A low-fat spread with added plant sterols and fish omega-3 fatty acids lowers serum triglyceride and LDL-cholesterol concentrations in individuals with modest hypercholesterolaemia and hypertriglyceridaemia.

PURPOSE: The primary and secondary objectives were to investigate the triglyceride (TG) and LDL-cholesterol (LDL-C) lowering effects of a spread with added plant sterols (PS) and fish oil as compared to a placebo spread. METHODS: This study had a randomized, double-blind, placebo-controlled, parallel group design with two intervention arms. Following a 2-week placebo run-in period, 260 healthy individuals with modestly elevated blood TG (≥ 1.4 mmol/L) and LDL-C (≥ 3.4 mmol/L) concentrations consumed either the placebo or intervention spread for 4 weeks. The intervention spread contained 2.0 g/day PS and 1.0 g/day eicosapentaenoic acid (EPA) + docosahexanoic acid (DHA) from fish oil. Fasting serum lipids and apolipoproteins (Apo) (exploratory) were measured at the end of the run-in and intervention phases. RESULTS: Four-week consumption of the intervention spread resulted in significantly lower TG (- 10.6%, 95% CI - 16.0 to - 4.9%; P < 0.001) and LDL-C concentrations (- 5.2%; 95% CI - 7.8 to - 2.4%) as compared to placebo. Total cholesterol (- 3.9%; 95% CI - 6.1 to - 1.5%), non-HDL-C (- 5.4%; 95% CI - 8.1 to - 2.7%), remnant-cholesterol (- 8.1%; 95% CI - 3.4 to - 12.5%), ApoAII (- 2.9%; 95% CI - 5.5 to - 0.2%), ApoCIII (- 7.7%; 95% CI - 12.1 to - 3.1%) and ApoB (- 3.2%; 95% CI - 5.9 to - 0.4%) concentrations were also significantly lower, as compared to placebo. No significant treatment effects were found for HDL-cholesterol, ApoAI, ApoCII, Apo E or ApoB/ApoAI. CONCLUSIONS: Four-week consumption of the intervention spread led to significant and clinically relevant decreases in serum TG, LDL-C and other blood lipid concentrations. The study was registered at clinicaltrials.gov (NCT02728583).

Supination Contractures in Brachial Plexus Birth Palsy: Long-Term Upper Limb Function and Recurrence After Forearm Osteotomy or Nonsurgical Treatment.

PURPOSE: Forearm osteotomy for supination deformity in brachial plexus birth palsy (BPBP) may lead to improved function of the upper limb. However, recurrence rates are high and limit satisfactory results. METHODS: We reviewed the long-term outcome of the entire upper limb of 22 BPBP patients with a supination contracture who were treated by forearm osteotomy and compared them with an age-matched group that was treated nonsurgically (n = 28). Recurrence was defined as a passive pronation below 30°. RESULTS: The median follow-up was 5.0 years (range, 1.5-14 years). The mean passive pronation after forearm osteotomy, including patients with recurrence at follow-up, improved from -1° (SD, 9°) to 33° (SD, 48°) at final follow-up, mean active wrist extension improved from 23° (SD, 40°) to 41° (SD, 38°). An overall improvement of wrist and hand strength was present. In patients without recurrence, pronation improved to a mean of 66° (SD, 23°) at final follow-up. Recurrence of the supination contracture was present in 9 cases (41%) and was only present in patients with a single bone osteotomy. Recurrence was associated with lower age at surgery (recurrence mean, 4 [SD, 1.2] and no recurrence 8 [SD 4.5]), lower shoulder external rotation (recurrence mean, 28 [SD, 17] and no recurrence 49 [SD, 23]), and overall lower hand function at baseline. CONCLUSIONS: Forearm osteotomy improves forearm pronation and hand function. Recurrence should be considered as a potential complication after forearm osteotomy and is associated with young age and lower function of shoulder and hand. Single-bone osteotomy might also be a risk factor for recurrence. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Sodium pyrophosphate enhances iron bioavailability from bouillon cubes fortified with ferric pyrophosphate.

Fe fortification of centrally manufactured and frequently consumed condiments such as bouillon cubes could help prevent Fe deficiency in developing countries. However, Fe compounds that do not cause sensory changes in the fortified product, such as ferric pyrophosphate (FePP), exhibit low absorption in humans. Tetra sodium pyrophosphate (NaPP) can form soluble complexes with Fe, which could increase Fe bioavailability. Therefore, the aim of this study was to investigate Fe bioavailability from bouillon cubes fortified with either FePP only, FePP+NaPP, ferrous sulphate (FeSO4) only, or FeSO4+NaPP. We first conducted in vitro studies using a protocol of simulated digestion to assess the dialysable and ionic Fe, and the cellular ferritin response in a Caco-2 cell model. Second, Fe absorption from bouillon prepared from intrinsically labelled cubes (2·5 mg stable Fe isotopes/cube) was assessed in twenty-four Fe-deficient women, by measuring Fe incorporation into erythrocytes 2 weeks after consumption. Fe bioavailability in humans increased by 46 % (P<0·005) when comparing bouillons fortified with FePP only (4·4 %) and bouillons fortified with FePP+NaPP (6·4 %). Fe absorption from bouillons fortified with FeSO4 only and with FeSO4+NaPP was 33·8 and 27·8 %, respectively (NS). The outcome from the human study is in agreement with the dialysable Fe from the in vitro experiments. Our findings suggest that the addition of NaPP could be a promising strategy to increase Fe absorption from FePP-fortified bouillon cubes, and if confirmed by further research, for other fortified foods with complex food matrices as well.

Sustained satiety induced by food foams is independent of energy content, in healthy adults.

Our previous research demonstrated high, sustained satiety effects of stabilized food foams relative to their non-aerated compositions. Here we test if the energy and macronutrients in a stabilized food foam are critical for its previously demonstrated satiating effects. In a randomized, crossover design, 72 healthy subjects consumed 400 mL of each of four foams, one per week over four weeks, 150 min after a standardized breakfast. Appetite ratings were collected for 180 min post-foam. The reference was a normal energy food foam (NEF1, 280 kJ/400 mL) similar to that used in our previous research. This was compared to a very low energy food foam (VLEF, 36 kJ/400 mL) and 2 alternative normal energy foams (NEF2 and NEF3) testing possible effects of compositional differences other than energy (i.e. emulsifier and carbohydrate source). Appetite ratings were quantified as area under the curve (AUC) and time to return to baseline (TTRTB). Equivalence to NEF1 was predefined as the 90% confidence interval of between-treatment differences in AUC being within -5 to +5 mm/min. All treatments similarly affected appetite ratings, with mean AUC for fullness ranging between 49.1 and 52.4 mm/min. VLEF met the statistical criterion for equivalence to NEF1 for all appetite AUC ratings, but NEF2 and NEF3 did not. For all foams the TTRTB for satiety and fullness were consistently between 150 and 180 min, though values were shortest for NEF2 and especially NEF3 foams for most appetite scales. In conclusion, the high, sustained satiating effects of these food foams are independent of energy and macronutrient content at the volumes tested.

Elimination of large uremic toxins by a dialyzer specifically designed for high-volume convective therapies.

BACKGROUND: Unlike conventional hemodialysis treatments, which rely almost solely on diffusion-related mechanisms for solute removal, hemodiafiltration (HDF) allows more efficient removal of higher molecular weight toxins due to convective transport mechanisms. To facilitate the removal of these toxins in HDF treatment modalities, dialyzers with highly efficient high-flux membranes are necessary. This study assessed the large uremic toxin removal ability of a high-flux dialyzer (FX CorDiax 60) specifically designed to facilitate convective therapies compared with a standard high-flux dialyzer (FX 60). METHODS: In an open, randomized, cross-over, single-center, controlled, prospective clinical study, 30 adult chronic hemodialysis patients were treated by post-dilution online HDF with the FX 60 or the FX CorDiax 60 dialyzer. All other dialysis parameters were kept constant in both study arms. The reduction rate (RR) of blood urea nitrogen, phosphate, ß2-microglobulin (ß2-m), myoglobin, prolactin, α1-microglobulin, α1-acid glycoprotein, albumin and total protein as well as the elimination into dialysate was intraindividually compared for the two dialyzer types. RESULTS: For FX CorDiax 60 versus FX 60, the RR was significantly higher for blood urea nitrogen (86.23 ± 4.14 vs. 84.89 ± 4.59%, p = 0.015), ß2-m (84.67 ± 3.79 vs. 81.30 ± 4.82%, p < 0.0001), myoglobin (75.23 ± 10.48 vs. 58.60 ± 12.1%, p < 0.0001), prolactin (72.96 ± 9.68 vs. 56.91 ± 13.01%, p < 0.0001) and α1-microglobulin (20.89 ± 18.27 vs. 13.60 ± 12.50%, p = 0.016). There were no significant differences in the RR for phosphate, α1-acid glycoprotein, albumin and total protein. Mass removal was significantly higher with the FX CorDiax 60 than with the FX 60 for ß2-m (0.26 ± 0.09 vs. 0.24 ± 0.09 g, p = 0.0006), myoglobin (1.83 ± 0.89 vs. 1.51 ± 0.76 mg, p = 0.0017), prolactin (0.17 ± 0.13 vs. 0.14 ± 0.08 mg, p = 0.02) and albumin (4.25 ± 3.49 vs. 3.01 ± 2.37 g, p = 0.03). CONCLUSIONS: This study demonstrates that treating patients with an FX CorDiax 60 instead of an FX 60 dialyzer in post-dilution HDF mode significantly increases the elimination of middle molecules.

Serum Concentration of Plant Sterol Oxidation Products (POP) Compared to Cholesterol Oxidation Products (COP) after Intake of Oxidized Plant Sterols: A Randomised, Placebo-Controlled, Double-Blind Dose‒Response Pilot Study.

Plant sterols (PS) are oxidized to PS oxidation products (POP). This study quantified the change in serum POP compared to cholesterol oxidation products (COP) after the intake of increasing POP doses. This was a double-blind, randomized, placebo-controlled, dose‒response pilot study with healthy individuals in four groups (15 per group). The control group received products with no added PS or POP and treatment groups received daily 20-25 g margarine with added PS (mean 3 g/d) and two cookies (~28 g) for six weeks. Cookies delivered 8.7 (low-dose), 15.2 (medium-dose), or 37.2 (high-dose) mg/d POP. Fasting serum POP and COP were measured at the baseline, days 14, 28, and 42 in all participants and days 7, 21, and 35 in a subset. Sixty individuals completed the study; 52 were included in per protocol analysis. Serum POP increased with increasing POP intake and plateaued at dose >15 mg/d. Stabilized POP concentrations were (mean ± SD) 38.9 ± 6.9, 91.0 ± 27.9, 144.4 ± 37.9 and 203.0 ± 63.7 nmol/L, for control, low-, medium-, and high-dose POP groups, respectively. For all groups, the serum COP ranged from 213 to 262 nmol/L and the average POP/COP ratio was <1. Serum POP concentrations increased non-linearly, reaching stabilized concentrations in <7 days, and remained below COP concentrations after the intake of increasing POP doses.

Assessing the effect of different operation techniques on postoperative duplex ultrasound quality after carotid endarterectomy.

BACKGROUND: Duplex ultrasound is the first choice in diagnostics and surveillance of stenoses of the internal carotid arteries before and even after surgery. Therefore, the quality of duplex ultrasound is crucial to investigate these vascular pathologies. OBJECTIVE: Aim of this study was the evaluation whether different surgical techniques affect the postoperative quality of duplex ultrasound. METHODS: In a time period from January to May 2015 duplex ultrasound of the cervical vessels was performed in 75 patients after unilateral endarterectomy of the internal carotid artery at our department between 2006 and 2012. Thereby, the non-operated contralateral side served as a control. Study groups were defined by the surgical techniques of eversion- or thrombendarterectomy with patch plasty using different patch materials and/or a haemostatic sealant. Duplex ultrasound analysis included acoustic impedance, extinction of ultrasound, thickness of skin and individual anatomic aspects of the patients. RESULTS: Carotid endarterectomy itself reduced intravascular grey levels, skin thickness and increased extinction of duplex ultrasound when compared to the non-operated side of the neck. In contrast, neither the kind of chosen operative technique nor the use of different patch materials or the application of a haemostatic sealant showed an effect in this regards. CONCLUSIONS: Whereas carotid endarterectomy per se worsens the quality of postoperative duplex ultrasound, the different analysed surgical techniques as well as used patches and the application of a haemostatic sealant can be assumed to be equal regarding the quality of postoperative ultrasound.

Plant sterols lower LDL-cholesterol and triglycerides in dyslipidemic individuals with or at risk of developing type 2 diabetes; a randomized, double-blind, placebo-controlled study.

BACKGROUND: Managing cardiovascular disease (CVD) risk factors, e.g., dyslipidemia in type-2 diabetes mellitus (T2DM) is critically important as CVD is the most common cause of death in T2DM patients. This study aimed to investigate the effect of plant sterols (PS) on lowering both elevated low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). METHODS: In a double-blind, randomized, placebo-controlled, parallel study, 161 individuals at increased risk of and with established T2DM, consumed low-fat spreads without or with added PS (2 g/d) for 6 weeks after a 2-week run-in period. Increased risk of developing T2DM was defined by the Australian T2DM Risk Assessment Tool (AUSDRISK). Fasting serum/plasma total cholesterol (TC), LDL-C, TG, high-density lipoprotein cholesterol (HDL-C), glucose and insulin were measured at baseline and after 6 weeks. Effects on acute and chronic postprandial blood lipids, glucose and insulin were measured over 4-h in 39 individuals with T2DM following a mixed meal challenge without and with added 2 g/d PS at week 6. The study was registered at clinicaltrials.gov (NCT02288585). RESULTS: Hundred fifty-one individuals completed the study and 138 (57% men, 43% women; 44 with and 94 at risk of T2DM) were included in per protocol analysis. Baseline LDL-C and TG were 3.8 ± 1.0 and 2.5 ± 0.8 mmol/l, respectively. PS intake significantly lowered fasting LDL-C (-4.6%, 95%CI -1.2; -8.0; p = 0.009), TC (-4.2%, 95%CI -1.2; -7.1; p = 0.006) and TG (-8.3%, 95% -1.1, -15.0; p = 0.024) with no significant changes in HDL-C, glucose or insulin. Postprandial lipid (TG, TC, LDL-C, HDL-C, remnant cholesterol), glucose and insulin responses did not differ. CONCLUSIONS: In individuals at risk of and with established T2DM and with elevated TG and LDL-C, 2 g/d of PS results in dual LDL-C plus TG lowering. Postprandial lipid or glycemic responses did not differ between PS and control treatment.

Increased sympathetic activity present in early hypertensive pregnancy is not lowered by plasma volume expansion.

OBJECTIVE: To evaluate whether sympathetic activity is increased in early-onset hypertensive pregnancy and whether this can be influenced by management with plasma volume expansion. METHODS: The study group consisted of 74 subjects, of which 37 had early-onset hypertensive disorders of pregnancy (preeclampsia or gestational hypertension with fetal growth restriction), who were included at 24 to 34 weeks in a randomized controlled trial of management with (n = 18) or without (n = 19) plasma volume expansion. Heart rate and blood pressure variabilities, LF/HF ratio for heart rate, baroreflex sensitivity, and phase difference at low frequency (LF approximately 0.1 Hz) were calculated by spectral analysis from continuous heart rate and blood pressure recordings of the finger pulse wave (Portaprestrade mark, TNO). Measurements were performed at inclusion, after 20 to 40 hours and after 65 to 100 hours. The control group consisted of 29 women with a normal pregnancy and 8 women who had late-onset preeclampsia after 34 weeks. Controls were measured at 32 weeks. All controls had a normal blood pressures at that time. RESULTS: LF variability of heart rate and blood pressure were significantly higher and baroreflex sensitivity was significantly lower in early-onset patients compared with normal controls. A significant trend towards higher LF variability of blood pressure and lower baroreflex sensitivity was found from normal controls to late-onset controls to early-onset patients. Parameters of sympathetic activity were not influenced by plasma volume expansion. CONCLUSION: Sympathetic activity was increased in early-onset hypertensive pregnancy. However, this was not affected by management with plasma volume expansion, suggesting that hypovolaemia in preeclampsia is a secondary phenomenon.

Long-term Functional and Radiographic Outcome of a Mobile Bearing Ankle Prosthesis.

BACKGROUND: Total ankle arthroplasty is an accepted alternative to arthrodesis of the ankle. However, complication and failure rates remain high. Long-term results of the Scandinavian Total Ankle Replacement (STAR) are limited, with variable complication and failure rates observed. This prospective study presents the long-term survivorship and postoperative complications of the STAR prosthesis. METHODS: Between May 1999 and June 2008, 134 primary total ankle arthroplasties were performed using the STAR prosthesis in 124 patients. The survivorship, postoperative complications, and reoperations were recorded, with a minimum follow-up period of 7.5 years. Clinical results were assessed using the Foot Function Index and the Kofoed score. The presence of component migration, cysts, and radiolucency surrounding the prosthesis components, heterotopic ossification, and progression of osteoarthritis in adjacent joints were determined. RESULTS: The cumulative survival was 78% after the 10-year follow-up period. An ankle arthrodesis was performed in 20 ankles (14.9%) that failed. Fourteen polyethylene insert fractures occurred (10.4%). Other complications occurred in 29 ankles (21.6%), requiring secondary procedures in 21 ankles (15.7%). Nevertheless, the postoperative clinical results improved significantly. Osteolytic cysts were observed in 61 ankles (59.8%) and the surface area of these cysts increased during follow-up, without any association with the prosthesis alignment or clinical outcome. Heterotopic ossification at the medial malleolus was present in 58 cases (56.8%) and at the posterior tibia in 73 cases (71.6%), with no effect on clinical outcome. Osteoarthritis of the subtalar and talonavicular joint developed in 9 (8.8%) and 11 cases (10.8%), respectively. CONCLUSION: The long-term clinical outcomes for the STAR were found to be satisfactory. Although these results are consistent with previous studies, the survival and complication rates are disappointing compared to knee and hip arthroplasty. Higher rates of successful outcomes following ankle arthroplasty are important, and these results highlight the need for further research to clarify the origin and significance of the reported complications. LEVEL OF EVIDENCE: Level II, prospective comparative study.

The effect of a low-fat spread with added plant sterols on vascular function markers: results of the Investigating Vascular Function Effects of Plant Sterols (INVEST) study.

BACKGROUND: Plant sterols (PSs) lower LDL cholesterol, an established risk factor for coronary artery disease (CAD). No direct evidence is available supporting a reduced risk of CAD for foods with added PSs. Endothelial dysfunction is seen as an early indicator of atherosclerotic damage. OBJECTIVES: This study was primarily designed to investigate the effect of a low-fat spread with added PSs on brachial artery endothelial function as measured by flow-mediated dilation (FMD). Second, effects on arterial stiffness, blood pressure, serum lipids, and plasma PS concentrations were investigated. We hypothesized that PSs would not worsen FMD but would rather modestly improve FMD. DESIGN: This study had a double-blind, randomized, placebo-controlled, parallel design. After a 4-wk run-in period, 240 hypercholesterolemic but otherwise healthy men and women consumed 20 g/d of low-fat spread without (control) or with added PSs (3 g/d) during 12 wk. Pre- and postintervention, vascular function measurements and blood sampling were performed. RESULTS: In total, 232 participants completed the study period. For the primary endpoint FMD, 199 participants were included in the statistical analysis. PS intake did not affect FMD (+0.01 percentage points; 95% CI: -0.73, 0.75) compared with control. Measures of arterial stiffness (pulse wave velocity and augmentation index) and blood pressure were also not significantly changed compared with control. After PS intervention, LDL cholesterol significantly decreased on average by 0.26 mmol/L (95% CI: -0.40, -0.12) or 6.7% compared with control. Plasma sitosterol and campesterol concentrations significantly increased in the PS group up to on average 11.5 µmol/L and 13.9 µmol/L (expressed as geometric means), respectively. CONCLUSIONS: The intake of a low-fat spread with added PSs neither improved nor worsened FMD or other vascular function markers in hypercholesterolemic men and women. As expected, serum LDL cholesterol decreased, whereas plasma PSs increased after PS intake. This study was registered at clinicaltrials.gov as NCT01803178.

A grading system of Alzheimer disease lesions in neocortical areas.

Progression of neuritic and Abeta pathology in the cerebral cortex during aging and Alzheimer disease is well known, but the chronology of the various types of lesions (Abeta deposition, amyloid formation, inflammation, ubiquitination, tangle formation) within a given area has not been fully elucidated. We examined these lesions in the primary visual cortex (Brodmann area 17), correlating them with the severity of the disease (as evaluated by the cognitive status and the number of cortical samples that contained neurofibrillary tangles). Four 'grades' were identified. At grade 1, only deposits of Abeta peptide were noticed. At grade 2, Congo red positive deposits, and processes containing ubiquitin and cathepsin D immunoreactivity around plaque cores could also be found. At grade 3, neuritic plaques and neuropil threads were present, and at grade 4, neurofibrillary tangles. The density of all the lesions dramatically increased at grade 4. The sequence of isocortical lesions from grade 1 to grade 4 is compatible with a cascade of events beginning with deposition of Abeta peptide and ending with neurofibrillary tangle.

Coeliac disease and autoimmune Addison's disease: a clinical pitfall.

BACKGROUND: Coeliac disease has an increased prevalence in a number of autoimmune endocrine conditions. An association between coeliac disease and Addison's disease has been proposed in isolated case reports, but has not been formally studied. AIM: To investigate the extent of this association. DESIGN: Prospective screening of patients with confirmed Addison's disease. METHODS: From central computerized records, we identified all living patients with a diagnosis of autoimmune Addison's disease in the past 30 years and presently attending our affiliated hospitals. After exclusions, 44 were invited to attend for screening. RESULTS: Of 41 patients screened, five (12.2%) had coeliac disease: Three were previously diagnosed coeliacs and this was confirmed on review, including examination of biopsy material. A further two had positive IgA-endomysial antibodies. Histological confirmation was obtained in both cases. Neither had laboratory or clinical evidence of malabsorption. DISCUSSION: In this series of patients with Addison's disease, a higher co-morbidity with coeliac disease was observed than in any previously studied endocrine condition. We recommend that coeliac serology (anti-endomysial and tissue transglutaminase antibody) testing be incorporated routinely into the autoimmune screen for other conditions in patients with Addison's disease.

Xenobiotic metabolism, genetic polymorphisms and male infertility.

Male reproductive function may be impaired by various occupational and environmental chemical agents. The majority of these xenobiotics, however, require metabolic activation in order to exert adverse effects via covalent interactions between intermediate metabolites and cellular macromolecules such as DNA or protein. In addition, metabolization may alter endocrine-disrupting properties of xenobiotics. Thus tissue-specific expression and regulation of multiple xenobiotic-metabolizing enzymes are likely to play an important role in chemically induced disorders of male reproductive organs. Recent studies suggest that genetic polymorphisms underlying inter-individual and inter-ethnic variability of xenobiotic metabolism modulate susceptibility to male reproductive disorders. For cytochrome P450 1A1 (CYP1A1), a key enzyme in extra-hepatic metabolic activation of lipophilic xenobiotics, increased frequencies of two genetically linked polymorphisms have been found among infertile men.

Rapid searches for complex patterns in biological molecules.

The intrinsic redundancy of genetic information makes searching for patterns in biological sequences a difficult task. We have designed an interactive self-documenting computer program called QUEST that allows rapid searching of large DNA and protein data banks for highly redundant consensus sequences or character patterns. QUEST uses a concise language for specifying character patterns containing several levels of ambiguity and pattern arrangement. Examples of the use of this program for sequence data are given. Details of the algorithm and pattern optimization are explained.