Comparison of the efficacies of five different statins on inhibition of human saphenous vein smooth muscle cell proliferation and invasion

Statins (HMG-CoA reductase inhibitors) exhibit beneficial effects on the vasculature independently of their cholesterol-lowering properties. These pleiotropic effects underlie the ability of statins to reduce intimal hyperplasia in saphenous vein (SV) bypass grafts by attenuating smooth muscle cell (SMC) invasion and proliferation. Although all statins can effectively lower cholesterol, the pleiotropic effects of individual statins may well differ. We therefore compared the concentration-dependent effects of 4 lipophilic statins (simvastatin, atorvastatin, fluvastatin, and lovastatin) and 1 hydrophilic statin (pravastatin) on the proliferation and invasion of SMC cultured from SV of 9 different patients undergoing coronary artery bypass grafting (CABG). The lipophilic statins inhibited SV-SMC proliferation over a 4-day period with an order of potency of fluvastatin > atorvastatin > simvastatin > lovastatin (IC50 range = 0.07 to 1.77 microM). Similarly, these statins also inhibited SV-SMC invasion through an artificial basement membrane barrier (fluvastatin > atorvastatin > simvastatin > lovastatin; IC50 range = 0.92 to 26.9 microM). In contrast, the hydrophilic pravastatin had no significant effect on SV-SMC proliferation at concentrations up to 10 microM, nor did it attenuate SV-SMC invasion (up to 30 microM). Our data provide strong evidence that individual statins possess differential pleiotropic effects on SV-SMC function. This may be of clinical relevance in the selection of individual statins for the treatment of CABG patients.     

Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome

Summary

Incident vertebral fractures and lumbar spine bone mineral density (BMD) were assessed in the 12 months following glucocorticoid initiation in 65 children with nephrotic syndrome. The incidence of vertebral fractures was low at 12 months (6 %) and most patients demonstrated recovery in BMD Z-scores by this time point.

Introduction

Vertebral fracture (VF) incidence following glucocorticoid (GC) initiation has not been previously reported in pediatric nephrotic syndrome.

Methods

VF was assessed on radiographs (Genant method); lumbar spine bone mineral density (LS BMD) was evaluated by dual-energy X-ray absorptiometry.

Results

Sixty-five children were followed to 12 months post-GC initiation (median age, 5.4 years; range, 2.3–17.9). Three of 54 children with radiographs (6 %; 95 % confidence interval (CI), 2–15 %) had incident VF at 1 year. The mean LS BMD Z-score was below the healthy average at baseline (mean ± standard deviation (SD), ?0.5?±?1.1; p?=?0.001) and at 3 months (?0.6?±?1.1; p?<?0.001), but not at 6 months (?0.3?±?1.3; p?=?0.066) or 12 months (?0.3?±?1.2; p?=?0.066). Mixed effect modeling showed a significant increase in LS BMD Z-scores between 3 and 12 months (0.22 SD; 95 % CI, 0.08 to 0.36; p?=?0.003). A subgroup (N?=?16; 25 %) had LS BMD Z-scores that were ≤?1.0 at 12 months. In these children, each additional 1,000 mg/m² of GC received in the first 3 months was associated with a decrease in LS BMD Z-score by 0.39 at 12 months (95 % CI, ?0.71 to ?0.07; p?=?0.017).

Conclusions

The incidence of VF at 1 year was low and LS BMD Z-scores improved by 12 months in the majority. Twenty-five percent of children had LS BMD Z-scores ≤?1.0 at 12 months. In these children, LS BMD Z-scores were inversely associated with early GC exposure, despite similar GC exposure compared to the rest of the cohort.     

Understanding optimal nutrition among women of childbearing age in the United States and Puerto Rico: employing formative research to lay the foundation for national birth defects prevention campaigns

Neural tube defects (NTDs) are serious birth defects of the brain and spine that affect approximately 3,000 pregnancies in the United States each year and affected 404 pregnancies in Puerto Rico from 1996 to 2002. Consuming the B vitamin folic acid can reduce the incidence of NTDs 50%-70%, and recent efforts to reduce NTD rates have focused on increasing the number of childbearing-aged women who take a vitamin containing folic acid every day. As the first stage of formative research in campaign planning, two exploratory, qualitative studies were conducted in order to (a) understand the complexity of vitamin use among women in the United States and Puerto Rico and (b) serve as a foundation on which to develop national communication and education interventions. Also, this information shed light on theories that might be used to guide campaign development. Results indicated that campaign messages designed to increase folic acid use through multivitamin supplementation in the United States must address women's barriers to vitamin use (e.g., cost, time), increase women's perceived need for multivitamins (e.g., identify immediate, tangible results from taking a daily multivitamin), and address the relationship between daily food choices and the need for supplementation. Future campaign messages in Puerto Rico must focus on many of these same issues, in addition to increasing women's knowledge about when folic acid should be taken in relation to pregnancy and addressing women's perceptions that vitamins cause weight gain (an undesirable outcome for most participants). The practical and theoretical implications of these results are discussed in terms of their contribution to the development of a creative new approach to increase multivitamin consumption among women of childbearing age in the United States and Puerto Rico.     

The Effects of Sleep Quality and Resilience on Perceived Stress,Dietary Behaviors,and Alcohol Misuse: A Mediation-Moderation Analysis of Higher Education Students from Asia,Europe, and North America during the COVID-19 Pandemic

Background: The coronavirus disease 2019 (COVID-19) pandemic has increased the already high levels of stress that higher education students experience. Stress influences health behaviors, including those related to dietary behaviors, alcohol, and sleep; yet the effects of stress can be mitigated by resilience. To date, past research studying the connections between dietary behaviors, alcohol misuse, sleep, and resilience commonly investigated singular relationships between two of the constructs. The aim of the current study was to explore the relationships between these constructs in a more holistic manner using mediation and moderation analyses. Methods: Higher education students from China, Ireland, Malaysia, South Korea, Taiwan, the Netherlands, and the United States were enrolled in a cross-sectional study from April to May 2020, which was during the beginning of the COVID-19 pandemic for most participants. An online survey, using validated tools, was distributed to assess perceived stress, dietary behaviors, alcohol misuse, sleep quality and duration, and resilience. Results: 2254 students completed the study. Results indicated that sleep quality mediated the relationship between perceived stress and dietary behaviors as well as the relationship between perceived stress and alcohol misuse. Further, increased resilience reduced the strength of the relationship between perceived stress and dietary behaviors but not alcohol misuse. Conclusion: Based on these results, higher education students are likely to benefit from sleep education and resilience training, especially during stressful events.     

Effectiveness of nursing-led inpatient care for patients with post-acute health care needs: secondary data analysis from a programme of randomized controlled trials

OBJECTIVES: To determine whether transfer to a nursing-led inpatient unit (NLIU) prior to discharge from hospital can improve clinical outcome and reduce length of stay and readmission rate for medically stable post-acute patients assessed as requiring inpatient care. METHOD: Retrospective secondary data analysis of individual patient data (n=471) from a programme of three, purposefully replicated, pragmatic randomized controlled trials. Patients were referred to the NLIU by their consultant (attending doctor/surgeon) for nursing-led subacute/post-acute care and randomly allocated to a treatment group for planned transfer to the NLIU for the remainder of their hospital stay or to a control group for traditional consultant-led care in acute wards. Outcome measures were physical function (Barthel Index), length of stay, discharge destination, mortality, psychological well-being (General Health Questionnaire-12), health-related distress (Nottingham Health Profile Distress Index), incidence of complications and readmission within 7, 28, 90 and 180 days. RESULTS: Patients allocated to the NLIU showed greater improvement in physical function (P<0.001) and were more likely to be discharged to live independently in the community than controls [odds ratio (OR)=0.42, P=0.001] although they spent longer in hospital (P= 0.003). They showed greater improvement in psychological well-being (P = 0.001) and health-related distress (P =0.025) and a lower incidence of pressure ulcers (OR=0.33, P=0.011). CONCLUSION: Transfer to a NLIU can have a beneficial effect on outcomes of care for post-acute patients with complex health and social needs although length of stay is longer. This study strengthens the evidence of effectiveness of the NLIU model of care and provides evidence of effectiveness of post-acute and subacute models of care.     

Magnetite morphology and life on Mars

Nanocrystals of magnetite (Fe(3)O(4)) in a meteorite from Mars provide the strongest, albeit controversial, evidence for the former presence of extraterrestrial life. The morphological and size resemblance of the crystals from meteorite ALH84001 to crystals formed by certain terrestrial bacteria has been used in support of the biological origin of the extraterrestrial minerals. By using tomographic and holographic methods in a transmission electron microscope, we show that the three-dimensional shapes of such nanocrystals can be defined, that the detailed morphologies of individual crystals from three bacterial strains differ, and that none uniquely match those reported from the Martian meteorite. In contrast to previous accounts, we argue that the existing crystallographic and morphological evidence is inadequate to support the inference of former life on Mars.