Defective collagen binding and increased bleeding in a murine model of von Willebrand disease affecting collagen IV binding.

Essentials Defective binding to collagen IV has been seen in von Willebrand factor (VWF) A1 domain variants. We developed a murine model of defective VWF-collagen IV interactions with VWF variant p.R1399H. p.1399HH homozygous mice had decreased binding to collagen IV and increased bleeding times. p.1399HH homozygous mice had increased time to thrombosis and decreased platelet adhesion. SUMMARY: Background von Willebrand factor (VWF) binding to type IV collagen occurs via the VWF A1 domain, with p.R1399H being the most common VWF variant affecting this interaction. Objectives We generated a murine model of 1399H VWF to investigate its in vivo effects. Methods Mice expressing the murine 1399H variant were generated via gene targeting in embryonic stem cells. VWF antigen and VWF collagen binding were measured with ELISA. Tail bleeding time assays were performed by clipping a 3-mm segment. Ferric chloride-induced thrombosis was measured via ultrasound in the carotid artery. Platelet aggregation in response to collagens I and IV was measured. VWF-dependent platelet adhesion to collagen IV was measured under flow. Results Breeding of heterozygous p.R1399H and homozygous p.1399HH mice was observed to follow normal Mendelian ratios. No spontaneous bleeding was observed for any of the offspring. VWF expression was normal, but VWF binding to collagen IV was decreased in both heterozygous and homozygous offspring. Blood loss following tail resection was increased for p.1399HH mice, and occlusion times following ferric chloride-induced thrombosis were prolonged. Platelet aggregation was unaffected, but platelet adhesion to collagen IV under flow was diminished for p.1399HH mice. Conclusions These results show that a decrease in the ability of 1399H VWF to bind collagen IV under static conditions corresponds to a decrease in binding under flow conditions, an increased bleeding time, and a prolonged time to thrombosis. This study supports the potential for a bleeding phenotype in patients with aberrant VWF-collagen IV binding.

General nutrition knowledge among carers at group homes for people with intellectual disability.

BACKGROUND: Good nutrition knowledge among carers of people with intellectual disability (ID) living in group homes is essential as they have a primary role in food provision for residents. Research on the nutrition knowledge of carers is limited. METHOD: This cross-sectional study assessed the level of general nutrition knowledge in a convenience sample of Australian carers (C) of people with ID and compared this to the general Australian community (CM). Nutrition knowledge was evaluated using the validated General Nutrition Knowledge Questionnaire. Total knowledge score as well as performance on instrument sub-sections (dietary guidelines, nutrient sources, healthy food choices and diet disease relationships) were assessed (expressed as %). Knowledge scores were adjusted for known confounders (age, sex, education level, BMI, living arrangement and English spoken at home) using generalised linear modelling. RESULTS: A total of 589 participants were recruited (C: n = 40; CM: n = 549). Age (C: 40.8 ± 12.1 year; CM: 37.8 ± 13.3 years; P = 0.145), sex distribution (C: 62.5%; CM: 67.2% female; P = 0.602) and English spoken at home (C: 82.5%; CM: 89.6%; P = 0.183) were similar between groups, but BMI (C: 28.5 ± 5.7 kgm-2 ; CM: 25.3 kgm-2 ; P = 0.002) was significantly lower and tertiary education (C: 52.5%; CM: 85.1%; P < 0.0005) significantly higher for CM. Total knowledge score (C: 56.6 ± 12.6%; CM: 67.2 ± 12.6%; P < 0.0005) and performance on all instrument sub-sections (P ≤ 0.004) were significantly lower for carers. This remained after confounder adjustment except for the knowledge of dietary guidelines sub-section (P = 0.116). CONCLUSION: Limited carer nutrition knowledge may compromise their ability to plan and adapt meals to support a healthy and appropriate diet for people with ID in group homes.

Evaluation of a peer education program on student leaders' energy balance-related behaviors.

BACKGROUND: Few studies have reported energy balance-related behavior (EBRB) change for peer leaders delivering health promotion programs to younger students in secondary schools. Our study assessed the impact of the Students As LifeStyle Activists (SALSA) program on SALSA peer leaders' EBRBs, and their intentions regarding these behaviors. METHODS: We used a pre-post study design to assess changes in EBRBs and intentions of Year 10 secondary school students (15-16 year olds) who volunteered to be peer leaders to deliver the SALSA program to Year 8 students (13-14 year olds). This research is part of a larger study conducted during 2014 and 2015 in 23 secondary schools in Sydney, Australia. We used an online questionnaire before and after program participation to assess Year 10 peer leaders' fruit and vegetable intake, daily breakfast eating, sugar sweetened beverage (SSB) intake, moderate-to-vigorous physical activity (MVPA) participation and school-day recreational screen time behaviors and intentions regarding these EBRBs. Generalized estimating equations with a robust variance structure and exchangeable correlation structure were used to estimate the individual-level summary statistics and their 95% CIs, adjusted for clustering. We further assessed the effect of covariates on EBRB changes. RESULTS: There were significant increases in the proportion of Year 10 peer leaders (n = 415) who reported eating ≥2 serves fruit/day fruit from 54 to 63% (P < 0.01); eating ≥5 serves vegetables/day from 8 to 12% (P < 0.01); and drinking <1 cup/day of SSBs from 56 to 62% (P < 0.01). Change in ≥60 min MVPA participation/day depended on gender (P < 0.01): Boys increased 14% while girls decreased -2%. Changes in eating breakfast daily also depended on gender (P < 0.004): Boys increased 13% while girls decreased -0.4%. The change in peer leaders recreational screen time differed by socio-economic status (P < 0.05): above average communities decreased by -2.9% while below average communities increased 6.0%. Significant shifts were seen in peer leaders' intentions, except MVPA which remained stable. CONCLUSIONS: The SALSA program had a positive impact on peer leaders' EBRBs, with gender and socio-economic status moderating some outcomes. TRIAL REGISTRATION: ACTRN12617000712303 retrospectively registered.

Clinical and laboratory phenotype variability in type 2M von Willebrand disease.

Essentials The pathophysiology of type 2M von Willebrand disease (VWD) is poorly understood. Sequence variations in type 2M VWD subjects were characterized. A high degree of clinical and laboratory variability exists within type 2M VWD variants. Some type 2M variants may share features of type 2A VWD. SUMMARY: Background von Willebrand factor (VWF) is a multimeric coagulation factor that tethers platelets to injured subendothelium. Type 2M von Willebrand disease (VWD) is characterized by a qualitative defect in VWF with preserved multimer distribution. Objectives Through the Zimmerman Program for the Molecular and Clinical Biology for VWD, five VWF sequence variations were studied in subjects diagnosed with type 2M VWD. Methods Bleeding phenotype was assessed using the ISTH bleeding assessment tool. Full-length VWF gene sequencing was performed for each subject. Each variant was placed into a recombinant VWF vector using site-directed mutagenesis and expressed in HEK293T cells as homozygous or heterozygous VWF. Variant expression, collagen binding and platelet GPIbα binding were studied through ELISA assays. Multimer analysis was performed by gel electrophoresis. Results Bleeding scores were elevated for all subjects except for the p.P1162L and p.R1374C variants. Although all had reduced VWF ristocetin cofactor activity/VWF antigen ratios on plasma testing, recombinant VWF did not show a classic type 2M phenotype for any of the five variants. Homozygous expression of variants p.D1283Y, p.R1349C, p.R1374C and p.I1453N was consistent with type 2A VWD, although all had normal expression as heterozygous recombinant VWF. Variant p.P1162L had normal VWF expression and function, consistent with the lack of bleeding symptoms. Conclusions Although originally classified as type 2M VWD, these homozygous recombinant VWF variants do not fulfill complete 2M VWD diagnostic criteria. A better classification schema and improved testing for putative type 2M variants is needed in order to effectively diagnose and treat affected patients.

Validity of short food questionnaire items to measure intake in children and adolescents: a systematic review.

BACKGROUND: Short food questions are appealing to measure dietary intakes. METHODS: A review of studies published between 2004 and 2016 was undertaken and these were included in the present study if they reported on a question or short item questionnaire (≤50 items, data presented as ≤30 food groups) measuring food intake or food-related habits, in children (aged 6 months to 18 years), and reported question validity or reliability. Thirty studies met the inclusion criteria. RESULTS: Most questions assessed foods or food groups (n = 29), with the most commonly assessed being fruit (n = 22) or vegetable intake (n = 23), dairy foods and discretionary foods (n = 20 studies each). Four studies assessed food habits, with the most common being breakfast and meal frequency (n = 4 studies). Twenty studies assessed reliability, and 25 studies determined accuracy and were most commonly compared against food records. Evaluation of question performance relied on statistical tests such as correlation. CONCLUSIONS: The present study has identified valid and reliable questions for the range of key food groups of interest to public health nutrition. Questions were more likely to be reliable than accurate, and relatively few questions were both reliable and accurate. Gaps in repeatable and valid short food questions have been identified that will provide direction for future tool development.

Trends in added sugar intake and food sources in a cohort of older Australians: 15 years of follow-up from the Blue Mountains Eye Study.

BACKGROUND: The trend of added sugar (AS) intake has not been investigated in the Australian population, including in older adults. The present study aimed to assess trends and food sources of AS intake among a cohort of older Australians during 15 years of follow-up. METHODS: Dietary data from participants of the Blue Mountains Eye Study (1264 men and 1614 women), aged ≥49 years at baseline, were collected. Dietary intakes were assessed at 5-yearly intervals (1992-94 to 2007-09) using a 145-item food frequency questionnaire (FFQ). AS content of FFQ food items was estimated using a stepwise systematic method. Trends for AS intake between baseline and the three follow-up periods were assessed using linear mixed modelling. RESULTS: In men, the mean (SEM) percentage of energy provided by AS intake (EAS%) declined from 10.4% (0.1%) at baseline to 9.4% (0.2%) at 15-year follow-up (Ptrend = 0.028). Women's mean (SEM) EAS% intake at baseline and 15-year follow-up was 9.2% (0.1%) and 8.8% (0.2%), respectively (Ptrend = 0.550). EAS% intake of men was significantly higher than that of women for 10 years (P < 0.05). Sugar products (table sugar, syrup, jam and honey) were the major sources of AS at all-time points and contributed to more than 40% and 35% of AS intake in men and women, respectively. Intake of sugar products decreased in men during follow-up (Ptrend < 0.001). CONCLUSIONS: An overall downward trend was observed in AS intake in both genders, however, was only significant for men during 15 years of follow-up. Table sugar and sugar-containing spreads represent the major source of AS in this cohort of older Australians.

Consumption of nuts and risk of total and cause-specific mortality over 15 years.

BACKGROUND AND AIMS: The published literature shows that nut consumption has a favorable impact on health. We aimed to assess the association between nut consumption and risk of 15-year total mortality, and mortality from cardiovascular disease (CVD) (including ischemic heart disease, IHD, and stroke), and cancer. METHODS AND RESULTS: Prospective analyses involved 2893 participants aged ≥49 years at baseline. Dietary data were collected by using a semi-quantitative food-frequency questionnaire, and nut intakes were calculated. Deaths and cause of death were confirmed by data linkage with the Australian National Death Index. Over 15 years, 1044 participants had died, of these 430 had died from stroke and another 430 had died from IHD. Participants in the second tertile of nut consumption versus those in the first tertile of intake had reduced risk of total mortality: multivariable-adjusted HR 0.76 (95% CI 0.65-0.89). Participants in the second tertile compared to those in the first tertile had 24% and 23% reduced risk of 15-year CVD and IHD mortality, respectively. Associations were more marked in women compared to men. Women in the second versus first tertile of nut consumption had 27%, 39%, 34% and 49% reduced risk of death from all causes (n = 489), CVD (n = 258), IHD (n = 188) and stroke mortality (n = 101), respectively. CONCLUSIONS: Nut consumption was independently associated with a decreased risk of overall and vascular-disease mortality, particularly in women.

The Nutritional Profile of Baby and Toddler Food Products Sold in Australian Supermarkets.

BACKGROUND/AIMS: To examine the nutritional profile of baby and toddler foods sold in Australia. METHODS: Nutrient information for baby and toddler foods available at Australian supermarkets was collected between Auguset and December 2013. Levels of declared energy, total fat, saturated fat, total sugar, sodium and estimated added sugar were examined, as well as the presence of additional micronutrients on the label. The Health Star Rating (HSR) system was used to determine nutritional quality. The range of products on offer was also examined by product type and by the age category for which the product was marketed. RESULTS: Of the 309 products included, 29% were fortified. On a per 100 g basis, these 309 products provided a mean (±SD) of 476 ± 486 kJ, 1.6 ± 2.4 g total fat, 10.7 ± 12.2 g total sugar, 2.7 ± 7.4 g added sugar, and 33.5 ± 66.5 mg sodium. Fruit-based products or products with fruit listed as an ingredient (58%) were the predominant product type. On the nutrition label, 42% displayed at least one additional micronutrient while 37% did not display saturated fat. The most common HSR was four stars (45%) and 6+ months was the most commonly identified targeted age group (36%). CONCLUSIONS: The majority of baby and toddler foods sold in Australian supermarkets are ready-made fruit-based products aimed at children under 12 months of age. Baby and toddler foods are overlooked in public policy discussions pertaining to population nutrient intake but their relatively high sugar content deriving from fruits requires close attention to ensure these foods do not replace other more nutrient dense foods, given children have an innate preference for sweet tastes.

Laboratory diagnosis of von Willebrand disease.

Von Willebrand disease (VWD) is considered the most common inherited bleeding disorder and may also be the most difficult to diagnose. Clinical symptoms of VWD include predominantly mild mucosal bleeding; surgical bleeding may occur with specific challenges and joint bleeding can occur in the most severe forms. A family history either of diagnosed VWD or of bleeding symptoms is typically present. Laboratory diagnosis requires a series of assays of von Willebrand factor (VWF) quantity and function, and factor VIII activity, with no single straightforward diagnostic test available to either confirm or exclude the diagnosis. Newer assays of VWF function are becoming more available and useful in determining the laboratory diagnosis of VWD.

A systematic methodology to estimate added sugar content of foods.

BACKGROUND/OBJECTIVES: The effect of added sugar on health is a topical area of research. However, there is currently no analytical or other method to easily distinguish between added sugars and naturally occurring sugars in foods. This study aimed to develop a systematic methodology to estimate added sugar values on the basis of analytical data and ingredients of foods. SUBJECTS/METHODS: A 10-step, stepwise protocol was developed, starting with objective measures (six steps) and followed by more subjective estimation (four steps) if insufficient objective data are available. The method developed was applied to an Australian food composition database (AUSNUT2007) as an example. RESULTS: Out of the 3874 foods available in AUSNUT2007, 2977 foods (77%) were assigned an estimated value on the basis of objective measures (steps 1-6), and 897 (23%) were assigned a subjectively estimated value (steps 7-10). Repeatability analysis showed good repeatability for estimated values in this method. CONCLUSIONS: We propose that this method can be considered as a standardised approach for the estimation of added sugar content of foods to improve cross-study comparison.

Dairy food consumption, blood pressure and retinal microcirculation in adolescents.

BACKGROUND AND AIMS: The relationship between dairy food consumption and dietary calcium intake, and vascular risk factors during adolescence remains unclear. We aimed to prospectively assess whether dairy food consumption (milk, cheese, yoghurt) is associated with blood pressure (BP) and retinal microvascular signs among adolescents. METHODS AND RESULTS: As many as 2353 and 1216 participants aged 12 and 17, respectively, were examined. Longitudinal analyses involved 888 subjects with complete baseline and follow-up data. Dairy consumption was assessed from validated semi-quantitative food frequency questionnaires. BP information was collected and retinal vessel caliber was quantified from digital photographs using computer software. In girls, after multivariable adjustment, each serve/day increase in total dairy intake was concurrently associated with 1.04 (p = 0.03) and 1.10 mm Hg (p = 0.02) decreases in mean diastolic and arterial BP, respectively. Also in girls, each serve/day increase in cheese intake over 5 years was concurrently related to 7.18 (p = 0.001), 5.28 (p = 0.002) and 5.79 mm Hg (p = 0.001) decrease in mean systolic, diastolic and arterial BP, respectively. Among girls, each 100 mg/day increase in dietary calcium intake was associated with a concurrent 0.5 (p = 0.01) and 0.3 mm Hg (p = 0.02) decrease in mean systolic and arterial BP, respectively. Cross-sectionally, adolescents in the highest versus lowest tertile of yoghurt intake had ∼ 1.3 µm wider retinal arterioles (p = 0.05) and ∼ 2.0 µm narrower venules (p = 0.04). CONCLUSIONS: Consumption of dairy products, particularly cheese, could have a beneficial effect on BP, particularly among girls.

Association between diet quality with concurrent vision and hearing impairment in older adults.

OBJECTIVES: Published literature shows that individual nutrients could influence the risk of developing vision and hearing loss. There is, however, a lack of population-based data on the relationship between overall patterns of food intake and the presence of concurrent vision and hearing impairment. We aimed to assess the associations between diet quality with the prevalence and 5-year incidence of dual sensory impairment (DSI). DESIGN: Cross-sectional and 5-year longitudinal analyses. SETTING: Blue Mountains, Sydney, Australia. PARTICIPANTS: 2443 participants aged ≥50 from baseline were examined and followed over 5 years. MEASUREMENTS: Dietary data were collected using a semi-quantitative food frequency questionnaire. A modified version of the Healthy Eating Index for Australians was developed to determine total diet score (TDS). Visual impairment was defined as visual acuity less than 20/40 (better eye), and hearing impairment as average pure-tone air conduction threshold greater than 25 dB HL (500-4000 Hz, better ear). RESULTS: After adjusting for age, sex, education, noise exposure, current smoking, and type 2 diabetes, participants in the lowest compared to the highest quintile of TDS had a 2-fold increased likelihood of having prevalent DSI, odds ratio, OR, 2.62 (95% confidence intervals, CI, 1.08-6.36), P-trend=0.04. Significant associations were not observed between TDS and the prevalence of having a single sensory impairment (vision or hearing loss). Baseline TDS was not significantly associated with the 5-year incidence of DSI. Adherence to dietary guidelines was associated with a reduced likelihood of having DSI in cross-sectional, but not in longitudinal analyses. CONCLUSIONS: Further studies with adequate power are warranted to assess the prospective relationship between diet quality and DSI.

Parental history of hypertension and dietary intakes in early adolescent offspring: a population-based study.

We investigated the cross-sectional association between parental history of hypertension and dietary intakes among early adolescent schoolchildren. A total of 1845 participants aged 12 years had complete data on diet and parental medical history, and thus they were included in the final analyses. Dietary data were assessed from validated semi-quantitative food-frequency questionnaires. Parents completed questionnaires about their medical conditions. Cases where the biological mother and/or father had hypertension were classified as positive parental history of hypertension. After multivariable adjustment, participants with positive versus negative parental history of hypertension had 33% greater likelihood of consuming soft drinks ⩾1 per week. Boys with a parental history versus boys without a parental history of hypertension consumed more energy-dense, nutrient-poor foods: 379.4 g per day and 318.0 g per day, respectively, P=0.02. Girls with a positive versus a negative parental history consumed more vegetables: 164.1 versus 142.6 g per day, P=0.01. Significant associations were not observed between those with and those without a positive parental history in mean dietary intakes of carbohydrates, fats, sugars and sodium. Children with a positive parental history of hypertension were 67% more likely to simultaneously engage in three unhealthy lifestyle behaviors (excessive recreational screen viewing, high consumption of snacks and and high consumption of soft drinks). Parental hypertension was associated with unhealthy dietary behaviors among offspring, including higher consumption of soft drinks and energy-dense, nutrient-poor foods.

Lower dairy products and calcium intake is associated with adverse retinal vascular changes in older adults.

BACKGROUND AND AIMS: Higher consumption of dairy products and calcium is likely to play a role in maintaining optimal vascular health. In this study, we aimed to explore the associations between consumption of total-, regular- and low-fat dairy foods, and total calcium intake with retinal vascular caliber. METHODS AND RESULTS: 2813 Blue Mountains Eye Study participants aged 50+ years had dietary data collected using a semi-quantitative food frequency questionnaire, and serves of dairy consumption were calculated. Fundus photographs were taken and retinal vascular caliber measured using computer-assisted techniques and summarized. After adjusting for age, sex, body mass index, smoking, mean arterial blood pressure, serum glucose, white cell count, history of diagnosed hypertension, stroke and coronary heart disease, plus retinal arteriolar caliber, participants in the lowest quintile of total dairy consumption compared to those in the remaining highest 4 quintiles had significantly wider retinal venular caliber, 227.2 versus 224.7 µm, respectively (multivariable-adjusted p = 0.002). Also, subjects in the lowest quintile of low-fat dairy product consumption versus those in the remaining quintiles of low-fat dairy intake had wider retinal venules (∼ 1.7 µm, p = 0.03) and narrower retinal arterioles (∼ 1.4 µm, p = 0.04). Participants in the lowest quintile versus highest quintile of total dietary calcium intake had ∼ 2.3 µm wider retinal venules (multivariable-adjusted p-trend = 0.02). CONCLUSIONS: A significant association was observed between lower intake of dairy products or calcium and adverse retinal vascular signs. We cannot discount the possibility of confounding from unmeasured risk factors; hence, further studies are warranted to confirm these findings.

Prevalence and risk factors of food insecurity among a cohort of older Australians.

OBJECTIVE: With ongoing national concern about food security, the aim of the study was to estimate the prevalence of food insecurity and to identify associated characteristics in a cohort of older Australians. DESIGN, SETTING AND PARTICIPANTS: The Blue Mountains Eye Study is a cohort study of community living participants aged 49 + years. The 12-item food security survey was completed by 3068 participants in the cross sectional study which comprised 2335 survivors from baseline and the recruitment of an additional 1174 eligible residents. MAIN OUTCOME MEASURES: Prevalence of self reported food insecurity was calculated and multivariate logistic regression provided odds ratios with 95% confidence intervals to determine risk factors. RESULTS: Overall prevalence of food insecurity was 13%. Women (15.7%) compared with men (9.4%) and younger participants, aged <70 years (15.7%) than older participants, ≥70 years (8.4%), were significantly more likely to report being food insecure. Characteristics for reporting food insecurity included participants living in rented accommodation (OR 4.10, 95% CI: 2.83, 5.89) and those living on a pension only (OR 1.90, 95%CI: 1.30, 2.78). CONCLUSIONS: A relatively high level of food insecurity among this representative population of older Australians should be an issue of concern for policy makers and health and welfare service providers. Addressing food insecurity should be a priority of integrated national food and nutrition policies and this should in turn inform health and welfare service provision to this vulnerable population.

Avoidance of meat and poultry decreases intakes of omega-3 fatty acids, vitamin B12 , selenium and zinc in young women.

BACKGROUND: Inadequate nutrient intake and physical inactivity may have adverse health consequences. The present study aimed to describe young female students' dietary intake, food choices and physical activity (PA) patterns, and also to determine the influence of dietary avoidance of meat and poultry on nutrient intake. METHODS: A cross-sectional study of female university students was conducted. Questionnaires were used to measure dietary intakes, food habits and PA. Anthropometric measurements of participants included height, weight and calculated body mass index (BMI). RESULTS: There were 308 participants with a mean (SD) age of 22.9 (3.9) years and a BMI of 21.5 (2.8) kg m(-2) ; 78% were in the BMI range 18.5-24.9 kg m(-2) . Of those who responded to the PA questionnaire (n = 218), 53% reported activity ≥150 min per week, with walking being the largest contributor. Completed food frequency questionnaires were returned by 256 participants. National recommendations for servings of cereals, vegetables, meat, fish and energy-dense 'extra foods' were not met by the majority of participants. Avoidance of animal foods was reported in 23% of women, and resulted in lower intakes of omega-3 fatty acids, vitamin B12 , selenium and zinc (P < 0.05) compared to non-avoidance. Iron intake from animal sources decreased significantly (P < 0.05) with the increase in meat and poultry avoidance. CONCLUSIONS: Female students had a healthy weight and reported adequate physical activity. However, in comparison to meat and poultry consumers, the avoidance of these foods was associated with a lower intake of some micronutrients. A sustained low intake of micronutrients may lead to adverse health effects in the longer-term, such as compromised immune function and iron deficiency anaemia.

Variability in platelet- and collagen-binding defects in type 2M von Willebrand disease.

Type 2M von Willebrand disease (VWD) includes qualitative defects in von Willebrand factor (VWF) function, with normal multimer distribution but a defect in VWF activity with respect to platelet or collagen binding. We characterized novel VWF gene mutations found in type 2M VWD subjects enrolled in the Zimmerman Program for the Molecular and Clinical Biology of VWD. Subjects were enrolled based on a pre-existing diagnosis of type 2M VWD. Testing included full-length gene sequencing, VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), VWF collagen binding and multimer distribution. Recombinant VWF variants were synthesized using site-directed mutagenesis and expressed in HEK293T cells. Platelet binding was measured by flow cytometry with fixed platelets and ELISA with recombinant glycoprotein Ibα (GPIbα). Four novel VWF A1 domain mutations were found in individuals with type 2M VWD: S1358N, S1387I, S1394F and Q1402P. All subjects had a history of bleeding, VWF:RCo < 40 IU dL(-1) , VWF:RCo/VWF:Ag ratios <0.6 and normal multimer distribution. No defect in expression, secretion, or multimerization was found for any of the mutations. All showed decreased binding to intact platelets, and decreased or absent binding to a mutant GPIbα construct with spontaneous VWF binding. 1387I had decreased binding to all collagen types tested. 1402P had reduced binding exclusively to type VI collagen. Type 2M VWD is a heterogeneous category comprised of both collagen- and platelet-binding defects. Understanding the precise defect for each mutation may ultimately lead to better diagnosis and treatment.

Third Åland islands conference on von Willebrand disease, 26-28 September 2012: meeting report.

The first meeting of international specialists in the field of von Willebrand disease (VWD) was held in the Åland islands in 1998 where Erik von Willebrand had first observed a bleeding disorder in some members of a family from Föglö and a summary of the meeting was published in 1999. The second meeting was held in 2010 and a report of the meeting was published in 2012. Topics covered included progress in understanding of VWD over the last 50 years; multimers; classification of VWD; pharmacokinetics and laboratory assays; genetics; treating the paediatric patient; prophylaxis; geriatrics; gene therapy and treatment guidelines. This third meeting held over 3 days covered the structure and function of von Willebrand factor (VWF); type 1 VWD, the most common form of the disease; a lifespan of pharmacokinetics in VWD; detecting inhibitors in VWD patients; and special challenges in understanding and treating the female VWD patient.

Diet quality is prospectively associated with incident impaired fasting glucose in older adults.

AIMS: Dietary modifications may play an important role in the prevention of diabetes. We aimed to assess the temporal association between diet quality and both impaired fasting glucose and Type 2 diabetes among older adults. METHODS: A total of 2564 participants aged 49+ years at baseline were examined between 1992 and 1994 and 2002-2004 and had their fasting blood glucose measured. Dietary data were collected using a semi-quantitative food frequency questionnaire. A modified version of the Healthy Eating Index for Australians was developed to determine Total Diet Score. Incident diabetes (or impaired fasting glucose) was defined in participants at risk who were newly diagnosed by a physician during the follow-up or found to have a fasting blood glucose level ≥ 7.0 mmol/l (or 6.1-6.9 mmol/l). RESULTS: After adjusting for age, sex, current smoking, body mass index, hypertension and serum triglycerides, comparing highest with lowest tertile of total diet score, a significant 75% decrease in risk of incident impaired fasting glucose was observed in men (P(trend) = 0.02). Also, in men, each two-point increase in Total Diet Score was associated with a 52% reduction in the 10-year incidence of impaired fasting glucose, (OR 0.48, 95% CI 0.33-0.69). No significant associations were observed among women or with the 10-year incidence of diabetes. CONCLUSIONS: Greater compliance with published dietary guidelines (better diet quality) was associated with a reduced risk of pre-diabetes in men, but not women.