Впровадження основних положень Болонського процесу в післядипломну освіту лікарів

Summary. This prospective analysis assessed the risk of mild mental retardation (MMR) associated with low birthweight (LBW) in the Child Health and Development Studies. Scores of 50–70 on the Raven Progressive Matrices, a relatively culture-free test of cognitive functioning, were used to categorise MMR. At the age of 5,13.8% of the 195 children with birthweights less than 2500 g (LBW) were MMR, whilst 4.2% of the 2293 children with normal birthweights (\u3e2955 grams) were MMR. After adjusting for confounders (maternal age, race, education, prenatal alcohol use, maternal conditions, and congenital anomalies), the relative risk of MMR for LBW was 3.4 (95% CI 1.2–5.4). For children aged 9–11, 7.7% of 194 LBW children were MMR, compared with 6.2% of the 2546 with normal birthweights; the adjusted relative risk for LBW was 1.2 (95% CI 0.7–2.0). Although a strong association between LBW and MMR was observed for both blacks and non-blacks at the age of 5, the association between birthweight and MMR was apparent only for blacks in the cohort of children aged 9–11. These findings suggest that race, a marker for environmental factors which were not measured in this study, may modify the LBW and MMR relationship

Systems Biology: A Therapeutic Target for Tumor Therapy

Tumor-related activities that seem to be operationally induced by the division of function, such as inflammation, neoangiogenesis, Warburg effect, immune response, extracellular matrix remodeling, cell proliferation rate, apoptosis, coagulation effects, present itself from a systems perspective as an enhancement of complexity. We hypothesized, that tumor systems-directed therapies might have the capability to use aggregated action effects, as adjustable sizes to therapeutically modulate the tumor systems’ stability, homeostasis, and robustness. We performed a retrospective analysis of recently published data on 224 patients with advanced and heavily pre-treated (10% to 63%) vascular sarcoma, melanoma, renal clear cell, cholangiocellular, carcinoma, hormone-refractory prostate cancer, and multivisceral Langerhans’ cell histiocytosis enrolled in nine multi-center phase II trials (11 centers). Each patient received a multi-targeted systems-directed therapy that consisted of metronomic low-dose chemotherapy, a COX-2 inhibitor, combined with one or two transcription modulators, pioglitazone +/− dexamethasone or IFN-alpha. These treatment schedules may attenuate the metastatic potential, tumor-associated inflammation, may exert site-specific activities, and induce long-term disease stabilization followed by prolonged objective response (3% to 48%) despite poor monoactivity of the respective drugs. Progression-free survival data are comparable with those of reductionist-designed standard first-line therapies. The differential response patterns indicate the therapies’ systems biological activity. Understanding systems biology as adjustable size may break through the barrier of complex tumor-stroma-interactions in a therapeutically relevant way: Comparatively high efficacy at moderate toxicity. Structured systems-directed therapies in metastatic cancer may get a source for detecting the topology of tumor-associated complex aggregated action effects as adjustable sizes available for targeted biomodulatory therapies

CCR2 Acts as Scavenger for CCL2 during Monocyte Chemotaxis

<div><h3>Background</h3><p>Leukocyte migration is essential for effective host defense against invading pathogens and during immune homeostasis. A hallmark of the regulation of this process is the presentation of chemokines in gradients stimulating leukocyte chemotaxis via cognate chemokine receptors. For efficient migration, receptor responsiveness must be maintained whilst the cells crawl on cell surfaces or on matrices along the attracting gradient towards increasing concentrations of agonist. On the other hand agonist-induced desensitization and internalization is a general paradigm for chemokine receptors which is inconsistent with the prolonged migratory capacity.</p> <h3>Methodology/Principal Findings</h3><p>Chemotaxis of monocytes was monitored in response to fluorescent CCL2-mCherry by time-lapse video microscopy. Uptake of the fluorescent agonist was used as indirect measure to follow the endogenous receptor CCR2 expressed on primary human monocytes. During chemotaxis CCL2-mCherry becomes endocytosed as cargo of CCR2, however, the internalization of CCR2 is not accompanied by reduced responsiveness of the cells due to desensitization.</p> <h3>Conclusions/Significance</h3><p>During chemotaxis CCR2 expressed on monocytes internalizes with the bound chemoattractant, but cycles rapidly back to the plasma membrane to maintain high responsiveness. Moreover, following relocation of the source of attractant, monocytes can rapidly reverse their polarization axis organizing a new leading edge along the newly formed gradient, suggesting a uniform distribution of highly receptive CCR2 on the plasma membrane. The present observations further indicate that during chemotaxis CCR2 acts as scavenger consuming the chemokine forming the attracting cue.</p> </div

Viscum album L. extracts in breast and gynaecological cancers: a systematic review of clinical and preclinical research

<p>Abstract</p> <p>Background</p> <p><it>Viscum album </it>L. extracts (VAE, European mistletoe) are a widely used medicinal plant extract in gynaecological and breast-cancer treatment.</p> <p>Methods</p> <p>Systematic review to evaluate clinical studies and preclinical research on the therapeutic effectiveness and biological effects of VAE on gynaecological and breast cancer. Search of databases, reference lists and expert consultations. Criteria-based assessment of methodological study quality.</p> <p>Results</p> <p>19 randomized (RCT), 16 non-randomized (non-RCT) controlled studies, and 11 single-arm cohort studies were identified that investigated VAE treatment of breast or gynaecological cancer. They included 2420, 6399 and 1130 patients respectively. 8 RCTs and 8 non-RCTs were embedded in the same large epidemiological cohort study. 9 RCTs and 13 non-RCTs assessed survival; 12 reported a statistically significant benefit, the others either a trend or no difference. 3 RCTs and 6 non-RCTs assessed tumour behaviour (remission or time to relapse); 3 reported statistically significant benefit, the others either a trend, no difference or mixed results. Quality of life (QoL) and tolerability of chemotherapy, radiotherapy or surgery was assessed in 15 RCTs and 9 non-RCTs. 21 reported a statistically significant positive result, the others either a trend, no difference, or mixed results. Methodological quality of the studies differed substantially; some had major limitations, especially RCTs on survival and tumour behaviour had very small sample sizes. Some recent studies, however, especially on QoL were reasonably well conducted. Single-arm cohort studies investigated tumour behaviour, QoL, pharmacokinetics and safety of VAE. Tumour remission was observed after high dosage and local application. VAE application was well tolerated. 34 animal experiments investigated VAE and isolated or recombinant compounds in various breast and gynaecological cancer models in mice and rats. VAE showed increase of survival and tumour remission especially in mice, while application in rats as well as application of VAE compounds had mixed results. <it>In vitro </it>VAE and its compounds have strong cytotoxic effects on cancer cells.</p> <p>Conclusion</p> <p>VAE shows some positive effects in breast and gynaecological cancer. More research into clinical efficacy is warranted.</p

Desempenho de cultivares de alface em cultivo hidropônico sob dois níveis de condutividade elétrica Evaluation of two electric conductivity levels on the hidroponic cultivation of lettuce

O objetivo do trabalho foi comparar cultivares de alface de folhas soltas lisas, submetidas a estresse osmótico em soluções nutritivas sob cultivo hidropônico. Foram realizados dois experimentos, cada um com uma condutividade elétrica (C.E.) de 2,0 dS m-1 e 2,5 dS m-1. Os tratamentos foram as cultivares de alface Babá de Verão, Floresta, Luisa, Manoa, Regina 579, Saia Véia e Vitória Verdinha. O delineamento experimental foi blocos casualizados, com três repetições. A colheita foi feita aos 45 dias após a semeadura. Nenhuma cultivar se destacou no conjunto das características avaliadas, embora a Manoa tenha apresentado o maior índice de queima de bordas das folhas, sem diferir estatisticamente da Saia Véia e Babá de Verão. As cultivares Regina 579 e Vitória Verdinha são as preferidas dos produtores hidropônico de Pernambuco, devido à falta de genótipos mais adaptados a essa modalidade de cultivo, e por apresentarem folhas lisas, levemente enrugadas e de textura macia.<br>The aim of this work was to compare loose-leaf lettuce cultivars submitted to osmotic stress in nutrient solutions in hydroponic culture. Two experiments were carried out, with electric conductivity of 2.0 or 2.5 dS m-1. The treatments were the cultivars Babá de Verão, Floresta, Luisa, Manoa, Regina 579, Saia Véia, and Vitória Verdinha. The experimental design was randomized blocks with three replications. Harvest was performed 45 days after sowing. None among the cultivars differed clearly on the characteristics evaluated. However, "Manoa" showed the highest rate of leaf-edge burning, without significant difference in comparison to "Saia Véia" and "Babá de Verão" for summer. The cultivars Regina 579 and Vitória Verdinha are preferred by the growers of hydroponic vegetables of Pernambuco, due to the lack of better genotypes for this type of cultivation and due to the presence of smooth slightly-wrinkled leaves with soft texture