Exploration of Novel Metabolic Features Reflecting Statin Sensitivity in Lung Cancer Cells.

Statins are cholesterol-lowering drugs often used for the treatment of dyslipidemia. Statins also exert anti-cancer effects by inhibiting hydroxymethylglutaryl-CoA reductase (HMGCR), a rate-limiting enzyme in cholesterol synthesis. We previously reported that the susceptibility to statin treatment differs among cancer cells and that functional E-cadherin expression on the plasma membrane could be a biomarker of statin sensitivity in cancer cells.

Repurposing of the Cardiovascular Drug Statin for the Treatment of Cancers: Efficacy of Statin-Dipyridamole Combination Treatment in Melanoma Cell Lines.

Metastatic melanoma has a very poor prognosis. Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) inhibitors, are cholesterol-lowering agents with a potential for cancer treatment. The inhibition of HMGCR by statins, however, induces feedback, which paradoxically upregulates HMGCR expression via sterol regulatory element-binding protein-2 (SREBP2).

Comparison of the anticancer effects of various statins on canine oral melanoma cells.

Canine oral melanoma is a highly malignant cancer with a poor prognosis. Statins, commonly used drugs for treating dyslipidemia, exhibit pleiotropic anticancer effects and marked anti-proliferative effects against melanoma cells. The anticancer effects among statins vary; in human cancers, lipophilic statins have shown stronger anticancer effects compared with hydrophilic statins.

Biomechanical assessment of gastrocnemii and Achilles tendon using MyotonPRO: measurements, and preliminary measurements using formalin-fixed tissues.

Purpose: This study aims to evaluate the reliability and validity of using MyotonPRO to quantify the mechanical properties of the muscle-tendon unit through in vivo measurements and preliminary in situ measurements using formalin-fixed tissues.

Materials And Methods: The mechanical properties of gastrocnemii and the Achilles tendon of 12 healthy adults (six males and six females, 34.9 ± 5.

CYP11A1 silencing suppresses HMGCR expression via cholesterol accumulation and sensitizes CRPC cell line DU-145 to atorvastatin.

Statins, which are cholesterol synthesis inhibitors, are well-known therapeutics for dyslipidemia; however, some studies have anticipated their use as anticancer agents. However, epithelial cancer cells show strong resistance to statins through an increased expression of HMG-CoA reductase (HMGCR), an inhibitory target of statins. Castration-resistant prostate cancer (CRPC) cells synthesize androgens from cholesterol on their own.

HMG-CoA reductase degrader, SR-12813, counteracts statin-induced upregulation of HMG-CoA reductase and augments the anticancer effect of atorvastatin.

Statins are cholesterol-lowering drugs that have exhibited potential as cancer therapeutic agents. However, as some cancer cells are resistant to statins, broadening an anticancer spectrum of statins is desirable. The upregulated expression of the statin target enzyme, 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase (HMGCR), in statin-treated cancer cells is a well-known mechanism of statin resistance, which can be counteracted by the downregulation of HMGCR gene expression, or degradation of the HMGCR protein.

Expression of housekeeping genes varies depending on mevalonate pathway inhibition in cancer cells.

Statins have anticancer effects and may be used as anticancer agents via drug repositioning. In reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assays, the internal reference gene must not be affected by any experimental conditions. As statins exert a wide range of effects on cells by inhibiting the mevalonate pathway, it is possible that statin treatment might alter the expression of housekeeping genes used as internal reference genes, thereby misleading the assessment of obtained gene expression data.

Is parental propensity to risk associated with their child's medically-attended injuries? A cross-sectional study.

Background: Societal expectations about safety influence parents' risk perceptions and children's risky play opportunities. This study examined parents' propensity to take risks themselves and their propensity to accept risks for their child, sex-related differences in parents' propensity to accept risks for their child, and the association between parents' propensity to accept risks for their child and that child's medically-attended injury history.

Methods: A total of 467 parents attending a pediatric hospital with their 6-12-year-old child completed a questionnaire about their risk propensity for themselves and for their child and reported their child's injury history.

Estrogen modulates the skeletal muscle regeneration process and myotube morphogenesis: morphological analysis in mice with a low estrogen status.

The purpose of this study was to elucidate the functions of estrogen and two estrogen receptors (ERs; ERα and ERβ) in the myoregeneration process and morphogenesis. Cardiotoxin (CTX) was injected into the tibialis anterior (TA) muscles of ovariectomized (OVX) mice to induce muscle injury, and subsequent myoregeneration was morphologically assessed. The diameter of regenerated myotubes in OVX mice was significantly smaller than that in intact mice at all time points of measurement.

Atorvastatin preferentially inhibits the growth of high ZEB-expressing canine cancer cells.

The epithelial-to-mesenchymal transition (EMT) is fundamental in cancer progression and contributes to the acquisition of malignant properties. The statin class of cholesterol-lowering drugs exhibits pleiotropic anticancer effects in vitro and in vivo, and many epidemiologic studies have reported a correlation between statin use and reduced cancer mortality. We have shown previously that sensitivity to the anti-proliferative effect of statins varies among human cancer cells and statins are more effective against mesenchymal-like cells than epithelial-like ones in human cancers.

Convergent Validity of Myheartsmap: A Pediatric Psychosocial Health Screening Tool.

Recognition of pediatric mental health concerns often depends on assessment by parents, educators, and primary care professionals. Therefore, a psychosocial screening instrument suitable for routine use in schools and primary care is needed. The Pediatric Quality of Life (PedsQL) and the Strengths and Difficulties Questionnaire (SDQ) are widely used for screening but lack adolescent-specific mental health measures.

Concomitant attenuation of HMGCR expression and activity enhances the growth inhibitory effect of atorvastatin on TGF-β-treated epithelial cancer cells.

Epithelial-mesenchymal transition (EMT) in primary tumor cells is a key prerequisite for metastasis initiation. Statins, cholesterol-lowering drugs, can delay metastasis formation in vivo and attenuate the growth and proliferation of tumor cells in vitro. The latter effect is stronger in tumor cells with a mesenchymal-like phenotype than in those with an epithelial one.

Absence of estrogen receptors delays myoregeneration and leads to intermuscular adipogenesis in a low estrogen status: Morphological comparisons in estrogen receptor alpha and beta knock out mice.

This study aimed to investigate the function of estrogen receptors (ERs) in myoregeneration and intermuscular adipogenesis. Ovariectomized (OVX) ERα knockout (KO) mice and ERβ KO mice were used to assess the effect of estrogen on the myoregenerative process. Tibialis anterior muscle was collected on days 7, 10, and 14 after cardiotoxin injection to assess myotube morphology and adipogenesis area.

Reducing length of stay and return visits for emergency department pediatric mental health presentations.

Background: Variability in expertise and risk tolerance among emergency departments (ED) clinicians, when assessing and managing pediatric mental health presentations, leads to increased resource utilization. HEARTSMAP is a validated electronic tool that supports ED clinicians in psychosocial assessments and disposition decision making.

Methods: We used interrupted time series analysis (September 2016-December 2019) and multivariable regressions to measure the impact of integrating HEARTSMAP into ED practice on pediatric mental health presentations length of stay and return visits, at two pediatric EDs.

Comparison of risk engagement and protection survey (REPS) among mothers and fathers of children aged 6-12 years.

Background: Parental attitudes regarding child safety and risk engagement play important roles in child injury prevention and health promotion efforts. Few studies have compared mothers' and fathers' attitudes on these topics. This study used the risk engagement and protection survey (REPS) previously validated with fathers to compare with data collected from mothers.

Changes in parents' perceived injury risk after a medically-attended injury to their child.

Unintentional injuries are a major cause of hospitalization and death for children worldwide. Since children who sustain a medically-attended injury are at higher risk of recurrence, it is crucial to generate knowledge that informs interventions to prevent re-incidence. This study examines when, in the year following a medically-attended injury, parents perceive the greatest risk of injury recurrence.

Concomitant attenuation of HMG-CoA reductase expression potentiates the cancer cell growth-inhibitory effect of statins and expands their efficacy in tumor cells with epithelial characteristics.

HMG-CoA reductase (HMGCR) inhibitors, statins, are potent cholesterol reducing drugs that exhibit anti-tumor effects and in animal models, including attenuation of metastasis formation, and their use correlates with reduced cancer-specific mortality in retrospective human cohort studies. However, E-cadherin expressing epithelial- and mixed epithelial-mesenchymal cancer cell lines (reflective of primary and outgrowing metastatic tumor cells, respectively) require higher statin concentrations than mesenchymal-like tumor cells (reflective of in-circulation metastatic tumor cells) to achieve the same degree of growth inhibition. Here, we show that attenuation of HMGCR expression in the presence of atorvastatin leads to stronger growth inhibition than dual target blockade of the mevalonate pathway in relatively statin resistant cell lines, mainly through inhibition of protein prenylation pathways.

Go Play Outside! Effects of a risk-reframing tool on mothers' tolerance for, and parenting practices associated with, children's risky play: study protocol for a randomized controlled trial.

Background: Children's risky play is associated with a variety of positive developmental, physical and mental health outcomes, including greater physical activity, self-confidence and risk-management skills. Children's opportunities for risky play have eroded over time, limited by parents' fears and beliefs about risk, particularly among mothers. We developed a digital tool and in-person Risk-reframing (RR) workshop to reframe parents' perceptions of risk and change parenting behaviours.

Risk Engagement and Protection Survey (REPS): developing and validating a survey tool on fathers' attitudes towards child injury protection and risk engagement.

Introduction: Fathers play a unique role in keeping children safe from injury yet understanding of their views and attitudes towards protecting children from injury and allowing them to engage in risks is limited. The purpose of this study was to develop and validate an instrument to measure fathers' attitudes towards these two constructs.

Methods And Findings: An instrument was developed that used prior qualitative research to inform item generation.

A longitudinal study on quality of life after injury in children.

Background: In high income countries, injuries account for 40 % of all child deaths, representing the leading cause of child mortality and a major source of morbidity. The need for studies across age groups, and use of health related quality of life measures that assess functional limitations in multiple health domains, with sampling at specific post-injury time points has been identified. The objective of this study was to describe the impact of childhood injury and recovery on health related quality of life (HRQoL) for the 12 months after injury.

Pediatric Canadian Triage and Acuity Scale (PaedsCTAS) as a Measure of Injury Severity.

This research explored whether the pediatric version of the Canadian Triage Acuity Scale (PaedsCTAS) represented a valid alternative indicator for surveillance of injury severity. Every patient presenting in a Canadian emergency department is assigned a CTAS or PaedsCTAS score in order to prioritize access to care and to predict the nature and scope of care that is likely to be required. The five-level PaedsCTAS score ranges from I (resuscitation) to V (non-urgent).

What is the Relationship between Risky Outdoor Play and Health in Children? A Systematic Review.

Risky outdoor play has been associated with promoting children's health and development, but also with injury and death. Risky outdoor play has diminished over time, concurrent with increasing concerns regarding child safety and emphasis on injury prevention. We sought to conduct a systematic review to examine the relationship between risky outdoor play and health in children, in order to inform the debate regarding its benefits and harms.

A systematic review of community interventions to improve Aboriginal child passenger safety.

We evaluated evidence of community interventions to improve Aboriginal child passenger safety (CPS) in terms of its scientific merit and cultural relevance. We included studies if they reported interventions to improve CPS in Aboriginal communities, compared at least pre- and postintervention conditions, and evaluated rates and severity of child passenger injuries, child restraint use, or knowledge of CPS. We also appraised quality and cultural relevance of studies.

Evaluating the benefits of second-eye cataract surgery among the elderly.

Unlabelled: The aim of this systematic review was to synthesize and appraise the evidence of benefits of second-eye cataract extraction for visual function, patient-reported quality of life, falls, and driving ability among the elderly. We conducted a comprehensive search in MEDLINE using "surgery," "cataract extraction," "second eye," and "bilateral." Ten studies met the inclusion and quality criteria.