The effect of local hospital waiting times on GP referrals for suspected cancer.

INTRODUCTION: Reducing waiting times is a major policy objective in publicly-funded healthcare systems. However, reductions in waiting times can produce a demand response, which may offset increases in capacity. Early detection and diagnosis of cancer is a policy focus in many OECD countries, but prolonged waiting periods for specialist confirmation of diagnosis could impede this goal. We examine whether urgent GP referrals for suspected cancer patients are responsive to local hospital waiting times. METHOD: We used annual counts of referrals from all 6,667 general practices to all 185 hospital Trusts in England between April 2012 and March 2018. Using a practice-level measure of local hospital waiting times based on breaches of the two-week maximum waiting time target, we examined the relationship between waiting times and urgent GP referrals for suspected cancer. To identify whether the relationship is driven by differences between practices or changes over time, we estimated three regression models: pooled linear regression, a between-practice estimator, and a within-practice estimator. RESULTS: Ten percent higher rates of patients breaching the two-week wait target in local hospitals were associated with higher volumes of referrals in the pooled linear model (4.4%; CI 2.4% to 6.4%) and the between-practice estimator (12.0%; CI 5.5% to 18.5%). The relationship was not statistically significant using the within-practice estimator (1.0%; CI -0.4% to 2.5%). CONCLUSION: The positive association between local hospital waiting times and GP demand for specialist diagnosis was caused by practices with higher levels of referrals facing longer local waiting times. Temporal changes in waiting times faced by individual practices were not related to changes in their referral volumes. GP referrals for diagnostic cancer services were not found to respond to waiting times in the short-term. In this setting, it may therefore be possible to reduce waiting times by increasing supply without consequently increasing demand.

How do hospitals respond to payment unbundling for diagnostic imaging of suspected cancer patients?

Payments for some diagnostic scans undertaken in outpatient settings were unbundled from Diagnosis Related Group based payments in England in April 2013 to address under-provision. Unbundled scans attracted additional payments of between £45 and £748 directly following the reform. We examined the effect on utilization of these scans for patients with suspected cancer. We also explored whether any detected effects represented real increases in use of scans or better coding of activity. We applied difference-in-differences regression to patient-level data from Hospital Episodes Statistics for 180 NHS hospital Trusts in England, between April 2010 and March 2018. We also explored heterogeneity in recorded use of scans before and after the unbundling at hospital Trust-level. Use of scans increased by 0.137 scans per patient following unbundling, a 134% relative increase. This increased annual national provider payments by £79.2 million. Over 15% of scans recorded after the unbundling were at providers that previously recorded no scans, suggesting some of the observed increase in activity reflected previous under-coding. Hospitals recorded substantial increases in diagnostic imaging for suspected cancer in response to payment unbundling. Results suggest that the reform also encouraged improvements in recording, so the real increase in testing is likely lower than detected.

Left ventricular assist devices for treatment of refractory advanced heart failure: the Western Australian experience.

BACKGROUND: Left ventricular (LV) assist devices (LVADs) can prolong survival and improve quality of life in end-stage heart failure. AIMS: Review outcomes of the Western Australian LVAD programme. METHODS: Retrospective database and medical record review. RESULTS: One hundred forty-seven LVADs have been implanted in 23 years, of which 95 were newer-generation devices (HeartWare HVAD [HW], HeartMate II and HeartMate 3). Presented data refer to these devices only. Most patients (94%) were classed as bridge-to-transplant or -candidacy/decision, with the remainder classed as 'destination therapy' (DT). Mean LV ejection fraction was 20%, and 36% had severe right ventricular dysfunction. Sixty-two percent of patients had a nonischaemic cardiomyopathy. Following LVAD implant, the median length of stay in intensive care was 2 days, and in the hospital overall was 23 days. Ninety-six percent of patients survived to hospital discharge, and, following discharge, 98% of days with LVAD were spent as an outpatient. The median number of hospital readmissions was 1.5 per patient per year. LVAD-associated infection requiring admission or intravenous antibiotics at any time after implant occurred in 36%, significant gastrointestinal bleeding in 19% and stroke in 11%. The percentage of patients alive with LVAD still in situ at 1, 2 and 5 years was 94%, 88% and 62% respectively, which exceeds current international registry outcomes. All DT patients survived at least 4 years, spending 97% of days with LVAD as an outpatient. The two longest-surviving HW DT patients worldwide (11.3 and 10.5 years) are among this cohort. CONCLUSIONS: Excellent outcomes can be achieved with LVADs in appropriately selected patients.

Pharmacokinetics and Safety Evaluation of Single-Dose Saroglitazar Magnesium in Subjects with Hepatic Impairment.

Saroglitazar magnesium, a dual peroxisome proliferator-activated receptor agonist, is under evaluation for treating various liver conditions. While the pharmacokinetics (PK) of saroglitazar have been extensively studied in diverse preclinical models and healthy subjects, a comprehensive assessment of its PK behavior under conditions of hepatic impairment is lacking. In this Phase 1, open-label, parallel-group study, the PK of a single dose of 4-mg saroglitazar magnesium was investigated in subjects having varying degrees of hepatic impairment with and without portal hypertension compared with appropriately matched individuals having normal hepatic function. Treatment-emergent adverse events for safety were also evaluated. Thirty-two subjects were enrolled in the hepatic-impaired groups and 23 subjects in the normal hepatic function group. Mild and moderate hepatic impairment did not significantly affect the PK of saroglitazar, compared with normal hepatic function. Although severe hepatic impairment did not alter maximum observed plasma concentration and half-life; saroglitazar exposure (area under the plasma concentration-time curve from time 0 to infinity) increased 3-fold, while the clearance was 61% lower compared to the subjects with normal hepatic function. This may require close monitoring or dose adjustments in individuals with severe hepatic impairment. A single oral dose of saroglitazar magnesium 4 mg was found to be safe and well tolerated in subjects with varying degrees of hepatic function.

How do family doctors respond to reduced waiting times for cancer diagnosis in secondary care?

Reducing waiting times is a priority in public health systems. Efforts of healthcare providers to shorten waiting times could be negated if they simultaneously induce substantial increases in demand. However, separating out the effects of changes in supply and demand on waiting times requires an exogenous change in one element. We examine the impact of a pilot programme in some English hospitals to shorten waiting times for urgent diagnosis of suspected cancer on family doctors' referrals. We examine referrals from 6,666 family doctor partnerships to 145 hospitals between 1st April 2012 and 31st March 2019. Five hospitals piloted shorter waiting times initiatives in 2017. Using continuous difference-in-differences regression, we exploit the pilot as a 'supply shifter' to estimate the effect of waiting times on referral volumes for two suspected cancer types: bowel and lung. The proportion of referred patients breaching two-week waiting times targets for suspected bowel cancer fell by 3.9 percentage points in pilot hospitals in response to the policy, from a baseline of 4.8%. Family doctors exposed to the pilot increased their referrals (demand) by 10.8%. However, the pilot was not successful for lung cancer, with some evidence that waiting times increased, and a corresponding reduction in referrals of -10.5%. Family doctor referrals for suspected cancer are responsive at the margin to waiting times. Healthcare providers may struggle to achieve long-term reductions in waiting times if supply-side improvements are offset by increases in demand.

Habitual consumption of high-fibre bread fortified with bean hulls increased plasma indole-3-propionic concentration and decreased putrescine and deoxycholic acid faecal concentrations in healthy volunteers.

Only 6 to 8 % of the UK adults meet the daily recommendation for dietary fibre. Fava bean processing lead to vast amounts of high-fibre by-products such as hulls. Bean hull fortified bread was formulated to increase and diversify dietary fibre while reducing waste. This study assessed the bean hull: suitability as a source of dietary fibre; the systemic and microbial metabolism of its components and postprandial events following bean hull bread rolls. Nine healthy participants (53·9 ± 16·7 years) were recruited for a randomised controlled crossover study attending two 3 days intervention sessions, involving the consumption of two bread rolls per day (control or bean hull rolls). Blood and faecal samples were collected before and after each session and analysed for systemic and microbial metabolites of bread roll components using targeted LC-MS/MS and GC analysis. Satiety, gut hormones, glucose, insulin and gastric emptying biomarkers were also measured. Two bean hull rolls provided over 85 % of the daily recommendation for dietary fibre; but despite being a rich source of plant metabolites (P = 0·04 v. control bread), these had poor systemic bioavailability. Consumption of bean hull rolls for 3 days significantly increased plasma concentration of indole-3-propionic acid (P = 0·009) and decreased faecal concentration of putrescine (P = 0·035) and deoxycholic acid (P = 0·046). However, it had no effect on postprandial plasma gut hormones, bacterial composition and faecal short chain fatty acids amount. Therefore, bean hulls require further processing to improve their bioactives systemic availability and fibre fermentation.

A comparison of the nutritional content and price between dairy and non-dairy milks and cheeses in UK supermarkets: A cross sectional analysis.

Background: Non-Dairy (ND) food consumption is rapidly increasing in the UK and for many consumers plant-based diets are presumed to be healthier than standard diets. ND alternatives have different nutritional compositions, and their consumption could present challenges on a public-health level. Aim: To compare the price and nutritional composition of dairy and ND milks and cheeses in UK supermarkets. Methods: Macro and micronutrient data was recorded from Alpro's website and the 6 leading UK grocers for their own-label ND milks and cheeses. For missing micronutrient values the McCance & Widdowson's dataset was used. 99 total products were extracted: 57 ND milks, 7 dairy milks, 10 dairy cheeses and 25 ND cheeses. Dairy milk and cheese were used as control against which all ND products were compared. Results: Soya and coconut milks had lower values of carbohydrates, sugars, calcium, iodine, and potassium (p < 0.01) than dairy. Almond milk had lower values of carbohydrates (p = 0.01), sugars, calcium, iodine, and potassium (p < 0.01) compared to dairy milk. Protein was significantly (p < 0.01) lower for all ND except soya. Dairy cheeses had higher values for energy, protein, iodine, potassium, riboflavin, vitamin B12 and calcium (p < 0.01) than ND. Median prices were similar between dairy and ND milks, whereas ND cheeses were significantly more expensive compared to dairy (p < 0.01). Conclusions: ND alternatives fall short in several key nutrients compared to dairy. Fortification, accurate labelling and nutrition education are needed to help consumers make healthy and informed choices.

Encapsulation of Vitamin E in Yogurt-Based Beverage Emulsions: Influence of Bulk Pasteurization and Chilled Storage on Physicochemical Stability and Starter Culture Viability.

Yogurt is a nutritious food that is regularly consumed in many countries around the world and is widely appreciated for its organoleptic properties. Despite its contribution to human dietary requirements, yogurt in its traditional recipe is a poor source of fat-soluble vitamins. To respond to consumer demands and further increase the nutritional value of this product, this work aimed to fortify yogurt with vitamin E by using emulsification as the method of encapsulation. The effects of thermal processing and chilled storage on the physicochemical stability of the yogurt-based beverage was investigated. Vitamin E was only minorly affected by bulk pasteurization at 63 °C for 30 min and remained stable during storage at 4 °C for 28 days. Fortified samples showed increased in vitro antioxidant activity compared with non-fortified samples. Lactic acid bacterial counts were above the minimum recommended levels (>106 cfu/g) after processing and storage. In conclusion, this work has demonstrated that emulsification can be an effective strategy for developing yogurt-based products fortified with fat soluble vitamins.

Understanding and Responding to Prescribing Patterns of Sodium Valproate-Containing Medicines in Pregnant Women and Women of Childbearing Age in Western Cape, South Africa.

INTRODUCTION: Growing evidence of the teratogenic potential of sodium valproate (VPA) has changed prescribing practices across the globe; however, the impact of this research and the consequent dissemination of a Dear Health Care Professional Letter (DHCPL) in December 2015, recommending avoidance of the teratogen VPA in women of childbearing age (WOCBA) and pregnant women in South Africa, is unknown. We explored trends and reasons for VPA use among pregnant women and WOCBA in the public sector in Western Cape Province from 1 January 2015 to 31 December 2017. METHODS: Using the provincial health information exchange that collates routine electronic health data via unique patient identifiers, we analysed clinical and pharmacy records from 2015 to 2017 to determine prescription patterns of VPA and other antiepileptic drug (AED) and mood-stabilising medicine (MSM) use in WOCBA and pregnant women. Senior clinicians and policy makers were consulted to understand the determinants of VPA use. RESULTS: At least one VPA prescription was dispensed to between 8205 (0.79%) and 9425 (0.94%) WOBCA from a cohort of approximately 1 million WOCBA attending provincial health care facilities per year. Prescriptions were more likely in HIV-infected women compared with HIV-uninfected women (1.1-1.3% vs. 0.7-0.9%; p < 0.001). VPA use in WOCBA remained stable at 0.8-0.9% over the review period despite the 2016 DHCPL. VPA was the most prescribed AED/MSM, constituting 43.2-45.5% of all WOCBA taking at least one such agent, while lamotrigine, the other recommended first-line agent, was only prescribed in 7.8-8.9% of WOCBA. Over 3 years, approximately 663 pregnancies were exposed to VPA, with a steady rise in the number of exposures each year (n = 204, 214 and 245, respectively). CONCLUSION: Despite warnings, VPA remained the most frequently prescribed AED or MSM in WOCBA. Contributing factors are described.

Twenty-four-month outcomes from a cluster-randomized controlled trial of extending antiretroviral therapy refills in ART adherence clubs.

INTRODUCTION: The antiretroviral therapy (ART) adherence club (AC) model has supported clinically stable HIV patients' retention with group ART refills and psychosocial support. Reducing visit frequency by increasing ART refills to six months could further benefit patients and unburden health systems. We conducted a pragmatic non-inferiority cluster randomized trial comparing standard of care (SoC) ACs and six-month refill intervention ACs in a primary care facility in Khayelitsha, South Africa. METHODS: Existing community-based and facility-based ACs were randomized to either SoC or intervention ACs. SoC ACs met five times annually, receiving two-month refills with a four-month refill over year-end. Blood was drawn at one AC visit with a clinical assessment at the next. Intervention ACs met twice annually receiving six-month refills, with an individual blood collection visit before the annual clinical assessment AC visit. The first study visits were in October and November 2017 and participants followed for 27 months. We report retention in care, viral load completion and viral suppression (<400 copies/mL) 24 months after enrolment and calculated intention-to-treat risk differences for the primary outcomes using generalized estimating equations specifying for clustering by AC. RESULTS: Of 2150 participants included in the trial, 977 were assigned to the intervention arm (40 ACs) and 1173 to the SoC (48 ACs). Patient characteristics at enrolment were similar across groups. Retention in care at 24 months was similarly high in both arms: 93.6% (1098/1173) in SoC and 92.6% (905/977) in the intervention arm, with a risk difference of -1.0% (95% CI: -3.2 to 1.3). The intervention arm had higher viral load completion (90.8% (999/1173) versus 85.1% (887/977)) and suppression (87.3% (969 /1173) versus 82.6% (853/977)) at 24 months, with a risk difference for completion of 5.5% (95% CI: 1.5 to 9.5) and suppression of 4.6% (95% CI: 0.2 to 9.0). CONCLUSIONS: Intervention AC patients receiving six-month ART refills showed non-inferior retention in care, viral load completion and viral load suppression to those in SoC ACs, adding to a growing literature showing good outcomes with extended ART dispensing intervals.

Physicochemical properties, texture, and probiotic survivability of oat-based yogurt using aquafaba as a gelling agent.

Despite high consumer demands, the manufacture of nondairy yogurt from oat milk is currently hindered due to the lack of consistency and texture. An oat-based yogurt was developed using oat milk and probiotics (Streptococcus thermophilus and Lactobacillus bulgaricus) with aquafaba (AF) and vegetable oil (VO) as added ingredients. Physicochemical analyses and viability of probiotics were investigated after yogurt formation and for 3 weeks under refrigerated storage. Results showed that adding AF decreased syneresis and increased water holding capacity during storage. Both AF and VO had a beneficial effect on hardness, the most important textural property of yogurt. Confocal laser scanning microscopy revealed that the added ingredients played a major role in the formation of the gel network structure of the yogurt. Both Streptococcus thermophilus and Lactobacillus bulgaricus remained at acceptable levels > 8.28 Log CFU/g and > 5.79 Log CFU/g after 3 weeks at 4°C regardless of the added ingredients.

Working lives of GPs in Scotland and England: cross-sectional analysis of national surveys.

OBJECTIVES: The UK faces major problems in retaining general practitioners (GPs). Scotland introduced a new GP contract in April 2018, intended to better support GPs. This study compares the career intentions and working lives of GPs in Scotland with GPs in England, shortly after the new Scotland contract was introduced. DESIGN AND SETTING: Comparison of cross-sectional analysis of survey responses of GPs in England and Scotland in 2017 and 2018, respectively, using linear regression to adjust the differences for gender, age, ethnicity, urbanicity and deprivation. PARTICIPANTS: 2048 GPs in Scotland and 879 GPs in England. MAIN OUTCOME MEASURES: Four intentions to reduce work participation (5-point scales: 1='none', 5='high'): reducing working hours; leaving medical work entirely; leaving direct patient care; or continuing medical work but outside the UK. Four domains of working life: job satisfaction (7-point scale: 1='extremely dissatisfied', 7='extremely satisfied'); job stressors (5-point-scale: 1='no pressure', 5='high pressure); positive and negative job attributes (5-point scales: 1='strongly disagree', 5='strongly agree'). RESULTS: Compared with England, GPs in Scotland had lower intention to reduce work participation, including a lower likelihood of reducing work hours (2.78 vs 3.54; adjusted difference=-0.52; 95% CI -0.64 to -0.41), a lower likelihood of leaving medical work entirely (2.11 vs 2.76; adjusted difference=-0.32; 95% CI -0.42 to -0.22), a lower likelihood of leaving direct patient care (2.23 vs 2.93; adjusted difference=-0.37; 95% CI -0.47 to -0.27), and a lower likelihood of continuing medical work but outside of the UK (1.41 vs 1.61; adjusted difference=-0.2; 95% CI -0.28 to -0.12). GPs in Scotland reported higher job satisfaction, lower job stressors, similar positive job attributes and lower negative job attributes. CONCLUSION: Following the introduction of the new contract in Scotland, GPs in Scotland reported significantly better working lives and lower intention to reduce work participation than England.

Addition of Broad Bean Hull to Wheat Flour for the Development of High-Fiber Bread: Effects on Physical and Nutritional Properties.

The seed coat (hull) of broad bean (Vicia faba) (BBH) is a significant secondary product of processing with a promising nutritional profile. Bean hull has a high fiber content (49%), yet it remains underexploited as an ingredient by the food industry. This study investigated the potential of this secondary product to partially replace wheat flour for the development of high-fiber breads. Bread formulations with a range of supplementation levels (0%, 11%, 21% and 31%) were developed and tested for their nutritional and physical properties. The proximate composition of breads revealed that at 31% replacement, the fiber content was 19.19 g/100 g bread, which was significantly higher (p < 0.05) than control breads (3.62 g/100 g bread). The physical (specific volume, density and color) and textural properties of breads were affected by the addition of bean hull. Specific volume and hardness of breads were significantly reduced at ≥21% replacement compared to the control, which may reduce acceptability of the product by some consumer groups. Enzyme-linked immunosorbent assay (ELISA) showed that the gluten content of breads was significantly reduced with bean hull addition (62% depletion for 31% replacement). At 11%, 21% and 31% replacement, one portion (80 g of bread) contains 6.8 g, 11.6 g and 15.3 g of dietary fiber, respectively, which contributes 23%, 38% and 51% of the recommended daily fiber intake (30 g/day). In conclusion, bean hull can be a valuable source of dietary fiber in bread formulations. The study showed BBH could be used to replace up to 21% of the wheat flour without significantly impacting on bread texture and volume.

Iron deficiency during pregnancy and lactation modifies the fatty acid composition of the brain of neonatal rats.

Iron deficiency is common in pregnant and lactating women and is associated with reduced cognitive development of the offspring. Since iron affects lipid metabolism, the availability of fatty acids, particularly the polyunsaturated fatty acids required for early neural development, was investigated in the offspring of female rats fed iron-deficient diets during gestation and lactation. Subsequent to the dams giving birth, one group of iron-deficient dams was recuperated by feeding an iron-replete diet. Dams and neonates were killed on postnatal days 1, 3 and 10, and the fatty acid composition of brain and stomach contents was assessed by gas chromatography. Changes in the fatty acid profile on day 3 became more pronounced on day 10 with a decrease in the proportion of saturated fatty acids and a compensatory increase in monounsaturated fatty acids. Long-chain polyunsaturated fatty acids in the n-6 family were reduced, but there was no change in the n-3 family. The fatty acid profiles of neonatal brain and stomach contents were similar, suggesting that the change in milk composition may be related to the changes in the neonatal brain. When the dams were fed an iron-sufficient diet at birth, the effects of iron deficiency on the fatty acid composition of lipids in both dam's milk and neonates' brains were reduced. This study showed an interaction between maternal iron status and fatty acid composition of the offspring's brain and suggests that these effects can be reduced by iron repletion of the dam's diet at birth.

A cluster randomized controlled trial of extending ART refill intervals to six-monthly for anti-retroviral adherence clubs.

BACKGROUND: The antiretroviral therapy (ART) adherence club (AC) differentiated service delivery model, where clinically stable ART patients receive their ART refills and psychosocial support in groups has supported clinically stable patients' retention and viral suppression. Patients and health systems could benefit further by reducing visit frequency and increasing ART refills. We designed a cluster-randomized control trial comparing standard of care (SoC) ACs and six-month ART refill (Intervention) ACs in a large primary care facility in Khayelitsha, South Africa. METHODS: Existing ACs were randomized to either the control (SOC ACs) or intervention (Intervention ACs) arm. SoC ACs meet five times annually, receiving two-month ART refills with a four-month ART refill over year-end. Blood is drawn at the AC visit ahead of the clinical assessment visit. Intervention ACs meet twice annually receiving six-month ART refills, with a third individual visit for routine blood collection anytime two-four weeks before the annual clinical assessment AC visit. Primary outcomes will be retention in care, annual viral load assessment completion and viral load suppression. (<400copies/mL) after 2 years. Ethics approval has been granted by the University of Cape Town (HREC 652/2016) and the Medecins Sans Frontieres (MSF) Ethics Review Board (#1639). Results will be published in peer-reviewed journals and made widely available through presentations and briefing documents. DISCUSSION: Evaluation of an extended ART refill interval in adherence clubs will provide evidence towards novel model adaptions that can be made to further improve convenience for patients and leverage health system efficiencies. TRIAL REGISTRATION: Registered with the Pan African Clinical Trial Registry: PACTR201810631281009. Registered 11 September 2018.

The effect of maternal iron deficiency on zinc and copper levels and on genes of zinc and copper metabolism during pregnancy in the rat.

Fe deficiency is relatively common in pregnancy and has both short- and long-term consequences. However, little is known about the effect on the metabolism of other micronutrients. A total of fifty-four female rats were fed control (50 mg Fe/kg) or Fe-deficient diets (7·5 mg/kg) before and during pregnancy. Maternal liver, placenta and fetal liver were collected at day 21 of pregnancy for Cu and Zn analysis and to measure expression of the major genes of Cu and Zn metabolism. Cu levels increased in the maternal liver (P=0·002) and placenta (P=0·018) of Fe-deficient rats. Zn increased (P<0·0001) and Cu decreased (P=0·006) in the fetal liver. Hepatic expression of the Cu chaperones antioxidant 1 Cu chaperone (P=0·042) and cytochrome c oxidase Cu chaperone (COX17, P=0·020) decreased in the Fe-deficient dams, while the expression of the genes of Zn metabolism was unaltered. In the placenta, Fe deficiency reduced the expression of the chaperone for superoxide dismutase 1, Cu chaperone for superoxide dismutase (P=0·030), ceruloplasmin (P=0·042) and Zn transport genes, ZRT/IRT-like protein 4 (ZIP4, P=0·047) and Zn transporter 1 (ZnT1, P=0·012). In fetal liver, Fe deficiency increased COX17 (P=0·020), ZRT/IRT-like protein 14 (P=0·036) and ZnT1 (P=0·0003) and decreased ZIP4 (P=0·004). The results demonstrate that Fe deficiency during pregnancy has opposite effects on Cu and Zn levels in the fetal liver. This may, in turn, alter metabolism of these nutrients, with consequences for development in the fetus and the neonate.

Incorporating salal berry (Gaultheria shallon) and blackcurrant (Ribes nigrum) pomace in yogurt for the development of a beverage with antidiabetic properties.

In this study aqueous extracts from salal berry (SB) and blackcurrant pomace (BCP) were used to reformulate yogurt and the anti-diabetic properties of the beverage were investigated during 4 weeks of cold storage at 4 °C. Results indicated that α-amylase, α-glucosidase and DPP-IV inhibitory activities increased with storage time for all samples. At the end of storage period α-amylase, α-glucosidase and DPP-IV inhibition were >61%, 62% and 56% respectively for all yogurt types. This increase in bioactivity during cold storage is attributed to the viability of lactic acid bacteria (∼108 cfu/g), which is maintained for 4 weeks. Enzyme inhibition increased similarly for all yogurt types at 4 °C except for α-glucosidase. Yogurt with BCP showed the highest potency to inhibit α-glucosidase (>90%) with an IC50 value of 0.20 mg/ml (week 4). A peptidomic approach based on liquid chromatography coupled with mass spectrometry (LC-MS) was used for the separation and identification of peptides generated in three types of yogurt. A total of 486 peptides mainly from caseins were identified, of which 15 have documented bioactivity, predominantly as antimicrobial agents or ACE-inhibitors.

Prenatal iron exposure and childhood type 1 diabetes.

Iron overload due to environmental or genetic causes have been associated diabetes. We hypothesized that prenatal iron exposure is associated with higher risk of childhood type 1 diabetes. In the Norwegian Mother and Child cohort study (n = 94,209 pregnancies, n = 373 developed type 1 diabetes) the incidence of type 1 diabetes was higher in children exposed to maternal iron supplementation than unexposed (36.8/100,000/year compared to 28.6/100,000/year, adjusted hazard ratio 1.33, 95%CI: 1.06-1.67). Cord plasma biomarkers of high iron status were non-significantly associated with higher risk of type 1 diabetes (ferritin OR = 1.05 [95%CI: 0.99-1.13] per 50 mg/L increase; soluble transferrin receptor: OR = 0.91 [95%CI: 0.81-1.01] per 0.5 mg/L increase). Maternal but not fetal HFE genotypes causing high/intermediate iron stores were associated with offspring diabetes (odds ratio: 1.45, 95%CI: 1.04, 2.02). Maternal anaemia or non-iron dietary supplements did not significantly predict type 1 diabetes. Perinatal iron exposures were not associated with cord blood DNA genome-wide methylation, but fetal HFE genotype was associated with differential fetal methylation near HFE. Maternal cytokines in mid-pregnancy of the pro-inflammatory M1 pathway differed by maternal iron supplements and HFE genotype. Our results suggest that exposure to iron during pregnancy may be a risk factor for type 1 diabetes in the offspring.

Use of ß-glucan from spent brewer's yeast as a thickener in skimmed yogurt: Physicochemical, textural, and structural properties related to sensory perception.

Powdered ß-glucan extracted from brewer's yeast (Yestimun, Leiber GmbH, Bramsche, Germany) was incorporated into skimmed-milk yogurt at varying concentrations (0.2-0.8% wt/wt) to investigate its potential application as a thickener. The effect of ß-glucan fortification on the nutritional profile, microstructure, physicochemical properties, and texture of freshly prepared yogurts was investigated. Sensory evaluation was also conducted and was correlated with instrumental analysis. The addition of Yestimun significantly reduced the fermentation time of the yogurt mix from 4 h to 3 h. Scanning electron microscopy revealed that ß-glucan particles formed small spherical clusters within the yogurt matrix. The majority of the physicochemical properties (syneresis, viscosity, color, and titratable acidity) remained unaffected by the incorporation of Yestimun in the recipe. Textural properties showed a gradual increment with increasing ß-glucan concentration. Hardness, total work done, adhesive force, and adhesiveness increased by 19.27, 23.3, 21.53, and 20.76%, respectively, when using the highest amount of Yestimun powder. Sensory analysis (n = 40) indicated that fortifying yogurt with Yestimun at 0.8% (wt/wt) concentration may affect overall acceptance ratings, which was attributed to adverse flavor and aftertaste effects. However, the overall liking score of the yogurt (5.0/9.0) shows potential for commercialization of the product.

The effect of iron deficiency on the temporal changes in the expression of genes associated with fat metabolism in the pregnant rat.

Iron is essential for the oxidative metabolism of lipids. Lipid metabolism changes during gestation to meet the requirements of the growing fetus and to prepare for lactation. The temporal effects of iron deficiency during gestation were studied in female rats fed complete or iron-deficient diets. Plasma triglycerides were elevated in the iron-deficient group throughout gestation. There were time-dependent changes in the triglyceride content of the maternal liver, falling at the midpoint of gestation and then increasing on d21.5. Compared to the control, triglycerides in the maternal liver were not different in the iron-deficient group prior to pregnancy and on d12.5, but were markedly reduced by d21.5. The abundance of mRNAs in the maternal liver suggests that lipogenesis is unchanged and beta-oxidation is reduced on d21.5 by iron deficiency. On d21.5 of gestation, the expression of placental lipase was unchanged by iron deficiency, however, the abundance of mRNAs for SREBP-1c, FABP4 were reduced, suggesting that there were changes in fatty acid handling. In the fetal liver, iron deficiency produced a marked decrease in the abundance of the L-CPT-1 mRNA, suggesting that beta-oxidation is reduced. This study shows that the major effect of iron deficiency on maternal lipid metabolism occurs late in gestation and that perturbed lipid metabolism may be a common feature of models of fetal programming.