Growth plate cartilage demonstrates a unique capacity for cell proliferation and matrix synthesis while sustaining mechanical stresses. To test the hypothesis that the extracellular matrices along ...various depth of growth plate cartilage have different elastic properties, microindentation by atomic force microscopy was applied to en bloc dissected rabbit cranial base growth plate samples from the reserve zone to mineralizing zone in 50-microm increments. The average elastic modulus upon transverse indentation orthogonal to the long axis of the growth plate showed a gradient distribution, increasing significantly from the reserve zone (0.57 +/- 0.05 MPa) to mineralizing zone (1.41 +/- 0.19 MPa). Longitudinal indentation of the reserve zone along the long axis of the growth plate revealed an average elastic modulus of 0.77 +/- 0.12 MPa, significantly different from the same zone upon transverse indentation. Thus, the extracellular matrix of growth plate cartilage seems to be inhomogenous in its capacity to withstand mechanical stresses.
•Cholesterol-like effects decrease in the order of 3β-ol>3α-ol>3-keto in the Δ5 compounds.•Cholesterol-like effects decrease in the reverse order in the Δ4,6 sterols/steroid.•The Δ5 are more ...effective than the Δ4,6 sterols, but this is reversed in the steroids.•Keto–enol tautomerism in the Δ4,6 keto-steroid only may increase its H-bonding potential.•The presence of a Δ5 double bond is required for maximum miscibility in DPPC bilayers.
We present the results of a comparative differential calorimetric and Fourier transform infrared spectroscopic study of the effect of cholesterol and five analogues on the thermotropic phase behaviour and organization of dipalmitoylphosphatidylcholine bilayer membranes. These sterols/steroids differ in both the nature and stereochemistry of the polar head group at C3 (βOH, αOH or CO) and in the position(s) of the double bond(s). In the Δ5 sterols/steroid series, the concentration of these compounds required to abolish the DPPC pretransition, inversely related to their relative ability to disorder gel state DPPC bilayers, decreases markedly in the order βOH>αOH>CO. However, in the Δ4,6 series, these concentrations are similar, regardless of polar head group chemical structure. Similarly, the residual enthalpy of the DPPC main phase transition at 50mol% sterol/steroid, which is inversely related to the miscibility of these compounds in the DPPC bilayer, also increases in the order βOH>αOH>CO, but this effect is attenuated in the Δ4,6 series. In the two pairs of sterol epimers, the Δ4,6 compounds exhibit a greater decrease in the temperature and enthalpy of both the pretransition and the main phase transition, whereas the opposite result is observed in the ketosteroid pair. Similarly, the ability of these compounds to order the DPPC hydrocarbon chains decreases in the order βOH>αOH>CO in both series of compounds, but in the two pairs of sterol epimers, hydrocarbon chain ordering is greater for the Δ5 than the Δ4,6 sterols, whereas the opposite is the case for the steroid pair. Thus, the characteristic effects of sterols/steroids on fluid lipid bilayers are optimal when an OH group rather than CO group is present at C3, and when this OH group is in the equatorial orientation. We suggest that the presence of keto–enol tautomerism in the conjugated Δ4,6 ketosteroid may provide additional H-bonding opportunities to adjacent DPPC molecules in the bilayer, which results in more cholesterol-like effects.
Synthesis of the Himandrine Skeleton O'Connor, Patrick D; Mander, Lewis N; McLachlan, Matthew M. W
Organic letters,
03/2004, Volume:
6, Issue:
5
Journal Article
Peer reviewed
Open access
The hexacyclic himandrine skeleton 5, which is present in the most complex alkaloids of the tropical rain forest tree Galbulimima belgraveana, has been prepared for the first time. The synthesis ...begins from the known 3.2.1benzobicyclooctene intermediate 10. Key steps include a Diels−Alder cycloaddition, Curtius rearrangement, Birch reduction, an intramolecular nucleophilic amination, and a palladium-mediated alkene amination.
Difficulties in measuring insulin sensitivity prevent the identification of insulin-resistant individuals in the general population. Therefore, we compared fasting insulin, homeostasis model ...assessment (HOMA), insulin-to-glucose ratio, Bennett index, and a score based on weighted combinations of fasting insulin, BMI, and fasting triglycerides with the euglycemic insulin clamp to determine the most appropriate method for assessing insulin resistance in the general population.
Family history of diabetes, BMI, blood pressure, waist and hip circumference, fasting lipids, glucose, insulin, liver enzymes, and insulin sensitivity index (ISI) using the euglycemic insulin clamp were obtained for 178 normoglycemic individuals aged 25-68 years. Product-moment correlations were used to examine the association between ISI and various surrogate measurements of insulin sensitivity. Regression models were used to devise weights for each variable and to identify cutoff points for individual components of the score. A bootstrap procedure was used to identify the most useful predictors of ISI.
Correlation coefficients between ISI and fasting insulin, HOMA, insulin-to-glucose ratio, and the Bennett index were similar in magnitude. The variables that best predicted insulin sensitivity were fasting insulin and fasting triglycerides. The use of a score based on Mffm/I = exp2.63 - 0.28ln(insulin) - 0.31ln(TAG) rather than the use of fasting insulin alone resulted in a higher sensitivity and a maintained specificity when predicting insulin sensitivity.
A weighted combination of two routine laboratory measurements, i.e., fasting insulin and triglycerides, provides a simple means of screening for insulin resistance in the general population.
Abstract Objective This study examines whether cancer patients’ Internet use leads them to prefer a more active role in medical decision making and whether the effects of Internet use on active ...participation preferences vary according to patients’ education levels. Methods Randomly drawn sample ( N = 2013) from the Pennsylvania Cancer Registry, comprised of breast, prostate, and colon cancer patients, completed mail surveys in the fall of 2006 (overall response rate = 64%). Of 2013 baseline respondents, 85% agreed to participate in follow-up survey ( N = 1703). Of those who agreed, 76% ( N = 1293) completed follow-up surveys in the fall of 2007. Results Cancer patients’ Internet use for health information at wave one led them to want to be more active participants in medical decision making at wave two ( β = .06, p < .05). This applied to all cancer patients regardless of their education levels. Conclusion Higher levels of Internet use among cancer patients may lead patients to want to be more actively involved in medical decision making. Practice Implications Considering the beneficial effects of patients’ active participation in medical decision making, it will be worthwhile for health educators to recommend Internet use to cancer patients.
A Web-based approach to blood donor preparation France, Christopher R.; France, Janis L.; Kowalsky, Jennifer M. ...
Transfusion (Philadelphia, Pa.),
February 2013, Volume:
53, Issue:
2
Journal Article
Peer reviewed
BACKGROUND: Written and video approaches to donor education have been shown to enhance donation attitudes and intentions to give blood, particularly when the information provides specific coping ...suggestions for donation‐related concerns. This study extends this work by comparing Web‐based approaches to donor preparation among donors and nondonors.
STUDY DESIGN AND METHODS: Young adults (62% female; mean ±SD age, 19.3 ±1.5 years; mean range number of prior blood donations, 1.1 0‐26; 60% nondonors) were randomly assigned to view 1) a study Web site designed to address common blood donor concerns and suggest specific coping strategies (n = 238), 2) a standard blood center Web site (n = 233), or 3) a control Web site where participants viewed videos of their choice (n = 202). Measures of donation attitude, anxiety, confidence, intention, anticipated regret, and moral norm were completed before and after the intervention.
RESULTS: Among nondonors, the study Web site produced greater changes in donation attitude, confidence, intention, and anticipated regret relative to both the standard and the control Web sites, but only differed significantly from the control Web site for moral norm and anxiety. Among donors, the study Web site produced greater changes in donation confidence and anticipated regret relative to both the standard and the control Web sites, but only differed significantly from the control Web site for donation attitude, anxiety, intention, and moral norm.
CONCLUSION: Web‐based donor preparation materials may provide a cost‐effective way to enhance donation intentions and encourage donation behavior.
The two isoforms of sphingosine kinase (SphK1 and SphK2) are the only enzymes that phosphorylate sphingosine to sphingosine-1-phosphate (S1P), which is a pleiotropic lipid mediator involved in a ...broad range of cellular processes including migration, proliferation, and inflammation. SphKs are targets for various diseases such as cancer, fibrosis, and Alzheimer’s and sickle cell disease. Herein, we disclose the structure–activity profile of naphthalene-containing SphK inhibitors and molecular modeling studies that reveal a key molecular switch that controls SphK selectivity.
The United States military relies on visual acuity standards to assess enlistment induction and military occupational specialty eligibility, as well as to monitor soldiers' combat vision readiness. ...However, these vision standards are not evidence based and may not accurately reflect appropriate standards for military readiness or reflect a correlation between visual acuity and occupational performance. The aim of this study was to investigate the relationship between visual acuity and marksmanship performance using a single blind trial with the Engagement Skills Trainer 2000. Marksmanship performance was evaluated in 28 subjects under simulated day and night conditions with habitual spectacle prescription and contact lenses that created visual blur. Panel Poisson regression using an independent correlation structure revealed significant differences (p < 0.001) as visual acuity decreased from 20/25 to 20/50. We conclude that marksmanship performance decreases as visual acuity decreases. We believe that this relationship supports the use of a visual acuity requirement.