Systemic cytokines, chemokines and growth factors reveal specific and shared immunological characteristics in infectious cardiomyopathies.

Heart disease is a major cause of death worldwide. Chronic Chagas cardiomyopathy (CCC) caused by infection with Trypanosoma cruzi leading to high mortality in adults, and rheumatic heart disease (RHD), resulting from infection by Streptococcus pyogenes affecting mainly children and young adults, are amongst the deadliest heart diseases in low-middle income countries. Despite distinct etiology, the pathology associated with both diseases is a consequence of inflammation. Here we compare systemic immune profile in patients with these cardiopathies, to identify particular and common characteristics in these infectious heart diseases. We evaluated the expression of 27 soluble factors, employing single and multivariate analysis combined with machine-learning approaches. We observed that, while RHD and CCC display higher levels of circulating mediators than healthy individuals, CCC is associated with stronger immune activation as compared to RHD. Despite distinct etiologies, univariate analysis showed that expression of TNF, IL-17, IFN-gamma, IL-4, CCL4, CCL3, CXCL8, CCL11, CCL2, PDGF-BB were similar between CCC and RHD, consistent with their inflammatory nature. Network analysis revealed common inflammatory pathways between CCC and RHD, while highlighting the broader reach of the inflammatory response in CCC. The final multivariate model showed a 100% discrimination power for the combination of the cytokines IL-12p70, IL-1Ra, IL-4, and IL-7 between CCC and RHD groups. Thus, while clear immunological distinctions were identified between CCC and RHD, similarities indicate shared inflammatory pathways in these infectious heart diseases. These results contribute to understanding the pathogenesis of CCC and RHD and may impact the design of immune-based therapies for these and other inflammatory cardiopathies that may also share immunological characteristics.

The influence of periapical lesions on the repeatability of two electronic apex locators in vivo.

OBJECTIVES: To determine the influence of periapical lesions on the repeatability of two electronic apex locators (EALs), Root ZX II, and RomiApex A-15, in maxillary anterior teeth, in vivo. MATERIALS AND METHODS: After approval by the local ethics committee, 43 maxillary anterior teeth scheduled for root canal therapy were assigned to two groups. The periapical lesion (PAL) group included 21 teeth with necrotic pulps and radiographically visible periapical lesion, and the normal periapex (NPA) group consisted of 22 teeth with vital pulps and no periapical lesion. In each canal, Root ZX II and RomiApex A-15 were used to determine working length defined as the "zero" reading on the display. Two consecutive measurements were performed with each EAL on each tooth and a second operator measured the endodontic file with a digital caliper without knowledge of the EAL being used or the tooth diagnosis. The absolute value of the difference between the first and second measurement (measurement pairs) was calculated. Repeatability was evaluated by the Bland-Altman method, and an aligned ranks transformation ANOVA was conducted to compare the EALs. RESULTS: The median absolute difference between measurement pairs was significantly lower (p < 0.001) and the limits of agreement were narrower in the NPA group. Among the EALs, median absolute differences were significantly smaller for Root ZX (p < 0.001). CONCLUSIONS: Measurements were more repeatable when no periapical lesion was present. Root ZX showed better repeatability than RomiApex. CLINICAL RELEVANCE: Periapical lesions seem to influence successive in vivo measurements with EALs.

Panoramic Dental Radiography Image Enhancement Using Multiscale Mathematical Morphology.

Panoramic dental radiography is one of the most used images of the different dental specialties. This radiography provides information about the anatomical structures of the teeth. The correct evaluation of these radiographs is associated with a good quality of the image obtained. In this study, 598 patients were consecutively selected to undergo dental panoramic radiography at the Department of Radiology of the Faculty of Dentistry, Universidad Nacional de Asunción. Contrast enhancement techniques are used to enhance the visual quality of panoramic dental radiographs. Specifically, this article presents a new algorithm for contrast, detail and edge enhancement of panoramic dental radiographs. The proposed algorithm is called Multi-Scale Top-Hat transform powered by Geodesic Reconstruction for panoramic dental radiography enhancement (MSTHGR). This algorithm is based on multi-scale mathematical morphology techniques. The proposal extracts multiple features of brightness and darkness, through the reconstruction of the marker (obtained by the Top-Hat transformation by reconstruction) starting from the mask (obtained by the classic Top-Hat transformation). The maximum characteristics of brightness and darkness are added to the dental panoramic radiography. In this way, the contrast, details and edges of the panoramic radiographs of teeth are improved. For the tests, MSTHGR was compared with the following algorithms: Geodesic Reconstruction Multiscale Morphology Contrast Enhancement (GRMMCE), Histogram Equalization (HE), Brightness Preserving Bi-Histogram Equalization (BBHE), Dual Sub-Image Histogram Equalization (DSIHE), Minimum Mean Brightness Error Bi-Histogram Equalization (MMBEBHE), Quadri-Histogram Equalization with Limited Contrast (QHELC), Contrast-Limited Adaptive Histogram Equalization (CLAHE) and Gamma Correction (GC). Experimentally, the numerical results show that the MSTHGR obtained the best results with respect to the Contrast Improvement Ratio (CIR), Entropy (E) and Spatial Frequency (SF) metrics. This indicates that the algorithm performs better local enhancements on panoramic radiographs, improving their details and edges.

Long-Term Safety of In Utero Exposure to Anti-TNFα Drugs for the Treatment of Inflammatory Bowel Disease: Results from the Multicenter European TEDDY Study.

OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox-regression analysis was performed to identify potential predictive factors for severe infections in the offspring. RESULTS: The study population comprised 841 children, of whom 388 (46%) had been exposed to anti-TNFα agents. Median follow-up after delivery was 47 months in the exposed group and 68 months in the non-exposed group. Both univariate and multivariate analysis showed the incidence rate of severe infections to be similar in non-exposed and exposed children (1.6% vs. 2.8% per person-year, hazard ratio 1.2 (95% confidence interval 0.8-1.8)). In the multivariate analysis, preterm delivery was the only variable associated with a higher risk of severe infection (2.5% (1.5-4.3)). CONCLUSIONS: In utero exposure to anti-TNFα drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children.

Correction: Humic-like substances from urban waste as auxiliaries for photo-Fenton treatment: a fluorescence EEM-PARAFAC study.

Correction for 'Humic-like substances from urban waste as auxiliaries for photo-Fenton treatment: a fluorescence EEM-PARAFAC study' by S. García Ballesteros et al., Photochem. Photobiol. Sci., 2017, 16, 38-45.

A comparison of 24 chemicals in the six-well bacterial reverse mutation assay to the standard 100-mm Petri plate bacterial reverse mutation assay in two laboratories.

The bacterial reverse mutation assay (Ames) is a fundamental genetic toxicology test, and efforts to miniaturize the regulatory GLP version are essential in assessing genotoxic liabilities earlier in the drug development pipeline. Two versions of the Ames were compared: the six-well (miniaturized) plate and the standard 100-mm plate test at two different laboratories. Of twenty-four chemicals tested, a subset of six chemicals was tested in the six-well test only and the remaining eighteen were evaluated in both versions of the test. The plate incorporation procedure was used with one Escherichia coli and four different Salmonella strains. The six-well test uses the same plating procedure and evaluation methods as the standard Ames assay in 100-mm plates, but the smaller format requires 20% of the test chemical. Additionally, the six-well test uses a limit concentration of 1000 µg/well versus the standard Petri plate test limit concentration of 5000 µg/plate. Testing across the two formats resulted in 100% concordance in overall mutagenicity judgement and 94% concordance across all tester strains and conditions. Known mutagenic positive control chemicals were correctly detected as positive in both formats. The overall conclusion is that the six-well assay results are concordant with the standard assay format in this evaluation and could be a reliable alternative.

Humic-like substances from urban waste as auxiliaries for photo-Fenton treatment: a fluorescence EEM-PARAFAC study.

In this work, analysis of excitation-emission-matrices (EEM) has been employed to gain further insight into the characterization of humic like substances (HLS) obtained from urban wastes (soluble bio-organic substances, SBOs). In particular, complexation of these substances with iron and changes along a photo-Fenton process have been studied. Recorded EEMs were decomposed by using parallel factor analysis (PARAFAC). Three fluorescent components were identified by PARAFAC modeling of the entire set of SBO solutions studied. The EEM peak locations (λex/λem) of these components were 310-330 nm/400-420 nm (C1), 340-360 nm/450-500 nm (C2), and 285 nm/335-380 nm (C3). Slight variations of the maximum position of each component with the solution pH were observed. The interaction of SBO with Fe(iii) was characterized by determining the stability constants of the components with Fe(iii) at different pH values, which were in the order of magnitude of the ones reported for humic substances and reached their highest values at pH = 5. Photochemical experiments employing SBO and Fe(iii), with and without H2O2, showed pH-dependent trends for the evolution of the modeled components, which exhibited a strong correlation with the efficiency reported for the photo-Fenton processes in the presence of SBO at different pH values.

A Ferromagnetic Salicylaldoximate/Azide Mn(II)2Mn(III)6 Cluster with an S = 17 Ground State and a Single-Molecule-Magnet Response.

One new Mn(II)2Mn(III)6 cluster exhibiting an S = 17 spin ground state and single-molecule-magnet properties has been designed linking Mn(III)3-salicylaldoximate triangles and tetracoordinated Mn(II) cations by means of end-on azido bridges. The ferromagnetic coupling has been rationalized as a function of their structural parameters.

IFN-gamma role in granuloma formation in experimental subcutaneous cysticercosis.

Cysticercosis is an infection caused by the metacestode larval stage of Taenia parasites in tissues and elicits a host-parasite reaction in which the immune response may be decisive in the disease development. The aim of this study was to evaluate the role of IFNγ (IFN-gamma) in the experimental model of subcutaneous infection with Taenia crassiceps (T. crassiceps) cysticerci using IFNγ knockout mice. Male C57BL/6 and C57BL/6 KO IFNγ mice 8-12 weeks of age were inoculated with T. crassiceps cysticerci into the subcutaneous tissue of the dorsum. At 7 and 30 (acute phase), 60 and 90 (chronic phase) days post infection, animals from each group had their blood and the subcutaneous tissues collected for serologic and pathological studies. IFNγ and IL-4 were dosed and the histopathological analysis was performed. In the presence of IFNγ there was the establishment of a mixed Th1/Th2 systemic immune profile. This profile also locally induced the granuloma formation which was constituted by cells that played important roles in the parasitary destruction and that were likely associated to the Th1 axis of mixed immune response. On the other hand, the absence of IFNγ appears to favor the parasitary growth which may be related to the development of a systemic Th2 immune response. This profile influenced the granuloma formation with immunoregulatory properties and appears to be important in the collagen synthesis.

Effects of seasonal ambient heat stress (spring vs. summer) on physiological and metabolic variables in hair sheep located in an arid region.

Twenty Dorper × Pelibuey primiparous ewes were used to evaluate effects of seasonal ambient heat stress (i.e., spring vs. summer) on physiological and metabolic responses under production conditions in an arid region. Ten ewes experiencing summer heat stress (i.e., temperature = 34.8 ± 4.6 °C; THI = 81.6 ± 3.2 units) and 10 under spring thermoneutral conditions (temperature = 24.2 ± 5.4 °C; THI = 68.0 ± 4.8 units) were corralled together to measure rectal temperature, respiratory frequency, and skin temperatures at 0600, 1200, 1800, and 2400 h on four occasions over 40 days. Blood metabolite and electrolyte concentrations were also measured at 0600 and 1800 hours. Data were analyzed with a completely randomized design using repeated measurements in time. Rectal and skin temperatures, as well as respiratory frequency, were higher (P < 0.01) in summer than spring at all measured days. Blood serum glucose, cholesterol, triglycerides, and chlorine concentrations were lower (P < 0.01) in summer than spring at 0800 and 1800 hours. In contrast, summer heat stress increased (P < 0.01) blood urea and potassium concentrations at 0800 and 1800 hours. Compared with spring thermoneutral conditions, summer heat stress affected the physiological and metabolic status of hair breed ewes in an arid region, which included blood metabolite and electrolyte adjustments to efficiently cope with summer heat stress.

Catastrophic flood of the Mediterranean after the Messinian salinity crisis.

The Mediterranean Sea became disconnected from the world's oceans and mostly desiccated by evaporation about 5.6 million years ago during the Messinian salinity crisis. The Atlantic waters found a way through the present Gibraltar Strait and rapidly refilled the Mediterranean 5.33 million years ago in an event known as the Zanclean flood. The nature, abruptness and evolution of this flood remain poorly constrained. Borehole and seismic data show incisions over 250 m deep on both sides of the Gibraltar Strait that have previously been attributed to fluvial erosion during the desiccation. Here we show the continuity of this 200-km-long channel across the strait and explain its morphology as the result of erosion by the flooding waters, adopting an incision model validated in mountain rivers. This model in turn allows us to estimate the duration of the flood. Although the available data are limited, our findings suggest that the feedback between water flow and incision in the early stages of flooding imply discharges of about 10(8) m(3) s(-1) (three orders of magnitude larger than the present Amazon River) and incision rates above 0.4 m per day. Although the flood started at low water discharges that may have lasted for up to several thousand years, our results suggest that 90 per cent of the water was transferred in a short period ranging from a few months to two years. This extremely abrupt flood may have involved peak rates of sea level rise in the Mediterranean of more than ten metres per day.

[Model for a comprehensive approach to maternal mortality and severe maternal morbidity]. / Modelo para abordar integralmente la mortalidad materna y la morbilidad materna grave.

Maternal mortality is an important public health and human rights problem and reflects the effects of social determinants on women's health. Understanding the extent and causes of maternal death has been insufficient to achieve the Millennium Development Goals. This article proposes a model for a comprehensive approach to maternal mortality, covering seven areas: prioritization and definition of the problem, contextual description, methodological scope, knowledge management, innovation, implementation, and a monitoring and evaluation system. This model helps address problems associated with maternal mortality and severe maternal morbidity through early monitoring of potentially fatal complications in the reproductive process. Knowledge management is important for the reorientation of policies, programs, and health care. Interaction and synergies among people, communities, and actors in the health system should be strengthened in order to improve the results of health programs. More validated scientific information is needed on how actions should be implemented in different environments. It is essential to strengthen communication among research centers, cooperation agencies, and government organizations and to include them in programs and in the definition of a new women's health agenda in the Region of the Americas.

Uric acid and acute kidney injury in high-risk patients for developing acute kidney injury undergoing cardiac surgery: A prospective multicenter study.

PURPOSE: It is unclear whether preoperative serum uric acid (SUA) elevation may play a role in the development of acute kidney injury (AKI) associated with cardiac surgery (CSA-AKI). We conducted a cohort study to evaluate the influence of preoperative hyperuricemia on AKI in patients at high risk for developing SC-AKI. DESIGN: Multicenter prospective international cohort study. SETTING: Fourteen university hospitals in Spain and the United Kingdom. PARTICIPANTS: We studied 261 consecutive patients at high risk of developing CSA-AKI, according to a Cleveland score ≥ 4 points, from July to December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: AKIN criteria were used for the definition of AKI. Multivariable logistic regression models and propensity score-matched pairwise analysis were used to determine the adjusted association between preoperative hyperuricemia (≥7 mg/dL) and AKI. Elevated preoperative AUS (≥7 mg/dL) was present in 190 patients (72.8%), whereas CSA-AKI occurred in 145 patients (55.5%). In multivariable logistic regression models, hyperuricemia was not associated with a significantly increased risk of AKI (adjusted Odds Ratio [OR]: 1.58; 95% confidence interval [CI]: 0.81-3; P = .17). In propensity score-matched analysis of 140 patients, the hyperuricemia group experienced similar adjusted odds of AKI (OR 1.05, 95%CI 0.93-1.19, P = .37). CONCLUSIONS: Hyperuricemia was not associated with an increased risk of AKI in this cohort of patients undergoing cardiac surgery at high risk of developing CSA-AKI.

Polymorphisms of estrogen receptor-α gene in Brazilian women with high breast density after menopause.

UNLABELLED: The association of genetic polymorphism in the estrogen receptor alpha (ERα) gene and risk for diseases including breast cancer (BC) has been the subject of great interest. OBJECTIVE: Checking on women with high breast density after menopause, the frequency of the Pvull and Xbal polymorphisms of the ERα gene and the correlation between them and the known risk factors for breast cancer. METHOD: Observational study with 308 women between 45 and 65 years old with high breast density, without hormonal therapy, menstruation for a year or more, breast and ovarian cancer history. It was characterized in clinical history and physical examination: menarche, menopause, parity, family history of BC, smoking, alcohol intake and body mass index. RESULTS: The allelic and genotypic frequencies for ERα-Pvull and Xbal: p = 43.99%; p = 56.01%; pp = 32.14%; Pp = 47.73% and PP = 20.13%; X = 41.56%; x = 58.44%; xx = 33.44%; Xx = 50.00% and XX = 16.56%, respectively. The most frequent risk factors for BC: menarche before 12 years old (35.38%), nulliparity or first child after 28 years old (41.66%), family history of BC (19.16%) and overweight/obesity (62.01%). CONCLUSION: Allelic and genotypic distribution similar to literature. The risk factors for BC were more prevalent in women with high breast density but without significant associations with these polymorphisms.

Visual analogue scales for grading faecal incontinence and quality of life: their relationship with the Jorge-Wexner score and Rockwood scale.

BACKGROUND: The purpose of this study was to determine the probability of substituting two validated methods frequently used for scoring severity and quality of life of faecal incontinence (FI) by a single score represented in a visual analogue scale (VAS). METHODS: One hundred and three consecutive unselected patients affected by FI of different aetiologies were prospectively included in the study. Evaluation of the continence status and quality of life referred to the last month was scored by (1) Jorge-Wexner score, (2) Rockwood FIQL scale, (3) Visual Analogue Scale for Faecal Incontinence (VASFI), and (4) Visual Analogue Scale for Quality of Life (VASQL). Patients unable to respond accurately to one or more of the questionnaires were excluded. The Bland and Altman method was applied to evaluate the agreement between Jorge-Wexner and VASFI. Correlation between both the analogue scales (VASFI and VASQL) and each one with each of the four FIQL scale scores was first determined by an analysis of simple correlation with each subscale and thereafter by multiple regression analysis following the backward strategy. RESULTS: Comparison of VASFI with the Jorge-Wexner score shows that the two methods are neither concordant nor interchangeable, and in a given patient, the differences between both may fluctuate between 5.4 and -10.6 (95 % confidence interval). Correlation of VASFI and VASQL shows that the correlation between both the analogue scales is middling (r (2) = 0.543, ß coefficient -0.538). Correlation of VASFI and FIQL subscales shows that in simple regression analysis, VASFI correlates with lifestyle, coping/behaviour, and embarrassment, but after multiple regression analysis, VASFI correlates significantly only with embarrassment. Correlation of VASQL and FIQL subscales shows that in simple regression analysis, VASQL correlates with lifestyle, coping/behaviour, and embarrassment, but after multiple regression analysis, VASQL only correlates significantly with coping/behaviour. CONCLUSIONS: This study shows that a VAS for FI cannot replace the Jorge-Wexner score and a VAS for quality of life cannot substitute all the four subscales of FIQL. Severity of FI and its impact on quality of life expressed in a VAS only have a fair correlation, showing that they do not assess the same issues, which is also supported by the finding that VASFI correlates significantly only with the embarrassment subscale of FIQL.

Extracorporeal membrane oxygenation in lung transplantation.

The use of extracorporeal techniques in cardiopulmonary support has spread in the last 20 years. ECMO (extracorporeal membrane oxygenation) devices are the most commonly employed option, and have been used for years in lung transplant programs. Nevertheless, few articles on the results of ECMO involving large numbers of cases have been published to date. The use of ECMO in respiratory failure affords immediate oxygen support in patients with severe hypoxia and/or acidosis, and moreover provides pulmonary protection, since it allows an instantaneous decrease in the ventilator pressure and FiO2 needs. The complications of ECMO have been minimized thanks to the technological improvements found in the latest devices, though renal failure, infections, bleeding, and vascular and mechanical complications are still reported in many studies. At present there is less controversy regarding the use of cardiorespiratory assists with ECMO as an alternative in decompensated patients who are on the waiting list, referred to the intra- and postoperative periods of lung transplantation.

[Antifungal prophylaxis in the postoperative period of lung transplant surgery in Spain]. / Profilaxis antifúngica en el postoperatorio de trasplante de pulmón en España.

OBJECTIVES: To examine the type and duration of antifungal prophylaxis provided during the postoperative period of lung transplant recipients, together with the most frequent complications during admission to Intensive Care Units in Spain. PATIENTS AND METHODS: A questionnaire was developed including demographic data on each transplant center, the type of antifungal prophylaxis used, its duration, and the most frequent complications. The questionnaire was distributed among the 7 Spanish national lung transplant centers, followed by analysis of the results obtained. RESULTS: All 7 centers completed the questionnaire. All of them provided universal prophylaxis in lung transplant patients. Monotherapy was the most widely used protocol (5/7; 71.4%), with amphotericin B in liposomal or conventional form being the most frequent drug, administered via the inhalatory route. In the case of combination therapy, a great diversity of drugs was observed. The most frequently administered second choice drug was anidulafungin (3/7; 43%), followed by voriconazole (2/7; 28.5%). Antifungal therapy was maintained on an indefinite basis by 43% of the centers. Invasive fungal infection (IFI) in the postoperative period of transplantation during admission to the Intensive Care Unit was suspected in 5-10% of the cases but was confirmed in less than 5%. Among other complications registered in these patients in the Intensive Care Unit, the most frequent problems were respiratory infections (5/7; 71.5%). CONCLUSIONS: Antifungal prophylaxis during the postoperative period of lung transplantation is provided on a universal basis, though consensus is lacking as to the drug of choice, the administration route and the duration of such treatment.

Thermal Performance of Multifunctional Facade Solution Containing Phase Change Materials: Experimental and Numerical Analysis.

This work focuses on the development and analysis of a new multifunctional facade panel incorporating PCM in foam layers. The thermal performance was analysed recurring to a hotbox heat flux meter method to determine the thermal transmittance (U-value) and the main findings are presented. The experimental setup was based on the steady-state approach, using climatic chambers, assuring a stable thermal environment. Even small fractions of PCM achieved a small reduction in thermal amplitude. Numerical simulations using Ansys Fluent were developed to evaluate the performance of PCM use over a wide range of temperature boundary conditions and operating modes. These numerical models were calibrated and validated using the results of experimental tests, achieving a correlation factor of 0.9674, and, thus, accurately representing a real-world scenario. The decrement factor (f) was used to analyse the data. It was identified that the efficiency of the panel and size of the optimum region increased with the PCM fraction growth. The results showed the significant potential of the multi-layered panel, with the thermal regulator effect of the PCM incorporated, on indoor space temperature so as to reach good thermal comfort levels. The efficiency of the panel can be improved by nearly 50% depending on the input boundary conditions. The efficiency of the panel and the size of the optimum region increase with growth in the PCM fraction. The simulated behaviour was at an optimum when the input mean temperature was 20 °C for a room temperature of between 18-20 °C.

Five-year performance analysis of a cystic fibrosis newborn screening program in northeastern Brazil.

OBJECTIVE: To analyze the performance of the cystic fibrosis (CF) newborn screening (NBS) program over its first five years in a Brazilian northeastern state. METHOD: A population-based study using a screening algorithm based on immunoreactive trypsinogen (IRT)/IRT. Data were retrieved from the state referral screening center registry. The program performance was evaluated using descriptive indicators such as the results of an active search, coverage, newborn's age at the time of blood sampling, the time between sample collection and its arrival at the laboratory, and the child's age at diagnosis of disease. RESULTS: The public CF screening program covered 82.6% of the 1,017,576 births that occurred, with an accumulated five-year incidence of 1:20,767 live births. The median (25th-75th) age at diagnosis was 3.5 (2.3-7.3) months. The sampling before 7 days of life for the first IRT (IRT1) increased between 2013 and 2017 from 42.2 to 48.3%. Around 5% of IRT1 samples and 30% of the second samples were collected after 30 days of life. In the first and second stages of screening, 23.6% and 19.9% of the infants, respectively, were lost to follow-up. In both stages of screening, the samples were retained at the health units for a median (25th-75th) of 9.0 (7.0-13.0) days. CONCLUSIONS: The coverage by the CF-NBS program was satisfactory as compared to other Brazilian state rates and the percentage of IRT1 samples collected within the first week of life increased progressively. However, time of samples retention at the health units, inappropriate sampling, inherent methodological problems, and loss of follow-up need to improve.

Synthesis, magnetostructural correlation, and catalytic promiscuity of unsymmetric dinuclear copper(II) complexes: models for catechol oxidases and hydrolases.

Herein, we report the synthesis and characterization, through elemental analysis, electronic spectroscopy, electrochemistry, potentiometric titration, electron paramagnetic resonance, and magnetochemistry, of two dinuclear copper(II) complexes, using the unsymmetrical ligands N',N',N-tris(2-pyridylmethyl)-N-(2-hydroxy-3,5-di-tert-butylbenzyl)-1,3-propanediamin-2-ol (L1) and N',N'-bis(2-pyridylmethyl)-N,N-(2-hydroxybenzyl)(2-hydroxy-3,5-di-tert-butylbenzyl)-1,3-propanediamin-2-ol (L2). The structures of the complexes [Cu(2)(L1)(µ-OAc)](ClO(4))(2)·(CH(3))(2)CHOH (1) and [Cu(2)(L2)(µ-OAc)](ClO(4))·H(2)O·(CH(3))(2)CHOH (2) were determined by X-ray crystallography. The complex [Cu(2)(L3)(µ-OAc)](2+) [3; L3 = N-(2-hydroxybenzyl)-N',N',N-tris(2-pyridylmethyl)-1,3-propanediamin-2-ol] was included in this study for comparison purposes only (Neves et al. Inorg. Chim. Acta2005, 358, 1807-1822). Magnetic data show that the Cu(II) centers in 1 and 2 are antiferromagnetically coupled and that the difference in the exchange coupling J found for these complexes (J = -4.3 cm(-1) for 1 and J = -40.0 cm(-1) for 2) is a function of the Cu-O-Cu bridging angle. In addition, 1 and 2 were tested as catalysts in the oxidation of the model substrate 3,5-di-tert-butylcatechol and can be considered as functional models for catechol oxidase. Because these complexes possess labile sites in their structures and in solution they have a potential nucleophile constituted by a terminal Cu(II)-bound hydroxo group, their activity toward hydrolysis of the model substrate 2,4-bis(dinitrophenyl)phosphate and DNA was also investigated. Double electrophilic activation of the phosphodiester by monodentate coordination to the Cu(II) center that contains the phenol group with tert-butyl substituents and hydrogen bonding of the protonated phenol with the phosphate O atom are proposed to increase the hydrolase activity (K(ass.) and k(cat.)) of 1 and 2 in comparison with that found for complex 3. In fact, complexes 1 and 2 show both oxidoreductase and hydrolase/nuclease activities and can thus be regarded as man-made models for studying catalytic promiscuity.