Nonselective Expression of Short-Wavelength Cone Opsin Improves Learning in Mice with Retinal Degeneration in a Visually Guided Task.

The study explored the potential of an animal opsin nonselectively expressed in various neuronal elements of the degenerative retina to restore the impaired visual function. A knockout murine model of inherited retinal dystrophy was used. Mice were injected intravitreally with either a virus carrying the gene of short-wavelength cone opsin associated with a reporter fluorescent protein or a control virus carrying the sequence of a modified fluorescent protein with enhanced membrane tropism. Viral transduction induced pronounced opsin expression in ganglion, bipolar, and horizontal retinal neurons. Behavioral testing included the visually guided task in the trapezoid Morris water maze and showed a partial recovery of the learning ability in the mice whose retinas had been transduced with cone opsin.

DELAYED SURGERY FOR GIANT SPONTANEOUS RUPTURE OF THE DISTAL THORACIC AORTA CAUSED BY CYSTIC MEDIAL NECROSIS.

Spontaneous (idiopathic) thoracic aortic rupture (STAR) is uncommon and assumes a rupture of the normal-sized thoracic aorta with no visually apparent aortic disease. Since 1961 about fifty reports have been published. STAR is established in cases of thoracic normal-sized aorta rupture with no traumas, aneurysms/dissections, infection, inflammation, connective tissue diseases, aortic and adjacent organs tumors/metastases, previous surgery, and occurring during pregnancy and the peripartum. Atherosclerosis penetrated atherosclerotic ulcer, neurofibromatosis type I, peri- and postpartum estrogen-mediated elastin irregularities of the aortic media, and cystic medial necrosis (CMN) were identified as a cause of STAR when histopathological examinations were performed. A case of a 68-year-old man with giant STAR of the descending aorta in the background of CMN is reported here. The patient in terminal hemodynamic condition was successfully treated by delayed open surgery two weeks after the disease's onset.

[Therapeutic hygiene of eyelids in dry eye disease prior to cataract phacoemulsification]. / Terapevticheskaya gigiena vek pri sindrome «sukhogo glaza¼ pered provedeniem fakoemul'sifikatsii katarakty.

PURPOSE: The study evaluates the effectiveness of eyelid hygiene (EH) in correction of the ocular surface (OS) condition in patients with dry eye disease (DED) ahead of cataract phacoemulsification (CPE). MATERIAL AND METHODS: The study included 90 patients with cataract: the first group consisted of 45 DED patients with lipid deficiency, the second group - 45 DED patients with lipid/mucous deficiency. Prior to CPE, all patients were randomized into three subgroups of 15 people each. In subgroups 1.1 and 2.1 patients did not receive any treatment for correction of the state of ocular surface. Patients in subgroups 1.2 and 1.3 were instilled 0.18% sodium hyaluronate (SH); in subgroups 2.2 and 2.3 - fixed combination of 0.15% SH and 3% trehalose. In subgroups 1.3 and 2.3 EH was performed (with «Blefarogel cleansing¼, «Blefarolotion¼, «Blefarogel-1¼ two times a day for one month before CPE). The control points were: 1) at study inclusion; 2) after correction of the ocular surface condition; 3) 30 days after CPE. The following parameters were evaluated: OSDI, TBUT (Norn's test), severity of meibomian gland dysfunction (MGD), patient satisfaction with CPE (CPE-PS). Statistical analysis: M±SD calculation, Mann--Whitney, Kruskal-Wallis and Wilcoxon tests. RESULTS: At the second control point, a statistically significant more pronounced OSDI decrease and bigger increase in TBUT were observed in subgroups 1.3 and 2.3 compared to subgroups 1.2 and 2.2 (Mann-Whitney U-test). Apparently, this was associated with a reduction in MGD severity in patients who received EH. At the third control point, significant lower values of OSDI and MGD severity, higher TBUT values and greater CFE-PS were recorded in subgroups 1.3 and 2.3 (Kruskal-Wallis test, Wilcoxon two-sample test). CONCLUSION: Carrying out EH using the «Blefarogel cleansing¼, «Blefarolotion¼, «Blefarogel-1¼ and artificial tear in patients with DED and cataract can increase the efficiency of correction of ocular surface condition and improve patient satisfaction with the outcome of CPE.

Charge transfer mechanisms in DNA at finite temperatures: From quasiballistic to anomalous subdiffusive charge transfer.

We address various regimes of charge transfer in DNA within the framework of the Peyrard-Bishop-Holstein model and analyze them from the standpoint of the characteristic size and timescales of the electronic and vibrational subsystems. It is demonstrated that a polaron is an unstable configuration within a broad range of temperatures and therefore polaronic contribution to the charge transport is irrelevant. We put forward an alternative fluctuation-governed charge transfer mechanism and show that the charge transfer can be quasiballistic at low temperatures, diffusive or mixed at intermediate temperatures, and subdiffusive close to the DNA denaturation transition point. Dynamic fluctuations in the vibrational subsystem is the key ingredient of our proposed mechanism which allows for explanation of all charge transfer regimes at finite temperatures. In particular, we demonstrate that in the most relevant regime of high temperatures (above the aqueous environment freezing point), the electron dynamics is completely governed by relatively slow fluctuations of the mechanical subsystem. We argue also that our proposed analysis methods and mechanisms can be relevant for the charge transfer in other organic systems, such as conjugated polymers, molecular aggregates, α-helices, etc.

[Ocular surface changes after cataract phacoemulsification]. / Izmeneniya glaznoi poverkhnosti posle fakoemul'sifikatsii.

PURPOSE: To assess the effects of phacoemulsification cataract surgery (PCS) and its pharmacological support on the prevalence of dry eye (DE) type ocular surface changes. MATERIAL AND METHODS: The study included 550 patients with age-related (369 patients) or complicated (181 patients) cataracts (247 men, 303 women; mean age 71.6±7.3 years) who were assessed using the Ocular Surface Disease Index (OSDI), tear break-up test (TBUT), Shirmer-1 test, lipid interference test, OCT meniscometry, examined for xerosis indicators and «lid vipers¼ symptom in order to detect DE before PCS, as well as on days 1, 7, 30 after PCS. Meibomian gland dysfunction (MGD) was determined by the Norn compression test, which was performed before PCS. The significance of differences was assessed using Pearson χ2 test. RESULTS: Before PCS the prevalence of DE was 51.1%, asymptomatic subclinical DE - 28.9%. MGD was detected in 79.4% of DE patients and in 50.3% subclinical DE patients. After PCS, an increase in DE prevalence was noted (due to increase in the prevalence of mild DE): on the 1st day - up to 58% (χ2=5.295; p=0.022; p<0.05), on the 7th day after surgery - up to 63.1% (χ2=16.165; p=0.001; p<0.01), on the 30th day - up to 55.6% (χ2=2.283; p=0.131; p>0.05). CONCLUSION: The study revealed a trend towards an increase in DE prevalence after PCS (due to an increase in the proportion of hypersecretory mild DE), which was statistically significant on days 1 and 7 after the operation and statistically insignificant by the 30th day after surgery. Apparently, it could be associated with aggravation of "background" asymptomatic ocular surface changes. From our point of view, the high prevalence of DE and subclinical DE in cataract patients before PCS makes it advisable to carry out preoperative preparation aimed at normalizing the condition of ocular surface. At the same time, the high prevalence of MGD in DE and subclinical DE patients determines one of the directions of preoperative treatment - eyelids hygiene.

Ab initio Calculations of Energy Levels in Be-Like Xenon: Strong Interference between Electron-Correlation and QED Effects.

The strong mixing of close levels with two valence electrons in Be-like xenon greatly complicates ab initio QED calculations beyond the first-order approximation. Because of a strong interplay between the electron-electron correlation and QED effects, the standard single-level perturbative QED approach may fail, even if it takes into account the second-order screened QED diagrams. In the present Letter, the corresponding obstacles are overcome by working out the QED perturbation theory for quasidegenerate states. The contributions of all the Feynman diagrams up to the second order are taken into account. The many-electron QED effects are rigorously evaluated in the framework of the extended Furry picture to all orders in the nuclear-strength parameter αZ. The higher-order electron-correlation effects are considered within the Breit approximation. The nuclear recoil effect is accounted for as well. The developed approach is applied to high-precision QED calculations of the ground and singly excited energy levels in Be-like xenon. The most accurate theoretical predictions for the binding and excitation energies are obtained. These results deviate from the most precise experimental value by 3σ but perfectly agree with a more recent measurement.

[Eyelid hygiene in preparing dry eye patients for cataract surgical treatment]. / Gigiena vek v podgotovke patsientov s sindromom «sukhogo glaza¼ k operativnomu lecheniyu katarakty.

PURPOSE: To evaluate the effectiveness of complex treatment, including eyelid hygiene, on the condition of ocular surface in dry eye patients before cataract surgery. MATERIAL AND METHODS: The study included 56 female age-related cataract patients (64±4.3 years old) with dry eye caused by Meibomian gland dysfunction (MGD). The main group patients (n=28) underwent eyelid hygiene therapy (2 times a day, 1 month) that involved Blefarogel cleansing, Blefarolotion, Blefarogel-1. The main and control (n=28) group patients performed (during the month): «fat-water¼ type nanoemulsion instillation (3 times a day); preservative free vitamin-A application (at night). Methods included dry eye symptoms assessment (OSDI scale); TBUT; Shirmer-1 test; lissamine green vital staining with xerosis indicator calculation (van Bijsterveld scale); "lid wipers" symptom evaluation; Norn compression test. Statistical evaluation included: mean and standard deviation calculation (M±s); significance of differences assessment (Mann-Whitney U-test; Wilcoxon's T-test). RESULTS: The main group patients (artificial tear, keratoprotection, eyelid hygiene) showed a statistically significant more pronounced decrease in OSDI (from 33.2±3.1 points to 15.2±1.8 points) and a significantly more pronounced increase in TBUT (from 4.8±0.5 s to 6.9±0.4 s) than in control group patients (artificial tear, keratoprotection; respectively, from 32.7±3.2 to 20.8±3.1 points and from 4.85±0.5 to 5.8±0.4 s; p<0.05). Apparently, this was associated with a significantly more pronounced relief of the MGD signs in main group patients (from 2.1±0.1 to 1.1±0.2 points; p<0.05) as a result of eyelid hygiene. In the control group, the dynamics of MGD severity (from 2.08±0.3 to 2.11±0.5 points) was statistically insignificant. CONCLUSION: Eyelid hygiene (based on Blefarogel cleansing, Blefarolotion, Blefarogel-1) increases the effectiveness of dry eye treatment in MGD patients, compared with isolated tear substitution and keratoprotection.

Beneficial effects of xenon inhalation on behavioral changes in a valproic acid-induced model of autism in rats.

BACKGROUND: Xenon (Xe) is a noble gas that has been used for the last several decades as an anesthetic during surgery. Its antagonistic effect on glutamate subtype of NMDA (N-methyl-D-aspartate) receptors resulted in evaluation of this gas for treatment of CNS pathologies, including psychoemotional disorders. The aim of this study was to assess the behavioral effects of acute inhalation of subanesthetic concentrations of Xe and to study the outcomes of Xe exposure in valproic acid (VPA)-induced rodent model of autism. METHODS: We have conducted two series of experiments with a battery of behavioral tests aimed to evaluate locomotion, anxiety- and depression-like behavior, and social behavior in healthy, VPA-treated and Xe-exposed young rats. RESULTS: We have shown that in healthy animals Xe exposure resulted in acute and delayed decrease of exploratory motivation, partial decrease in risk-taking and depressive-like behavior as well as improved sensorimotor integration during the negative geotaxis test. Acute inhalations of Xe in VPA-exposed animals led to improvement in social behavior, decrease in exploratory motivation, and normalization of behavior in forced-swim test. CONCLUSION: Behavioral modulatory effects of Xe are probably related to its generalized action on excitatory/inhibitory balance within the CNS. Our data suggest that subanesthetic short-term exposures to Xe have beneficial effect on several behavioral modalities and deserves further investigation.

Quantum nanoconstrictions fabricated by cryo-etching in encapsulated graphene.

We report on a novel implementation of the cryo-etching method, which enabled us to fabricate low-roughness hBN-encapsulated graphene nanoconstrictions with unprecedented control of the structure edges; the typical edge roughness is on the order of a few nanometers. We characterized the system by atomic force microscopy and used the measured parameters of the edge geometry in numerical simulations of the system conductance, which agree quantitatively with our low temperature transport measurements. The quality of our devices is confirmed by the observation of well defined quantized 2e2/h conductance steps at zero magnetic field. To the best of our knowledge, such an observation reports the clearest conductance quantization in physically etched graphene nanoconstrictions. The fabrication of such high quality systems and the scalability of the cryo-etching method opens a novel promising possibility of producing more complex truly-ballistic devices based on graphene.

Bicistronic Construct for Optogenetic Prosthesis of Ganglion Cell Receptive Field of Degenerative Retina.

To perform optogenetic prosthetics of the retinal ganglion cell receptive field, a bicistronic genetic construct carrying the genes encoding the excitatory (channelrhodopsin-2) and inhibitory (Guillardia theta anion channelrhodopsin GtACR2) rhodopsins was created. A characteristic feature of this construct was the combination of these two genes with a mutant IRES insertion between them, which ensures the exact ratio of expression levels of the first and second genes in each transfected cell. Illumination of the central part of the neuron with light with a wavelength of 470 nm induced the action potential generation in the cell. Stimulation of the peripheral neuronal region with light induced the inhibition of action potential generation. Thus, using optogenetics methods, we simulated the ON-OFF interaction in the retinal ganglion cell receptive field. Theoretically, this construct can be used for optogenetic prosthetics of degenerative retina in the case of its delivery to the ganglion cells with lentiviral vectors.

Statistical symmetry restoration in fully developed turbulence: Renormalization group analysis of two models.

In this paper we consider the model of incompressible fluid described by the stochastic Navier-Stokes equation with finite correlation time of a random force. Inertial-range asymptotic behavior of fully developed turbulence is studied by means of the field theoretic renormalization group within the one-loop approximation. It is corroborated that regardless of the values of model parameters and initial data the inertial-range behavior of the model is described by the limiting case of vanishing correlation time. This indicates that the Galilean symmetry of the model violated by the "colored" random force is restored in the inertial range. This regime corresponds to the only nontrivial fixed point of the renormalization group equation. The stability of this point depends on the relation between the exponents in the energy spectrum E∝k^{1-y} and the dispersion law ω∝k^{2-η}. The second analyzed problem is the passive advection of a scalar field by this velocity ensemble. Correlation functions of the scalar field exhibit anomalous scaling behavior in the inertial-convective range. We demonstrate that in accordance with Kolmogorov's hypothesis of the local symmetry restoration the main contribution to the operator product expansion is given by the isotropic operator, while anisotropic terms should be considered only as corrections.

Genetically encoded calcium indicator with NTnC-like design and enhanced fluorescence contrast and kinetics.

BACKGROUND: The recently developed genetically encoded calcium indicator (GECI), called NTnC, has a novel design with reduced size due to utilization of the troponin C (TnC) as a Ca2+-binding moiety inserted into the mNeonGreen fluorescent protein. NTnC binds two times less Ca2+ ions while maintaining a higher fluorescence brightness at the basal level of Ca2+ in neurons as compared with the calmodulin-based GECIs, such as GCaMPs. In spite of NTnC's high brightness, pH-stability, and high sensitivity to single action potentials, it has a limited fluorescence contrast (F-Ca2+/F+Ca2+) and slow Ca2+ dissociation kinetics. RESULTS: Herein, we developed a new NTnC-like GECI with enhanced fluorescence contrast and kinetics by replacing the mNeonGreen fluorescent subunit of the NTnC indicator with EYFP. Similar to NTnC, the developed indicator, named iYTnC2, has an inverted fluorescence response to Ca2+ (i.e. becoming dimmer with an increase of Ca2+ concentration). In the presence of Mg2+ ions, iYTnC2 demonstrated a 2.8-fold improved fluorescence contrast in vitro as compared with NTnC. The iYTnC2 indicator has lower brightness and pH-stability, but similar photostability as compared with NTnC in vitro. Stopped-flow fluorimetry studies revealed that iYTnC2 has 5-fold faster Ca2+ dissociation kinetics than NTnC. When compared with GCaMP6f GECI, iYTnC2 has up to 5.6-fold faster Ca2+ association kinetics and 1.7-fold slower dissociation kinetics. During calcium transients in cultured mammalian cells, iYTnC2 demonstrated a 2.7-fold higher fluorescence contrast as compared with that for the NTnC. iYTnC2 demonstrated a 4-fold larger response to Ca2+ transients in neuronal cultures than responses of NTnC. iYTnC2 response in neurons was additionally characterized using whole-cell patch clamp. Finally, we demonstrated that iYTnC2 can visualize neuronal activity in vivo in the hippocampus of freely moving mice using a nVista miniscope. CONCLUSIONS: We demonstrate that expanding the family of NTnC-like calcium indicators is a promising strategy for the development of the next generation of GECIs with smaller molecule size and lower Ca2+ ions buffering capacity as compared with commonly used GECIs.

Chloride conducting light activated channel GtACR2 can produce both cessation of firing and generation of action potentials in cortical neurons in response to light.

Optogenetics is a powerful technique in neuroscience that provided a great success in studying the brain functions during the last decade. Progress of optogenetics crucially depends on development of new molecular tools. Light-activated cation-conducting channelrhodopsin2 was widely used for excitation of cells since the emergence of optogenetics. In 2015 a family of natural light activated chloride channels GtACR was identified which appeared to be a very promising tool for using in optogenetics experiments as a cell silencer. Here we examined properties of GtACR2 channel expressed in the rat layer 2/3 pyramidal neurons by means of in utero electroporation. We have found that despite strong inhibition the light stimulation of GtACR2-positive neurons can surprisingly lead to generation of action potentials, presumably initiated in the axonal terminals. Thus, when using the GtACR2 in optogenetics experiments, its ability to induce action potentials should be taken into account. Our results also open an interesting possibility of using the GtACR2 both as cell silencer and cell activator in the same experiment varying the pattern of light stimulation.

Recoil Effect on the g Factor of Li-Like Ions.

The nuclear recoil effect on the g factor of Li-like ions is evaluated. The one-electron recoil contribution is treated within the framework of the rigorous QED approach to the first order in the electron-to-nucleus mass ratio m/M and to all orders in the parameter αZ. These calculations are performed in a range Z=3-92. The two-electron recoil term is calculated for low- and middle-Z ions within the Breit approximation using a four-component approach. The results for the two-electron recoil part obtained in the Letter strongly disagree with the previous calculations performed using an effective two-component Hamiltonian. The obtained value for the recoil effect is used to calculate the isotope shift of the g factor of Li-like ^{A}Ca^{17+} with A=40 and A=48 which was recently measured. It is found that the new theoretical value for the isotope shift is closer to the experimental one than the previously obtained value.

[Eye lid hygiene in chronic allergic blepharoconjunctivitis patients before laser refractive surgery]. / Gigiena vek v podgotovke k lazernoi refraktsionnoi khirurgii.

AIM: To evaluate the effectiveness of eyelid hygiene in patients with chronic allergic blepharoconjunctivitis (ABC) as a part of their preparation for laser refractive surgery. MATERIAL AND METHODS: The study involved 32 patients (12 males and 20 females aged 25-42 years) with refractive errors, namely, compound myopic astigmatism (23 patients) and hyperopic astigmatism (9 patients) suffering from chronic ABC and secondary dry eye syndrome (DES). All the patients initially received a standard treatment for ABC and DES, that is olopatodin hydrochloride instillations - 1 mg/ml 2 times daily, preservative-free hyaluronic acid preparation - 1 mg/ml 3 times daily, and polyacrylic acid and dexpanthenol gel at night for one month. The scheme, however, appeared not effective enough. Hence, the patients were prescribed eyelid hygiene (Blepharolotion or Blepharosalfetka plus Blepharogel-1 2 times daily) to relive meibomian gland dysfunction (MGD). They also underwent a conventional ophthalmic examination, allergy tests, evaluation of ABC and DES signs and symptoms, tear film break-up time test, Schirmer's test, meibomian glands evaluation, optical coherence tomography with meniscometry, xerosis index evaluation, and lissamine green staining for lid wiper epitheliopathy. RESULTS: At the beginning of the study signs and symptoms of MGD-associated DES were predominant in all patients. Chronic ABC signs were mild. In 2-3 months, meibomian gland function and tear film break-up time improved significantly in most patients, while xerosis index decreased and lid wiper epitheliopathy resolved. Laser refractive surgery (LASIK) was performed in 81.25% of patients, all of whom were satisfied with the results. CONCLUSION: Inclusion of eyelid hygiene into preoperative management of patients with chronic ABC and DES allows to achieve optimum conditions for laser refractive surgery in most cases.

Comparative characteristics of two anion-channel rhodopsins and prospects of their use in optogenetics.

Anion-selective opsins slow ChloC and ACR2 were expressed in rat brain cortical neurons by electroporation in utero. It is shown that the light-activated channel ACR2 has pronounced advantages in terms of both the inactivation kinetics and the neuron inhibition intensity, which is associated with a more negative value of the light-activated current reversal potential compared to the slow ChloC channel. The identified properties of opsin ACR2 indicate that it can be used for strictly controlled suppression of neuronal activity in optogenetic experiments, including the expression in the retinal ganglionic cells for reconstituting the OFF-component of their receptive field, which is essential for optogenetic prosthetics of degenerative retina.

[Physiological Aspects of the Application of Hodgkin-Huxley Model of Action Potential Initiation for Invertebrate and Vertebrate Neurons].

Recent studies have revealed.that in contrast to invertebrate systems, the initiation of action potentials in vertebrate neurons significantly differ from the relatively slow exponential dynamics predicted by Hodgkin-Huxley equations, but rather is characterized by a sharp onset with a kink. These data provided new insights into the link between action potential initiation and abilities of neurons and neuronal networks to encode. high frequency signals. Here, we review recent models describing sharp onset dynamics of action potential initiation, including an alternative model of cooperative activation of sodium channels, as well as the influence of the dynamics of action potential initiation on computational abili- ties of neuronal networks. The importance this topic is due to the fact that, despite the rapid development of neuronal modeling during last decades, the well established models are unable to capture experimentally observed details of the onset dynamics of action potentials in mammalian neurons and the abilities of neurons to reliably encode code high frequency signals Recent advances of experimental and theoretical analysis of generation of action potentials and neuronal encoding, presented in this review, are ofgreat importance for better understanding of neuronal processing and development of a more precise and realistic neuronal model.

[Effect of prolonged epidupal analgesia on respiratory function after major laparoscopic surgery].

UNLABELLED: The article deals with a study of role of epidural analgesia, used as a part of intra- and postoperative analgesia in patients underwent major laparoscopic surgery (gastric resections, pancreas and duodenal resections, hemicolectomy, resections of colon). PATIENTS AND METHODS: The study included 127 patients aged 65 ± 13 years. Main group--patients who had undergone extensive and prolonged laparoscopic surgery; comparison group--patients after traditional open surgery. Terms of laparoscopic and open surgeries was similar Postoperatively we assessed dynamics ofpostoperative pain and physical activity (using appropriate scales), dynamics of respiratory function (spirometry) in with and without use of epidural analgesia. CONCLUSION: major laparoscopic surgery accompanied with lower decreasing of speed and volume figures of spirometry if epidural analgesia is used as a part of intra- and postoperative analgesia.

[Effect of surgery on quality of life in patients with epiretinal membrane].

OBJECTIVE: To study the effect of surgical treatment on quality of life (QOL) in patients with epiretinal membrane (EM). MATERIAL AND METHODS: A total of 48 patients who underwent surgical treatment for EM were examined. QOL was assessed with the VFQ-25 questionnaire before and after the surgery (at 1 week and 6 months). RESULTS: Before the surgery the total QOL index was significantly decreased by an average of 25% as compared with the controls (p<0.001). In the late postoperative period there was a progressive increase in the total index of QOL up to the level of the control group (p>0.05). CONCLUSION: Vitrectomy surgery improves visual functions and quality of life in patients with epiretinal membrane.

Anion-selective channelrhodopsin expressed in neuronal cell culture and in vivo in murine brain: Light-induced inhibition of generation of action potentials.

Anionic channelrhodopsin slow ChloC was expressed in the culture of nerve cells and in vivo in mouse brain. We demonstrated ability of slow ChloC to suppress effectively the activity of the neuron in response to the illumination with the visible light. It has been shown for a first time that slow ChloC works equally efficiently in both neuronal culture and in the whole brain being expressed in vivo. Thus, slow ChloC could be considered as an effective optogenetic tool capable in response to light stimulation to inhibit the generation of action potentials in the neuron.