[The relationship of cytochrome P450 isoforms with the efficacy and safety of antipsychotic and antidepressant therapy]. / Svyaz' izoform tsitokhroma P450 s effektivnost'yu i bezopasnost'yu terapii antipsikhotikami i antidepressantami.

Cytochrome P450 (CYP450) is the leading enzyme in the biotransformation of most psychotropic drugs. CYP450 gene polymorphisms determine a patient's endophenotype with respect to the activity of enzymes of the family and affect the metabolism of prescribed antipsychotics and antidepressants. Categorizing patients by endophenotype during genotyping is likely to help simplify the selection of therapy in clinical practice. Co-prescribing drugs that may be inhibitors or inducers of CYP450 isoforms, in turn, may lead to adverse reactions or no effect of therapy. The article presents a compilation of known pharmacogenetic recommendations regarding the four major endophenotypes of metabolizers.

Imaging Breast Microcalcifications Using Dark-Field Signal in Propagation-Based Phase-Contrast Tomography.

Breast microcalcifications are an important primary radiological indicator of breast cancer. However, microcalcification classification and diagnosis may be still challenging for radiologists due to limitations of the standard 2D mammography technique, including spatial and contrast resolution. In this study, we propose an approach to improve the detection of microcalcifications in propagation-based phase-contrast X-ray computed tomography of breast tissues. Five fresh mastectomies containing microcalcifications were scanned at different X-ray energies and radiation doses using synchrotron radiation. Both bright-field (i.e. conventional phase-retrieved images) and dark-field images were extracted from the same data sets using different image processing methods. A quantitative analysis was performed in terms of visibility and contrast-to-noise ratio of microcalcifications. The results show that while the signal-to-noise and the contrast-to-noise ratios are lower, the visibility of the microcalcifications is more than two times higher in the dark-field images compared to the bright-field images. Dark-field images have also provided more accurate information about the size and shape of the microcalcifications.

[Primary amyloidoma of the brain]. / Pervichnaya amiloidoma golovnogo mozga.

Primary brain amyloidoma is rare tumor-like lesion characterized by focal accumulation of insoluble fibrillar aggregates of amyloid in brain tissue without systemic amyloidosis. Literature review and a case report of primary brain amyloidoma in 61 years old female are given with a special attention on the complexity of preoperative diagnosis.

Tomographic phase and attenuation extraction for a sample composed of unknown materials using x-ray propagation-based phase-contrast imaging.

Propagation-based phase-contrast x-ray imaging (PB-PCXI) generates image contrast by utilizing sample-imposed phase-shifts. This has proven useful when imaging weakly attenuating samples, as conventional attenuation-based imaging does not always provide adequate contrast. We present a PB-PCXI algorithm capable of extracting the x-ray attenuation  ß and refraction  δ, components of the complex refractive index of distinct materials within an unknown sample. The method involves curve fitting an error-function-based model to a phase-retrieved interface in a PB-PCXI tomographic reconstruction, which is obtained when Paganin-type phase retrieval is applied with incorrect values of δ and ß. The fit parameters can then be used to calculate true δ and ß values for composite materials. This approach requires no a priori sample information, making it broadly applicable. Our PB-PCXI reconstruction is single-distance, requiring only one exposure per tomographic angle, which is important for radiosensitive samples. We apply this approach to a breast-tissue sample, recovering the refraction component  Î´, with 0.6-2.4% accuracy compared with theoretical values.

Tomographic reconstruction using tilted Laue analyser-based X-ray phase-contrast imaging.

Analyser-based phase-contrast imaging (ABPCI) is a highly sensitive phase-contrast imaging method that produces high-contrast images of weakly absorbing materials. However, it is only sensitive to phase gradient components lying in the diffraction plane of the analyser crystal [i.e. in one dimension (1-D)]. In order to accurately account for and measure phase effects produced by the wavefield-sample interaction, ABPCI and other 1-D phase-sensitive methods must achieve 2-D phase gradient sensitivity. An inclined geometry method was applied to a Laue geometry setup for X-ray ABPCI through rotation of the detector and object about the optical axis. This allowed this traditionally 1-D phase-sensitive phase-contrast method to possess 2-D phase gradient sensitivity. Tomographic datasets were acquired over 360° of a multi-material phantom with the detector and sample tilted by 8°. The real and imaginary parts of the refractive index were reconstructed for the phantom.

[Surgical treatment of lung injuries and diseases in patients with blunt chest trauma]. / Khirurgicheskoe lechenie povrezhdenii i boleznei legkikh u patsientov s zakrytoi travmoi grudi.

OBJECTIVE: To establish the indications for optimal open lung surgery in patients with severe blunt chest injury. MATERIAL AND METHODS: Hematomas, lung wounds and purulent pulmonary complications were studied in four groups of victims. Causes of injuries included road accidents (n=426), falling and beating (n=387), catatrauma (n=217), squeezing the body with a massive weight (n=46). Majority of victims (n=731, 67.9%) were transferred to the hospital within 1-5 hours after injury; 345 (32.1%) patients were transferred from other hospitals to treat combined injuries of head, chest, abdomen and complications within 1-49 days after injury. RESULTS: Lung surgery was applied in 48 patients. Typical resections and pneumonectomies made up 77.1%. Indications for surgery included lung wounds complicated by pulmonary hemorrhage grade IIa and severe hemothorax, intrapulmonary hematoma ≥6 cm with high risk of bleeding and suppuration, gangrene, gangrenous and purulent abscesses of aspiration genesis, lung cancer first diagnosed in victims. Postoperative mortality was 14.6%. Twelve victims with unrecognized deep lung wounds and pulmonary root rupture were not operated. Thus, 5.6% of victims with severe blunt chest trauma need for open lung surgery.

Social and Cognitive Impairments in Rat Offspring after Ultrasound-Induced Prenatal Stress.

We studied the possibility of developing an autism model based on chronic prenatal psychological stress caused by variable frequency ultrasound 20-45 kHz. The offspring of female rats stressed during pregnancy demonstrated reduced time of social contacts in the social interaction test, increased anxiety in the open-field test, and memory impairment in the Morris water maze test in comparison with the control (intact) rat offspring. We also found a reducing trend in the BDNF gene expression in the amygdala in males of the experimental group. The results showed the possibility of developing the animal autism model based on prenatal stress.

[Primary splenic angiosarcoma]. / Pervichnaia angiosarkoma selezenki.

Primary splenic angiosarcoma is a rare and high-grade vascular tumor having a significant metastatic potential. The authors give the data available in the literature and describe their own case of primary splenic angiosarcoma in a 42-year-old male patient with multiple distant metastases in the lymph nodes and skin. The paper shows some difficulties in the morphologic diagnosis of this tumor.

[Morphological features of IgG4-related lesions at various sites]. / Morfologicheskie osobennosti IgG4-sviazannykh porazhenii razlichnykh lokalizatsii.

OBJECTIVE: To determine the morphological features of IgG4-related lesions and to improve pathomorphological criteria for diagnosing various clinical variants of IgG4-related disease. MATERIAL AND METHODS: Biopsy and surgical materials from 100 patients with tumor-like lesions at various sites (63 cases of IgG4-related lesion and 37 cases of non-IgG4-related inflammatory processes) were studied. Histological and immunohistochemical studies were conducted to determine the absolute counts of CD138+ cells, IgG+ and IgG4+ in the inflammatory infiltrates, as well as IgG4/IgG and IgG4/CD138 cell ratios. RESULTS: When IgG4-related disease manifested, pancreatic, lacrimal, and salivary gland lesions prevailed. Brisk lymphoplasmacytic infiltration is characteristic for tissue damage in the eye, salivary glands, thyroid, pancreas, and skin. The formation of moiré fibrosis was specific to damages to the pancreas, liver and bile ducts, and eye tissues. Obliterative phlebitis is most often observed in pancreatic and salivary gland lesions. According to international criteria, the frequency of achieving the required level of IgG4+ plasma cells in each organ was high in lesions of the pancreas, bile ducts, and lymph nodes and that was low in lesions of the salivary and lacrimal glands and skin. The IgG4+/CD138+ and IgG4+/IgG+ cell ratios exceeded 40% in all cases. CONCLUSION: The morphologic diagnosis of IgG4-related disease is based on the detection of lymphoplasmacytic infiltration, moiré fibrosis, and obliterative phlebitis, as well as on the calculation of the absolute number of IgG4+ plasma cells in the inflammatory infiltrate and on the determination of IgG4+/IgG+ and IgG4+/CD138+ cell ratios. The number of IgG4+ plasma cells depends on the location of the lesion and on the phase of the process.

Propagation-based x-ray phase-contrast tomography of mastectomy samples using synchrotron radiation.

PURPOSE: Propagation-based phase-contrast computed tomography (PB-CT) is a method for three-dimensional x-ray imaging that utilizes refraction, as well as absorption, of x rays in the tissues to increase the signal-to-noise ratio (SNR) in the resultant images, in comparison with equivalent conventional absorption-only x-ray tomography (CT). Importantly, the higher SNR is achieved without sacrificing spatial resolution or increasing the radiation dose delivered to the imaged tissues. The present work has been carried out in the context of the current development of a breast CT imaging facility at the Australian Synchrotron. METHODS: Seven unfixed complete mastectomy samples with and without breast cancer lesions have been imaged using absorption-only CT and PB-CT techniques under controlled experimental conditions. The radiation doses delivered to the mastectomy samples during the scans were comparable to those approved for mammographic screening. Physical characteristics of the reconstructed images, such as spatial resolution and SNR, have been measured and compared with the results of the radiological quality assessment of the complete absorption CT and PB-CT image stacks. RESULTS: Despite the presence of some image artefacts, the PB-CT images have outperformed comparable absorption CT images collected at the same radiation dose, in terms of both the measured objective image characteristics and the radiological image scores. The outcomes of these experiments are shown to be consistent with predictions of the theory of PB-CT imaging and previous reported experimental studies of this imaging modality. CONCLUSIONS: The results presented in this paper demonstrate that PB-CT holds a high potential for improving on the quality and diagnostic value of images obtained using existing medical x-ray technologies, such as mammography and digital breast tomosynthesis (DBT). If implemented at suitable synchrotron imaging facilities, PB-CT can be used to complement existing imaging modalities, leading to more accurate breast cancer diagnosis.

Free propagation phase-contrast breast CT provides higher image quality than cone-beam breast-CT at low radiation doses: a feasibility study on human mastectomies.

In this study we demonstrate the first direct comparison between synchrotron x-ray propagation-based CT (PB-CT) and cone-beam breast-CT (CB-CT) on human mastectomy specimens (N = 12) including different benign and malignant lesions. The image quality and diagnostic power of the obtained data sets were compared and judged by two independent expert radiologists. Two cases are presented in detail in this paper including a comparison with the corresponding histological evaluation. Results indicate that with PB-CT it is possible to increase the level of contrast-to-noise ratio (CNR) keeping the same level of dose used for the CB-CT or achieve the same level of CNR reached by CB-CT at a lower level of dose. In other words, PB-CT can achieve a higher diagnostic potential compared to the commercial breast-CT system while also delivering a considerably lower mean glandular dose. Therefore, we believe that PB-CT technique, if translated to a clinical setting, could have a significant impact in improving breast cancer diagnosis.

Features of emotional and social behavioral phenotypes of calsyntenin2 knockout mice.

Calsyntenin-2 (Clstn2) is the synaptic protein that belongs to the super family of cadherins, playing an important role in learning and memory. We recently reported that Clstn2 knockout mice (Clstn2-KO) have a deficit of GABAergic interneurons coupled with hyperactivity and deficient spatial memory. Given, that impaired functioning of GABA receptors is linked to several psychopathologies, including anxiety and autism, we sought to further characterize Clstn2-KO mice with respect to emotional and social behavior. Clstn2-KO males and females were tested in the elevated plus-maze (EPM), open field (OF), forced swim test, social affiliation and recognition test, social transmission of food preference (STFP), dyadic social interactions and marble burying test. Clstn2-KO mice demonstrated high exploration and hyperactivity in the dimly lit EPM that affect anxiety parameters. In contrast, in a more adverse situation in the OF have increased emotionality in Clstn2-KO males, not females. Assessment of hyperactivity for prolong period in the OF showed that Clstn2-KO animals were able to decline their hyperactivity, but their ambulation still remained higher than in WT littermates. Additionally, Clstn2-KO mice expressed stereotyped behavior. Strikingly, analysis of social behavior identified deficient social motivation and social recognition only in Clstn2-KO males, but not in females. Further analysis of social communication in the STFP and direct observation of agonistic interactions confirmed the reduced social behavior in Clstn2-KO males. Altogether, current results showed Clstn2 gene and sex interactions on socio-emotional performance in mice, suggesting a possible role of calsyntenin2 in psychopathological mechanisms of autism.

[Telomere-telomerase system in aging, norm and pathology (literature review)].

This literature review presents results of research showing association between functional activity of the telomere-telomerase system and mental cognitive and emotional processes in normal and various pathological states: chronic stress, depression, bipolar disorder, schizophrenia, mild cognitive impairment and dementia in aging. It also refers to age-specific, psycho-social, economic, immunological, genetic and epigenetic factors that influence these relationships.

[Gastric cancer concurrent with IgG4-related disease: A clinical case and a review of literature]. / Sochetanie raka zheludka s IgG4-svyazannoi bolezn'yu (klinicheskoe nablyudenie i obzor literatury).

The paper presents the data available in the literature on IgG4-related disease (IgG4-RD) concurrent with malignancies at different sites, as well as possible common pathogenetic mechanisms of their development and morphological diagnostic criteria for IgG4-RD. The authors give their own observation of gastric signet ring cell carcinoma concurrent with morphologically verified IgG4-RD.

[THE INTEGRATIVE LEVEL OF THE HIERARCHICAL SYSTEM OF SPATIAL ORIENTATION OF ANIMALS].

The purpose of this review is to analyze the current knowledge about the higher, integrative level of the physiological system of orientation of animals in space. The significance of the study of this level caused by the fact that its disruption can cause deterioration of the capacity for spatial orientation (spatial agnosia) which is an important sign of some diseases of the brain, and in particular Alzheimer's disease. In recent decades, the main functional components of integration of information on space position of animals were discovered. The significance of these discoveries was reflected in a number of prestigious awards and honors, including the Nobel Prize in Physiology or Medicine for 2014.

[MECHANISMS OF NEURONAL LOSS IN ALZHEIMER''S DISEASE].

One of the main elements of the pathogenesis of Alzheimer's disease is neuronal loss in different areas of the brain, which is more intensive than in normal aging. Necessity of studying the pathogenesis of this process is determined by the fact that the loss of neurons begins at the preclinical stage of Alzheimer's disease when the amyloid plaques and neurofibrillary tangles (main morphological manifestations of the disease) is not yet formed and that the loss of neurons correlates with the severity of clinical symptoms. To date, there is evidence that allows delineating probable pathogenetic mechanisms of neuronal loss. This is the purpose of this review of the literature.

[FACTORS AFFECTING SPERMATOGENESIS PRESERVATION IN RATS WITH SEMINIFEROUS TRACT OBSTRUCTION].

The aim of the study was to examine the effect of the seminal tract obstruction of different degree and duration on the morphological and functional condition of testicular tissue. The study was conducted in 50 male Wistar rats. Three experimental models of seminiferous tract obstruction were set up: obstruction of the proximal part of the ductus deferens, obstruction of the distal part of the ductus deferens and obstruction of at the epididymis level. Morphological evaluation of testicular tissue was performed at 3 and 6 months after the obstruction. It was found that obstruction at the epididymis level caused the most severe impairment of spermatogenesis.

[Effects of activation of kappa-opioid receptors on the behavior at the postnatal development of the stress reactivity systems].

It is known that stress changes state and reactivity of humoral systems of stress, particularly the hypothalamic-pituitary-adrenal system (HPA) and the dynorphin-K-opioid system (DKOS) in any age periods, including ones of early postnatal development. Supposedly these changes are underlying some disorders. Difference in state and reactivity of the HPA system is well established. But the role of DKOS is not clear. Further study of this requires summarizing of the literature data on physiology of DKOS activation and ethological features of the activation in different periods of postnatal development. It is possible to conclude that the mode of reaction to stimulation of the DKOS differs in the early development in contrast to adult animals. The mode of reaction can be changed in relation to the periods of development of the system of stress-reactivity and can depend on prior activation of the stress system in a particular period.

Caspase expression in placental terminal villi in spontaneous and induced pregnancy.

Placental levels of caspase 1, 8, and 10 were studied by the immunohistochemical method in full-term spontaneous and induced pregnancies. The levels of these caspases in the placental terminal villi were significantly higher in induced pregnancy. The changes were more marked after intracytoplasmatic injection of spermatozoa.