Chicken soup for the skin!

Chicken soup is a worldwide dish used in folk medicine to treat respiratory infections. In ancient and medieval times, it was used to treat leprosy. Anecdotally, it is claimed that chicken soup promotes healthy skin because it is rich in collagen and hyaluronic acid. One clinical study found that consumption of chicken soup by human individuals increased skin elasticity and decreased facial pigmentation. More research is needed to confirm these benefits and better define the role chicken soup consumption might have in promoting healthy, youthful skin.

Avaliação do desempenho de oleogéis estruturados com ceras vegetais como base lipídica reduzida em ácidos graxos saturados aplicados em cream cheeses / Performance evaluation of structured oleogels with vegetable waxes as a reduced lipid base in saturated fatty acids applied in cream cheeses

Diante das exigências crescentes das agências regulatórias do mundo todo quanto à redução/eliminação de ácidos graxos trans nos alimentos industrializados, bem como da conscientização do consumidor sobre a relação entre alimentação e saúde, o desenvolvimento de alternativas mais saudáveis aos óleos parcialmente hidrogenados e a outras fontes lipídicas com alto grau de saturaçã o se faz necessário. O oleogel, um sistema composto por um óleo preso em uma rede tridimensional formada por um agente estruturante, se apresenta como uma solução promissora. Dentre os diversos agentes estruturantes, as ceras vegetais se destacam por sua excelente capacidade de gelificação de óleos. Contudo, apresentam uma desvantagem sob o aspecto sensorial, pois podem conferir cerosidade e sabor residual desagradável aos alimentos. Com o objetivo de viabilizar o uso das ceras como agentes estruturantes em oleogéis face ao seu excelente desempenho tecnológico, este projeto propõe o estudo e a aplicação de oleogéis à base de óleo de soja (SBO) estruturado com ceras de farelo de arroz (RBW) a 2 e 4 % (m/m) ou carnaúba (CBW) a 3 e 6% (m/m), isoladamente. As matérias-primas foram caracterizadas e o comportamento de gelificação de cada cera foi avaliado por análises de textura por penetração de cone, estabilidade à perda de óleo por centrifugação, energia coesiva por parâmetro de solubilidade de Hansen (HSP) e comportamento de cristalização e fusão por calorimetria exploratória diferencial (DSC). Os resultados mostraram que ambas as ceras são capazes de formar oleogéis estruturalmente estáveis, contudo, o oleogel com 2% de RBW apresentou maior firmeza a 20 °C (190,4 gf/cm2) do que o oleogel com 6% de CBW a 5 °C (186,1 gf/cm2). Ao final de 5 dias, a capacidade de retenção de óleo do oleogel preparado com RBW foi de 100% às concentrações de 2 e 4% (m/m), contra 61 e 99,3% do oleogel elaborado com CBW às concentrações de 3 e 6% (m/m), respectivamente. Esses resultados podem ser explicados pela diferença entre as energias coesivas, ou seja, do grau de interação molecular entre o solvente e o soluto de cada oleogel. De acordo com os resultados de distância, que prevê se o gel formado será forte, fraco ou se não haverá formação de gel, o soluto CBW apresentou menor interação com o óleo (3,3 MPa1/2) do que o soluto RBW (3,7 MPa1/2). Os oleogéis foram aplicados como ingredientes em diferentes formulações de cream cheese, que foram analisados quanto a diferentes parâmetros de textura e esses resultados foram comparados a uma referência comercial. Nenhuma das amostras produzidas obteve resultados de textura estatisticamente iguais aos do cream cheese comercial (CC), o que pode ser explicado pelas diferenças de formulação e processamento dos produtos. Face aos resultados para textura e estabilidade à perda de óleo dos oleogéis de RBW, este agente estruturante apresenta ria maior potencial de aplicação, porém o oleogel CBW6 obteve alta capacidade de retenção de óleo (99,3%) e quando aplicado na formulação de cream cheese (CCBW6) apresentou resultados de firmeza e espalhabilidade mais próximos da amostra de referência, feita com gordura do leite (CMF)

Given the growing demands of regulatory agencies around the world regarding the reduction/elimination of trans fatty acids in processed foods, as well as consumer awareness about the relationship between food and health, the development of healthier alternatives to partially hydrogenated oils and others lipid sources with a high degree of saturation are necessary. Oleogel, a system composed of an oil trapped in a three-dimensional network formed by a structuring agent, presents itself as a promising solution. Among the various structuring agents, vegetable waxes stand out for their excellent oil gelling capacity. However, they have a sensory disadvantage, as they can give waxy and unpleasant aftertaste to foods. Aiming at enabling the use of waxes as structuring agents in oleogels in view of their excellent technological performance, this study proposes the evaluation and application of oleogels based on soybean oil (SBO) structured with rice bran wax (RBW) at 2 and 4% (m/m) or carnauba (CBW) at 3 and 6% (m/m). The raw materials were characterized and the gelling behavior of each wax was evaluated by analysis of texture by cone penetration, stability to oil loss by centrifugation, cohesive energy by Hansen solubility parameter (HSP) and crystallization and melting behavior. by differential scanning calorimetry (DSC). The results showed that both waxes are able to form structurally stable oleogels, however, oleogel with 2% RBW showed greater firmness at 20 °C (190.4 gf/cm2) than oleogel with 6% CBW at 5° C (186.1 gf/cm2). At the end of 5 days, the oil retention capacity of oleogel prepared with RBW was 100% at concentrations of 2 and 4% (m/m), against 61 and 99.3% of oleogel prepared with CBW at concentrations of 3 and 6% (m/m), respectively. These results can be explained by the difference between the cohesive energies, that is, the degree of molecular interaction between the solvent and the solute of each oleogel. According to the distance results, which predicts if the formed gel will be strong, weak or if there will be no gel formation, the CBW solute showed less interaction with the oil (3.3 MPa1/2) than the RBW solute (3 ,7 MPa1/2). Oleogels were applied as ingredients in different cream cheese formulations, which were analyzed for different texture parameters and these results were compared to a commercial reference. None of the samples produced had texture results statistically equal to those of commercial cream cheese (CC), which can be explained by the differences in formulation and processing of the products. Given the results for texture and oil binding capacity of RBW oleogels, this structuring agent would present greater application potential, but CBW6 oleogel obtained high oil biding capacity (99.3%) and when applied in cream cheese formulation (CCBW6) showed firmness and spreadability results closer to the reference sample, made with milk fat (CMF)

Diet and nutrition: An important risk factor in leprosy.

Leprosy, once considered as poor man's disease may cause severe neurological complications and physical disabilities. Classification of leprosy depends upon the cell mediated and humoral immune responses of the host, from tuberculoid to lepromatous stage. Current therapy to prevent the disease is not only very lengthy but also consists of expensive multiple antibiotics in combination. Treatment and the duration depend on the bacillary loads, from six months in paucibacillary to a year in multibacillary leprosy. Although as per WHO recommendations, these antibiotics are freely available but still out of reach to patients of many rural areas of the world. In this review, we have focused on the nutritional aspect during the multi-drug therapy of leprosy along with the role of nutrition, particularly malnutrition, on susceptibility of Mycobacterium leprae and development of clinical symptoms. We further discussed the diet plan for the patients and how diet plans can affect the immune responses during the disease.

An Expanded Synthetic Biology Toolkit for Gene Expression Control in Acetobacteraceae.

The availability of different host chassis will greatly expand the range of applications in synthetic biology. Members of the Acetobacteraceae family of Gram-negative bacteria form an attractive class of nonmodel microorganisms that can be exploited to produce industrial chemicals, food and beverage, and biomaterials. One such biomaterial is bacterial cellulose, which is a strong and ultrapure natural polymer used in tissue engineering scaffolds, wound dressings, electronics, food additives, and other products. However, despite the potential of Acetobacteraceae in biotechnology, there has been considerably little effort to fundamentally reprogram the bacteria for enhanced performance. One limiting factor is the lack of a well-characterized, comprehensive toolkit to control expression of genes in biosynthetic pathways and regulatory networks to optimize production and cell viability. Here, we address this shortcoming by building an expanded genetic toolkit for synthetic biology applications in Acetobacteraceae. We characterized the performance of multiple natural and synthetic promoters, ribosome binding sites, terminators, and degradation tags in three different strains, namely, Gluconacetobacter xylinus ATCC 700178, Gluconacetobacter hansenii ATCC 53582, and Komagataeibacter rhaeticus iGEM. Our quantitative data revealed strain-specific and common design rules for the precise control of gene expression in these industrially relevant bacterial species. We further applied our tools to synthesize a biodegradable cellulose-chitin copolymer, adjust the structure of the cellulose film produced, and implement CRISPR interference for ready down-regulation of gene expression. Collectively, our genetic parts will enable the efficient engineering of Acetobacteraceae bacteria for the biomanufacturing of cellulose-based materials and other commercially valuable products.

[Instrument to evaluate the combination of foods to make iron more bioavailable in the diet]. / Instrumento para avaliar a combinação de alimentos para tornar o ferro mais biodisponível na dieta.

The scope of this research was to develop an instrument to evaluate the knowledge which adult women have of food combinations in order to make iron bioavailable in the diet of children. An exploratory factor analysis study (Likert scale) was conducted applying a questionnaire on a sample comprising 151 women and then applying Principal Factor Analysis and Likelihood Ratio Analysis. The Kaiser-Meyer-Olkin (KMO) test, the Doornik-Hansen test, the Kaiser Guttman criterion and the correlation between factors and theoretical assumptions were applied. Reliability was assessed by Cronbach's alpha and composite reliability. Total KMO (0.5942) showed the adequacy of the sample. The Doornik-Hansen test showed multivariate normality of the scores observed. Factorial loads, error variance of items and correlation between factors pointed to the two-dimensional nature of the questionnaire, which decreased from 30 to 15 items. Total Cronbach's alpha was 0.8018 (95% CI = 0.7429 to 0.8606) and composite reliability (Factor 1 = 0.3125 and Factor 2 = 0.3263). Convergent and discriminant factorial validity revealed acceptable results. A decision was taken to reduce the instrument (from 30 to 15 items) with sufficient reliability and validity that enable it to qualify for further confirmatory factor analysis procedures.

O objetivo foi desenvolver um instrumento para avaliar o conhecimento de mulheres adultas sobre a combinação de alimentos de forma a tornar o ferro biodisponível na dieta infantil. Estudo fatorial exploratório de questionário (escala Likert) utilizando-se Análise de Fator Principal e estimador de razão de verossimilhança. Aplicaram-se teste KMO, teste Doornik-Hansen, critério de Kaiser Guttman, correlação entre fatores e pressupostos teóricos. Confiabilidade avaliada pelo Alfa de Cronbach e confiabilidade composta. Participaram do estudo 151 mulheres. KMO total (0,5942) mostrou adequação da amostra. Teste Doornik-Hansen atestou normalidade multivariada dos escores observados. Cargas fatoriais, variância do erro dos itens e correlação entre os fatores apontaram para a bidimensionalidade do questionário, que passou de 30 para 15 itens. Alfa de Cronbach total de 0,8018 (95% IC = 0,7429 a 0,8606) e confiabilidade composta (Fator 1 = 0,3125 e Fator 2 = 0,3263). Validade fatorial convergente e discriminante apresentaram resultados aceitáveis. Concluiu-se por redução de instrumento validado (30 para 15 itens) com confiabilidade e validade que o habilita para posterior procedimento de análise fatorial confirmatória.

Instrumento para avaliar a combinação de alimentos para tornar o ferro mais biodisponível na dieta / Instrument to evaluate the combination of foods to make iron more bioavailable in the diet

Resumo O objetivo foi desenvolver um instrumento para avaliar o conhecimento de mulheres adultas sobre a combinação de alimentos de forma a tornar o ferro biodisponível na dieta infantil. Estudo fatorial exploratório de questionário (escala Likert) utilizando-se Análise de Fator Principal e estimador de razão de verossimilhança. Aplicaram-se teste KMO, teste Doornik-Hansen, critério de Kaiser Guttman, correlação entre fatores e pressupostos teóricos. Confiabilidade avaliada pelo Alfa de Cronbach e confiabilidade composta. Participaram do estudo 151 mulheres. KMO total (0,5942) mostrou adequação da amostra. Teste Doornik-Hansen atestou normalidade multivariada dos escores observados. Cargas fatoriais, variância do erro dos itens e correlação entre os fatores apontaram para a bidimensionalidade do questionário, que passou de 30 para 15 itens. Alfa de Cronbach total de 0,8018 (95% IC = 0,7429 a 0,8606) e confiabilidade composta (Fator 1 = 0,3125 e Fator 2 = 0,3263). Validade fatorial convergente e discriminante apresentaram resultados aceitáveis. Concluiu-se por redução de instrumento validado (30 para 15 itens) com confiabilidade e validade que o habilita para posterior procedimento de análise fatorial confirmatória.

Abstract The scope of this research was to develop an instrument to evaluate the knowledge which adult women have of food combinations in order to make iron bioavailable in the diet of children. An exploratory factor analysis study (Likert scale) was conducted applying a questionnaire on a sample comprising 151 women and then applying Principal Factor Analysis and Likelihood Ratio Analysis. The Kaiser-Meyer-Olkin (KMO) test, the Doornik-Hansen test, the Kaiser Guttman criterion and the correlation between factors and theoretical assumptions were applied. Reliability was assessed by Cronbach's alpha and composite reliability. Total KMO (0.5942) showed the adequacy of the sample. The Doornik-Hansen test showed multivariate normality of the scores observed. Factorial loads, error variance of items and correlation between factors pointed to the two-dimensional nature of the questionnaire, which decreased from 30 to 15 items. Total Cronbach's alpha was 0.8018 (95% CI = 0.7429 to 0.8606) and composite reliability (Factor 1 = 0.3125 and Factor 2 = 0.3263). Convergent and discriminant factorial validity revealed acceptable results. A decision was taken to reduce the instrument (from 30 to 15 items) with sufficient reliability and validity that enable it to qualify for further confirmatory factor analysis procedures.

Práticas de autocuidado em hanseníase: face, mãos e pés / Prácticas de autocuidado en hanseniasis: cara, manos y pies / Practices for self-care in Hansen's disease: face, hands and feet

Resumo OBJETIVO Analisar as práticas de autocuidado em face, mãos e pés realizadas por pessoas atingidas pela hanseníase. METODOLOGIA Estudo qualitativo, realizado em unidades de referência para hanseníase em Pernambuco, entre maio de 2014 e abril de 2015, com 24 pessoas. Os dados foram coletados por meio da entrevista semiestruturada e realizada a análise de conteúdo. RESULTADOS Emergiram duas categorias: Conhecimento e realização de práticas de autocuidado em Hanseníase e Singularidades e desafios do autocuidado. O estudo apontou que os entrevistados conhecem as informações sobre os cuidados com a face, mãos e pés, mas relatam dificuldades como baixa renda para adquirir material para o autocuidado, falta de tempo, e alguns falta de interesse. A maior parte já apresentava grau de incapacidade. CONCLUSÕES É necessário a capacitação de profissionais que atuem no empoderamento das pessoas frente à doença e orientações sobre prevenção de incapacidades e acesso à insumos para realizar o autocuidado.

Resumen OBJETIVO Analizar las prácticas de autocuidado en cara, manos y pies realizadas por personas afectadas por la hanseniasis. METODOLOGÍA Estudio cualitativo, realizado en unidades de referencia para hanseniasis en Pernambuco, entre mayo de 2014 y abril de 2015, con 24 personas. Los datos fueron recolectados por medio de la entrevista semiestructurada y realizada el análisis de contenido. RESULTADOS emergieron dos categorías: Conocimiento y realización de prácticas de autocuidado en Hanseniasis y Singularidades y desafíos del autocuidado. El estudio apuntó que los entrevistados conocen las informaciones sobre los cuidados con la cara, manos y pies, pero relatan dificultades como bajas rentas para adquirir material para el autocuidado, falta de tiempo, y algunos falta de interés. La mayor parte ya presentaba grado de incapacidad. CONCLUSIONES Es necesario la capacitación de profesionales que actúen en el empoderamiento de las personas frente a la enfermedad y orientaciones sobre prevención de discapacidades y acceso a insumos para realizar el autocuidado.

ABSTRACT OBJECTIVE To analyze the self-care practices on the face, hands and feet carried out by people affected by Hansen's disease. METHODOLOGY A qualitative study, carried out in reference units for Hansen's disease in Pernambuco, between May 2014 and April 2015, with 24 people. Data was collected through the semi-structured interview and content analysis was carried out. RESULTS Two categories emerged: Knowledge and execution of self-care practices in Leprosy and Singularities and challenges for self-care. The study found that respondents are familiar with information about face, hand and foot care, but report difficulties such as low income to acquire material for self-care, lack of time, and some lack of interest. Most of them already presented a degree of incapacity. CONCLUSIONS The training of professionals who work on the empowerment of people facing the disease, guidelines on prevention of disabilities and access to inputs for carrying out self-care are necessary.

Role of cultural factors in the biopsychosocial model of psychosomatic skin diseases: an Indian perspective.

Cultural factors can influence the experience and presentation of diseases, including psychosomatic diseases. Psychosomatic dermatology refers to skin diseases in which psychogenic causes, consequences, or concomitant circumstances have an essential and therapeutically important influence. Indian culture is one of the oldest and most diverse, and encompasses the various traditions and beliefs of people all over the vast Indian subcontinent. This paper discusses how cultural factors can influence the clinical course of some dermatologic problems and reviews the cultural dimension of some common skin conditions in India, including vitiligo, facial hypermelanosis, acne, atopic dermatitis, psoriasis, and leprosy. The paper illustrates some examples of the contributions of a patient's cultural values, beliefs, and practices to the biopsychosocial model of psychosomatic skin disorders.

Growth of non-Saccharomyces yeasts affects nutrient availability for Saccharomyces cerevisiae during wine fermentation.

Yeast produces numerous secondary metabolites during fermentation that impact final wine quality. Although it is widely recognized that growth of diverse non-Saccharomyces (NS) yeast can positively affect flavor complexity during Saccharomyces cerevisiae wine fermentation, the inability to control spontaneous or co-fermentation processes by NS yeast has restricted their use in winemaking. We selected two NS yeasts from our Uruguayan native collection to study NS-S. cerevisiae interactions during wine fermentation. The selected strains of Hanseniaspora vineae and Metschnikowia pulcherrima had different yeast assimilable nitrogen consumption profiles and had different effects on S. cerevisiae fermentation and growth kinetics. Studies in which we varied inoculum size and using either simultaneous or sequential inoculation of NS yeast and S. cerevisiae suggested that competition for nutrients had a significant effect on fermentation kinetics. Sluggish fermentations were more pronounced when S. cerevisiae was inoculated 24h after the initial stage of fermentation with a NS strain compared to co-inoculation. Monitoring strain populations using differential WL nutrient agar medium and fermentation kinetics of mixed cultures allowed for a better understanding of strain interactions and nutrient addition effects. Limitation of nutrient availability for S. cerevisiae was shown to result in stuck fermentations as well as to reduce sensory desirability of the resulting wine. Addition of diammonium phosphate (DAP) and a vitamin mix to a defined medium allowed for a comparison of nutrient competition between strains. Addition of DAP and the vitamin mix was most effective in preventing stuck fermentations.

Effect of nutrient supplementation of crude or detoxified concentrated distilled grape marc hemicellulosic hydrolysates on the xylitol production by Debaryomyces hansenii.

Biosynthesis of xylitol using the yeast Debaryomyces hansenii NRRL Y-7426 was carried out using distilled grape marc (DGM) hemicellulosic hydrolysates directly concentrated by vacuum evaporation or after detoxification with activated charcoal. The effect of nutrient supplementation with vinasses, corn steep liquor (CSL) or commercial nutrients was explored. Using crude concentrated hemicellulosic hydrolysates, the maximum xylitol concentration, 11.3 g/L, was achieved after 172 hr (Q ( xylitol ) = 0.066 g/L-hr; Y ( xylitol ) (/SC) = 0.21 g/g); meanwhile, using detoxified concentrated hydrolysates, the concentration increased up to 19.7 g/L after 72 hr (Q ( xylitol ) = 0.274 g/L-hr; Y ( xylitol ) (/SC) = 0.38 g/g). On the other hand, using crude or detoxified hydrolysates, the xylose-to-xylitol bioconversion was strongly affected by the addition of nutrients, suggesting that these hydrolysates present essential nutrients favouring the growth of D. hansenii.

Pharmacokinetics and relative bioavailability of clofazimine in relation to food, orange juice and antacid.

BACKGROUND: Clofazimine is potentially useful for the treatment of disease due to multidrug resistant Mycobacterium tuberculosis, as well as leprosy and certain chronic skin diseases. Its pharmacokinetics have been incompletely characterized. This study was conducted to explore issues relating to bioavailability in the presence of food, orange juice, and antacid. METHODS: A 5 drug regimen consisting of clofazimine, cycloserine, ethionamide, para-aminosalicyclic acid, and pyridoxime was administered to healthy subjects four times using a four period cross-over design with two weeks washout between treatments. Subjects also received orange juice, a high fat meal, aluminum/magnesium antacid, or only water in random order with the drug regimen. The pharmacokinetics of clofazimine were assessed using individual- and population-based methods and relative bioavailability compared to fasting administration was determined. RESULTS: Clofazimine exhibited a sometimes prolonged and variable lag-time and considerable variability in plasma concentrations. From the population analysis (one-compartment model), the mean oral clearance was 76.7 l/h (CV=74.2%) and mean apparent volume of distribution was 1470 l (CV=36.3%). The first-order absorption rate constant ranged from 0.716 to 1.33 h(-1) (pooled CV=61.7%). Residual (proportional) error was 49.1%. Estimates of bioavailability compared to fasting administration were 145% (90% CI, 107-183%) for administration with high fat food, 82.0% (63.2-101%) for administration with orange juice, and 78.5% (55.1-102%) for administration with antacid. CONCLUSION: Administration of clofazimine with a high fat meal provides the greatest bioavailability, however, bioavailability is associated with high inter- and intra-subject variability. Both orange juice and aluminum-magnesium antacid produced a reduction in mean bioavailability of clofazimine.

Impact of knowledge of leprosy on the attitude towards leprosy patients: a community study.

NLEP, through its survey-education-treatment (SET) pattern, attempts to educate the community members about the scientific facts of leprosy with the view to improve their knowledge leading to a more positive attitude towards the leprosy afflicted. This paper explores the impact of knowledge on the attitudes of 1199 community members drawn from two States, Andhra Pradesh and Orissa, towards leprosy. The results show that, overall, a high knowledge level did not necessarily generate positive attitudes. There was a general negative attitude despite 35% to 50% of the respondents having high knowledge level. There were, however, situations in which a high level of knowledge helps to have positive attitudes. These situations differ in the two states studied.

Tatu e hanseníase / Armadillus and hanseaniasis

Grande número de hansenianos admite a possibilidade de que o uso da carne de tatu na sua alimentaçäo possa ser meio de transmissäo da hanseníase. Tentando esclarecer se esta crença é verdadeira os autores entrevistaram 205 doentes dos quais 132 eram do sexo masculino e 73 do sexo feminino, indagando pormenorizadamente sobre o hábito alimentar com carne de tatu. Dos 205 doentes entrevistados, 127 referiram o uso da carne, destes 127 doentes, 101 consumiam o alimento antes do início da doença e 26 doentes referiram o seu uso quando já apresentavam manifestaçöes clínicas da moléstia. Os autores realizarma pesquisa bibliografica sobre o assunto estudado e tecem comentários sobre os resultados obtidos e os dados da literatura

Pharmacokinetics of clofazimine in healthy volunteers.

The pharmacokinetics of clofazimine was evaluated in 12 healthy male volunteers following single and multiple oral doses of clofazimine. Six volunteers received a single dose of 200 mg together with food. A 200-mg dose was administered to three volunteers either with or without food. In a multiple-dose experiment, three volunteers were repeatedly dosed with 50 mg per day together with food for 8 days. Following a single oral dose of 200 mg, the mean peak plasma concentration of clofazimine was 861 +/- 289 pmol/g (+/- S.D., N = 6) after 8 hr (median). The mean terminal half-life was 10.6 +/- 4.0 days. Comparison of the bioavailability of clofazimine administered with or without food revealed a 60% higher mean area under the curve (AUC) value and a 30% higher mean maximum concentration (Cmax) value with food (N = 3). The median of times to peak (Tmax) was 8 hr with food and 12 hr without food. In the multiple-dose study, good agreement was found between the mean experimental plasma concentration values and the plasma concentration profile predicted from the single-dose pharmacokinetics. The elimination half-life calculated from the terminal phase of the individual profiles after the last dose was 8.8 +/- 1.0 days (+/- S.D., N = 3). The half-life obtained from the fitted mean multiple-dose profile was 10.5 days. The slow elimination of clofazimine has its implications for the treatment regimen in patients. To avoid the long-lasting accumulation toward the steady state, higher daily loading doses are recommended at the beginning of therapy followed by a daily maintenance dose.