Dereplication of Natural Product Antifungals via Liquid Chromatography-Tandem Mass Spectrometry and Chemical Genomics.

Recently expanded reports of multidrug-resistant fungal infections underscore the need to develop new and more efficient methods for antifungal drug discovery. A ubiquitous problem in natural product drug discovery campaigns is the rediscovery of known compounds or their relatives; accordingly, we have integrated Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) for structural dereplication and Yeast Chemical Genomics for bioprocess evaluation into a screening platform to identify such compounds early in the screening process. We identified 450 fractions inhibiting and the resistant strains of and among more than 40,000 natural product fractions.

Cell-free, high-density lipoprotein-specific phospholipid efflux assay predicts incident cardiovascular disease.

BACKGROUNDCellular cholesterol efflux capacity (CEC) is a better predictor of cardiovascular disease (CVD) events than HDL-cholesterol (HDL-C) but is not suitable as a routine clinical assay.METHODSWe developed an HDL-specific phospholipid efflux (HDL-SPE) assay to assess HDL functionality based on whole plasma HDL apolipoprotein-mediated solubilization of fluorescent phosphatidylethanolamine from artificial lipid donor particles. We first assessed the association of HDL-SPE with prevalent coronary artery disease (CAD): study I included NIH severe-CAD (n = 50) and non-CAD (n = 50) participants, who were frequency matched for sex, BMI, type 2 diabetes mellitus, and smoking; study II included Japanese CAD (n = 70) and non-CAD (n = 154) participants.

Mental Health Screening in General Practices as a Means for Enhancing Uptake of Digital Mental Health Interventions: Observational Cohort Study.

Background: Digital mental health interventions stand to play a critical role in managing the mental health impact of the COVID-19 pandemic. Thus, enhancing their uptake is a key priority. General practitioners (GPs) are well positioned to facilitate access to digital interventions, but tools that assist GPs in identifying suitable patients are lacking.

The Framingham Risk Score Is Associated with Chronic Graft Failure in Renal Transplant Recipients.

Predicting chronic graft failure in renal transplant recipients (RTR) is an unmet clinical need. Chronic graft failure is often accompanied by transplant vasculopathy, the formation of de novo atherosclerosis in the transplanted kidney. Therefore, we determined whether the 10-year Framingham risk score (FRS), an established atherosclerotic cardiovascular disease prediction module, is associated with chronic graft failure in RTR.

Statin use and incident cardiovascular events in renal transplant recipients.

Background: Statins achieve potent LDL lowering in the general population leading to a significant cardiovascular (CV) risk reduction. In renal transplant recipients (RTR) statins are included in treatment guidelines, however, conclusive evidence of improved cardiovascular outcomes has not been uniformly provided and concerns have been raised about simultaneous use of statins and the immunosuppressant cyclosporine. This study aimed to elucidate the effect of statins on a compound CV endpoint, comprised of ischaemic CV events and CV mortality in RTR, with subgroup analysis focussing on cyclosporine users.

Proteoglycan binding as proatherogenic function metric of apoB-containing lipoproteins and chronic kidney graft failure.

Lipoprotein-proteoglycan binding is an early key event in atherosclerotic lesion formation and thus conceivably could play a major role in vasculopathy-driven chronic graft failure and cardiovascular mortality in renal transplant recipients. The present study investigated whether lipoprotein-proteoglycan binding susceptibility (LPBS) of apoB-containing lipoproteins and levels of the classical atherosclerosis biomarker LDL-C were associated with cardiovascular mortality (n = 130) and graft failure (n = 73) in 589 renal transplant recipients who were followed up from at least 1 year after transplantation for 9.5 years.

High-Density Lipoprotein Anti-Inflammatory Capacity and Incident Cardiovascular Events.

Background: The role of high-density lipoprotein (HDL) function in cardiovascular disease represents an important emerging concept. The present study investigated whether HDL anti-inflammatory capacity is prospectively associated with first cardiovascular events in the general population.

Methods: HDL anti-inflammatory capacity was determined as its ability to suppress TNFα (tumor necrosis factor α)-induced VCAM-1 (vascular cell adhesion molecule-1) mRNA expression in endothelial cells in vitro (results expressed as achieved percent reduction by individual HDL related to the maximum TNFα effect with no HDL present).

IDTWO: A Protocol for a Randomised Controlled Trial of a Web-Based Mental Health Intervention for Australians with Intellectual Disability.

People with intellectual disability (ID) experience higher rates of mental illness and reduced access to appropriate care and treatment. Tailored electronic mental health (eMH) programs offer opportunities to address these disparities. The aim of this study is to examine whether a fully automated and self-guided eMH program tailored to the needs of people with ID can reduce symptoms of anxiety and depression and improve daily functioning in people with borderline-to-mild ID.

The triglyceride to HDL-cholesterol ratio and chronic graft failure in renal transplantation.

Background: Transplant vasculopathy (TV) is a major contributing factor to chronic graft failure in renal transplant recipients (RTR). TV lesions resemble atherosclerosis in several ways, and it is plausible to believe that some risk factors influence both atherosclerotic plaque formation and formation of TV.

Objective: The objective of this prospective longitudinal study was to determine if dyslipidemia reflected by the triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio is prospectively associated with death censored chronic graft failure in RTR.

Improving treatment decision-making in bipolar II disorder: a phase II randomised controlled trial of an online patient decision-aid.

Background: Many patients with bipolar II disorder (BPII) prefer to be more informed and involved in their treatment decision-making than they currently are. Limited knowledge and involvement in one's treatment is also likely to compromise optimal BPII management. This Phase II RCT aimed to evaluate the acceptability, feasibility, and safety of a world-first patient decision-aid website (e-DA) to improve treatment decision-making regarding options for relapse prevention in BPII.

Stepped care mental health service in Australian primary care: codesign and feasibility study.

Objective In 2015, the Australian Government introduced several mental health reforms, including the requirement that Primary Health Networks (PHNs) provide stepped care services for Australians with mental health needs such as anxiety and depression. This paper reports on the development and feasibility study of StepCare, an online stepped mental healthcare service in general practice that screens patients, provides immediate feedback to patients and general practitioners (GPs), transmits stepped treatment recommendations to GPs and monitors patients' progress, including notification of deterioration. Methods The present codesign and feasibility study in one PHN examined: (1) the acceptability and feasibility of StepCare to GPs, practice staff and patients; (2) the impact of StepCare on clinical practice; and (3) the barriers to and facilitators of implementation.

Anti-oxidative function of follicular fluid HDL and outcomes of modified natural cycle-IVF.

High density lipoproteins (HDL) are the main cholesterol carriers in follicular fluid (FF), the natural environment of oocyte development. Additionally, HDL have critical biological functions such as anti-oxidative capacity, which have not been studied in reproduction. Therefore, this study aimed to investigate whether the anti-oxidative function of FF-HDL is associated with fertility outcomes.

HDL Cholesterol Efflux Predicts Incident New-Onset Diabetes After Transplantation (NODAT) in Renal Transplant Recipients Independent of HDL Cholesterol Levels.

In renal transplant recipients (RTRs), new-onset diabetes after transplantation (NODAT) is a frequent and serious complication limiting survival of graft and patient. However, the underlying pathophysiology remains incompletely understood. In vitro and in preclinical models, HDL can preserve β-cell function, largely by mediating cholesterol efflux, but this concept has not been evaluated in humans.

Autoantibodies to Apolipoprotein A-1 as Independent Predictors of Cardiovascular Mortality in Renal Transplant Recipients.

Renal transplant recipients (RTRs) are known to have a high cardio-vascular disease (CVD) burden only partly explained by traditional CVD risk factors. The aim of this paper was therefore to determine: i) the prognostic value of autoantibodies against apoA-1 (anti-apoA-1 IgG) for incidence of CVD mortality, all-cause mortality and graft failure in RTR. Four hundred and sixty two (462) prospectively included RTRs were followed for 7.

Economic Evaluations of Stepped Models of Care for Depression and Anxiety and Associated Implementation Strategies: A Review of Empiric Studies.

Since the mid-2000s stepped care, a model of integrated healthcare delivery, has been promoted for offering accessible, effective and efficient services for individuals with mental health conditions. However, adoption of the model has not been widespread warranting additional investment by way of implementation strategies to encourage uptake. These strategies also require funding and their value for money should be assessed to inform decision making and practice.

Phase II Randomised Controlled Trial of a patient decision-aid website to improve treatment decision-making for young adults with bipolar II disorder: A feasibility study protocol.

Background/aims: This paper describes the protocol for a feasibility study for a parallel Phase II randomised control trial (RCT) aiming to evaluate a novel decision-aid website (e-DA) to support young adults with bipolar II disorder (BPII), and their families.

Material And Methods: The e-DA was developed according to the International Patient Decision-Aid Standards (IPDAS). Participants will be 40 young adults (18-30 years) referred to a specialist outpatient clinical facility, who have a confirmed clinical diagnosis of BPII.

Consumption of fruits and vegetables and cardiovascular mortality in renal transplant recipients: a prospective cohort study.

Background: It currently remains understudied whether low consumption of fruits and vegetables after kidney transplantation may be a modifiable cardiovascular risk factor. We aimed to investigate the associations between consumption of fruits and vegetables and cardiovascular mortality in renal transplant recipients (RTRs).

Methods: Consumption of fruits and vegetables was assessed in an extensively phenotyping cohort of RTRs.

Development and pilot of a decision-aid for patients with bipolar II disorder and their families making decisions about treatment options to prevent relapse.

Introduction: Treatment decisions in bipolar II disorder (BPII) are finely-balanced and sensitive to patient preferences. This pilot study evaluated a decision-aid booklet (DA) for patients with BPII (and their family) to obtain evidence on its acceptability, feasibility, safety, and usefulness in potential end-users.

Methods: The DA booklet was developed according to International Patient Decision-Aid Standards.

Glomerular filtration rate is associated with free triiodothyronine in euthyroid subjects: Comparison between various equations to estimate renal function and creatinine clearance.

Background: Effects of variations in thyroid function within the euthyroid range on renal function are unclear. Cystatin C-based equations to estimate glomerular filtration rate (GFR) are currently advocated for mortality and renal risk prediction. However, the applicability of cystatin C-based equations is discouraged in patients with overt thyroid dysfunction, since serum cystatin C and creatinine levels are oppositely affected by thyroid dysfunction.

High density lipoprotein (HDL) particles from end-stage renal disease patients are defective in promoting reverse cholesterol transport.

Atherosclerotic cardiovascular disease (CVD) represents the largest cause of mortality in end-stage renal disease (ESRD). CVD in ESRD is not explained by classical CVD risk factors such as HDL cholesterol mass levels making functional alterations of lipoproteins conceivable. HDL functions in atheroprotection by promoting reverse cholesterol transport (RCT), comprising cholesterol efflux from macrophage foam cells, uptake into hepatocytes and final excretion into the feces.

Gender differences in depression severity and symptoms across depressive sub-types.

Background: Lifetime rates of depression are distinctly higher in women reflecting both real and artefactual influences. Most prevalence studies quantifying a female preponderance have examined severity-based diagnostic groups such as major depression or dysthymia. We examined gender differences across three depressive sub-type conditions using four differing measures to determine whether any gender differences emerge more from severity or symptom prevalence, reflect nuances of the particular measure, or whether depressive sub-type is influential.

Clinical and cognitive associations with aggression in the first episode of psychosis.

Objective: Although there may be an increased risk of aggression in first-episode psychosis, little is known about the clinical and cognitive associations of serious and less serious aggression during this phase of psychotic illness.

Methods: Eighty-five patients in the first episode of psychosis under the age of 26 underwent comprehensive clinical assessment and cognitive testing. Aggression was assessed using a purpose-designed rating scale based on corroborative interviews to record 10 types of aggressive behaviour in the 3 months before presenting for treatment.