Dietary patterns are related to cognitive functioning in elderly enriched with individuals at increased risk for Alzheimer's disease.

PURPOSE: To investigate cross-sectional associations between dietary patterns and cognitive functioning in elderly free of dementia. METHODS: Data of 389 participants from the German DELCODE study (52% female, 69 ± 6 years, mean Mini Mental State Score 29 ± 1) were included. The sample was enriched with elderly at increased risk for Alzheimer's disease (AD) by including participants with subjective cognitive decline, mild cognitive impairment (MCI) and siblings of AD patients. Mediterranean and MIND diets were derived from 148 Food Frequency Questionnaire items, and data-driven patterns by principal component analysis (PCA) of 39 food groups. Associations between dietary patterns and five cognitive domain scores were analyzed with linear regression analyses adjusted for demographics (model 1), and additionally for energy intake, BMI, other lifestyle variables and APOe4-status (model 2). For PCA-derived dietary components, final model 3 included all other dietary components. RESULTS: In fully adjusted models, adherence to Mediterranean and MIND diet was associated with better memory. The 'alcoholic beverages' PCA component was positively associated with most cognitive domains. Exclusion of MCI subjects (n = 60) revealed that Mediterranean and MIND diet were also related to language functions; associations with the alcoholic beverages component were attenuated, but most remained significant. CONCLUSION: In line with data from elderly population samples, Mediterranean and MIND diet and some data-derived dietary patterns were related to memory and language function. Longitudinal data are needed to draw conclusions on the putative effect of nutrition on the rate of cognitive decline, and on the potential of dietary interventions in groups at increased risk for AD.

Implementation and Benefit Evaluation of Recommendations for Patient Safety in Ambulatory Surgical Care.

Objective: The aim of this study was to evaluate the degree of implementation of recommendations for patient safety in ambulatory surgical care and their benefit as perceived by surgeons in the ambulatory sector. Based on 2 practice recommendations issued by the Association of Statutory Health Insurance Physicians in Westphalia-Lippe, recommendations were formulated specifically for ambulatory surgery and distributed in 2013 to all physicians licensed to conduct ambulatory surgery in Westphalia-Lippe. Methods: We conducted a written survey covering all safety measures addressed by the 2 practice recommendations and assessed the degree of implementation and the perceived benefit for each of these measures as well as the strengths of the recommendations and the challenges of implementing them. The survey was distributed in late 2014 to 2 454 surgeons in the ambulatory setting. The survey period was 7 weeks. The analysis of the quantitative data was mainly descriptive and we conducted thematic summaries of free text answers to open-ended questions. Results: The participation rate was 17% (n=405). The recommendations were known to 86% of the respondents. The majority of recommended safety measures had been implemented systemically in more than 50% of the participating institutions. An increased interprofessional awareness of patient safety measurements was reported as the main impact of the recommendations. Respondents indicated further need for information and practice recommendations concerning the following topics: risk and error management, implementation of the Medical Devices Act, hygiene in medical practice and processing of instruments. Conclusion: This study highlights the valuable contribution practice recommendations can make to patient safety improvement in ambulatory surgical care. Their dissemination to other regions as well as to other ambulatory care settings such as family practice can therefore be recommended.

Corrigendum: Incidence, prevalence and care of type 1 diabetes in children and adolescents in Germany: Time trends and regional socioeconomic situation.

[This corrects the article on p. 57-78 in vol. 8.].

[Community pharmacy and general internal medicine are at the same crossroads: some opportunities should be seized]. / Pharmacie d'officine et médecine interne générale à la croisée des mêmes chemins: des opportunités à saisir.

The medicines give some symptoms relief and save lives every day. However, the responsible use of medicines is not definitively attained for the modern health systems. The shortcomings in this area are the cause of major negative clinical outcomes for the patients and the cause of additional cost for the health financing system. The two centenarians, as the International Pharmaceutical Federation (FIP) and the "Policlinique Médicale Universitaire (PMU)" in Lausanne, preview the solutions from now on for reversing this trend, such as the interdisciplinary collaborative approaches, the introduction of adequate financial incentives and the strengthening of education and research in community medicine, pharmacy and health.

[The Federal Joint Committee resolution on staged emergency care and impact on nursing education for emergency care : Cross-sectional survey on the status quo in Germany]. / Der Beschluss des Gemeinsamen Bundesausschusses zur gestuften Notfallversorgung und seine Auswirkung auf die Weiterbildung Notfallpflege : Eine deutschlandweite Querschnittserhebung.

BACKGROUND: Decisive steps towards securing the advancement of emergency nursing care (ENC) include the establishment of state-approved training curricula and qualifications in Berlin and Bremen, the recommendation on ENC training issued by the German Hospital Federation (DKG), and the experts' report prepared by the Federal Joint Committee (G-BA) on how the provision of ENC should continue to evolve. The G­BA resolution specifies that at least one specialist nurse with a specific qualification in emergency care must be on hand as required in every emergency department once this qualification becomes available in the relevant federal state. This poses the question as to how well established qualification programmes are in Germany. METHODS: Cross-sectional data were collected between November 2018 and January 2019 in a whole-population descriptive study based largely on structured telephone interviews with directors of ENC training programmes in Germany. As a mixed-methods approach was considered desirable, an online search on training programmes was performed. RESULTS: In all, 42 directors of a current 44 training programmes were interviewed. A temporal link is evident between the G­BA resolution, the DKG recommendation, and an increase in the provision of ENC courses designed around the DKG's transitional arrangements for recognising the skills of existing nursing practitioners as new training requirements are phased in. Currently, 30 recognition examinations (without supporting courses) and 31 courses offering 170 h of training are available. Two-year programmes are provided at 28 locations, with four more currently at the planning stage. The qualifications of trainers and the modalities and duration of examinations vary strongly between programmes. An ENC qualification is currently held by 1861 nurses; 85% of programme directors expressed confidence that the G­BA resolution will boost demand for education and training in ENC. CONCLUSIONS: The number of 2­year training programmes offered continues to increase. The demand for emergency care nurses with the qualification level specified in the G­BA resolution is expected to rise again from 2020 as transitional arrangements cease.

Asthma prediction in school children; the value of combined IgE-antibodies and obstructive airways disease severity score.

BACKGROUND: Allergic sensitisation increases the risk for asthma development. In this prospective birth cohort (Environment and Childhood Asthma) study, we hypothesized that combining quantitative measures of IgE antibodies (Sigma-IgE) and Severity score of obstructive airways disease (OAD) at 2 years of age (Severity score) is superior to predict current asthma (CA) at 10 years than either measure alone. Secondarily, we assessed if gender modified the prediction of CA. METHODS: A follow-up study at 10 years of age was performed in 371 2-year-old children with recurrent (n = 219) or no (n = 152) bronchial obstruction with available serum analysed for Sigma-IgE to common food and inhalant allergens through a panel test, Phadiatop Infant) (Phadia, Uppsala, Sweden). Clinical variables included allergic sensitisation and exercise testing to characterise children with CA vs not CA at 10 years and the Severity score (0-12, 0 indicating no OAD) was used to assess risk modification. RESULTS: Severity score alone explained 24% (Nagelkerke R(2) = 0.24) of the variation in CA, whereas Sigma-IgE explained only 6% (R(2) = 0.06). Combining the two increased the explanatory capacity to R(2) = 0.30. Gender interacted significantly with Sigma-IgE; whereas Severity score predicted CA in both genders, the predictive capacity of Sigma-IgE for CA at 10 years was significant in boys only. CONCLUSION: Combining Sigma-IgE to inhalant allergens and Severity score at 2 years was superior to predict asthma at 10 years than either alone. Severity score predicted CA in both genders, whereas Sigma-IgE significantly predicted CA in boys only.

A novel pathway for biosynthesis of cholestanol with 7 alpha-hydroxylated C27-steroids as intermediates, and its importance for the accumulation of cholestanol in cerebrotendinous xanthomatosis.

A mixture of 7 alpha-3H- and 4-14C-labeled cholesterol was administered intravenously to rats. Cholestanol with 20-30% lower ratio between 3H and 14C than in cholesterol could be isolated from different organs. In a healthy human control, cholestanol isolated from feces had a 3H/14C ratio which was 28% lower than in administered cholesterol. Cholesterol and coprostanol reisolated in these experiments had the same ratio between 3H and 14C as in the precursor. A previously unknown pathway for formation of cholestanol, involving 7 alpha-hydroxylated intermediates, may explain these results. Under normal conditions, this pathway is responsible for at most 30% of the cholestanol synthesized from cholesterol. Intravenous administration of the 7 alpha-3H- and 4-14C-labeled cholesterol to a patient with cerebrotendinous xanthomatosis (CTX) resulted in formation of cholestanol which had 70-75% lower 3H/14C ratio. It is concluded that the novel pathway involving 7 alpha-hydroxylated intermediates is accelerated in patients with CTX. This acceleration may contribute essentially to the accumulation of cholestanol, which is a predominant feature of this disease. 7 alpha-Hydroxycholesterol and 7 alpha-hydroxy-4-cholesten-3-one might be intermediates in the novel pathway to cholestanol. After intravenous administration of 7 beta-3H-labeled 7 alpha-hydroxycholesterol in a patient with CTX, significant amounts of 3H were incorporated into plasma and fecal cholestanol. Only small amounts of 7 alpha-hydroxycholesterol and 7 alpha-hydroxy-4-cholesten-3-one are excreted into the intestine, and we therefore conclude that the 7 alpha-dehydroxylation step mainly occurs in the liver. In CTX, the synthesis of cholestanol may be accelerated because the concentrations of 7 alpha-hydroxylated bile acid intermediates in the liver are increased. A possible mechanism for the conversion of a minor fraction of 7 alpha-hydroxycholesterol into cholestanol is suggested.

Lack of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase/isomerase in fibroblasts from a child with urinary excretion of 3 beta-hydroxy-delta 5-bile acids. A new inborn error of metabolism.

Cultured fibroblasts were shown to be capable of catalyzing the conversion of 7 alpha-hydroxy-cholesterol to 7 alpha-hydroxy-4-cholesten-3-one, an important reaction in bile acid synthesis. The apparent Km was approximately 7 mumol/liter and Vmax varied between 3 and 9 nmol/mg protein per h under the assay conditions used. The assay was used to investigate fibroblasts from a patient who presented with a familial giant cell hepatitis and who was found to excrete the monosulfates of 3 beta, 7 alpha-dihydroxy-5-cholenoic acid and 3 beta, 7 alpha, 12 alpha-trihydroxy-5-cholenoic acid in urine (Clayton, P. T., J. V. Leonard, A. M. Lawson, K. D. R. Setchell, S. Andersson, B. Egestad, and J. Sjövall. 1987. J. Clin. Invest. 79:1031-1038). In addition 7 alpha-hydroxy-cholesterol was found to accumulate in the circulation. Cultured fibroblasts from this boy were completely devoid of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase/isomerase activity. Fibroblasts from his parents had reduced activity, compatible with a heterozygous genotype. The results provide strong evidence for the suggestion that this patient's liver disease was caused by a primary defect in the 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase/isomerase involved in bile acid biosynthesis.

Demonstration of 26-hydroxylation of C27-steroids in human skin fibroblasts, and a deficiency of this activity in cerebrotendinous xanthomatosis.

26-Hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol and other C27-steroids was demonstrated in cultured skin fibroblasts from healthy individuals. Activities in skin fibroblasts were approximately 5-10% of those previously found in human liver homogenates, and were inhibited by CO. The apparent Km was lowest for 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol (1.3 mumol/liter) and highest for 5-cholestene-3 beta, 7 alpha-diol (12 mumol/liter). The rate of 26-hydroxylation was highest with 7 alpha-hydroxy-4-cholesten-3-one. These characteristics are similar to those of hepatic mitochondrial C27-steroid 26-hydroxylase. In skin fibroblasts from three patients with cerebrotendinous xanthomatosis (CTX), 26-hydroxylation of C27-steroids proceeded at a rate of only 0.2-2.5% of healthy controls. No accumulation of endogenous 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol could be demonstrated in these cells, and the lowered formation of radioactive, 26-hydroxylated products could not be explained by dilution of the labeled exogenous substrate. The present results add strong evidence to the concept that the primary metabolic defect in CTX is a deficiency of C27-steroid 26-hydroxylase.

Metabolism of the cholestanol precursor cholesta-4,6-dien-3-one in different tissues.

Cerebrotendinous xanthomatosis (CTX) is a lipid storage disease where the basic defect is a lack of the mitochondrial C27-steroid 26-hydroxylase involved in bile acid synthesis (EC 1.14.13.15). Cholestanol and cholesterol accumulate in all tissues. At least part of the accumulation of cholestanol is due to a 7 alpha-dehydroxylation of early bile acid intermediates. Cholesta-4,6-dien-3-one, a proposed intermediate in this pathway, is found in increased concentrations in serum of the patients. This study shows that cholesta-4,6-dien-3-one may be metabolized to 4-cholesten-3-one and cholestanol by liver, adrenals and brain. No conversion was found in intestinal mucosa or in kidneys. The capacity to convert cholesta-4,6-dien-3-one into 4-cholesten-3-one and cholestanol varied in different tissues as well as in different species. The results are discussed in relation to the cholestanol accumulation in CTX.

On the structural specificity in the regulation of the hydroxymethylglutaryl-CoA reductase and the cholesterol-7 alpha-hydroxylase in rats. Effects of cholestanol feeding.

The effect of feeding 2% cholestanol or cholesterol on cholesterol-7 alpha-hydroxylase activity and hydroxymethylglutaryl (HMG)-CoA reductase activity was studied in rats. The rate of 7 alpha-hydroxylation of a trace amount of labelled cholesterol increased by about 80% after the cholestanol feeding, whereas the 7 alpha-hydroxylation of endogenous microsomal cholesterol increased by about 40%. The latter conversion was measured with an accurate technique based on isotope dilution-mass spectrometry. After cholesterol feeding, the corresponding figures were about 50 and 60%, respectively. The cholestanol feeding had no significant effect on the HMG-CoA reductase activity, whereas the cholesterol feeding decreased the activity by about 80%. From the results obtained, it is concluded that the increased 7 alpha-hydroxylation observed after cholesterol feeding can not be explained only by a simple expansion of the substrate pool. The similar effect of both cholesterol and cholestanol on the cholesterol 7 alpha-hydroxylase activity and the diverging effect on the HMG-CoA reductase activity show that there is no coupling between cholesterol synthesis and degradation under the conditions employed. The lack of effect of cholestanol on the HMG-CoA reductase activity indicates a high structural specificity of the receptor involved in regulation of the enzyme. If a receptor mechanism is involved in the stimulation of the cholesterol-7 alpha-hydroxylase by cholesterol and cholestanol, these receptor(s) must be different from those involved in the regulation of the HMG-CoA reductase.

Isolation of 5 alpha-cholestane-3 beta, 7 alpha-diol from bile of patients with cerebrotendinous xanthomatosis. Inefficiency of this steroid as a precursor to cholestanol.

Cerebrotendinous xanthomatosis is a rare, inherited disease characterized by defective bile acid biosynthesis as well as by accumulation of cholesterol and cholestanol. The mechanism behind the accumulation of cholestanol is unknown. Using combined gas chromatography-mass spectrometry, 5 alpha-cholestane-3 beta, 7 alpha-diol could be identified as a minor component in bile from two such patients. There were no significant amounts of this steroid in bile from control subjects. Most probably, the 5 alpha-cholestan-3 beta, 7 alpha-diol found is formed from 7 alpha-hydroxy-4-cholesten-3-one in the liver. 7 alpha-Hydroxy-1-cholesten-3-one, being a normal intermediate in bile acid biosynthesis, is known to accumulate in the liver and bile of patients with cerebrotendinous xanthomatosis, due to a defect of the mitochondrial 26-hydroxylase. The possibility was tested that (7 beta-3H)-labeled 5 alpha-cholestane-3 beta, 7 alpha-diol could be converted into cholestanol by a direct 7 alpha-dehydroxylation in the intestine. This conversion did not occur in rabbits, however, regardless of whether the labelled steroid was administered orally or intracoecally. It is concluded that 5 alpha-cholestane-3 beta, 7 alpha-diol is of little or no importance as a precursor to cholestanol in rabbits. Most probably, this is also the case in patients with cerebrotendinous xanthomatosis.

Efficacy and tolerability of the renin inhibitor Ro 42-5892 in patients with hypertension.

The efficacy of multiple oral administration of the renin inhibitor Ro 42-5892 [(S)-alpha-](t-butylsulfonyl)-methyl]hydrocinnamamido]-N-[1S , 2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl]-imi dazole-4- propionamide] was studied. Forty-nine patients with moderate essential hypertension were randomly assigned to three groups that entered an 8-day double-blind oral treatment period: daily administration of placebo (group A), 300 mg Ro 42-5892 (group B), or 600 mg Ro 42-5892 (group C). Four hours after the last oral drug intake, placebo was administered intravenously to subjects in group A and 100 mg Ro 42-5892 was administered intravenously to subjects in groups B and C. Sitting systolic and diastolic blood pressures were measured on days 1 and 8 with a blood pressure device. On day 1, systolic blood pressure maximally decreased by 13.3 +/- 9.3, 20.2 +/- 11.2, and 24.1 +/- 11.3 mm Hg in groups A, B, and C, respectively (mean +/- SD; p < 0.01 for group A versus group C). Diastolic blood pressure maximally decreased 9.4 +/- 5.7, 13.9 +/- 8.7, and 11.8 +/- 5.7 mm Hg (difference not significant). On day 8, systolic blood pressure maximally decreased 19.5 +/- 16.5, 26.5 +/- 17.4, and 30.5 +/- 18.4 mm Hg and diastolic blood pressure maximally decreased 14.8 +/- 5.0, 16.2 +/- 9.0, and 17.9 +/- 12.7 mm Hg (difference not significant) compared with pretreatment values. Intravenous drug administration did not further reduce blood pressure, suggesting that the mode of action and not the low bioavailability was the limiting factor for the low efficacy.

Hydrophobic effect at the origin of the low solubility of inert solid substances in hydrogen-bonded solvents.

The new solubility equation derived from the thermodynamics of mobile order in liquids is used to predict the solubility of four solid aliphatic and aromatic hydrocarbons, namely, tricosane, octacosane, biphenyl and pyrene, in nonassociated and hydrogen-bonded solvents. The analysis of the relative importance of the different terms contributing to the solubility shows that (1) the fluidization of the solute always represents a barrier to the solubility, (2) in non-hydrogen-bonded solvents, the solubility essentially results from the balance of the exchange entropy correction and the change in the nonspecific cohesion forces upon mixing, (3) in alcohols or in water, the solubility is mainly determined by the hydrophobic effect which corresponds to a solute rejecting effect of the solvent. This effect is responsible for the lower solubility values of the inert substances in associated solvents with respect to those in nonassociated solvents.

Determination of partial and total cohesion parameters of caffeine, theophylline, and methyl p-hydroxybenzoate by gas-solid chromatography.

For the first time, the total and partial solubility parameters, delta t, delta d, and delta s, of caffeine, theophylline, and methyl p-hydroxybenzoate were obtained by gas-solid chromatography (from the adsorption internal energy), by using the Keller, Karger, and Snyder equation. In comparison with the solubilization techniques, this method has the advantage of giving single solubility parameter values. The experimental work has been reduced to a minimum by the optimization of the matrix of experiments, according to the D-criterion, without any diminution in the quality of the results.

Determination of the total and partial cohesion parameters of lipophilic liquids by gas-liquid chromatography and from molecular properties.

The total and partial cohesion parameters of seven lipophilic liquids (one alkane, two alcohols, one acid, and three esters) have been determined. The proposed procedure involves knowledge of the structure, and determination of dipole moment, refractive index, and dielectric constant of the substances. The total cohesion parameters are experimentally determined for four liquids by gas-liquid chromatography, and also calculated for these and three additional liquids according to Fedors by summation of group increments. The dispersion cohesion parameter is calculated from the refractive index, and the polar cohesion parameter by Taft's polarity function, and Carr's relationship. The hydrogen bonding cohesion parameter is then obtained by difference. The results are self-consistent and coherent. In particular, it may be seen that the difference between the various lipophilic liquids, from the point of view of intermolecular interactions, is essentially due to the variation in strength of hydrogen bonds and dipole-dipole interactions, whereas the interactions stemming from the dispersion forces are similar.

Determination of partial solubility parameters of lactose by gas-solid chromatography.

On the basis of the Snyder/Karger-Hansen interaction model, where delta EA = Vi(delta di delta dj + delta pi delta pi + delta hi delta nj), the partial solubility parameters of a solid used as the stationary phase may be determined through gas-solid chromatography by null-injection of solutes with known solubility parameters. Using n-decane, acetonitrile, and 1-propanol as molecular probes, the values found for unhydrated lactose were 9.6, 12.8, 11.3, and 19.5 (cal1/2/cm3/2) for delta d, delta p, delta h, and delta t, respectively; relative standard errors were better than 3%. The choice and the minimum number of the best molecular probes were determined by optimization of the experimental matrix according to the D-criterion, which permits considerable reduction of experimental time yet enhances total precision.

Effects of cholestanol feeding and cholestyramine treatment on the tissue sterols in the rabbit.

Rabbits were fed diets enriched with cholestanol or cholesterol (3.5 g/wk) for 4-12 weeks. During cholestanol feeding, the concentration of cholestanol in blood serum, liver, heart and aorta increased 15-30 times. In serum and liver, the concentration of cholesterol also increased. Cholestanol-fed rabbits developed inflammatory changes in the liver, with proliferation of small bile ducts. Liver tests were only slightly abnormal. Morphological atherosclerosis of the aorta was only occasionally seen in rabbits receiving cholestanol for eight weeks or less. During cholesterol feeding, the amounts of cholesterol in different tissues increased dramatically, most in the aorta. Morphological atherosclerosis in the aorta was found in all rabbits fed cholesterol-enriched diets for more than four weeks. Brain cholestanol was doubled in rabbits fed cholestanol for eight weeks, whereas brain sterols did not change significantly during cholesterol feeding. After an additional regression period with cholestyramine for eight weeks, the increased content of cholestanol in the brain was unchanged in cholestanol-fed rabbits. These observations are discussed in relation to the cholestanolosis of the brain that develops in the rare inherited human disease cerebrotendinous xanthomatosis.

[Health and disease: concepts, values amd practices in everyday life]. / Gesundheit und Krankheit: Sichtweisen, Werthaltungen und Praxisformen im Alltag.

The article deals with the health and illness concepts and values of different social groups. The results are based on a survey of 443 persons, 20 to 65 years old, living in the German or French speaking part of Switzerland. The health and illness concepts and values are analyzed and their impact on the everyday health and illness practices is shown. Based on these results some conclusions concerning health education programs are drawn.

On the mechanism of biosynthesis of cholestanol from 7 alpha-hydroxycholesterol.

In a patient with cerebrotendinous xanthomatosis (CTX), a small part of i.v. administered [7 beta-3H]-7 alpha-hydroxycholesterol was converted into cholestanol. Traces of 3H were also found in plasma cholesterol, but its specific radioactivity was only about 1% of that of cholestanol. When [7 beta-3H]-7 alpha-hydroxycholesterol was given orally to rabbits, significant amounts of 3H were found in cholestanol in different organs. Much less 3H was found in cholesterol. Our results support the conclusion that the pathway from 7 alpha-hydroxycholesterol to cholestanol does not involve cholesterol, but 7 alpha-hydroxy-4-cholesten-3-one and cholesta-4,6-dien-3-one as intermediates.