Correction: Effect of Providing Multiple Micronutrients in Powder through Primary Healthcare on Anemia in Young Brazilian Children: A Multicentre Pragmatic Controlled Trial.

[This corrects the article DOI: 10.1371/journal.pone.0151097.].

Effect of Providing Multiple Micronutrients in Powder through Primary Healthcare on Anemia in Young Brazilian Children: A Multicentre Pragmatic Controlled Trial.

BACKGROUND: Multiple micronutrients in powder (MNP) are recommended by WHO to prevent anemia in young children. However, evidences for its effectiveness in different populations and improvements in other outcomes (e.g. linear growth and vitamin A deficiency) are scarce. METHODS: A multicentre pragmatic controlled trial was carried out in primary health centres. At study baseline, a control group (CG) of children aged 10- to 14 months (n = 521) was recruited in the routine healthcare for assessing anemia, anthropometric and micronutrient status. At the same time, an intervention group (IG) of infants aged 6- to 8 months (n = 462) was recruited to receive MNP daily in complementary feeding over a period of 60 days. Both study groups were compared when the IG infants reached the age of the CG children at enrolment. RESULTS: In CG, the prevalence of anemia [hemoglobin (Hb) < 110 g/L], iron deficiency (ID, plasma ferritin < 12 µg/L or TfR > 8.3 mg/L), and vitamin A deficiency (VAD, serum retinol < 0.70µmol/L) were 23.1%, 37.4%, and 17.4%, respectively. Four to six months after enrolment, when the IG participants had the same age of the controls at the time of testing, the prevalence of anemia, ID and VAD in IG were 14.3%, 30.1% and 7.9%, respectively. Adjusting for city, health centre, maternal education, and age, IG children had a lower likelihood of anemia and VAD [Prevalence Ratio (95% CI) = 0.63 (0.45, 0.88) and 0.45 (0.29, 0.69), respectively] when compared with CG children. The adjusted mean distributions of Hb and length-for-age Z-scores improved by 2 SE in the IG compared to CG children. CONCLUSIONS: MNP effectively reduced anemia and improved growth and micronutrient status among young Brazilian children. TRIAL REGISTRATION: Registro Brasileiro de Ensaios Clinicos RBR-5ktv6b.

Efficacy of treatment for hyperglycemic crisis in elderly diabetic patients in a day hospital.

BACKGROUND: The purpose of this prospective cohort study was to compare the costs of day hospital (DH) care for hyperglycemic crisis in elderly diabetic patients with those of conventional hospitalization (CH). Secondary objectives were to compare these two clinical scenarios in terms of glycemic control, number of emergency and outpatient visits, readmissions, hypoglycemic episodes, and nosocomial morbidity. METHODS: The study population comprised diabetic patients aged >74 years consecutively admitted to a tertiary teaching hospital in Spain for hyperglycemic crisis (sustained hyperglycemia [>300 mg/dL] for at least 3 days with or without ketosis). The patients were assigned to DH or CH care according to time of admission and were followed for 6 months after discharge. Exclusion criteria were ketoacidosis, hyperosmolar crisis, hemodynamic instability, severe intercurrent illness, social deprivation, or Katz index >D. RESULTS: Sixty-four diabetic patients on DH care and 36 on CH care were included, with no differences in baseline characteristics. The average cost per patient was 1,345.1±793.6 € in the DH group and 2,212.4±982.5 € in the CH group (P<0.001). There were no differences in number of subjects with mild hypoglycemia during follow-up (45.3% DH versus 33.3% CH, P=0.24), nor in the percentage of patients achieving a glycated hemoglobin (HbA(1c)) <8% (67.2% DH versus 58.3% CH, P=0.375). Readmissions for hyperglycemic crisis and pressure ulcer rates were significantly higher in the CH group. CONCLUSION: DH care for hyperglycemic crises is more cost-effective than CH care, with a net saving of 1,418.4 € per case, lower number of readmissions and pressure ulcer rates, and similar short-term glycemic control and hypoglycemia rates.

Hipotiroidismo y síndrome de Down / Hypothyroidism and Down’s syndrome

Introducción: el hipotiroidismo subclínico es frecuente en los primeros años de vida de los niños con síndrome de Down (SD). El objetivo del estudio fue analizar la evolución natural de esta patología identificando los factores que predicen su remisión espontánea. Material y métodos: estudio observacional retrospectivo sobre pacientes con SD e hipotiroidismo diagnosticado antes de los 5 años de edad, atendidos en un centro médico de referencia para SD. Resultados: se identificó a 53 pacientes con hipotiroidismo subclínico, 28 niños y 25 niñas, con una media de edad de 2,4 ± 1,1 años. El hipotiroidismo se resolvió espontáneamente en 39 casos (73,6%), en un tiempo medio de 13,2 ± 11,1 meses, y la tasa de resolución fue significativamente superior en los pacientes sin bocio: 94,9% (intervalo de confianza [IC] del 95%: 81,2-99,3%) frente a 28,6% (IC del 95%: 4,4-37,7%), p < 0,05, y con anticuerpos antitiroideos negativos: 89,7% (IC del 95%: 74,6-96,2%) frente a 42,9% (IC del 95%: 20,7-56%), p < 0,05. Un total de 15 pacientes (28,3%) fueron tratados con levotiroxina. Conclusiones: el hipotiroidismo subclínico que aparece en la primera infancia en el SD suele ser transitorio. La ausencia de bocio y anticuerpos se asocia a una mayor tasa de resolución espontánea (AU)

Introduction: Subclinical hypothyroidism is common in the first years of life of children with Down’s syndrome (DS). The aim of this study was to analyse the natural evolution of this disease and to identify the factors that predict its spontaneous remission. Material and methods: A retrospective, observational study conducted on patients with DS and hypothyroidism diagnosed before 5 years of age, who were seen in a DS reference medical centre. Results: A total of 53 patients, 28 boys and 25 girls, with a mean age 2.4 ± 1.1 years, were identified with subclinical hypothyroidism. The hypothyroidism resolve spontaneously in 39 cases (73.6%), in a mean time of 13.2 ± 11.1 months, this resolution rate being significantly higher in the patients without goitre: 94.9% (95% confidence interval [CI]: 81.2-99.3%) vs 28.6% (95% CI: 4.4-37.7%), p < .05, and with negative antithyroid antibodies: 89.7% (95% CI: 74.6-96.2%), vs 42.9% (95% CI: 20.7–56%), p < .05). Fifteen patients (28.3%) were treated with levothyroxine. Conclusions: The subclinical hypothyroidism that appears in early infancy in DS is usually transient. The absence of goitre and antibodies is associated with a higher spontaneous resolution rate (AU)

Primary hypothyroidism with pericardial tamponade.

We report a rare case of pericardial effusion and tamponade in a 10-yr-old child with undiagnosed primary hypothyroidism, who presented to us with delayed milestones, anasarca for 7 mth and respiratory distress for 20 days. The child recovered with ultrasound guided pericardial tap and thyroxine replacement therapy.

Risks of anemia in infants according to dietary iron density and weight gain rate.

BACKGROUND: The objective of the study was to identify risk factors of infant anemia and to assess a new indirect method to identify the risks of anemia using a probability curve based on dietary iron density and weight gain rate. METHODS: A cross-sectional study was conducted on 110 term infants in a public health unit in Goiania, Brazil. A socioeconomic, demographic, anthropometric survey and dietary assessment were performed. Hemoglobin, red blood cell distribution width (RDW), ferritin, and C-reactive protein were determined. RESULTS: The risk factors identified by final adjusted logistic regression were male infants (OR = 2.38), infants whose mothers were housewives (OR = 5.01), and households with more than three members (OR = 3.08). Another risk factor was the introduction of meat after 6 months (OR = 3.3). There was a positive dose-response effect between milk consumption and prevalence of anemia adjusted for sex and age (Effect = 0.120; 95% CI: 0.015, 0.225). Dietary iron density (from 6 to 9 months) and weight gain rate (from 9 to 12 months) significantly affected the probability of the infant having anemia. CONCLUSIONS: The probability curve for anemia obtained from dietary iron density and weight gain rate can be used to identify the risks of anemia, and together with the risk factors identified are important for anemia prevention programs.

Anemia do lactente: etiologia e prevalência / Anemia in infancy: etiology and prevalence

Objetivos: verificar a prevalênciade anemia, anemia ferropriva e deficiência de ferro em lactentes, de unidade pública de saúde, no município de Goiânia, Brasil, analisar e correlacionar as variáveis bioquímicas e hematológicas.Métodos: realizou-se estudo transversal. De 120 mães entrevistadas, foram incluídos 1101actentesde6a 12 meses de idade, a termo e não gemelares. Dados socioeconômicos e hematológicos foram obtidos. Colheu-se sangue venoso dos lactentes em jejum para realização do hemograma completo por contagem eletrônica, ferrosérico, ferritinaséricae proteína C-reativa, os quais foram utilizados na avaliação da etiologia ferropriva nos anêmicos. Crianças com hemoglobina < llg/dl foram consideradas anêmicas.Resultados: a prevalência de anemia observada foi de 60,9por cento.Ao se considerar no diagnóstico da etiologia ferropriva nos lactentes sem processo inflamatório, a alteração da hemoglobina mais dois índices entre volume corpuscular médio (VCM), ou hemoglobina corpuscular média (HCM), ou ferritina, ou ferro sérico, a prevalência de etiologia ferropriva foi de 87por cento. Porém, ao se incluir nos índices a amplitude de distribuição dos eritrócitos (RDW), a prevalência foi de 97,8por cento. Nos não anêmicos, considerando a ferritina e o RDW, observou-se 28por cento de prevalência de deficiência de ferro. As melhores correlações entre as variáveis hematológicas e bioquímicas foram hemoglobina e hematócrito (r = 0,946), e HCM com o VCM (r = 0,950).Conclusão: a principal etiologia da anemia nos lactentes foi a ferropriva, cuja prevalência variou com os diferentes parâmetros utilizados e critérios adotados

Mechanisms of desorption of 134Cs and 85Sr aerosols deposited on urban surfaces.

The radioactive isotopes of cesium and strontium may be deposited on urban surfaces in the case of an accidental atmospheric discharge from a nuclear facility and thus imply a health hazard. In order to handle the decontamination of these surfaces, we have carried out experiments under controlled conditions on tiles and concrete and we have studied.the physical and chemical mechanisms at the solid-liquid interface. The deposition of radionuclides was carried out in the form of aerosols indicating an accidental source term. Their desorption by rainwater is low in all cases, of the order of 5-6% for cesium for any material and 29 and 12% for strontium on tile and concrete, respectively. The low desorption values of cesium may be explained by the strong bonding that occurs with the silicates constituting the tile due to virtually irreversible processes of exchange of ions and by the formation of insoluble complexes with the C--S-H gel of concrete. The strontium-tile bonds are weaker, while strontium precipitates with the carbonates of concrete in the form of SrCO3. In view of these characteristics, washing solutions with high concentrations of chloride and oxalate of ammonium chosen for their ion-exchanging and sequestering properties were tested on these surfaces. The desorption of cesium improved strongly since it reached 70% on tile and 90% on concrete after 24h of contact, which is consistent with our knowledge of the; bonds between this element and the surfaces. Strontium, given the greater complexity of physical and chemical forms that it may take is less well desorbed. The ammonium chloride improves the desorption (50% and 40%, for tile and concrete, respectively) but the oxalate, while it does not affect desorption on the tiles, decreases that on the concrete since by strongly etching the concrete, it causes the release of carbonate ions that precipitate with strontium.

[Anemia in infancy: etiology and prevalence]. / Anemia do lactente: etiologia e prevalência.

OBJECTIVE: To verify the prevalence of anemia, iron deficiency anemia and iron deficiency in infants, at a Public Health Unit in the city of Goiânia-Brazil; to analyze and to correlate the hematologic and biochemical variables. METHODS: A cross-sectional study was carried out. One hundred and ten full-term infants of the 120 mothers interviewed were included. The infants aged between six and twelve months and there were not twins. Socioeconomic and hematologic data was obtained. Venous blood was taken from fasting infants in order to carry out a complete hemogram through electronic cell counting, serum iron, serum ferritin and C-reactive protein, which were used in the evaluation of the etiology of iron deficiency in the anemic infants. Children with hemoglobin <11 g/dL were considered anemic. RESULTS: The prevalence of anemia was 60.9%. In the diagnosis of the iron deficiency etiology in infants without an inflammation process, when considering the alteration of hemoglobin plus two more indices among mean corpuscular volume (MCV) or mean corpuscular hemoglobin (MCH) or serum ferritin or serum iron, the prevalence of the iron deficiency was 87%. Nevertheless, when red cell distribution width (RDW) was included in the indices, the prevalence was 97.8%. In the non-anemic infants, considering ferritin and RDW, the prevalence of iron deficiency observed was 28%. The best correlation among hematologic and biochemical variables were between hemoglobin and hematocrit (r=0.946), and MCH with MCV (r=0.950). CONCLUSIONS: The main etiology in infants was iron deficiency anemia and its prevalence varied according to different parameters and criteria.

Time-co-ordinated control of glycogen synthase, protein phosphatase 2A and protein kinase CK2 during culture growth in Yarrowia lipolytica in relation to glycogen metabolism.

In the growth course of the lipolytic yeast Yarrowia lipolytica, the activities of protein phosphatase 2A (PP2A) and glycogen synthase (GS) rise during the exponential phase and concomitantly glycogen storage occurs in the cells. There is also an increase in the independence ratio (RI) indicating a shift from an inactive phosphorylated GS form to an active dephosphorylated GS form. During the early stationary phase, an increase in protein kinase CK2 (CK2) activity, a reversion of RI variation and a glycogen content decrease are observed. GS activity proved to be a good indicator of early culture growth phase. Experiments carried out with enzymes purified from Y. lipolytica show strong RI variations upon the action of CK2 and PP2Ac, and 32P incorporation into GS protein through phosphorylation by CK2. GS activity would be controlled by the sequential action of PP2A and CK2.

Characterization of an exocellular protein phosphatase with dual substrate specificity from the yeast Yarrowia lipolytica.

In previous work, the major endocellular protein phosphatase activity has been identified in the secretory yeast Yarrowia lipolytica as a PP2A. The aim of the present work was to seek the presence of one protein phosphatase excreted in the exocellular medium and to study its activity during yeast growth in media supplemented or not supplemented with inorganic phosphate. Protein phosphatase was purified and activity was assayed by following the dephosphorylation of three substrates, [32P]casein, phosphotyrosine and a synthetic tyrosine-phosphorylated peptide. Phosphatase activity recovered in the medium after 25 h culture was greatly enhanced by Pi-deficiency. After several purification steps, the enzyme preparation presents an apparent electrophoretic homogeneity on SDS-PAGE with associated phosphoseryl/threonyl and phosphotyrosyl activities. The kinetic properties exclude contamination by a copurified protein and it is concluded that the two activities are carried by the same single proteic species. It was characterized by gel filtration as a 33 kDa protein with one single subunit demonstrated by SDS-PAGE. An absolute requirement for reducing-agents is observed suggesting that the enzyme contains at least one essential reactive cysteinyl residue. Optimum pH value is 6.1, apparent K(m) for phosphotyrosine was calculated to be 760 microM and Hill coefficient 3.2 indicating a rather high cooperativity. These results showed that the involvement of alkaline and/or acid phosphatase was unlikely. In conclusion, a protein phosphatase distinct from endocellular PP2A is secreted by Yarrowia lipolytica and characterized as a phosphotyrosine protein phosphatase with associated phosphoseryl/threonyl activity.

Purification and characterization of a type 2A protein phosphatase from Yarrowia lipolytica grown on a phosphate-deficient medium.

Intracellular protein phosphatase activity has been identified in the yeast Yarrowia lipolytica. This activity was maximal early in its exponential growth phase, and it was enhanced by Pi-deficiency of the culture medium. On a Pi-deficient medium, the major protein phosphatase was purified. This enzyme was dissociated with 80% ethanol treatment, its activity was slightly increased (30%) with heparine and largely enhanced (1.5 to 3-fold) with polycations. This enzyme could be classified as a type 2A protein phosphatase. It is composed of a catalytic subunit and other subunits. Its optimum pH value is 7.2, the apparent Km for casein is 37 microM and the apparent velocity 3.6 pmol hydrolyzed32 Pi min-1 pmol-1 enzyme.

Staining technique for phosphatases in polyacrylamide gels.

The described staining technique affords a means to detect and evaluate directly on the electrophoresis polyacrylamide gel the activity of phosphatases present in complex extracts or in purified solutions, in particular phosphatases requiring alkaline pH for optimum activity, e.g. fructose bisphosphatase, sedoheptulose bisphosphatase, and alkaline phosphatase, and 5'-nucleotidase. The method is based on a modified malachite green procedure determining orthophosphate released by the specific enzyme reactions carried out in the gel and leads to the formation of sharp blue-green-colored bands on a pale blue background. Staining intensity is proportional to the amount of Pi formed. The lower limit of phosphate detection was in the order of 0.2 nmol. This method provides a routine tool for comparative studies of biochemical properties and isozymic composition of phosphatases from diverse sources.

Non reductive activation of spinach chloroplastic fructose-1,6-bisphosphatase: evidence for structural modification of the enzyme.

Preincubation of chloroplastic fructose-1,6-bisphosphatase (FBPase) in the presence of Ca2+/fructose-1,6-bisphosphate (FBS) gives rise to an active enzyme. This non-reductive activation at pH 8 occurs in the same range of time (min) as the well known reductive activation by thioredoxins and this process is reversible. A conformational change of the enzyme occurs upon the activation by Ca2+/FBP. Indeed, the circular dichroism and the fluorescence spectra of the inactive and active enzymes are different. The titration of the sulfhydryl groups of both enzymes indicates that one -SH group per monomer is unmasked upon activation, and the isoelectrofocusing pattern shows that the pI of inactive FBPase is shifted from 4.26 to 4.56 upon this non-reductive process.

Multiple levels in the control of rhythms in enzyme synthesis and activity by circadian clocks: recent trends.

It is now well established that circadian clocks can control rhythmicity at different stages of the sequence of events leading from gene activity to a functional enzyme molecule. Conceptual and experimental distinction of the effective control targets is emphasized, with particular attention to recent results obtained on circadian clock control of transcription and to data indicating that proteins can behave as conformational oscillators. Thus circadian rhythmicity both in gene expression and in the dynamics of the enzyme molecule would contribute to the temporal compartmentation of processes such as metabolic co-ordination and channeling necessary for the adaptive efficiency of physiological programmes.

Are spontaneous conformational interconversions a molecular basis for long-period oscillations in enzyme activity?

An unconventional hypothesis to the molecular basis of enzyme rhythms is that the intrinsic physical instability of the protein molecules which, in an aqueous medium, tend to move continuously from one conformational state to another could lead, in the population of enzyme molecules, to sizeable long-period oscillations in affinity for substrate and sensitivity to ligands and regulatory effects. To investigate this hypothesis, malate dehydrogenase was extracted and purified from leaves of the plant Kalanchoe blossfeldiana. The enzyme solutions were maintained under constant conditions and sampled at regular intervals for up to 40 or 70 h for measurements of activity as a function of substrate concentration, Km for oxaloacetic acid and sensitivity to the action of 2,3-butanedione, a modifier of active site arginyl residues. The results show that continuous slow oscillations in the catalytic capacity of the enzyme occur in all the extracts checked, together with fluctuations in Km. Apparent circadian periodicities were observed in accordance with previous data established during long run (100 h) experiments. The saturation curves for substrate showed multiple kinetic functions, with various pronounced intermediary plateaus and "bumps" depending on the time of sampling. Variation in the response to the effect of butanedione indicated fluctuation in the accessibility to the active site. Taken together, the results suggest that, under constant conditions, the enzyme in solution shifts continuously and reversibly between different configurations. This was confirmed by parallel studies on the proton-NMR spectrum of water aggregates in the enzyme solution and proton exchange rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in oxidative properties of Kalanchoe blossfeldiana leaf mitochondria during development of Crassulacean acid metabolism.

Kalanchoe blossfeldiana plants grown under long days (16 h light) exhibit a C3-type photosynthetic metabolism. Switching to short days (9 h light) leads to a gradual development of Crassulacean acid metabolism (CAM). Under the latter conditions, dark CO2 fixation produces large amounts of malate. During the first hours of the day, malate is rapidly decarboxylated into pyruvate through the action of a cytosolic NADP(+)-or a mitochondrial NAD(+)-dependent malic enzyme. Mitochondria were isolated from leaves of plants grown under long days or after treatment by an increasing number of short days. Tricarboxylic acid cycle intermediates as well as exogenous NADH and NADPH were readily oxidized by mitochondria isolated from the two types of plants. Glycine, known to be oxidized by C3-plant mitochondria, was still oxidized after CAM establishment. The experiments showed a marked parallelism in the increase of CAM level and the increase in substrate-oxidation capacity of the isolated mitochondria, particularly the capacity to oxidize malate in the presence of cyanide. These simultaneous variations in CAM level and in mitochondrial properties indicate that the mitochondrial NAD(+)-malic enzyme could account at least for a part of the oxidation of malate. The studies of whole-leaf respiration establish that mitochondria are implicated in malate degradation in vivo. Moreover, an increase in cyanide resistance of the leaf respiration has been observed during the first daylight hours, when malate was oxidized to pyruvate by cytosolic and mitochondrial malic enzymes.