Can We Really Prevent Suicide?

Every year, suicide is among the top 20 leading causes of death globally for all ages. Unfortunately, suicide is difficult to prevent, in large part because the prevalence of risk factors is high among the general population. In this review, clinical and psychological risk factors are examined and methods for suicide prevention are discussed. Prevention strategies found to be effective in suicide prevention include means restriction, responsible media coverage, and general public education, as well identification methods such as screening, gatekeeper training, and primary care physician education. Although the treatment for preventing suicide is difficult, follow-up that includes pharmacotherapy, psychotherapy, or both may be useful. However, prevention methods cannot be restricted to the individual. Community, social, and policy interventions will also be essentia

Identifying microRNA/mRNA dysregulations in ovarian cancer

Abstract Background MicroRNAs are a class of noncoding RNA molecules that co-regulate the expression of multiple genes via mRNA transcript degradation or translation inhibition. Since they often target entire pathways, they may be better drug targets than genes or proteins. MicroRNAs are known to be dysregulated in many tumours and associated with aggressive or poor prognosis phenotypes. Since they regulate mRNA in a tissue specific manner, their functional mRNA targets are poorly understood. In previous work, we developed a method to identify direct mRNA targets of microRNA using patient matched microRNA/mRNA expression data using an anti-correlation signature. This method, applied to clear cell Renal Cell Carcinoma (ccRCC), revealed many new regulatory pathways compromised in ccRCC. In the present paper, we apply this method to identify dysregulated microRNA/mRNA mechanisms in ovarian cancer using data from The Cancer Genome Atlas (TCGA). Methods TCGA Microarray data was normalized and samples whose class labels (tumour or normal) were ambiguous with respect to consensus ensemble K-Means clustering were removed. Significantly anti-correlated and correlated genes/microRNA differentially expressed between tumour and normal samples were identified. TargetScan was used to identify gene targets of microRNA. Results We identified novel microRNA/mRNA mechanisms in ovarian cancer. For example, the expression level of RAD51AP1 was found to be strongly anti-correlated with the expression of hsa-miR-140-3p, which was significantly down-regulated in the tumour samples. The anti-correlation signature was present separately in the tumour and normal samples, suggesting a direct causal dysregulation of RAD51AP1 by hsa-miR-140-3p in the ovary. Other pairs of potentially biological relevance include: hsa-miR-145/E2F3, hsa-miR-139-5p/TOP2A, and hsa-miR-133a/GCLC. We also identified sets of positively correlated microRNA/mRNA pairs that are most likely result from indirect regulatory mechanisms. Conclusions Our findings identify novel microRNA/mRNA relationships that can be verified experimentally. We identify both generic microRNA/mRNA regulation mechanisms in the ovary as well as specific microRNA/mRNA controls which are turned on or off in ovarian tumours. Our results suggest that the disease process uses specific mechanisms which may be significant for their utility as early detection biomarkers or in the development of microRNA therapies in treating ovarian cancers. The positively correlated microRNA/mRNA pairs suggest the existence of novel regulatory mechanisms that proceed via intermediate states (indirect regulation) in ovarian tumorigenesis.</p

Interactions between growth-dependent changes in cell size, nutrient supply and cellular elemental stoichiometry of marine Synechococcus

The factors that control elemental ratios within phytoplankton, like carbon:nitrogen:phosphorus (C:N:P), are key to biogeochemical cycles. Previous studies have identified relationships between nutrient-limited growth and elemental ratios in large eukaryotes, but little is known about these interactions in small marine phytoplankton like the globally important Cyanobacteria. To improve our understanding of these interactions in picophytoplankton, we asked how cellular elemental stoichiometry varies as a function of steady-state, N- and P-limited growth in laboratory chemostat cultures of Synechococcus WH8102. By combining empirical data and theoretical modeling, we identified a previously unrecognized factor (growth-dependent variability in cell size) that controls the relationship between nutrient-limited growth and cellular elemental stoichiometry. To predict the cellular elemental stoichiometry of phytoplankton, previous theoretical models rely on the traditional Droop model, which purports that the acquisition of a single limiting nutrient suffices to explain the relationship between a cellular nutrient quota and growth rate. Our study, however, indicates that growth-dependent changes in cell size have an important role in regulating cell nutrient quotas. This key ingredient, along with nutrient-uptake protein regulation, enables our model to predict the cellular elemental stoichiometry of Synechococcus across a range of nutrient-limited conditions. Our analysis also adds to the growth rate hypothesis, suggesting that P-rich biomolecules other than nucleic acids are important drivers of stoichiometric variability in Synechococcus. Lastly, by comparing our data with field observations, our study has important ecological relevance as it provides a framework for understanding and predicting elemental ratios in ocean regions where small phytoplankton like Synechococcus dominates

Distress and quality of life characteristics associated with seeking surgical treatment for stress urinary incontinence

<p>Abstract</p> <p>Background</p> <p>Current research focuses on three variables in evaluating the impact of stress urinary incontinence (SUI) on daily living: severity of incontinence, distress or bother resulting from incontinence, and effect on health related quality of life (HRQoL). Understanding the impact of these variables is important as they are the driving force behind women seeking surgical treatment. Given the importance of HRQoL in determining need for treatment, as well as evaluating treatment success, this review provides an assessment of the degree to which HRQoL is impaired in women seeking surgical treatment.</p> <p>Methods</p> <p>PubMed searches for the terms "quality of life and distress and urinary incontinence" and "quality of life and bother and urinary incontinence" were performed with limits of English, human and female subjects through May 2008. All studies using validated instruments were included. No time limit was placed on the search.</p> <p>Results</p> <p>Of 178 articles retrieved, 21 met the inclusion criteria, and 17 reported methods of scoring. The studies used the Urogenital Distress Inventory (UDI) and the Incontinence Impact Questionnaire (IIQ). Wide ranges of mean and individual levels of severity of symptoms, UDI and IIQ scores were seen among women seeking surgical treatment. Fourteen studies reported baseline and post-surgical treatment distress and QoL data. Statistically significant improvements between baseline and post-surgical UDI and IIQ scores were reported in 12 studies. Reported cure rates ranged from 46% to 97%. Satisfaction with the procedure was reported in 4 studies and ranged from 84% to 91%. A minority of studies reported the relationship between reduction in symptoms and change in HRQoL.</p> <p>Conclusion</p> <p>HRQoL is the main reason women seek surgical treatment for incontinence and surgical treatment leads to a significant improvement in mean HRQoL scores. Assessment of HRQoL has proved less useful in identifying why individual women seek treatment for incontinence. Preliminary work has begun to characterize the interaction between severity of symptoms, distress or bother resulting from these urinary symptoms, impact on HRQoL, and treatment seeking behavior, but further research is needed. Greater standardization in the reporting of results of distress or bother and HRQoL would allow for comparison across studies.</p

Distress and quality of life characteristics associated with seeking surgical treatment for stress urinary incontinence

<p>Abstract</p> <p>Background</p> <p>Current research focuses on three variables in evaluating the impact of stress urinary incontinence (SUI) on daily living: severity of incontinence, distress or bother resulting from incontinence, and effect on health related quality of life (HRQoL). Understanding the impact of these variables is important as they are the driving force behind women seeking surgical treatment. Given the importance of HRQoL in determining need for treatment, as well as evaluating treatment success, this review provides an assessment of the degree to which HRQoL is impaired in women seeking surgical treatment.</p> <p>Methods</p> <p>PubMed searches for the terms "quality of life and distress and urinary incontinence" and "quality of life and bother and urinary incontinence" were performed with limits of English, human and female subjects through May 2008. All studies using validated instruments were included. No time limit was placed on the search.</p> <p>Results</p> <p>Of 178 articles retrieved, 21 met the inclusion criteria, and 17 reported methods of scoring. The studies used the Urogenital Distress Inventory (UDI) and the Incontinence Impact Questionnaire (IIQ). Wide ranges of mean and individual levels of severity of symptoms, UDI and IIQ scores were seen among women seeking surgical treatment. Fourteen studies reported baseline and post-surgical treatment distress and QoL data. Statistically significant improvements between baseline and post-surgical UDI and IIQ scores were reported in 12 studies. Reported cure rates ranged from 46% to 97%. Satisfaction with the procedure was reported in 4 studies and ranged from 84% to 91%. A minority of studies reported the relationship between reduction in symptoms and change in HRQoL.</p> <p>Conclusion</p> <p>HRQoL is the main reason women seek surgical treatment for incontinence and surgical treatment leads to a significant improvement in mean HRQoL scores. Assessment of HRQoL has proved less useful in identifying why individual women seek treatment for incontinence. Preliminary work has begun to characterize the interaction between severity of symptoms, distress or bother resulting from these urinary symptoms, impact on HRQoL, and treatment seeking behavior, but further research is needed. Greater standardization in the reporting of results of distress or bother and HRQoL would allow for comparison across studies.</p

Roles of the creatine kinase system and myoglobin in maintaining energetic state in the working heart

<p>Abstract</p> <p>Background</p> <p>The heart is capable of maintaining contractile function despite a transient decrease in blood flow and increase in cardiac ATP demand during systole. This study analyzes a previously developed model of cardiac energetics and oxygen transport to understand the roles of the creatine kinase system and myoglobin in maintaining the ATP hydrolysis potential during beat-to-beat transient changes in blood flow and ATP hydrolysis rate.</p> <p>Results</p> <p>The theoretical investigation demonstrates that elimination of myoglobin only slightly increases the predicted range of oscillation of cardiac oxygenation level during beat-to-beat transients in blood flow and ATP utilization. In silico elimination of myoglobin has almost no impact on the cytoplasmic ATP hydrolysis potential (Δ<it>G</it>_ATPase). In contrast, disabling the creatine kinase system results in considerable oscillations of cytoplasmic ADP and ATP levels and seriously deteriorates the stability of Δ<it>G</it>_ATPasein the beating heart.</p> <p>Conclusion</p> <p>The CK system stabilizes Δ<it>G</it>_ATPaseby both buffering ATP and ADP concentrations and enhancing the feedback signal of inorganic phosphate in regulating mitochondrial oxidative phosphorylation.</p

Echocardiographic prediction of outcome after cardiac resynchronization therapy: conventional methods and recent developments

Echocardiography plays an important role in patient assessment before cardiac resynchronization therapy (CRT) and can monitor many of its mechanical effects in heart failure patients. Encouraged by the highly variable individual response observed in the major CRT trials, echocardiography-based measurements of mechanical dyssynchrony have been extensively investigated with the aim of improving response prediction and CRT delivery. Despite recent setbacks, these techniques have continued to develop in order to overcome some of their initial flaws and limitations. This review discusses the concepts and rationale of the available echocardiographic techniques, highlighting newer quantification methods and discussing some of the unsolved issues that need to be addressed

Targeted genome engineering via zinc finger nucleases

With the development of next-generation sequencing technology, ever-expanding databases of genetic information from various organisms are available to researchers. However, our ability to study the biological meaning of genetic information and to apply our genetic knowledge to produce genetically modified crops and animals is limited, largely due to the lack of molecular tools to manipulate genomes. Recently, targeted cleavage of the genome using engineered DNA scissors called zinc finger nucleases (ZFNs) has successfully supported the precise manipulation of genetic information in various cells, animals, and plants. In this review, we will discuss the development and applications of ZFN technology for genome engineering and highlight recent reports on its use in plants

Transcriptome dynamics of a broad host-range cyanophage and its hosts

Cyanobacteria are highly abundant in the oceans and are constantly exposed to lytic viruses. The T4-like cyanomyoviruses are abundant in the marine environment and have broad host-ranges relative to other cyanophages. It is currently unknown whether broad host-range phages specifically tailor their infection program for each host, or employ the same program irrespective of the host infected. Also unknown is how different hosts respond to infection by the same phage. Here we used microarray and RNA-seq analyses to investigate the interaction between the Syn9 T4-like cyanophage and three phylogenetically, ecologically and genomically distinct marine Synechococcus strains: WH7803, WH8102 and WH8109. Strikingly, Syn9 led a nearly identical infection and transcriptional program in all three hosts. Different to previous assumptions for T4-like cyanophages, three temporally regulated gene expression classes were observed. Furthermore, a novel regulatory element controlled early-gene transcription, and host-like promoters drove middle gene transcription, different to the regulatory paradigm for T4. Similar results were found for the P-TIM40 phage during infection of Prochlorococcus NATL2A. Moreover, genomic and metagenomic analyses indicate that these regulatory elements are abundant and conserved among T4-like cyanophages. In contrast to the near-identical transcriptional program employed by Syn9, host responses to infection involved host-specific genes primarily located in hypervariable genomic islands, substantiating islands as a major axis of phage-cyanobacteria interactions. Our findings suggest that the ability of broad host-range phages to infect multiple hosts is more likely dependent on the effectiveness of host defense strategies than on differential tailoring of the infection process by the phage