We aimed to explore whether frailty was associated with fracture risk and whether frailty could modify the propensity of type 2 diabetes toward increased risk of fractures.
Data were from a ...prospective cohort study. Our primary outcome was time to the first incident clinical fragility fracture; secondary outcomes included time to hip fracture and to clinical spine fracture. Frailty status was measured by a Frailty Index (FI) of deficit accumulation. The Cox model incorporating an interaction term (frailty × diabetes) was used for analyses.
The analysis included 3,149 (70% women) participants; 138 (60% women) had diabetes. Higher bone mineral density and FI were observed in participants with diabetes compared with control subjects. A significant relationship between the FI and the risk of incident fragility fractures was found, with a hazard ratio (HR) of 1.02 (95% CI 1.01-1.03) and 1.19 (95% CI 1.10-1.33) for per-0.01 and per-0.10 FI increase, respectively. The interaction was also statistically significant (
= 0.018). The HR for per-0.1 increase in the FI was 1.33 for participants with diabetes and 1.19 for those without diabetes if combining the estimate for the FI itself with the estimate from the interaction term. No evidence of interaction between frailty and diabetes was found for risk of hip and clinical spine fractures.
Participants with type 2 diabetes were significantly frailer than individuals without diabetes. Frailty increases the risk of fragility fracture and enhances the effect of diabetes on fragility fractures. Particular attention should be paid to diabetes as a risk factor for fragility fractures in those who are frail.
Background
According to the Dual-factor Model, mental health is comprised of two related constructs: subjective well-being and psychopathology. Combining these constructs can provide a more accurate ...and comprehensive assessment of adolescent mental health than considering either on its own. The model suggests the need to group mental health into four distinct categories, which does not recognize its potential continuum and adds statistical complexity. In this study, we developed a continuous measure inspired by, and as a complement to, the Dual-factor Model. Our goal was to demonstrate a novel approach to developing a valid measure for use in public health research that captures varying mental health states more accurately than traditional approaches and has advantages over the categorical version.
Methods
Self-report data are from the 2014 Canadian Health Behavior in School-aged Children study (
n
= 21,993). Subjective well-being was measured by combining indicators of life satisfaction, positive affect, and negative affect. Internalized and externalized symptoms scales were combined to measure psychopathology. The continuous dual-factor measure was created by subtracting standardized psychopathology scores from standardized subjective well-being scores. Construct validity was assessed using multivariable linear regression by examining associations between factors known to be associated with adolescent mental health status (demographic characteristics, social and academic functioning, and specific indicators of mental health) and average mental health scores.
Results
The average age was 14.0 (SD = 1.41) years. The continuous mental health score ranged from 5 to 67 Mean (SD): 50.1 (9.8), with higher scores indicating better overall mental health. The nature and direction of the associations examined supported construct validity. Being from a more affluent family, and having more supportive relationships with family, peers, teachers, and classmates was associated with greater mental health (Cohen’s d: 0.65 to 1.63). Higher average marks were also associated with better mental health. Average mental health scores were much lower if students reported feeling hopeless or rated their health as fair or poor.
Conclusion
A continuous measure of mental health based on the Dual-factor Model appears to be a comprehensive and valid measure with applications for research aimed at increasing our understanding of adolescent mental health.
Purpose: The cause of coagulopathic hemorrhage during thoracoabdominal aneurysm (TAA) repair has not been well defined in human studies. We investigated changes in the coagulation system associated ...with supraceliac versus infrarenal cross-clamping to address this critical issue.
Methods: Blood levels of fibrinogen, the prothrombin fragment F1.2, D-dimer, and factors II, V, VII, VIII, IX, X, XI, and XII were analyzed in 19 patients with TAAs and four patients with abdominal aortic aneurysms (AAAs) at: (A) induction; (B) 30 minutes into supraceliac (TAA) or infrarenal (AAA) clamping; (C) 30 minutes after release of supraceliac or infrarenal clamps; and (D) immediately after surgery. Preoperative and intraoperative variables, including but not limited to aneurysm type, pathologic findings, comorbid conditions, clamp times, volume and timing of blood products, and clinical outcome, were prospectively recorded. Significance was determined by analysis of variance, Student's
t test, and univariate linear regression.
Results: Levels of fibrinogen and factors II, V, VIII, VIII, IX, X, XI, and XII decreased (
p < 0.05) at time B versus time A and returned to near baseline by time D. D-dimer and F1.2 increased starting at time B and reached significance (
p < 0.05) by time D. Data points were compared for the TAA and AAA groups. Although AAA groups demonstrated a trend to factor activity reduction and increased fibrinolysis, the effect was much less pronounced than in TAA and did not approach significance. No correlation of coagulation change with clamping time was present; however, visceral clamping times were all less than 65 minutes (mean, 44 minutes). Blood and factor replacement was initiated after time B. Univariate regression analysis of factor level versus total blood replacement demonstrated a significant (
p < 0.04) correlation between the reduction in the levels of factors II, V, VII, VIII, X, and XII, and the increase in the level of D-dimer at time B and subsequent total blood replacement.
Conclusions: Thoracoabdominal aneurysm repair is associated with a reduction in clotting factor activity and an increase in fibrinolytic function, which occurs after placement of the supraceliac clamp. Explanations include visceral ischemia or a greater and longer ischemic tissue burden as the likely cause of coagulation alterations. Total blood replacement during TAA procedures was correlated to the degree of factor reduction and fibrinolysis at the time of visceral cross-clamping. An aggressive approach to early blood component replacement and to coagulation monitoring could lessen blood loss during TAA repair and avoid potentially disastrous bleeding complications. (J Vasc Surg 1996;24;936-45.)
IntroductionStudies of adolescent mental health require valid measures that are supported by evidence-based theories. An established theory is the dual-factor model, which argues that mental health ...status is only fully understood by incorporating information on both subjective well-being and psychopathology.ObjectivesTo develop a novel measure of adolescent mental health based on the dual-factor model and test its construct validity.DesignCross-sectional analysis of national health survey data.Setting and participantsNationally weighted sample of 21 993 grade 6–10 students; average age: 14.0 (SD 1.4) years from the 2014 Canadian Health Behaviour in School-aged Children study.MeasuresSelf-report indicators of subjective well-being (life satisfaction, positive and negative affect), and psychopathology (psychological symptoms and overt risk-taking behaviour) were incorporated into the dual-factor measure. Characteristics of adolescents families, specific mental health indicators and measures of academic and social functioning were used in the assessment of construct validity.ResultsProportions of students categorised to the four mental health groups indicated by the dual-factor measure were 67.6% ‘mentally healthy’, 17.5% ‘symptomatic yet content’, 5.5% ‘asymptomatic yet discontent’ and 9.4% ‘mentally unhealthy’. Being mentally healthy was associated with the highest functioning (greater social support and academic functioning) and being mentally unhealthy was associated with the worst. A one-unit increase (ranges=0–10) in peer support (OR 1.19; 95% CI 1.15 to 1.22), family support (OR 1.32; 95% CI 1.28 to 1.36), student support (OR 1.20; 95% CI 1.17 to 1.24) and average school marks (OR 1.18; 95% CI 1.10 to 1.27) increased the odds of being symptomatic yet content versus mentally unhealthy. Mentally healthy youth were the most likely to live with both parents (77% vs ≤65%) and report their family as well-off (62% vs ≤53%).ConclusionsWe developed a novel, construct valid dual-factor measure of adolescent mental health. This potentially provides a nuanced and comprehensive approach to the assessment of adolescent mental health that is direly needed.
Learning-related plasticity at excitatory synapses in the mammalian brain requires the trafficking of AMPA receptors and the growth of dendritic spines. However, the mechanisms that couple plasticity ...stimuli to the trafficking of postsynaptic cargo are poorly understood. Here we demonstrate that myosin Vb (MyoVb), a Ca
2+-sensitive motor, conducts spine trafficking during long-term potentiation (LTP) of synaptic strength. Upon activation of NMDA receptors and corresponding Ca
2+ influx, MyoVb associates with recycling endosomes (REs), triggering rapid spine recruitment of endosomes and local exocytosis in spines. Disruption of MyoVb or its interaction with the RE adaptor Rab11-FIP2 abolishes LTP-induced exocytosis from REs and prevents both AMPA receptor insertion and spine growth. Furthermore, induction of tight binding of MyoVb to actin using an acute chemical genetic strategy eradicates LTP in hippocampal slices. Thus, Ca
2+-activated MyoVb captures and mobilizes REs for AMPA receptor insertion and spine growth, providing a mechanistic link between the induction and expression of postsynaptic plasticity.
Cold storage of potato tubers is commonly used to reduce sprouting and extend postharvest shelf life. However, cold temperature stimulates the accumulation of reducing sugars in potato tubers. Upon ...high‐temperature processing, these reducing sugars react with free amino acids, resulting in brown, bitter‐tasting products and elevated levels of acrylamide—a potential carcinogen. To minimize the accumulation of reducing sugars, RNA interference (RNAi) technology was used to silence the vacuolar invertase gene (VInv), which encodes a protein that breaks down sucrose to glucose and fructose. Because RNAi often results in incomplete gene silencing and requires the plant to be transgenic, here we used transcription activator‐like effector nucleases (TALENs) to knockout VInv within the commercial potato variety, Ranger Russet. We isolated 18 plants containing mutations in at least one VInv allele, and five of these plants had mutations in all VInv alleles. Tubers from full VInv‐knockout plants had undetectable levels of reducing sugars, and processed chips contained reduced levels of acrylamide and were lightly coloured. Furthermore, seven of the 18 modified plant lines appeared to contain no TALEN DNA insertions in the potato genome. These results provide a framework for using TALENs to quickly improve traits in commercially relevant autotetraploid potato lines.
The metabolic clearance rate (MCR) of arginine vasopressin (AVP) increases fourfold during human pregnancy. To explore whether circulating vasopressinase may play a role in this change, six women ...underwent a three-tier infusion clearance study, twice, in random order, to determine the MCRs of either AVP or 1-deamino-8-D-AVP (dDAVP, an analogue resistant to degradation by vasopressinase). Volunteers were tested in late pregnancy (LP), 24-48 h postdelivery (PD), and 5-6 (PP1) and 10-12 (PP2) wk postpartum, thus examining MCRs when vasopressinase levels were high, before and after removal of the placenta (LP and PD), and when plasma enzyme activity was becoming (PP1) and became (PP2) undetectable. Manipulation of infusate permitted comparison of MCRs at three plasma levels whose range was similar at each test period. PAVP and PdDAVP (2.2 and 10 pg/ml, respectively, during the initial infusion) increased to 8 and 31 pg/ml, stepwise increments that had no influence on respective MCRs (AVP: 3.4, 2.2, 0.77, and 0.67 l/min during LP, PD, PP1, and PP2 compared with 0.18, 0.21, 0.17, and 0.15 l/min for dDAVP). Comparison of similar and submaximal urinary osmolality revealed PdDAVP values three- to fourfold greater than PAVP. Von Willebrand factor (VWF) and factor VIIIc levels increased almost fourfold in response to dDAVP during pregnancy, but only doubled in the nonpregnant state; these differences did not reach significance. We conclude that although AVP disposal rates increase fourfold in pregnancy, those of dDAVP change little, suggesting a role of vasopressinase in the increased MCR of AVP in gestation (as well as in the genesis of certain polyuric disorders of pregnancy).
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