Breeding for Virus Resistance and Its Effects on Deformed Wing Virus Infection Patterns in Honey Bee Queens

Viruses, and in particular the deformed wing virus (DWV), are considered as one of the main antagonists of honey bee health. The ‘suppressed in ovo virus infection’ trait (SOV) described for the first time that control of a virus infection can be achieved from genetically inherited traits and that the virus state of the eggs is indicative for this. This research aims to explore the effect of the SOV trait on DWV infections in queens descending from both SOV-positive (QDS+) and SOV-negative (QDS–) queens. Twenty QDS+ and QDS– were reared from each time four queens in the same starter–finisher colony. From each queen the head, thorax, ovaries, spermatheca, guts and eviscerated abdomen were dissected and screened for the presence of the DWV-A and DWV-B genotype using qRT-PCR. Queens descending from SOV-positive queens showed significant lower infection loads for DWV-A and DWV-B as well as a lower number of infected tissues for DWV-A. Surprisingly, differences were less expressed in the reproductive tissues, the ovaries and spermatheca. These results confirm that selection on the SOV trait is associated with increased virus resistance across viral genotypes and that this selection drives DWV towards an increased tissue specificity for the reproductive tissues. Further research is needed to explore the mechanisms underlying the interaction between the antiviral response and DWV.     

Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization

Human factor VIII(FVIII) inhibitors are pathologic, circulating antibodies that inactivate FVIII. We have examined the location of epitopes on the FVIII protein for inhibitors from hemophilia A and nonhemophilic individuals. The inhibitors were of type I or type II in the kinetics of their inactivation of FVIII. A cDNA clone of human FVIII was used to express defined FVIII protein fragments in Escherichia coli for immunoblotting with inhibitor plasma. An epitope for 18 heavy-chain inhibitors was localized to the aminoterminal 18.3 Kd of the A2 domain. Two of these inhibitors also recognized an epitope located between A1 and A2 domains. Similarly, an epitope for 23 light- chain inhibitors was localized to the C2 domain. Weaker epitopes for 13 of the same inhibitors within the C1 and C2 domains were also observed. Four of the 23 inhibitors in addition bound strongly to the A3 domain. Most inhibitors (22 of 23) were neutralized in vitro only by the FVIII fragments to which they bound on immunoblots; however, one inhibitor that was neutralized by a fragment containing the A1 domain did not bind to it on immunoblots. Conversely, 3 of 3 inhibitors that bound to the A3 domain and 5 of 15 that bound to the A2 domain were not neutralized by the corresponding fragments. The epitope specificity of an inhibitor did not depend on its source or type. Our results show that FVIII inhibitors bind to limited areas within the heavy and light chains of FVIII. Some inhibitor plasmas contain additional antibodies that may not be inhibitory.     

Effect of metabolic syndrome or type II diabetes mellitus on the occurrence of recurrent vascular events in hypertensive patients

Patients with hypertension and manifest vascular disease are at high risk for recurrent cardiovascular diseases. It is unknown if the metabolic syndrome further increases the risk in these patients. This study aims to quantify the effect of metabolic syndrome and type II diabetes on cardiovascular events in hypertensive patients with vascular disease. A total of 2,196 hypertensive patients with vascular disease (cerebrovascular disease (34%), coronary heart disease (50%), peripheral arterial disease (28%), abdominal aortic aneurysm (13%)) from the Second Manifestations of Arterial Disease study were followed for up to 10 years (mean 3.9 years) for death, stroke and myocardial infarction. Age and sex adjusted hazard ratios (HR) were calculated for hypertensive patients with metabolic syndrome but without diabetes (n=775) and for hypertensive patients with type II diabetes (n=381), compared to merely hypertensive patients (n=1,040). Forty-nine percent had metabolic syndrome (NCEP ATPIII definition) and 17% had type II diabetes. Metabolic syndrome predicted vascular death (HR 1.41, 95% confidence interval (CI) 1.01-1.98), stroke (HR 1.36, 95% CI 0.85-2.16) and myocardial infarction (HR 1.40, 95% CI 0.97-2.01). Type II diabetes accounted for even higher risks of vascular end points (HR 1.41-1.64). The effect of metabolic syndrome on future events could not be explained by the presence of type II diabetes. Even in high-risk patients with hypertension and vascular disease, presence of metabolic syndrome or type II diabetes identifies patients at high risk for future cardiovascular events. Identifying metabolic syndrome patients may direct therapy focusing on treatment of insulin resistance by reducing weight and increasing physical activity.     

High blood pressure is inversely related with the presence and extent of coronary collaterals

Patients with hypertension have an increased case fatality during acute myocardial infarction (MI). Coronary collateral (CC) circulation has been proposed to reduce the risk of death during acute ischaemia. We determined whether and to which degree high blood pressure (BP) affects the presence and extent of CC circulation. A cross-sectional study in 237 patients (84% males), admitted for elective coronary angioplasty between January 1998 and July 2002, was conducted. Collaterals were graded with Rentrop's classification (grade 0-3). CC presence was defined as Rentrop-grade > or =1. BP was measured twice with an inflatable cuff manometer in seated position. Pulse pressure was calculated by systolic blood pressure (SBP)-diastolic blood pressure (DBP). Mean arterial pressure was calculated by DBP+1/3 x (SBP-DBP). Systolic hypertension was defined by a reading > or =140 mmHg. We used logistic regression with adjustment for putative confounders. SBP (odds ratio (OR) 0.86 per 10 mmHg; 95% confidence interval (CI) 0.73-1.00), DBP (OR 0.67 per 10 mmHg; 95% CI 0.49-0.93), mean arterial pressure (OR 0.73 per 10 mmHg; 95% CI 0.56-0.94), systolic hypertension (OR 0.49; 95% CI 0.26-0.94), and antihypertensive treatment (OR 0.53; 95% CI 0.27-1.02), each were inversely associated with the presence of CCs. Also, among patients with CCs, there was a graded, significant inverse relation between levels of SBP, levels of pulse pressure, and collateral extent. There is an inverse relationship between BP and the presence and extent of CC circulation in patients with ischaemic heart disease.     

Psychological distress among recipients of Björk-Shiley convexo-concave valves: the impact of information

Objective—To establish whether there is more psychological distress among recipients of Björk-Shiley convexo-concave (BScc) valves than among recipients of other valves not known to fracture.
Design—Cross sectional study.
Patients—137 patients who received either a BScc valve or a Sorin Biomedical spherical valve during a randomised trial between 1982 and 1983 at St Antonius Hospital, Nieuwegein. Systematic notification of the risk of strut fracture in recipients of BScc valves was carried out at St Antonius Hospital in 1991.
Mean outcome measures—Psychological distress as assessed with the General Severity Index from the Symptom Checklist 90. 
Results—Psychological distress between recipients of BScc and Sorin valves did not differ irrespective of whether the recipients knew their valve type. More recipients of BScc valves, however, knew their valve type and of problems associated with artificial heart valves.
Conclusions—Information about an increased risk of strut fracture does not induce psychological distress among well informed recipients of BScc valves. All recipients of heart valves should be systematically informed about their valve type—for example, by issuing data cards with valve serial numbers and other relevant information.

Keywords: psychological distress;  artificial heart valves;  Björk-Shiley valves     

Impaired sensory functioning in elders: the relation with its potential determinants and nutritional intake.

This study assessed the relation of an impaired taste and smell perception with (a) potential determinants and (b) nutritional intake and status in elderly people. Determinants examined were age, gender, functional category (institutionalized vs independently living), dental state, illnesses, smoking behavior, drug usage, and saliva excretion and composition. Nutritional intake and status were measured by an "appetite and hunger" questionnaire, a food frequency questionnaire, and body mass index (BMI). In order to have access to a large heterogeneous group, two different categories of elderly people were studied. We enrolled independently living elders (n=89) assumed to have a relatively good taste and smell perception, and institutionalized elders (n=67) with a potential poorer taste and smell perception. Scores at the smell identification (range: 0-10) and taste perception (range: 0-4) test were, respectively, 5.7 (independently living) versus 3.5 (institutionalized); p < .0001 and 3.3 versus 3.0; p < .05. Correlation between smell test scores and outcomes of the "appetite and hunger" questionnaire ranged from r: .19 to .50; p values < .05. There was, however, no clear correlation of any sensory outcome with energy and food intake, nor with BMI. Regression analyses revealed that age and the functional category were the most important determinants of the scores on the taste perception and smell identification tests. It is concluded that a poor performance on sensory tests is related to a poor appetite but not necessarily to low energy intake or low BMI. Age-related factors and smoking are important determinants of impaired sensory functioning.     

Comparison of the Framingham Risk Score,SCORE and WHO/ISH cardiovascular risk prediction models in an Asian population

Background

Cardiovascular risk-prediction models are used in clinical practice to identify and treat high-risk populations, and to communicate risk effectively. We assessed the validity and utility of four cardiovascular risk-prediction models in an Asian population of a middle-income country.

Methods

Data from a national population-based survey of 14,863 participants aged 40 to 65 years, with a follow-up duration of 73,277 person-years was used. The Framingham Risk Score (FRS), SCORE (Systematic COronary Risk Evaluation)-high and -low cardiovascular-risk regions and the World Health Organization/International Society of Hypertension (WHO/ISH) models were assessed. The outcome of interest was 5-year cardiovascular mortality. Discrimination was assessed for all models and calibration for the SCORE models.

Results

Cardiovascular risk factors were highly prevalent; smoking 20%, obesity 32%, hypertension 55%, diabetes mellitus 18% and hypercholesterolemia 34%. The FRS and SCORE models showed good agreement in risk stratification. The FRS, SCORE-high and -low models showed good discrimination for cardiovascular mortality, areas under the ROC curve (AUC) were 0.768, 0.774 and 0.775 respectively. The WHO/ISH model showed poor discrimination, AUC = 0.613. Calibration of the SCORE-high model was graphically and statistically acceptable for men (χ² goodness-of-fit, p = 0.097). The SCORE-low model was statistically acceptable for men (χ² goodness-of-fit, p = 0.067). Both SCORE-models underestimated risk in women (p < 0.001).

Conclusions

The FRS and SCORE-high models, but not the WHO/ISH model can be used to identify high cardiovascular risk in the Malaysian population. The SCORE-high model predicts risk accurately in men but underestimated it in women.