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Drug resistance and toxicity are the most widespread limitations in the pursuit of sufficient antitumor effectiveness and successful control of oncological diseases, including colorectal cancer (CRC). Herein the objective was to investigate some hematological side effects of the chemotherapeutic regimen FOLFOX-4, their relation to dihydropyrimidine dehydrogenase (DPD) levels and the associated alterations in CRC patients' plasma free-radical scavenging properties and extent of oxidative molecular damage. Thirty-eight patients with histologically confirmed CRC diagnoses, assigned to chemotherapy with the FOLFOX-4 regimen, were recruited. The diagnostic methods included a complete physical examination, blood routine test and general biochemistry. The DPD levels were assayed. The patients' plasma free-radical scavenging properties and extent of molecular oxidative damage were determined by spectrophotometry and enhanced chemiluminescence. The clinico-pathological and demographics characteristics of the patients were in agreement with the reports from retrospective cohort studies. The FOLFOX-4 regimen induced a decrease in plasma free-radical scavenging properties and increased extent of lipid peroxidation. White blood cells, granulocytes and lymphocytes decreased significantly after the first cycle of the therapy. The patients' DPD level decreased statistically significantly in the case of severe reduction (more than 25%) of white blood cells and granulocyte counts. The obtained data are in agreement with already known facts concerning the side effects of the FOLFOX-4 regimen and associated changes in redox homeostasis. Genetic predisposition to effectively metabolize and tolerate the applied therapy, i.e. DPD levels, could modulate some aspects of the observed changes in the aforementioned parameters. [ABSTRACT FROM AUTHOR]

Some social movements researchers argue that the Internet globalises protest and equalises cross-national inequalities in opportunities for activism. Critics warn against such techno-optimism, highlighting continued individual-level inequalities and country-level variation in protest participation. In this paper, we operationalise Manuel Castells' theory of social movement development to test the extent to which contemporary demonstrators share the characteristics of global activists. We also examine how country-level economic and political institutions affect levels of protest and moderate the relationship between individual-level predictors and activism. We find support for Castells' contention that use of online media is a significant predictor of protest. However, we also find that having a sense of global connectedness does not significantly affect one's likelihood of engaging in demonstrations. Protest participation continues to be stratified by traditional markers of social privilege including education and gender. Moreover, national political and economic contexts have independent effects on protest and moderate how individual-level political and economic grievances affect civic engagement. [ABSTRACT FROM AUTHOR]

We have recently identified several aroylhydrazone-based molecular hybrids with antiseizure activity. We aimed to investigate the analgesic activity of these molecules further. Male ICR mice were injected intraperitoneally with the tested substances or with the vehicle only (controls). We performed hot plate tests, formalin test and maximal electroshock (MES) test and further studied the cytokine proteome in the brain. In silico analysis was performed for prediction of the physicochemical parameters and activity. The furan-substituted aroylhydrazone-based 2H-chromene hybrid showed a significant increase of the latent time as compared with the baseline values (p <.05). Both the chlorine-substituted and the methyl-substituted aroylhydrazone-based coumarin derivatives significantly decreased the first phase of the formalin test (p <.05). We also found suppression of all the cytokines which were overexpressed in the model of acute seizures (MES test) and in the formalin paw test. The in silico model predicted hydroxymethylglutaryl coenzyme A synthetase 2 (HMGCS2) enhancer activity. Further testing is needed to confirm the mechanism of the potentially beneficial effects of the tested substances and to evaluate the toxicity and efficacy of the proposed molecules. [ABSTRACT FROM AUTHOR]

Epilepsy is one of most reported neurological disorders after migraine, stroke and Alzheimer's disease. Empiric clinical data reveal that seizures and epilepsy more likely affect men than women. The aim of present study was to investigate the effect of steroid adrenal and gonadal hormones on the intensity, dynamics and latency of kainic acid-evoked seizure and lethality in a rat model of epileptogenesis. After surgical adrenalectomy/gonadectomy, male rats wereat randomassorted in groups and treated from postoperative day 1 to day 5 with corticosterone (30 mg/kg), estradiol (0.03 mg/kg), progesterone (75 mg/kg), dihydroprogesterone (75 mg/kg) and dihydrotestosterone (0.75 mg/kg). Spontaneous recurrent seizures generated by kainic acid were assessed. The treatment with corticosterone eliminated the aggravation of kainic acid-evoked seizures produced by adrenalectomy/gonadectomy. The application of corticosterone decreased the seizure intensity by 31% and prevented seizure-associated animal death. The effect of estradiol treatment was quite opposite. Estradiol treatment exacerbated the somatic and behavioural aspects of kainic acid-evoked epilepsy-like syndrome. The hormone increased the intensity of kainic acid-evoked seizures by 31%, decreased the latency of clonic weak seizures by 49% and enhanced the associated lethality by 133%. The treatment with progesterone or dihydroprogesterone produced minor alterations in intensity and latency of kainic acid-evoked seizures in the operated male rats. The application of dihydrotestosterone significantly aggravated the kainic acid-evoked seizures. In summary, hormonal unbalance could play an important role for seizure susceptibility in epileptogenesis. Corticosterone has better anti-seizure activity than progesterone and testosterone has significant pro-convulsive activity. [ABSTRACT FROM PUBLISHER]

Pregabalin and gabapentin are amino-acid derivatives of gamma-aminobutyric acid. They have a high affinity to the α2δ protein in the central nervous system and both have been shown to be effective for neuropathic pain disorder. The aim of this study was to investigate the efficacy of gabapentin and pregabalin in animal models of neuropathic pain, and to correlate with clinical outcomes in patients with diabetic neuropathy. Gabapentin (60 mg/kg) and pregabalin (30 mg/kg) attenuate mechanical, tactile and heat hypersensitivity in rats with chronic constriction injury of the sciatic nerve and streptozotocin (STZ)-induced diabetes. There is no evidence that one of the drugs is superior to another at the different rat models and tests. In the incisional pain model, there was partial efficacy of gabapentin. Our clinical data suggest that relative to the baseline pain score, the treatment with pregabalin at doses of 300 mg/day or gabapentin at doses of 900 mg/day would be effective and well tolerated in patients diagnosed with moderate diabetic polyneuropathy. The study suggested that pregabalin may provide better analgesic outcomes than gabapentin on the sixth month of treatment. In conclusion, the comparative effects of gabapentinoids in animal models of neuropathic pain and neuropathic patients are suggestive of similar pathophysiological mechanisms being involved, but successful outcome is determined by a patient's individuality and the drug nature as well as the drug tolerability. [ABSTRACT FROM AUTHOR]

The aim of this article is to examine the evolution of institutions of social dialogue and actors’ perceptions in Bulgaria within the context of the process of Europeanization. The research question addressed by the paper is how and under what external and internal conditions the institutions of social dialogue in Bulgaria have been built and have evolved over time. The methodology is based on previous academic research in this field, official national and EU documents, newspapers and semi-structured interviews with representatives from trade unions and employers’ organisations as well as foreign experts. The overall conclusions comprise two interrelated points. First of all, EU conditionality became the main source of change in the area of social dialogue at the national level through technical assistance and the dissemination of ideas and “best practices”. However, it didn’t have the same impact in respect of negotiations at sectoral/branch and local levels. Secondly, its role was limited to the time of enlargement negotiations, and above all the effects of its influence were strongly dependent on the commitment of internal actors. These findings therefore support the idea of an impact of the EU mediated primarily by internal actors. However, it is necessary to add a further consideration regarding the intrinsic reasons for the limited and temporary influence of the EU. Concerning the notion of a European social model, the development of integration in this respect can in fact be considered as being only embryonic at the present moment. This becomes even more evident when we look at the secondary role played by those issues during accession. Therefore, if it is possible to draw conclusions about the more general process of Europeanization, these inevitably comprise recognising the causal link between the delay of European integration in the field of social dialogue, and the subsequently limited ability of the EU to play a role in candidate countries and even Member States. [ABSTRACT FROM PUBLISHER]

A prior study found that one ketamine-assisted psychotherapy session was significantly more effective than active placebo in promoting abstinence (Krupitsky et al. 2002). In this study of the efficacy of single versus repeated sessions of ketamine-assisted psychotherapy in promoting abstinence in people with heroin dependence, 59 detoxified inpatients with heroin dependence received a ketamine- assisted psychotherapy (KPT) session prior to their discharge from an addiction treatment hospital, and were then randomized into two treatment groups. Participants in the first group received two addiction counseling sessions followed by two KPT sessions, with sessions scheduled on a monthly interval (multiple KPT group). Participants in the second group received two addiction counseling sessions on a monthly interval, but no additional ketamine therapy sessions (single KPT group). At one-year follow-up, survival analysis demonstrated a significantly higher rate of abstinence in the multiple KPT group. Thirteen out of 26 subjects (50%) in the multiple KPT group remained abstinent, compared to 6 out of 27 subjects (22.2%) in the single KPT group (p < 0.05). No differences between groups were found in depression, anxiety, craving for heroin, or their understanding of the meaning of their lives. It was concluded that three sessions of ketamine-assisted psychotherapy are more effective than a single session for the treatment of heroin addiction. [ABSTRACT FROM AUTHOR]

The beginning of the twentieth century is characterized by the emergence among progressively oriented pedagogs of a tendency to depend on data from the science of psychology and to build the pedagogical process in line with characteristics of the psychological development of children. It is in just this period that pedagogical psychology was separated off as an independent branch of scientific knowledge. [ABSTRACT FROM AUTHOR]

The beginning of the 20th century is marked by the striving of progressive-minded pedagogues to be guided by the data of psychological science. It is at this time that pedagogical psychology emerges as an independent branch of scientific knowledge. [ABSTRACT FROM AUTHOR]

The beginning of the 20th century is marked by the striving of progressive-minded pedagogues to be guided by the data of psychological science. It is at this time that pedagogical psychology emerges as an independent branch of scientific knowledge.In elaborating the principles of organizing the "new school," which would ensure complete and free development of the personality in each child, N. K. Krupskaya stressed that the child is "a living human individual with a complex inner life," who must be treated seriously and with respect. [ABSTRACT FROM AUTHOR]

Every parent worries about this question when sending his child to school. [ABSTRACT FROM AUTHOR]