RESUMO
BACKGROUND: The dyslipidemia associated with obesity plays a major role in the development of atherosclerosis and cardiovascular disease. Dyslipidemia in childhood can progress in adult stage. APOE is one of the most important genes that regulate plasma lipid transport and clearance. The study aimed to assess whether the common APOE polymorphism is associated with lipid profiles and dyslipidemia, and it could be modulated by obesity-related traits (body mass index, waist circumference, hip circumference, and waist-to-hip ratio) in Vietnamese children. METHODS: A case-control study was designed including 249 cases with dyslipidemia and 600 controls without dyslipidemia. Dyslipidemia is defined as elevated total or low-density lipoprotein (LDL) cholesterol levels, or low levels of high-density lipoprotein (HDL) cholesterol. Genotype for APOE polymorphism (rs7412 and rs429358) was determined by the polymerase chain reaction and restriction fragment length polymorphism method. The association of APOE genotypes with plasma lipid disorders was tested by binary logistic regression analysis, taking into account the confounding factors of age, sex, residence, province and obesity-related traits. RESULTS: In comparison with ε3/ε3 carriers, the ε4 carriers had the highest concentration of serum TC and LDL-C in cases and controls (P ≤ 0.001), while ε2 carriers had the lowest. Carriers without TT haplotype had higher serum TC than those with TT haplotype. The ε4 carriers had higher hypoalphalipoproteinemia risk than ε3/ε3 carriers (OR = 2.78, P = 0.02) before and after adjustment for age, gender, residence and obesity-related traits. CONCLUSIONS: The study suggested that the APOE genotype and haplotype significantly associated with plasma TC and LDL-C level in Vietnamese children. The association of APOE genotype with hypoalphalipoproteinemia was independent of obesity-related traits.
Assuntos
Apolipoproteínas E/genética , Aterosclerose/genética , Dislipidemias/genética , Transtornos do Metabolismo dos Lipídeos/genética , Adolescente , Aterosclerose/sangue , Aterosclerose/patologia , Criança , LDL-Colesterol/sangue , LDL-Colesterol/genética , Dislipidemias/sangue , Dislipidemias/patologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Transtornos do Metabolismo dos Lipídeos/sangue , Transtornos do Metabolismo dos Lipídeos/patologia , Lipoproteínas HDL/sangue , Lipoproteínas HDL/genética , Masculino , Obesidade/genética , Obesidade/metabolismo , Polimorfismo de Nucleotídeo Único , Triglicerídeos/sangue , Triglicerídeos/genéticaRESUMO
BACKGROUND: In Vietnam, malnutrition remains a public health problem, even though much progress has been made in the last decades. The number of cases of severe acute malnutrition (SAM) is more than 200,000 per year. To accelerate the treatment of SAM, community-based treatment with ready-to-use-therapeutic foods (RUTFs) is preferred. However, a locally available and acceptable RUTF for the treatment of SAM was lacking. OBJECTIVE: In a joint effort by the National Institute of Nutrition, UNICEF, and the Institut de Recherche pour le Développement, a local RUTF was developed and tested. METHODS: The product was optimalized for impact and acceptability. At the same time, capacity for the Integrated Management of Acute Malnutrition (IMAM) was developed. RESULTS: The local product was found to be highly acceptable and effective. After training of health staff the product could be introduced in the IMAM program. CONCLUSIONS: The IMAM program was highly successful in treating children with SAM, with more than 90% of the children recovering. Production capacity of the factory is currently being increased to enable up-scaling of the IMAM program and potential export of the product to countries in the region.
Assuntos
Fast Foods , Implementação de Plano de Saúde , Desnutrição/terapia , Pré-Escolar , Serviços de Saúde Comunitária/organização & administração , Alimentos Fortificados , Humanos , Lactente , Agências Internacionais , Política Nutricional , Estado Nutricional , VietnãRESUMO
BACKGROUND: To further reduce stunting in Southeast Asia, a rapidly changing region, its main causes need to be identified. OBJECTIVE: Assess the relationship between different causes of stunting and stunting prevalence over time in Southeast Asia. METHODS: Review trends in mortality, stunting, economic development, and access to nutritious foods over time and among different subgroups in Southeast Asian countries. RESULTS: Between 1990-2011, mortality among under-five children declined from 69/1,000 to 29/1,000 live births. Although disease reduction, one of two direct causes of stunting, has played an important role which should be maintained, improvement in meeting nutrient requirements, the other direct cause, is necessary to reduce stunting further. This requires dietary diversity, which is affected by rapidly changing factors: economic development; urbanization, giving greater access to larger variety of foods, including processed and fortified foods; parental education; and modernizing food systems, with increased distance between food producers and consumers. Wealthier consumers are increasingly able to access a more nutritious diet, while poorer consumers need support to improve access, and may also still need better hygiene and sanitation. CONCLUSIONS: In order to accelerate stunting reduction in Southeast Asia, availability and access to nutritious foods should be increased by collaboration between private and public sectors, and the Association of Southeast Asian Nations (ASEAN) can play a facilitating role. The private sector can produce and market nutritious foods, while the public sector sets standards, promotes healthy food choices, and ensures access to nutritious foods for the poorest, e.g, through social safety net programs.
Assuntos
Transtornos do Crescimento/prevenção & controle , Sudeste Asiático/epidemiologia , Mortalidade da Criança , Fenômenos Fisiológicos da Nutrição Infantil , Pré-Escolar , Dieta , Alimentos/economia , Qualidade dos Alimentos , Alimentos Fortificados , Transtornos do Crescimento/epidemiologia , Educação em Saúde , Humanos , Renda , Lactente , Recém-Nascido , Desnutrição/prevenção & controle , Necessidades Nutricionais , Pais/educaçãoRESUMO
Severe acute malnutrition (SAM) remains a main cause of mortality among children under five years old. Vietnam needs further study to establish the optimal mid-upper-arm circumference (MUAC) cutoff for improving the accuracy of the MUAC indicator in screening SAM children aged 6-59 months. A survey was conducted at all 16 subdistricts across four provinces in Northern Midlands and mountainous areas. The data of 4,764 children showed that an optimal MUAC cutoff of 13.5 cm would allow the inclusion of 65% of children with weight-for-height z-scores (WHZs) below -3SD. A combination of MUAC and WHZ may achieve a higher impact on therapeutic feeding programs for SAM children. The MUAC cutoff of 13.5 cm (65% sensitivity and 72% specificity) should be used as the cutoff for improving and/or preventing SAM status among children under 5 in the Midlands and mountainous areas in Vietnam.
RESUMO
BACKGROUND/AIMS: To evaluate the FAO/WHO/UNU equations for predicting resting metabolic rate (RMR) in elderly Vietnamese. METHODS: A cross-sectional study involving healthy and elderly subjects was carried out at the Basic Nutrition Department, National Institute of Nutrition, Vietnam. A total of 75 subjects who had a normal body mass index (BMI) were divided into two groups according to sex. The RMR was measured by indirect calorimetry and anthropometric indices were recorded. Equations derived by linear regression of RMR and body weight were compared to the FAO/WHO/UNU (1985) predictive equations. RESULTS: The mean age of males and females were 65.03 +/- 4.0 and 66.48 +/- 4.61 years, respectively. Mean RMRs (MJ/kg/day) were 0.0963 +/- 0.0121 for males and 0.0925 +/- 0.0117 for females. Compared to the FAO/WHO/UNU equations, our findings were 10.9 and 11.1% lower in males and females, respectively (p < 0.05). CONCLUSION: Our findings suggest that the FAO/WHO/UNU equations may overestimate RMR in elderly Vietnamese. Further studies to find out the most appropriate equation or to establish new predictive equations for RMR in elderly Vietnamese should be conducted.
Assuntos
Metabolismo Basal/fisiologia , Idoso , Antropometria , Povo Asiático , Estudos Transversais , Metabolismo Energético/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vietnã/etnologiaRESUMO
Infants in developing countries are at risk of concurrent micronutrient deficiencies, because the same causative factors may lead to deficiencies of different micronutrients. Inadequate dietary intake is considered one of the major causes of micronutrient deficiencies, especially among poor and underprivileged children in developing countries. Operational strategies and distribution systems are often duplicated when supplementation programs for single micronutrients are implemented at the same time. The International Research on Infant Supplementation (IRIS) trial was conducted in four distinct populations on three continents: Africa, Latin America, and Asia. The participating countries were South Africa, Peru, Vietnam, and Indonesia. The study had a randomized, doubleblind, placebo-controlled design. Each country aimed to enroll at least 70 infants per intervention group (65 + 5 anticipated dropouts). The micronutrient vehicle was in the form of a "foodlet" (food-like tablet) manufactured as chewable tablets, which were easy to break and dissolve, and which had the same taste, color, and flavor for all countries. Children were randomly assigned to one of four 6-month intervention groups: group 1 received a daily foodlet containing multiple micronutrients; group 2 received a daily placebo foodlet containing no micronutrients; group 3 received a weekly foodlet that contained multiple micronutrients (twice the dose of the daily foodlet) and placebo foodlets on the other days of the week; group 4 received a daily foodlet containing only 10 mg of elemental iron. The IRIS Trial aimed to examine the prevalence of multi-micronutrient deficiencies in 6- to 12-month-old infants from rural populations, and to examine the efficacy of multi-micronutrient supplementation in infants from the different countries included in the study. This paper describes the general methodology of the IRIS trial and the operational differences among the country sites.
Assuntos
Deficiências Nutricionais/prevenção & controle , Suplementos Nutricionais , Crescimento , Micronutrientes/administração & dosagem , Biomarcadores/sangue , Comparação Transcultural , Deficiências Nutricionais/sangue , Deficiências Nutricionais/epidemiologia , Método Duplo-Cego , Feminino , Humanos , Indonésia/epidemiologia , Lactente , Transtornos da Nutrição do Lactente/sangue , Transtornos da Nutrição do Lactente/epidemiologia , Transtornos da Nutrição do Lactente/prevenção & controle , Fenômenos Fisiológicos da Nutrição do Lactente , Masculino , Peru/epidemiologia , Saúde da População Rural , África do Sul/epidemiologia , Resultado do Tratamento , Vietnã/epidemiologiaRESUMO
Fortified rice has the potential to improve the micronutrients status of vulnerable populations. However, fortified rice has to have acceptable organoleptic--the sensory properties of a particular food--qualities. Few data exist on the acceptability of fortified rice in Asia. To assess the acceptability of two types of fortified rice (cold and hot extruded) in Vietnam and Cambodia, triangle tests were conducted in Vietnam (53 women) and Cambodia (258 adults), testing fortified rice against conventional rice, with participants being asked to score the organoleptic qualities. In addition, Cambodian schoolchildren (n = 1700) were given conventional rice and two types of fortified rice for two week periods as part of a World Food Program school meal program, with intake monitored. Fortified rice differed significantly in organoleptic qualities from conventional rice, with most subjects correctly identifying fortified rice (P < 0.001). However, fortified rice was found to be highly acceptable in both countries. In Cambodia, schoolchildren consuming fortified rice had higher intakes than when consuming conventional rice (176 g/child/day and 168 g/child/day, respectively; P < 0.05). This study shows that fortified rice is acceptable in two countries in Southeast Asia. However, specific information is needed to explain the organoleptic qualities of fortified rice as perceived by end-users.
Assuntos
Culinária/métodos , Qualidade dos Alimentos , Alimentos Fortificados , Oryza , Paladar , Adolescente , Adulto , Criança , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Targeted fortification programs for infants and young children are an effective strategy to prevent micronutrient deficiencies in developing countries, but the role of large-scale fortification of staple foods and condiments is less clear. Dietary modeling in children aged 6-60 months was undertaken, based on food consumption patterns described in the 2009 national food consumption survey, using a 24-h recall method. Consumption data showed that the median intake of a child for iron, vitamin A and zinc, as a proportion of the Vietnamese Recommended Dietary Allowance (VRDA), is respectively 16%-48%, 14%-49% and 36%-46%, (depending on the age group). Potential fortification vehicles, such as rice, fish/soy sauces and vegetable oil are consumed daily in significant amounts (median: 170 g/capita/day, 4 g/capita/day and 6 g/capita/day, respectively) by over 40% of the children. Vegetable oil fortification could contribute to an additional vitamin A intake of 21%-24% of VRDA recommended nutrient intake, while fortified rice could support the intakes of all the other micronutrients (14%-61% for iron, 4%-11% for zinc and 33%-49% of folate requirements). Other food vehicles, such as wheat flour, which is consumed by 16% of children, could also contribute to efforts to increase micronutrient intakes, although little impact on the prevalence of micronutrient deficiencies can be expected if used alone. The modeling suggests that fortification of vegetable oil, rice and sauces would be an effective strategy to address micronutrient gaps and deficiencies in young children.
Assuntos
Condimentos , Comportamento Alimentar , Alimentos Fortificados , Desnutrição/prevenção & controle , Anemia Ferropriva/prevenção & controle , Pré-Escolar , Análise por Conglomerados , Países em Desenvolvimento , Dieta , Ingestão de Energia , Feminino , Farinha/análise , Humanos , Lactente , Ferro da Dieta/administração & dosagem , Masculino , Micronutrientes/administração & dosagem , Micronutrientes/deficiência , Política Nutricional , Fatores Socioeconômicos , Vietnã , Vitamina A/administração & dosagem , Deficiência de Vitamina A/prevenção & controle , Zinco/administração & dosagem , Zinco/deficiênciaRESUMO
The food based dietary guidelines (FBDGs) is a crucial tool for nutrition education and communication in Vietnam. Together with the changes of socio-economic situation, Vietnam needs to deal with different nutritional problems including malnutrition, overweight and undiversified diets at the same time. From 1995 to the present, three versions of FBDGs have been developed and revised in a period of every 5 years. The FBDGs, Food Guide Pyramid and Food Square made a good set of nutritional education tool which were disseminated through a wide range of activities and communication channels. The evaluation of FBDGs will be carried out before its revisions to reflect eating patterns and lifestyles of consumers whom the nutritional education programs wish to reach. In developing countries like Vietnam, the socio-economic situation is changing over short period of time. Therefore, the assessment of appropriateness and implementation progress of the FBDGs is necessary and should be done after a period of every 5 or 10 years. The implementation of the FBDGs should be closely connected with the activities of the National Plan for Nutrition and should have involvement from multi-sectoral organizations. Training, monitoring and evaluation for implementation of the FBDGs are essential for the success of guiding consumers to convert advices into action. The lessons learned from previous FBDGs' implementation can be used to develop a new version of FBDGs that is more appropriate.
Assuntos
Dieta/métodos , Alimentos , Guias como Assunto , Educação em Saúde/métodos , Política Nutricional , Necessidades Nutricionais , Promoção da Saúde/métodos , Humanos , VietnãRESUMO
This is a follow-up study to an investigation on the prevalence of malnutrition and micronutrient deficiencies among Vietnamese primary schoolchildren. A total of 454 children aged 7 to 8 years attending three primary schools in the Northern delta province of Vietnam were either provided with regular milk, milk fortified with vitamins, minerals and inulin or served as a reference control group. Children were monitored for anthropometrics, (micro)-nutritional status, faecal microbiota composition, school performance, and health indices. Both weight-for-age (WAZ) and height-for-age (HAZ) significantly improved during 6 months of milk intervention; and underweight and stunting dropped by 10% in these groups. During intervention the incidence of anemia decreased and serum ferritin levels increased significantly in all groups. Serum zinc levels increased and consequently the incidence of zinc deficiency improved significantly in all three groups. Serum retinol levels and urine iodine levels remained stable upon intervention with fortified milk whereas in the control group the incidence of iodine deficiency increased. Bifidobacteria composed less than 1% of the total faecal bacteria. After three months of milk intervention total bacteria, bifidobacteria and Bacteroides sp. increased significantly in both milk and inulin fortified milk groups. Children in the milk consuming groups had significantly better short-term memory scores. Parent reported that health related quality of life status significantly improved upon milk intervention. In conclusion, (fortified) milk consumption benefited the children in rural Vietnam including lowering the occurrence of underweight and stunting, improving micronutrients status and better learning indicators as well as improving the quality of life.
Assuntos
Alimentos Fortificados , Indicadores Básicos de Saúde , Memória de Curto Prazo , Leite , Estado Nutricional , População Rural , Anemia/prevenção & controle , Animais , Estatura , Criança , Transtornos da Nutrição Infantil/prevenção & controle , Dieta , Fezes/microbiologia , Feminino , Seguimentos , Humanos , Inulina/administração & dosagem , Masculino , Micronutrientes/administração & dosagem , Micronutrientes/sangue , Micronutrientes/urina , Leite/química , Qualidade de Vida , Inquéritos e Questionários , Magreza/prevenção & controle , VietnãRESUMO
The prevalence of trace elements deficiencies, vitamin A deficiency, anemia, and their relationships were investigated in a cross sectional study involving 243 children aged from 12 to 72 months in rural Vietnam. Serum levels of copper, zinc, selenium and magnesium were determined by inductively coupled plasma mass spectrometer and that of retinol by high performance liquid chromatography. Hemoglobin concentration in whole blood was measured by the cyanmethemoglobin method. The prevalence of deficiencies in zinc, selenium, magnesium, and copper was 86.9%, 62.3%, 51.9%, and 1.7%, respectively. On the other hand, 55.6% were anemic and 11.3% had vitamin A deficiency. Deficiency in two or more micronutrient was found in 79.4% of the children. Parameters associated significantly with anemia were selenium deficiency (OR 2.80 95% CI 1.63-4.80, p=0.0002) and serum retinol<1.05 micromol/L (OR 1.83, 95% CI 1.10-3.05, p=0.021). Magnesium deficiency (OR 3.09 95% CI 1.36-7.03) was found to be a risk factor for zinc deficiency and vice versa. The results indicate that micronutrient deficiencies are prevalent among preschool children in Vietnam. In addition, the results also demonstrate a strong relationship between selenium deficiency and anemia. Clearly, sustainable strategies are urgently required to overcome the problems in the country.
Assuntos
Anemia Ferropriva/epidemiologia , Micronutrientes/sangue , Micronutrientes/deficiência , Estado Nutricional , População Rural/estatística & dados numéricos , Deficiência de Vitamina A/epidemiologia , Anemia Ferropriva/sangue , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Intervalos de Confiança , Estudos Transversais , Feminino , Hemoglobinas/análise , Humanos , Lactente , Magnésio/sangue , Deficiência de Magnésio/sangue , Deficiência de Magnésio/epidemiologia , Masculino , Razão de Chances , Prevalência , Fatores de Risco , Selênio/sangue , Selênio/deficiência , Vietnã/epidemiologia , Deficiência de Vitamina A/sangue , Zinco/sangue , Zinco/deficiênciaRESUMO
Over the years many approaches have been used in communication for behavioral changes in nutrition. The overall aim of this study was to provide practical insights into how participatory, audience-centered communication activities can be effectively used for imparting information and for behavioral change promotion on the topic of dietary diversity and micronutrient nutrition, among reproductive-age women in Vietnam. The communication initiatives for improving nutrition knowledge and practices of the women in two selected communes (Dongky and Donglac) in Bacgiang province were carried out from January, 2003 to December, 2005. The Dongky commune was selected as the intervention commune, while the Donglac commune served as the control. In the intervention commune of Dongky the problems and strategies of nutrition communication and education were defined, IEC materials and some seeds of iron-rich vegetables and fruits were provided. Besides that, a contest on nutrition knowledge at a primary school and a competition between nutrition collaborators were held. The results of the study showed that food consumption of the women in both communes improved compared to levels at the baseline survey, especially in the intervention commune. The total knowledge scores and the nutrition practices of the women in the Dongky commune significantly improved compared to the data at baseline and were higher compared to that of the control commune.
RESUMO
A randomized, double-blind, placebo-controlled trial was performed to assess the efficacy of different micronutrient supplementation regimes for improving micronutrient status, preventing anemia, and growth faltering of Vietnamese infants. A population-based sample of 306 infants aged 6-12 mo, split in 4 treatment groups, received daily multiple micronutrient (DMM), daily placebo (P), weekly multiple micronutrient (WMM), or daily iron (DI) supplements for 6 mo, 7 d/wk, under supervision. Weight and length were measured monthly, and anemia and plasma levels of ferritin, zinc, riboflavin, retinol, tocopherol, and homocysteine were determined before and after the supplementation. Z-scores for length-for-age and weight-for-age worsened significantly in all groups, but the length-for-age Z-score decreased significantly less in the DMM group (-0.32 +/- 0.05) than in the P and WMM groups (-0.49 +/- 0.05 and -0.51 +/- 0.05, respectively, P = 0.001). Hemoglobin levels increased significantly more in the DMM group [mean (95%CI): 16.4 g/L (12.4-20.4)] than in the P group [8.6 g/L (5.0-12.2), P = 0.04), with intermediate nonsignificant increases in the WMM [15.0 g/L (11.5-18.5)] and the DI [12.9 g/L (8.4-17.3)] groups. Ferritin changes were significantly greater in DMM (12.1 microg/L) and DI (9.5 microg/L) than in P (-14.7 microg/L) and WMM groups (-9.7 microg/L). Of the other micronutrients, only tocopherol showed a significantly greater level in the DMM group compared with P. Anemia still affected a quarter and zinc deficiency affected a third of infants although there was no iron deficiency after 6 mo of supplementation with DMM, suggesting that multiple factors are causing anemia and that the dose of zinc is too small.
Assuntos
Anemia/prevenção & controle , Suplementos Nutricionais , Crescimento/fisiologia , Alimentos Infantis , Micronutrientes , Método Duplo-Cego , Ingestão de Energia , Feminino , Homocisteína/sangue , Humanos , Lactente , Masculino , Estado Nutricional , Placebos , Tocoferóis/sangue , Vietnã , Vitamina A/sangue , Zinco/sangueRESUMO
Diets of infants across the world are commonly deficient in multiple micronutrients during the period of growth faltering and dietary transition from milk to solid foods. A randomized placebo controlled trial was carried out in Indonesia, Peru, South Africa, and Vietnam, using a common protocol to investigate whether improving status for multiple micronutrients prevented growth faltering and anemia during infancy. The results of the pooled data analysis of the 4 countries for growth, anemia, and micronutrient status are reported. A total of 1134 infants were randomized to 4 treatment groups, with 283 receiving a daily placebo (P), 283 receiving a weekly multiple micronutrient supplement (WMM), 280 received a daily multiple micronutrient (DMM) supplement, and 288 received daily iron (DI) supplements. The DMM group had a significantly greater weight gain, growing at an average rate of 207 g/mo compared with 192 g/mo for the WMM group, and 186 g/mo for the DI and P groups. There were no differences in height gain. DMM was also the most effective treatment for controlling anemia and iron deficiency, besides improving zinc, retinol, tocopherol, and riboflavin status. DI supplementation alone increased zinc deficiency. The prevalence of multiple micronutrient deficiencies at baseline was high, with anemia affecting the majority, and was not fully controlled even after 6 mo of supplementation. These positive results indicate the need for larger effectiveness trials to examine how to deliver supplements at the program scale and to estimate cost benefits. Consideration should also be given to increasing the dosages of micronutrients being delivered in the foodlets.
Assuntos
Anemia/prevenção & controle , Países em Desenvolvimento , Dieta , Suplementos Nutricionais , Transtornos do Crescimento/prevenção & controle , Micronutrientes , Geografia , Humanos , Indonésia , Lactente , Peru , Ensaios Clínicos Controlados Aleatórios como Assunto , África do Sul , VietnãRESUMO
The objective of this paper is to review programs to improve production of animal source foods in Vietnam, emphasizing the VAC ecosystem and trends in undernutrition during past decades. The food consumption surveys of the Vietnamese population in 1985 showed that food intake was inadequate, especially animal protein. Most protein came from rice; the consumption of meats, beans and fish was negligible. During the last 10 y, much attention was paid to improving the health and nutritional status of the Vietnamese people. Many programs were implemented in Vietnam to improve the food intake and nutritional status of the people, and especially the intake of animal source foods. The VAC system is a traditional type of farming for Vietnamese people. The aim of VAC is to provide diversified agricultural products to meet the complex nutritional demands of man. Based on the scientific fundamentals of VAC, many different models of VAC have been developed at a national level. The intervention programs to improve production and consumption of animal source foods, and the VAC ecosystem in Vietnam during the last decade have been successful. The population's dietary intakes have clearly improved in terms of both quality and quantity. The consumption of staple foods in 2000, including meats, fish, fats and oils, and ripe fruits was much higher compared to 1987. The prevalence of undernutrition in children <5 y old, and of chronic energy deficiency (CED) in women of reproductive age, has been remarkably reduced.