RESUMEN

Leptomeningeal metastases are lesions of brain and/or spinal cord sheaths by tumor cells. They occur in 5% of patients with solid tumors, although autopsies reveal these lesions much more often (10-20% of cases). Leptomengeal metastases are an unfavorable prognostic factor. Despite the modern NCCN treatment standards, including intrathecal therapy (ITT), such patients receive only irradiation of the entire brain and/or spinal cord in most cases. OBJECTIVE: To evaluate the effectiveness of ITT in patients with leptomeningeal metastases in breast cancer. MATERIAL AND METHODS: Twenty-five patients with breast cancer and leptomeningeal metastases underwent intrathecal administration of methotrexate between 2016 and 2022. Intrathecal chemotherapy was administered through lumbar puncture. We performed an intensive course (intrathecal methotrexate 15 mg 2 times a week for 1 month (8 injections), then intrathecal methotrexate 15 mg 1 time a week (4 injections), and then 15 mg 1 time a month until progression or unacceptable toxicity). RESULTS: The median duration of ITT was 2.5 months. Complete neurological responses were observed in 3 out of 25 (12%) patients, partial neurological response - in 15 out of 25 (60%) patients, progression of neurological symptoms - in 7 (28%) patients. The number of complete cytological responses was observed in 6 out of 25 (24%) patients. The median overall survival after ITT was 6.7 months. CONCLUSION: Effectiveness of ITT is confirmed by higher quality of life (72% of patients), complete cytological responses (24%) and improvement in neuroimaging data. This is an important criterion for severe patients with limited treatment options. First-stage ITT before whole-brain irradiation is preferable, as this approach increases overall survival by 3 months. Undoubtedly, ITT is a treatment option that can be used in routine clinical practice for lesions of brain and spinal cord sheaths.

Asunto(s)

Neoplasias de la Mama , Inyecciones Espinales , Neoplasias Meníngeas , Metotrexato , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Persona de Mediana Edad , Adulto , Neoplasias Meníngeas/secundario , Neoplasias Meníngeas/tratamiento farmacológico , Metotrexato/administración & dosificación , Anciano , Carcinomatosis Meníngea/tratamiento farmacológico , Carcinomatosis Meníngea/secundario , Antimetabolitos Antineoplásicos/administración & dosificación

RESUMEN

OBJECTIVE: To assess the validity of the screening method based on EEG analysis using predictive analytics algorithms with the calculation of linear discriminant functions (LDFs), in comparison with a classification system based on psychometric self-report scales. MATERIAL AND METHODS: A comparative cross-sectional study with partial blinding involving healthy volunteers was conducted at two investigational sites. The calculated scores of LDFs used to assess risks of impulsivity, depression and anxiety acted as quantitative characteristics of subjects' mental state. Testing included completing psychometric scales. RESULTS: As a result of the performed validation of the original screening method based on EEG analysis in comparison with the scores of psychometric scales chosen as a reference method, satisfactory results were obtained with the best parameters of sensitivity, specificity, and accuracy for detecting high levels of impulsivity associated with pronounced aggressiveness. Of considerable interest is also the direct correlation found between high levels of LDF impulsivity scores and high levels of self-rated aggression on a psychometric scale (BPAQ-24). CONCLUSION: The results open up the possibility of using the proposed method to predict a number of emotional and behavioral characteristics of subjects, including a high risk of aggressive behavior as part of professional selection.

Asunto(s)

Trastornos de Ansiedad , Electroencefalografía , Humanos , Proyectos Piloto , Estudios Transversales , Trastornos de Ansiedad/psicología , Medición de Riesgo , Psicometría , Reproducibilidad de los Resultados

RESUMEN

In this work, we synthesized two new benzo-18-azacrown-6 ethers bearing picolinate and pyridine pendant arms and studied the copper complexes of these ligands, as well as those of an acetate analog. All considered ligands were capable of forming mono- and dinuclear complexes due to their large size and large number of donor sites. Among all forms of complexes, the coordination of cations inside the macrocycle has only been shown for the mononuclear form of the acetate complex, while out-cage coordination has been observed for other forms. Electrochemical studies have shown the instability of the mononuclear form of the complex with the pyridine ligand to the reduction in the range of redox potentials of bioreductants. The stabilities of labeled acetate complexes with "in-cage" coordination of the cation and picolinate with "out-cage" coordination were compared in an excess of serum and superoxide dismutase; while the former turned out to be unstable to transchelation, the latter was stable throughout the experiment. Additional studies in biologically relevant media were performed for the picolinate complex and demonstrated its stability in vitro. The biodistribution of this complex in mice after 6 hours post-injection demonstrates a slow excretion from the body; however, the accumulation is noticeably lower than that of free copper cations.

Asunto(s)

Quelantes , Cobre , Ratones , Animales , Cobre/química , Distribución Tisular , Ligandos , Piridinas

RESUMEN

The authors present a patient and neurosurgical nuances of total resection of recurrent meningioma of posterior surface of petrous bone 65´35´30 mm. The tumor captured two critical zones of posterior cranial fossa with unusual frontal growth and spread from the surface of petrous bone to the fourth ventricle. The neoplasm filled the ventricle without lesion of ependyma. Extensive fibrous meningioma of posterior surface of petrous bone was totally excised 18 years ago. MRI was annually carried out for 5 years. Surgical nuances that ensured total extraction of tumor without cytoreduction were as follows: 1) en-bloc resection of tumor from the fourth ventricle due to smooth surface of tumor and minimum number of adhesions with cerebellum; MR-confirmed CSF strip between the tumor edges and walls of the ventricle; no signs of hydrocephalus in subtotal ventricular tamponade; 2) unusual frontal tumor growth under 45º required appropriate angular traction of tumor with minimal rotation; 3) traction was followed by sequential appearance of 3 segments of tumor: petrous, apertural and ventricular; 4) topography of the area of lateral eversion of the fourth ventricle was established by identifying the narrowing (constriction) of tumor; 5) in extracting the tumor from the fourth ventricle, we performed minimal rotation to avoid damage to ventricular walls and lateral aperture due to difference between the larger and smaller diameters (by 6 mm) of ovoid ventricular segment of tumor; 6) no CSF leakage following appearance of ventricular segment (tumor enlargement) indicated integrity of ependyma of the fourth ventricle. Histological examination confirmed fibrous meningioma. Fast and complete regression of focal symptoms was observed after surgery. A 3-year follow-up after surgery revealed no signs of tumor recurrence.

Asunto(s)

Neoplasias Meníngeas , Meningioma , Fosa Craneal Posterior/patología , Cuarto Ventrículo/diagnóstico por imagen , Cuarto Ventrículo/cirugía , Humanos , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/cirugía , Meningioma/diagnóstico por imagen , Meningioma/patología , Meningioma/cirugía , Procedimientos Neuroquirúrgicos , Hueso Petroso/patología , Hueso Petroso/cirugía

RESUMEN

We identify the physical factors that limit the terahertz (THz) yield of an optical rectification (OR) of ultrashort multiterawatt laser pulses in large-area quadratically nonlinear crystals. We show that the THz yield tends to slow its growth as a function of the laser driver energy, saturate, and eventually decrease as the laser beam picks up a spatiotemporal phase due to the intensity-dependent refraction of the OR crystal. We demonstrate that, with a careful management of the driver intensity aimed at keeping the nonlinear length larger than the coherence length, OR-based broadband THz generation in large-area lithium niobate (LN) crystals is energy-scalable, enabling an OR of multiterawatt laser pulses, yielding ∼10µJ/cm2 of THz output energy per unit crystal area. With a 27-fs, 10-TW, 800-nm Ti:sapphire laser output used as a driver for OR in large-area LN crystals, this approach is shown to provide a THz output with a pulse energy above 10 µJ and a bandwidth extending well beyond 6 THz, supporting single-cycle THz waveforms.

RESUMEN

Spectral analysis of high-order harmonics generated by ultrashort mid-infrared pulses in molecular nitrogen reveals well-resolved signatures of inverse Raman scattering, showing up near the frequencies of prominent vibrational transitions of nitrogen molecules. When tuned on a resonance with the v'=0→v''=0 pathway within the B3Πg→C3Πu second positive system of molecular nitrogen, the eleventh harmonic of a 3.9 µm, 80 fs driver is shown to acquire a distinctive antisymmetric spectral profile with red-shifted bright and blue-shifted dark features as indicators of stimulated Raman gain and loss. This high-harmonic setting extends the inverse Raman effect to a vast class of strong-field light-matter interaction scenarios.

RESUMEN

Ultrafast ionization of a gas medium driven by ultrashort midinfrared laser pulses provides a source of bright ultrabroadband radiation whose spectrum spans across the entire microwave band, reaching for the sub-gigahertz range. We combine multiple, mutually complementary detection techniques to provide an accurate polarization-resolved characterization of this broadband output as a function of the gas pressure. At low gas pressures, the lowest-frequency part of this output is found to exhibit a drastic enhancement as this field builds up its coherence, developing a well-resolved emission cone, dominated by a radial radiation energy flux. This behavior of the intensity, coherence, and polarization of the microwave output is shown to be consistent with Cherenkov-type radiation by ponderomotively driven plasma currents.

RESUMEN

Background. Previously, treatment of women with brain metastases following reproductive system cancers was palliative and included whole brain radiotherapy. Currently, treatment approaches have changed and life expectancy has increased. Nevertheless, the role of surgical treatment in these patients is still discussed. OBJECTIVE: To demonstrate an appropriateness and role of neurosurgical care in the complex management of women with brain metastases following reproductive system cancers. MATERIAL AND METHODS: There were 78 women with brain metastases following reproductive system cancer. All patients were treated at the Blokhin National Cancer Medical Research Center for the period 2004-2019. We have also reviewed the literature data for the last 30 years.Results and discussion. Resection of brain metastases in complex treatment of endometrial, ovarian and cervical cancer ensured favorable long-term survival in our material. Thus, mean life expectancy after resection of brain metastases was 16.3 months in patients with ovarian cancer, uterine cancer - 15.6 months, cervical cancer - 10.25 months. Obviously, surgery is not indicated in all cases. However, this approach improves local control and should be used in combination with other treatment methods for improvement of life expectancy and its quality in certain patients. CONCLUSION: Selective surgical approach should be essential in the treatment of patients with brain metastases following reproductive system cancer. A multidisciplinary approach ensures the best treatment outcomes.

Asunto(s)

Neoplasias Encefálicas , Neoplasias Encefálicas/cirugía , Femenino , Genitales Femeninos , Humanos , Resultado del Tratamiento

RESUMEN

OBJECTIVE: To search for electroencephalographic markers of alexithymia in patients with moderate depression. MATERIAL AND METHODS: Sixty-four right-handed inpatients (20 men and 44 women, mean age 29.3+10.7 years), were studied. The level of alexithymia was assessed by the Russian version of the Toronto Alexithymia Scale (TAS-20-R). Patients were stratified into 4 groups by TAS-20-R scores. Two main groups of 22 patients each included people with high (>60 scores) and low (20-51 scores) levels of alexithymia. Control groups included 10 patients with 60-85 scores and 10 patients with 52-54 scores. Current methods of electroencephalographic analysis were used. RESULTS: Alexithymia in patients with moderate depression is characterized by a restructuring of the integrative activity of the brain detected by electroencephalography at rest. Patients with high alexithymia differ from those with low alexithymia by (1) lower values of the real part of the coherence between the frontal and anterior temporal leads of the left hemisphere in the band 28-30 Hz; (2) lower values of the imaginary part of coherence in the band 11-12 Hz between the posterior temporal and parietal as well as the posterior temporal and occipital cortical zones of the right hemisphere; (3) higher rates of the real part of the coherence between the right frontal and central leads in the frequency ranges 12-14 and 6-7 Hz; (4) large values of the imaginary part of the coherence between the left parietal and right posterior temporal cortex in the band 24-26 Hz; (5) higher values of the square of the coherence modulus between the left frontal and anterior temporal cortical zones in the band 17-18 Hz. CONCLUSION: Large cortical representations with involvement of theta, alpha, beta-1 and beta-2 rhythms can contribute to the pathogenesis of alexithymia.

Asunto(s)

Síntomas Afectivos , Depresión , Adolescente , Adulto , Síntomas Afectivos/diagnóstico , Encéfalo , Electroencefalografía , Femenino , Humanos , Masculino , Federación de Rusia , Adulto Joven

RESUMEN

BACKGROUND: A search for accurate linear discriminant function (LDF) allowing the diagnosis of schizophrenia and estimation of treatment effectiveness according to EEG is an urgent problem. OBJECTIVE: To develop a methodology for discriminant EEG analysis for minimizing the overlearning effect, selection of optimal LDF model and evaluation of its generalizing ability. MATERIAL AND METHODS: Two hundred and twenty patients with schizophrenia and 1400 people without psychiatric diseases, who were comparable in basic characteristics, were enrolled. EEG was recorded using 16 leads, 10-20 system and aural reference electrodes. EEG was processed by spectral and coherent analysis. RESULTS: After linear discriminant analysis, LDF was obtained to differentiate people with schizophrenia from healthy subjects and a formula was selected from LDF that included 8 predictors (spectral and coherent parameters of standard EEG ranges theta, alpha and beta) with 90% sensitivity and 80% specificity, significance level for Wilks' lambda p<3.9E-28 and the Mahalanobis distance between training set centroids 4,6. CONCLUSION: A method for obtaining optimal LDF models and selection the best one with further LDF generalizing ability assessment is suggested.

Asunto(s)

Esquizofrenia , Diagnóstico Diferencial , Análisis Discriminante , Electroencefalografía , Humanos , Sensibilidad y Especificidad

RESUMEN

Serum levels of glial fibrillar acidic protein (GFAP) were analyzed in 317 patients with primary and metastatic tumors of the brain, 78 patients with neurological diseases, and 66 normal subjects. A significant increase in the basal level of GFAP was typical of patients with glioblastomas in comparison with other groups (patients with astrocytomas, cerebral metastases, benign tumors, non-tumor diseases, and healthy subjects). An association of GFAP levels with unfavorable prognosis of overall survival in patients with glioblastoma was revealed. The data attest to high specificity and sensitivity of GFAP as a biochemical marker of glioblastoma.

Asunto(s)

Astrocitoma/genética , Biomarcadores de Tumor/genética , Neoplasias Encefálicas/genética , Proteína Ácida Fibrilar de la Glía/genética , Glioblastoma/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/genética , Astrocitoma/sangre , Astrocitoma/diagnóstico , Astrocitoma/mortalidad , Biomarcadores de Tumor/sangre , Encéfalo/metabolismo , Encéfalo/patología , Neoplasias Encefálicas/sangre , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/mortalidad , Estudios de Casos y Controles , Femenino , Proteína Ácida Fibrilar de la Glía/sangre , Glioblastoma/sangre , Glioblastoma/diagnóstico , Glioblastoma/mortalidad , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/sangre , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/genética , Neuroglía/metabolismo , Neuroglía/patología , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/genética , Pronóstico , Análisis de Supervivencia

RESUMEN

Coherent-wake plasma emission induced by ultrashort mid-infrared laser pulses on a solid target is shown to give rise to high-brightness, high-order harmonic radiation, offering a promising source of attosecond pulses and a probe for ultrafast subrelativistic plasma dynamics. With 80-fs, 0.2-TW pulses of 3.9-µm radiation used as a driver, optical harmonics up to the 34th order are detected, with their spectra stretching from the mid-infrared region to the extreme ultraviolet region. The harmonic spectrum is found to be highly sensitive to the chirp of the driver. Particle-in-cell analysis of this effect suggests, in agreement with the generic scenario of coherent-wake emission, that optical harmonics are radiated as trains of extremely short, attosecond ultraviolet pulses with a pulse-to-pulse interval varying over the pulse train. A positive chirp of the driver pulse can partially compensate for this variation in the interpulse separation, allowing harmonics of the highest orders to be generated in the plasma emission spectrum.

RESUMEN

Formation of light bullets-tightly localized in space and time light packets, retaining their spatiotemporal shape during propagation-is, for the first time, experimentally observed and investigated in a new regime of mid-infrared filamentation in ambient air. It is suggested that the light bullets generated in ambient air by multi-mJ, positively chirped 3.9-µm pulses originate from a dynamic interplay between the anomalous dispersion in the vicinity of CO2 resonance and positive chirp, both intrinsic, carried by the driver pulse, and accumulated, originating from nonlinear propagation in air. By adjusting the initial chirp of the driving pulses, one can control the spatial beam profile, energy losses, and spectral-temporal dynamics of filamenting pulses and deliver sub-3-cycle mid-IR pulses in high-quality beam on a remote target.

RESUMEN

Polarization maps of high-order harmonics are shown to enable a full vectorial characterization of petahertz electron currents generated in a crystalline solid by an ultrashort laser driver. As a powerful resource of this methodology, analysis of energy-momentum dispersion landscapes, defined by the electron band structure, can help identify, as our analysis shows, special directions within the Brillouin zone that can provide a preferable basis for polarization-sensitive high-harmonic mapping of anisotropic petahertz photocurrents in solids.

RESUMEN

AIM: There have been no criteria found so far to quantify the wide range of EEG spectral and coherent indicators, which would allow discrimination between schizophrenia disorders and healthy human states. The goal of this research is to find objective EEG-based schizophrenia criteria through a discriminant analysis and to obtain a linear discriminant function (LDF) with sensitivity and specificity of at least 85%. MATERIAL AND METHODS: The study covered 83 schizophrenia patients and 116 healthy individuals, with similar major characteristics. EEGs were recorded in EDF format using 16 leads under the 10-20 system and ear reference electrodes, with further spectral and coherent analysis. RESULTS: A discriminant analysis has provided LDFs from which a formula with 5 predictors was extracted. The most valuable diagnostic predictors were beta2 and theta rhythm powers in the F3 lead. In the same manner, interhemispheric theta rhythm coherence in the pair T5-T6 and interhemispheric beta rhythm coherence in the pairs F3-C3 and T3-C3 were significant predictors. All of them being negative, the EEG supplied thereby most likely relates to the schizophrenia class. CONCLUSION: The novel methods used for selecting EEG features and choosing their combinations to obtain LDFs and verify the outcomes will give the researcher a powerful and flexible tool to perform an EEG discriminant analysis which allows obtaining linear discriminant functions in short terms without routine procedures, performance of preliminary diagnosis using an expert system based on the obtained LDF, evaluation of treatment efficacy by the LDF score dynamics. During treatment and changes of predicting modules function, variables may increase or decrease depending on the direction of predictors that may serve as an indicator of treatment efficacy.

Asunto(s)

Electroencefalografía , Esquizofrenia , Ritmo beta , Análisis Discriminante , Humanos , Ritmo Teta

RESUMEN

High-order harmonic generation (HHG) in plasmas induced by ultrashort, relativistic-intensity laser pulses on solid surfaces can provide an efficient source of attosecond pulses and opens routes toward new regimes of laser-matter interactions, x-ray generation, laser particle acceleration, and relativistic nonlinear optics. However, field intensities in the range of Irel∼1019 W/cm2 are typically needed to achieve the relativistic regime of HHG in experiments with near-infrared laser pulses. Here, we show that, in the mid-infrared range, due to the λ-2 scaling of Irel with the driver wavelength λ, relativistic HHG can be observed at much lower levels of laser field intensities. High-peak-power 80-fs, 3.9-µm pulses are focused in our experiments on a solid surface to provide field intensities in the range of 1017 W/cm2. Remarkably, this level of field intensities, considered as low by the standards of relativistic optics in the near infrared, is shown to be sufficient for generation of high-order harmonics with signature properties of relativistic HHG-beam directionality, spectra with extended plateaus, and a high HHG yield sustained for both p- and s-polarized driver fields.

RESUMEN

Properties of filaments ignited by multi-millijoule, 90 fs mid-infrared pulses centered at 3.9 µm are examined experimentally by monitoring plasma density, losses, spectral dynamics and beam profile evolution at different focusing strengths. By changing from strong (f=0.25 m) to loose (f=7 m) focusing, we observe a shift from plasma-assisted filamentation to filaments with low plasma density. In the latter case, filamentation manifests itself by beam self-symmetrization and spatial self-channeling. Spectral dynamics in the case of loose focusing is dominated by the nonlinear Raman frequency downshift, which leads to the overlap with the CO2 resonance in the vicinity of 4.2 µm. The dynamic CO2 absorption in the case of 3.9 µm filaments with their low plasma content is the main mechanism of energy losses and, either alone or together with other nonlinear processes, contributes to the arrest of intensity.

Asunto(s)

Compuestos Aza/química , Bismuto/uso terapéutico , Éteres/química , Piridinas/química , Piridinas/farmacocinética , Radioisótopos/uso terapéutico , Animales , Bovinos , Estabilidad de Medicamentos , Femenino , Marcaje Isotópico , Ratones , Modelos Moleculares , Conformación Molecular , Piridinas/sangre , Piridinas/uso terapéutico , Distribución Tisular

RESUMEN

We present experimental studies of long-distance transmission of ultrashort mid-infrared laser pulses through atmospheric air, probing air dispersion in the 3.6-4.2-µm wavelength range. Atmospheric air is still highly transparent to electromagnetic radiation in this spectral region, making it interesting for long-distance signal transmission. However, unlike most of the high-transmission regions in gas media, the group-velocity dispersion, as we show in this work, is anomalous at these wavelengths due to the nearby asymmetric-stretch rovibrational band of atmospheric carbon dioxide. The spectrograms of ultrashort mid-infrared laser pulses transmitted over a distance of 60 m in our experiments provide a map of air dispersion in this wavelength range, revealing clear signatures of anomalous dispersion, with anomalous group delays as long as 1.8 ps detected across the bandwidth covered by 80-fs laser pulses.

RESUMEN

Direct metrology of coherent short-wavelength beamlines is important for obtaining operational beam characteristics at the experimental site. However, since beam-time limitation imposes fast metrology procedures, a multi-parametric metrology from as low as a single shot is desirable. Here a two-dimensional (2D) procedure based on high-resolution Fresnel diffraction analysis is discussed and applied, which allowed an efficient and detailed beamline characterization at the SACLA XFEL. So far, the potential of Fresnel diffraction for beamline metrology has not been fully exploited because its high-frequency fringes could be only partly resolved with ordinary pixel-limited detectors. Using the high-spatial-frequency imaging capability of an irradiated LiF crystal, 2D information of the coherence degree, beam divergence and beam quality factor M2 were retrieved from simple diffraction patterns. The developed beam metrology was validated with a laboratory reference laser, and then successfully applied at a beamline facility, in agreement with the source specifications.