Tubular vs. mini-open lumbar discoidectomy: surgical-clinical outcome.

OBJECTIVE: To evaluate the clinical-surgical results of the tubular vs. mini-open approach in lumbar discoidectomy. The tubular approach promises to reduce the number of rest days and an earlier return to daily activities and work. METHOD: A case-control study of patients operated on for disc herniation using tubular surgery (case) and mini-open (control) was carried out. The variables investigated were as follow: radicular and lumbar pain, sex, age, failure in conservative treatment, single-level lumbar hernia, surgical time, bleeding, length of hospital stay, persistence of symptoms, complications, occupational activity, and reintegration into everyday activities. RESULTS: Through 100 surgeries performed, two groups were created, tubular and mini-open, with 50 patients each, with L4-L5 or L5-S1 disc herniation, respectively. The most affected level was L4-L5 (69%). Of the total cases, a significant improvement was found (p < 0.05) at 15 postoperative days in the VAS and ODI scale in the tubular group with respect to mini-open. Complications such as surgical wound infection, durotomy, and persistent pain occurred. CONCLUSIONS: The tubular approach is a safe and effective option for herniated discs of the lumbar segment, and reduces surgical times, bleeding, and the time of reinsertion to daily activities of the patient.

OBJETIVO: Evaluar los resultados clínico-quirúrgicos del abordaje tipo tubular en comparación con el mini-open en la discoidectomía lumbar. El abordaje tubular promete reducir el número de días de reposo y una reincorporación más temprana a las actividades diarias y laborales. MÉTODO: Se realizó un estudio de casos y controles de pacientes operados por hernia discal mediante cirugía tubular (casos) o mini-open (controles). Las variables investigadas fueron: dolor radicular y lumbar, sexo, edad, falla en el tratamiento conservador, hernia lumbar de un solo nivel, tiempo quirúrgico, sangrado, tiempo de estancia hospitalaria, persistencia de síntomas, complicaciones, tipo de actividad ocupacional y reinserción a las actividades cotidianas. RESULTADOS: Se realizaron 100 cirugías y se crearon dos grupos, tubular y mini-open, con 50 pacientes cada uno, con hernia discal de L4-L5 o L5-S1, respectivamente. El nivel más afectado fue L4-L5 (69%). Del total de los casos, se encontró mejoría significativa (p < 0.05) a los 15 días posquirúrgicos en la escala EVA y ODI en el grupo tubular con respecto al mini-open. Ocurrieron complicaciones como infección de herida quirúrgica, durotomía y dolor persistente. CONCLUSIONES: El abordaje tubular es una opción segura y efectiva para hernias discales del segmento lumbar, y reduce los tiempos quirúrgicos, el sangrado y el tiempo de reinserción a las actividades cotidianas del paciente.

Safety and Immunogenicity of Inactivated Whole Virion COVID-19 Vaccine CoviVac in Clinical Trials in 18-60 and 60+ Age Cohorts.

We present the results of a randomized, double-blind, placebo-controlled, multi-center clinical trial phase I/II of the tolerability, safety, and immunogenicity of the inactivated whole virion concentrated purified coronavirus vaccine CoviVac in volunteers aged 18-60 and open multi-center comparative phase IIb clinical trial in volunteers aged 60 years and older. The safety of the vaccine was assessed in 400 volunteers in the 18-60 age cohort who received two doses of the vaccine (n = 300) or placebo (n = 100) and in 200 volunteers in 60+ age cohort all of whom received three doses of the vaccine. The studied vaccine has shown good tolerability and safety. No deaths, serious adverse events (AEs), or other significant AEs related to vaccination have been detected. The most common AE in vaccinated participants was pain at the injection site (p < 0.05). Immunogenicity assessment in stage 3 of Phase II was performed on 167 volunteers (122 vaccinated and 45 in Placebo Group) separately for the participants who were anti-SARS-CoV-2 nAB negative (69/122 in Vaccine Group and 28/45 in Placebo Group) or positive (53/122 in Vaccine Group and 17/45 in Placebo Group) at screening. On Day 42 after the 1st vaccination, the seroconversion rate in participants who were seronegative at screening was 86.9%, with the average geometric mean neutralizing antibody (nAB) titer of 1:20. A statistically significant (p < 0.05) increase in IFN-γ production by peptide-stimulated T-cells was observed at Days 14 and 21 after the 1st vaccination. In participants who were seropositive at screening but had nAB titers below 1:256, the rate of fourfold increase in nAB levels was 85.2%, while in the participants with nAB titers > 1:256, the rate of fourfold increase in nAB levels was below 45%; the participants who were seropositive at screening of the 2nd vaccination did not lead to a significant increase in nAB titers. In conclusion, inactivated vaccine CoviVac has shown good tolerability and safety, with over 85% NT seroconversion rates after complete vaccination course in participants who were seronegative at screening in both age groups: 18-60 and 60+. In participants who were seropositive at screening and had nAB titers below 1:256, a single vaccination led to a fourfold increase in nAB levels in 85.2% of cases. These findings indicate that CoviVac can be successfully used both for primary vaccination in a two-dose regimen and for booster vaccination as a single dose in individuals with reduced neutralizing antibody levels.

Neuroinflammation in Pathogenesis of Audiogenic Epilepsy: Altered Proinflammatory Cytokine Levels in the Rats of Krushinsky-Molodkina Seizure-Prone Strain.

Neuroinflammation plays an important role in epileptogenesis, however, most studies are performed using pharmacological models of epilepsy, while there are only few data available for non-invasive, including genetic, models. The levels of a number of pro-inflammatory cytokines were examined in the Krushinsky-Molodkina (KM) rat strain with high audiogenic epilepsy (AE) proneness (intense tonic seizure fit in response to loud sound) and in the control strain "0" (not predisposed to AE) using multiplex immunofluorescence magnetic assay (MILLIPLEX map Kit). Cytokine levels were determined in the dorsal striatum tissue and in the brain stem. Background levels of IL-1ß, IL-6, and TNF-α in the dorsal striatum of the KM rats were significantly lower than in the rats "0" (by 32.31, 27.84, and 38.87%, respectively, p < 0.05, 0.05, and 0.01), whereas no inter-strain differences in the levels of these metabolites were detected in the brain stem in the "background" state. Four hours after sound exposure, the TNF-α level in the dorsal striatum of the KM rats was significantly lower (by 38.34%, p < 0.01) than in the "0" rats. In the KM rats, the dorsal striatal levels of IL-1ß and IL-6 were significantly higher after the sound exposure and subsequent seizure fit, compared to the background (35.29 and 50.21% increase, p < 0.05, 0.01, respectively). In the background state the IL-2 level in the KM rats was not detected, whereas after audiogenic seizures its level was 14.01 pg/ml (significant difference, p < 0.01). In the KM rats the brain stem levels of IL-1ß and TNF-α after audiogenic seizures were significantly lower than in the background (13.23 and 23.44% decrease, respectively, p < 0.05). In the rats of the "0" strain, the levels of cytokines in the dorsal striatum after the action of sound (which did not induce AE seizures) were not different from those of the background, while in the brain stem of the "0" strain the levels of IL-1ß were lower than in the background (40.28%, p < 0.01). Thus, the differences between the background levels of cytokines and those after the action of sound were different in the rats with different proneness to AE. These data suggest involvement of the analyzed cytokines in pathophysiology of the seizure state, namely in AE seizures.

Diffuse reflectance spectroscopy of the cartilage tissue in the fourth optical window.

Studies of the optical properties of biological tissues in the infrared range have demonstrated significant potential for diagnostic tasks. One of the insufficiently explored ranges for diagnostic problems at the moment is the fourth transparency window, or short wavelength infrared region II (SWIR II). A Cr2+:ZnSe laser with tuning capability in the range from 2.1 to 2.4 µm was developed to explore the possibilities in this region. The capability of diffuse reflectance spectroscopy to analyze water and collagen content in biosamples was investigated using the optical gelatin phantoms and the cartilage tissue samples during their drying process. It was demonstrated that decomposition components of the optical density spectra correlated with the partial content of the collagen and water in the samples. The present study indicates the possibility of using this spectral range for the development of diagnostic methods, in particular, for observation of the changes in the content of cartilage tissue components in degenerative diseases such as osteoarthritis.

Chemogenetic emulation of intraneuronal oxidative stress affects synaptic plasticity.

Oxidative stress, a state of disrupted redox signaling, reactive oxygen species (ROS) overproduction, and oxidative cell damage, accompanies numerous brain pathologies, including aging-related dementia and Alzheimer's disease, the most common neurodegenerative disorder of the elderly population. However, a causative role of neuronal oxidative stress in the development of aging-related cognitive decline and neurodegeneration remains elusive because of the lack of approaches for modeling isolated oxidative injury in the brain. Here, we present a chemogenetic approach based on the yeast flavoprotein d-amino acid oxidase (DAAO) for the generation of intraneuronal hydrogen peroxide (H2O2). To validate this chemogenetic tool, DAAO and HyPer7, an ultrasensitive genetically encoded H2O2 biosensor, were targeted to neurons. Changes in the fluorescence of HyPer7 upon treatment of neurons expressing DAAO with d-norvaline (D-Nva), a DAAO substrate, confirmed chemogenetically induced production of intraneuornal H2O2. Then, using the verified chemogenetic tool, we emulated isolated intraneuronal oxidative stress in acute brain slices and, using electrophysiological recordings, revealed that it does not alter basal synaptic transmission and the probability of neurotransmitter release from presynaptic terminals but reduces long-term potentiation (LTP). Moreover, treating neurons expressing DAAO with D-Nva via the patch pipette also decreases LTP. This observation indicates that isolated oxidative stress affects synaptic plasticity at single cell level. Our results broaden the toolset for studying normal redox regulation in the brain and elucidating the role of oxidative stress to the pathogenesis of cognitive aging and the early stages of aging-related neurodegenerative diseases. The proposed approach is useful for identification of early markers of neuronal oxidative stress and may be used in screens of potential antioxidants effective against neuronal oxidative injury.

Parental Burnout Assessment (PBA) in Different Hispanic Countries: An Exploratory Structural Equation Modeling Approach.

Parental burnout is a unique and context-specific syndrome resulting from a chronic imbalance of risks over resources in the parenting domain. The current research aims to evaluate the psychometric properties of the Spanish version of the Parental Burnout Assessment (PBA) across Spanish-speaking countries with two consecutive studies. In Study 1, we analyzed the data through a bifactor model within an Exploratory Structural Equation Modeling (ESEM) on the pooled sample of participants (N = 1,979) obtaining good fit indices. We then attained measurement invariance across both gender and countries in a set of nested models with gradually increasing parameter constraints. Latent means comparisons across countries showed that among the participants' countries, Chile had the highest parental burnout score, likewise, comparisons across gender evidenced that mothers displayed higher scores than fathers, as shown in previous studies. Reliability coefficients were high. In Study 2 (N = 1,171), we tested the relations between parental burnout and three specific consequences, i.e., escape and suicidal ideations, parental neglect, and parental violence toward one's children. The medium to large associations found provided support for the PBA's predictive validity. Overall, we concluded that the Spanish version of the PBA has good psychometric properties. The results support its relevance for the assessment of parental burnout among Spanish-speaking parents, offering new opportunities for cross-cultural research in the parenting domain.

Safety and immunogenicity of inactivated whole virion vaccine CoviVac against COVID-19: a multicenter, randomized, double-blind, placebo-controlled phase I/II clinical trial

We present the results of a randomized, double-blind, placebo-controlled, multi-center clinical trial of the tolerability, safety, and immunogenicity of the inactivated whole virion concentrated purified coronavirus vaccine CoviVac in adult volunteers aged 18-60. Safety of the vaccine was assessed in 398 volunteers who received two doses of the vaccine (n=298) or placebo (n=100). The studied vaccine has shown good tolerability and safety. No deaths, serious adverse events (AE), or other significant AE related to vaccination have been detected. The most common AE in vaccinated participants was pain at the injection site (p<0.05). Immunogenicity assessment was performed in 167 volunteers (122 vaccinated and 45 in Placebo Group) separately for the participants who were anti-SARS-CoV-2 nAB negative (69/122 in Vaccine Group and 28/45 in Placebo Group) or positive (53/122 in Vaccine Group and 17/45 in Placebo Group) at screening. At Day 42 after the first immunization the seroconversion rate in participants who were seronegative at screening was 86.9% with average the geometric mean neutralizing antibody (nAB) titer of 1:20. Statistically significant (p<0.05) increase of IFN-{gamma} production by peptide-stimulated T-cells was observed at Days 14 and 21 after the first immunization. In participants who were seropositive at screening but had nAB titers below 1:256 the rate of 4-fold increase in nAB levels was 85.2%, while in the participants with nAB titers >1:256 the rate of 4-fold increase in nAB levels was below 45%. For the participants who were seropositive at screening the second immunization did not lead to a significant increase in nAB titers. In conclusion, inactivated vaccine CoviVac has shown good tolerability and safety, with 86.9% seroconversion rates in participants, who were seronegative at screening. In participants who were seropositive at screening and had nAB titers below 1:256, a single immunization lead to a 4-fold increase in nAB levels in 85.2% cases.

Rodent Brain Pathology, Audiogenic Epilepsy.

The review presents data which provides evidence for the internal relationship between the stages of rodent audiogenic seizures and post-ictal catalepsy with the general pattern of animal reaction to the dangerous stimuli and/or situation. The wild run stage of audiogenic seizure fit could be regarded as an intense panic reaction, and this view found support in numerous experimental data. The phenomenon of audiogenic epilepsy probably attracted the attention of physiologists as rodents are extremely sensitive to dangerous sound stimuli. The seizure proneness in this group shares common physiological characteristics and depends on animal genotype. This concept could be the new platform for the study of epileptogenesis mechanisms.

Assisted dorso-lumbar instrumentation with O-arm neuronavegation and minimally invasive surgery: clinical-surgical outcome.

OBJECTIVE: To evaluate the clinical-surgical outcomes after dorso-lumbar instrumentation using O-arm assisted neuronavigation and minimally invasive surgery. METHOD: In this retrospective cohort, 104 patients who underwent dorso-lumbar instrumentation with the use of O-arm from September 2013 to May 2020 were studied. Variables investigated included: symptoms, number of screws, levels approached, bleeding, surgical time, hospital stay, complications and clinical improvement after the surgical procedure. RESULTS: The most frequent symptoms were: unilateral or bilateral radiculopathy of the pelvic extremities, paresthesia, mechanical low back pain and progressive decrease in strength. A total of 542 screws were placed, with the lumbar spine being the site with the highest prevalence. The average bleeding, surgical time, and hospital stay was: 50 ml, 160 minutes, and 24 hours, respectively. The most frequent complications were: Residual neuropathy, dura mater tear and surgical site infection. Clinical improvement at 24 hours, 4 weeks and 6 months was achieved in: 77.3%, 86.5% y 94.8% of the patients, respectively. CONCLUSIONS: Neuronavigation with the use of O-arm along with mini-open surgery approach results in good clinical-surgical outcomes in the correction of complex disorders of the dorso-lumbar spine.

OBJETIVO: Evaluar los resultados clínico-quirúrgicos de la instrumentación dorso-lumbar mediante neuronavegación asistida con O-arm y cirugía mínimamente invasiva. MÉTODO: En esta cohorte retrospectiva se estudiaron 104 pacientes sometidos a instrumentación dorso-lumbar con uso de O-arm, operados entre septiembre de 2013 y mayo de 2020. Las variables investigadas fueron sintomatología, cantidad de tornillos, niveles abordados, sangrado, tiempo quirúrgico, estancia hospitalaria, complicaciones y mejoría clínica posterior al procedimiento quirúrgico. RESULTADOS: La sintomatología más frecuente fue radiculopatía unilateral o bilateral de extremidades pélvicas, parestesias, lumbalgia mecánica y disminución progresiva de la fuerza. Se utilizaron en total 542 tornillos, siendo la columna lumbar el sitio de mayor prevalencia. Los promedios de sangrado, tiempo quirúrgico y estancia hospitalaria fueron de 50 ml, 160 minutos y 24 horas, respectivamente. Las complicaciones más frecuentes fueron neuropatía residual, rasgadura de la duramadre e infección del sitio quirúrgico. La mejoría clínica a las 24 horas, 4 semanas y 6 meses se logró en el 77.3%, el 86.5% y el 94.8% de los pacientes, respectivamente. CONCLUSIONES: La neuronavegación con O-arm junto con el abordaje quirúrgico de tipo mini-open permite buenos resultados clínico-quirúrgicos en la corrección de los trastornos complejos de la columna dorso-lumbar.

Recent advances in nucleotide analogue-based techniques for tracking dividing stem cells: An overview.

Detection of thymidine analogues after their incorporation into replicating DNA represents a powerful tool for the study of cellular DNA synthesis, progression through the cell cycle, cell proliferation kinetics, chronology of cell division, and cell fate determination. Recent advances in the concurrent detection of multiple such analogues offer new avenues for the investigation of unknown features of these vital cellular processes. Combined with quantitative analysis, temporal discrimination of multiple labels enables elucidation of various aspects of stem cell life cycle in situ, such as division modes, differentiation, maintenance, and elimination. Data obtained from such experiments are critically important for creating descriptive models of tissue histogenesis and renewal in embryonic development and adult life. Despite the wide use of thymidine analogues in stem cell research, there are a number of caveats to consider for obtaining valid and reliable labeling results when marking replicating DNA with nucleotide analogues. Therefore, in this review, we describe critical points regarding dosage, delivery, and detection of nucleotide analogues in the context of single and multiple labeling, outline labeling schemes based on pulse-chase, cumulative and multilabel marking of replicating DNA for revealing stem cell proliferative behaviors, and determining cell cycle parameters, and discuss preconditions and pitfalls in conducting such experiments. The information presented in our review is important for rational design of experiments on tracking dividing stem cells by marking replicating DNA with thymidine analogues.

Long-term humoral immunogenicity, safety and protective efficacy of inactivated vaccine against COVID-19 (CoviVac) in preclinical studies.

The unprecedented in recent history global COVID-19 pandemic urged the implementation of all existing vaccine platforms to ensure the availability of the vaccines against COVID-19 to every country in the world. Despite the multitude of high-quality papers describing clinical trials of different vaccine products, basic detailed data on general toxicity, reproductive toxicity, immunogenicity, protective efficacy and durability of immune response in animal models are scarce. Here, we developed a ß-propiolactone-inactivated whole virion vaccine CoviVac and assessed its safety, protective efficacy, immunogenicity and stability of the immune response in rodents and non-human primates. The vaccine showed no signs of acute/chronic, reproductive, embryo- and fetotoxicity, or teratogenic effects, as well as no allergenic properties in studied animal species. The vaccine induced stable and robust humoral immune response both in form of specific anti-SARS-CoV-2 IgG and NAbs in mice, Syrian hamsters, and common marmosets. The NAb levels did not decrease significantly over the course of one year. The course of two immunizations protected Syrian hamsters from severe pneumonia upon intranasal challenge with the live virus. Robustness of the vaccine manufacturing process was demonstrated as well. These data encouraged further evaluation of CoviVac in clinical trials.

"Flora of Russia" on iNaturalist: a dataset.

BACKGROUND: The "Flora of Russia" project on iNaturalist brought together professional scientists and amateur naturalists from all over the country. Over 10,000 people were involved in the data collection. NEW INFORMATION: Within 20 months, the participants accumulated 750,143 photo observations of 6,857 species of the Russian flora. This constitutes the largest dataset of open spatial data on the country's biodiversity and a leading source of data on the current state of the national flora. About 87% of all project data, i.e. 652,285 observations, are available under free licences (CC0, CC-BY, CC-BY-NC) and can be freely used in scientific, educational and environmental activities.

Interaction between thrombin and oligonucleotide RA36 is a two-stage process.

Oligonucleotide RA36 contains two G-quadruplex modules with thrombin binding aptamer sequence GGTTGGTGTGGTTGG. Each of the modules potentially can bind thrombin while differing in functional activity. Despite that, previously published studies report a single dissociation constant for the thrombin:RA36 complex, which value varies widely. Here we address this discrepancy using electrophoretic mobility shift assay. Our results reveal that the interaction between RA36 and thrombin is a two-stage process. The two modules have different affinities for thrombin, which explains the discrepancy in the published data.

Species richness and taxonomic composition of trawl macrofauna of the North Pacific and its adjacent seas.

A checklist is presented of animal species obtained in 68,903 trawl tows during 459 research surveys performed by the Pacific Research Fisheries Center (TINRO-Center) over an area measuring nearly 25 million km2 in the Chukchi and Bering seas, Sea of Okhotsk, Sea of Japan and North Pacific Ocean in 1977-2014 at depths of 5 to 2,200 m. The checklist comprises 949 fish species, 588 invertebrate species, and four cyclostome species (some specimens were identified only to genus or family level). For each species details are given on the type of trawl (benthic and/or pelagic) and basins where the species was found. Comprehensiveness of data, taxonomic composition of catches, dependence of species richness on the survey area, sample size, and habitat, are considered. Ratios of various taxonomic groups of trawl macrofauna in pelagic and benthic zones and in different basins are analysed. Basins are compared based on species composition.

Association between Type 1 Modic Changes and Propionibacterium Acnes Infection in the Cervical Spine: An Observational Study.

BACKGROUND AND PURPOSE: Research on the association between Propionibacterium acnes in the disc space and type 1 Modic changes in adjacent vertebrae is limited and has produced mixed results. The prevalence of bacteria in intervertebral discs contradicts the prior understanding that skeletal areas in the human anatomy are sterile; yet it opens new treatment possibilities. We investigated the relationship of P acnes and type 1 Modic changes in the cervical spine. MATERIALS AND METHODS: Over a 36-month period, we collected intraoperative biopsies of patients undergoing a routine cervical spine operation for degenerative disc diseases. The disc material was cultured aerobically and anaerobically for 7 days. All preoperative MR images were evaluated for Modic changes by a board-certified neuroradiologist. Medical records were reviewed for other spine interventions before the operation. RESULTS: The study population consisted of 48 patients. Of these, 14 patients tested positive for P acnes (29%) at ≥1 level. Additionally, 13 patients had type 1 Modic changes (27%) at ≥1 level; 54% (95% CI, 27%-84%) of patients who had type 1 Modic changes were also positive for P acnes compared with 20% (95% CI, 7%-33%) of patients without type 1 Modic changes. The difference between these proportions was 34% (95% CI, 4%-64%). The Fisher exact test produced a P value of .03 for the association between P acnes and MC1, and .53 for the association between P acnes and prior procedures. CONCLUSIONS: We conclude that P acnes was prevalent in the degenerated cervical spine and that type 1 Modic changes were predictive of a culture positive for P acnes. We also found that the prevalence of P acnes was not associated with previous interventions. If these results are validated by future studies, they could have a major impact on the standard of care for back and neck pain.

Towards the interaction between calcium carbide and water during gas-chromatographic determination of trace moisture in ultra-high purity ammonia.

The current study focuses on the processes involved during the flow conversion of water into acetylene in a calcium carbide reaction cell for the trace moisture analysis of ammonia by reaction gas chromatography. The factors negatively affecting the reproducibility and the accuracy of the measurements are suggested and discussed. The intramolecular reaction of the HOCaCCH intermediate was found to be a side reaction producing background acetylene during the contact of wet ammonia gas with calcium carbide. The presence of the HOCaCCH intermediate among the reaction products is confirmed by an FTIR spectral study of calcium carbide powder exposed to wet gas. The side reaction kinetics is evaluated experimentally and its influence on the results of the gas chromatographic measurements is discussed in relation to the determination of the optimal operating parameters for ammonia analysis. The reaction gas chromatography method for the trace moisture measurements in an ammonia matrix was experimentally compared to an FTIR long-path length gas cell technique to evaluate the accuracy limitations and the resource intensity.

Neurobiological parameters in quantitative prediction of treatment outcome in schizophrenic patients.

The aim of the study was to reveal the set of neurobiological parameters informative for individual quantitative prediction of therapeutic response in schizophrenic patients. Correlation and regression analyses of quantitative clinical scores (by Positive And Negative Syndromes Scale - PANSS), together with background EEG spectral power values and four immunological parameters: enzymatic activity of leukocyte elastase and of alpha-1 proteinase inhibitor, as well as serum levels of autoantibodies to common myelin protein and to nerve growth factor, were performed in 50 patients (all females, aged 32.9±10.8 years) with hallucinatory-delusional disorders in the frames of attack-like paranoid schizophrenia. Background neurobiological data obtained before the beginning of syndrome based treatment course (at visit 1) were matched with PANSS clinical scores of the same patients after treatment course at the stage of remission establishment (at visit 2). The multiple linear regression equations were created which contained only 3 to 4 (from initial 80) background EEG parameters and one of four immunological parameters. These mathematical models allowed prediction from 65% to 76% of PANSS scores variance after treatment course (at visit 2). The data obtained may be used for elaboration of methods of individual quantitative prediction of treatment outcome in schizophrenic patients.

Safety and efficacy of p62 DNA vaccine ELENAGEN in a first-in-human trial in patients with advanced solid tumors.

Elenagen is a plasmid encoding p62/SQSTM1, the first DNA vaccine possessing two mutually complementing mechanisms of action: it elicits immune response against p62 and mitigates systemic chronic inflammation. Previously, Elenagen demonstrated anti-tumor efficacy and safety in rodent tumor models and spontaneous tumors in dogs. This multicenter I/IIa trial evaluated safety and clinical activity of Elenagen in patients with advanced solid tumors. Fifteen patients were treated with escalating doses of Elenagen (1- 5 mg per doses, 5 times weekly) and additional 12 patients received 1 mg dose. Ten patients with breast and ovary cancers that progressed after Elenagen were then treated with conventional chemotherapy. Adverse events (AE) were of Grade 1; no severe AE were observed. Cumulatively twelve patients (44%) with breast, ovary, lung, renal cancer and melanoma achieved stable disease for at least 8 wks, with 4 of them (15%) had tumor control for more than 24 wks, with a maximum of 32 wks. The patients with breast and ovary cancers achieved additional tumor stabilization for 12-28 wks when treated with chemotherapy following Elenagen treatment. Therefore, Elenagen demonstrated good safety profile and antitumor activity in advanced solid tumors. Especially encouraging is its ability to restore tumor sensitivity to chemotherapy.

Visualization of Electron Paramagnetic Resonance Hyperfine Structure Coupling Pathways.

The close relation between the EPR hyperfine coupling constant and NMR indirect spin-spin coupling constant is well-known. For example, the Karplus-type dependence of hyperfine constants on the dihedral angle, originally proposed for NMR spin-spin coupling, is widely used in pNMR studies. In the present work we propose a new tool for visualization of hyperfine coupling pathways based on our experience with visualization of NMR indirect spin-spin couplings. The plotted 3D-function is the difference between the total electron densities when the magnetic moment of the nucleus of interest changes its sign and as such is an observable from the physical point of view. It has been shown that it is proportional to the linear response of the spin density to the nuclear spin (i.e., magnetic moment). In contrast to the widely used visualization of spin density, our new approach depicts only the part of the electron cloud of a molecule that is affected by the interaction of the unpaired electron(s) with the desired nuclear magnetic moment. Because visualization of NMR spin-spin couplings and hyperfine interaction is based on the same ideas and done using similar techniques, it allows a direct comparison of the corresponding pathways for the two phenomena so as to analyze their resemblance and/or dissimilarity.

Genetic background contributes to the co-morbidity of anxiety and depression with audiogenic seizure propensity and responses to fluoxetine treatment.

BACKGROUND: Anxiety and depression are the most frequent comorbidities of different types of convulsive and non-convulsive epilepsies. Increased anxiety and depression-like phenotype have been described in the genetic absence epilepsy models as well as in models of limbic epilepsy and acquired seizure models, suggesting a neurobiological connection. However, whether anxiety and/or depression are comorbid to audiogenic epilepsy remains unclear. The aim of this study was to investigate whether anxiety or depression-like behavior can be found in rat strains with different susceptibility to audiogenic seizures (AS) and whether chronic fluoxetine treatment affects this co-morbidity. METHODS: Behavior in the elevated plus-maze and the forced swimming test was studied in four strains: Wistar rats non-susceptible to AS; Krushinsky-Molodkina (KM) strain, selectively bred for AS propensity from outbred Wistar rats; and a selection lines bred for maximal AS expression (strain "4") and for a lack of AS (strain "0") from KM×Wistar F2 hybrids. Effects of chronic antidepressant treatment on AS and behavior were also evaluated. RESULTS: Anxiety and depression levels were higher in KM rats (with AS) compared with Wistar rats (without AS), indicating the comorbidity with AS. However, in strains "4" and "0" with contrasting AS expression, but with a genetic background close to KM rats, anxiety and depression were not as divergent as in KMs versus Wistars. Fluoxetine treatment exerted an antidepressant effect in all rat strains irrespective of its effect on AS. CONCLUSIONS: Genetic background contributes substantively to the co-morbidity of anxiety and depression with AS propensity.