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PubMed1996

Explaining sex differences in course and outcome in the functional psychoses.

We addressed the following three questions: (i) are there sex differences in outcome in the functional psychoses?, (ii) what is their effect size, and which variables mediate the effect of sex on outcome?, (iii) is the effect of sex diagnosis-specific? In a prospective study of 166 patients with recent onset psychosis, we established that 4-year outcome was more favourable for women. Female patients more often had a remitting illness course (OR = 3.0; 95% CI: 1.5-5.9), were living independently 14% (4-24%) more of the time, had less evidence of negative symptoms over the follow-up period (OR = 0.3; 0.2-0.7) and were more likely to be employed at follow-up (3.6; 1.8-7.6). The findings did not appear diagnosis-specific, although the sample size was small to test for interaction with diagnostic category. Baseline occupational and social adjustment, clinical expression of illness and age and type of onset explained up to 60% of the sex effect. The processes underlying these factors mediate the effect of sex on outcome.

Adolescent↗

PubMed1991

Does trans-lesion synthesis explain the UV-radiation resistance of DNA synthesis in C. elegans embryos?

Over 10-fold larger fluences were required to inhibit both DNA synthesis and cell division in wild-type C. elegans embryos as compared with other model systems or C. elegans rad mutants. In addition, unlike in other organisms, the molecular weight of daughter DNA strands was reduced only after large, superlethal fluences. The molecular weight of nascent DNA fragments exceeded the interdimer distance by up to 19-fold, indicating that C. elegans embryos can replicate through non-instructional lesions. This putative trans-lesion synthetic capability may explain the refractory nature of UV radiation on embryonic DNA synthesis and nuclear division in C. elegans.

Animals↗

PubMed2004

Reinforcement expectations explain the relationship between depressive history and smoking status in college students.

Little is understood about biobehavioral mechanisms that mediate the comorbidity between cigarette smoking and depression. We hypothesized that expectancies about nicotine's reinforcing effects are associated with vulnerability to depression, and may partially explain the relationship between history of depression and smoking. Young adult smokers and never smokers (N=175, mean age=19.9 years, S.D.=3.2) were assessed for history of depression and expectations about the negative (e.g., dispels bad moods) and positive (e.g., increases pleasure) reinforcing effects of smoking. Results are inconsistent with the premise that negative reinforcement expectancies mediate the comorbidity between depression and nicotine dependence. Instead, findings suggest that young adults with a prior history of major depression hold exaggerated expectations about nicotine's positive effects, which could enhance their likelihood of initiating smoking.

Adult↗

PubMed2006

Underuse of evidence-based treatment partly explains the worse clinical outcome in diabetic patients with acute coronary syndromes.

BACKGROUND: Diabetes-related differences in treatment and clinical outcome of patients across the entire spectrum of acute coronary syndromes (ACSs) have potential clinical implications but have not been well studied. METHODS: The multicenter, prospective, Canadian ACS Registry enrolled 4578 patients hospitalized for ACS between 1999 and 2001 across 9 provinces in Canada. We compared baseline characteristics, in-hospital and post-discharge treatments, and clinical outcome of diabetic and non-diabetic patients. The impact of diabetes on use of thrombolytic therapy and coronary revascularization; and the independent association between diabetes, treatments, and diabetes-treatment interactions on outcome were examined. RESULTS: Diabetic patients with ACS had more cardiovascular risk factors and higher-risk clinical presentation. They paradoxically received less evidence-based medications in-hospital, at discharge, and at 1-year. Although diabetes independently predicted higher 1-year mortality (OR 1.47, 95% CI 1.15-1.87; P = .002) after adjustment for validated prognosticators, it was also an independent predictor of not receiving thrombolytic therapy (OR 0.72, 95% CI 0.54-0.95; P = .021) and coronary revascularization (OR 0.69, 95% CI 0.59-0.82; P < .001). These underused therapies were all independently associated with reduced 1-year mortality, with no significant diabetes-related treatment-outcome heterogeneity. Importantly, diabetes remained an independent adverse prognosticator even after further adjustment for these differences in treatment. CONCLUSIONS: Evidence-based therapies are underused in the contemporary management of diabetic patients with ACS, which partly explains their worse outcome. Diabetes should be considered a high-risk feature in ACS risk stratification that encourages more intensive treatments. Continued efforts to promote adherence to existing proven therapies and to develop novel treatment strategies targeting diabetes-specific cardiovascular pathophysiology are imperative to improve their adverse prognosis.

Acute Disease↗

PubMed2006

Allogeneic blood transfusions explain increased mortality in women after coronary artery bypass graft surgery.

BACKGROUND: Postoperative mortality is greater in women than men after coronary artery bypass graft surgery. Because allogeneic blood transfusions are more common in women and have been associated with immunomodulation, the impact of transfusion on sex differences in infection and mortality was examined. METHODS: A cohort study was conducted using Michigan Medicare beneficiaries who had undergone coronary artery bypass graft surgery. Information was used regarding allogeneic blood transfusion, infection, and mortality within the 100-day period after surgery. RESULTS: Blood transfusions were more common in women than in men (88.2%, 95% CI 87.1%-89.2% vs 66.7%, 95% CI 65.5%-67.9%). Patients who received transfused blood were more likely to have an infection than patients who did not (14.6%, 95% CI 13.8%-15.5% vs 4.9%, 95% CI 4.1%-5.9%). There was a dose-response relationship between the number of units of whole blood or packed red cells received and the prevalence of infection (P = .035). The unadjusted risk of mortality attributable to female sex was 13.9% (95% CI 8.1%-19.6%), but was no longer statistically significant when adjusted for blood transfusion (population attributable risk 0.6%, 95% CI -6.0% to 6.6%). Patients who received a transfusion were 5.6 times as likely to die within 100 days after surgery as those who did not receive a transfusion (95% CI 3.7-8.6). CONCLUSION: The increased risk of mortality in women after bypass surgery may be explained by transfusion-related immunosuppression.

Blood Transfusion↗

PubMed2006

Intrinsic racial differences in the risk of cesarean delivery are not explained by differences in caregivers or hospital site of delivery.

OBJECTIVE: This study was undertaken to assess whether racial differences in the risk of cesarean delivery result from differing practices of their caregivers or the hospitals at which they deliver. STUDY DESIGN: A retrospective cohort study was performed using the Perinatal Database of the Memorial Health Care System. Logistic regression was used to estimate the risk of primary cesarean delivery among patients eligible for labor. The contribution of hospital and physician level cluster correlation was evaluated using fixed and random effects regression models. RESULTS: Compared with white patients, black and Hispanic patients were 75% and 22% more likely to undergo primary cesarean delivery. Further adjustment for hospital and physician level cluster correlation resulted in persistently increased risks of primary cesarean delivery in black (54%) and Hispanic patients (12%). CONCLUSION: Hospital site of delivery and individual physician practices do not fully explain racial differences in the risk of primary cesarean delivery.

Adult↗

PubMed2006

Actions of peroxisome proliferator-activated receptors-gamma agonists explaining a possible blood pressure-lowering effect.

The metabolic syndrome is a cluster of disturbances such as type 2 diabetes mellitus, hypertension, central obesity, dyslipidemia, and others for which insulin resistance and compensatory hyperinsulinemia have been proposed to be the underlying disorders. Several possible mechanisms linking insulin resistance and compensatory hyperinsulinemia with hypertension have been described, such as renal sodium reabsorption enhancement, sympathetic nervous system activation, and blunted insulin-mediated vasodilation caused by endothelial dysfunction. Peroxisome proliferator-activated receptors-gamma agonists or thiazolidinediones (TZD) are a class of agents for the treatment of type 2 diabetes mellitus that act through improvement of insulin sensitivity. In parallel to their antihyperglycemic action, these drugs were found to exert beneficial effects on other components of the metabolic syndrome. For example all TZD have been shown to reduce blood pressure (BP) levels in both animal and human studies. In addition a considerable number of in vitro and in vivo studies report actions of TZD on the cardiovascular system that could explain this blood pressure-lowering effect of TZD, such as restoration of blunted endothelium-mediated vasodilation, attenuation of sympathetic overactivity, inhibition of intracellular Ca(2+) increase, and proliferation of vascular smooth muscle cells and others. This review summarizes the current evidence about these actions of TZD that could positively influence BP, representing possible mechanisms of BP amelioration.

Animals↗

PubMed2004

Microvascular responses to adenosine help explain functional and pathologic differences between intestinal segments.

BACKGROUND: Many physiologic (post-prandial hyperemia), pathologic (inflammatory bowel disease), and clinical (enteral feeding) phenomena involve changes in microvascular blood flow to the intestine. Adenosine (Ado) derived from energy metabolism causes vasodilation and appears to be involved in some of these events. The Ado-mediated control mechanisms appear to vary with the diameter of the microvessels and the function of the tissue. This suggests the possibility that Ado-based microvascular control varies between anatomic intestinal segments and microvascular levels in those intestinal segments. METHODS: In vivo digital intravital microscopy was used to measure the responses of larger distributing (A1) and smaller premucosal (A3) vessels to Ado in intact neurovascular loops of jejunum and terminal ileum of the rat. Dose-response curves to Ado were determined. RESULTS: Microvascular dilation and augmented blood flow to Ado were significantly greater in the jejunum than in the terminal ileum. Ado-induced dilation was greater in the smaller A3 than in the larger A1 microvessels. DISCUSSION: These data indicate (1) different vasodilator mechanisms for the jejunum and the terminal ileum, (2) a greater role for Ado-related microvascular control in the jejunum compared with the ileum, and (3) a greater Ado-related control in the premucosal (A3) vessels. These findings suggest that Ado-mediated microvascular effects could explain why some clinical phenomena vary in intensity in selective intestinal segments, and are likely to involve different microvascular control mechanisms in the different segments. Knowledge of these Ado mechanisms could be beneficial in certain clinical scenarios to control blood flow during pathologic conditions.

Adenosine↗

PubMed2005

A longitudinal study to explain strategies to change weight and muscles among normal weight and overweight children.

Previous research has indicated that both boys and girls strive for a slim body, with boys having an additional focus on a muscular body build. The current study was designed to evaluate the utility of a biopsychosocial model to explain body image and body change strategies among children. The study evaluated changes over time in body image and strategies to lose weight and increase muscles among 132 normal weight and 67 overweight boys (mean age = 9.23 years) and 158 normal weight and 55 overweight girls (mean age = 9.33 years). The predictive role of BMI, positive and negative affect, self-esteem and perceived sociocultural pressures to lose weight or increase muscle on body image and body change strategies over a 16 month period was evaluated. All participants completed the questionnaire on both occasions. The results demonstrated that both overweight boys and girls were more likely to be dissatisfied with their weight, place more importance on their weight, engage in more strategies to lose weight as well as perceive more pressure to lose weight. Overweight boys and girls were also more likely to report lower levels of self-esteem and positive affect, and higher levels of negative affect, and reported a reduction in their self-esteem over time. Regression analyses demonstrated that among overweight boys, low self-esteem and high levels of perceived pressure to lose weight predicted weight dissatisfaction; for overweight girls, weight dissatisfaction was also predicted by low levels of self-esteem. The implication of these findings in terms of factors contributing to the adoption of health risk behaviors among children is discussed.

Body Composition↗

PubMed2005

Self-rated health and mortality: could clinical and performance-based measures of health and functioning explain the association?

It is well established that self-rated health (SRH) predicts mortality even when other indicators of health status are taken into account. It has been suggested that SRH measures a wide array of mortality-related physiological and pathological characteristics not captured by the covariates included in the analyses. Our aim was to test this hypothesis by examining the predictive value of SRH on mortality controlling for different measurements of body structure, performance-based functioning and diagnosed diseases with a population-based, prospective study over an 18-year follow-up. Subjects consisted of 257 male residents of the city of Jyväskylä, central Finland, aged 51-55 and 71-75 years. Among the 71-75-year-olds the association between SRH and mortality was weaker over the longer compared to shorter follow-up period. In the multivariate Cox regression models with an 18-year follow-up time for middle-aged and a10-year follow-up time for older men, SRH predicted mortality even when the anthropometrics, clinical chemistry and performance-based measures of functioning were controlled for, but not when the number of chronic diseases was included. Although our results confirm the hypothesis that the predictive value of SRH can be explained by diagnosed diseases, its predictive power remained, when the clinical and performance-based measures of health and functioning were controlled.

Activities of Daily Living↗

PubMed2005

Explainable and critical periods during human dental morphogenesis and their control.

OBJECTIVE: To what extent is the current knowledge about regulatory and patterning processes gained from research on animal models (predominantly mouse) applicable to describe certain aspect of human prenatal dental development? METHODS: 3D-reconstructions were produced from serial sections of human dental primordia (Radlanski collection, Berlin) and scanning electron microscopic visualisation techniques were applied. RESULTS AND CONCLUSION: There are several examples, where present knowledge of regulatory processes allows the understanding of changes in outline and form. However, many other examples show that much more complex regulatory mechanisms should be expected to explain the details of human prenatal dental development.

Computer Graphics↗

PubMed2004

Explaining disparities in access to high-quality cardiac surgeons.

BACKGROUND: Racial disparities in access to coronary artery bypass graft (CABG) surgery are well documented. Recent evidence shows that even when patients receive CABG surgery, racial minorities are more likely to be treated by lower quality providers. METHODS: New York State (NYS) hospital discharge data for 1996 and 1997 for patients undergoing CABG surgery were combined with risk-adjusted mortality rates for cardiac surgeons calculated by the NYS Department of Health. Statistical analysis was performed to determine the relationship between patients' race and the quality of the surgeon performing the CABG, as measured by the surgeon's risk-adjusted mortality rate, after controlling for patient characteristics such as comorbidities and socioeconomic status; the hospital where the surgery was performed; and the number of surgeries the surgeon performed over a 3-year period. RESULTS: African Americans and Asian/Pacific Islanders are treated by surgeons with higher risk-adjusted mortality rates compared with whites. This association does not appear to be a result of inadequate risk adjustment. It is explained to some degree by the hospital to which these patients are admitted, and to a lesser degree by (1) the education and income level in the patient's zipcode of residence and (2) being treated by a low-volume surgeon. After controlling for these factors, race continues to be associated with treatment by a surgeon with a higher risk-adjusted mortality rate. CONCLUSIONS: Efforts to achieve the "Healthy People 2010" goals of eliminating health disparities should address not only access to care, but also access to high-quality care.

Black or African American↗

PubMed2004

Enhanced cardiac vagal efferent activity does not explain training-induced bradycardia.

Studies of heart rate variability (HRV) have so far produced contradictory evidence to support the common belief that endurance training enhances cardiac parasympathetic tone. This may be related to the fact that most studies failed to specifically isolate the vagally mediated influence of respiration. This study used a cross-sectional comparison of endurance athletes (n=20; ATHL) exhibiting resting bradycardia and age-matched nonathletes (n=12; CRTL) to indirectly assess training effects on amplitude and timing characteristics of respiratory sinus arrhythmia (RSA). Continuous electrocardiogram (ECG) and ventilatory flows were recorded during spontaneous breathing (SP), as well as during breathing at four cycles less than (M4) or more (P4) than SP, to also examine potential repercussions of training on the sensitivity of the cardiac vagal responses to breathing. A fast Fourier transform procedure was used to quantify the standard spectral high-frequency (HF) and low-frequency (LF) components and a respiratory-centered frequency (RCF) component of HRV. RSA was assessed using a breath-by-breath quantification of the amplitude and timing of the maximum change in instantaneous heart rate. Under baseline SP conditions, heart rate was lower in ATHL (62.6+/-6.5 vs. 75.2+/-9 beats/min; p<0.05) while blood pressure (BP), breath cycle duration, tidal volume, and ventilatory drive were similar in both groups. HRV total spectral power density, LF, HF, or RCF was not different between groups at either the SP, M4, or P4 conditions. Changes in total breath duration similarly affected RSA amplitude in all groups, while HR and BP remained unchanged from SP. RSA phase was not affected by training status or by changes in total breath duration. RSA amplitude was negatively related to breathing frequency in all groups (p<0.05), while the mean slope of the relationship (sensitivity) was not different between groups. In as much as RSA is an adequate marker of cardiac vagal efferent activity, these results add support to a contribution of a decrease in intrinsic heart rate to explain training-induced bradycardia.

Adolescent↗

PubMed2006

Hospitalization for depression is associated with an increased risk for myocardial infarction not explained by lifestyle, lipids, coagulation, and inflammation: the SHEEP Study.

BACKGROUND: Depression is considered a risk factor for coronary heart disease (CHD) in initially CHD-free populations. Subclinical CHD or other somatic causes of depressive symptoms might account for the association, however. METHODS: In this case-control study, patients had had their first acute myocardial infarction (AMI). The study included 1799 cases, aged 45-70 years, and 2339, age-, gender-, and hospital-catchment-area-matched control subjects. We calculated odds ratios (OR) with 95% confidence intervals (CI) by multivariate logistic regressions to assess the AMI risk associated with a hospitalization for depression. RESULTS: Forty-seven cases and 22 control subjects had been hospitalized for depression. After adjustment for matching criteria and socioeconomic status, the OR for AMI was 2.9 (1.8-4.9) for ever hospitalized for depression. Patients hospitalized for depression before or after the median time, 15 years and 2 months, between the first hospitalization for depression and AMI, were at similar risk. Adjustment for lifestyle, lipid profile, coagulation, inflammation, prior cardiovascular events, and comorbidity only partly decreased the observed association. CONCLUSIONS: Depression was associated with increased risk for AMI. Subclinical CHD or other somatic causes are unlikely to account for our findings, which also appear not to be explained by established risk factors for AMI.

Aged↗

PubMed2004

Adenine derived inhibitors of the molecular chaperone HSP90-SAR explained through multiple X-ray structures.

Multiple co-crystal structures of an adenine-based series of inhibitors bound to the molecular chaperone Hsp90 have been determined. These structures explain the observed SAR for previously described compounds and new compounds, which possess up to 8-fold improved potency against the isolated enzyme. Anti-tumour cell potency and mechanism of action data is also described for the most potent compounds. These data should enable the design of more potent Hsp90 inhibitors.

Adenine↗

PubMed2004

Does hip strength analysis explain the lower incidence of hip fracture in the People's Republic of China?

To explore whether there are ethnic differences in calculated hip strength that might explain the low incidence of hip fracture in China, we used Lunar DPX 'beta' version of hip strength analysis (HAS) and hip axis length (HAL) programs to compare hip geometry, calculated strength and densitometric values from Chinese subjects in Shenyang to those of Caucasian subjects in Oslo and Leuven participating in the European Prospective Osteoporosis Study (EPOS). Subjects were 210 Chinese and 403 Caucasian men and women aged 53-77 years. Parameters investigated included bone mineral density (BMD), bone mineral content (BMC), bone area (BA), cross-sectional moment of inertia (CSMI) and section modulus (both indicating strength and rigidity of the femoral neck), HAL, neck length (NL), neck diameter, tensile stress (Tstress) and compressive stress (Cstress) (indicating the stress in the femoral neck at its weakest cross section arising from walking or a standard fall, respectively), safety factor (SF, indicating the resistance to fracture for forces generated during walking) and fall index (FI, indicating the resistance to fracture from force generated during a fall in the greater trochanter). The Chinese men and women were significantly shorter and lighter than their Caucasian counterparts (P<0.01) and had significantly lower BMD, BMC and BA of the femoral neck (P<0.01). After adjusting for BA, weight and height, there was no significant ethnic difference in either gender in BMC. CSMI and section modulus were significantly lower, and HAL, NL and neck diameter were significantly shorter in the Chinese men and women (P<0.01). These differences all remained after adjusting for weight and height. There were no significant differences in Tstress, Cstress, SF and FI between ethnic groups in either gender. Most of the parameters of calculated hip strength in the Chinese subjects were similar to or poorer than those in the Caucasian subjects. There was no evidence to indicate that Shenyang Chinese have superior BMD or BMC or better calculated hip strength. The short HAL and NL of the population, however, could be an independent factor contributing to the low incidence of hip fracture.

Aged↗

PubMed2006

Biphasic change in BDNF gene expression following antidepressant drug treatment explained by differential transcript regulation.

Brain-derived neurotrophic factor (BDNF) has been suggested as a possible target for the treatment of depression. The effect by antidepressant drugs on BDNF mRNA expression is, however, strictly dependent on both treatment duration and time after the last administration. The rat BDNF gene itself is complex and expresses four different mRNA isoforms which can be regulated by different signaling cascades. The aim of the present study was to test the hypothesis that the previously shown biphasic action by the antidepressant drugs on total BDNF expression is explained by differential BDNF transcript regulation. For this purpose, we used in situ hybridization with exon-specific oligo nucleotides for exon V (total BDNF mRNA), exon I (protein synthesis-dependent transcripts), exon III and exon IV (immediate early-gene like-transcripts). Following an acute injection, all three drugs tested: fluoxetine, desipramine and TCP decreased total BDNF mRNA (exon V) as well as exon IV mRNA, while no significant effect was recorded for exons I and III mRNAs. In contrast chronic administration of all three drugs resulted in increased expression of exon V- and exon I-containing transcripts (fluoxetine and TCP only) but no significant changes were recorded for exon III and IV mRNAs. Electroconvulsive shock administration showed up-regulation of all four BDNF mRNAs following a single shock, but after repeated administration increases were restricted to exons I- and V-containing transcripts. In summary, this study shows clear evidence of differential BDNF transcript regulation following acute and chronic antidepressant drug treatment.

Animals↗

PubMed2005

Corticosterone inhibits feather growth: potential mechanism explaining seasonal down regulation of corticosterone during molt.

Corticosterone (CORT) is seasonally modulated in many passerines, with plasma CORT concentrations lowest during the prebasic molt when all feathers are replaced. To explain why, we proposed that the birds downregulate natural CORT release during molt in order to avoid CORT's degradative effects on proteins and its inhibition of protein synthesis. If CORT exerted these effects during molt, it could slow protein deposition during feather production and potentially result in a longer period of degraded flight performance. To test this hypothesis, either empty or CORT-filled silastic implants were inserted into captive European starlings (Sturnus vulgaris) and white-crowned sparrows (Zonotrichia leucophrys) undergoing induced (feather replacement after plucking) and natural molts. We then measured the rate of feather re-growth by regularly measuring the length of primary, secondary, and tail feathers. CORT implanted birds showed a significantly decreased rate of feather growth compared to control animals. Basal CORT concentrations of induced molt and non-molting birds were also compared but no difference was noted. The results suggest a tradeoff; a complete set of new feathers may be more important to the survival of a bird than the ability of CORT to respond maximally to a stressor.

Animals↗