[A model of primary open-angle glaucoma: manifestations and outcomes].

OBJECTIVE: To determine the expected duration of the disease and the age of the patients with different stages ofprimary open-angle glaucoma complicated by pseudoexfoliation syndrome (PES) and/or patients with pseudoexfoliation glaucoma (PEG). METHODS: The study protocol included data from 120 patients (50 males (41.7%), 70 females (58.3%)); 189 eyes; 102 right eyes; 87 left eyes). The first study group (28 patients, 44 eyes) comprised patients with suspected glaucoma. The second group (53 patients, 84 eyes) consisted ofpatients with early glaucoma. The third group (21 patient, 33 eyes) included patients with advanced glaucoma, the forth group (18 patients, 28 eyes) comprised patients with terminal glaucoma. Mean age of the patients at diagnosis was 61.6 (58.4; 66.9) years and 66.9 (63.4; 72.8) years at the endpoint visit in 2013. In all cases, diagnosis was made in accordance with the differential diagnostics system and confirmed by special diagnostic techniques. The database included data from 3 qualified examinations taking account of the results of tonometry and static automated perimetry. RESULTS: The mean expected age of the patients age at the onset of blindness was 75.1 years. The occurrence of the event was limited to a period of 6.1 years. Mean age at the time of possible glaucoma development was 59.58 (56.14; 64.36) years. The disease itself could develop within 3.24 (-5.38; -1.2) years prior to diagnosis. CONCLUSION: Studies for glaucoma diagnosis should be focused on the age group of 55-60 years. The degree of IOP reduction in patients with advanced glaucoma does not agree with the Russian glaucoma society recommendations which accounts for progression of the disease.

Unconventional high-temperature superconductivity from repulsive interactions: theoretical constraints.

Unconventional symmetries of the order parameter allowed some researchers to maintain that a purely repulsive interaction between electrons provides superconductivity without phonons in a number of high-temperature superconductors. It is shown that the Cooper pairing in p and d states is not possible with the realistic Coulomb repulsion between fermions at relevant temperatures in any dimension.

Molecular dynamics simulations of oxide memory resistors (memristors).

Reversible bipolar nanoswitches that can be set and read electronically in a solid-state two-terminal device are very promising for applications. We have performed molecular dynamics simulations that mimic systems with oxygen vacancies interacting via realistic potentials and driven by an external bias voltage. The competing short- and long-range interactions among charged mobile vacancies lead to density fluctuations and short-range ordering, while illustrating some aspects of observed experimental behavior, such as memristor polarity inversion. The simulations show that the 'localized conductive filaments' and 'uniform push/pull' models for memristive switching are actually two extremes of the one stochastic mechanism.

Superconducting gap, normal state pseudogap, and tunneling spectra of bosonic and cuprate superconductors.

We develop a theory of normal metal-superconductor and superconductor tunneling in "bosonic" superconductors with strong attractive correlations taking into account coherence effects in single-particle excitation spectrum and disorder. The theory accounts for the existence of two energy scales, their temperature and doping dependencies, asymmetry, and inhomogeneity of tunneling spectra of underdoped cuprate superconductors.

Key pairing interaction in layered doped ionic insulators.

A controversial issue on whether the electron-phonon interaction (EPI) is crucial for high-temperature superconductivity or it is weak and inessential has remained one of the most challenging problems of contemporary condensed matter physics. We employ a continuum random phase approximation for the dielectric response function allowing for a self-consistent semianalytical evaluation of the EPI strength, electron-electron attractions, and the carrier mass renormalization in layered high-temperature superconductors. We show that the Fröhlich EPI with high-frequency optical phonons in doped ionic lattices is the key pairing interaction, which is beyond the BCS-Migdal-Eliashberg approximation in underdoped superconductors, and it remains a significant player in overdoped compounds.

Electron-phonon coupling in high-temperature cuprate superconductors determined from electron relaxation rates.

We determined electronic relaxation times via pump-probe optical spectroscopy using sub-15 fs pulses for the normal state of two different cuprate superconductors. We show that the primary relaxation process is the electron-phonon interaction and extract a measure of its strength, the second moment of the Eliashberg function λ[ω2] = 800 ± 200 meV2 for La(1.85)Sr(0.15)CuO4 and λ[ω2] = 400 ± 100 meV2 for YBa(2)Cu(3)O(6.5). These values suggest a possible fundamental role of the electron-phonon interaction in the superconducting pairing mechanism.

Zero-temperature phase transitions in dilute bosonic superfluids on a lattice.

Kinetic energy driven phase transitions in Bose superfluids occur at low values of the repulsion when the values of the next-to-nearest and next-to-next-to-nearest hopping term attain certain critical values, resulting in alterations in the wavevector of the condensate. We map out the space of possible phases allowed by particular forms of the single-particle energy dispersion in the superfluid state, noting the appearance of a new phase, and examine in more detail the effects of additional repulsive terms on the form of the condensate wavefunction. We also examine the effect of these additional hopping terms on the formation of inhomogeneities in the condensate.

Increased plasma endothelin level as an endothelial marker of cardiovascular risk in patients with active acromegaly: a comparison with plasma homocysteine.

The aim of the present study was to evaluate the plasma endothelin-1 (ET-1) and total homocysteine (tHcy) levels as biochemical markers of endothelial dysfunction and atherosclerosis in patients with active and cured acromegaly in order to assess the relationship between the secretory status of growth hormone (GH)/insulin-like growth factor I (IGF-I) and ET-1/tHcy levels. The patients were divided in two subgroups: 1) patients with active disease (n = 30); and 2) patients with nonactive cured acromegaly (n = 21). Plasma ET-1 levels were directly determined by a highly sensitive enzyme immunoassay and plasma tHcy concentrations were measured by a fluorescence polarization immunoassay. In active acromegaly subjects, plasma ET-1 levels were 1.24 +/- 0.2 pmol/L, significantly higher than in both nonactive acromegalics (0.39 +/- 0.1 pmol/L) and age-matched healthy controls (0.49 +/- 0.2 pmol/L) (P < 0.001). Plasma tHcy concentrations, however, did not differ significantly in all studied groups: nonactive acromegalics: 9.54 +/- 4.42 micromol/L; active acromegalics: 9.0 +/- 3.14 micromol/L; and control subjects: 9.96 +/- 2.95 micromol/L (P > 0.05). In conclusion, our study demonstrated that elevated ET-1 levels probably contributed to premature atherosclerosis and cardiovascular disease and represent a new risk factor for endothelial dysfunction and early vascular complications in acromegaly. We propose that GH and IGF-I secretory status are important determinants of plasma ET-1 but not tHcy levels.

Simulating mild systematic and focal demyelinating neuropathies: membrane property abnormalities.

This study provides numerical simulations of some of the abnormalities in the potentials and axonal excitability indices of human motor nerve fibers in simulated cases of internodal, paranodal and simultaneously of paranodal internodal demyelinations, each of them systematic or focal. A 70% reduction of the myelin lamellae (defining internodal demyelination), or of the paranodal seal resistance (defining paranodal demyelination), or simultaneously both of them (defining paranodal internodal demyelination) was uniform along the fiber length for the systematically demyelinated subtypes. These permutations were termed internodal systematic demyelination (ISD), paranodal systematic demyelination (PSD) and paranodal internodal systematic demyelination (PISD). In other tests, the same reductions of the myelin sheath parameters were used but restricted to only three (8th, 9th and 10th) consecutive internodes. Such fiber demyelinations were termed internodal focal demyelination (IFD), paranodal focal demyelination (PFD) and paranodal internodal focal demyelination (PIFD). The computations used our previous double cable model of the fibers. The axon model was comprised of 30 nodes and 29 internodes. The 70% reduction value was not sufficient to develop conduction block in all investigated demyelinations, which were regarded as mild. The membrane property abnormalities obtained in the ISD, PSD and PISD cases were quite different and abnormally greater than those in the IFD, PFD and PIFD cases. The changes in the excitability indices such as strength-duration time constants, rheobasic currents and recovery cycles in the focally demyelinated subtypes were so slight as to be essentially indistinguishable from normal values. Consequently, the excitability based approaches that have shown strong potential as diagnostic tools in systematically demyelinated conditions may not be useful in detecting mild focal demyelinations. The membrane property changes simulated in the systematically demyelinated subtypes are in good accordance with the data from patients with Charcot-Marie-Tooth disease type 1A (CMT1A) and chronic inflammatory demyelinating polyneuropathy (CIDP). The excitability abnormalities obtained in each focally demyelinated subtype match those observed in vivo in patients with demyelinating forms of Guillain-Barré syndrome (GBS). The results indicate that the model that was used is a rather promising tool in studying the membrane property abnormalities of hereditary, chronic and acquired demyelinating neuropathies, which up till now, have not been sufficiently well understood.

Differences in potentials and excitability properties in simulated cases of demyelinating neuropathies. Part I.

OBJECTIVE: The aim of this study is to investigate the potentials (intracellular, extracellular, electrotonic) and excitability properties (strength-duration and charge-duration curves, strength-duration time constants, rheobases, recovery cycles) in three cases of uniform myelin wrap reduction (20, 50 and 70%) along the fibre length. METHODS: The internodally systematically demyelinated cases (termed as ISD1, ISD2 and ISD3) are simulated using our previous double cable model of human motor fibres. RESULTS: In the more severely demyelinated cases, the intracellular potentials are with significantly reduced amplitude, prolonged duration and slowed conduction velocity, whereas the electrotonic potentials show greater increase in the early part of the hyperpolarizing responses. The radial decline of the extracellular potential amplitudes depends on the radial distance of the field point and increases with the increase of the distance and demyelination. The time constants and rheobasic currents increase with the increase of the degree of demyelination. In the recovery cycles, the more severely demyelinated cases have greater refractoriness (the increase in threshold current during the relative refractory period), supernormality and less late subnormality than the normal case. CONCLUSIONS: The myelin thickness has significant effects on the potentials and axonal excitability properties of the simulated demyelinated human motor fibres. The obtained abnormalities in the potentials and excitability properties can be observed in Charcot-Marie-Tooth disease type 1A (CMT1A). SIGNIFICANCE: The study provides new information about the pathophysiology of human demyelinating neuropathies.

Elevated plasma endothelin as an additional cardiovascular risk factor in patients with Cushing's syndrome.

BACKGROUND: Recently the pathophysiological role of endothelin (ET) has been presumed in a number of adrenal disorders such as primary hyperaldosteronism, pheochromocytoma and adrenocortical insufficiency. AIM: The aim of the present study was to evaluate circulating ET-1 levels in patients with endogenous Cushing's syndrome. METHODS AND RESULTS: Plasma ET-1 levels were determined by highly sensitive RIA. Thirteen untreated subjects with Cushing's syndrome were studied: eight women and five men of mean age 44.2+/-9.5 Years (s.d.). In ten of them, Cushing's disease had been diagnosed and three had adrenal adenomas. ET-1 was 3-fold higher in the patient group than in age-matched healthy controls (n=13): 1.59+/-0.78 vs 0.46+/-0.20 pmol/l respectively, P<0.001. In adrenal adenoma patients, ET-1 was not significantly higher than in the Cushing's disease subjects (1.84+/-0.67 vs 1.51+/-0.83 pmol/l respectively, P>0.05). In three patients who died of severe cardiovascular complications, plasma ET-1 was significantly higher than in the remaining patients (2.34+/-0.35 pmol/l, P<0.05). A positive correlation was found between the total cholesterol (6.94+/-1.75 mmol/l) and ET-1 levels in the patients with Cushing's syndrome: r=+0.73, P<0.02. No correlation was observed, however, between the levels of ET-1 and blood pressure (183+/-37/106+/-18 mmHg), plasma cortisol levels (455.2+/-74.5 nmol/l) or urinary cortisol excretion (1463+/-726 nmol/24 h). The successful treatment and correction of hypercortisolism in seven patients led to insignificant reduction in plasma ET from 1.34+/-0.69 to 0.73+/-0.53 pmol/l, P>0.05. CONCLUSION: Our results clearly demonstrate that the ET system is activated in Cushing's syndrome. Elevated plasma ET-1 levels probably play a role in the pathogenesis of accelerated and early atherosclerosis development in this disorder.

Comparison between normal and parkinsonian pattern of motor unit firing.

There are many approaches to the study of the activity of separate motor units (MU) in man. In humans alpha motoneuron activity consists in generating spike trains that innervate groups of muscle fibers thus building MU. In the present study we used a new evolution of the joint interval density analysis in patients with Parkinson disease.

Peripheral late waves in patients with hereditary motor sensory neuropathy.

Patents with different forms of hereditary motor sensory neuropathy (HMSN) were investigated. Peripheral late waves (PLWs) were recorded when determining F wave at supramaximal stimulation. We registered them most frequently in patients with demyelinating neuropathies (HMSN1--58% and HMSN3--100%) and in patients with HMSN2--24% and HMN--13%. In patients with HMSN1 and HMSN3 the peripheral late waves sometimes were more than one--two or three. They had a consistent appearance above a maximal threshold of stimulation, an invariable latency, amplitude and wave-form. Their latency times were in parallel with the M-response latency. These PLWs can be explained by collateral regeneration in case of axonal neuropathy. The ephaptic transmission might be taken in consideration when interpreting data from patients with demyelinating processes.

Comparative analysis between Duchenne and Becker types muscular dystrophy.

Duchenne and Becker types of muscular dystrophy are usually differentiated according to age of onset and rate of progression criteria which are not sufficient. The aim of this paper was to re-establish the clues for distinguishing Duchenne from Becker types of muscular dystrophy. According to the onset and progression of the disease, one hundred and eleven patients were subdivided into two groups. First group--Becker muscular dystrophy--consisted of 40 patients and second one of 71 patients with Duchenne type of muscular dystrophy. Clinical data confirm some well known differences between Duchenne and Becker muscular dystrophy concerning the age of onset, severity of disease and rate of progression. Electromyographic signs of myopathic changes and spontaneous activity were found in both diseases. Spontaneous activity--bizarre and fibrillation potentials, as well as sharp waves are more common for Duchenne type. The differences between the Becker from Duchenne type of muscular dystrophy can be described on the basis of complex investigations (clinical, electromyographical, histological and biochemical).

Extraordinary magnetoresistance in graphite: experimental evidence for the time-reversal symmetry breaking.

We report a highly anisotropic in-plane magnetoresistance (MR) in graphite that possesses in-plane parallel line-like structural defects. In a current direction perpendicular to the line defects (LD), MR is negative and linear in low fields with a crossover to a positive MR at higher fields, while in a current direction parallel to LD, we observed a giant super-linear positive MR. These extraordinary MRs are respectively explained by a hopping magnetoresistance via non-zero angular momentum orbitals, and by the magnetoresistance of inhomogeneous media. The linear negative orbital MR is a unique signature of the broken time-reversal symmetry (TRS). We discuss the origin of the disorder-induced TRS-breaking in graphite.

Diamagnetism of real-space pairs above T(c) in hole doped cuprates.

The nonlinear normal state diamagnetism reported by Li et al (2010 Phys. Rev. B 81 054510) is shown to be incompatible with a claimed Cooper pairing and vortex liquid above the resistive critical temperature. However, it is perfectly compatible with the normal state Landau diamagnetism of real-space composed bosons, which provides a description of the nonlinear magnetization curves of the less anisotropic cuprates La-Sr-Cu-O (LSCO) and Y-Ba-Cu-O (YBCO) as well as for strongly anisotropic bismuth-based cuprates over the whole range of available magnetic fields.

Theory of extrinsic and intrinsic tunnelling in cuprate superconductors.

There has been a huge theoretical and experimental push to try to illuminate the mechanism behind the high-temperature superconductivity of copper oxides. Cuprates are distinguishable from conventional metallic superconductors in originating from the doping of the parent charge-transfer insulators. The superconducting parts are weakly coupled two-dimensional doped layers held together by the parent lattice. Apart from their high-T(c) they have other characteristic features including the 'superconducting' gap (SG) which develops below the superconducting critical temperature and can be seen in extrinsic and intrinsic tunnelling experiments as well as using high-resolution angle-resolved photoemission (ARPES); there also exists another energy gap, the 'pseudogap' (PG), which is a large anomalous gap that exists well above T(c). We present a brief review of recent theories behind the pseudogap and discuss in detail one specific (polaronic) approach which explains the SG, PG and unusual tunnelling characteristics of cuprate superconductors.

Simulating focal demyelinating neuropathies: membrane property abnormalities.

Membrane properties such as potentials (intracellular, extracellular, electrotonic) and axonal excitability indices (strength-duration and charge-duration curves, strength-duration time constants, rheobasic currents, recovery cycles) can now be measured in healthy subjects and patients with demyelinating neuropathies. They are regarded here in two cases of simultaneously reduced paranodal seal resistance and myelin lamellae in one to three consecutive internodes of human motor nerve fiber. The investigations are performed for 70 and 96% myelin reduction values. The first value is not sufficient to develop a conduction block, but the second leads to a block and the corresponding demyelinations are regarded as mild and severe. For both the mild and severe demyelinations, the paranodally internodally focally demyelinated cases (termed as PIFD1, PIFD2, and PIFD3, respectively, with one, two, and three demyelinated internodes) are simulated using our previous double-cable model of the fiber. The axon model consists of 30 nodes and 29 internodes. The membrane property abnormalities obtained can be observed in vivo in patients with demyelinating forms of Guillain-Barré syndrome (GBS) and multifocal motor neuropathy (MMN). The study confirms that focal demyelinations are specific indicators for acquired demyelinating neuropathies. Moreover, the following changes have been calculated in our previous papers: (1) uniform reduction of myelin thickness in all internodes (Stephanova et al. in Clin Neurophysiol 116: 1153-1158, 2005); (2) demyelination of all paranodal regions (Stephanova and Daskalova in Clin Neurophysiol 116: 1159-1166, 2005a); (3) simultaneous reduction of myelin thickness and paranodal demyelination in all internodes (Stephanova and Daskalova in Clin Neurophysiol 116: 2334-2341, 2005b); and (4) reduction of myelin thickness of up to three internodes (Stephanova et al., in J Biol Phys, 2006a,b, DOI: 10.1007/s10867-005-9001-9; DOI: 10.1007/s10867-006-9008-x). The membrane property abnormalities obtained in the homogeneously demyelinated cases are quite different and abnormally greater than those in the case investigated here of simultaneous reduction in myelin thickness and paranodal demyelination of up to three internodes. Our previous and present results show that unless focal demyelination is severe enough to cause outright conduction block, changes are so slight as to be essentially indistinguishable from normal values. Consequently, the excitability-based approaches that have shown strong potential as diagnostic tools in systematically demyelinated conditions may not be useful in detecting mild focal demyelinations, independently of whether they are internodal, paranodal, or paranodal internodal.

Superlight small bipolarons in the presence of a strong Coulomb repulsion.

We study a lattice bipolaron on a staggered triangular ladder and triangular and hexagonal lattices with both long-range electron-phonon interaction and strong Coulomb repulsion using a novel continuous-time quantum Monte Carlo algorithm to solve the two-particle Coulomb-Fröhlich model. The algorithm is preceded by an exact integration over phonon degrees of freedom, and as such is extremely efficient. The bipolaron effective mass and radius are computed. Bipolarons on lattices constructed from triangular plaquettes have a novel crablike motion, and are small but very light over a wide range of parameters. We discuss the conditions under which such particles may form a Bose-Einstein condensate with high transition temperature, proposing a route to room temperature superconductivity.

Normal-state diamagnetism of charged bosons in cuprate superconductors.

Normal-state orbital diamagnetism of charged bosons quantitatively accounts for recent high-resolution magnetometery results near and above the resistive critical temperature T(c) of superconducting cuprates. The parameter-free descriptions of normal-state diamagnetism, T(c), upper critical fields, and specific heat anomalies support the 3D Bose-Einstein condensation of preformed real-space pairs with a zero off-diagonal order parameter above T(c) at variance with phase fluctuation scenarios of cuprates.