Maternal smoking during pregnancy and appetite control in offspring

Aims: Intrauterine exposure to tobacco smoke products has been associated with long-term neurobehavioral effects. Modified appetite control might explain the recently observed association between maternal smoking during pregnancy and obesity in offspring. Methods: Some 10,557 British adults aged 42 years born between 3-9 March 1958 were followed up in a birth cohort study (NCDS). The main outcome measure was self-reported poor appetite at age 42 years and main exposure was maternal smoking during pregnancy. Results: The proportion of offspring with poor appetite increased with maternal smoking during pregnancy: nonsmoking 4.5%; (4.0% - 5.0%), medium smoking 5.6%; (4.5 % - 6.8 %), variable smoking 6.8 %; (4.9 % - 9.1 %) and heavy smoking 7.7 %; (6.3 % - 9.4 %). The unadjusted odds ratios for maternal smoking during pregnancy (ever/never) and poor appetite is 1.49 (1.25 - 1.77) and after adjustment for BMI at 42 years and other potential confounding factors it is 1.22 (1.07 - 1.48). Conclusions: Offspring of mothers who smoked during pregnancy were more likely to report a poor appetite independent of a number of potential confounding factors. Although not in the expected direction, the results suggest maternal smoking during pregnancy may influence appetite perception through a developmental influence or through confounding by social factors

Vinylphosphonites for staudinger-induced chemoselective peptide cyclization and functionalization

In this paper, we introduce vinylphosphonites for chemoselective Staudinger-phosphonite reactions (SPhR) with azides to form vinylphosphonamidates for the subsequent modification of cysteine residues in peptides and proteins. An electron-rich alkene is turned into an electron-deficient vinylphosphonamidate, thereby inducing electrophilic reactivity for a following thiol addition. We show that by varying the phosphonamidate ester substituent we can fine-tune the reactivity of the thiol addition and even control the functional properties of the final conjugate. Furthermore, we observed a drastic increase in thiol addition efficiency when the SPhR is carried out in the presence of a thiol substrate in a one-pot reaction. Hence, we utilize vinylphosphonites for the chemoselective intramolecular cyclization of peptides carrying an azide-containing amino acid and a cysteine in high yields. Our concept was demonstrated for the stapling of a cell-permeable peptidic inhibitor for protein–protein interaction (PPI) between BCL9 and beta-catenin, which is known to create a transcription factor complex playing a role in embryonic development and cancer origin, and for macrocyclization of cell-penetrating peptides (CPPs) to enhance the cellular uptake of proteins

Assessment of varicella vaccine effectiveness in Germany: a time-series approach

A multivariate time-series regression model was developed in order to describe the 2005-2008 age-specific time-course of varicella sentinel surveillance data following the introduction of a varicella childhood vaccination programme in Germany. This ecological approach allows the assessment of vaccine effectiveness under field conditions by relating vaccine coverage in cohorts of 24-month-old children to the mean number of cases per reporting unit in the sentinel network. For the 1-2 years age group, which is directly affected by the vaccination programme, a one-dose vaccine effectiveness of 83·2% (95% CI 80·2-85·7) was estimated which corresponds to previous approaches assessing varicella vaccine effectiveness in the field in the US

Latent class analysis of diagnostic tests for adenovirus, Bordetella pertussis and influenza virus infections in German adults with longer lasting coughs

Laboratory tests in adult outpatients with longer lasting coughs to identify a potential causal pathogen are rarely performed, and there is no gold standard for these diagnostic tests. While the diagnostic validity of serological tests for pertussis is well established their potential contribution for diagnosing adenovirus and influenza virus A and B infections is unclear. A sentinel study into the population-based incidence of longer lasting coughs in adults was done in Rostock (former East Germany) and Krefeld (former West Germany). A total of 971 outpatients who consulted general practitioners or internists were included. Inclusion criteria were coughing for 51 week and no chronic respiratory diseases. We evaluated the performance of polymerase chain reaction (PCR) as well as IgG and IgA serology, applying a latent class model for diagnosing infections with adenovirus, B. pertussis, and influenza virus A and B. The adult outpatients first sought medical attention when they had been coughing for a median of 3 weeks. In this situation, direct detection of infectious agents by PCR had a low sensitivity. Modelling showed that additional serological tests equally improved sensitivity and specificity for diagnosis for adenovirus, B. pertussis and influenza virus A and B infections. The combination of serology and PCR may improve the overall performance of diagnostic tests for B. pertussis and also for adenovirus, and influenza virus A and B infections

Self-reported neck pain is associated with migraine but not with tension-type headache in adolescents

AIM: The aim of the present analysis is to confirm or refute the association of neck pain to migraine or tension-type headache and to assess whether this association is independent of other risk factors for headache. METHODS: Secondary school students were invited to complete a questionnaire on headache and lifestyle factors in a cross-sectional study. Neck pain was assessed via (a) a screening question concerning neck pain and (b) denoting affected areas in schematic drawings of the human body. RESULTS: Absolute increment in prevalence of headache with pain in the shoulder-neck region was between 7.5 and 9.6. Gender, grade, stress and lifestyle factors were assessed as potential confounding factors. Nearly all factors were associated with shoulder-neck pain and most with headache. After adjustment for confounders, the association of neck pain with headache was almost completely confined to migraine (OR 2.39; 95 CI 1.48-3.85) and migraine + tension-type headache (OR 2.12; 95 CI 1.50-2.99), whereas the association with isolated tension-type headache was negligible (OR 1.22, 95 CI 0.87-1.69). CONCLUSION: Neck pain is associated with migraine but not with tension-type headache. A possible link between migraine and neck pain may be the cervico-trigeminal convergence of neck and meningeal sensory afferents or a disturbed descending inhibition in migraine

A small-molecule antagonist of the β-catenin/TCF4 interaction blocks the self-renewal of cancer stem cells and suppresses tumorigenesis

Wnt/beta-catenin signaling is a highly conserved pathway essential for embryogenesis and tissue homeostasis. However, deregulation of this pathway can initiate and promote human malignancies, especially of the colon and head and neck. Therefore, Wnt/beta-catenin signaling represents an attractive target for cancer therapy. We performed high-throughput screening (HTS) using AlphaScreen and ELISA techniques to identify small molecules that disrupt the critical interaction between beta-catenin and the transcription factor TCF4 required for signal transduction. We found that compound LF3, a 4-thioureido-benzenesulfonamide derivative, robustly inhibited this interaction. Biochemical assays revealed clues that the core structure of LF3 was essential for inhibition. LF3 inhibited Wnt/beta-catenin signals in cells with exogenous reporters and in colon cancer cells with endogenously high Wnt activity. LF3 also suppressed features of cancer cells related to Wnt signaling, including high cell motility, cell cycle progression, and the overexpression of Wnt target genes. However, LF3 did not cause cell death or interfere with cadherin-mediated cell-cell adhesion. Remarkably, the self-renewal capacity of cancer stem cells was blocked by LF3 in concentration-dependent manners, as examined by sphere formation of colon and head and neck cancer stem cells under non-adherent conditions. Finally, LF3 reduced tumor growth and induced differentiation in a mouse xenograft model of colon cancer. Collectively, our results strongly suggest that LF3 is a specific inhibitor of canonical Wnt signaling with anticancer activity that warrants further development for preclinical and clinical studies as a novel cancer therapy

Self-reported neck pain is associated with migraine but not with tension-type headache in adolescents

AIM: The aim of the present analysis is to confirm or refute the association of neck pain to migraine or tension-type headache and to assess whether this association is independent of other risk factors for headache. METHODS: Secondary school students were invited to complete a questionnaire on headache and lifestyle factors in a cross-sectional study. Neck pain was assessed via (a) a screening question concerning neck pain and (b) denoting affected areas in schematic drawings of the human body. RESULTS: Absolute increment in prevalence of headache with pain in the shoulder-neck region was between 7.5 and 9.6. Gender, grade, stress and lifestyle factors were assessed as potential confounding factors. Nearly all factors were associated with shoulder-neck pain and most with headache. After adjustment for confounders, the association of neck pain with headache was almost completely confined to migraine (OR 2.39; 95 CI 1.48-3.85) and migraine + tension-type headache (OR 2.12; 95 CI 1.50-2.99), whereas the association with isolated tension-type headache was negligible (OR 1.22, 95 CI 0.87-1.69). CONCLUSION: Neck pain is associated with migraine but not with tension-type headache. A possible link between migraine and neck pain may be the cervico-trigeminal convergence of neck and meningeal sensory afferents or a disturbed descending inhibition in migraine

Разработка и внедрение системы мотивации персонала на основе ключевых критериев результатив-ности

Выпускная квалификационная работа содержит 119 с., 1 рис., 17 табл., 46 источников, 6 приложений. Ключевые слова: мотивация, система мотивации персонала, ключевые критерии/показатели результативности, мотивация на основе ключевых показателей результативности, управление персоналом, управление результативностью. Объектом исследования выпускной квалификационной работы является система менеджмента качества ООО «Томскводоканал». Целью данной работы является разработка и внедрение системы мотивации персонала на основе ключевых критериев результативности на предприятии ООО «Томскводоканал». В результате исследования будут разработаны ключевые показатели результативности и методика расчета по вычислению премии за достижение каждого показателя сотрудниками организации.Final qualifying work contains 119 p., 1 fig., 17 tab., 46 sources, 6 applications. Keywords: motivation, motivation system, key performance indicators, motivation based on key performance indicators, personnel management, performance management. The object of study of final qualifying work is the quality management system "Tomskvodokanal". The aim of this work is the development and implementation of personnel motivation system based on key performance indicators of the company "Tomskvodokanal". The study will develop key performance indicators and the method of calculation for the calculation of premiums for the achievement of each indicator in the organization