High proportions of older people with normal nutritional status have poor protein intake and low diet quality.

INTRODUCTION: The Mini Nutritional Assessment (MNA) is a well-validated instrument examining the nutritional status of older people. The aim of this study was to examine how older people's energy and nutrient intakes are associated with the MNA and to determine how sensitive and specific MNA is in identifying those having low energy and protein intakes. MATERIALS AND METHODS: This cross-sectional study combined data from five nutritional studies (N=900): both home-dwelling and institutionalized older people without and with disabilities. Their nutritional status was assessed with MNA, and nutrient intakes were retrieved from 1 to 3day food diaries. Nutrient intakes were divided according to MNA status (normal nutritional status, at-risk of malnutrition, malnourished). Sensitivity, specificity, and likelihood ratios of MNA of various cut-off points were tested with recommended protein and energy intakes. ROC curves was constructed. RESULTS: Energy, protein and most nutrient intakes showed logical linear trends according to MNA classes. However, more than three-fourths of the participants with MNA>23.5 had lower than recommended protein intakes. Sensitivity of MNA ranged from 0.32 to 0.82 for recommended energy (F:1570kcal/d/M:2070kcal/d) and protein intakes (1.0g/kg BW or 1.2g/kgBW) cut-off points, and specificity from 0.75 to 0.25, respectively. AUC values were low (0.52-0.53). CONCLUSIONS: MNA status was consistently associated with nutrient intakes and diet quality. However, a high proportion of older people even with normal nutritional status had poor energy and protein intakes. Thus, MNA does not identify all those with poor nutrient intakes who may be at risk of developing malnutrition.

Nutritional Guidance Improves Nutrient Intake and Quality of Life, and May Prevent Falls in Aged Persons with Alzheimer Disease Living with a Spouse (NuAD Trial).

OBJECTIVE: The aim was to examine the effect of tailored nutritional guidance on nutrition, health-related quality of life (HRQoL) and falls in persons with Alzheimer disease (AD). DESIGN: Randomised controlled trial. SETTING AND PARTICIPANTS: Persons with AD living with a spouse. INTERVENTION: Tailored nutritional guidance with home visits during one year. The control group received a written guide about nutrition in older adults and all community-provided normal care. MEASUREMENTS: The primary outcome measure was weight change, and secondary outcomes included changes in protein and micronutrient intakes from three-day food records, HRQoL (15D) and rate of falls. RESULTS: Of the participants (n = 78) with AD (mean age 77.4, 69% males), 40% were at risk for malnutrition, 77% received < 1.2 g/bodyweight (kg) of protein at baseline. We found no difference in weight change between the groups. At 12 months, the mean change in protein intake was 0.05 g/bodyweight (kg) (95% CI -0.06 to 0.15) in the intervention group (IG), and -0.06 g/kg (95% CI -0.12 to 0.02) in the control group (CG) (p = 0.031, adjusted for baseline value, age, sex, MMSE and BMI). Participants' HRQoL improved by 0.006 (95% CI -0.016 to 0.028) in the IG, but declined by -0.036 (95% CI -0.059 to 0.013) in the CG (p = 0.007, adjusted for baseline value, age, sex, MMSE and BMI). Dimensions that differed included mental functioning, breathing, usual activities and depression. The fall rate was 0.55 falls/person per year (95% CI 0.34 to 0.83) in the IG, and 1.39 falls/person per year (95% CI 1.04 to 1.82) in the CG (IRR 0.55; 95% CI 2.16 to 6.46; p < 0.001 adjusted for age, sex and MMSE). CONCLUSIONS: Tailored nutritional guidance improves nutrition and HRQoL, and may prevent falls among AD people living with a spouse.

Low protein and micronutrient intakes in heterogeneous older population samples.

BACKGROUND: Malnutrition is associated with comorbidities and functional decline among older people. Less is known about nutrient intakes across heterogeneous older populations. OBJECTIVE: We examined nutritional status and nutrient intakes in different samples of older people representing broad spectrum of healthy and frail populations. We evaluated adequacy of their energy, protein and micronutrient intakes in comparison to recommendations. DESIGN AND PARTICIPANTS: Cross-sectional study combined five datasets: home-dwelling older people participating in nutrition education and cooking classes (NC) [n=54], participants from Helsinki Businessmen Study [n=68], home-dwelling people with Alzheimer disease (AD) [n=99] and their spousal caregivers (n=97), participants from Porvoo Sarcopenia and Nutrition Trial (n=208), and residents of Helsinki assisted living facilities (ALF) [n=374]. Nutritional status was assessed using Mini Nutritional Assessment and nutrient intakes retrieved from 1 to 3 day food records. RESULTS: Those suffering most from mobility limitation and cognitive decline had the poorest nutritional status (p<0.001; adjusted for age, sex, comorbidities). However, low intakes of energy, protein, and micronutrients were observed in high proportion in all groups, inadequate intakes of vitamins D, E, folate, and thiamine being most common. Protein intakes did not differ between the groups, but 77% of all participants had lower than recommended protein intake. In general, the NC group had highest micronutrient intakes and the ALF group the lowest. However, AD females had the lowest energy, protein, and vitamin C intakes. CONCLUSIONS: Our study provides a detailed picture of risks related to nutrient intakes in various groups of older people. These findings could be used in planning tailored nutrition interventions.

Tailored nutritional guidance for home-dwelling AD families: the Feasibility of and Elements Promoting Positive Changes in Diet (NuAD-Trial).

OBJECTIVES: To describe the process and feasibility of our randomised, controlled intervention study (NuAD trial) that positively affected the nutrition and quality of life, and prevented falls of home-dwelling persons with Alzheimer disease (AD). DESIGN, SETTING, PARTICIPANTS: This qualitative study comprised 40 persons with AD and spousal caregivers of our trial. Our intervention during one year involved tailored nutritional guidance for these couples. The nutritionist's field notes (about 100 pages) and the participant feedback questionnaires (N = 28) served to analyse the feasibility of intervention, factors promoting the application of intervention and challenges hindering it. Thematic content analysis served to analyse our data with the grounded theory approach. RESULTS: We identified several positive elements promoting better nutrition: positive attitudes on nutrition to participants including a participant-centred approach, positive feedback, findings of food diaries and practical suggestions. Home visits by the nutritionist were convenient and participants felt that someone cares. Group meetings which included protein-rich snacks strengthened the nutritional message by enabling discussions and socialising. The oral nutritional supplements (ONS) helped participants to regain their energy and to motivate them to exercise and make changes in their diets. Obstacles to making changes in diets included participants' false ideas about nutrition, especially with regard to weight gain. Health problems and functional limitations hampered food management, and some families had inveterate eating habits. The positive feedback from participants indicated the feasibility of our tailored nutritional guidance. CONCLUSIONS: Assessment-based, tailored nutritional guidance implemented with a personal and positive approach may inspire and empower AD families to make positive changes in their diets, leading them to improved nutrition and quality of life.

Caregivers' male gender is associated with poor nutrient intake in AD families (NuAD-trial).

OBJECTIVE: Alzheimer patients (AD) are known to be at risk for malnutrition and their older spouses may also have nutritional problems. The aim of our study was to clarify the association of caregivers' sex on the nutrient intake of AD couples. SETTING: Our study uses the baseline data of a randomized nutritional trial exploring the effectiveness of nutrition intervention among home-dwelling AD patients. PARTICIPANTS: The central AD register in Finland was used to recruit AD patients living with a spousal caregiver, 99 couples participated in our study. MEASUREMENTS: Nutritional status was assessed using the Mini-Nutritional Assessment (MNA). Nutrient intakes for both AD patients and their spouses were calculated from 3-day food diaries. RESULTS: The mean age of caregivers and AD spouses was 75.2 (SD 7.0) and 77.4 years (SD 5.6), respectively. According to the MNA, 40% of male and 52% of female AD spouses were at risk for malnutrition. Among male caregivers, the mean energy and protein intakes were 1605 kcal (SD 458) and 0.93 g/body kg (SD 0.30), whereas the respective figures for their female AD spouses were 1313 kcal (SD 340) and 0.86 g/body kg (SD 0.32), respectively. Among female caregivers, the mean energy and protein intakes were 1536 kcal (SD 402) and 1.00 g/body kg (SD 0.30), whereas the respective figures for their male AD spouses were 1897 kcal (SD 416) and 1.04 g/body kg (SD 0.30). The interaction between male caregiver sex and lower energy (p<0.001) and lower protein intake (p=0.0048) (adjusted for age and MMSE) was significant. Similar differences between caregiver sexes were observed with the intake of various nutrients. CONCLUSIONS: A gender difference exists in the ability to cope with caregiver responsibilities related to nutrition. A need exists for tailored nutritional guidance among older individuals and especially among male caregivers.

Hydrolysis and composition of recovered fibres fractionated from solid recovered fuel.

Fibres fractionated from solid recovered fuel (SRF), a standardised market combustion fuel produced from sorted waste, were considered as a source of lignocellulosic fermentable sugars. The fibre yield from four samples of SRF was 25-45%, and the separated material consisted of 52-54% carbohydrates, mainly glucan, with a high content of ash (12-17%). The enzymatic digestibility of recovered fibres was studied at low and high solids loading and compared with model substrates containing only chemical and mechanical pulps. Above 80% hydrolysis yield was reached at 20% solids loading in 48 h, but variation was observed between different samples of recovered fibres. Surfactants were found to improve the hydrolysis yield of recovered fibres especially in tumbling-type of mixing at low solids loading, where hydrolysis was found to stagnate without surfactants. The results suggest that SRF is a potential source of easily digestible lignocellulosic carbohydrates for use in biorefineries.

Nutritional Intervention Via Videoconferencing for Older Adults Receiving Home Care - A Pilot Study.

BACKGROUND: Malnutrition is common in aged home care clients and that affects negatively the health of aged people. Nutritional screening is recommended for early detection of malnutrition. OBJECTIVES: The aim was to assess the nutritional status and food intake of home care receivers and improve their nutrient intake with tailored nutritional advice administered via videoconferencing. DESIGN: Intervention with follow-up. SETTING: Home care in the city of Helsinki. PARTICIPANTS: 25 older (>65 years) adults receiving home care. INTERVENTION: After an initial assessment determining their needs, participants received tailored nutritional advice via videoconferencing over a six-month follow-up period. MEASUREMENTS: Participants nutritional status was assessed with a Mini Nutritional Assessment -test (MNA). Nutrient intake was calculated based on a detailed three-day food diary compiled twice during the six-month follow-up period. RESULTS: Altogether 25 persons participated in the study (mean age 78.5 years, 88 % females). According to the MNA test 80 % were at risk of malnutrition at the outset. Energy (1329 kcal) and mean nutrient intakes of protein (54 g) and folic acid (210 µg), for example, were inadequate. After six months of intervention, the mean energy intake had increased to 1450 (SD 319) kcal, protein to 65 (SD 20) g, and folic acid to 231 (SD 105) µg per day. CONCLUSIONS: The energy, protein and other nutrient intake of the study participants increased during the six-month intervention. Videoconferencing seemed to be a well-accepted and feasible method for providing nutritional advice to older home care clients.

Characterization of molecular and catalytic properties of intact and truncated human 17beta-hydroxysteroid dehydrogenase type 2 enzymes: intracellular localization of the wild-type enzyme in the endoplasmic reticulum.

Human 17beta-hydroxysteroid dehydrogenase (17HSD) type 2 is a widely distributed enzyme that primarily converts the highly active 17beta-hydroxysteroids to their inactive keto forms. In the present study, full-length human 17HSD type 2 was localized in the endoplasmic reticulum using a double immunofluorescence labeling technique. As a consequence of its strong membrane interaction, full-length human 17HSD type 2 could not be solubilized as a biologically active form in vitro. However, by deleting the first 29 amino acids from the N-terminus, we were able to purify a catalytically active enzyme from the cytosolic fraction of Sf9 insect cells. Biochemical and catalytic properties of the purified truncated human 17HSD type 2 protein confirm its suitability for structure-function analyses of the enzyme. Both intact and truncated 17HSD type 2 enzymes efficiently catalyzed the oxidation of estradiol, testosterone, dihydrotestosterone, androstenediol, and 20alpha-dihydroprogesterone. The oxidation of estradiol brought about by human 17HSD type 2 was effectively inhibited by several other steroidal compounds, such as 2-hydroxyestradiol, 5beta-androstan-3alpha,17beta-diol, 5alpha-androstan-3alpha,17beta-diol, and 5alpha-androstan-3beta,17beta-diol. The broad substrate specificity of human 17HSD type 2 together with its predominant oxidative activity and intracellular location, as observed in this study, indicate the physiological role of the enzyme to be primarily an inactivator of highly active 17beta-hydroxysteroids.

Structure of the ternary complex of human 17beta-hydroxysteroid dehydrogenase type 1 with 3-hydroxyestra-1,3,5,7-tetraen-17-one (equilin) and NADP+.

Excess 17beta-estradiol (E2), the most potent of human estrogens, is known to act as a stimulus for the growth of breast tumors. Human estrogenic 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1), which catalyzes the reduction of inactive estrone (E1) to the active 17beta-estradiol in breast tissues, is a key enzyme responsible for elevated levels of E2 in breast tumor tissues. We present here the structure of the ternary complex of 17beta-HSD1 with the cofactor NADP+ and 3-hydroxyestra-1,3,5,7-tetraen-17-one (equilin), an equine estrogen used in estrogen replacement therapy. The ternary complex has been crystallized with a homodimer, the active form of the enzyme, in the asymmetric unit. Structural and kinetic data presented here show that the 17beta-HSD1-catalyzed reduction of E1 to E2 in vitro is specifically inhibited by equilin. The crystal structure determined at 3.0-A resolution reveals that the equilin molecule is bound at the active site in a mode similar to the binding of substrate. The orientation of the 17-keto group with respect to the nicotinamide ring of NADP+ and catalytic residues Tyr-155 and Ser-142 is different from that of E2 in the 17beta-HSD1-E2 complex. The ligand and substrate-entry loop densities are well defined in one subunit. The substrate-entry loop adopts a closed conformation in this subunit. The result demonstrates that binding of equilin at the active site of 17beta-HSD1 is the basis for inhibition of E1-to-E2 reduction by this equine estrogen in vitro. One possible outcome of estrogen replacement therapy in vivo could be reduction of E2 levels in breast tissues and hence the reduced risk of estrogen-dependent breast cancer.

Origin of substrate specificity of human and rat 17beta-hydroxysteroid dehydrogenase type 1, using chimeric enzymes and site-directed substitutions.

Human 17beta-hydroxysteroid dehydrogenase (17-HSD) type 1 predominantly catalyzes the 17beta-reduction of estrone to estradiol. The present results, however, show that rat 17-HSD type 1 equally uses both estrone and androstenedione as substrates. Analyzing the activity of various rat/human chimeric enzymes indicated that the region between amino acids 148 and 268 is responsible for the difference in substrate specificity, which is in line with the structural data showing that the recognition end of the active site is primarily at residues 185-230. The enzymes are highly conserved between amino acids 148-191, and the data indicate that in this region Asn152HisAsp153Glu and Pro187Ala variations are most closely related to the differential steroid specificity. The structural analyses furthermore suggested that the presence of His instead of Asn at position 152 of the human enzyme might result in considerable rearrangement of the loop located close to the beta-face of the A- and B-rings of the bound substrate, and that the Pro187Ala variation could modify the flexible region involved in substrate recognition and access of the substrate to the active site. Altogether, our results indicate that the Asn152His and Pro187Ala variations, together with several amino acid variations at the recognition end of the catalytic cleft built by residues 190-230, alter the structure of the active site of rat 17-HSD type 1 to one more favorable to an androgenic substrate.

Characterization of structural and functional properties of human 17 beta-hydroxysteroid dehydrogenase type 1 using recombinant enzymes and site-directed mutagenesis.

Human 17 beta-hydroxysteroid dehydrogenase (17-HSD) type 1 catalyzes the conversion of the low activity estrogen, estrone, into highly active estradiol, both in the gonads and in target tissues. The present study was carried out to characterize the dimerization, microheterogeneity, and phosphorylation of human 17-HSD type 1 and to evaluate the current model of hydride transfer and substrate recognition of the enzyme, based on its x-ray structure. 17-HSD type 1 is a homodimer consisting of noncovalently bound subunits, and the data in the present study indicate an exceptionally strong association between the monomers [dissociation constant (Kd) < 5 pmol/monomers liter]. Furthermore, substitutions constructed at the hydrophobic dimer interface always resulted in inactive aggregates of the protein. The enzyme was shown to be phosphorylated by protein kinase A exclusively at Ser134 only in vitro. However, in contrast to previous suggestions, phosphorylation of Ser134 was shown to play no role in the activity or microheterogeneity of human 17-HSD type 1. The presence of microheterogeneity in the recombinant enzyme also indicates that it does not result from the frequent protein polymorphism previously found for the enzyme. In line with the x-ray structure and the proposed catalytic mechanism of the enzyme, our results indicate that Ser142, Tyr155, and Lys159 are all critical for hydride transfer in human 17-HSD type 1. In contrast, the proposed interaction between His221, Glu282, and the 3-OH group of the steroid at the substrate recognition helix could not be shown to exist. Neither of these residues plays a critical role in the catalytic action of the enzyme in cultured cells.

Molecular cloning of mouse 17 beta-hydroxysteroid dehydrogenase type 1 and characterization of enzyme activity.

The biological activity of certain estrogens and androgens is modulated by enzymes called 17 beta-hydroxysteroid dehydrogenases (17 beta-HSDs), which catalyze the interconversion between less active 17-oxosteroid and more active 17 beta-hydroxysteroid forms. In the present report, we describe cloning of mouse 17 beta-HSD type-1 cDNA from an ovarian library generated from 4,4'-(1,2-diethyl-1,2-ethenediyl)bisphenol-(diethylstilbestrol)-tr eated mice, and characterization of the corresponding enzyme. The open reading frame of the mouse 17 beta-HSD type-1 cDNA encodes a peptide of 344 amino acid residues with a predicted molecular mass of 36785 Da. The mouse 17 beta-HSD type-1 enzyme shares 63% and 93% overall identity with human and rat 17 beta-HSD type-1 enzymes, respectively, and the most striking differences between the mouse and human type-1 enzymes are between the amino acid residues 197 and 230 and in the carboxy terminus of the enzymes. Similarly to the human 17 beta-HSD type-1 enzyme, the mouse type-1 enzyme primarily catalyzes reductive reactions from 17-oxo forms to 17 beta-hydroxy forms in intact cultured cells, but unlike the human type-1 enzyme, the mouse enzyme does not prefer phenolic over neutral substrates. Thus, mouse 17 beta-HSD type 1 catalyzes reduction of androst-4-ene-3,17-dione (androstenedione) to 17 beta-hydroxyandrost-4-en-3-one (testosterone) as efficiently as 3 beta-hydroxyestra-1,3,5(10)-trien-17-one (estrone) to estra-1,3,5(10)-triene-3 beta, 17 beta-diol (estradiol). 17 beta-HSD type 1 is predominantly expressed in mouse ovaries, in which it is located in granulosa cells.

Site-directed mutagenesis of the putative active site of human 17 beta-hydroxysteroid dehydrogenase type 1.

Several amino acid residues (Cys54, Tyr155, His210, His213 and His221) at a putative catalytic site of human 17 beta-hydroxysteroid dehydrogenase type 1 were mutated to Ala. Replacement of His221 by Ala remarkably reduced the catalytic activity, which resulted from a change of both the Km and the Vmax. values of the enzyme. Compared with the wild-type enzyme, the catalytic efficiency of the His221-->Ala mutant was reduced 20-fold for the oxidative reaction and 11-fold for the reductive reaction. With similar mutations at His210 or His213, no notable effects on the catalytic properties of the enzyme were detected. However, a simultaneous mutation of these amino acid residues decreased the Vmax. values of both oxidation and reduction by about 50% from those measured for the wild-type enzyme. Although Cys54 has been localized in the cofactor-binding region of the enzyme, a Cys54-->Ala mutation did not lead to changes in the enzymic activity. The most dramatic effects on the catalytic properties of the enzyme were achieved by mutating Tyr155, which resulted in an almost completely inactivation of the enzyme. The decreased enzymic activities of the Tyr155-->Ala, His210-->Ala + His213-->Ala and His221-->Ala mutations were also reflected in a reduced immunoreactivity of the enzymes. The results thus suggest that the lower catalytic efficiency of the mutant enzymes is due to an exchange of catalytically important amino acid residues and/or remarkable alterations in the three-dimensional structure of the enzyme. The recently detected polymorphisms (Ala237<-->Val and Ser312<-->Gly) were not found to affect either the catalytic or the immunological properties of the type 1 enzyme.