Nutritional impact of sodium reduction strategies on sodium intake from processed foods.

BACKGROUND/OBJECTIVES: Sodium intake in the Netherlands is substantially above the recommended intake of 2400 mg/day. This study aimed to estimate the effect of two sodium reduction strategies, that is, modification of the composition of industrially processed foods toward the technologically feasible minimum level or alteration of consumers' behavior on sodium intake in the Netherlands. SUBJECTS/METHODS: Data from the Dutch National Food Consumption Survey (2007-2010) and the Food Composition Table (2011) were used to estimate the current sodium intake. In the first scenario, levels in processed foods were reduced toward their technologically feasible minimum level (sodium reduction in processed foods scenario). The minimum feasible levels were based on literature searches or expert judgment. In the second scenario, foods consumed were divided into similar food (sub)groups. Subsequently, foods were replaced by low-sodium alternatives (substitution of processed foods scenario). Sodium intake from foods was calculated based on the mean of two observation days for the current food consumption pattern and the scenarios. RESULTS: Sodium levels of processed foods could be reduced in most food groups by 50%, and this may reduce median sodium intake from foods by 38% (from 3042 to 1886 mg/day in adult men). Substitution of foods may reduce sodium intake by 47% (from 3042 to 1627 mg/day in adult men), owing to many low-sodium alternatives within food groups. CONCLUSIONS: In the Netherlands, reduction of sodium intake by modification of food composition or by alteration of behavior may substantially reduce the median sodium intake from foods below the recommended sodium intake.

Mapping low intake of micronutrients across Europe.

Achieving an understanding of the extent of micronutrient adequacy across Europe is a major challenge. The main objective of the present study was to collect and evaluate the prevalence of low micronutrient intakes of different European countries by comparing recent nationally representative dietary survey data from Belgium, Denmark, France, Germany, The Netherlands, Poland, Spain and the United Kingdom. Dietary intake information was evaluated for intakes of Ca, Cu, I, Fe, Mg, K, Se, Zn and the vitamins A, B1, B2, B6, B12, C, D, E and folate. The mean and 5th percentile of the intake distributions were estimated for these countries, for a number of defined sex and age groups. The percentages of those with intakes below the lower reference nutrient intake and the estimated average requirement were calculated. Reference intakes were derived from the UK and Nordic Nutrition Recommendations. The impact of dietary supplement intake as well as inclusion of apparently low energy reporters on the estimates was evaluated. Except for vitamin D, the present study suggests that the current intakes of vitamins from foods lead to low risk of low intakes in all age and sex groups. For current minerals, the study suggests that the risk of low intakes is likely to appear more often in specific age groups. In spite of the limitations of the data, the present study provides valuable new information about micronutrient intakes across Europe and the likelihood of inadequacy country by country.

Contribution of highly industrially processed foods to the nutrient intakes and patterns of middle-aged populations in the European Prospective Investigation into Cancer and Nutrition study.

OBJECTIVES: To describe the contribution of highly processed foods to total diet, nutrient intakes and patterns among 27 redefined centres in the 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Single 24-hour dietary recalls were collected from 36,034 individuals (aged 35-74 years) using a standardized computerized interview programme (EPIC-SOFT). Centre-specific mean food intakes (g/day) were computed according to their degree of food processing (that is, highly, moderately and non-processed foods) using a specifically designed classification system. The contribution (%) of highly processed foods to the centre mean intakes of diet and 26 nutrients (including energy) was estimated using a standardized nutrient database (ENDB). The effect of different possible confounders was also investigated. RESULTS: Highly processed foods were an important source of the nutrients considered, contributing between 61% (Spain) and 78-79% (the Netherlands and Germany) of mean energy intakes. Only two nutrients, beta-carotene (34-46%) and vitamin C (28-36%), had a contribution from highly processed foods below 50% in Nordic countries, in Germany, the Netherlands and the United Kingdom, whereas for the other nutrients, the contribution varied from 50 to 91% (excluding alcohol). In southern countries (Greece, Spain, Italy and France), the overall contribution of highly processed foods to nutrient intakes was lower and consisted largely of staple or basic foods (for example, bread, pasta/rice, milk, vegetable oils), whereas highly processed foods such as crisp bread, breakfast cereals, margarine and other commercial foods contributed more in Nordic and central European centres. CONCLUSIONS: Highly industrially processed foods dominate diets and nutrient patterns in Nordic and central European countries. The greater variations observed within southern countries may reflect both a larger contribution of non/moderately processed staple foods along with a move from traditional to more industrialized dietary patterns.

Evidence for an extraterrestrial impact 12,900 years ago that contributed to the megafaunal extinctions and the Younger Dryas cooling.

A carbon-rich black layer, dating to approximately 12.9 ka, has been previously identified at approximately 50 Clovis-age sites across North America and appears contemporaneous with the abrupt onset of Younger Dryas (YD) cooling. The in situ bones of extinct Pleistocene megafauna, along with Clovis tool assemblages, occur below this black layer but not within or above it. Causes for the extinctions, YD cooling, and termination of Clovis culture have long been controversial. In this paper, we provide evidence for an extraterrestrial (ET) impact event at approximately equal 12.9 ka, which we hypothesize caused abrupt environmental changes that contributed to YD cooling, major ecological reorganization, broad-scale extinctions, and rapid human behavioral shifts at the end of the Clovis Period. Clovis-age sites in North American are overlain by a thin, discrete layer with varying peak abundances of (i) magnetic grains with iridium, (ii) magnetic microspherules, (iii) charcoal, (iv) soot, (v) carbon spherules, (vi) glass-like carbon containing nanodiamonds, and (vii) fullerenes with ET helium, all of which are evidence for an ET impact and associated biomass burning at approximately 12.9 ka. This layer also extends throughout at least 15 Carolina Bays, which are unique, elliptical depressions, oriented to the northwest across the Atlantic Coastal Plain. We propose that one or more large, low-density ET objects exploded over northern North America, partially destabilizing the Laurentide Ice Sheet and triggering YD cooling. The shock wave, thermal pulse, and event-related environmental effects (e.g., extensive biomass burning and food limitations) contributed to end-Pleistocene megafaunal extinctions and adaptive shifts among PaleoAmericans in North America.

Application of adjoint Monte Carlo to accelerate simulations of mono-directional beams in treatment planning for boron neutron capture therapy.

This paper deals with the application of the adjoint transport theory in order to optimize Monte Carlo based radiotherapy treatment planning. The technique is applied to Boron Neutron Capture Therapy where most often mixed beams of neutrons and gammas are involved. In normal forward Monte Carlo simulations the particles start at a source and lose energy as they travel towards the region of interest, i.e., the designated point of detection. Conversely, with adjoint Monte Carlo simulations, the so-called adjoint particles start at the region of interest and gain energy as they travel towards the source where they are detected. In this respect, the particles travel backwards and the real source and real detector become the adjoint detector and adjoint source, respectively. At the adjoint detector, an adjoint function is obtained with which numerically the same result, e.g., dose or flux in the tumor, can be derived as with forward Monte Carlo. In many cases, the adjoint method is more efficient and by that is much quicker when, for example, the response in the tumor or organ at risk for many locations and orientations of the treatment beam around the patient is required. However, a problem occurs when the treatment beam is mono-directional as the probability of detecting adjoint Monte Carlo particles traversing the beam exit (detector plane in adjoint mode) in the negative direction of the incident beam is zero. This problem is addressed here and solved first with the use of next event estimators and second with the application of a Legendre expansion technique of the angular adjoint function. In the first approach, adjoint particles are tracked deterministically through a tube to a (adjoint) point detector far away from the geometric model. The adjoint particles will traverse the disk shaped entrance of this tube (the beam exit in the actual geometry) perpendicularly. This method is slow whenever many events are involved that are not contributing to the point detector, e.g., neutrons in a scattering medium. In the second approach, adjoint particles that traverse an adjoint shaped detector plane are used to estimate the Legendre coefficients for expansion of the angular adjoint function. This provides an estimate of the adjoint function for the direction normal to the detector plane. In a realistic head model, as described in this paper, which is surrounded by 1020 mono-directional neutron/gamma beams and from which the best ones are to be selected, the example calculates the neutron and gamma fluxes in ten tumors and ten organs at risk. For small diameter beams (5 cm), and with comparable relative errors, forward Monte Carlo is seen to be 1.5 times faster than the adjoint Monte Carlo techniques. For larger diameter neutron beams (10 and 15 cm), the Legendre technique is found to be 6 and 20 times faster, respectively. In the case of gammas alone, for the 10 and 15 cm diam beams, both adjoint Monte Carlo Legendre and point detector techniques are respectively 2 and 3 times faster than forward Monte Carlo.

[Folic acid fortification: prevention as well as promotion of cancer]. / Foliumzuurverrijking: zowel preventie als bevordering van kanker.

In many countries foods are fortified with folic acid to prevent neural-tube defects. Beneficial effects on cancer, cardiovascular diseases and dementia are also assumed. Fortification with folic acid is not allowed in The Netherlands, although exemption can be granted. As well as beneficial effects, harmful effects may also occur. In addition to masking vitamin-B12 deficiency, there is some evidence that folic acid may promote progression of established tumours in laboratory animals and humans. In addition, it has been hypothesized that fortification with folic acid may have further negative effects on cancer through genetic selection. Given the high prevalence of cancer, these potentially harmful effects should also be taken into account in the Dutch debate on the advantages and disadvantages of folic acid fortification.

Design of a rotating facility for extracorporal treatment of an explanted liver with disseminated metastases by boron neutron capture therapy with an epithermal neutron beam.

In 2001, at the TRIGA reactor of the University of Pavia (Italy), a patient suffering from diffuse liver metastases from an adenocarcinoma of the sigmoid was successfully treated by boron neutron capture therapy (BNCT). The procedure involved boron infusion prior to hepatectomy, irradiation of the explanted liver at the thermal column of the reactor, and subsequent reimplantation. A complete response was observed. This encouraging outcome stimulated the Essen/Petten BNCT group to investigate whether such an extracorporal irradiation could be performed at the BNCT irradiation facility at the HFR Petten (The Netherlands), which has very different irradiation characteristics than the Pavia facility. A computational study has been carried out. A rotating PMMA container with a liver, surrounded by PMMA and graphite, is simulated using the Monte Carlo code MCNP. Due to the rotation and neutron moderation of the PMMA container, the initial epithermal neutron beam provides a nearly homogeneous thermal neutron field in the liver. The main conditions for treatment as reported from the Pavia experiment, i.e. a thermal neutron fluence of 4 x 10(12) +/- 20% cm(-2), can be closely met at the HFR in an acceptable time, which, depending on the defined conditions, is between 140 and 180 min.

A parameter study to determine the optimal source neutron energy in boron neutron capture therapy of brain tumours.

The values of the parameters used in boron neutron capture therapy (BNCT) to calculate a given dose to human tissue vary with patients due to different physical, biological and/or medical circumstances. Parameters include the tissue dimensions, the 10B concentration and the relative biological effectiveness (RBE) factors for the different dose components associated with BNCT. Because there is still no worldwide agreement on RBE values, more often than not, average values for these parameters are used. It turns out that the RBE-problem can be circumvented by taking into account all imaginable parameter values. Approaching this quest from another angle: the outcome will also provide the parameters (and values) which influence the optimal source neutron energy. For brain tumours it turns out that the 10B concentration, the RBE factors for 10B as well as fast neutrons, together with the dose limit set for healthy tissue, affect the optimal BNCT source neutron energy. By using source neutrons of a few keV together with neutrons of a few eV, it ensures that, under all imaginable circumstances, a maximum of alpha (and lithium) particles can be delivered in the tumour.

TP53 mutations in human meningiomas.

Overexpression of p53 has been reported to play a role in the development of neoplasms of the central nervous system. Meningiomas are generally benign intracranial tumors originating from the meninges. Overexpression of the p53 protein in meningiomas and an association with histological type and recurrence has been reported. Mutation of the TP53 gene leads to a more stable p53 protein in quantities high enough for detection by immunohistochemistry. In the search for these mutations the core domain of the TP53 gene of meningiomas has been analyzed. Only a very low incidence of mutations was reported. The apparent discordance between overexpression of p53 protein and TP53 gene mutations may be explained by mutations located outside the core domain. This issue was addressed in the present study. All 11 exons of 17 meningiomas were analyzed for DNA alterations by PCR single-strand conformation polymorphism (PCR-SSCP) analysis with subsequent sequencing. PCR-SSCP analysis showed a various number of band shifts and nucleotide alterations, caused either by alterations in the flanking introns or common polymorphisms (codon 36 and 72). The allele frequencies of the polymorphisms found in this small population of tumors resemble the frequencies reported in the literature. In addition, three nucleotide changes located in introns 2, 3 and 7 were found in 11, 3 and 4, respectively, of 17 specimens. Based on this study and on reports by others we conclude that it is not very likely that TP53 mutations are involved in the etiology of meningiomas.

The association between antihypertensive drug therapies and plasma lipid levels in the general population.

OBJECTIVE: To assess the association between different antihypertensive drug regimens and plasma lipid levels in the general population. METHODS: The Monitoring Project on Cardiovascular Risk Factors was conducted from 1987 to 1991 as a cross-sectional study in The Netherlands. Antihypertensive drug-users and untreated hypertensives were selected. After exclusion of users of cholesterol-lowering drugs 2997 subjects remained for the analysis. The plasma lipid concentrations of the users and non-users of antihypertensives were compared by multiple linear regression. RESULTS: In the univariate analysis patients using beta-blockers had lower high-density lipoprotein (HDL) concentrations (1.13 mmol/l, P < 0.05) and higher cholesterol ratios (5.74, P < 0.05) than untreated hypertensives (Total cholesterol = 6.07 mmol/l, HDL = 1.20 mmol/l and ratio = 5.44). Patients using diuretics had higher total cholesterol levels (6.34 mmol/l) and higher HDL levels (1.26 mmol/l) compared to untreated hypertensives. After adjustment for possible confounders these differences were smaller and no longer statistically significant. After adjustment we found a significant lower HDL cholesterol (mean difference of -0.10 mmol/l, P < 0.05) for users of a combination of a beta-blocker and a diuretic. CONCLUSIONS: Although randomised, controlled trials have demonstrated that antihypertensive drugs may influence plasma lipid levels we observed no substantial association for single antihypertensive drug therapy in the general population. The combination of a diuretic and a beta-blocker was associated with a worse lipid profile.

Drug-Induced lipid changes: a review of the unintended effects of some commonly used drugs on serum lipid levels.

Many drugs besides lipid-lowering drugs affect serum lipid levels in either a potentially harmful or beneficial way, and may therefore increase or decrease the risk of cardiovascular disease. Diuretics, beta-blocking agents, progestogens, combined oral contraceptives containing 'second generation' progestogens, danazol, immunosuppressive agents, protease inhibitors and enzyme-inducing anticonvulsants adversely affect the lipid profile. They increase total cholesterol, low density lipoprotein cholesterol and triglycerides by up to 40, 50 and 300%, respectively, and decrease high density lipoprotein cholesterol by a maximum of 50%. Conversely, alpha-blocking agents, estrogens, hormone replacement therapy, combined oral contraceptives containing 'third generation' progestogens, selective estrogen receptor modulators, growth hormone and valproic acid show mostly beneficial effects on the lipd profile. Some drugs, for example, isotretinoin, acitretin and antipsychotics, mainly elevate triglyceride levels. Adverse or beneficial effects on serum cholesterol levels do not always translate into a higher or lower, respectively, incidence of cardiovascular disease. because these drugs may influence cardiovascular risk through multiple pathways. In some cases, excessive cholesterol levels occur, for example, with protease inhibitor therapy, and several cases of pancreatitis attributable to drug-induced hypertriglyceridaemia have been reported. Some general guidelines on the management of drug-induced dyslipidaemia can be given. Replacement of the dyslipidaemia-inducing drug by an equivalent alternative therapy is preferred. However, such alternatives are often difficult to find. If there is no equivalent alternative and treatment with the dyslipidaemia-inducing drug must be initiated, monitoring of serum lipid levels is important. If drug use is expected to be long term, the existing guidelines for the management of dyslipidaemia in the general population can be applied to drug-induced dyslipidaemia. In cases of extreme hyperlipidaemia, medication use should be reassessed.

Pilot-plant production of prednisolone using calcium alginate immobilized Arthrobacter simplex.

The maximum conversion of hydrocortisone suspensions at initial substrate concentrations greater than 4 g/L by immobilized Arthrobacter simplex in a batch reactor was 80-85%. By feeding hydrocortisone suspensions continuously to either a fed-batch-operated stirred tank reactor or to a continuous-flow airlift loop reactor, at a rate such that the soluble hydrocortisone concentration in the reactor remained ca. 0.05 g/L, 95% conversion of substratewas obtained at final product concentrations exceeding 4 g/L.

Köle's osteotomy, a follow-up study.

A retrospective investigation into Köle's (1959) osteotomy for the correction of anterior open bite was performed. Changes in occlusion were seen in 32%. Bone graft incorporation was satisfactory. The vitality of the teeth adjacent to the osteotomy and the periodontal condition were satisfactory if a tooth at the osteotomy site was extracted. The sensibility of the lip was, in general, good.