Assessment of possible impact of a health promotion program in Korea from health risk trends in a longitudinally observed cohort

BACKGROUND: Longitudinally observed cohort data can be utilized to assess the potential for health promotion and healthcare planning by comparing the estimated risk factor trends of non-intervened with that of intervened. The paper seeks (1) to estimate a natural transition (patterns of movement between states) of health risk state from a Korean cohort data using a Markov model, (2) to derive an effective and necessary health promotion strategy for the population, and (3) to project a possible impact of an intervention program on health status. METHODS: The observed transition of health risk states in a Korean employee cohort was utilized to estimate the natural flow of aggregated health risk states from eight health risk measures using Markov chain models. In addition, a reinforced transition was simulated, given that a health promotion program was implemented for the cohort, to project a possible impact on improvement of health status. An intervened risk transition was obtained based on age, gender, and baseline risk state, adjusted to match with the Korean cohort, from a simulated random sample of a US employee population, where a health intervention was in place. RESULTS: The estimated natural flow (non-intervened), following Markov chain order 2, showed a decrease in low risk state by 3.1 percentage points in the Korean population while the simulated reinforced transition (intervened) projected an increase in low risk state by 7.5 percentage points. Estimated transitions of risk states demonstrated the necessity of not only the risk reduction but also low risk maintenance. CONCLUSIONS: The frame work of Markov chain efficiently estimated the trend, and captured the tendency in the natural flow. Given only a minimally intense health promotion program, potential risk reduction and low risk maintenance was projected

Self-harm in young people with perinatal HIV and HIV negative young people in England: cross sectional analysis.

BACKGROUND: Self-harm in adolescents is of growing concern internationally but limited evidence exists on the prevalence of self-harm in those living with HIV, who may be at higher risk of poor mental health outcomes. Therefore our aim was to determine the prevalence and predictors of self-harm among young people with perinatally-acquired HIV (PHIV) and HIV negative (with sibling or mother living with HIV) young people living in England. METHODS: 303 PHIV and 100 HIV negative young people (aged 12-23 years) participating in the Adolescents and Adults Living with Perinatal HIV cohort study completed an anonymous self-harm questionnaire, as well as a number of standardised mental-health assessments. Logistic regression investigated predictors of self-harm. RESULTS: The median age was 16.7 years in both groups, and 40.9% of the PHIV and 31.0% of the HIV negative groups were male. In total 13.9% (56/403) reported having ever self-harmed, with no difference by HIV status (p = 0.089). Multivariable predictors of self-harm were female sex (adjusted odds ratio (AOR) 5.3, (95% confidence interval 1.9, 14.1), p = 0.001), lower self-esteem (AOR 0.9 (0.8, 0.9) per 1 point increase, p < 0.001) and having ever used alcohol (AOR 3.8 (1.8, 7.8), p < 0.001). Self-esteem z-scores for both PHIV and HIV negative participants were 1.9 standard deviations below the mean for population norms. CONCLUSIONS: Self-harm is common among PHIV and HIV negative adolescents in England. Reassuringly however, they do not appear to be at an increased risk compared to the general adolescent population (15-19% lifetime prevalence). The low level of self-esteem (compared to available normative data) in both groups is worrying and warrants further attention

Optimizing the Design of Oligonucleotides for Homology Directed Gene Targeting

BACKGROUND: Gene targeting depends on the ability of cells to use homologous recombination to integrate exogenous DNA into their own genome. A robust mechanistic model of homologous recombination is necessary to fully exploit gene targeting for therapeutic benefit. METHODOLOGY/PRINCIPAL FINDINGS: In this work, our recently developed numerical simulation model for homology search is employed to develop rules for the design of oligonucleotides used in gene targeting. A Metropolis Monte-Carlo algorithm is used to predict the pairing dynamics of an oligonucleotide with the target double-stranded DNA. The model calculates the base-alignment between a long, target double-stranded DNA and a probe nucleoprotein filament comprised of homologous recombination proteins (Rad51 or RecA) polymerized on a single strand DNA. In this study, we considered different sizes of oligonucleotides containing 1 or 3 base heterologies with the target; different positions on the probe were tested to investigate the effect of the mismatch position on the pairing dynamics and stability. We show that the optimal design is a compromise between the mean time to reach a perfect alignment between the two molecules and the stability of the complex. CONCLUSION AND SIGNIFICANCE: A single heterology can be placed anywhere without significantly affecting the stability of the triplex. In the case of three consecutive heterologies, our modeling recommends using long oligonucleotides (at least 35 bases) in which the heterologous sequences are positioned at an intermediate position. Oligonucleotides should not contain more than 10% consecutive heterologies to guarantee a stable pairing with the target dsDNA. Theoretical modeling cannot replace experiments, but we believe that our model can considerably accelerate optimization of oligonucleotides for gene therapy by predicting their pairing dynamics with the target dsDNA

Identification and functional characterization of small non-coding RNAs in Xanthomonas oryzae pathovar oryzae

<p>Abstract</p> <p>Background</p> <p>Small non-coding RNAs (sRNAs) are regarded as important regulators in prokaryotes and play essential roles in diverse cellular processes. <it>Xanthomonas oryzae </it>pathovar <it>oryzae </it>(<it>Xoo</it>) is an important plant pathogenic bacterium which causes serious bacterial blight of rice. However, little is known about the number, genomic distribution and biological functions of sRNAs in <it>Xoo</it>.</p> <p>Results</p> <p>Here, we performed a systematic screen to identify sRNAs in the <it>Xoo </it>strain PXO99. A total of 850 putative non-coding RNA sequences originated from intergenic and gene antisense regions were identified by cloning, of which 63 were also identified as sRNA candidates by computational prediction, thus were considered as <it>Xoo </it>sRNA candidates. Northern blot hybridization confirmed the size and expression of 6 sRNA candidates and other 2 cloned small RNA sequences, which were then added to the sRNA candidate list. We further examined the expression profiles of the eight sRNAs in an <it>hfq </it>deletion mutant and found that two of them showed drastically decreased expression levels, and another exhibited an Hfq-dependent transcript processing pattern. Deletion mutants were obtained for seven of the Northern confirmed sRNAs, but none of them exhibited obvious phenotypes. Comparison of the proteomic differences between three of the ΔsRNA mutants and the wild-type strain by two-dimensional gel electrophoresis (2-DE) analysis showed that these sRNAs are involved in multiple physiological and biochemical processes.</p> <p>Conclusions</p> <p>We experimentally verified eight sRNAs in a genome-wide screen and uncovered three Hfq-dependent sRNAs in <it>Xoo</it>. Proteomics analysis revealed <it>Xoo </it>sRNAs may take part in various metabolic processes. Taken together, this work represents the first comprehensive screen and functional analysis of sRNAs in rice pathogenic bacteria and facilitates future studies on sRNA-mediated regulatory networks in this important phytopathogen.</p

Single step links of the superdeformed band in Pb-194:A measure of the absolute excitation energy, spin and parity of the superdeformed states

The EUROGAM array has been used to investigate the decay out of the yrast superdeformed (SD) band in Pb-194. Six single step decays from the lowest observed SD slates to low-lying states at normal deformation (ND) have been identified. From this observation, the excitation energy of the SD band in Pb-194 is established at 4877 +/- 1.5 keV for the 6(+) SD state. The most probable spins and parities of all members of the SD band are also deduced assuming that the SD states have even spin and positive parity

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Aziridinyl anions from a chiral, nonracemic 2-isopropylidineaziridine: surprisingly diastereoselective alkylation reactions

Lithiation and alkylation of a 2-isopropylidineaziridine bearing an (S)-alpha-methylbenzyl group on nitrogen proceeds with high levels of diastereocontrol (80-90% de).</p

Aziridinyl anions from a chiral, nonracemic 2-isopropylidineaziridine: surprisingly diastereoselective alkylation reactions

Lithiation and alkylation of a 2-isopropylidineaziridine bearing an (S)-alpha-methylbenzyl group on nitrogen proceeds with high levels of diastereocontrol (80-90% de).</p