A clinical case of restoration of the destroyed crown part of the tooth complicated by changes in the bifurcation area

The destruction of the tooth crown should be regarded as the cause leading over time to the disruption of the morphofunctional unity of the dentition and pathological condition of the entire dentoalveolar system. Untimely treatment of defects of hard tooth tissues leads to functional disorganization of the dentoalveolar system. The most eliminated defects are those of crowns of teeth determining the quality of aesthetics, phonetics, functions of biting and chewing. The destruction of the tooth crowns, which do not cause significant disruption of the above functions, are painless and almost asymptomatic. In such cases, deformation of the dentition and occlusion, dysfunction of masticatory muscles and temporomandibular joints as well as the development of pathological changes in periodontium occur slowly. Of great importance are the early diagnosis of pathological reconstruction of dentoalveolar system and the knowledge of pathogenesis of possible complications after the extraction of the teeth that determine the indications for prophylactic orthopedic dental treatment. The article presents a clinical case of restoration of destructed tooth crown 3.6 complicated by changes in bifurcation area. The patient underwent coronary-radicular separation with the use of cast metal cores, which allowed restoration of the sufficient size of the stump, function and anatomical shape of the tooth and hence the unity of dental arch

Aspects of psychosomatic disorders in highly qualified athletes

Objective: to observe general abundance of various psychosomatic disorders among highly qualified athletes. Materials and methods: the study involved 3 094 athletes of Russian national teams with age range from 18 to 77 years. Analysis of data collected during the extend medical examinations (EME) of the national Russian team athletes in 2014-2016 years was conducted. Results: research shows high frequency of psychosomatic disorders among athletes of Russian national teams - 28,1%. The most common conditions among diseases with psychosomatic mechanisms in athletes of Russian national teams were disorders of the musculoskeletal system, the gastrointestinal tract, and the nervous system. Gender and age specific differences were shown. Conclusions: both psychological and psycho-physiological factors play significant role in the formation of psychosomatic disorders in athletes. Apparently, in view of the importance of social status (success) and, consequently, the tendency to negate problems, we expect late medical resource utilization in this group of the population (only in the case of a long and severe somatic disorder)

EPR study of polycrystalline superconductors with YBa2Cu3O7 structure

Electron paramagnetic resonance (EPR) of Gd3+, Eu2+, and copper ions has been investigated in the high-Tc superconductor with YBa2Cu3O7-α structure. It has been established that the system is heterogeneous at 0.15≤δ≤0.5 and consists of metallic and dielectric regions. The former arises due to oxygen enrichment while the later due to oxygen deficiency. The integral of exchange interaction between Gd3+ localized moments and conduction electrons Jsf=0.016 eV has been determined from the normal state temperature dependence of Gd3+ EPR linewidth for metallic regions. Tc depression by gadolinium-localized moments for GdBa2Cu3O7-α was estimated to be ΔTc{reversed tilde equals}-2K. Anomalies in linewidth temperature dependence upon transition from the normal to the superconducting state have given information about the value and temperature behavior of the superconductor's energy gap. The model, which gives the opportunity to understand some peculiarities of the EPR signal for YBa2Cu3O7-α samples, is proposed in terms of several bottlenecked spinsubsystems: spin-liquid in CuO planes and Cu2+-O- and Cu2+-O2- fragments in CuO chains. © 1989 Plenum Publishing Corporation

Revisiting the need for optimization of psychological interventions in the medical service system for elite athletes

Objective: revelation of disadaptation among Russian elite athletesof necessity to optimize psychological interventions among biomedical support system for elite athletes. All participants were athletes of several Russian national teams, among them cyclic sports, game sports, complex coordination sports, and combat sports. Materials and methods: data obtained from 1176 elite athletes during extended medical examinations (EME) within the period from 2015 to 2018 were studied. Results: research reveals the relationship between psychical adaptation and athletes’ gender, age, level of experience, and sport-related specifics. Conclusions: athletes of various Russian national teams (from juniors to elite) suffer from notable disadaptation. Thereupon the necessity of changes to the existing system of psychophysiological interventions within national teams (namely: development of preventive treatment programs and correction of disadaptation programs) verify its importance

Psychophysiological and psychological features of elite young volleyball players

Objective: to analyze the psychological and psychophysiological features of effective volleyball play. Materials and methods: the study involved 19 female athlets with average age of 17±1 years. The study was conducted during the pre-competition period. Personality traits, sport motivation, coping strategies, emotional burnout, skills of mental training and visualization, were assessed by adapted Russian-language versions of questionnaires «Freiburg multi-factor personal questionnaire (FPI)», «Sport motivation scale (SMS)», «The Sport Imagery Questionnaire (SIQ)», «Strategic Approach to Coping Scale (SACS)», «Maslach burnout inventory». The levels of chronic and acute stress were assessed by «Acute and chronic stress scale». Attentional set-shifting, concentration of attention were examined by the Munsterberg test and the «Entangled lines» test. The speed and stability of sensorimotor functioning were assessed by Simple Reaction Time test and Choice Reaction Time test. Stress load was simulated by the game-biofeedback approach to examine the effectiveness of self-regulation. The obtained data were compared with the assessment of athletes’ gaming efficiency. Results: Revealed significant connection between game effectiveness and the reduced level of stress: high speed, reaction stability, internal motivation, decreased neuroticity, depressiveness, aggressiveness, emotional lability, developed skills of self-regulation, visualization and ideomotor training are discussed. Conclusions: Revealed psychological and psychophysiological features might be considered as components of the young female volleyball players’ model psychophysiological state

Differential requirement of CAAX-mediated posttranslational processing for Rheb localization and signaling

The Rheb1 and Rheb2 small GTPases and their effector mTOR are aberrantly activated in human cancer and are attractive targets for anti-cancer drug discovery. Rheb is targeted to endomembranes via its C-terminal CAAX (C = cysteine, A = aliphatic, X = terminal amino acid) motif, a substrate for posttranslational modification by a farnesyl isoprenoid. Following farnesylation, Rheb undergoes two additional CAAX-signaled processing steps, Rce1-catalyzed cleavage of the AAX residues and Icmt-mediated carboxylmethylation of the farnesylated cysteine. However, whether these post-prenylation processing steps are required for Rheb signaling through mTOR is not known. We found that Rheb1 and Rheb2 localize primarily to the endoplasmic reticulum and Golgi apparatus. We determined that Icmt and Rce1 processing is required for Rheb localization, but is dispensable for Rheb-induced activation of the mTOR substrate p70 S6 kinase (S6K). Finally, we evaluated whether farnesylthiosalicylic acid (FTS) blocks Rheb localization and function. Surprisingly, FTS prevented S6K activation induced by a constitutively active mTOR mutant, indicating that FTS inhibits mTOR at a level downstream of Rheb. We conclude that inhibitors of Icmt and Rce1 will not block Rheb function, but FTS could be a promising treatment for Rheb- and mTOR-dependent cancers

Executive Summary of the American Radium Society Appropriate Use Criteria for Radiation Treatment of Node-Negative Muscle Invasive Bladder Cancer

PURPOSE: Definitive radiation therapy (RT), with or without concurrent chemotherapy, is an alternative to radical cystectomy for patients with localized, muscle-invasive bladder cancer (MIBC) who are either not surgical candidates or prefer organ preservation. We aim to synthesize an evidence-based guideline regarding the appropriate use of RT. METHODS AND MATERIALS: We performed a Preferred Reporting Items for Systematic Reviews and Meta-analyses literature review using the PubMed and Embase databases. Based on the literature review, critical management topics were identified and reformulated into consensus questions. An expert panel was assembled to address key areas of both consensus and controversy using the modified Delphi framework. RESULTS: A total of 761 articles were screened, of which 61 were published between 1975 and 2019 and included for full review. There were 7 well-designed studies, 20 good quality studies, 28 quality studies with design limitations, and 6 references not suited as primary evidence. Adjuvant radiation therapy after cystectomy was not included owing to lack of high-quality data or clinical use. An expert panel consisting of 14 radiation oncologists, 1 medical oncologist, and 1 urologist was assembled. We identified 4 clinical variants of MIBC: surgically fit patients who wish to pursue organ preservation, patients surgically unfit for cystectomy, patients medically unfit for cisplatin-based chemotherapy, and borderline cystectomy candidates based on age with unilateral hydronephrosis and normal renal function. We identified key areas of controversy, including use of definitive radiation therapy for patients with negative prognostic factors, appropriate radiation therapy dose, fractionation, fields and technique when used, and chemotherapy sequencing and choice of agent. CONCLUSIONS: There is limited level-one evidence to guide appropriate treatment of MIBC. Studies vary significantly with regards to patient selection, chemotherapy use, and radiation therapy technique. A consensus guideline on the appropriateness of RT for MIBC may aid practicing oncologists in bridging the gap between data and clinical practice

Effects of breast cancer adjuvant chemotherapy regimens on expression of the aging biomarker, p16ink4a

Background: Although chemotherapy saves lives, increasing evidence shows that chemotherapy accelerates aging. We previously demonstrated that mRNA expression of p16INK4a, a biomarker of senescence and molecular aging, increased early and dramatically after beginning adjuvant anthracycline-based regimens in early stage breast cancer patients. Here, we determined if changes in p16INK4a expression vary by chemotherapy regimen among early stage breast cancer patients. Methods: We conducted a study of stage I-III breast cancer patients receiving adjuvant or neoadjuvant chemotherapy. p16INK4a expression was analyzed prechemotherapy and postchemotherapy (median 6.2 months after the last chemotherapy) in peripheral blood T lymphocytes. Chemotherapy-induced change in p16INK4a expression was compared among regimens. All statistical tests were 2-sided. Results: In 146 women, chemotherapy was associated with a statistically significant increase in p16INK4a expression (accelerated aging of 17 years; P < .001). Anthracycline-based regimens were associated with the largest increases (accelerated aging of 23 to 26 years; P ≤ .008). Nonanthracycline-based regimens demonstrated a much smaller increase (accelerated aging of 9 to 11 years; P ≤ .15). In addition to the type of chemotherapy regimen, baseline p16INK4a levels, but not chronologic age or race, were also associated with the magnitude of increases in p16INK4a. Patients with lower p16INK4a levels at baseline were more likely to experience larger increases. Conclusions: Our findings suggest that the aging effects of chemotherapy may be influenced by both chemotherapy type and the patient's baseline p16INK4a level. Measurement of p16INK4a expression is not currently available in the clinic, but nonanthracycline regimens offering similar efficacy as anthracycline regimens might be favored

A RasGAP SH3 Peptide Aptamer Inhibits RasGAP-Aurora Interaction and Induces Caspase-Independent Tumor Cell Death

The Ras GTPase-activating protein RasGAP catalyzes the conversion of active GTP-bound Ras into inactive GDP-bound Ras. However, RasGAP also acts as a positive effector of Ras and exerts an anti-apoptotic activity that is independent of its GAP function and that involves its SH3 (Src homology) domain. We used a combinatorial peptide aptamer approach to select a collection of RasGAP SH3 specific ligands. We mapped the peptide aptamer binding sites by performing yeast two-hybrid mating assays against a panel of RasGAP SH3 mutants. We examined the biological activity of a peptide aptamer targeting a pocket delineated by residues D295/7, L313 and W317. This aptamer shows a caspase-independent cytotoxic activity on tumor cell lines. It disrupts the interaction between RasGAP and Aurora B kinase. This work identifies the above-mentioned pocket as an interesting therapeutic target to pursue and points its cognate peptide aptamer as a promising guide to discover RasGAP small-molecule drug candidates

Rho GTPase Cdc42 Is a Direct Interacting Partner of Adenomatous Polyposis Coli Protein and Can Alter Its Cellular Localization

Adenomatous Polyposis Coli (APC) is a tumor suppressor gene product involved in colon cancer. APC is a large multidomain molecule of 2843 amino acid residues and connects cell-cell adhesion, the F-actin/microtubule cytoskeleton and the nucleus. Here we show that Cdc42 interacts directly with the first three armadillo repeats of APC by yeast two-hybrid screens. We confirm the Cdc42-APC interaction using pulldown assays in vitro and FRET assays in vivo. Interestingly, Cdc42 interacts with APC at leading edge sites where F-actin is enriched. In contrast, Cdc42 interacts with the truncated mutant APC1–1638 in cellular puncta associated with the golgi-lysozome pathway in transfected CHO cells. In HCT116 and SW480 cells, Cdc42 induces the relocalization of endogenous APC and the mutant APC1–1338 to the plasma membrane and cellular puncta, respectively. Taken together, these data indicate that the Cdc42-APC interaction induces localization of both APC and mutant APC and may thus play a direct role in the functions of these proteins