Antidepressant Treatment and Manic Switch in Bipolar I Disorder: A Clinical and Molecular Genetic Study.

Affective switch is an important clinical issue when treating bipolar disorder. Though commonly seen in clinical practice, the benefits of prescribing antidepressants for bipolar depression are still controversial. To date, there have been few genetic studies and no genome-wide association study (GWAS), focusing on manic switch following bipolar depression.

Genome-wide association study of early-onset bipolar I disorder in the Han Taiwanese population.

The search for susceptibility genes underlying the heterogeneous bipolar disorder has been inconclusive, often with irreproducible results. There is a hope that narrowing the phenotypes will increase the power of genetic analysis. Early-onset bipolar disorder is thought to be a genetically homogeneous subtype with greater symptom severity.

Immunophenotypes associated with bipolar disorder and lithium treatment.

Immune dysfunction is implicated in the etiology of bipolar disorder. The single-nucleotide polymorphism rs17026688 in the gene encoding glutamate decarboxylase-like protein 1 (GADL1) has been found to be associated with lithium response in Han Chinese patients with bipolar I disorder (BDI). However, whether patients with GADL1 polymorphisms have different immunophenotypes is unknown.

Lithium and GADL1 regulate glycogen synthase kinase-3 activity to modulate KCTD12 expression.

Potassium channel tetramerization domain containing 12 (KCTD12), the auxiliary GABA receptor subunit, is identified as a susceptibility gene for bipolar I (BPI) disorder in the Han Chinese population. Moreover, the single-nucleotide polymorphism (SNP) rs17026688 in glutamate decarboxylase-like protein 1 (GADL1) is shown to be associated with lithium response in Han Chinese BPI patients. In this study, we demonstrated for the first time the relationship among lithium, GADL1, and KCTD12.

Effects of GADL1 overexpression on cell migration and the associated morphological changes.

Lithium has been used for maintenance treatment of bipolar disorder, but drug response varies among patients. Single-nucleotide polymorphisms in glutamate decarboxylase-like protein 1 (GADL1) are found to be associated with lithium response in Han Chinese bipolar patients. In this study, we assessed GADL1 function using a neuroblastoma cell line that stably overexpressed GADL1.

Communication with Families Regarding Organ and Tissue Donation after Death in Intensive Care (COMFORT): a multicentre before-and-after study.

Objective: To implement a best-practice intervention offering deceased organ donation, testing whether it increased family consent rates.

Design: A multicentre before-and-after study of a prospective cohort compared with pre-intervention controls.

Setting: Nine Australian intensive care units.

NtrC Adds a New Node to the Complex Regulatory Network of Biofilm Formation and Expression in Vibrio cholerae.

The biofilm growth mode is important in both the intestinal and environmental phases of the life cycle. Regulation of biofilm formation involves several transcriptional regulators and alternative sigma factors. One such factor is the alternative sigma factor RpoN, which positively regulates biofilm formation.

The Two-Component Signal Transduction System VxrAB Positively Regulates Vibrio cholerae Biofilm Formation.

Two-component signal transduction systems (TCSs), typically composed of a sensor histidine kinase (HK) and a response regulator (RR), are the primary mechanism by which pathogenic bacteria sense and respond to extracellular signals. The pathogenic bacterium is no exception and harbors 52 RR genes. Using in-frame deletion mutants of each RR gene, we performed a systematic analysis of their role in biofilm formation.

COMmunication with Families regarding ORgan and Tissue donation after death in intensive care (COMFORT): protocol for an intervention study.

Background: Discussing deceased organ donation can be difficult not only for families but for health professionals who initiate and manage the conversations. It is well recognised that the methods of communication and communication skills of health professionals are key influences on decisions made by families regarding organ donation.

Methods: This multicentre study is being performed in nine intensive care units with follow-up conducted by the Organ and Tissue Donation Service in New South Wales (NSW) Australia.

variant and medication adherence in predicting response to lithium maintenance treatment in bipolar I disorder.

Background: Genetic variants and medication adherence have been identified to be the main factors contributing to lithium treatment response in bipolar disorders.

Aims: To simultaneously examine effects of variant glutamate decarboxylase-like protein 1 () and medication adherence on response to lithium maintenance treatment in Han Chinese patients with bipolar I (BPI) disorder.

Method: Frequencies of manic and depressive episodes between carriers and non-carriers of the effective rs17026688 T allele during the cumulative periods of off-lithium, poor adherence to lithium treatment and good adherence to lithium treatment were compared in Han Chinese patients with BPI disorder (=215).

Biofilm Formation and Detachment in Gram-Negative Pathogens Is Modulated by Select Bile Acids.

Biofilms are a ubiquitous feature of microbial community structure in both natural and host environments; they enhance transmission and infectivity of pathogens and provide protection from human defense mechanisms and antibiotics. However, few natural products are known that impact biofilm formation or persistence for either environmental or pathogenic bacteria. Using the combination of a novel natural products library from the fish microbiome and an image-based screen for biofilm inhibition, we describe the identification of taurine-conjugated bile acids as inhibitors of biofilm formation against both Vibrio cholerae and Pseudomonas aeruginosa.

Association Study of Gene Polymorphisms in GABA, Serotonin, Dopamine, and Alcohol Metabolism Pathways with Alcohol Dependence in Taiwanese Han Men.

Background: The roles of GABA, serotonin, dopamine, and alcohol metabolism pathways in alcohol dependence (AD) are evident from animal models and human studies. Aims of this study were to investigate associations between genes in the 4 pathways and AD.

Methods: Male subjects from 2 independent samples of Taiwanese Han descent, a family sample of 179 trios and a case-control sample of 262 AD cases and 273 normal controls, were included in this study.

Vibrio cholerae Response Regulator VxrB Controls Colonization and Regulates the Type VI Secretion System.

Two-component signal transduction systems (TCS) are used by bacteria to sense and respond to their environment. TCS are typically composed of a sensor histidine kinase (HK) and a response regulator (RR). The Vibrio cholerae genome encodes 52 RR, but the role of these RRs in V.

Integrative epigenetic profiling analysis identifies DNA methylation changes associated with chronic alcohol consumption.

Alcoholism has always been a major public health concern in Taiwan, especially in the aboriginal communities. Emerging evidence supports the association between DNA methylation and alcoholism, though very few studies have examined the effect of chronic alcohol consumption on the epignome. Since 1986, we have been following up on the mental health conditions of four major aboriginal peoples of Taiwan.

Development of benzo[1,4]oxazines as biofilm inhibitors and dispersal agents against Vibrio cholerae.

Bacterial biofilms are estimated to be associated with over 65 percent of all nosocomial infections. However, no therapeutics have been approved by the FDA which directly mediate biofilm formation or persistence. Herein we report oxazine as a highly potent inhibitor, disperser and in the presence of the appropriate antibiotic eradicator of V.

Vibrio cholerae utilizes direct sRNA regulation in expression of a biofilm matrix protein.

Vibrio cholerae biofilms contain exopolysaccharide and three matrix proteins RbmA, RbmC and Bap1. While much is known about exopolysaccharide regulation, little is known about the mechanisms by which the matrix protein components of biofilms are regulated. VrrA is a conserved, 140-nt sRNA of V.

Variant GADL1 and response to lithium therapy in bipolar I disorder.

Background: Lithium has been a first-line choice for maintenance treatment of bipolar disorders to prevent relapse of mania and depression, but many patients do not have a response to lithium treatment.

Methods: We selected subgroups from a sample of 1761 patients of Han Chinese descent with bipolar I disorder who were recruited by the Taiwan Bipolar Consortium. We assessed their response to lithium treatment using the Alda scale and performed a genomewide association study on samples from one subgroup of 294 patients with bipolar I disorder who were receiving lithium treatment.

Image-based 384-well high-throughput screening method for the discovery of skyllamycins A to C as biofilm inhibitors and inducers of biofilm detachment in Pseudomonas aeruginosa.

To date, most antibiotics have primarily been developed to target bacteria in the planktonic state. However, biofilm formation allows bacteria to develop tolerance to antibiotics and provides a mechanism to evade innate immune systems. Therefore, there is a significant need to identify small molecules to prevent biofilm formation and, more importantly, to disperse or eradicate preattached biofilms, which are a major source of bacterial persistence in nosocomial infections.

Discovery and biological characterization of the auromomycin chromophore as an inhibitor of biofilm formation in Vibrio cholerae.

Bacterial biofilms pose a significant challenge in clinical environments due to their inherent lack of susceptibility to antibiotic treatment. It is widely recognized that most pathogenic bacterial strains in the clinical setting persist in the biofilm state, and are the root cause of many recrudescent infections. The discovery and development of compounds capable of either inhibiting biofilm formation or initiating biofilm dispersal might provide new therapeutic avenues for reducing the number of hospital-acquired, biofilm-mediated infections.

Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report.

Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study.

A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010.

Background: Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time.

Methods: We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010.

Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010.

Background: Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study.