The consequences of growth hormone deficiency in adulthood, and the effects of growth hormone replacement

The availability of recombinant human growth hormone (GH) has resulted in investigation of the role of GH in adulthood and the effects of GH replacement in the GH-deficient adult. These studies have led to the recognition of a specific syndrome of GH-deficiency, characterized by symptoms, signs and investigative findings. Adults with long-standing growth hormone deficiency are often overweight, have altered body composition, with reduced lean body mass (LBM), increased fat mass (FM), reduced total body water and reduced bone mass. In addition, there is reduced physical and cardiac performance, altered substrate metabolism and an abnormal lipid profile predisposing to the development of cardiovascular disease. Adults with GH deficiency report reduced psychological well-being and quality of life. These changes may contribute to the morbidity and premature mortality observed in hypopituitary adults on conventional replacement therapy. GH treatment restores LBM, reduces FM, increases total body water and increases bone mass. Following GH therapy, increases are recorded in exercise capacity and protein synthesis, and "favourable" alterations occur in plasma lipids. In addition, psychological well-being and quality of life improve with replacement therapy. GH is well tolerated; adverse effects are largely related to fluid retention and respond to dose adjustment. It is likely that GH replacement will become standard therapy for the hypopituitary adult in the near future. The benefits of GH replacement in the GH-deficient adult have been unequivocally demonstrated in studies lasting up to 3 years. The results of longer term studies are awaited to determine whether these benefits are sustained over a lifetime.

The Development of Social Work as a Speciality and the Profession in Estonia

For Estonia and its people social work is one of the vitally important fields that had to be built up from almost nothing since independence was regained in 1991. During Soviet times social work and social workers did not receive the necessary attention. Severe social problems were denied and kept hidden since according to official communist ideology, life in the Soviet Union was the best in the world and getting better all the time. Social workers did not receive specialised education and their functions were to be carried out by the workers of trade unions and the party, by teachers and by the workers of the personnel departments. In the 1990s big changes, having also an effect on social life, took place in the development of Estonian society. Concepts such as social work and social worker were rediscovered in Estonia. There are certain prerequisites for the success of any activity (including social work). One of the most important ones is being a professional, a worker with thorough preparation. Social work as an occupation requires specialised academic education, which is based on theoretical knowledge and practical skills that have been acquired through theoretical knowledge. Specialised knowledge is a foundation for attaining a specialised qualification. However, at the same time one has to keep in mind that social work as an occupation is constantly changing, there is no absolute knowledge - everything is relative, dynamic and changing (Tamm, 1998). The changing nature of the activity requires reflection by a social worker, who also has to be able to evaluate his/her work and its basis and learn from experiences. Academic specialised education implies also the development of a new professional identity and higher levels of competence. This underlines the necessity of specialised education.

Presence of UV filters in surface water and the effects of phenylbenzimidazole sulfonic acid on rainbow trout (Oncorhynchus mykiss) following a chronic toxicity test

UV filters belong to a group of compounds that are used by humans and are present in municipal waste-waters, effluents from sewage treatment plants and surface waters. Current information regarding UV filters and their effects on fish is limited. In this study, the occurrence of three commonly used UV filters - 2-phenylbenzimidazole-5-sulfonic acid (PBSA), 2-hydroxy-4-methoxybenzophenone (benzophenone-3, BP-3) and 5-benzoyl-4-hydroxy-2-methoxy-benzenesulfonic acid (benzophenone-4, BP-4) - in South Bohemia (Czech Republic) surface waters is presented. PBSA concentrations (up to 13μgL(-1)) were significantly greater than BP-3 or BP-4 concentrations (up to 620 and 390ngL(-1), respectively). On the basis of these results, PBSA was selected for use in a toxicity test utilizing the common model organism rainbow trout (Oncorhynchus mykiss). Fish were exposed to three concentrations of PBSA (1, 10 and 1000µgL(-1)) for 21 and 42 days. The PBSA concentrations in the fish plasma, liver and kidneys were elevated after 21 and 42 days of exposure. PBSA increased activity of certain P450 cytochromes. Exposure to PBSA also changed various biochemical parameters and enzyme activities in the fish plasma. However, no pathological changes were obvious in the liver or gonads.

Actor and partner effects of self-esteem on relationship satisfaction and the mediating role of secure attachment between the partners

We examined actor and partner effects of self-esteem on relationship satisfaction, using the actor-partner interdependence model and data from five independent samples of couples. The results indicated that self-esteem predicted the individual’s own relationship satisfaction (i.e., an actor effect) and the relationship satisfaction of his or her partner (i.e., a partner effect), controlling for the effect of the partner’s selfesteem. Gender, age, and length of relationship did not moderate the effect sizes. Moreover, using one of the samples, we tested whether secure attachment to the current partner (assessed as low attachment-related anxiety and avoidance) mediated the effects. The results showed that attachment-related anxiety and avoidance independently mediated both the actor and the partner effect of self-esteem on relationship satisfaction.

Identification of the signal pathways modulated by expression of p210$\rm\sp{bcr-abl}$ and the inhibition of p210$\rm\sp{bcr-abl}$ transforming activity by polypeptides interacting with p210$\rm\sp{bcr-abl}$ in murine myeloid 32D cells

The Bcr-Abl fusion oncogene which resulted from a balanced reciprocal translocation between chromosome 9 and 22, t(9;22)(q11, q34), encodes a 210 KD elevated tyrosine specific protein kinase that is found in more than 95 percent of chronic myelogenous leukemia patients (CML). Increase of level of phosphorylation of tyrosine is observed on cell cycle regulatory proteins in cells overexpressing the Bcr-Abl oncogene, which activates multiple signaling pathways. In addition, distinct signals are required for transforming susceptible fibroblast and hematopoietic cells, and the minimal signals essential for transforming hematopoietic cells are yet to be defined. In the present study, we first established a tetracycline repressible p210$\rm\sp{bcr-abl}$ expression system in a murine myeloid cell line 32D c13, which depends on IL3 to grow in the presence of tetracycline and proliferate independent of IL3 in the absence of tetracycline. Interestingly, one of these sublines does not form tumors in athymic nude mice suggesting that these cells may not be completely transformed. These cells also exhibit a dose-dependent growth and expression of p210$\rm\sp{bcr-abl}$ at varying concentrations of tetracycline in the culture. However, p210$\rm\sp{bcr-abl}$ rescues IL3 deprivation induced apoptosis in a non-dose dependent fashion. DNA genotoxic damage induced by gamma-irradiation activates c-Abl tyrosine kinase, the cellular homologue of p210$\rm\sp{bcr-abl},$ and leads to activation of p38 MAP kinase in the cells. However, in the presence of p210$\rm\sp{bcr-abl}$ the irradiation failed to activate the p38 MAP kinase as examined by an antibody against phosphorylated p38 MAP kinase. Similarly, an altered tyrosine phosphorylation of the JAK1-STAT1 pathways was identified in cells constitutively overexpressing p210$\rm\sp{bcr-abl}.$ This may provided a molecular mechanism for altered therapeutic response of CML patients to IFN-$\alpha.$^ Bcr-Abl oncoprotein has multiple functional domains which have been identified by the work of others. The Bcr tetramerization domain, which may function to stabilize the association of the Bcr-Abl with actin filaments in p210$\rm\sp{bcr-abl}$ susceptible cells, are essential for transforming both fibroblast and hematopoietic cells. We designed a transcription unit encoding first 160 amino acids polypeptide of Bcr protein to test if this polypeptide can inhibit the transforming activity of the p210$\rm\sp{bcr-abl}$ oncoprotein in the 32D c13 cells. When this vector was transfected transiently along with the p210$\rm\sp{bcr-abl}$ expression vector, it can block the transforming activity of p210$\rm\sp{bcr-abl}.$ On the other hand, the retinoblastoma tumor suppressor protein (Rb), a naturally occurring negative regulator of the c-Abl kinase, the cellular homologue of Bcr-Abl oncoprotein, binds to and inhibits the c-Abl kinase in a cell cycle dependent manner. A polypeptide obtained from the carboxyl terminal end of the retinoblastoma tumor suppressor protein, in which the nuclear localization signal was mutated, was used to inhibit the kinase activity of the p210$\rm\sp{bcr-abl}$ in the cytoplasm. This polypeptide, called Rb MC-box, and its wild type form, Rb C-box, when overexpressed in the 32D cells are mainly localized in the cytoplasm. Cotransfection of a plasmid transcription unit coding for this polypeptide and the gene for the p210$\rm\sp{bcr-abl}$ resulted in reduced plating efficiency of p210$\rm\sp{bcr-abl}$ transfected IL3 independent 32D cells. Together, these results may lead to a molecular approach to therapy of CML and an in vitro assay system to identify new targets to which an inhibitory polypeptide transcription unit may be directed. ^

Tissue metabolomics of hepatocellular carcinoma: Tumor energy metabolism and the role of transcriptomic classification

Hepatocellular carcinoma (HCC) is one of the commonest causes of death from cancer. A plethora of metabolomic investigations of HCC have yielded molecules in biofluids that are both up- and down-regulated but no real consensus has emerged regarding exploitable biomarkers for early detection of HCC. We report here a different approach, a combined transcriptomics and metabolomics study of energy metabolism in HCC. A panel of 31 pairs of HCC tumors and corresponding nontumor liver tissues from the same patients was investigated by gas chromatography-mass spectrometry (GCMS)-based metabolomics. HCC was characterized by ∼2-fold depletion of glucose, glycerol 3- and 2-phosphate, malate, alanine, myo-inositol, and linoleic acid. Data are consistent with a metabolic remodeling involving a 4-fold increase in glycolysis over mitochondrial oxidative phosphorylation. A second panel of 59 HCC that had been typed by transcriptomics and classified in G1 to G6 subgroups was also subjected to GCMS tissue metabolomics. No differences in glucose, lactate, alanine, glycerol 3-phosphate, malate, myo-inositol, or stearic acid tissue concentrations were found, suggesting that the Wnt/β-catenin pathway activated by CTNNB1 mutation in subgroups G5 and G6 did not exhibit specific metabolic remodeling. However, subgroup G1 had markedly reduced tissue concentrations of 1-stearoylglycerol, 1-palmitoylglycerol, and palmitic acid, suggesting that the high serum α-fetoprotein phenotype of G1, associated with the known overexpression of lipid catabolic enzymes, could be detected through metabolomics as increased lipid catabolism. Conclusion: Tissue metabolomics yielded precise biochemical information regarding HCC tumor metabolic remodeling from mitochondrial oxidation to aerobic glycolysis and the impact of molecular subtypes on this process.

Molecular epidemiology of Mycoplasma hyopneumoniae from outbreaks of enzootic pneumonia in domestic pig and the role of wild boar.

Mycoplasma hyopneumoniae is the major cause of enzootic pneumonia (EP) in domestic pigs, a disease with low mortality but high morbidity, having a great economic impact for producers. In Switzerland EP has been successfully eradicated, however, sporadic outbreaks are observed with no obvious source. Besides the possibility of recurrent outbreaks due to persisting M. hyopneumoniae strains within the pig population, there is suspicion that wild boars might introduce M. hyopneumoniae into swine herds. To elucidate possible links between domestic pig and wild boar, epidemiological investigations of recent EP outbreaks were initiated and lung samples of pig and wild boar were tested for the presence of specific genotypes by multilocus sequence typing (MLST). Despite generally different genotypes in wild boar, outbreak strains could be found in geographically linked wild boar lungs after, but so far not before the outbreak. Recurrent outbreaks in a farm were due to the same strain, indicating unsuccessful sanitation rather than reintroduction by wild boar. In another case outbreaks in six different farms were caused by the same strain never found in wild boar, confirming spread between farms due to hypothesized animal transport. Results indicate the presence of identical lineages of wild boar and domestic pig strains, and possible transmission of M. hyopneumoniae between wild boar and pig. However, the role of wild boar might be rather one as a recipient than a transmitter. More important than contact to wild boar for sporadic outbreaks in Switzerland is apparently persistence of M. hyopneumoniae within a farm as well as transmission between farms.

Longitudinal Measurement Invariance Issues Illustrated by Examples of Marital Satisfaction in Later Life and the Structure of Psychopathology Before and After Psychotherapy

Talk at the Symposium "Opportunities and Challenges of Longitudinal Perspectives"

The impacts of volcanic aerosol on stratospheric ozone and the Northern Hemisphere polar vortex: separating radiative-dynamical changes from direct effects due to enhanced aerosol heterogeneous chemistry

After major volcanic eruptions the enhanced aerosol causes ozone changes due to greater heterogeneous chemistry on the particle surfaces (HET-AER) and from dynamical effects related to the radiative heating of the lower stratosphere (RAD-DYN). We carry out a series of experiments with an atmosphere–ocean–chemistry–climate model to assess how these two processes change stratospheric ozone and Northern Hemispheric (NH) polar vortex dynamics. Ensemble simulations are performed under present day and preindustrial conditions, and with aerosol forcings representative of different eruption strength, to investigate changes in the response behaviour. We show that the halogen component of the HET-AER effect dominates under present-day conditions with a global reduction of ozone (−21 DU for the strongest eruption) particularly at high latitudes, whereas the HET-AER effect increases stratospheric ozone due to N2O5 hydrolysis in a preindustrial atmosphere (maximum anomalies +4 DU). The halogen-induced ozone changes in the present-day atmosphere offset part of the strengthening of the NH polar vortex during mid-winter (reduction of up to −16 m s-1 in January) and slightly amplify the dynamical changes in the polar stratosphere in late winter (+11 m s-1 in March). The RAD-DYN mechanism leads to positive column ozone anomalies which are reduced in a present-day atmosphere by amplified polar ozone depletion (maximum anomalies +12 and +18 DU for present day and preindustrial, respectively). For preindustrial conditions, the ozone response is consequently dominated by RAD-DYN processes, while under present-day conditions, HET-AER effects dominate. The dynamical response of the stratosphere is dominated by the RAD-DYN mechanism showing an intensification of the NH polar vortex in winter (up to +10 m s-1 in January). Ozone changes due to the RAD-DYN mechanism slightly reduce the response of the polar vortex after the eruption under present-day conditions.