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Introduction: Sickle cell anemia (SCA) is a Mendelian disorder with a heterogeneous clinical course. The reasons for this phenotypic diversity are not entirely established, but it is known that high fetal hemoglobin levels lead to a milder course of the disease. Additionally, genetic variants in the intergenic region HBS1L-MYB promote high levels of fetal hemoglobin into adulthood. Objective: In the present study, we investigated the HMIP1 C-839A (rs9376092) polymorphism, located at the HBS1L-MYB intergenic region block 1, in SCA patients. Method: We analyzed 299 SCA patients followed in two reference centers in Brazil. The HMIP1 C-839A (rs9376092) genotypes were determined by allele specific polymerase chain reactions. Clinical and laboratory data were obtained from patient interviews and medical records. Results: The median fetal hemoglobin levels were higher in patients with the HMIP1 C-839A (rs9376092) AA genotype (CC = 6.4%, CA = 5.6% and AA = 8.6%), but this difference did not reach significance (p = 0.194). No association between HMIP1 C-839A (rs9376092) genotypes and other clinical and laboratorial features was detected (p > 0.05). Conclusion: In summary, our data could not support the previously related association between the HMIP1 C-893A (rs9376092) polymorphism and differential fetal hemoglobin levels.

[This corrects the article DOI: 10.1371/journal.pone.0165833.].

Sickle cell disease (SCD) is an inherited hemolytic anemia whose pathophysiology is driven by polymerization of the hemoglobin S (Hb S), leading to hemolysis and vaso-occlusive events. Inflammation is a fundamental component in these processes and a continuous inflammatory stimulus can lead to tissue damages. Thus, pro-resolving pathways emerge in order to restore the homeostasis. For example there is the annexin A1 (ANXA1), an endogenous anti-inflammatory protein involved in reducing neutrophil-endothelial interactions, accelerating neutrophil apoptosis and stimulating macrophage efferocytosis. We investigated the expression of ANXA1 in plasma of SCD patients and its relation with anemic, hemolytic and inflammatory parameters of the disease. Three SCD genotypes were considered: the homozygous inheritance for Hb S (Hb SS) and the association between Hb S and the hemoglobin variants D-Punjab (Hb SD) and C (Hb SC). ANXA1 and proinflammatory cytokines were quantified by ELISA in plasma of SCD patients and control individuals without hemoglobinopathies. Hematological and biochemical parameters were analyzed by flow cytometry and spectrophotometer. The plasma levels of ANXA1 were about three-fold lesser in SCD patients compared to the control group, and within the SCD genotypes the most elevated levels were found in Hb SS individuals (approximately three-fold higher). Proinflammatory cytokines were higher in SCD groups than in the control individuals. Anemic and hemolytic markers were higher in Hb SS and Hb SD genotypes compared to Hb SC patients. White blood cells and platelets count were higher in Hb SS genotype and were positively correlated to ANXA1 levels. We found that ANXA1 is down-regulated and differentially expressed within the SCD genotypes. Its expression seems to depend on the inflammatory, hemolytic and vaso-occlusive characteristics of the diseased. These data may lead to new biological targets for therapeutic intervention in SCD.

Os distúrbios hereditários das hemoglobinas são as doenças genéticas mais frequentes do homem e mais difundidas no mundo, abrangendo sobretudo continentes como África, Américas, Europa e extensas regiões da Ásia. Estima-se que haja 270 milhões de portadores de hemoglobinopatias no mundo, dos quais 80 milhões são portadores de talassemia. Aproximadamente 60 mil crianças nascem anualmente no mundo com talassemia e 250 mil com anemia falciforme, dando uma frequência de 2,4 crianças afetadas para cada 1.000 nascimentos. No Brasil, a doenca falciforme é a doença hereditária monogênica mais comum, estimando-se que haja entre 20 a 30 mil pacientes portadores desta doenca. O transplante de células-tronco hematopoéticas alogênico (TCTH alo) é atualmente a única modalidade terapêutica capaz de curar pacientes com hemoglobinopatias. Neste artigo discutiremos os dados disponíveis na literatura e sugerimos os critérios para a indicação do TCTH nas hemoglobinopatias.Hemoglobinopathies are the most prevalent genetic diseases in man. Most cases are described in Europe, Africa and in the Americas. About 270 million hemoglobinopathy carriers are alive today with 80 million being carriers of thalassemia. We estimate that, throughout the world, about 60,000 children are born annually with thalassemia and 250,000 with sickle cell disease with an estimated frequency of 2.4 children in every 1000 births. Sickle cell disease is the most common monogenic hereditary disease in Brazil with a total of from 20,000 to 30,000 patients. Allogeneic stem cell transplantation is the only curative approach. Here we describe published data and propose criteria to indicate stem cell transplantation in thalassemia and sickle cell disease patients.

A doença de Gaucher (DG) é um erro inato do metabolismo do grupo das doenças lisossômicas de depósito, sendo a mais freqüente do referido grupo. É de herança autossômica recessiva, portanto com risco de 25% a cada gestação de casal heterozigoto. A doença é resultante da deficiência da beta-glicosidase ácida ou beta-glicocerebrosidase, que leva ao acúmulo de glicolipídios nos macrófagos principalmente em baço, fígado, medula óssea e pulmão. As manifestações clínicas ou fenotípicas da DG vão depender do grau de deficiência da enzima, existindo três tipos: Tipo I, forma não neuropática, afeta crianças e adultos com hepatoesplenomegalia, anemia, trombocitopenia, leucopenia e lesões ósseas; Tipo II, forma neuropática aguda, afeta crianças com 4-5 meses com quadro neurológico grave, hepatoesplenomegalia e comprometimento pulmonar e o Tipo III, forma neuropática crônica, afeta crianças e adolescentes com quadro neurológico menos grave que o Tipo II e ainda pode comprometer fígado, baço e ossos. Um grupo de catorze médicos com experiência no tratamento da DG com reposição enzimática realizaram extensa revisão da literatura, confrontaram com os dados evolutivos dos pacientes brasileiros e chegaram a um consenso quanto aos critérios para iniciar o tratamento, a dose da enzima e freqüência das infusões, do acompanhamento ambulatorial, laboratorial e radiológico. O Grupo Brasileiro de Estudos em Doença de Gaucher e outras Doenças de Depósito Lisossômico (GBDDL) tem o objetivo de estabelecer diretrizes para o diagnostico, tratamento e acompanhamento de pacientes com doença de Gaucher no Brasil. Esta iniciativa pioneira visa uniformizar a conduta no país com relação ao tratamento de DG com reposição enzimática, tratamento de alto custo porém de grande eficácia.

A doença falciforme é caracterizada por apresentar várias alterações clinicas e fisiopatológicas nos pacientes que por ela são acometidos. Uma dessas alterações é presença de úlceras de perna dolorosas e de difícil cicatrização, sendo necessário o apoio de equipe multiprofissional no seu manejo e tratamento. Com o objetivo de reduzir a dor associada a úlcera de perna, o paciente falcêmico faz uso de opioides parenterais e enterais que normalmente estão associados a efeitos colaterais indesejados. Com o objetivo de reduzir o uso desses opioides sistêmicos, avaliamos um gel de morfina, de fácil manipulação e baixo custo, que foi utilizado antes e após o processo de troca de curativo das úlceras de perna dos pacientes falcêmicos atendidos em nossa instituição. Baseados na escala analógica da dor foi avaliado o efeito analgésico do gel em 28 pacientes. Todos apresentavam dor grau 7 ou 8 antes da aplicação do gel. Vinte e quatro pacientes (85,7%) apresentaram total ausência de dor por um período de 24 horas, não sendo necessário o uso de analgésicos sistêmicos. Em três pacientes (10,7%) a ausência de dor durou um periodo de 12horas. Somente um paciente (3,6%) não relatou analgesia apos o uso do gel. Os resultados demonstraram que o gel é altamente eficaz no controle da dor das úlceras de perna de pacientes falcêmicos.Sickle cell disease is characterized by several clinical and pathophysiological changes including painful leg ulcers. These are difficult to heal and require the support of a multidisciplinary team in their management. The treatment of pain in these patients usually involves the use of opioids. In order to reduce the use of systemic opioids, we evaluated an easy-to-use low-cost morphine gel (0.12%) that was applied before and after changing leg ulcer dressings of sickle cell patients treated in Hemorio hospital. Based on the Analogue Pain Scale (APS) we evaluated the analgesic effect of the gel with 28 patients. All presented with a degree of pain of 7 or 8 before applying the gel. A total absence of pain was observed by 24 patients (85.7%) within thirty minutes of applying the gel, with the analgesia effect being maintained for a period of 24 hours and thus the use of other analgesics was not requiring. In 3 patients (10.7%) no pain was reported for a period of 12 hours. Only 1 patient (3.6%) reported no analgesic effect thirty minutes after the application of the gel. Our results indicate that the morphine gel was effective in controlling the pain of leg ulcers in this group of sickle cell patients. A controlled study should be designed to assess this important subject.

The 2010 eruptions of the Icelandic volcano Eyjafjallajökull attracted the attention of the public and the scientific community to the vulnerability of the European airspace to volcanic eruptions. The European Space Agency project “Satellite Monitoring of Ash and Sulphur Dioxide for the mitigation of Aviation Hazards”, called for the creation of an optimal End-to-End System for Volcanic Ash Plume Monitoring and Prediction. This system is based on improved and dedicated satellite-derived ash plume and sulphur dioxide level assessments, as well as an extensive validation, using among others ground-based measurements (Koukouli et al., 2014). The validation of volcanic ash levels and height extracted from IASI/MetopA is presented in this work with emphasis on the ash plume height and ash optical depth levels. European Aerosol Research Lidar Network [EARLINET] lidar measurements are compared to different satellite estimates for two eruptive episodes. The validation results are extremely promising within the estimated uncertainties of each of the comparative datasets.

Atmospheric acidity is increasingly determined by carbon dioxide and organic acids.sup.1-3. Among the latter, formic acid facilitates the nucleation of cloud droplets.sup.4 and contributes to the acidity of clouds and rainwater.sup.1,5. At present, chemistry-climate models greatly underestimate the atmospheric burden of formic acid, because key processes related to its sources and sinks remain poorly understood.sup.2,6-9. Here we present atmospheric chamber experiments that show that formaldehyde is efficiently converted to gaseous formic acid via a multiphase pathway that involves its hydrated form, methanediol. In warm cloud droplets, methanediol undergoes fast outgassing but slow dehydration. Using a chemistry-climate model, we estimate that the gas-phase oxidation of methanediol produces up to four times more formic acid than all other known chemical sources combined. Our findings reconcile model predictions and measurements of formic acid abundance. The additional formic acid burden increases atmospheric acidity by reducing the pH of clouds and rainwater by up to 0.3. The diol mechanism presented here probably applies to other aldehydes and may help to explain the high atmospheric levels of other organic acids that affect aerosol growth and cloud evolution. The oxidation of hydrated formaldehyde from cloud droplets is the dominant source of atmospheric formic acid, increasing atmospheric acidity by reducing cloud and rainwater pH., Author(s): B. Franco [sup.1] [sup.2] , T. Blumenstock [sup.3] , C. Cho [sup.1] , L. Clarisse [sup.2] , C. Clerbaux [sup.2] [sup.4] , P.-F. Coheur [sup.2] , M. De Mazière [...]

Dietary supplements (DS) are intended for healthy people to maintain or improve their overall health. Its consumption is widespread in large part of the general population and at all levels of athletes. Nevertheless, DS use can also pose health risks to individuals and, in the case of athletes, may lead to adverse analytical findings (AAFs) due to the possibility of DS contamination or adulteration with doping agents banned by the World Anti‐Doping Agency. Although educational initiatives are being performed in Brazil to warn the sports community about inadvertent doping cases, AAFs connected to the DS administration have been increasingly growing. The findings of DS analyzed by the Brazilian Doping Control Laboratory (LBCD), between 2017 and 2022, after Testing Authorities (TAs) analysis requests, showed an alarming number of tainted samples. Diuretics were the most common adulterants found in all supplement types. However, the profile of prohibited substances in manufactured and compounded dietary supplements (MDS and CDS, respectively) were distinct, with stimulants being most prevalent in MDS and anabolic agents in CDS products. Additionally, MDS samples generally presented higher estimated concentrations of banned substances (mg/g) than CDS samples (μg/g). The common practice of DS intake by athletes continues to be of great concern for a doping‐free sport, given the high prevalence of prohibited substances detected in the analyzed samples by the LBCD. The current Brazilian scenario reinforces the importance of raising awareness in the sports community of the possible consequences of an unintentional doping case linked to DS use. [ABSTRACT FROM AUTHOR]

This study provides improved methanol emission estimates on the global scale, in particular for the largest methanol source, the terrestrial biosphere, and for biomass burning. To this purpose, one complete year of spaceborne measurements of tropospheric methanol columns retrieved for the first time by the thermal infrared sensor IASI aboard the MetOp satellite are compared with distributions calculated by the IMAGESv2 global chemistry-transport model. Two model simulations are performed using a priori biogenic methanol emissions either from the new MEGANv2.1 emission model, which is fully described in this work and is based on net ecosystem flux measurements, or from a previous parameterization based on net primary production by Jacob et al. (2005). A significantly better model performance in terms of both amplitude and seasonality is achieved through the use of MEGANv2.1 in most world regions, with respect to IASI data, and to surface- and air-based methanol measurements, even though important discrepancies over several regions are still present. As a second step of this study, we combine the MEGANv2.1 and the IASI column abundances over continents in an inverse modelling scheme based on the adjoint of the IMAGESv2 model to generate an improved global methanol emission source. The global optimized source totals 187 Tg yr−1 with a contribution of 100 Tg yr−1 from plants, only slightly lower than the a priori MEGANv2.1 value of 105 Tg yr−1. Large decreases with respect to the MEGANv2.1 biogenic source are inferred over Amazonia (up to 55 %) and Indonesia (up to 58 %), whereas more moderate reductions are recorded in the Eastern US (20-25 %) and Central Africa (25-35 %). On the other hand, the biogenic source is found to strongly increase in the arid and semi-arid regions of Central Asia (up to a factor of 5) and Western US (factor of 2), probably due to a source of methanol specific to these ecosystems which is unaccounted for in the MEGANv2.1 inventory. The most significant error reductions achieved by the optimization concern the derived biogenic emissions over the Amazon and over the Former Soviet Union. The robustness of the derived fluxes to changes in convective updraft fluxes, in methanol removal processes, and in the choice of the biogenic a priori inventory is assessed through sensitivity inversions. Detailed comparisons of the model with a number of aircraft and surface observations of methanol, as well as new methanol measurements in Europe and in the Reunion Island show that the satellite-derived methanol emissions improve significantly the agreement with the independent data, giving thus credence to the IASI dataset. © 2011 Author(s).

Extreme enhancements in the total columns of carbon monoxide (CO), peroxyacetyl nitrate (PAN), ethylene (C2H4), methanol (CH3OH), and formic acid (HCOOH) were observed over the Canadian high Arctic during the period of 17–22 August 2017 by a ground‐based Fourier transform infrared (FTIR) spectrometer at Eureka, Nunavut (80.05°N, 86.42°W), and by the Infrared Atmospheric Sounding Interferometer (IASI) satellite instruments. These enhancements have been attributed to wildfires in British Columbia (BC) and the Northwest Territories (NWT) of Canada, and represent the largest short‐term perturbations of PAN, C2H4, and HCOOH above ambient concentrations over the 14‐year (2006–2020) Eureka time‐series. Enhancement ratios, emission ratios, and emission factors relative to CO were calculated for all species for both FTIR and IASI observations. The C2H4 and HCOOH emission factors are significantly larger than previous studies, suggesting unusually high emissions from these fires. The wildfire plumes were also simulated using the GEOS‐Chem model. Initial GEOS‐Chem simulations displayed a severe under‐estimation relative to observations for these fire plumes resulting from the injection height scheme of the model. Sensitivity tests highlighted that injection heights of 12.5 km for BC (based on previous studies) and 10 km for the NWT fires yielded the strongest correlations with ground‐based measurements. Applying these injection heights to the model significantly improves the simulated plume transport and agreement with ground‐ and space‐based observations. GEOS‐Chem was also used to estimate the magnitude of secondary in‐plume production of CH3OH and HCOOH; it was found to be an important component (∼18%) of the enhanced HCOOH columns at Eureka. Plain Language Summary: Wildfires are a significant natural source of pollution to the atmosphere. During mid‐August 2017, two extremely large wildfires occurred simultaneously in British Columbia (BC) and the Northwest Territories (NWT) of Canada. These fires produced an exceptional amount of smoke, which was subsequently transported to the Canadian high Arctic region. The atmospheric concentrations of carbon monoxide (CO), peroxyacetyl nitrate (PAN), ethylene (C2H4), methanol (CH3OH), and formic acid (HCOOH) contained within these transported smoke plumes were measured using both a ground‐based infrared spectrometer located at Eureka, Nunavut (80.05°N, 86.42°W) and satellite instruments. The largest concentrations of CO, PAN, C2H4, and HCOOH observed over the 14‐year measurement record (2006–2020) of the ground‐based spectrometer were due to these wildfires. The emissions of these fires were estimated from both the ground‐ and space‐based measurements and were found to be unusually high in comparison to previous studies. The wildfire smoke plumes were also simulated using a chemical transport model, but the model was found to inject the smoke too low into the atmosphere above the fires; after adjustments to the injection scheme were made, the agreement of the model with the measurements was significantly improved. Key Points: The 2017 Canadian wildfires produced the largest PAN, C2H4, and HCOOH column enhancements observed in the high Arctic from 2006 to 2020GEOS‐Chem effectively simulates the observed plume transport, but required modifications to the injection heights of the fire emissionsMid‐latitude wildfires may become an increasingly significant source of reactive VOC species to the high Arctic during the summer months [ABSTRACT FROM AUTHOR]

We examine parents' knowledge of discrete, verifiable facts--what we call "hard knowledge"--in a high school application process. Using parent survey data (n = 658) from the School District of Philadelphia, this study examines whether parents knew the admission criteria and acceptance rate at the high school they most wanted their child to attend. We argue that these two facts are critical to making strategic application decisions. We find that hard knowledge is low overall but varies by parent education, and that all parents are more likely to have information if it is provided directly to them by the district. (Contains 5 tables and 1 figure.)

This article uses qualitative and quantitative data for a recent birth cohort from the Fragile Families and Child Wellbeing study to compare kin support patterns between African Americans and Hispanics. It focuses on financial and housing support from grandparents and other kin during the transition to parenthood. Qualitative analysis (n = 122 parents) uncovers distinctions in the way African American and Hispanic parents discuss their family networks, with African Americans emphasizing relations with female kin and Hispanics emphasizing a more integrated system. Consistent with these findings, quantitative analysis (n = 2,472 mothers and n = 2,639 fathers) finds that compared with Hispanic parents, African American parents are more likely to receive financial and housing support from grandmothers and less likely to receive support from both grandparents. Contrary to expectations that fathers would be the primary support recipients in Hispanic households, the authors find that mothers are the more common recipients of support among African Americans and Hispanics. (Contains 1 table and 2 notes.)

Today's "out-of-school learning" is dominated by PC games, videos, and TV. These media provide children with optimal conditions for nurturing their visuospatial intelligence. In "chemistry" and biochemistry, over the past 125 years, thinking has shifted from the "logical-mathematical" to the "logical-visuospatial." In chemistry visuospatial thinking has never been so dominant as today. Thus in chemistry, a truly international, pictorial language has evolved. Yet, the founding and growth of chemical education as a separate discipline has resulted, albeit unintended, in an alienation of chemistry educators from these dramatic changes in chemistry. By confining themselves in their teaching of chemistry to the logical-mathematical and the verbal, teachers and chemical educators are conveying a false and abandoned conception of chemistry in the class rooms. And, they fail to address the most important developed intelligence of our young.

Reports on a study exploring why students are not studying chemistry. Three groups of graduating high school students and their chemistry teachers stayed at a research institute working on molecular modeling and wrote essays on school chemistry versus chemistry in research. Concludes that school chemistry does not convey today's chemistry in research and industry. (Author/MM)

To date, hydroxyurea is the only effective and safe drug that significantly reduces morbidity and mortality of individuals with Sickle cell disease. Twenty years of real-life experience has demonstrated that hydroxyurea reduces pain attacks, vaso-occlusive events, including acute chest syndrome, the number and duration of hospitalizations and the need for transfusion. The therapeutic success of hydroxyurea is directly linked to access to the drug, the dose used and adherence to treatment which, in part, is correlated to the availability of hydroxyurea. This consensus aims to reduce the number of mandatory exams needed to access the drug, prioritizing the requesting physician's report, without affecting patient safety.

Pseudomonas aeruginosa is an opportunistic pathogen causing chronic infections that are related to its ability to form biofilms. Mechanosensitive ion channels (Mcs) are cytoplasmic membrane proteins whose opening depends on a mechanical stress impacting the lipid bilayer. CmpX is a homologue of the small conductance MscS of Escherichia coli. The cmpX gene is part of a transcriptional cfrX-cmpX unit that is under the control of the cell envelope stress response ECF sigma factor SigX. CmpX was shown to regulate the activity of the hybrid sensor kinase PA1611 involved in the regulation of transition from a planktonic to a biofilm lifestyle. The deletion of cmpX leads to increased biofilm formation under static conditions. Herein, the effect of cmpX overexpression was investigated by confocal laser scanning microscopy in terms of biofilm formation and architecture, and matrix components production, in dynamic conditions. We show that overexpression of cmpX in P. aeruginosa leads to enhanced and altered biofilm architecture that seems to be associated to increased matrix components and the emergence of filamentous cells. These phenotypic alterations might occur potentially through a shear stress induced by the medium flow rate. Importance: CmpX is involved in biofilm formation and cell filamentation with regards to the medium flow.

This article uses qualitative and quantitative data for a recent birth cohort from the Fragile Families and Child Wellbeing study to compare kin support patterns between African Americans and Hispanics. It focuses on financial and housing support from grandparents and other kin during the transition to parenthood. Qualitative analysis (n = 122 parents) uncovers distinctions in the way African American and Hispanic parents discuss their family networks, with African Americans emphasizing relations with female kin and Hispanics emphasizing a more integrated system. Consistent with these findings, quantitative analysis (n = 2,472 mothers and n = 2,639 fathers) finds that compared with Hispanic parents, African American parents are more likely to receive financial and housing support from grandmothers and less likely to receive support from both grandparents. Contrary to expectations that fathers would be the primary support recipients in Hispanic households, the authors find that mothers are the more common recipients of support among African Americans and Hispanics. Keywords: African American; Hispanic; kin support; Fragile Families; mixed methods