Measuring postnatal demoralisation: adaptation of the Demoralisation Scale-II (DS-II) for postnatal use.

Objective: To examine the psychometric properties of the Demoralisation Scale II (DS-II) and adapt it for use with women in the postnatal period.

Background: Demoralisation is a psychological state characterised by a sense of incompetence and feelings of helplessness and hopelessness in response to a stressful situation. The postnatal period is a life stage of many disruptions.

Symptom attribution and treatment seeking in Australian veterans.

To understand the role of symptom attribution in treatment-seeking behaviours, survey results of 1356 veterans (age = 38-72 years) were analysed. Controlling for symptom frequency, significant relationships were found for specialist and psychological-related consultations. Those who favoured psychological explanations for symptoms were more likely to attend specialist and psychology-related consultations and filled significantly more prescriptions than people who predominantly explained symptoms by situational factors (normalisers).

Medical student psychological distress and academic performance.

Introduction: The impact of medical student psychological distress on academic performance has not been systematically examined. This study provided an opportunity to closely examine the potential impacts of workplace and study related stress factors on student's psychological distress and their academic performance during their first clinical year.

Methods: This one-year prospective cohort study was performed at a tertiary hospital based medical school in Melbourne, Australia.

A short cross-linker activates human P-glycoprotein missing a catalytic carboxylate.

P-glycoprotein (P-gp) is an ATP-dependent drug pump that protects us from toxic agents and confers multidrug resistance. It has a tweezer-like structure with each arm consisting of a transmembrane domain (TMD) and a nucleotide-binding domain (NBD). Drug substrates bind to sites within the TMDs to activate ATPase activity by promoting a tweezer-like closing of the gap between the NBDs.

Thiol-reactive drug substrates of human P-glycoprotein label the same sites to activate ATPase activity in membranes or dodecyl maltoside detergent micelles.

P-glycoprotein (P-gp, ABCB1) is an ABC drug pump that is clinically important because it is involved in multidrug resistance. Many studies have used purified P-gp in detergent (n-dodecyl-β-D-maltoside; DM) micelles to map the locations of the drug-binding sites. A potential problem is that DM could be a substrate and affect binding of drugs to P-gp.

Corrector VX-809 promotes interactions between cytoplasmic loop one and the first nucleotide-binding domain of CFTR.

A large number of correctors have been identified that can partially repair defects in folding, stability and trafficking of CFTR processing mutants that cause cystic fibrosis (CF). The best corrector, VX-809 (Lumacaftor), has shown some promise when used in combination with a potentiator (Ivacaftor). Understanding the mechanism of VX-809 is essential for development of better correctors.

Attachment of a 'molecular spring' restores drug-stimulated ATPase activity to P-glycoprotein lacking both Q loop glutamines.

P-glycoprotein (P-gp) is an ABC (ATP-Binding Cassette) drug pump that is clinically important because it confers multidrug resistance. Drugs bind at the interface between the transmembrane domains to activate ATPase activity at the two nucleotide-binding domains (NBDs). Drug transport involves ATP-dependent conformational changes between inward- (open, NBDs far apart) and outward-facing (closed, NBDs close together) conformations.

Refinement and revalidation of the demoralization scale: The DS-II-internal validity.

Background: The Demoralization Scale (DS) was initially validated in 2004 to enable the measurement of demoralization in patients with advanced cancer. Subsequent shortcomings indicated the need for psychometric strengthening. Here, the authors report on the refinement and revalidation of the DS to form the DS-II, specifically reporting the scale's internal validity.

Refinement and revalidation of the demoralization scale: The DS-II-external validity.

Background: The recently refined Demoralization Scale-II (DS-II) is a 16-item, self-report measure of demoralization. Its 2 factors-Meaning and Purpose and Distress and Coping Ability-demonstrate sound internal validity, including item fit, unidimensionality, internal consistency, and test-retest reliability. The convergent and discriminant validity of the DS-II with various measures is reported here.

Drugs Modulate Interactions between the First Nucleotide-Binding Domain and the Fourth Cytoplasmic Loop of Human P-Glycoprotein.

Drug substrates stimulate ATPase activity of the P-glycoprotein (P-gp) ATP-binding cassette drug pump by an unknown mechanism. Cross-linking analysis was performed to test if drug substrates stimulate P-gp ATPase activity by altering cross-talk at the first transmission interface linking the drug-binding [intracellular loop 4 (S909C)] and first nucleotide-binding domains [NBD1 (V472C or L443C)]. In the absence of lipid (inactive P-gp), only V472C/S909C showed cross-linking.

P-glycoprotein ATPase activity requires lipids to activate a switch at the first transmission interface.

P-glycoprotein (P-gp) is an ABC (ATP-Binding Cassette) drug pump. A common feature of ABC proteins is that they are organized into two wings. Each wing contains a transmembrane domain (TMD) and a nucleotide-binding domain (NBD).

Health Anxiety and Its Relationship to Disability and Service Use: Findings From a Large Epidemiological Survey.

Objective: To explore the contribution of health anxiety to disability and use of mental health and medical services, independently of co-occurring mental and physical conditions.

Methods: Data from the Australian National Survey of Mental Health and Wellbeing 2007 were analyzed (n = 8841). Participants were aged 16 to 85 years (mean [standard deviation] = 46.

Mapping the Binding Site of the Inhibitor Tariquidar That Stabilizes the First Transmembrane Domain of P-glycoprotein.

ABC (ATP-binding cassette) transporters are clinically important because drug pumps like P-glycoprotein (P-gp, ABCB1) confer multidrug resistance and mutant ABC proteins are responsible for many protein-folding diseases such as cystic fibrosis. Identification of the tariquidar-binding site has been the subject of intensive molecular modeling studies because it is the most potent inhibitor and corrector of P-gp. Tariquidar is a unique P-gp inhibitor because it locks the pump in a conformation that blocks drug efflux but activates ATPase activity.

Developing a brief depression screen and identifying associations with comorbid physical and psychological illness in Australian Gulf War veterans.

Objective: Major depression occurs frequently in veterans, and is associated with comorbid psychological and physical disorders and poorer quality of life. Depression can be difficult to detect in primary care, while lengthy assessment instruments can deter use. Our study aimed to develop a brief depression screen that could be used by veterans and caregivers, and then to compare the association between the brief screen and comorbidities and quality of life with that of a longer instrument.

Early postnatal demoralisation among primiparous women in the community: measurement, prevalence and associated factors.

Background: Demoralisation is a psychological state occurring in stressful life situations where a person feels unable to respond effectively to their circumstances, characterised by feelings of distress, subjective incompetence, helplessness and hopelessness. The period after the birth of a first baby is a time of great changes and disruptions to many aspects of the mother's physical, psychological and social functioning. This can lead to feelings of distress, a sense of incompetence and helplessness.

Symptom attribution and symptom reporting in Australian Gulf War veterans.

Objective: To better understand the consistent elevated symptom reporting by Gulf War veterans; we compared Australian Gulf War veterans and military-comparison group on symptom attributional styles and the relationship with total number and grouping of somatic and psychological symptoms.

Method: Postal questionnaires were completed by Australian Gulf War veterans (n=697) and military-comparison group (n=659) in 2000-2002 and 2011-2012. Data were collected on deployments, military-psychological stressors, symptom reporting, symptom factors and attributional style (normalising, psychologising, somatising, mixed-attribution).

The Transmission Interfaces Contribute Asymmetrically to the Assembly and Activity of Human P-glycoprotein.

P-glycoprotein (P-gp; ABCB1) is an ABC drug pump that protects us from toxic compounds. It is clinically important because it confers multidrug resistance. The homologous halves of P-gp each contain a transmembrane (TM) domain (TMD) with 6 TM segments followed by a nucleotide-binding domain (NBD).

Tariquidar inhibits P-glycoprotein drug efflux but activates ATPase activity by blocking transition to an open conformation.

P-glycoprotein (P-gp, ABCB1) is a drug pump that confers multidrug resistance. Inhibition of P-gp would improve chemotherapy. Tariquidar is a potent P-gp inhibitor but its mechanism is unknown.

Cysteines introduced into extracellular loops 1 and 4 of human P-glycoprotein that are close only in the open conformation spontaneously form a disulfide bond that inhibits drug efflux and ATPase activity.

P-glycoprotein (P-gp) is an ATP-binding cassette drug pump that protects us from toxic compounds and confers multidrug resistance. The protein is organized into two halves. The halves contain a transmembrane domain (TMD) with six transmembrane segments and a nucleotide-binding domain (NBD).

GILZ: Glitzing up our understanding of the glucocorticoid receptor in psychopathology.

Dysfunction of the hypothalamic-pituitary-adrenal axis, particularly the glucocorticoid receptor, is a commonly implicated link between stress and psychopathology. GR abnormalities are frequently reported in depression, and these anomalies must be resolved before depressive symptoms remit. This biological finding is rendered clinically relevant by the knowledge that only select antidepressants alter GR function.

Identification of the distance between the homologous halves of P-glycoprotein that triggers the high/low ATPase activity switch.

P-glycoprotein (P-gp, ABCB1) is an ATP-binding cassette drug pump that protects us from toxic compounds and confers multidrug resistance. Each homologous half contains a transmembrane domain with six transmembrane segments followed by a nucleotide-binding domain (NBD). The drug- and ATP-binding sites reside at the interface between the transmembrane domain and NBDs, respectively.

The INSPIRED study: a randomised controlled trial of the Whole Person Model of disease self-management for people with type 2 diabetes.

Background: The prevalence of type 2 diabetes has increased dramatically in the last decade, and is continuing to rise. It is a chronic condition, often related to obesity, diet and sedentary lifestyles, and can lead to significant health complications, disability and early death. Diabetes is commonly associated with depression, which can impact significantly on a person's ability to manage their illness and, consequently, on disease outcomes.

The cystic fibrosis V232D mutation inhibits CFTR maturation by disrupting a hydrophobic pocket rather than formation of aberrant interhelical hydrogen bonds.

Processing mutations that inhibit folding and trafficking of CFTR are the main cause of cystic fibrosis. Repair of CFTR mutants requires an understanding of the mechanisms of misfolding caused by processing mutations. Previous studies on helix-loop-helix fragments of the V232D processing mutation suggested that its mechanism was to lock transmembrane (TM) segments 3 and 4 together by a non-native hydrogen bond (Asp232(TM4)/Gln207(TM3)).

Locking intracellular helices 2 and 3 together inactivates human P-glycoprotein.

The P-glycoprotein (P-gp) drug pump (ABCB1) has two transmembrane domains and two nucleotide-binding domains (NBDs). Coupling of the drug-binding sites in the transmembrane domains to the NBDs occurs through interaction of the intracellular helices (IHs) with residues in the NBDs (IH1/IH4/NBD1 and IH2/IH3/NBD2). We showed previously that cross-linking of cysteines in IH3 and IH1 with a short cross-linker mimicked drug binding as it activated P-gp ATPase activity.

Evaluating the impact of depression, anxiety & autonomic function on health related quality of life, vocational functioning and health care utilisation in acute coronary syndrome patients: the ADVENT study protocol.

Background: Depression and anxiety are highly prevalent and co-morbid in acute coronary syndrome patients. Somatic and cognitive subtypes of depression and anxiety in acute coronary syndrome have been shown to be associated with mortality although their association with patient outcomes is unknown, as are the mechanisms that underpin these associations. We are conducting a prospective cohort study which aims to examine in acute coronary syndrome patients: (1) the role of somatic subtypes of depression and anxiety as predictors of health related quality of life outcomes; (2) how somatic subtypes of depression and anxiety relate to long term vocational functioning and healthcare utilisation; and (3) the role of the autonomic nervous system assessed by heart rate variability as a moderator of these associations.