[Prospects for use of short peptides in pharmacotherapeutic correction of Alzheimer's disease.]

Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized by progressive cognitive decline. This review discusses current therapeutic strategies for the treatment of Alzheimer's disease, their limitations, and potential prospects. The feasibility of comprehensive approach for AD therapy is considered in contrast to the classical method in the development of therapeutic strategy. Leu-Ile, Glu-Trp, Lys-Glu, Gly-Pro, Glu-Asp-Arg, Lys-Glu-Asp, Met-Glu-His-Phe-Pro-Gly-Pro short peptides are described as multitarget agents with a wide range of activity.

MEDICAL AND LEGAL ISSUES OF OBSERVING THE RIGHTS OF A PERSON WITH A MENTAL ILLNESS WHO HAS BECOME A PARTICIPANT IN CRIMINAL PROCEEDINGS.

There is no health without mental health. The rich links between mind, body and the environment have been well-documented for decades. As the third decade of the millennium begins, nowhere in the world has achieved parity between mental and physical health and this remains a significant human development challenge. An important message within that collective failure is that without addressing human rights seriously, any investment in mental health will not be effective. Attacks on universal human rights principles threaten the physical, political, social, and economic environment, and actively undermine the struggle for positive mental health and well-being. Mental health systems worldwide are dominated by a reductionist biomedical model that uses medicalization to justify coercion as a systemic practice and qualifies the diverse human responses to harmful underlying and social determinants (such as inequalities, discrimination, and violence) as "disorders" that need treatment. In such a context, the main principles of the Convention on the Rights of Persons with Disabilities are actively undermined and neglected. This approach ignores evidence that effective investments should target populations, relationships, and other determinants, rather than individuals and their brains. How that dominance is overcome requires transformative human rights action. However, action that focuses only on strengthening failing mental health-care systems and institutions is not compliant with the right to health. The locus of the action must be recalibrated to strengthen communities and expand evidence-based practice that reflects a diversity of experiences. Such community-led recalibration enables the necessary social integration and connection required to promote mental health and well-being more effectively and humanely.

MEDICAL AND FORENSIC IDENTIFICATION OF PERSONS WHO HAVE BECOME VICTIMS OF WAR CRIMES OF THE RUSSIAN WAR AGAINST UKRAINE.

The relevance of the study is determined by necessity of accurate forensic studies to identify victims of war crimes in Ukraine for the practical use of the most effective measures by law enforcement agencies to establish such persons. The aim of the research is to reveal procedure and opportunities of identification of victims of war crimes, who may be combatants and civilians are according to the results of the analysis of regulations, practices of forensic identification of corpses of unidentified persons. Methodological framework of research are scientific and theoretical methods, which are analysis, synthesis, concretization, generalization, analogy, as well as the empirical method of studying normative sources and special literature, the method of systematic approach in order to form conclusions to reveal ways to solve the problem. Result of the research is conclusion that the standards that are used today in Ukraine and the opportunity of conducting medical and forensic examination to identify unidentified persons who have become victims of war crimes, corresponding to modern European approaches. It is noted that it is impossible to solve the problem of identification only with the help of traditional methods of medical and forensic identification of a person. It is substantiated that the use of modern methods of deoxyribonucleic acid identification by forensic doctors can be promising for ensuring of tasks of the identification of unidentified corpses and fragments of human bodies. It was emphasized that the disadvantage is that today in Ukraine there is no database of deoxyribonucleic acid identification of all or some categories of citizens of Ukraine. It was concluded that it would be effective to approve the concept of the State Target Program to expand the network of deoxyribonucleic acid laboratories and create a National Database of Human Genetic Traits, to do this. The practical value of the work consists in ensuring that forensic doctors perform the tasks of identifying persons of unrecognizable corpses and fragments of human bodies using the modern method of deoxyribonucleic acid identification.

[Neuroprotective effects of peptides.]

Neurodegenerative diseases are a heterogeneous group of nervous system pathologies. They are found mainly in people of an older age group. The incidence of neurodegenerative diseases is continuously growing due to an increase in the average life expectancy of the population. At the moment, there are no effective and safe treatments for neurodegenerative diseases, which are most often diagnosed at the stage of decompensation, when therapy is ineffective and does not bring positive outcomes. Most of the currently used drugs act only symptomatically. The review provides analyzed data and information about the prospects of using peptide bioregulators as neuroprotectors with high physiological activity and low immunogenicity.

[Gender-specific effects of neonatal administration of melatonin on lifespan and age-associated patholgy in 129/Sv mice.]

Melatonin was administered at the dose of 1,2 mcg per capita (an equivalent to pediatric dosages) at days 1, 3 and 5 postpartum to 129/Sv mice, which were followed thereafter till their natural deaths. In adult males, findings included a decrease in body weight and an increase in the contribution of pulmonary lesions, which were revealed upon postmortem examinations, to the overall mortality. In adult females, no changes in body weight occurred, the proportion of middle- and late-age mice having irregular estrous cycles increased, and mortality associated with uterine hemangiomas was accelerated. Trends in malignant tumor yields were different: a decrease in males and an increase in females. Tends in survival patterns were expressed as significant increases or decreases in the lifespans of the last 25% and 10% of male or female survivors respectively. An analysis of the complete survivorships curves in terms of the Gompertz model showed that changes in the initial mortality and aging rate were within the limits determined by the artifactual component of the Strehler-Mildvan correlation between these parameters. On a whole, the trends found in the present work were opposite in males and females being mostly favorable for the former and adverse for the latter. Gender specificity should be kept in mind upon considering the use of melatonin by children and their mothers.

[Melatonin enhances antitumor effect of doxorubicin on a model of transplantable Ehrlich tumor in female sHR mice].

A combined antitumor effect of a single injection of doxorubicin and the indole hormone melatonin was investigated in the model of transplantable Ehrlich carcinoma in female SHR mice. Animals received melatonin either subcutaneous 10 mg/ kg in the evening or with water 10 mg/l at night (from 20 pm to 8 am) for 3 weeks. The results of an experiment showed that combined use of doxorubicin and melatonin both subcutaneous and with water leads to statistically significant inhibition of tumor growth compared with control and doxorubicin alone.

[Prospects of use of antidiabetic biguanides for cancer prevention and treatment: results of preclinical studies].

The critical analysis of preclinical testing of anticarcinogenic and antitumor activity of biguanides presented in this paper. Experiments have been conducted using in total more than 20 models of carcinogenesis including models of spontaneous , chemically- , radiation- and virus-induced carcinogenesis, as well as carcinoigenesis induced by special fat diets and by genetic modification in rodents. Cancer preventive effect of buiguanides has been studied in relation to total tumor incidence and to 17 target organs in animals of 3 species, including 25 various strains of mice, 4 strains of rats and 1 strain of hamsters using various routs of administration and doses. In the majority of cases (86%) the exposure to biguanides leads to inhibition of carcinogenesis. In 14% of the cases inhibitory effect of the drugs was not observed, however there was no any case of stimulation of carcinogenesis by antidiabetic biguanides., Metformin suppressed tumor growth in the majority of in vitro studies conducted in 46 different cell lines originated from malignant tumors of 15 localization as well as in athymic mice with xenografts of 31 tumor lines. It was concluded that there are sufficient experimental evidences of anticarcinogenic and antitumor effects of antidiabetic biguanides revealed in a number of models of induced and spontaneous carcinogenesis.

[Age dynamics of angiogenesis markers in transgenic HER-2/neu (FBV/N) mammary adenocarcinoma-prone mice].

Age-dependent angiogenesis intensity changes have been studied in transgenic HER-2/neu (FBV/N) mice characteristic of breast tumors' high incidence with hyperexpression of HER-2/neu. Concentration of vascular endothelial growth factor, insulin-dependent growth factor 1, nitrogen monoxide, tissue plasminogen activator and type 1 plasminogen activator inhibitor were assessed by means of immune-enzyme assay. The results testify to angiogenesis processes activation side by side with aging and growth of the tumors. Maximum manifestation of these disturbances (growth factors' blood concentrations increase and endotheliocytes' functional activity inhibition) has been revealed in 6-month-old mice during neoplasma maximum intensive and aggressive growth period.

[STUDYING OF BIOMECHANICAL PROPERTIES OF SKIN IN THE MASTOID REGION WHILE THE COSMETIC OTOPLASTY PERFORMANCE].

The present methods for a droopy ears correction do not guarantee the optimal cosmetic effect achievement. Optimal borders of deformity in cutaneo-adiposal flap of the mastoid region while cosmetic otoplasty performance were studied. Basing on analysis of biomechanical investigations, there were determined the optimal corners of stretching and direction of the strength vector in cutaneo-adiposal flaps while otoplasty performance, securing conditions for surgical intervention performance with preservation of a natural topographo-anatomical ratios in the head and neck tissues.

[Light-induced disruption of the circadian clock and risk of malignant tumors in laboratory animals: state of the problem].

There were obtained sufficient experimental evidence of the stimulating effect on the development of tumors (transplanted, spontaneous and induced by various carcinogenic agents), disorders of circadian function of the pineal gland (light-induced desynchronosis) caused by knockout or mutation of clock genes, pinealectomy, content in conditions of constant light or natural light regime of the North, as well as jetlag modeling in laboratory rodents. In experiments on various models of carcinogenesis it was found that sympathectomy (removal of the superior cervical ganglion), light deprivation, hibernation and application of melatonin, the natural hormone of the pineal gland, had an inhibitory effect on the development of transplanted, spontaneous and induced tumors of different histogenesis.

[Effect of epsilon-aminocaproic acid, cyclophosphamide and their combination on the growth of autochthonous sarcomas of mice induced by benzo(a)pyrene].

Antifibrinolytic drug epsilon-aminocaproic acid as a therapeutic form (5% solution in saline) was tested for antitumor activity in the autochthonous subcutaneous tumors of mice, induced by benzo (a) pyrene, in monotherapy mode (instead animals received drinking water) and in combination with cyclophosphamide, which was administered once intraperitoneally in the dose of 200 mg/kg. In the control groups, treated with drinking water and saline solution instead of water, there was no stabilization and reduction in tumor volume, while in the groups receiving epsilon-aminocaproic acid, cyclophosphamide and their combination statistically significantly in comparison with the control groups there was increased the proportion of tumors with not changed or reduced volume; epsilon-aminocaproic acid enhanced the antitumor effect of cyclophosphamide. The data obtained are for further study of the antitumor effect of epsilon-aminocaproic acid.

Exploring cartilage damage in gout using 3-T MRI: distribution and associations with joint inflammation and tophus deposition.

OBJECTIVE: Few imaging studies have investigated cartilage in gout. Magnetic resonance imaging (MRI) can image cartilage damage and also reveals other features of gouty arthropathy. The objective was to develop and validate a system for quantifying cartilage damage in gout. METHODS: 3-T MRI scans of the wrist were obtained in 40 gout patients. MRI cartilage damage was quantified using an adaptation of the radiographic Sharp van der Heijde score. Two readers scored cartilage loss at 7 wrist joints: 0 (normal), 1 (partial narrowing), 2 (complete narrowing) and concomitant osteoarthritis was recorded. Bone erosion, bone oedema and synovitis were scored (RAMRIS) and tophi were assessed. Correlations between radiographic and MRI cartilage scores were investigated, as was the reliability of the MRI cartilage score and its associations. RESULTS: The GOut MRI Cartilage Score (GOMRICS) was highly correlated with the total Sharp van der Heijde (SvdH) score and the joint space narrowing component (R = 0.8 and 0.71 respectively, p < 0.001). Reliability was high (intraobserver, interobserver ICCs = 0.87 [0.57-0.97], 0.64 [0.41-0.79] respectively), and improved on unenhanced scans; interobserver ICC = 0.82 [0.49-0.95]. Cartilage damage was predominantly focal (82% of lesions) and identified in 40 out of 280 (14%) of joints. Cartilage scores correlated with bone erosion (R = 0.57), tophus size (R = 0.52), and synovitis (R = 0.55), but not bone oedema scores. CONCLUSIONS: Magnetic resonance imaging can be used to investigate cartilage in gout. Cartilage damage was relatively uncommon, focal, and associated with bone erosions, tophi and synovitis, but not bone oedema. This emphasises the unique pathophysiology of gout.

[The effect of sodium fluoroacetate and metformin on the antitumor activity of cyclophosphamide on the autochthonous mice sarcoma model].

Previously it was found that sodium fluoroacetate (SF) inhibited the growth of the Ehrlich cancer by means of monotherapy and enhanced the antitumor effect of cyclophosphamide (CP) in experiments with autochthonous subcutaneous tumors induced by benzo (a) pyrene. In this study a comparison of the antitumor activity of SF and metformin showed that both substances did not have significant effect in monotherapy but enhanced the effect of CP, increasing the percentage of tumors with the same or reduced volume. Besides, SF, unlike metformin increased the average duration of effect. The data obtained promoted further study of the mechanism of the antitumor effect of SF and the search effective combination with already known antitumor drugs.

[Effect of plastoquinone derivative SkQ1 on benzo(a)pyrene-induced soft tissue carcinogenesis].

Ninety female SHR mice were subcutaneously injected with a single dose of 2 mg benzo(a)pyrene (BaP) dissolved in 0.2 ml of vegetable oil. Since the next day after BaP injection mice were started to treat with mitochondria-targeted antioxidant SkQ1 at the doses of 5 and 50 nmol/kg/day in drinking water. Control animals received tap water. Study was finished by 358th day. Number of tumor-bearing mice increased in all groups exposed to BaP but retarded since 20th week in SkQ1-treated groups in comparison with control. Maximal tumor volume gain was observed in control mice resulting in premature death. By the 30th week of study only 20% of control animals survived, whereas SkQ1 treatment increased survival up to 30% at the dose of 5 nmol and 40% at the dose of 50 nmol. By the 40th week mean tumor volume in 5 and 50 nmol SkQ1-treated mice was 13 and 21 cm3 respectively, whereas in control--40 cm3. In SkQ1-treated mice pneumonia was observed rarely as compared with controls. It could be supposed, SkQ1 at the doses of 5 and 50 nmol/kg/day retarted BaP-induced soft tissue carcinogenesis in SHR mice.

[Effect of sodium fluoroacetate on Ehrlich solid tumor and autochthonous sarcoma growth in mice].

Due to biochemical characteristics of toxic action of fluoroacetate on energetics and metabolism of cells, including tumor cells, it was interesting to testify sodium fluoroacetate (SFA) for its antitumor activity in vivo. We have estimated that SFA significantly inhibits growth of Ehrlich tumor carcinoma. In experiments with autochthonous induced by benzo[a]pyrene subcutaneous tumors, SFA was not active in monotherapy regime, though potentiated antitumor effect of cyclophosphamide, significantly increasing the relative number of mice with stabilized or decreased tumor volume as well as the duration of this effect. The data obtained render basis for additional studies of mechanism of antitumor effect of SFA.

Methodological quality of systematic reviews in subfertility: a comparison of Cochrane and non-Cochrane systematic reviews in assisted reproductive technologies.

STUDY QUESTION: Are there differences in the methodological quality of Cochrane systematic reviews (CRs) and non-Cochrane systematic reviews (NCRs) of assisted reproductive technologies? SUMMARY ANSWER: CRs on assisted reproduction are of higher methodological quality than similar reviews published in other journals. WHAT IS KNOWN ALREADY: The quality of systematic reviews varies. STUDY DESIGN, SIZE AND DURATION: This was a cross-sectional study of 30 CR and 30 NCR systematic reviews that were randomly selected from the eligible reviews identified from a literature search for the years 2007-2011. MATERIALS, SETTING AND METHODS: We extracted data on the reporting and methodological characteristics of the included systematic reviews. We assessed the methodological quality of the reviews using the 11-domain Measurement Tool to Assess the Methodological Quality of Systematic Reviews (AMSTAR) tool and subsequently compared CR and NCR systematic reviews. MAIN RESULTS AND THE ROLE OF CHANCE: The AMSTAR quality assessment found that CRs were superior to NCRs. For 10 of 11 AMSTAR domains, the requirements were met in >50% of CRs, but only 4 of 11 domains showed requirements being met in >50% of NCRs. The strengths of CRs are the a priori study design, comprehensive literature search, explicit lists of included and excluded studies and assessments of internal validity. Significant failings in the CRs were found in duplicate study selection and data extraction (67% meeting requirements), assessment for publication bias (53% meeting requirements) and reporting of conflicts of interest (47% meeting requirements). NCRs were more likely to contain methodological weaknesses as the majority of the domains showed <40% of reviews meeting requirements, e.g. a priori study design (17%), duplicate study selection and data extraction (17%), assessment of study quality (27%), study quality in the formulation of conclusions (23%) and reporting of conflict of interests (10%). LIMITATIONS, REASONS FOR CAUTION: The AMSTAR assessment can only judge what is reported by authors. Although two of the five authors are involved in the production of CRs, the risk of bias was reduced by not involving these authors in the assessment of the systematic review quality. WIDER IMPLICATIONS OF THE FINDINGS: Not all systematic reviews are equal. The reader needs to consider the quality of the systematic review when they consider the results and the conclusions of a systematic review. STUDY FUNDING/COMPETING INTEREST(S): There are no conflicts with any commercial organization. Funding was provided for the students by the summer studentship programme of the Faculty of Medical and Health Sciences of the University of Auckland.

[Hyperplastic skin growth on the head of goldfish--comparative oncology aspects].

Dynamics of development and morphology of hyperplastic skin lesions ("hoods") on the head of goldfish, which were bred using artificial selection for more than thousand years, were studied. During monitoring of hundred fishes, at the age of 6 months "hoods" were found in 39.5%, among 14 months-old fishes in 60,7%. Morphologic examination of "hoods" on various stages of development revealed epithelial hyperplasia with increased clear mucous cells number, dermis thickening and oedema. On later stages developed papillomatous outgrowth and areas of epithelial intrusion. The comparative oncology analysis allow to hypothesize these skin growth to be a genetically determined benign neoplasm. This is the first example of artificially selected neoplasm described in the literature. It supports our hypothesis of the possible evolutionary role of tumors.

[The effect of SSH&H on the lifespan and spontaneous cancer development in transgenic mice with HER-2/neu mutation].

10 months old mice receiving SSH&H with daily food increased the lifespan in comparison to the control group. The maximal lifespan was increased by 1,6 months. For the long-living 10% group the mean lifespan increased by 8,7% compared to the control group (p<0,05). The mammary gland neoplasia rate was the same in both groups. The mean latent tumor development period duration, number and size of the tumors were also similar. There was a tendency to lower lung metastases rate in the experimental group. The cumulative neoplastic frequency curve for the experimental group was shifted to the right in comparison to the control group curve giving evidence to the inhibitory effect of SSH&H on the neoplastic rate in transgenic mice with HER-2/neu mutation.