Thermoradiotherapy optimization strategies accounting for hyperthermia delivery uncertainties.

INTRODUCTION: The combined effect of hyperthermia and radiotherapy can be quantified by an enhanced equivalent radiation dose (EQDRT). Uncertainties in hyperthermia treatment planning and adjustments during treatment can impact achieved EQDRT. We developed and compared strategies for EQDRT optimization of radiotherapy plans, focusing on robustness against common adjustments. METHODS: Using Plan2Heat, we computed pre-planning hyperthermia plans and treatment adjustment scenarios for three cervical cancer patients. We imported these scenarios into RayStation 12A for optimization with four different strategies: (1) Conventional radiotherapy optimization prescribing 46 Gy to the planning target volume (PTV), (2) Nominal EQDRT optimization using the pre-planning scenario, targeting uniform 58 Gy in the gross tumor volume (GTV), keeping organs at risk (OAR) doses as in plan (1), (3) Robust EQDRT optimization, as (2) but adding adjusted scenarios for optimization, (4) Library of Plans (four plans), with strategy (2) criteria but optimizing on one adjusted scenario per plan. We calculated for each radiotherapy plan EQDRT distributions for pre-planning and adjusted scenarios, evaluating for each combination GTV coverage and homogeneity objectives. RESULTS: EQDRT95% increased from 49.9-50.9 Gy in strategy (1) to 56.1-57.4 Gy in strategy (2) with the pre-planning scenario, improving homogeneity in ∼10%. Strategy (2) demonstrated the best overall robustness, with 62% of all GTV objectives within tolerance. Strategy (3) had higher percentage of coverage objectives within tolerance than strategy (2) (68% vs 54%), but lower percentage for uniformity (44% vs 71%). Strategy (4) showed similar EQDRT95% and homogeneity for adjusted scenarios than strategy (2) for pre-planning scenario. D0.1% for OARs was increased by strategies (2-4) by up to ∼6 Gy. CONCLUSIONS: EQDRT optimization enhances EQDRT levels and uniformity compared to conventional optimization. Better overall robustness is achieved optimizing on the pre-planning hyperthermia plan. Robust optimization improves coverage but reduces homogeneity. A library of plans ensures coverage and uniformity when dealing with adjusted hyperthermia scenarios.

Biological treatment evaluation in thermoradiotherapy: application in cervical cancer patients.

BACKGROUND: Hyperthermia treatment quality is usually evaluated by thermal (dose) parameters, though hyperthermic radiosensitization effects are also influenced by the time interval between the two modalities. This work applies biological modelling for clinical treatment evaluation of cervical cancer patients treated with radiotherapy plus hyperthermia by calculating the equivalent radiation dose (EQDRT, i.e., the dose needed for the same effect with radiation alone). Subsequent analyses evaluate the impact of logistics. METHODS: Biological treatment evaluation was performed for 58 patients treated with 23-28 fractions of 1.8-2 Gy plus 4-5 weekly hyperthermia sessions. Measured temperatures (T50) and recorded time intervals between the radiotherapy and hyperthermia sessions were used to calculate the EQDRT using an extended linear quadratic (LQ) model with hyperthermic LQ parameters based on extensive experimental data. Next, the impact of a 30-min time interval (optimized logistics) as well as a 4­h time interval (suboptimal logistics) was evaluated. RESULTS: Median average measured T50 and recorded time intervals were 41.2 °C (range 39.7-42.5 °C) and 79 min (range 34-125 min), respectively, resulting in a median total dose enhancement (D50) of 5.5 Gy (interquartile range [IQR] 4.0-6.6 Gy). For 30-min time intervals, the enhancement would increase by ~30% to 7.1 Gy (IQR 5.5-8.1 Gy; p < 0.001). In case of 4­h time intervals, an ~ 40% decrease in dose enhancement could be expected: 3.2 Gy (IQR 2.3-3.8 Gy; p < 0.001). Normal tissue enhancement was negligible (< 0.3 Gy), even for short time intervals. CONCLUSION: Biological treatment evaluation is a useful addition to standard thermal (dose) evaluation of hyperthermia treatments. Optimizing logistics to shorten time intervals seems worthwhile to improve treatment efficacy.

The burden of chronic obstructive pulmonary disease among hospitalised women in a developing country.

BACKGROUND: The course of chronic obstructive pulmonary disease (COPD) is different in men and women. There are limited data in Latin America regarding COPD exacerbations (ECOPD) in women. This study aims to determine the sociodemographic and clinical profile of ECOPD adjusted by gender.METHODS: Cross-sectional analytical study of all patients hospitalised due to an ECOPD in a tertiary university hospital in Colombia between 2015 and 2019. A group comparison analysis was performed between male and female groups.RESULTS: A total of 81 patients met the inclusion criteria (35.8% were women). The mean age was 71.49 years. Most of the patients were GOLD (Global Initiative for Obstructive Lung Disease) 3 and 4. A history of TB was present in 15% of our cohort. While the proportion of smokers was higher among men (OR 5.11; P = 0.013), exposure to wood smoke was significantly higher in women (OR 24; P < 0.001). Females were associated with a lower probability of having forced expiratory volume in 1 sec >0,87 L (OR 0.11; P = 0.013) and were associated with an increased probability of receiving inhaled corticosteroids during hospitalisation (OR 3.33; P = 0.023). No differences in terms of mortality or complications were found.CONCLUSION: Women with COPD are underrepresented in literature. This study was able to identify some factors related to female sex among patients hospitalised for severe ECOPD.

Development of an HPLC-DAD method for the simultaneous analysis of four xenoestrogens in water and its application for monitoring photocatalytic degradation.

A high-performance liquid chromatography with diode array detector (HPLC-DAD) method was developed and validated for the simultaneous quantification of 4 xenoestrogens in water for monitoring their photocatalytic degradation in synthetic water. The analytical parameters evaluated were linearity, limits of detection, and quantification (LODs and LOQs), selectivity, and accuracy, according to the US Food and Drug Administration (FDA) and Eurachem guidelines. The developed method shows good linearity (R2 > 0.995 for all compounds), and LODs ranged from 0.02 to 0.04 mg L-1, while LOQs ranged from 0.05 to 0.11 mg L-1. Moreover, accuracy expressed as recovery and precision were within the required limits. Therefore, the developed method was considered accurate, and reliable. In addition, it was successfully applied for monitoring a mixture of 4 xenoestrogens in water during the photocatalytic treatment.•An HPLC-DAD method was developed to quantify 4 xenoestrogens in water simultaneously.•The developed HPLC-DAD method shows excellent linearity, selectivity, and accuracy.•A mixture of 4 xenoestrogens was reliably monitored during their photocatalytic degradation.

Biological modeling in thermoradiotherapy: present status and ongoing developments toward routine clinical use.

Biological modeling for anti-cancer treatments using mathematical models can be very supportive in gaining more insight into dynamic processes responsible for cellular response to treatment, and predicting, evaluating and optimizing therapeutic effects of treatment. This review presents an overview of the current status of biological modeling for hyperthermia in combination with radiotherapy (thermoradiotherapy). Various distinct models have been proposed in the literature, with varying complexity; initially aiming to model the effect of hyperthermia alone, and later on to predict the effect of the combined thermoradiotherapy treatment. Most commonly used models are based on an extension of the linear-quadratic (LQ)-model enabling an easy translation to radiotherapy where the LQ model is widely used. Basic predictions of cell survival have further progressed toward 3 D equivalent dose predictions, i.e., the radiation dose that would be needed without hyperthermia to achieve the same biological effect as the combined thermoradiotherapy treatment. This approach, with the use of temperature-dependent model parameters, allows theoretical evaluation of the effectiveness of different treatment strategies in individual patients, as well as in patient cohorts. This review discusses the significant progress that has been made in biological modeling for hyperthermia combined with radiotherapy. In the future, when adequate temperature-dependent LQ-parameters will be available for a large number of tumor sites and normal tissues, biological modeling can be expected to be of great clinical importance to further optimize combined treatments, optimize clinical protocols and guide further clinical studies.

The unfinished work of neonatal very low birthweight infants quality improvement: Improving outcomes at a continental level in South America.

Neonatal mortality rate varies between 4.2 and 18.6 per thousand by country in South America. There is little information regarding the outcomes of very low birth weight infants in the region and mortality rates are extremely variable ranging from 6% to over 50%. This group may represent up to 50-70% of the neonatal mortality and approximately 25-30% of infant mortality. Some initiatives, like the NEOCOSUR Network, have systematically collected and analyzed epidemiological information on VLBW infants' outcomes in the region. Over a 16-year period, survival without major morbidity improved from 37 to 44%. However, mortality has remained almost unchanged at approximately 27%, despite an increase in the implementation of the best available evidence in perinatal practices over time. Implementing quality improvement initiatives in the continent is particularly challenging but represents a great opportunity considering that there is a wide margin for progress in both care and outcomes.

Distribution of Burkholderia cepacia complex species isolated from industrial processes and contaminated products in Argentina.

Burkholderia cepacia complex (Bcc) members have clinical relevance as opportunistic pathogens in patients with cystic fibrosis and are responsible of numerous nosocomial infections. These closely related bacteria are also reported as frequent contaminants of industrial products. In this retrospective study, we use PCR and recA gene sequence analysis to identify at species level Bcc isolates recovered from massive consumption products and industrial processes in Argentina during the last 25 years. The sequences obtained were also compared with recA sequences from clinical Bcc isolates deposited in GenBank database. We detected Bcc in purified water and preserved products from pharmaceutics, cosmetics, household cleaning articles, and beverages industries. B. contaminans (which is prevalent among people with cystic fibrosis in Argentina) was the most frequent Bcc species identified (42% of the Bcc isolates studied). B. cepacia (10%), B. cenocepacia (5%), B. vietnamiensis (16%), B. arboris (3%), and the recently defined B. aenigmatica (24%) were also detected. Rec A sequences from all B. cepacia and most B. contaminans industrial isolates obtained in this study displayed 100% identity with recA sequences from isolates infecting Argentinean patients. This information brings evidence for considering industrial massive consumption products as a potential source of Bcc infections. In addition, identification at species level in industrial microbiological laboratories is necessary for a better epidemiological surveillance. Particularly in Argentina, more studies are required in order to reveal the role of these products in the acquisition of B. contaminans infections.

How Can We Improve the Selection of Patients Awaiting Liver Retransplantation?

OBJECTIVE: To analyze predictors of survival involved in liver retransplantation (LRT), including the Rosen Model (RM). MATERIALS AND METHODS: This was a descriptive, observational, and unicentric study based on predictors of survival including patients who underwent LRT in a tertiary medical center between April 2002 and December 2018. Recipient, donor, and transplant data were collected, and RM score was calculated for every patient. Fisher exact test and Student t test were used for qualitative and quantitative variables, respectively. The Shapiro-Wilks test was applied to verify the normality of the sample. Survival differences between subgroups were checked using the log-rank test. Statistical significance was stated at P < .05. RESULTS: Among 32 retransplanted patients in this period, 17 (53.1%) survived more than 12 months after LRT. The results of statistical associations between prognostic factors and overall survival highlighted that an older recipient age was significantly correlated with a lower overall survival. The 3-month overall survival was 84.3%. Nineteen patients had a low risk according to RM, with a 3-month survival rate of 78.9%. Eight had a RM intermediate risk, with a survival rate of 21%. Despite the aforementioned data, the log-rank test did not find statistical differences in survival (P = .488). CONCLUSION: We should consider older recipient age as a negative prognostic factor of overall survival. Also, we should contemplate intermediate risk according to RM as an adverse predictor regarding survival in LRT. Both data are of interest regarding the indication or not of LRT and prioritization on the waiting list.

Liver Retransplantation: The Changing Scenario in a Tertiary Medical Center.

AIM: To analyze the causes of liver retransplantation (LRT), which mostly depend on recipient factors. MATERIALS AND METHODS: A descriptive, observational, and unicentric study including patients who underwent an LRT in a tertiary medical center between April 2002 and December 2018. Recipient, donor, and liver transplant data were collected. RESULTS: During the period under review a total of 468 transplants were made; among them, 32 (6.8%) were LRT. The most common indication (25%) was hepatic artery thrombosis (HAT) developing ischemic cholangiopathy followed by chronic rejection (21.8%). Late LRT was performed in 71.8%. A total of 96.8% of donations were after brain death with a donor median age of 65 years. Six patients (18.7%) had HAT as a postoperative complication. The recipients' 3-, 6-, and 12-month overall survival was 72.7%, 54.6%, and 51.5%, respectively, and the 5-year was 46.8%. Leading cause of death was septic shock (42.1%). CONCLUSION: In our patients, the most common cause of LRT is HAT. We had an LRT rate of 6.8%, which is consistent with national and international registers.

GlSir2.1 of Giardia lamblia is a NAD+-dependent cytoplasmic deacetylase.

The sirtuins are a group of well-conserved proteins widely distributed across all domains of life. These proteins are clustered in the class III of histone deacetylases and are distinctly characterized by their dependence upon NAD+ to carry out the deacetylation of lysine residues in histone proteins (H3 and H4) and non-histones such as the transcription factor p53. The requirement of NAD+ for sirtuin activity makes this group of proteins metabolic sensors, which are favored during caloric stress. Currently, it is known that these proteins are involved in numerous cellular processes that are fundamental for the proper functioning of cells, including control of the cell cycle and cellular survival. In spite of the importance of sirtuins in cell functions, the role that these proteins play in protozoan parasites is not completely understood. In this study, bioinformatic modeling and experimental characterization of the candidate G1Sir2.1 present in the genome of Giardia lamblia were carried out. Consequently, cloning, expression, purification, and in vitro evaluation of the recombinant GlSir2.1 protein's capacity for deacetylation were performed. This allowed for the identification of the NAD+-dependent deacetylase activity of the identified candidate. Production of anti-rHis-GlSir2.1 polyclonal antibodies enabled the observation of a cytoplasmic localization for the endogenous protein in trophozoites, which exhibited a perinuclear aggregation and co-localization with acetylated cytoskeleton structures such as the flagella and median body. Currently, GlSir2.1 is the second sirtuin family member identified in G. lambia, with a demonstrated cytoplasmic localization in the parasite.

Liver Transplantation in Recipients With High Model for End-stage Liver Disease Score.

OBJECTIVES: The score in the Model of End-stage Liver Disease, or MELD, is a good indicator of the survival in patients on the liver transplant waiting list. In this study, an analysis is performed on the benefits of liver transplant on those patients with a very high MELD score and who thus start from a very severe baseline state that could affect the surgical outcome. MATERIALS AND METHODS: A prospective study was conducted on a cohort of 331 patients that received a liver transplant between 2002 and 2014. The patients were divided into 2 groups according to the MELD score (<28 vs ≥28), and differences in age, postoperative complications, stay in the intensive care unit (ICU), hospital stay, and survival were compared. RESULTS: Of the total of 331 patients, 21 (6.3%) had a MELD score ≥ 28. The mean age of the group with MELD score ≥ 28 was lower than the age in the group with MEDL score < 28 (42.5 vs 53.7 years; P < .0001). No significant increase was observed in postoperative complications. Although there were also no differences in survival, the group with MELD score ≥ 28 did have a longer stay in ICU and a longer hospital stay (with a mean of 6.7 days in ICU and 41.5 days admission vs 4.1 and 26.9, respectively). CONCLUSIONS: A very high MELD score is associated with a longer stay in ICU and more days of hospital admission, although no differences were observed in postoperative complications or survival. Therefore, there does not seem to be any contraindication in transplantation in this group of patients.

Analysis of Indications and Results in Liver Retransplantation: Is Late Retransplantation Worthwhile?

BACKGROUND: Liver retransplantation (LrT) is the only therapeutic option for irreversible hepatic graft failure. Despite various improvements, its technical complexity entails a greater morbidity in the short and long term. The main goal of the study was to analyze the activity of LrT at our center, as well as its indications, timing, postoperative evolution, and the long-term survival of patients. METHODS: We designed a descriptive study of a cohort of patients who underwent LrT in a Spanish Hepatic Transplant Unit, between April 1, 2002 and December 31, 2015. RESULTS: A total of 366 primary orthotopic liver transplantations were performed, 20 of which were LrTs, resulting in a 5.5% retransplantation rate. The most frequent indication for LrT was hepatic artery thrombosis (HAT) (35%). Twenty-five percent of the LrTs were early retransplantations and 75% were late retransplantations. After LrT, 35% of the grafts showed liver dysfunction. The overall mortality rate was 45%: in early LrT this was 25% and in late LrT it was 46.7%. Graft actuarial survival at 1 month post-LrT was 75% and at 5 years it was 63.6%. The overall actuarial survival after LrT at month 1, year 1, year 3, and year 5 was 80%, 69.6%, 58.9%, and 50.5%, respectively. In the late LrT group, the results proved less favorable, so it is necessary to define the minimum acceptable result before proceeding to a second graft. CONCLUSION: Our LrT rate was lower than that reported by other groups in our country. The actuarial survival rates for graft and patient are comparable to those obtained by other groups.

Spatial distribution and seasonality of ichthyoplankton and anthropogenic debris in a river delta in the Caribbean Sea.

Temporal changes in larval fish species composition and abundance compared with other components of the seston are described in four estuarine habitats in the Atrato Delta, Colombia. In comparison with zooplankton, fish larvae and egg density and anthropogenic debris abundance were low in the South Atrato Delta. Transparency, water temperature and chlorophyll a were the major factors influencing the spatiotemporal distribution of ichthyoplankton in the delta. The most abundant fish larvae were Astyanax sp. 1, Anchovia clupeoides, Cetengraulis edentulus, Anchoa sp., Bathygbius curacao, Dormitator maculatus, Hyporhamphus sp., Atherinella blackburni, Gobiosoma sp. 1 and Menticirrhus americanus (92·8% of total abundance). Spatial temporal analysis shows that in this delta, shrub (arracachal) and grass (eneal) habitats are important for freshwater and estuarine species, whilst mudflat and mangrove are important for estuarine species and estuarine-marine species, since most flexion and post-flexion stages of these species were found there. Anthropogenic debris density never surpassed the total ichthyoplankton density, but was ubiquitous. Shrub and mangrove habitats had higher densities of anthropogenic debris, since these are flood-stem habitats that trap solids.

Fish species from a micro-tidal delta in the Caribbean Sea.

A total of 66 fish species belonging to 32 families were recorded between November 2012 and April 2014 in the southern arm of the delta to the Atrato River. Total length (LT ; range: 1·7-48 cm), total mass (MT ), LT and MT relationships (b values ranged from 1·8 to 3·7, mostly with negative allometric growth), and LT frequency (for 25 species) were estimated for freshwater, estuarine and marine species. LT and MT of Porichthys pauciradiatus and Membras argentea are given for the first time and maximum LT records for 14 species exceed those in the literature.

Tuberculosis in prisoners and their contacts in Chile: estimating incidence and latent infection.

SETTING: Contact investigation of tuberculosis (TB) patients in Chilean prisons. OBJECTIVE: 1) To estimate TB incidence and the prevalence of latent tuberculous infection (LTBI) among prisoners and their contacts; and 2) to determine factors associated with disease transmission. DESIGN: Cross-sectional study conducted in 46 prisons (51% of the total prison population) to assess the prevalence of and risk factors for LTBI among contacts of prisoners newly diagnosed with pulmonary TB. We used in vitro interferon-gamma release assays to establish LTBI and a questionnaire to address risk factors. RESULTS: During the 1-year follow-up, we studied 418 contacts of 33 active TB cases. We found high TB incidence (123.9 per 100,000 prisoners) and high LTBI prevalence (29.4%) among contacts. LTBI rates are significantly higher in prison inmates than in non-prisoners (33.2% vs. 15.6%). Male sex, illicit drugs, malnutrition, corticosteroid use, low educational level and sharing a cell with a case increase the risk of LTBI. Multivariate analyses showed that corticosteroid use, duration of incarceration and overcrowding are the most relevant determinants for LTBI among all contacts. CONCLUSIONS: Our results confirm that incarceration increases the risk of tuberculous infection and TB disease, and that it was associated not only with origin from vulnerable groups, but also with the prison environment. Reinforcing TB control is essential to prevent TB transmission in prisons.

Efecto de los micronutrientes en polvo en el estado nutricional y en los valores hemáticos de preescolares sanos. Medellín, 2013 / The effect of powdered micronutrients on the hematologic values and nutritional status of healthy preschoolers. Medellín, 2013 / Efeito dos micronutrientes em pó no estado nutricional e nos valores hemáticos de crianças sadias em idade pré-escolar. Medellín, 2013

Las carencias de micronutrientes son un problema de salud pública común en muchos países, principalmente en aquellos en vía de desarrollo; las deficiencias más prevalentes son las de vitamina A, hierro y yodo, para reducirlas se pueden ejecutar estrategias como la fortificación de alimentos. OBJETIVO: evaluar el efecto de la fortificación de la dieta con micronutrientes en polvo en el estado nutricional y los valores hemáticos de preescolares sanos. METODOLOGIA: ensayo clínico triple ciego, con asignación aleatoria de grupos y controlado con placebo. Se analizaron 90 preescolares sanos a quienes se suministró 1g de mezcla de micronutrientes al día con 12,50 mg de hierro (fumarato ferroso). Antes y después de nueve semanas, se midieron los niveles de hemoglobina, ferritina sérica, transferrina, ácido fólico y los indicadores nutricionales. RESULTADOS :la concentración de hemoglobina disminuyó en el grupo de intervención, pasando de 12,80 g/dL a 12,10 g/dL (p=0,000), mientras que en el grupo placebo no hubo variación (p=0,639); así mismo la transferrina disminuyó significativamente solo en el grupo intervenido (p=0,004); el nivel de ferritina al final del estudio no difirió intra o entre grupos de intervención. Las reacciones adversas fueron similares en ambos grupos: dos niños presentaron náusea y dos tuvieron dolor abdominal, sin diferencias estadísticas. CONCLUSIONES:la fortificación de alimentos durante nueve semanas con los micronutrientes en polvo empleados en el estudio, no mejoró los niveles hematológicos, ni el estado nutricional de los niños sanos estudiados; los alimentos fortificados fueron bien tolerados por los preescolares.

Micronutrient deficiencies are a common public health problem, particularly in developing countries. Vitamin A, iron and iodine deficiencies are the most prevalent. To reduce these, many strategies such as food fortification can be implemented. OBJECTIVE:to assess the effect of a diet fortified with powdered micronutrients on the nutritional status and hematological values of healthy preschoolers. METHODOLOGY: a randomized, triple-blind, placebo-controlled trial conducted with 90 healthy preschoolers who were given 1g of powdered micronutrients per day with 12.5 mg of iron (ferrous fumarate).The levels of hemoglobin, serum ferritin, transferrin, folic acid and the nutritional indicators were measured before and after nine weeks. RESULTS:for the group receiving powdered micronutrients, hemoglobin concentration decreased from 12.80 g / dL to 12.10 g / dL (p = 0.000), whereas the placebo group showed no change (p = 0.639); likewise, transferrin decreased significantly only for the powdered micronutrients group (p = 0.004); the ferritin level showed no difference between groups or inside any of them. Adverse reactions were similar for both groups:two children had nausea and two abdominal pain. There were no statistically significant differences. CONCLUSIONS:fortifying the individuals' diet with the powdered micronutrients used in this study for nine weeks did not improve the hematological levels or the nutritional status of the healthy preschoolers. Additionally, the fortified foods were well tolerated by the children.

As carências de micronutrientes são um problema de saúde pública comum em muitos países, principalmente naqueles em via de desenvolvimento; as deficiências mais prevalentes são de vitamina A, ferro e iodo, para reduzi-las podem ser realizadas estratégias como a fortificação de alimentos. OBJETIVO: avaliar o efeito da fortificação da dieta com micronutrientes em pó no estado nutricional e os valores hemáticos de pré-escolares sadios. METODOLOGIA: ensaio clínico triplo-cego, com afetação aleatória de grupos e controlado com placebo.Foram analisados 90 pré-escolares sadios aos quais foi proporcionado 1g de mescla de micronutrientes por dia com 12,50 mg de ferro (fumarato ferroso).Antes e após nove semanas, foram medidos os níveis de hemoglobina, ferritina sérica, transferrina, ácido fólico e os indicadores nutricionais. RESULTADOS: a concentração de hemoglobina diminuiu no grupo de intervenção, passando de 12,80 g/dL a 12,10 g/dL (p=0,000), enquanto no grupo placebo não houve variação(p=0,639); do mesmo modo, a transferrina apenas diminuiu expressivamente no grupo intervindo (p=0,004); o nível de ferritina no final do estudo não divergiu intra ou entre os grupos de intervenção.As reações adversas foram semelhantes em ambos os grupos:duas crianças apresentaram náusea e duas tiveram dor abdominal, sem diferenças estatísticas. CONCLUSÕES: a fortificação de alimentos durante nove semanas com os micronutrientes em pó utilizados no estudo não melhorou os níveis hematológicos, nem o estado nutricional das crianças saudáveis analisadas; os alimentos fortificados foram bem tolerados pelas crianças.