented paroxysmal atrial fibrillation and implanted loop recorders (ILR) for continuous ECG monitoring were included in this study. All the patients underwent a radiofrequency catheter ablation with PVI. RESULTS: The plasmatic concentration of apelin increased after PVI. The average plasmatic concentration of apelin before PVI was 0.299 ng/ml (±0.16), 3 months after PVI 0.462 ng/ml (±0.10) and 9 months after PVI 0.565 ng/ml (±0.146). There was an increase in the concentration of apelin 3 months and 9 months after the PVI by 0.163 ng/ml (p=0.07) and by 0.266 ng/ml (p=0.01), respectively. The concentration of apelin inversely correlated with the AF burden (r=-0.44, p=0.03). CONCLUSIONS: Our study showed a significant increase in apelin levels after the reduction of AF burden via PVI and an inverse correlation with AF burden. Apelin might be a promising marker of AF (Tab. 2, Fig. 2, Ref. 28).

The relation between oxidative stress biomarkers and atrial fibrillation after pulmonary veins isolation.

INTRODUCTION: The current paradigm claims a link between oxidative stress and atrial fibrillation. The aim of our research was to study a relation between the percentage of time spent in atrial fibrillation (AF burden) and concentrations of oxidative stress biomarkers, before and after pulmonary veins isolation (PVI). METHODOLOGY: We included 19 patients (mean age 55±10years, 4 females and 15 males) with implanted loop recorders undergoing PVI. Plasmatic concentrations of advanced glycation end-products (AGEs), fructosamine, advanced oxidation protein products and thiobarbituric-acid reacting substances (TBARS) were measured and AF burden was recorded immediately before and 3months after the PVI. AF burden was also recorded 9months after the PVI. RESULTS: Post procedural AGEs concentration significantly negatively correlated with AF burden after 3months (ρ=-0.63; p<0.01) and 9months (ρ=-0.5; p=0.04), respectively as well as TBARS concentration significantly negatively correlated with AF burden after 9months (ρ=-0.61; p=0.01). CONCLUSION: Our study showed AGEs and TBARS to be potential predictors for AF burden after the PVI. We suppose that the more oxidative stress after the PVI is provoked, the more fibrotic tissue is produced. That means a better electrical isolation of pulmonary veins and consequently a lower AF burden.

[Functional morphology of recently discovered telocytes inside the female reproductive system]. / Funkcná morfológia novo objavených telocytov v zenskom pohlavnom systéme.

Discovery of telocytes has become an important and key challenge in past few years. These cells are interstitial cells extending very long cytoplasmic processes named telopodes, by which they create functional networks in the interstitium of different organs. Telocytes are considered to be connective tissue elements that create contacts among each other, but they also function as intercellular structures, functionally connected with cells of the immune system, neurons and smooth muscle cells. Telocytes can be found also in the different parts of female reproductive system with functions and purpose, which is summarized in our overview. Telocytes regulate for example peristaltic movements in fallopian tubes. The decrease of their number (due to inflammatory disease or endometriosis) causes impairment in transport through fallopian tubes which may result in sterility or tubal gravidity. In uterus they regulate contraction of myometrial smooth muscle (blood expulsion in menstrual phase, childbirth) as well as they contribute in immunological care during embryo implantation. Telocytes probably control also the involution of uterus after delivery. Their function in vagina has not been yet clearly defined; they probably take part in slow muscle contraction movement during sexual intercourse. In mammary glands some scientists suppose their function in control of cell proliferation and apoptosis, that is why, they may play a role in carcinogenesis. In placenta they probably monitor and regulate flow of blood in vessels of chorionic villi and they may be responsible also for etiopathogenesis of pre-eclampsy. All these mentioned functions of telocytes are only in the level of hypothesis and have been published recently. New research and studies will try to answer the questions whether telocytes play a key role in these processes. Our review we completed with some original microphotographs of telocytes in different organs of female reproductive system.

Telocytes (interstitial Cajal-like cells) in human Fallopian tubes.

BACKGROUND: Telocytes represent a relatively newly discovered population of cells found within the various tissues and organs, including Fallopian tubes. It is presumed that telocytes could serve as a sensor of hormone levels or regulate activity of muscle peristaltic movement. METHODS: Tissue sections from anatomically different parts of Fallopian tubes of 48 women (age 48.8±9.1) were stained for the expression of five different antigens: c-kit (CD117), CD34, vimentin, podoplanin (D2-40) and Dog-1. RESULTS: Telocytes form a network associated with the smooth muscle cells. From the mentioned antibodies, only anti-c-kit (CD117) seems to be relatively selective specific to the telocytes, others react also with numerous other cells and tissue structures. Our results when using antibodies against podoplanin and Dog-1 are in dissonance with recent literature - with regards to our results, they are not suitable for detection of telocytes. CONCLUSION: Methods of immunohistochemistry are suitable for identification of telocytes in Fallopian tubes. C-kit (CD117) antigens are useful for routine identification of telocytes in histological sections. This antigen can be combined with CD34 or vimentin in cases of double staining immunohistochemistry.

Occurrence of symptoms after catheter ablation of atrial fibrillation.

OBJECTIVES: The aim of our study was to verify the efficiency of catheter ablation of atrial fibrillation (CA AF) according to the "atrial fibrillation (AF) burden"(time spent in AF) and symptoms related to AF. METHODS: We retrospectively analysed a selected set of 133 patients with atrial fibrillation (81% men, 19% women) who underwent an invasive therapy in the form of CA AF and at the same time had an implanted long-term ECG loop recorder (Reveal XT) in a period of eight years. We investigated AF burden and objective symptoms of AF by data obtained from a long-term implantable ECG loop recorder. Subjective symptoms related to AF were identified during outpatient controls. RESULTS: Firstly, our results demonstrate for the first time a clinically relevant increase in the occurrence of asymptomatic episodes of AF after CA AF. Secondly, when analysing AF symptoms and AF burden at the same time, CA AF in terms of reduction of symptoms and shortening the time in AF had a better effect in patients undergoing 1 procedure (CA AF) compared to patients undergoing repeated procedures (re CA AF). CONCLUSION: The increase in the occurrence of asymptomatic episodes of AF is of considerable importance both for the clinical evaluation of ablation efficacy and for individualized clinical management of patients, especially with respect to antithrombotic therapy (Fig. 10, Ref. 19).

Carotenoid responses to environmental stimuli: integrating redox and carbon controls into a fruit model.

Carotenoids play an important role in plant adaptation to fluctuating environments as well as in the human diet by contributing to the prevention of chronic diseases. Insights have been gained recently into the way individual factors, genetic, environmental or developmental, control the carotenoid biosynthetic pathway at the molecular level. The identification of the rate-limiting steps of carotenogenesis has paved the way for programmes of breeding, and metabolic engineering, aimed at increasing the concentration of carotenoids in different crop species. However, the complexity that arises from the interactions between the different factors as well as from the coordination between organs remains poorly understood. This review focuses on recent advances in carotenoid responses to environmental stimuli and discusses how the interactions between the modulation factors and between organs affect carotenoid build-up. We develop the idea that reactive oxygen species/redox status and sugars/carbon status can be considered as integrated factors that account for most effects of the major environmental factors influencing carotenoid biosynthesis. The discussion highlights the concept of carotenoids or carotenoid-derivatives as stress signals that may be involved in feedback controls. We propose a conceptual model of the effects of environmental and developmental factors on carotenoid build-up in fruits.

Hydrogen bonding of nitroxide spin labels in membrane proteins.

On the basis of experiments at 275 GHz, we reconsider the dependence of the continuous-wave EPR spectra of nitroxide spin-labeled protein sites in sensory- and bacteriorhodopsin on the micro-environment. The high magnetic field provides the resolution necessary to disentangle the effects of hydrogen bonding and polarity. In the gxx region of the 275 GHz EPR spectrum, bands are resolved that derive from spin-label populations carrying no, one or two hydrogen bonds. The gxx value of each population varies hardly from site to site, significantly less than deduced previously from studies at lower microwave frequencies. The fractions of the populations vary strongly, which provides a consistent description of the variation of the average gxx and the average nitrogen-hyperfine interaction Azz from site to site. These variations reflect the difference in the proticity of the micro-environment, and differences in polarity contribute marginally. Concomitant W-band ELDOR-detected NMR experiments on the corresponding nitroxide in perdeuterated water resolve population-specific nitrogen-hyperfine bands, which underlies the interpretation for the proteins.

[New views on the functional morphology of human clitoris]. / Nové pohlady na funkcnú morfológiu klitorisu.

The clitoris is the female external sexual organ and is composed of erectile bodies. The distal portion of the vagina, clitoris and urethra form an integrated entity sui generis. All these components share a common vasculature and nerve supply and during sexual stimulation they respond as one functional unit. The clitoris is closely linked to the mechanism of sexual arousal in women. Glans has a dense network of receptors, innervated often with a several nerves at the same time - taking care of tactile sensitivity, thus, standing on the beginning of the journey, which culminates in orgasm. Nervus dorsalis clitoridis, which is a branch of n. pudendus, takes care of sensitive innervation. For blood supply is responsible a. clitoridis, which is a branch of a. pudenda interna. The most common congenital developmental anomalies of the clitoris include: clitoromegaly, penis-like clitoris and bifid clitoris. All, however, are among the relatively rare birth defects. Mechanism of orgasm gets attention between both laic and scientific community, although to this date there are speculations about its exact mechanism. There is relevant opinion, influenced by Freuds doctrine, which strictly recognizes two kinds of female orgasms - vaginal and clitoral, and, according to proponents of this theory, only the second mentioned is caused by stimulation of the clitoris. The second school unifies the term orgasm and claims that only clitoral stimulation (digital, penile, cunnilingus) and contraction of striated perineal muscle are responsible for orgasm, whether the glans (external part) or the body of the clitoris from the vaginal approach is stimulated. Therewithal, special term for mythical and still undocumented (despite many attempts and bold claims about its finding) G spot (named after Ernst Gräfenberg, a German doctor who predicted the existence of this place) is redundant. Important role in the regulation of female sexuality and responsiveness play a hormonal influences and varying concentrations of neurotransmitters.

Measurements of the magnetic-field-tuned conductivity of disordered two-dimensional Mo43Ge57 and InOx superconducting films: evidence for a universal minimum superfluid response.

Our measurements of the low frequency ac conductivity in strongly disordered two-dimensional films near the magnetic-field-tuned superconductor-to-insulator transition show a sudden drop in the phase stiffness of superconducting order with either increased temperature or magnetic field. Surprisingly, for two different material systems, the abrupt drop in the superfluid density in a magnetic field has the same universal value as that expected for a Berezinskii-Kosterlitz-Thouless transition in a zero magnetic field. The characteristic temperature at which phase stiffness is suddenly lost can be tuned to zero at a critical magnetic field, following a power-law behavior with a critical exponent consistent with that obtained in previous dc transport studies on the dissipative side of the transition.

[The structural basis for transport through the Fallopian tube]. / Struktúrny základ transportnej funkcie vajíckovodu.

The Fallopian tube has until recently been a neglected structure, bypassed by in vitro fertilization and seen only as a tube that transports the oocyte or early embryo to the uterus. More recently, its role is even more undervalued after the introduction of techniques of assisted reproduction, in which the Fallopian tubes become like unnecessary. The Fallopian tube performs several important functions. It captures the oocyte after ovulation, maintains and controls the migration of spermatozoa to the site of fertilization. It provides the special microenvironment for fertilization; nourishes the early embryo while it is being carried to the uterus and amplifies signals from embryo to the mother. In our article we conducted a systematic review of relevant articles found in PubMed, Scopus and ISI Web of Knowledge, focused on the new insights into the functional morphology of Fallopian tube. We described the possible function of muscle layer motility, ciliary activity and tubal fluid movement on transport of gamets / embryo, as well as we mentioned the negative factors (such as smoking, chlamydial infection or endometriosis) affecting the transport through the Fallopian tube.

Genistein does not inhibit TGF-beta1-induced conversion of human dermal fibroblasts to myofibroblasts.

Transforming growth factor beta 1 (TGF-beta1) is a pro-fibrotic cytokine with a key role in wound repair and regeneration, including induction of fibroblast-to-myofibroblast transition. Genistein is a naturally occurring selective estrogen receptor modulator with promising anti-fibrotic properties. In the present study we aimed to investigate whether genistein modulates TGF-beta1 (canonical and non-canonical) signaling in normal dermal fibroblasts at the protein level (Western blot and immunofluorescence). We demonstrated that TGF-beta1 induces the myofibroblast-like phenotype in the studied fibroblast signaling via canonical (SMAD) and non-canonical (AKT, ERK1/2, ROCK) pathways. Genistein induced only ERK1/2 expression, whereas the combination of TGF-beta1 and genistein attenuated the ERK1/2 and ROCK signaling. Of note, the other studied pathways remained almost unaffected. From this point of view, genistein does not impair conversion of normal fibroblasts to myofibroblast-like cells.

Long-term cardiac effects of treatment for childhood leukemia.

Late cardiac complications in cancer survivors may develop from subclinical myocardial damage. Biochemical correlates of minimal myocardial changes can be analyzed using a commercially available rapid assay. Biomarkers are considered more sensitive markers of subclinical cardiotoxicity than conventional electrocardiographic and echocardiographic methods. The aim of this study was to determine the values of plasma N-terminal pro brain natriuretic peptide (NT-pro-BNP) and cardiac troponin T (cTnT) in asymptomatic childhood leukemia survivors after anthracycline therapy in comparison with healthy volunteers. The survivors also underwent a detailed echocardiography. Twenty six survivors of leukemia previously treated with anthracyclines with total cumulative dose 95-600 (median 221) mg/m(2) were evaluated. Analyses of cTnT and NT-proBNP from blood samples and echocardiography were performed 5-25 years after completion of therapy for childhood leukemia. Control group for biochemical analyses consisted of 22 age- and gender- matched apparently healthy volunteers. Values of NT-proBNP were significantly elevated in ANT group compared to controls (35.1 +/- 37.8 vs. 9.6 +/- 6.7 pg/ml, P<0.010). CTnT remained below the diagnostic cut-off values in both groups. All echocardiographic parameters of patients remained normal. In conclusion, differences in NT-proBNP values between patients treated with anthracyclines and healthy volunteers might signal an initial stage of anthracycline-induced myocardial damage. The potential of this biomarker to detect subclinical anthracycline-induced myocardial alterations before development of echocardiographic and clinical changes is promising.

Frequency-domain analysis of the signal-averaged electrocardiogram in hematological malignancies survivors.

OBJECTIVES: The aim of the presented study was to evaluate the frequency-domain signal-averaged ECGs (SAECG) abnormalities in childhood and adolescence acute leukemia and lymphoma survivors treated either with or without anthracyclines (ANT) containing chemotherapy in comparison with healthy volunteers. BACKGROUND: The late development of chemotherapy-induced myocardial complications becomes an issue as the number of childhood cancer survivors is increasing. Underlying cardiac impairment may progress to serious cardiac diseases. Therefore, an early identification of myocardial injury is essential. PATIENTS AMD METHODS: Study population was divided into two treatment groups: ANT group (31 patients previously treated with ANT), and non-ANT group (32 patients who underwent chemotherapy without ANT, both more than 5 years ago). SAECG was added to routine cardiology examination in the whole population study and 32 controls. Using the frequency-domain analysis within the QRS complex a ratio (AR) of 20-50 (Hz)/0-20 (Hz) was calculated. RESULTS: AR 20-50/0-20 in SAECG was significantly higher in ANT and non-ANT groups, relative to controls (262.5 p < 0.00001 vs. 135.9 p < 0.001 vs. 74.7). The difference between both patient groups was also evident p < 0.01. CONCLUSION: Significant differences in frequency-domain SAECG parameters between patients (with or without anthracyclines) and controls might indicate the increased risk of electrical instability particularly in anthracycline-treated patients (Tab. 2, Fig. 1, Ref. 34).

Epilepsy, hyperalgesia, impaired memory, and loss of pre- and postsynaptic GABA(B) responses in mice lacking GABA(B(1)).

GABA(B) (gamma-aminobutyric acid type B) receptors are important for keeping neuronal excitability under control. Cloned GABA(B) receptors do not show the expected pharmacological diversity of native receptors and it is unknown whether they contribute to pre- as well as postsynaptic functions. Here, we demonstrate that Balb/c mice lacking the GABA(B(1)) subunit are viable, exhibit spontaneous seizures, hyperalgesia, hyperlocomotor activity, and memory impairment. Upon GABA(B) agonist application, null mutant mice show neither the typical muscle relaxation, hypothermia, or delta EEG waves. These behavioral findings are paralleled by a loss of all biochemical and electrophysiological GABA(B) responses in null mutant mice. This demonstrates that GABA(B(1)) is an essential component of pre- and postsynaptic GABA(B) receptors and casts doubt on the existence of proposed receptor subtypes.

Natriuretic peptides: biochemical markers of anthracycline cardiac toxicity?

Patients with cancer are often treated with potentially cardiotoxic chemotherapeutics. Cardiotoxicity ranges from relatively benign arrhythmias to serious conditions such as myocardial ischemia/infarction, congestive heart failure, and cardiomyopathy. In spite of different diagnostic methods, with echocardiography as a gold standard, there is an intensive search for new diagnostic tools for the early detection of myocardial abnormalities. Available data suggest that the levels of circulating cardiomarkers can monitor the extent and severity of the myocardial damage. The role of routinely used cardiomarkers is controversial and limited in this setting. Natriuretic peptides have shown promising results in assessment and monitoring of both acute and late clinical and subclinical damage of the myocardium in association with chemotherapy. This article reviews clinical studies evaluating the role of natriuretic peptides in the early diagnosis of anthracycline cardiotoxicity, and their use in the management of cancer survivors.

Taking the sting out of pain.

While the role of the brain kallikrein-kinin system in the development of various pathological processes, such as oedema formation following brain injury or induction of central hypertonia has generated major interest, the possible role of this system in nociceptive processing has received little attention. In their present paper, Mortari et al. (2007) show that bradykinin B2 receptor activation in the brain by the bradykinin analogue, Thr(6)-bradykinin, isolated from the venom of the social wasp, Polybia occidentalis potently reduces acute, noxious heat-evoked reflex responses in naive rats. The unknown underlying mechanism of this powerful antinociceptive effect reminds us that the supraspinal antinociceptive system is still a "black box" in many aspects and awaits thorough investigation.

Girdling decreases photosynthetic electron fluxes and induces sustained photoprotection in mango leaves.

Girdling has been suggested as a way to improve earliness and intensity of flowering in mango (Mangifer indica L.). However, the accumulation of carbohydrates associated with girdling may result in a decrease in photosynthesis. We assessed the long-term effect of branch girdling during the prefloral period on leaf net photosynthesis (A(n)) of 3-year old mango trees, cv. Cogshall, growing on La Réunion island. Leaf gas exchange and chlorophyll fluorescence parameters were measured monthly from March to August 2004 on recently matured leaves on girdled and non-girdled branches. Within 28 days after girdling, A(n) was reduced by 77% and remained at about 2 micromol CO(2) m(-2 ) s(-1) until the beginning of flowering. The decrease in photosynthetic electron transport rate (J) and sustained photoprotection (reflected by the decrease in predawn maximal efficiency of photosystem II) effectively protected leaves on girdled branches from photodamage, as shown by the vigorous recovery of A(n) and J observed immediately after the appearance of inflorescences. These increases in A(n) and J were unaccompanied by a decrease in leaf carbohydrate concentration during the first month following the onset of flowering, indicating that there are carbohydrate-dependent and carbohydrate-independent mechanisms of sink regulation of photosynthesis. It is concluded that girdling does not necessarily lead to irreversible damage, even in the presence of a fourfold increase in leaf starch concentration and in the absence of any sink activity. However, the decrease in leaf nitrogen concentration indicates that there may exist long-term negative effects of branch girdling on photosynthetic capacity. A modified version of the biochemical model of A(n) is presented that takes account of the effect of leaf starch concentration on J.