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Abstract Aim of this project was to assess occupational biological hazards with regard to the risk of hepatitis A (HAV) and hepatitis B (HBV) and the need for occupational health care in schools for pupils with special needs. Teachers and educational specialists were surveyed about activities potentially providing exposure to biological agents and their individual immune status regarding HAV and HBV by a detailed questionnaire. Descriptive analyses, group comparisons and logistic regression were performed to identify factors influencing the HAV and HBV immune status. 1398 teachers and educational specialists took part. 1381 respondents reported having physical contact with pupils at work (98%). Daily contact was reported by up to 84% of all employees. Being scratched, bitten or spat at was reported by up to 93%. Hazardous activities are performed by both teachers and educational specialists. The vaccination rate was reported to be 58% for HAV and 64% for HBV. In regression analyses, failing to receive vaccine counselling [HAV: aOR 0.36 (95% CI 0.28; 0.46; p

Abstract Reconstructing gene regulatory networks is crucial to understand biological processes and holds potential for developing personalized treatment. Yet, it is still an open problem as state-of-the-art algorithms are often not able to process large amounts of data within reasonable time. Furthermore, many of the existing methods predict numerous false positives and have limited capabilities to integrate other sources of information, such as previously known interactions. Here we introduce KBoost, an algorithm that uses kernel PCA regression, boosting and Bayesian model averaging for fast and accurate reconstruction of gene regulatory networks. We have benchmarked KBoost against other high performing algorithms using three different datasets. The results show that our method compares favorably to other methods across datasets. We have also applied KBoost to a large cohort of close to 2000 breast cancer patients and 24,000 genes in less than 2 h on standard hardware. Our results show that molecularly defined breast cancer subtypes also feature differences in their GRNs. An implementation of KBoost in the form of an R package is available at: https://github.com/Luisiglm/KBoost and as a Bioconductor software package.

Purpose: To compare the impact of institutional and epidemiologic factors on differences in application trends of Canadian medical graduates (CMGs) from different medical schools to FRCPC emergency medicine (EM) residency programs. Methods: This was a retrospective cohort study. Data from 2013-2018 were obtained from the Canadian Resident Matching Service (CaRMS) database and standardized questionnaires sent to Canadian medical schools. Results: CaRMS data were available for all schools and survey data was available for 76% schools. Five schools yielded significantly higher rates of applications to FRCPC-EM programs (8.8-13.1%, p

Abstract The Hippo signaling pathway is involved in organ size regulation and tumor suppression. Although inhibition of Hippo leads to tumorigenesis, activation of Hippo may play a role in neurodegeneration. Specifically, activation of the upstream regulator, mammalian sterile 20 (STE20)-like kinase 1 (MST1), reduces activity of the transcriptional co-activator Yes-Associated Protein (YAP), thereby mediating oxidative stress-induced neuronal death. Here, we investigated the possible role of this pathway in Huntington’s disease (HD) pathogenesis. Our results demonstrate a significant increase in phosphorylated MST1, the active form, in post-mortem HD cortex and in the brains of CAG knock-in Hdh Q111/Q111 mice. YAP nuclear localization was also decreased in HD post-mortem cortex and in neuronal stem cells derived from HD patients. Moreover, there was a significant increase in phosphorylated YAP, the inactive form, in HD post-mortem cortex and in Hdh Q111/Q111 brain. In addition, YAP was found to interact with huntingtin (Htt) and the chaperone 14-3-3, however this interaction was not altered in the presence of mutant Htt. Lastly, YAP/TEAD interactions and expression of Hippo pathway genes were altered in HD. Together, these results demonstrate that activation of MST1 together with a decrease in nuclear YAP could significantly contribute to transcriptional dysregulation in HD.

Beauty is the single most frequently and most broadly used aesthetic virtue term. The present study aimed at providing higher conceptual resolution to the broader notion of beauty by comparing it with three closely related aesthetically evaluative concepts which are likewise lexicalized across many languages: elegance, grace(fulness), and sexiness. We administered a variety of questionnaires that targeted perceptual qualia, cognitive and affective evaluations, as well as specific object properties that are associated with beauty, elegance, grace, and sexiness in personal looks, movements, objects of design, and other domains. This allowed us to reveal distinct and highly nuanced profiles of how a beautiful, elegant, graceful, and sexy appearance is subjectively perceived. As aesthetics is all about nuances, the fine-grained conceptual analysis of the four target concepts of our study provides crucial distinctions for future research.

One response of cells to growth factor stimulus involves changes in morphology driven by the actin cytoskeleton and actin associated proteins which regulate functions such as cell adhesion, motility and in neurons, synaptic plasticity. Previous studies suggest that Huntingtin may be involved in regulating morphology however, there has been limited evidence linking endogenous Huntingtin localization or function with cytoplasmic actin in cells. We found that depletion of Huntingtin in human fibroblasts reduced adhesion and altered morphology and these phenotypes were made worse with growth factor stimulation, whereas the presence of the Huntington's Disease mutation inhibited growth factor induced changes in morphology and increased numbers of vinculin-positive focal adhesions. Huntingtin immunoreactivity localized to actin stress fibers, vinculin-positive adhesion contacts and membrane ruffles in fibroblasts. Interactome data from others has shown that Huntingtin can associate with α-actinin isoforms which bind actin filaments. Mapping studies using a cDNA encoding α-actinin-2 showed that it interacts within Huntingtin aa 399-969. Double-label immunofluorescence showed Huntingtin and α-actinin-1 co-localized to stress fibers, membrane ruffles and lamellar protrusions in fibroblasts. Proximity ligation assays confirmed a close molecular interaction between Huntingtin and α-actinin-1 in human fibroblasts and neurons. Huntingtin silencing with siRNA in fibroblasts blocked the recruitment of α-actinin-1 to membrane foci. These studies support the idea that Huntingtin is involved in regulating adhesion and actin dependent functions including those involving α-actinin.

Individual regulatory proteins are typically charged with the simultaneous regulation of a battery of different genes. As a result, when one of these proteins is limiting, competitive effects have a significant impact on the transcriptional response of the regulated genes. Here we present a general framework for the analysis of any generic regulatory architecture that accounts for the competitive effects of the regulatory environment by isolating these effects into an effective concentration parameter. These predictions are formulated using the grand-canonical ensemble of statistical mechanics and the fold-change in gene expression is predicted as a function of the number of transcription factors, the strength of interactions between the transcription factors and their DNA binding sites, and the effective concentration of the transcription factor. The effective concentration is set by the transcription factor interactions with competing binding sites within the cell and is determined self-consistently. Using this approach, we analyze regulatory architectures in the grand-canonical ensemble ranging from simple repression and simple activation to scenarios that include repression mediated by DNA looping of distal regulatory sites. It is demonstrated that all the canonical expressions previously derived in the case of an isolated, non-competing gene, can be generalised by a simple substitution to their grand canonical counterpart, which allows for simple intuitive incorporation of the influence of multiple competing transcription factor binding sites. As an example of the strength of this approach, we build on these results to present an analytical description of transcriptional regulation of the lac operon.

Emiliania huxleyi, a key player in the global carbon cycle is one of the best studied coccolithophores with respect to biogeochemical cycles, climatology, and host-virus interactions. Strains of E. huxleyi show phenotypic plasticity regarding growth behaviour, light-response, calcification, acidification, and virus susceptibility. This phenomenon is likely a consequence of genomic differences, or transcriptomic responses, to environmental conditions or threats such as viral infections. We used an E. huxleyi genome microarray based on the sequenced strain CCMP1516 (reference strain) to perform comparative genomic hybridizations (CGH) of 16 E. huxleyi strains of different geographic origin. We investigated the genomic diversity and plasticity and focused on the identification of genes related to virus susceptibility and coccolith production (calcification). Among the tested 31940 gene models a core genome of 14628 genes was identified by hybridization among 16 E. huxleyi strains. 224 probes were characterized as specific for the reference strain CCMP1516. Compared to the sequenced E. huxleyi strain CCMP1516 variation in gene content of up to 30 percent among strains was observed. Comparison of core and non-core transcripts sets in terms of annotated functions reveals a broad, almost equal functional coverage over all KOG-categories of both transcript sets within the whole annotated genome. Within the variable (non-core) genome we identified genes associated with virus susceptibility and calcification. Genes associated with virus susceptibility include a Bax inhibitor-1 protein, three LRR receptor-like protein kinases, and mitogen-activated protein kinase. Our list of transcripts associated with coccolith production will stimulate further research, e.g. by genetic manipulation. In particular, the V-type proton ATPase 16 kDa proteolipid subunit is proposed to be a plausible target gene for further calcification studies.

As in any vertebrate, heads of fishes are densely packed with functions. These functions often impose conflicting mechanical demands resulting in trade-offs in the species-specific phenotype. When phenotypical traits are linked to gender-specific parental behavior, we expect sexual differences in these trade-offs. This study aims to use mouthbrooding cichlids as an example to test hypotheses on evolutionary trade-offs between intricately linked traits that affect different aspects of fitness. We focused on the oral apparatus, which is not only equipped with features used to feed and breathe, but is also used for the incubation of eggs. We used this approach to study mouthbrooding as part of an integrated functional system with diverging performance requirements and to explore gender-specific selective environments within a species.Because cichlids are morphologically very diverse, we hypothesize that the implications of the added constraint of mouthbrooding will primarily depend on the dominant mode of feeding of the studied species. To test this, we compared the trade-off for two maternal mouthbrooding cichlid species: a "suction feeder" (Haplochromis piceatus) and a "biter" (H. fischeri). The comparison of morphology and performance of both species revealed clear interspecific and intersex differences. Our observation that females have larger heads was interpreted as a possible consequence of the fact that in both the studied species mouthbrooding is done by females only. As hypothesized, the observed sexual dimorphism in head shape is inferred as being suboptimal for some aspects of the feeding performance in each of the studied species. Our comparison also demonstrated that the suction feeding species had smaller egg clutches and more elongated eggs.Our findings support the hypothesis that there is a trade-off between mouthbrooding and feeding performance in the two studied haplochromine cichlids, stressing the importance of including species-specific information at the gender level when addressing interspecific functional/morphological differences.

Introducción: en julio de 2002, en el Centro Hospitalario Pereira Rossell (CHPR) se implementó una pauta de profilaxis antibiótica en la cesárea que consiste en la administración de cefazolina 2g intravenosa posclampeo del cordón umbilical. Objetivo: evaluar el cumplimiento de la pauta de profilaxis antibiótica en la cesárea en el CHPR y su impacto sobre el consumo y gasto de antibióticos. Material y método: se comparó el cumplimiento de la pauta a través del análisis del perfil farmacológico individual (antibiótico indicado; vía, momento y duración de la administración) en noviembre de 2002 versus noviembre de 2004. Se comparó el impacto de la aplicación de la pauta a través de la evolución mensual del consumo (DDD/100 camas día) (dosis diarias definidas/días camas ocupadas) y gasto en antibióticos (U$S) en el período mayo-noviembre de 2002 versus mayo-noviembre de 2004. Los datos fueron obtenidos a través del sistema de distribución y dispensación de medicamentos por dosis unitaria y de las historias clínicas. Resultados: la pauta se cumplió en 85% (n=41) de las pacientes analizadas en 2002 y en 65% (n=47) de las analizadas en 2004 (p

Introducción: El uso irracional de los medicamentos constituye un riesgo inadmisible para los pacientes y un continuo derroche de recursos. De los diversos factores que contribuyen a esta realidad, el hábito de prescripción de los médicos es uno de los más frecuentes. La prescripción es un proceso razonado que exige el uso de información actualizada e independiente sobre los medicamentos. Objetivo: Conocer la información que tienen los médicos residentes de pediatría y medicina interna sobre medicamentos de uso frecuente. Material y método: En diciembre de 2002 se encuestaron en forma personal y anónima, 69 médicos residentes (38 de pediatría y 31 de medicina interna). Se evaluó el conocimiento sobre nombre genérico, dosis, efectos adversos y contraindicaciones absolutas de medicamentos de uso frecuente en cada una de las disciplinas. Las respuestas fueron catalogadas como verdaderas o falsas utilizando un estándar elaborado por los autores. Resultados: Los porcentajes de respuestas verdaderas entre los residentes de pediatría fueron: genérico 82%, dosis 42%, efectos adversos comunes 16%, efectos adversos graves 16% y contraindicaciones 32%. Entre los residentes de medicina interna: genérico 89%, dosis 53%, efectos adversos comunes 16%, efectos adversos graves 45% y contraindicaciones 46%. Se observó una proporción mayor de respuestas verdaderas estadísticamente significativa, entre los residentes de medicina interna en relación a las dosis, efectos adversos graves y contraindicaciones. Conclusiones: Una elevada proporción de los residentes encuestados no tiene conocimientos suficientes en relación a las dosis, los efectos adversos y las contraindicaciones de estos medicamentos de uso frecuente. Esto constituye un factor determinante en la prescripción irracional de los medicamentos. Es necesario fortalecer la formación continua en farmacología y terapéutica de los médicos residentes para revertir este problema.