[Detection rates and high concentration of herpesvirus (Orthoherpesviridae) DNA in autopsy materials from patients with COVID-19 fatal outcome].

INTRODUCTION: SARS-CoV-2 infection causes immune disorders that create conditions for the reactivation of human herpesviruses (HHVs). However, the estimates of the HHVs effect on the course and outcome of COVID-19 are ambiguous. Аim - to study the possible relationship between the HHV reactivation and the adverse outcome of COVID-19. MATERIALS AND METHODS: Postmortem samples from the brain, liver, spleen, lymph nodes and lungs were obtained from 59 patients treated at the Moscow Infectious Diseases Hospital No.1 in 2021-2023. The group 1 comprised 39 patients with fatal COVID-19; group 2 (comparison group) included 20 patients not infected with SARS-CoV-2 who died from various somatic diseases. HHV DNA and SARS-CoV-2 RNA were determined by PCR. RESULTS: HHV DNA was found in autopsy samples from all patients. In group 1, EBV was most often detected in lymph nodes (94%), HHV-6 in liver (68%), CMV in lymph nodes (18%), HSV in brain (16%), VZV in lung and spleen (3% each). The detection rates of HHVs in both groups was similar. Important differences were found in viral load. In patients with COVID-19, the number of samples containing more than 1,000 copies of HHV DNA per 100,000 cells was 52.4%, in the comparison group - 16.6% (p < 0.002). An association has been established between the reactivation of HSV and HHV-6 and the severity of lung damage. Reactivation of EBV correlated with increased levels of liver enzymes. CONCLUSION: Reactivation of HHVs in patients with fatal COVID-19 was associated with severe lung and liver damages, which indicates a link between HHV reactivation and COVID-19 deaths.

[Problems in organizing neurosurgical care for patients with Parkinson's disease in the Russian Federation]. / Problemy organizatsii neirokhirurgicheskoi pomoshchi patsientam s bolezn'yu Parkinsona v Rossiiskoi Federatsii.

BACKGROUND: Currently, there are some problems in the Russian Federation complicating development of neurosurgical care for patients with Parkinson's disease (PD). MATERIAL AND METHODS: In 2022, neurologists - movement disorders specialists were surveyed to analyze situation with PD pharmacological treatment and referral of patients for surgical treatment in Russian constituent entities. Data on neurosurgical treatment of PD were obtained by collecting information on the surgical activity of medical institutions in the Russian Federation. Most hospitals involved in PD treatment took part in this study. RESULTS: The state of neurosurgical care for patients with PD is analyzed and possible ways to improve the quality of treatment are discussed. CONCLUSION: Over the past 20 years, a system of neurosurgical care for patients with PD has been formed in 14 centers in the Russian Federation (2022). Obstacles to its further development can be divided into 3 categories: problems of patient selection and routing, complexity of organization and financing surgeries, and imperfect postoperative patient management. Ways to overcome these obstacles imply expanding the network of centers for extrapyramidal diseases, development of domestic neurostimulation systems, improving the distribution of quotas taking into account the capabilities of hospitals, specialized training of neurologists for extrapyramidal centers and neurosurgeons for deep brain stimulation centers, adequate financing and systematization of postoperative management of patients with PD.

Alterations in the chromatin packaging, driven by transcriptional activity, revealed by AFM.

BACKGROUND: The gene expression differs in the nuclei of normal and malignant mammalian cells, and transcription is a critical initial step, which defines the difference. The mechanical properties of transcriptionally active chromatin are still poorly understood. Recently we have probed transcriptionally active chromatin of the nuclei subjected to mechanical stress, by Atomic Force Microscopy (AFM) [1]. Nonetheless, a systematic study of the phenomenon is needed. METHODS: Nuclei were deformed and studied by AFM. Non-deformed nuclei were studied by fluorescence confocal microscopy. Their transcriptional activity was studied by RNA electrophoresis. RESULTS: The malignant nuclei under the study were stable to deformation and assembled of 100-300 nm beads-like units, while normal cell nuclei were prone to deformation. The difference in stability to deformation of the nuclei correlated with DNA supercoiling, and transcription-depended units were responsive to supercoils breakage. The inhibitors of the topoisomerases I and II disrupted supercoiling and made the malignant nucleus prone to deformation. Cell nuclei treatment with histone deacetylase inhibitors (HDACIs) preserved the mechanical stability of deformed malignant nuclei and, at the same time, made it possible to observe chromatin decondensation up to 20-60 nm units. The AFM results were supplemented with confocal microscopy and RNA electrophoresis data. CONCLUSIONS: Self-assembly of transcriptionally active chromatin and its decondensation, driven by DNA supercoiling-dependent rigidity, was visualized by AFM in the mechanically deformed nuclei. GENERAL SIGNIFICANCE: We demonstrated that supercoiled DNA defines the transcription mechanics, and hypothesized the nuclear mechanics in vivo should depend on the chromatin architecture.

Lithium-Modified Sorbent: Effects on Hemostatic Responses In Vitro.

The effects of a lithium-modified sorbent based on aluminum oxide and polydimethylsiloxane (Al2O3@PDMS/Li) and a lithium-free sorbent (Al2O3@PDMS) on some indicators characterizing blood clotting under hemosorption conditions were compared in vitro. Sorbent Al2O3@PDMS/Li had significantly lower reactogenic effect on the blood passed through the column than the sorbent without lithium. This was seen from the degree of platelet reduction (66×109 vs 19×109/liter) as well as a less pronounced hypercoagulation shift in chronometric indicators. In contrast to lithium-free sorbent, Al2O3@PDMS/Li demonstrated the ability to reduce the concentration of fibrinogen. However, this had no impact on the density characteristics of the blood clot assessed by thromboelastometry such as maximum clot firmness, angle and fibrin clot formation time, amplitudes at 10 and 15 min after clotting time, which are known to depend on the quantity of platelets and the concentration of functionally active fibrinogen.

The influence of social and medical factors on the quality of life in elderly and senile people.

The object of the study was senile people, who sought dental orthopedic care in municipal healthcare institutions of the town of Cheboksary, the Chuvash Republic. The sample size was 1 000 people. The obtained quantitative indicators were subjected to statistical processing using parametric and nonparametric statistical methods. The analysis of mounted orthopedic dent prosthetic structures manufactured and installed in elderly and senile patients shows that the choice of material and method of manufacture is largely determined by such a social factor as the average monthly income. This, in turn, largely depends on income-generating employment and the possibility of obtaining additional financial support from family members in which the patient lives. Social factors have a significant impact on the quality of life in elderly and senile people.

AFM imaging of the transcriptionally active chromatin in mammalian cells' nuclei.

BACKGROUND: Nuclear rigidity is traditionally associated with lamina and densely packed heterochromatin. Actively transcribed DNA is thought to be less densely packed. Currently, approaches for direct measurements of the transcriptionally active chromatin rigidity are quite limited. METHODS: Isolated nuclei were subjected to mechanical stress at 60 g and analyzed by Atomic Force Microscopy (AFM). RESULTS: Nuclei of the normal fibroblast cells were completely flattened under mechanical stress, whereas nuclei of the cancerous HeLa were extremely resistant. In the deformed HeLa nuclei, AFM revealed a highly-branched landscape assembled of ~400 nm closed-packed globules and their structure was changing in response to external influence. Normal and cancerous cells' isolated nuclei were strikingly different by DNA resistance to applied mechanical stress. Paradoxically, more transcriptionally active and less optically dense chromatin of the nuclei of the cancerous cells demonstrated higher physical rigidity. A high concentration of the transcription inhibitor actinomycin D led to complete flattening of HeLa nuclei, that might be related to the relaxation of supercoiled DNA tending to deformation. At a low concentration of actinomycin D, we observed the intermediary formation of stochastically distributed nanoloops and nanofilaments with different shapes but constant width ~ 180 nm. We related this phenomenon with partial DNA relaxation, while non-relaxed DNA still remained rigid. CONCLUSIONS: The resistance to deformation of nuclear chromatin correlates with fundamental biological processes in the cell nucleus, such as transcription, as assessed by AFM. GENERAL SIGNIFICANCE: A new outlook to studying internal nuclei structure is proposed.

Characteristics of Stenotrophomonas maltophilia isolates from cystic fibrosis patients in Russia.

Stenotrophomonas maltophilia is a common opportunistic microorganism and an important respiratory pathogen in cystic fibrosis (CF). The aim of this study was to determine antimicrobial resistance phenotypes, sequence-types (ST) and genetic determinants of antibiotic resistance in S. maltophilia strains recovered from CF patients in Russia. S. maltophilia isolates recovered from 170 CF patients were analyzed. Minimum inhibitory concentrations of antibacterial agents were determined using Sensititre Gram Negative GNX2F plates and the results were interpreted according to Clinical and Laboratory Standards Institute (CLSI) criteria. Whole-genome sequencing (WGS) was performed on MGISEQ-2000 platform. SPAdes software, Galaxy, ResFinder, Integrall and PubMLST were used for analysis of WGS data. S. maltophilia strains were identified from 24/170 (14%) CF patients. In total, 25 isolates were detected, two strains were isolated from the same patient. The isolates belonged to 17 different STs, including 5 new STs; ST4 was the most prevalent ST. Resistance to ceftazidime was observed in 60% of strains, to ticarcillin-clavulanate - in 32%, to levofloxacin - in 24%, to trimethoprim/sulfamethoxazole - in 12% of strains. All isolates were susceptible to minocycline. All ST4 isolates were resistant or intermediate to ceftazidime and ticarcillin-clavulanate. In two isolates, the sul1 gene was detected. In one isolate, sul1 was part of a class 1 integron. The detected integron also contained the blaGES-7 and aac(6')-Ib-cr genes. The ST4 sequence-type was the most prevalent ST among S. maltophilia strains recovered from CF patients in Russia. Antibiotic resistance genes, including sul1, blaGES-7, aac(6')-Ib-cr, were detected in single strains.

[Communication with a neurological patient]. / Kommunikatsiya s nevrologicheskim patsientom.

Patient communication skills are critical for the management of neurological patients, in particular for discussing neurological diagnosis and prognosis. The key communication tools are SPIKES protocol for delivering «bad news¼ and the Calgary-Cambridge model. These communication tools allow to implement a patient-oriented approach to treatment, build effective communication with the patients, and thus provide them high-quality and personalized medical care.

Genome features and antibiotic resistance of Pseudomonas aeruginosa strains isolated in patients with cystic fibrosis in the Russian Federation.

Cystic fibrosis (CF) is a common genetic disease, manifested by airway obstruction and chronic respiratory infection. The most prevalent infectious agent in airways of CF patients is Pseudomonas aeruginosa. This study aimed to determine sequence-types, antimicrobial resistance phenotypes and genes defining adaptive antibiotic resistance in P. aeruginosa isolates recovered from CF patients in Russia. In total, 84 P. aeruginosa strains from 64 CF patients were analyzed. Susceptibility to antibiotics was determined by disk diffusion test. Whole-genome sequencing (WGS) was performed on MGISEQ-2000 platform. SPAdes software, Galaxy, ResFinder, PubMLST were used for analysis of WGS data. Examined P. aeruginosa isolates belonged to 53 different sequence-types (STs), including 6 new STs. High-risk epidemic clone ST235 (10%) and clonal CF P. aeruginosa strains ST17, ST242, ST274 (7%) were detected. Non-susceptibility to ticarcillin-clavulanate, cefepime, imipenem was observed in 63%, 12% and 25% of isolates, respectively; to tobramycin - in 24%, to amikacin - in 35%; to ciprofloxacin, levofloxacin - in 35% and 57% of strains, respectively. Multidrug-resistant phenotype was detected in 18% of isolates. In examined strains, genes of beta-lactamases VIM-2 (5 ST235 strains), VEB-1 (two ST2592 strains), GES-1 (1 ST235 strain), PER-1 (1 ST235 strain) were found. Ciprofloxacin-modifying enzyme CrpP gene was detected in 67% of isolates, aminoglycoside-modifying enzymes AAD, ANT, AAC genes - in 7%, 4%, 12% of strains, respectively. P. aeruginosa isolates from CF patients in Russia demonstrate a high clonal diversity, which is similar to other P. aeruginosa infections. The isolates of high-risk clone and clonal CF P. aeruginosa strains are detected.

[Progressive supranuclear palsy]. / Progressiruyushchii nad"yadernyi paralich.

Progressive supranuclear palsy (PSP) is a heterogeneous progressive neurodegenerative disease characterized by onset after 50 years old, Parkinson's syndrome, early development of postural instability, absence or transient reaction to levodopa drugs, neuropsychological disorders, dysphagia and dysarthria and eye movement disorders. The review provides an analysis of modern data on etiology, clinical presentation, differential diagnosis of the disease. The morphological picture and neuroimaging features, as well as modern ideas about treatment, are described. A great clinical polymorphism of the disease, as well as its similarity to other neurodegenerative diseases, manifested by Parkinson's syndrome, complicates the diagnosis of PSP. Establishing an accurate diagnosis makes it possible to determine the prognosis and further tactics of patient management.

Evaluation of monomeric prolactin level by TRACE method and precipitation with polyethylene glycol.

Prolactin exists in various forms including the monomeric biologically active form (23kDa) and a higher molecular weight form, bound most commonly to IgG, known as macroprolactin (>100kDa). Macroprolactin lacks biological activity and is one of the causes of false-positive results. In Russian Federation the most common method for macroprolactin determination is PEG precipitation test. We had conducted a retrospective analysis of 37 samples of patients with hyperprolactinemia (3 of them were males). The mean age was 30 [25;35] years. Prolactin level was measured by the immunoenzyme method with manual PEG precipitation and TRACE. The mean values found by the immunoenzyme method with manual PEG precipitation were 461,6 [375,0;821,2] mU/l, by TRACE - 449,9 [357,2;749,2] mU/l. The number of patients with normal prolactin levels was 30% (11) confirmed by two methods, high prolactin level at 46% (17). The prevalence of clinical symptoms of hyperprolactinemia was not differ depend the groups. The phenomenon of macroprolactinemia was registered in 32% (12) of patients. In 8 persons of this group normal prolactin level was revealed and in 4 patients hyperprolactinemia was found by TRACE. Measurements of prolactin levels by the TRACE method is useful for correct diagnosis in patients with equivocal results received by traditional method with PEG precipitation.

Bifractal structure of chromatin in rat lymphocyte nuclei.

The small-angle neutron scattering (SANS) on the rat lymphocyte nuclei demonstrates the bifractal nature of the chromatin structural organization. The scattering intensity from rat lymphocyte nuclei is described by power law Q^{-D} with fractal dimension approximately 2.3 on smaller scales and 3 on larger scales. The crossover between two fractal structures is detected at momentum transfer near 10^{-1}nm^{-1}. The use of contrast variation (D_{2}O-H_{2}O) in SANS measurements reveals clear similarity in the structural organizations of nucleic acids (NA) and proteins. Both chromatin components show bifractal behavior with logarithmic fractal structure on the large scale and volume fractal with slightly smaller than 2.5 structure on the small scale. Scattering intensities from chromatin, protein component, and NA component demonstrate an extremely extensive range of logarithmic fractal behavior (from 10^{-3} to approximately 10^{-1}nm^{-1}). We compare the fractal arrangement of rat lymphocyte nuclei with that of chicken erythrocytes and the immortal HeLa cell line. We conclude that the bifractal nature of the chromatin arrangement is inherent in the nuclei of all these cells. The details of the fractal arrangement-its range and correlation/interaction between nuclear acids and proteins are specific for different cells and is related to their functionality.

[Palliative care in Parkinson's disease and neurodegenerative diseases]. / Palliativnaya pomoshch' pri bolezni Parkinsona i neirodegenerativnykh zabolevaniyakh.

Palliative care is traditionally associated with cancer and pain relief: however, the range of diseases requiring palliative care is much wider and includes many neurodegenerative diseases (Alzheimer's disease and Parkinson's disease (PD)). Provision of palliative care to patients with PD and other neurodegenerative diseases, such as multisystem atrophy, progressive supranuclear palsy, dementia with Lewy bodies, etc. is «terra incognita¼ for many neurologists who are not acknowledged with palliative medicine as well as for specialists in palliative medicine, who are mainly trained in providing care to patients with oncological profile and do not know the intricacies of managing patients in the late stages of PD and other neurodegenerative diseases. The aim of the article is to systematize modern knowledge in the field of palliative medicine and neurodegenerative diseases.

Characterization of Tobacco Mosaic Virus Virions and Repolymerized Coat Protein Aggregates in Solution by Small-Angle X-Ray Scattering.

The structure of tobacco mosaic virus (TMV) virions and stacked disk aggregates of TMV coat protein (CP) in solution was analyzed by synchrotron-based small-angle X-ray scattering (SAXS) and negative contrast transmission electron microscopy (TEM). TMV CP aggregates had a unique stability but did not have helical symmetry. According to the TEM data, they were stacked disks associated into transversely striated rod-shaped structures 300 to 800 Å long. According to modeling based on the crystallographic model of the 4-layer TMV CP aggregate (PDB: 1EI7), the stacked disks represented hollow cylinders. The calculated SAXS pattern for the disks was compared to the experimental one over the entire measured range. The best correlation with the SAXS data was found for the model with the repeating central pair of discs; the SAXS curves for the stacked disks were virtually identical irrespectively of the protein isolation method. The positions of maxima on the scatter curves could be used as characteristic features of the studied samples; some of the peaks were assigned to the existing elements of the quaternary structure (periodicity of aggregate structure, virion helix pitch). Low-resolution structural data for the repolymerized TMV CP aggregates in solution under conditions similar to natural were produced for the first time. Analysis of such nano-size objects is essential for their application in biomedicine and biotechnology.

[Deep brain stimulation effect on postural instability and gait disorders in Parkinson's disease]. / Narusheniia khod'by i postural'naia neustoichivost' pri bolezni Parkinsona na fone khronicheskoi stimuliatsii podkorkovykh struktur.

An effect of deep brain stimulation on postural instability and gait disorders in Parkinson's disease S.G. Sultanova, N.V. Fedorova, E.V. Bril, A.A. Gamaleya, A.A. Tomskiy During the last time, surgical treatment of patients with Parkinson's disease has firmly taken its place in the general algorithm for managing patients with this pathology. Deep brain electrostimulation is the most advanced and promising method, which allows the reduction in the severity of main clinical manifestations of the disease, including axial symptoms. It is noted that certain temporal aspects of parkinsonian gait disorder remain therapeutically resistant. Subthalamic nucleus stimulation was also reported to improve levodopa-responsive freezing of gait. In this review, the authors summarize the effects of deep brain stimulation on gait and postural symptoms.

[Development and properties of neutralizing monoclonal antibodies for fusion protein of respiratory syncytial virus.]

INTRODUCTION: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections in infants and the elderly. The absence of a wide range of therapeutic drugs and vaccines indicates to the high relevance of the development of new effective drugs for the prevention and treatment of RSV infections. PURPOSE: to obtain highly active and specific monoclonal antibodies (MAbs) capable of detecting RSV in infected cells and neutralizing the infectious activity of the virus in vitro. MATERIAL AND METHODS: RSV reference strains of group A 2 subgroups (A2 and Long) were propagated in HEp-2 and MA-104 cell lines, respectively. Mice were immunized with purified RSV A2 virus. MAbs were obtained using hybridoma technology. RESULTS: A panel of 6 MAbs reacting with RSV strains А2 and Long has been obtained. Four MAbs were IgG (IgG2a or IgG2b subtype), two MAbs were IgM. All MAbs reacted with RSV F-protein in immunochemical tests. The MAbs actively reacted with RSV in ELISA, in immufluorescence and peroxidase staining of infected cells, and in immunodot test. Five out of 6 MAbs neutralized of RSV in cell culture. Different properties of MAbs suggest that they target different antigenic sites of F-protein. DISCUSSION: Comparative analysis suggests that the obtained MAbs can be used for the development of diagnostic preparations, for RSV detection in clinical materials and confirmation of infection etiology by rapid culture method. CONCLUSION: High activity and specificity of MAbs indicate that they can serve as a basis for development vaccines and preventive medicines.

Resistance of THP-1 Leukemia Cells Infected with Cytomegalovirus to Anti-tumor Antibiotic Doxorubicin and Restoration of the Sensitivity by Inhibitors of the PI3K/AKT/mTOR Molecular Pathway.

Results obtained showed that infection with HCMV prevented the death of THP-1 cells treated with DOX in both active and latent forms of infection. In the presence of mTOR inhibitors (rapamycin and Torin2), the sensitivity of the infected cells to DOX was restored. Rapamycin inhibited the expression of the HCMV protein IE1-p72 and increased sensitivity to DOX. Molecular targets for the creation of new drugs for the treatment of leukemia in patients infected with HCMV were determined.

Solution Structure, Self-Assembly, and Membrane Interactions of the Matrix Protein from Newcastle Disease Virus at Neutral and Acidic pH.

Newcastle disease virus (NDV) is an enveloped paramyxovirus. The matrix protein of the virus (M-NDV) has an innate propensity to produce virus-like particles budding from the plasma membrane of the expressing cell without recruiting other viral proteins. The virus predominantly infects the host cell via fusion with the host plasma membrane or, alternatively, can use receptor-mediated endocytic pathways. The question arises as to what are the mechanisms supporting such diversity, especially concerning the assembling and membrane binding properties of the virus protein scaffold under both neutral and acidic pH conditions. Here, we suggest a novel method of M-NDV isolation in physiological ionic strength and employ a combination of small-angle X-ray scattering, atomic force microscopy with complementary structural techniques, and membrane interaction measurements to characterize the solution behavior/structure of the protein as well as its binding to lipid membranes at pH 4.0 and pH 7.0. We demonstrate that the minimal structural unit of the protein in solution is a dimer that spontaneously assembles in a neutral milieu into hollow helical oligomers by repeating the protein tetramers. Acidic pH conditions decrease the protein oligomerization state to the individual dimers, tetramers, and octamers without changing the density of the protein layer and lipid membrane affinity, thus indicating that the endocytic pathway is a possible facilitator of NDV entry into a host cell through enhanced scaffold disintegration.IMPORTANCE The matrix protein of the Newcastle disease virus (NDV) is one of the most abundant viral proteins that regulates the formation of progeny virions. NDV is an avian pathogen that impacts the economics of bird husbandry due to its resulting morbidity and high mortality rates. Moreover, it belongs to the Avulavirus subfamily of the Paramyxoviridae family of Mononegavirales that include dangerous representatives such as respiratory syncytial virus, human parainfluenza virus, and measles virus. Here, we investigate the solution structure and membrane binding properties of this protein at both acidic and neutral pH to distinguish between possible virus entry pathways and propose a mechanism of assembly of the viral matrix scaffold. This work is fundamental for understanding the mechanisms of viral entry as well as to inform subsequent proposals for the possible use of the virus as an adequate template for future drug or vaccine delivery.

[Pituitary lactotroph adenomas resistant to dopamine agonist treatment: histological and immunohistochemical characteristics]. / Laktotrofnye adenomy gipofiza, rezistentnye k lecheniiu agonistami dofamina: gistologicheskaia i immunogistokhimicheskaia kharakteristika.

OBJECTIVE: To present the histological and immunohistochemical characteristics of pituitary lactotroph adenomas (PLAs) resistant to dopamine agonist treatment. SUBJECT AND METHODS: The investigators examined paraffin-embedded blocks and histological sections obtained from 19 patients (13 women, 6 men), whose median age was 29 (19, 38) years, after surgical treatment (adenomectomy) for PLAs resistant to dopamine agonist treatment. Immunohistological examination was performed using antibodies against prolactin (PRL), growth hormone (GH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), type 2 dopamine receptors (DR2), estrogen receptors-α (ERα), the proliferation marker Ki-67, and the endothelial cell marker CD34. RESULTS: The expression of PRL by adenoma cells was revealed in all the patients. The coexpression of PRL and GH without clinical and laboratory signs of acromegaly was established in 3 cases. No expression of TSH, ACTH, LH, or FSH was revealed in any cases. Positive immunoreaction using antibodies against DR2 and ERα was detected in 8 and 6 cases, respectively. No expression of any of the studied receptors was found in 6 patients. Ki-67 was more than 3% in 3 patients and higher in patients with supra- or retrosellar growth. There was a positive correlation between the serum level of Ki-67 and that of PRL at the onset of the disease. There were 37 (25, 85) adenoma vessels, as measured by CD34 immunoexpression. It was ascertained that the patients with parasellar adenoma had more tumor vessels than those without parasellar growth of adenoma and that with the latter invading the cavernous vessels, the number of vessels was statistically significantly more. CONCLUSION: PLAs resistant to dopamine agonists in addition to PRL (100%) can express GH in 16% of cases are characterized by the immunoexpression of DR2 (42%) and ERα (32%), a low proliferative activity, increased angiogenesis in the adenomas with parasellar growth and invasion into the cavernous sinus.