Declining transition rates to psychosis: The role of diagnostic spectra and symptom overlaps in individuals with attenuated psychosis syndrome

Transition to psychosis in at-risk individuals has markedly declined in recent years. So far it has never been discussed in detail that with the growing awareness and increasing availability of early psychosis services, a much broader diagnostic spectrum is now being seen in these services. Subsequently, subjects present with symptoms that meet psychosis risk on a purely psychometric basis but may be the phenotypical expression of another underlying mental disorder. Here we critically review four groups of symptoms and clinical features that are frequently reported by individuals with suspected psychosis risk states, yet share strong commonalities with other mental disorders and conditions: isolated hallucinations; unusual bodily perceptions, hypochondriatic fears and cenesthetic psychotic symptoms; depersonalization; obsessive–compulsive, overvalued and delusional ideas. Of the 616 individuals so far assessed in the Bruderholz Early Psychosis Outpatient Service for Adolescents and Young Adults, 218 (30.5%) met ultra-high risk (UHR) criteria, 188 (86.2%) of whom suffered from one of the four above-mentioned symptom groups. The appraisal of the diagnostic spectra and their overlapping symptoms constitute a tremendous challenge in the clinical assessment of each referred individual. The final conclusion of a clinical assessment should not end with the mere assignment – or non-assignment – to a presumed psychosis risk group, but needs to take into account the ‘Gestalt’ of these particular symptoms and clinical features and thus be based on many more facets than solely a psychometric or nosological approach. Such an approach may break down the heterogeneous psychosis risk group and enable appropriate treatment regimes.

Cholesterol metabolism, transport, and hepatic regulation in dairy cows during transition and early lactation

The transition from the nonlactating to the lactating state represents a critical period for dairy cow lipid metabolism because body reserves have to be mobilized to meet the increasing energy requirements for the initiation of milk production. The purpose of this study was to provide a comprehensive overview on cholesterol homeostasis in transition dairy cows by assessing in parallel plasma, milk, and hepatic tissue for key factors of cholesterol metabolism, transport, and regulation. Blood samples and liver biopsies were taken from 50 multiparous Holstein dairy cows in wk 3 antepartum (a.p.), wk 1 postpartum (p.p.), wk 4 p.p., and wk 14 p.p. Milk sampling was performed in wk 1, 4, and 14 p.p. Blood and milk lipid concentrations [triglycerides (TG), cholesterol, and lipoproteins], enzyme activities (phospholipid transfer protein and lecithin:cholesterol acyltransferase) were analyzed using enzymatic assays. Hepatic gene expression patterns of 3-hydroxy-3-methylglutaryl-coenzyme A (HMGC) synthase 1 (HMGCS1) and HMGC reductase (HMGCR), sterol regulatory element-binding factor (SREBF)-1 and -2, microsomal triglyceride transfer protein (MTTP), ATP-binding cassette transporter (ABC) A1 and ABCG1, liver X receptor (LXR) α and peroxisome proliferator activated receptor (PPAR) α and γ were measured using quantitative RT-PCR. Plasma TG, cholesterol, and lipoprotein concentrations decreased from wk 3 a.p. to a minimum in wk 1 p.p., and then gradually increased until wk 14 p.p. Compared with wk 4 p.p., phospholipid transfer protein activity was increased in wk 1 p.p., whereas lecithin:cholesterol acyltransferase activity was lowest at this period. Total cholesterol concentration and mass, and cholesterol concentration in the milk fat fraction decreased from wk 1 p.p. to wk 4 p.p. Both total and milk fat cholesterol concentration were decreased in wk 4 p.p. compared with wk 1 and 14 p.p. The mRNA abundance of genes involved in cholesterol synthesis (SREBF-2, HMGCS1, and HMGCR) markedly increased from wk 3 a.p. to wk 1 p.p., whereas SREBF-1 was downregulated. The expression of ABCA1 increased from wk 3 a.p. to wk 1 p.p., whereas ABCG1 was increased in wk 14 p.p. compared with other time points. In conclusion, hepatic expression of genes involved in the biosynthesis of cholesterol as well as the ABCA1 transporter were upregulated at the onset of lactation, whereas plasma concentrations of total cholesterol, phospholipids, lipoprotein-cholesterol, and TG were at a minimum. Thus, at the gene expression level, the liver seems to react to the increased demand for cholesterol after parturition. Whether the low plasma cholesterol and TG levels are due to impaired hepatic export mechanisms or reflect an enhanced transfer of these compounds into the milk to provide essential nutrients for the newborn remains to be elucidated.

Transition metal ligands as novel DNA-base substitutes

The base modified nucleoside dBP, carrying a non-hydrogen-bonding non-shape complementary base was incorporated into oligonucleotides (Brotschi, C.; Haberli, A.; Leumann C.J. Angew. Chem. Int. Ed. 2001, 40, 3012-3014). This base was designed to coordinate transition metal ions into well defined positions within a DNA double helix. Melting experiments revealed that the stability of a dBP:dBP base couple in a DNA duplex is similar to a dG:dC base pair even in the absence of transition metal ions. In the presence of transition metal ions, melting experiments revealed a decrease in duplex stability which is on a similar order for all metal ions (Mn2+, Cu2+, Zn2+, Ni2+) tested

Alpha1a-adrenoceptor genetic variant induces cardiomyoblast-to-fibroblast-like cell transition via distinct signaling pathways.

The role of naturally occurring human α1a-Adrenergic Receptor (α1aAR) genetic variants associated with cardiovascular disorders is poorly understood. Here, we present the novel findings that expression of human α1aAR-247R (247R) genetic variant in cardiomyoblasts leads to transition of cardiomyoblasts into a fibroblast-like phenotype, evidenced by morphology and distinct de novo expression of characteristic genes. These fibroblast-like cells exhibit constitutive, high proliferative capacity and agonist-induced hypertrophy compared with cells prior to transition. We demonstrate that constitutive, synergistic activation of EGFR, Src and ERK kinases is the potential molecular mechanism of this transition. We also demonstrate that 247R triggers two distinct EGFR transactivation-dependent signaling pathways: 1) constitutive Gq-independent β-arrestin-1/Src/MMP/EGFR/ERK-dependent hyperproliferation and 2) agonist-induced Gq- and EGFR/STAT-dependent hypertrophy. Interestingly, in cardiomyoblasts agonist-independent hyperproliferation is MMP-dependent, but in fibroblast-like cells it is MMP-independent, suggesting that expression of α1aAR genetic variant in cardiomyocytes may trigger extracellular matrix remodeling. Thus, these novel findings demonstrate that EGFR transactivation by α1aAR-247R leads to hyperproliferation, hypertrophy and alterations in cardiomyoblasts, suggesting that these unique genetically-mediated alterations in signaling pathways and cellular function may lead to myocardial fibrosis. Such extracellular matrix remodeling may contribute to the genesis of arrhythmias in certain types of heart failure.

Marital breakup in later adulthood and self-rated health: a cross-sectional survey in Switzerland

This research examines the impact of relationship status on self-rated health (SRH) by taking into account intrapersonal and social resources. Data stem from a Swiss-based survey of 1355 participants aged 40-65 years. Three groups are compared: continuously married (n = 399), single divorcees (n = 532) and repartnered divorcees (n = 424). Linear regression models are used to examine the predictive role of relationship status on SRH and to investigate the moderating role of intrapersonal and social resources on SRH. Single divorcees show the lowest SRH scores, whereas their repartnered counterparts reported scores comparable to the continuously married – even after controlling for socio-demographic and economic variables. Although single divorcees reported higher levels of loneliness and agreeableness in addition to lower levels of resilience when compared with the other groups, none of these variables had a significant modification effect on SRH. Our results underscore the positive effect of relationship status on SRH, and contribute new insights on the impact of later-life divorce. Given the growing number of divorcees, related public health challenges are likely to increase.

Marital breakup in later adulthood and self-rated health: a cross-sectional survey in Switzerland

Objectives This research examines the impact of relationship status on self-rated health (SRH) by taking into account intrapersonal and social resources. Methods Data stem from a Swiss-based survey of 1355 participants aged 40–65 years. Three groups are compared: continuously married (n = 399), single divorcees (n = 532) and repartnered divorcees (n = 424). Linear regression models are used to examine the predictive role of relationship status on SRH and to investigate the moderating role of intrapersonal and social resources on SRH. Results Single divorcees show the lowest SRH scores, whereas their repartnered counterparts reported scores comparable to the continuously married—even after controlling for socio-demographic and economic variables. Although single divorcees reported higher levels of loneliness and agreeableness in addition to lower levels of resilience when compared with the other groups, none of these variables had a significant moderation effect on SRH. Conclusions Our results underscore the positive effect of relationship status on SRH, and contribute new insights on the impact of later-life divorce. Given the growing number of divorcees, related public health challenges are likely to increase.

The International Financial Reporting Standards and Their Implementation into the US Accounting System

This paper examines the differences between the International Financial Reporting Standards (IFRS) and Generally Accepted Accounting Principles (GAAP). The areas closely examined are the differences inrevenue recognition and reporting of intangibles. By investigating the differences in the two sets of standards I put into context the changes that would be necessary for domestic companies adopting the IFRS. The differences between these two standards are important because the implementation of IFRS into the U.S. is a current issue for domestic companies. It is important to note how the new standards will affect different companies in different ways. Depending on the size and industry, some companies will have a harder time transitioning to the new standards. However, once these companies make the transition to IFRS they will have better recognition and reporting of revenues and intangibles.

Economic Growth, Longevity, and the Epidemiological Transition

This paper integrates investments in health to a standard growth model where physical and human capital investments are the combined engines of growth. It shows the existence of two distinct health regimes separated by an 'Epidemiological Transition'. The various patterns of the transition identified in the epidemiological literature can be mapped into the model. The model also leads to the important hypothesis that the epidemiological transition may induce an economy to switch to a modern growth regime.

Importance of sperm transition proteins demonstrated in mice carrying Tnp1- and Tnp2-null alleles

Chromatin condensation within the nucleus of developing spermatids involves replacement of histones by transition proteins, which are in turn replaced by protamines. The importance of transition proteins in the complex process of spermiogenesis has, to date, been only speculative. This study sought to investigate the extent to which transition proteins are essential or have redundant functions by characterizing sperm produced in mice expressing all combinations of Tnp-null alleles. Results from breeding trials of 8 weeks duration revealed that, on average, wildtype males produced about 14 offspring whereas TP2 and TP1 single-knockout males produced about 8 and 1 offspring, respectively, demonstrating their subfertility. Genotypes with less than two Tnp wildtype alleles, as well as double-knockout mutants, were completely infertile. Sperm from males with impaired fertility had poor progressive motility, heterogeneous chromatin condensation, incompletely processed protamine 2 and head and tail abnormalities. Generally, as the number of Tnp-null alleles increased so did the severity of abnormalities. However, specific morphological abnormalities were associated with the absence of an individual TP. Studies which sought to identify possible root causes for abnormalities in thiol-rich sperm structures revealed no differences in thiol content or sulfhydryl oxidation status within the nucleus but nuclei and tails from single-knockout mutants were severely disrupted following thiol reduction. Binding of fluorescent dyes to DNA was normal in sperm recovered from caput but abnormal in cauda epididymal sperm from TP1 knockouts and infertile double mutants. Injection of cauda epididymal sperm from double knockouts into oocytes produced very few offspring; however, after injection with testicular sperm, the efficiency was no different from wildtype. These results suggest DNA structural alterations or degradation during epididymal transport of sperm resulting in a diminished capacity of the paternal DNA of these sperm to produce offspring. The overall importance of transition proteins for normal chromatin condensation and production of fertile sperm has been demonstrated. Furthermore, identification of specific morphological abnormalities associated with the absence of an individual transition protein provides new evidence that the proteins are not completely redundant and each fulfills some unique function. ^

MOLECULAR AND GENOMIC BASED INSIGHTS INTO THE EVOLUTION OF ENTEROCOCCUS FAECIUM FROM COMMENSAL TO HOSPITAL-ADAPTED PATHOGEN

The basis for the recent transition of Enterococcus faecium from a primarily commensal organism to one of the leading causes of hospital-acquired infections in the United States is not yet understood. To address this, the first part of my project assessed isolates from early outbreaks in the USA and South America using sequence analysis, colony hybridizations, and minimal inhibitory concentrations (MICs) which showed clinical isolates possess virulence and antibiotic resistance determinants that are less abundant or lacking in community isolates. I also revealed that the level of ampicillin resistance increased over time in clinical strains. By sequencing the pbp5 gene, I demonstrated an ~5% difference in the pbp5 gene between strains with MICs <4ug/ml and those with MICs >4µg/ml, but no specific sequence changes correlated with increases in MICs within the latter group. A 3-10% nucleotide difference was also seen in three other genes analyzed, which suggested the existence of two distinct subpopulations of E. faecium. This led to the second part of my project analyzing concatenated core gene sequences, SNPs, the 16S rRNA, and phylogenetics of 21 E. faecium genomes confirming two distinct clades; a community-associated (CA) clade and hospital-associated (HA) clade. Molecular clock calculations indicate that these two clades likely diverged ~ 300,000 to > 1 million years ago, long before the modern antibiotic era. Genomic analysis also showed that, in addition to core genomic differences, HA E. faecium harbor specific accessory genetic elements that may confer selection advantages over CA E. faecium. The third part of my project discovered 6 E. faecium genes with the newly identified “WxL” domain. My analyses, using RT-PCR, western blots, patient sera, whole-cell ELISA, and immunogold electron microscopy, indicated that E. faecium WxL genes exist in operons, encode bacterial cell surface localized proteins, that WxL proteins are antigenic in humans, and are more exposed on the surface of clinical isolates versus community isolates (even though they are ubiquitous in both clades). ELISAs and BIAcore analyses also showed that proteins encoded by these operons bind several different host extracellular matrix proteins, as well as to each other, suggesting a novel cell-surface complex. In summary, my studies provide new insights into the evolution of E. faecium by showing that there are two distantly related clades; one being more successful in the hospital setting. My studies also identified operons encoding WxL proteins whose characteristics could also contribute to colonization and virulence within this species.

The transition school-university

This paper presents partial results of a research in the area of Vocational Occupational Guidance at the National University of San Luis on the subject "Transition School-University". The information offered here follows a survey on the relationship between the educational area and the organizations, persons and programs of the work and employment area. Reference is made to the information the different participants get as well as the importance they assign to said relationship. The interest of the results obtained is discussed with a view to optimize interventions in the speciality by taking into account the need of articulation of actions between the areas involved.

The transition school-university

This paper presents partial results of a research in the area of Vocational Occupational Guidance at the National University of San Luis on the subject "Transition School-University". The information offered here follows a survey on the relationship between the educational area and the organizations, persons and programs of the work and employment area. Reference is made to the information the different participants get as well as the importance they assign to said relationship. The interest of the results obtained is discussed with a view to optimize interventions in the speciality by taking into account the need of articulation of actions between the areas involved.

Planktic foraminifera across the Cretaceous-Tertiary transition in the Antarctic Ocean

Three Antarctic Ocean K/T boundary sequences from ODP Site 738C on the Kerguelen Plateau, ODP Site, 752B on Broken Ridge and ODP Site 690C on Maud Rise, Weddell Sea, have been analyzed for stratigraphic completeness and faunal turnover based on quantitative planktic foraminiferal studies. Results show that Site 738C, which has a laminated clay layer spanning the K/T boundary, is biostratigraphically complete with the earliest Tertiary Zones P0 and P1a present, but with short intrazonal hiatuses. Site 752B may be biostratigraphically complete and Site 690C has a hiatus at the K/T boundary with Zones P0 and P1a missing. Latest Cretaceous to earliest Tertiary planktic foraminiferal faunas from the Antarctic Ocean are cosmopolitan and similar to coeval faunas dominating in low, middle and northern high latitudes, although a few endemic species are present. This allows application of the current low and middle latitude zonation to Antarctic K/T boundary sequences. The most abundant endemic species is Chiloguembelina waiparaensis, which was believed to have evolved in the early Tertiary, but which apparently evolved as early as Chron 30N at Site 738C. Since this species is only rare in sediments of Site 690C in the Weddell Sea, this suggests that a watermass oceanographic barner may have existed between the Indian and Atlantic Antarctic Oceans. The cosmopolitan nature of the dominant fauna began during the last 200,000 to 300,000 years of the Cretaceous and continued at least 300,000 years into the Tertiary. This indicates a long-term environmental crisis that led to gradual elimination of specialized forms and takeover by generalists tolerant of wide ranging temperature, oxygen, salinity and nutrient conditions. A few thousand years before the K/T boundary these generalists gradually declined in abundance and species became generally dwarfed due to increased environmental stress. There is no evidence of a sudden mass killing of the Cretaceous fauna associated with a bolide impact at the K/T boundary. Instead, the already declining Cretaceous taxa gradually disappear in the early Danian and the opportunistic survivor taxa (Ch. waiparaensis and Guembelitria cretacea) increase in relative abundance coincident with the evolution of the first new Tertiary species.

The transition school-university

This paper presents partial results of a research in the area of Vocational Occupational Guidance at the National University of San Luis on the subject "Transition School-University". The information offered here follows a survey on the relationship between the educational area and the organizations, persons and programs of the work and employment area. Reference is made to the information the different participants get as well as the importance they assign to said relationship. The interest of the results obtained is discussed with a view to optimize interventions in the speciality by taking into account the need of articulation of actions between the areas involved.

Transformation of the Rice Marketing System and Myanmar's Transition to a Market Economy

Creating a rice marketing system has been one of the central policy issues in Myanmar's move to a market economy since the end of the 1980s. Two liberalizations of rice marketing were implemented in 1987 and 2003. This paper examines the essential aspects of the liberalizations and the subsequent transformation of Myanmar's rice marketing sector. It attempts to bring into clearer focus the rationale of the government's rice marketing reforms which is to maintain a stable supply of rice at a low price to consumers. Under this rationale, however, the state rice marketing sector continued to lose efficiency while the private sector was allowed to develop on condition that it did not jeopardize the rationale of stable supply at low price. The paper concludes that the prospect for the future development of the private rice marketing sector is dim since a change in the rice market's rationale is unlikely. Private rice exporting is unlikely to be permitted, while the domestic market is approaching the saturation point. Thus, there is little momentum for the private rice sector to undertake any substantial expansion of investment.