Targeting MDM2 homodimer and heterodimer disruption with DRx-098D in wild-type and mutant cancer cells.

Novel pharmacological strategies capable of inhibiting pro-oncogenic MDM2 beyond its p53-dependent functions represent increasingly attractive therapeutic strategies to treat solid and hematological cancers that are dependent upon MDM2/MDMX, regardless of mutational status. Utilizing a novel first-in-class cell-penetrating peptide disruptor of MDM2 homo- and heterodimerization (DRx-098D), we demonstrate the anti-proliferative potential of blocking MDM2 dimerization against a panel of human cancer cell lines that are wild type, mutant, or null. DRx-098D elicits its anti-cancer activity via a differentiated mechanism vs.

extract lowers periodontal inflammation under high-glucose conditions via inhibiting NF-κB signaling pathway.

Periodontal disease is more prevalent in patients with diabetes, and it has a negative impact on their quality of life. Inhibiting the infection and inflammation processes that cause periodontal disease can reduce the severity of the disease and chances of serious complications. In this study, we aimed to demonstrate the effectiveness of extract in reducing the inflammation in gingival fibroblast cells induced by lipopolysaccharide (LPS).

Disruption of the pro-oncogenic c-RAF-PDE8A complex represents a differentiated approach to treating KRAS-c-RAF dependent PDAC.

Pancreatic ductal adenocarcinoma (PDAC) is considered the third leading cause of cancer mortality in the western world, offering advanced stage patients with few viable treatment options. Consequently, there remains an urgent unmet need to develop novel therapeutic strategies that can effectively inhibit pro-oncogenic molecular targets underpinning PDACs pathogenesis and progression. One such target is c-RAF, a downstream effector of RAS that is considered essential for the oncogenic growth and survival of mutant RAS-driven cancers (including KRAS PDAC).

Cancer: Phosphodiesterase type 4C (PDE4C), the forgotten subfamily as a therapeutic target.

Phosphodiesterase type 4 (PDE4) enzymes specifically hydrolyse cAMP in many cell signalling systems that are transduced by hormones and other primary messengers. The physiological function of the four PDE4 subfamilies (A, B, C and D) are numerous and varied due to the differentially localised plethora of isoforms that can be detected in cardiovascular, CNS and immune systems. Of the four subfamilies, least is known about PDE4C probably due to its restricted distribution pattern, scarcity of selective inhibitors and the lack of developed research tools.

A head-to-head comparison of 16 cataract surgery outcome questionnaires.

Purpose: To investigate the responsiveness of 16 questionnaires used in cataract surgery outcomes.

Design: Prospective, observational study.

Participants: Patients at the Ophthalmology Eye Clinic, Flinders Medical Centre, Adelaide, Australia, and 1 matched eye clinic in Sweden.

Improvements in visual ability with first-eye, second-eye, and bilateral cataract surgery measured with the visual symptoms and quality of life questionnaire.

Purpose: To determine whether the Visual Symptoms and Quality of Life Questionnaire (VSQ), which was developed to be sensitive to second-eye cataract surgery, has satisfactory psychometric properties and, if so, to examine first-eye, second-eye, and bilateral cataract surgery outcomes.

Setting: Ophthalmology Clinic, Flinders Medical Centre, Adelaide, Australia.

Design: Cohort study.

Multiplicative rating scales do not enable measurement of vision-related quality of life.

Purpose:   Many questionnaires for the measurement of visual impairment exist. One, the Houston Vision Assessment Test (HVAT), takes a different approach: the patient is asked to rate overall impairment and the proportion attributed to vision, then through multiplication the visual and non-visual (physical) impairments are calculated. The purpose of this study was to determine whether the scores derived from this approach can be considered to be measures.

Measuring outcomes of cataract surgery using the Visual Function Index-14.

Purpose: To determine which version of the Visual Function Index-14 (VF-14) most precisely measured cataract surgery outcomes, rescale the VF-14 using Rasch analysis, and create a short-form version for comparison.

Setting: Flinders Medical Centre, Adelaide, South Australia, Australia.

Methods: In this cohort study incorporating questionnaire development, participants were drawn from the cataract surgery waiting list at Flinders Medical Centre.

The refractive status and vision profile: Rasch analysis of subscale validity.

Purpose: To determine whether the eight subscales of the Refractive Status and Vision Profile (RSVP) questionnaire provide valid measurement.

Methods: Two hundred patients, recruited from a refractive surgery clinic and general optometric practice, self-administered the 42-item RSVP questionnaire. Psychometric properties investigated included measurement of a single construct (unidimensionality), item fit to construct, measurement precision (represented by person separation), targeting of item difficulty to patient's quality of life (QOL), and differential item functioning.

Visual disability assessment: valid measurement of activity limitation and mobility in cataract patients.

Aim: The Visual Disability Assessment (VDA), a questionnaire for measuring the impact of cataract on visual functioning, was developed using classical test theory. Since this approach is limited, our aim was to further investigate the psychometric properties of the VDA using Rasch analysis.

Methods: 613 patients from the Flinders Medical Centre cataract surgery self-administered the VDA.

McMonnies questionnaire: enhancing screening for dry eye syndromes with Rasch analysis.

Purpose: To determine, by using Rasch analysis, whether the McMonnies questionnaire possesses the properties of a measure and whether screening for dry eye syndromes (DESs) can be enhanced by using different scoring approaches.

Methods: The questionnaire was self-administered by 43 female Sjögren syndrome patients (>45 years) recruited from a specialized rheumatology clinic and 140 age-matched control subjects. Data were scaled by using Rasch analysis and were assessed for response category behavior and ability to reliably discriminate between severity of the participant's dry eye symptoms (i.

Visual Activities Questionnaire: assessment of subscale validity for cataract surgery outcomes.

Purpose: To examine the psychometric properties of the Visual Activities Questionnaire (VAQ) and each of its subscales in a modern cataract population using Rasch analysis and if flawed, to revise the VAQ and create a valid measure that maximizes its measurement properties.

Setting: Flinders Eye Centre, Flinders Medical Centre, Adelaide, Australia.

Methods: Patients with cataract in 1 or both eyes drawn from the surgical waiting list were mailed the 33-item VAQ for self-administration.

Catquest questionnaire: re-validation in an Australian cataract population.

Background: The Catquest questionnaire was developed using traditional methodology to enable cataract surgery outcomes assessment in European countries. Recently, it has been validated using Rasch analysis in a Swedish population resulting in the Catquest-9SF. The aim of the present study was to assess the performance of the Catquest and the Catquest-9SF questionnaires using Rasch analysis in Australian cataract patients.

The impact of cataract surgery questionnaire: re-evaluation using Rasch analysis.

Purpose: The Impact of Cataract Surgery (ICS) questionnaire was designed to assess cataract surgery outcomes. The aim of this study was to describe the psychometric properties of the ICS questionnaire using the Rasch model in a cataract population.

Methods: Ninety-one patients waiting to undergo cataract surgery in the first or second eye at the Flinders Medical Centre, Adelaide, South Australia self-administered the four-item ICS questionnaire.

Cataract symptom score questionnaire: Rasch revalidation.

Purpose: The 5-item Cataract Symptom Score (CSS) was developed using classical test theory to determine appropriate timing for cataract surgery, its outcomes, and whether the symptoms included bother cataract patients. The purpose of this study was to investigate the psychometric properties of the 5-item CSS using Rasch analysis.

Methods: Responses from 113 patients awaiting cataract surgery to the 5-item CSS (bothered by double or distorted vision, glare or halos, blurry vision, colors looking different and worsening of vision) were subjected to Rasch analysis.

Rasch analysis of visual function and quality of life questionnaires.

Purpose: To investigate the psychometric properties of the Visual Function (VF) and Quality of Life (QOL) questionnaires, using the Rasch measurement model.

Methods: Four hundred eighty-nine patients with cataract awaiting surgery, drawn from the surgical waiting list of the Flinders Medical Centre, Adelaide, South Australia, were mailed the VF and QOL questionnaires for self-administration. Rasch analysis was undertaken to assess the following properties: measurement of a single construct (i.

Activities of Daily Vision Scale: what do the subscales measure?

Purpose: Previous Rasch analysis of the Activities of Daily Vision Scale (ADVS) did not address psychometric properties of its subscales or provide detailed assessment of dimensionality (whether the ADVS measures one or multiple constructs). This study was designed to examine these properties.

Methods: Two hundred thirty-two participants (mean age, 74.

Using Rasch analysis to revisit the validity of the Cataract TyPE Spec instrument for measuring cataract surgery outcomes.

Purpose: To assess the psychometric properties of the Cataract TyPE Specification (Spec) questionnaire using the Rasch model.

Setting: Flinders Medical Centre, Adelaide, Australia.

Methods: The 12-item Cataract TyPE Spec questionnaire was self-administered to patients drawn from the cataract surgery waiting list.

Rasch analysis of the quality of life and vision function questionnaire.

Purpose: The Quality of life and Vision Function Questionnaire (QOL-VFQ) was developed using classical test theory to assess outcomes of cataract surgery. The aim of this study was to examine the psychometric properties of this questionnaire using Rasch analysis in a cataract population.

Methods: The 17-item QOL-VFQ was self-administered to 389 patients waiting to undergo cataract surgery.

Guttman scale analysis of the distance vision scale.

Purpose: The Distance Vision Scale (DVS) is a self-assessment of visual acuity (VA). Like VA testing in which letter reading becomes progressively difficult through the test, DVS questions have a hierarchy of difficulty (Guttman scale). The aims were to determine whether the DVS fulfills Guttman scaling criteria and to test the relationship between DVS score and VA in a cataract population.

The moderating role of employee positive well being on the relation between job satisfaction and job performance.

This research provides further clarification to the age-old quest to better understand the happy/productive worker thesis. Using data from 109 managers employed by a large (over 5000 employees) customer services organization on the West Coast of the United States, both job satisfaction (r=.36, p<.

The moderating effects of employee tenure on the relation between organizational commitment and job performance: a meta-analysis.

This meta-analysis investigated the correlation between attitudinal commitment and job performance for 3,630 employees obtained from 27 independent studies across various levels of employee tenure. Controlling for employee age and other nuisance variables, the authors found that tenure had a very strong nonlinear moderating effect on the commitment-performance correlation, with correlations tending to decrease exponentially with increasing tenure. These findings do not appear to be the result of differences across studies in terms of the type of performance measure (supervisory vs.

The role of organizational behavior in occupational health psychology: a view as we approach the millennium.

This special section of the Journal of Occupational Health Psychology provides ample illustration of the increasingly important role of organizational behavior research on work-related issues of health and well-being. More specifically, the 9 articles contained in this special section highlight the varied application and potentially widespread benefit of considering the main effects of employee physical health and psychological well-being. The authors conclude with a discussion of how emerging research issues in occupational health psychology can be used to build a stronger science of organizational behavior.