Assessing the reclamation of a contaminated site affected by the Fundão dam tailings trough phytoremediation and bioremediation.

The rupture of the Fundão dam (Brazil) spread tailings contaminated with sodium and ether-amine into the Doce River Basin. Aiming at rehabilitating a contaminated riparian site, phytoremediation with native species of the Atlantic Forest was performed under four treatments: ES-1: physical remediation (sediment scraping) + chemical remediation (organic matter) + bioremediation (double inoculation with the arbuscular mycorrhizal fungus (AMF) Rhizophagus irregularis and the plant growth-promoting bacteria Bacillus subtilis); ES-2: chemical remediation + bioremediation; ES-3: physical remediation + chemical remediation; ES-4: chemical remediation. Ether-amine and sodium contents, plant growth and, soil quality parameters were compared among treatments and relative to preserved and degraded sites. Two years after planting, the outstanding plant growth was attributed to the phytoremediation of ether-amine and ammonium, followed by a significant increase in soil microbial biomass (Phospholipid fatty acids-PLFAs), particularly the Gram+ bacteria and total fungi but not AMF, whose response was independent of the inoculation. While sodium and ether-amine declined, soil K, P, NO3- contents, dehydrogenase and acid phosphatase activities, cation exchange capacity (CEC) and soil aggregation increased, especially in ES-1. Thus, such remediation procedures are recommended for the restoration of riparian areas affected by the Fundão tailings, ultimately improving sediment fertility, aggregation and stabilization.

To the best of our knowledge, this is the only successful example of fragment of riparian Atlantic Forest successfully rehabilitated using native trees from the Atlantic Forest in the riparian zone affected by the contaminated Fundão dam tailings. For that, phytoremediation and bioremediation procedures were adopted to alleviate etheramine and sodium toxicity, resulting in the amelioration of soil fertility and particularly the stabilization of such highly disaggregated sediments, ultimately protecting the Doce river basin against these contaminants.

Umbilical Cord Mesenchymal Stromal Cells for Steroid-Refractory Acute Graft-versus-Host Disease.

BACKGROUND: Steroid-refractory acute graft-vs.-host disease (SR-aGVHD) is a complication of allogeneic hematopoietic stem cell transplantation with a dismal prognosis and for which there is no consensus-based second-line therapy. Ruxolitinib is not easily accessible in many countries. A possible therapy is the administration of mesenchymal stromal cells (MSCs). METHODS: In this retrospective study, 52 patients with severe SR-aGVHD were treated with MSCs from umbilical cord (UC-MSCs) in nine institutions. RESULTS: The median (range) age was 12.5 (0.3-65) years and the mean ± SD dose (×106/kg) was 4.73 ± 1.3 per infusion (median of four infusions). Overall (OR) and complete response (CR) rates on day 28 were 63.5% and 36.6%, respectively. Children (n = 35) had better OR (71.5% vs. 47.1%, p = 0.12), CR (48.6% vs. 11.8%, p = 0.03), overall survival (p = 0.0006), and relapse-free survival (p = 0.0014) than adults (n = 17). Acute adverse events (all of them mild or moderate) were detected in 32.7% of patients, with no significant difference in children and adult groups (p = 1.0). CONCLUSIONS: UC-MSCs are a feasible alternative therapy for SR-aGVHD, especially in children. The safety profile is favorable.

Violência e desigualdades de gênero: relato de experiência sobre ações desenvolvidas e resultados alcançados durante o mês da mulher em um hospital universitário / Violence and gender inequalities: experience report on actions developed and results achieved during women's month in a university hospital

Introdução: O 8 de março, Dia Internacional da Mulher, é uma data mundialmente lembrada como momento oportuno de reflexão e discussão sobre inúmeras desigualdades ainda vivenciadas pelas mulheres, que impactam a saúde dessa parcela da população. Objetivo: Apresentar ações desenvolvidas por um grupo de trabalho multiprofissional de um hospital universitário e os resultados alcançados. Relato de Experiência: Desde 2022, o hospital institucionalizou a comemoração do 8 de março, como uma data para ações e atividades informativas, orientativas e de acolhimento junto a colaboradores e usuários. Em 2023, foram escolhidos dois temas centrais para discussão: Trabalho/Família e Violência contra a Mulher. Dessa forma, foram promovidas rodas de conversa com trabalhadores em visita aos setores e salas de espera com usuários, norteadas por materiais didáticos confeccionados sobre os dois temas. Também houve panfletagem e apresentação musical no dia 8 de março, além de capacitação oferecida aos profissionais de saúde da instituição, abordando a relação entre corpo feminino e peculiaridades no atendimento à saúde. Conclusão: Durante as ações desenvolvidas, as mulheres puderam expressar suas realidades e rotinas, conhecer dados que comprovam desigualdades e leis que garantem direitos. Pode-se destacar, como resultado alcançado, a discussão das questões históricas e culturais de menosprezo à mulher como responsáveis por iniquidades, com prejuízos à saúde física e mental feminina. É dever de toda a sociedade combater a violência doméstica/familiar, incluindo como aliadas nessa batalha as instituições de saúde e educação integrantes do Sistema Único de Saúde (SUS).

Introduction: March 8th, International Women's Day, is a globally recognized date that serves as an opportune moment for reflection and discussion on numerous inequalities still experienced by women, which impact the health of this segment of the population. Objective: To present actions developed by a multidisciplinary working group at a university hospital and the results achieved. Experience Report: Since 2022, the hospital has institutionalized the celebration of March 8th as a date for informative, educational, and supportive actions and activities for employees and users. In 2023, two central themes for discussion were chosen: Work/Family and Violence against Women. In this way, discussion sessions were held with employees visiting different departments and waiting rooms with users, guided by educational materials prepared on the two topics. There was also pamphleteering and a musical presentation on March 8th, in addition to training offered to healthcare professionals within the institution, addressing the relationship between the female body and specific healthcare needs. Conclusion: During the activities conducted, women were able to express their realities and routines, learn about data confirming inequalities and laws guaranteeing rights. One noteworthy result achieved was the discussion of historical and cultural factors contributing to the belittlement of women as responsible for inequities, with consequences for women's physical and mental health. It is the duty of society as a whole to combat domestic/family violence, with healthcare and educational institutions within the Unified Health System of Brazil serving as allies in this battle.

Long-term functioning status of COVID-19 survivors: a prospective observational evaluation of a cohort of patients surviving hospitalisation.

OBJECTIVES: The study investigated the long-term functional status of hospitalised COVID-19 survivors to explore and document their functional situation. DESIGN: This prospective observational study assessed 801 COVID-19 survivors at 3-11 months after hospital discharge. It analyses participants' sociodemographic background, COVID-19 clinical manifestations, and clinical and functional evaluations. SETTING: Tertiary-level university hospital in São Paulo, Brazil. PARTICIPANTS: Study participants are COVID-19 survivors admitted to hospital care for at least 24 hours to treat acute SARS-CoV-2 infection. OUTCOME MEASURES: Epworth Sleepiness Scale, EuroQoL-5 Dimensions-5 Levels, Functional Assessment of Chronic Illness Therapy-Fatigue, Functional Independence Measure, Functional Oral Intake Scale, Handgrip Strength, Insomnia Severity Index, Medical Research Council (MRC) Dyspnea Scale, MRC sum score, Modified Borg Dyspnea Scale, pain Visual Analogue Scale, Post-COVID-19 Functional Status, Timed Up and Go, WHO Disability Assessment Schedule 2.0, 1-Minute Sit to Stand Test. RESULTS: Many participants required invasive mechanical ventilation (41.57%, 333 of 801). Mean age was 55.35±14.58 years. With a mean of 6.56 (SD: 1.58; 95% CI: 6.45 to 6.67) months after hospital discharge, 70.86% (567 of 800) reported limited daily activities, which were severe in 5.62% (45 of 800). They also reported pain and discomfort (64.50%, 516 of 800), breathlessness (64.66%, 514 of 795), and anxiety and depression (57.27%, 457 of 798). Daytime sleepiness and insomnia evaluations showed subthreshold results. Most (92.85%, 727 of 783) participants reported unrestricted oral intake. Data indicated no generalised fatigue (mean score: 39.18, SD: 9.77; 95% CI: 38.50 to 39.86). Assessments showed poor handgrip strength (52.20%, 379 of 726) and abnormal Timed Up and Go results (mean 13.07 s, SD: 6.49). The invasive mechanical ventilation group seemed to have a better handgrip strength however. We found no clear trends of change in their functional status during months passed since hospital discharge. CONCLUSIONS: Muscle weakness, pain, anxiety, depression, breathlessness, reduced mobility, insomnia and daytime sleepiness were the most prevalent long-term conditions identified among previously hospitalised COVID-19 survivors.

COVID-19 in HSCT recipients: a collaborative study of the Brazilian Society of Marrow Transplantation (SBTMO).

In the COVID-19 scenario, patients undergoing hematopoietic stem cell transplantation (HSCT) infected with SARS-CoV-2 may have an increased risk of death. Through a national multicenter study, we aimed to describe the impact of COVID-19 on the survival of HSCT recipients in Brazil. Eighty-six patients with a confirmed diagnosis of SARS-CoV-2 (92% by RT-PCR) were included. There were 24 children and 62 adults receiving an autologous (n = 25) and allogeneic (n = 61) HSCT for malignant (n = 72) and non-malignant (n = 14) disorders. Twenty-six patients died, (10 on autologous (38%) and 16 patients (62%) on allogeneic group). The estimated overall survival (OS) at day 40 was 69%. Adults had decreased OS compared to children (66% vs 79%, p = 0.03). The severity of symptoms at the time of diagnosis, ECOG score, laboratory tests (C-reactive protein, urea values) were higher in patients who died (p < 0.05). In conclusion, HSCT recipients infected with SARS-CoV-2 have a high mortality rate mainly in adults and patients with critical initial COVID-19 presentation. These findings show the fragility of HSCT recipients with SARS-CoV-2 infection. Therefore, the importance of adherence to preventive measures is evident, in addition to prioritizing the vaccination of family members and the HSCT team.

Oral mucositis in paediatric cancer patients undergoing allogeneic hematopoietic stem cell transplantation preventively treated with professional dental care and photobiomodulation: Incidence and risk factors.

BACKGROUND: Oral mucositis (OM) is an important side effect related to allogeneic hematopoietic stem cell transplantation (allo-HSCT), and it has been associated with a significative reduction of quality of life. A negative impact of OM in paediatric patients could result in increased use of parenteral feeding and opioids, longer periods of hospitalization, and a higher risk of systemic infection. AIM: To investigate the clinical features and clinical outcomes associated with OM development and severity in hematological cancer paediatric patients undergoing allo-HSCT who underwent professional dental care (PDC) and photobiomodulation (PBM) as prophylactic treatment. DESIGN: Medical data and OM presentation were retrieved retrospectively from all patients younger than 18 years who received allo-HSCT between 2013 and 2016. The incidence of OM was assessed and graded by two oral medicine specialists following the WHO guidelines, and it was correlated with clinical parameters. RESULTS: Forty-nine consecutive paediatric patients were included. OM was diagnosed in 73.5% of patients, and in 36.1% of patients, OM was classified as severe. Acute lymphoblastic leukemia as a primary diagnosis and the use of a myeloablative regimen were associated with OM development. The primary diagnosis and use of total body irradiation (TBI) were associated with aggressive OM. Neither the incidence nor the severity of OM affected the overall survival, whereas only the use of a myeloablative regimen and a high body mass index (BMI) were determinants of lower OM-free survival rates. CONCLUSIONS: A myeloablative conditioning and a high BMI were observed to be independent prognostic determinants of a lower OMFS rate. The cluster analysis allowed us to outline patient profiles with greater susceptibility to the development and severity of oral mucositis, which seems to be a useful tool to determine the risk of OM in paediatric patients.

Rehabilitation of a Riparian Site Contaminated by Tailings from the Fundão Dam, Brazil, Using Different Remediation Strategies.

The tailings spilled by the Fundão Dam rupture in the Doce River basin (Brazil) had a high pH, elevated sodium (Na) and ether amine, and low soil organic matter. With the aim of decreasing the toxic compounds, we established 2 remediation strategies: treatment 1, phytoremediation with tolerant native species of the Atlantic Forest cultivated on scraped sediment plus the incorporation of organic matter; and treatment 2, phytoremediation with native species plus superficial deposition of organic matter. The experimental site was compared with a degraded site that the dam tailings had reached and with a preserved site, a fragment of preserved Atlantic Forest. After 12 mo, plants showed an outstanding growth, especially after treatment 1 (~4 m), and the remediation procedures resulted in significant decreases in pH (from 8.0 to ~ 6.0), Na (from 154 to 22-35 mg/kg), electrical conductivity, and ether amine (from 6.0 to 0.5 mg/kg) in both treatments. By contrast, ammonium, a product of ether amine degradation, showed a significant increase in the experimental site, along with a significant increase in nitrate and improvement of soil microbial populations assessed by phospholipid fatty acid analysis. The treatments also improved soil fertility in the experimental site, as estimated by soil nutrients, cation exchange capacity, and soil aggregation. Based on the parameters analyzed, a principal component analysis showed that samples from the degraded site and the preserved site clustered in an opposite position and those from the experimental site clustered in an intermediate position but closer to the samples from the preserved site. Overall, our results demonstrated that the remediation procedures adopted were effective and resulted in rehabilitation of a riparian forest contaminated with dam tailings that included Na and ether amine. Environ Toxicol Chem 2021;40:2359-2373. © 2021 SETAC.

Hereditary angioedema: Report of the dental treatment of 12 Brazilian patients.

OBJECTIVE: The aim of this study was to report on clinical experience in Brazil in the dental treatment and the oral conditions of a group of patients with hereditary angioedema (HAE). STUDY DESIGN: The study analyzed demographic data, type of HAE, intensity of attacks, long-term and short-term prophylaxis, dental procedures, and occurrence of crises after the procedures were performed. Radiographic evaluation of the number of teeth and bone loss was also performed. RESULTS: Data from 12 patients were collected; most were women, presenting with C1-INH-HAE type I and a history of severe attacks. All patients reported use of regular medications (long-term prophylaxis), mostly attenuated androgens, to prevent/attenuate HAE attacks. These patients had several missing teeth and alveolar bone loss. Tooth extraction was the most common procedure. In half the patients, the procedures had been performed without modification in long-term prophylaxis. The others were treated with an additional prophylaxis protocol (short-term prophylaxis), particularly those who underwent tooth extraction. None of the study patients developed HAE attacks after dental procedures. CONCLUSION: The occurrence and intensity of a possible HAE attack after dental procedures are unpredictable, but with careful preliminary screening by dental and immunology teams and the use of therapeutic prophylaxis, the risk could be minimized.

Impact of CD34 Cell Dose and Conditioning Regimen on Outcomes after Haploidentical Donor Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide for Relapsed/Refractory Severe Aplastic Anemia.

Severe aplastic anemia (SAA) is a life-threatening disease that can be cured with allogeneic cell transplantation (HCT). Haploidentical donor transplantation with post-transplantation cyclophosphamide (haplo-PTCy) is an option for patients lacking an HLA-matched donor. We analyzed 87 patients who underwent haplo-PTCy between 2010 and 2019. The median patient age was 14 years (range, 1 to 69 years), most were heavily transfused, and all received previous immunosuppression (25% without antithymocyte globulin). Almost two-thirds (63%) received standard fludarabine (Flu)/cyclophosphamide (Cy) 29/total body irradiation (TBI) 200 cGy conditioning, and the remaining patients received an augmented conditioning: Flu/Cy29/TBI 300-400 (16%), Flu/Cy50/TBI 200 (10%), or Flu/Cy50/TBI 400 (10%). All patients received PTCy-based graft-versus-host disease (GVHD) prophylaxis. Most grafts (93%) were bone marrow (BM). The median duration of follow-up was 2 years and 2 months. The median time to neutrophil recovery was 17 days. Primary graft failure occurred in 15% of the patients, and secondary or poor graft function occurred in 5%. The incidences of grade II-IV acute GVHD was 14%, and that of chronic GVHD was 9%. Two-year overall survival and event-free survival (EFS) were 79% and 70%, respectively. EFS was higher for patients who received augmented Flu/Cy/TBI (hazard ratio [HR], .28; P = .02), and those who received higher BM CD34 cell doses (>3.2 × 10E6/kg) (HR, .29; P = .004). The presence of donor-specific antibodies before HSCT was associated with lower EFS (HR, 3.92; P = .01). Graft failure (HR, 7.20; P < .0001) was associated with an elevated risk of death. Cytomegalovirus reactivation was frequent (62%). Haploidentical HCT for SAA is a feasible procedure; outcomes are improved with augmented conditioning regimens and BM grafts with higher CD34 cell doses.

Allogeneic Hematopoietic Stem Cell Transplantation for Children and Adolescents with Acute Myeloid Leukemia in Brazil: A Multicentric Retrospective Study.

The survival rates of children with high-risk acute myeloid leukemia (AML) treated with hematopoietic stem cell transplant (HSCT) range from 60% to 70% in high-income countries. The corresponding rate for Brazilian children with AML who undergo HSCT is unknown. We conducted a retrospective analysis of 114 children with AML who underwent HSCT between 2008 and 2012 at institutions participating in the Brazilian Pediatric Bone Marrow Transplant Working Group. At transplant, 38% of the children were in first complete remission (CR1), 37% were in CR2, and 25% were in CR3+ or had persistent disease. The donors included 49 matched-related, 59 matched-unrelated, and six haploidentical donors. The most frequent source of cells was bone marrow (69%), followed by the umbilical cord (19%) and peripheral blood (12%). The 4-year overall survival was 47% (95% confidence interval [CI] 30%-57%), and the 4-year progression-free survival was 40% (95% CI 30%-49%). Relapse occurred in 49 patients, at a median of 122 days after HSCT. There were 65 deaths: 40 related to AML, 19 to infection, and six to graft versus host disease. In conclusion, our study suggests that HSCT outcomes for children with AML in CR1 or CR2 are acceptable and that this should be considered in the overall treatment planning for children with AML in Brazil. Therapeutic standardization through the adoption of multicentric protocols and appropriate supportive care treatment will have a significant impact on the results of HSCT for AML in Brazil and possibly in other countries with limited resources.

Outcomes after Haploidentical Stem Cell Transplantation with Post-Transplantation Cyclophosphamide in Patients with Primary Immunodeficiency Diseases.

Allogeneic hematopoietic stem cell transplantation (HCT) can cure primary immunodeficiency diseases (PID). When a HLA-matched donor is not available, a haploidentical family donor may be considered. The use of T cell-replete haploidentical HCT with post-transplantation cyclophosphamide (haplo-PTCy) in children with PID has been reported in few case series. A donor is usually readily available, and haplo-PTCy can be used in urgent cases. We studied the outcomes of 73 patients with PID who underwent haplo-PTCy, including 55 patients who did so as a first transplantation and 18 who did so as a salvage transplantation after graft failure of previous HCT. The median patient age was 1.6 years. Most of the children were male (n = 54) and had active infection at the time of transplantation (n = 50); 10 children had severe organ damage. The diagnosis was severe combined immunodeficiency (SCID) in 34 patients and non-SCID in 39 (Wiskott-Aldrich syndrome; n = 14; chronic granulomatous disease, n = 10; other PID, n = 15). The median duration of follow-up of survivors was 2 years. The cumulative incidence of neutrophil recovery was 88% in the SCID group and 84% in non-SCID group and was 81% for first transplantations and 83% after a salvage graft. At 100 days, the cumulative incidence of acute GVHD grade II-IV and III-IV was 33% and 14%, respectively. The majority of patients reached 200/µL CD4+ and 1000/µL CD3+ cell counts between 3 and 6 months. The estimated 2-year overall survival was 66%; it was 64% for SCID patients and 65% for non-SCID patients and 63% for first HCT and 77% for salvage transplantations. Twenty-five patients died, most of them due to infection early after transplantation (before 100 days). In conclusion, haplo-PTCy is a feasible procedure, can cure two-thirds of children with PID, and can be used as rescue treatment for previous graft failure. © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Hematopoietic cell transplantation for Diamond Blackfan anemia: A report from the Pediatric Group of the Brazilian Bone Marrow Transplantation Society.

OBJECTIVES: The aim of this study was to analyze the outcomes of children with Diamond-Blackfan anemia (DBA) treated in Brazil with hematopoietic cell transplantation (HCT). METHODS: We performed a retrospective analysis of 44 pediatrics patients transplanted between 1990 and 2018. The median age of patients was 5 years, and 57% were male. Twenty-five received their first HCT from an HLA-matched sibling donor (MSD), 12 from a HLA matched unrelated bone marrow donor (MUD 10/10, n = 12) and 7 other HLA mismatched donors (MMD). RESULTS: After a median follow-up of 4 years, estimate 5-year overall survival (OS) for the entire cohort was 70%, 80% for MSD group, 73% for MUD, and 29% for MMD. Thirty-eight out of the 44 evaluable patients engrafted successfully. Primary and secondary graft failure was observed in five and three patients, respectively. Rates of grade II-IV and III-IV acute graft-versus-host disease (aGVHD) were 25% and 18%, respectively. Nine patients developed chronic GVHD (cGVHD). CONCLUSION: Overall survival rates observed after HLA matched donors transplant for DBA were comparable to those reported from higher-income countries and international registries.

Remediation of a Riparian Site in the Brazilian Atlantic Forest Reached by Contaminated Tailings from the Collapsed Fundão Dam with Native Woody Species.

The failure of the Fundão dam in Brazil spilled alkaline contaminated sediments (pH ~8) into the Doce River basin. The contaminated sediments had high levels of ether amine (6 mg/kg) and Na (54 mg/kg) in relation to those in preserved sites. In the present study, a riparian forest was established over contaminated sediment using 2 main remediation strategies: phytoremediation with species native to the Atlantic forest and previously selected for their tolerance to sediment toxicity, and physicochemical remediation by incorporating organic matter (OM) into the sediment. In the experimental site (ES), the tolerant native woody species were cultivated in 2 treatments: T1, scraping of the sediments and incorporation of the OM, and T2, nonmanaged sediment and superficial deposition of the OM. The results were compared with the findings from a degraded site (DS), which was reached by the contaminated sediments but lacked vegetation, and a preserved site (PS), which was composed of a fragment of preserved Atlantic forest. Six months after transplanting, the plants from T1 showed a better height growth performance and survival index in relation to those from T2. Furthermore, T1 showed a significant decline in the pH (to ~6) concomitant with a reduction in the ether amine and Na contents (to ~0.4 mg/kg and 23 mg/kg, respectively). There was an improvement in the soil fertility and total microbial biomass in both treatments, especially in T1. Therefore, the adopted phyto- and physicochemical remediation procedures are recommended to reclaim zones reached by dam tailings containing Na and ether amine. Integr Environ Assess Manag 2020;16:669-675. © 2020 SETAC.

A ruptura da Barragen de Fundão em Mariana (Brazil) lançou um sedimento alcalino (pH ~8) ao longo da Bacia do Rio Doce. O sedimento contaminado apresentou altos níveis de éter-amina (6 mg/kg) e Na (54 mg/kg) em relação aqueles encontrados na área preservada. No presente estudo, uma floresta riparia foi estabelecida sobre este sedimento contaminado usando-se 2 estratégias de remediação: Fito-remediação com espécies nativas da Mata Atlântica, previamente selecionadas pela tolerância à toxicidade do sedimento, e remediação físico química pela raspagem superficial do sedimento e aplicação de matéria orgânica (OM). Na área experimental (ES) as espécies arbóreas da mata Atlântica selecionadas foram plantadas sob 2 tratamentos: T1, Raspagem superficial do sedimento e incorporação da OM, e T2, sedimento não foi manejado e recebeu aplicação superficial de OM. Os resultados foram comparados com aqueles obtidos na área degradada (DS), atingida pelo sedimento contaminado e sem vegetação, assim como com aqueles obtidos em uma área preservada (PS), constituída de um fragmento de Mata Atlântica. Após seis meses do plantio as plantas de T1 apresentaram um maior crescimento em altura e maior taxa de sobrevivência que as plantas de T2. Além disto ES, especialmente T1 mostraram um significante declínio do pH (~6.0) e concomitante redução nos teores de éter-amina e Na (~0.4 mg/kg e 23 mg/kg, respectivamente). Os procedimentos de remediação permitiram também um significativo aumento da fertilidade química e da biomassa microbiana do sedimento em ambos os tratamentos, especialmente em T1. Assim, os procedimentos de remediação físico-quimica e fitoremediação aqui adotados, são recomendados para recuperar as zonas atingidas pelo rejeito da barragem contaminado com sódio e éter-amina. Integr Environ Assess Manag 2020;16:669-675.

Transplantation of Hematopoietic Stem Cells for Primary Immunodeficiencies in Brazil: Challenges in Treating Rare Diseases in Developing Countries.

The results of hematopoietic stem cell transplant (HSCT) for primary immunodeficiency diseases (PID) have been improving over time. Unfortunately, developing countries do not experience the same results. This first report of Brazilian experience of HSCT for PID describes the development and results in the field. We included data from transplants in 221 patients, performed at 11 centers which participated in the Brazilian collaborative group, from July 1990 to December 2015. The majority of transplants were concentrated in one center (n = 123). The median age at HSCT was 22 months, and the most common diseases were severe combined immunodeficiency (SCID) (n = 67) and Wiskott-Aldrich syndrome (WAS) (n = 67). Only 15 patients received unconditioned transplants. Cumulative incidence of GVHD grades II to IV was 23%, and GVHD grades III to IV was 10%. The 5-year overall survival was 71.6%. WAS patients had better survival compared to other diseases. Most deaths (n = 53) occurred in the first year after transplantation mainly due to infection (55%) and GVHD (13%). Although transplant for PID patients in Brazil has evolved since its beginning, we still face some challenges like delayed diagnosis and referral, severe infections before transplant, a limited number of transplant centers with expertise, and resources for more advanced techniques. Measures like newborn screening for SCID may hasten the diagnosis and ameliorate patients' conditions at the moment of transplant.

The frequency of oral conditions detected in hematology inpatients

ABSTRACT Background: Oral manifestations may be the first signs of hematologic diseases, and may occur due to the disease itself or to treatment. Objective: To evaluate the frequency and types of oral conditions presented by patients on a hematology ward. Methods: Data were collected by oral examinations during weekly visits to a hematology ward. Six trained dentists performed the oral assessment based on the principles of oral semiology. All patients who accepted to be examined were included in the study. Patients who were unavailable or unable to have oral examinations were excluded. Data were recorded on protocol forms and in the electronic records of the institution. A descriptive analysis was performed. Results: Seventy-nine patients were included in the analysis; 50.6% were female and the mean age was 41.49 years. The most common reasons for hospitalization were chemotherapy and complications (81%), relapse (13.9%) and pre-transplant preparation (5%). The most frequent underlying diseases were multiple myeloma (17.7%), acute myeloid leukemia (15.4%) and acute lymphocytic leukemia (11.5%). Oral conditions were found in 36 (45.6%) patients, some of whom presented more than one condition. The most common oral conditions were dry lips (12.6%), mucositis (10.1%), petechiae (8.9%) and candidiasis (7.6%). Of the detected oral conditions, 56.9% were related to the underlying disease or chemotherapy and 20.2% were not related to the disease. Conclusion: This study shows the types and frequency of oral conditions observed in hematological inpatients. Awareness of these conditions is important for prevention and planning the care of patients with hematological diseases.

The frequency of oral conditions detected in hematology inpatients.

BACKGROUND: Oral manifestations may be the first signs of hematologic diseases, and may occur due to the disease itself or to treatment. OBJECTIVE: To evaluate the frequency and types of oral conditions presented by patients on a hematology ward. METHODS: Data were collected by oral examinations during weekly visits to a hematology ward. Six trained dentists performed the oral assessment based on the principles of oral semiology. All patients who accepted to be examined were included in the study. Patients who were unavailable or unable to have oral examinations were excluded. Data were recorded on protocol forms and in the electronic records of the institution. A descriptive analysis was performed. RESULTS: Seventy-nine patients were included in the analysis; 50.6% were female and the mean age was 41.49 years. The most common reasons for hospitalization were chemotherapy and complications (81%), relapse (13.9%) and pre-transplant preparation (5%). The most frequent underlying diseases were multiple myeloma (17.7%), acute myeloid leukemia (15.4%) and acute lymphocytic leukemia (11.5%). Oral conditions were found in 36 (45.6%) patients, some of whom presented more than one condition. The most common oral conditions were dry lips (12.6%), mucositis (10.1%), petechiae (8.9%) and candidiasis (7.6%). Of the detected oral conditions, 56.9% were related to the underlying disease or chemotherapy and 20.2% were not related to the disease. CONCLUSION: This study shows the types and frequency of oral conditions observed in hematological inpatients. Awareness of these conditions is important for prevention and planning the care of patients with hematological diseases.

Inhibition of the classical pathway of the complement system by saliva of Amblyomma cajennense (Acari: Ixodidae).

Inhibition of the complement system during and after haematophagy is of utmost importance for tick success in feeding and tick development. The role of such inhibition is to minimise damage to the intestinal epithelium as well as avoiding inflammation and opsonisation of salivary molecules at the bite site. Despite its importance, the salivary anti-complement activity has been characterised only in species belonging to the Ixodes ricinus complex which saliva is able to inhibit the alternative and lectin pathways. Little is known about this activity in other species of the Ixodidae family. Thus, the aim of this study was to describe the inhibition of the classical pathway of the complement system by the saliva of Amblyomma cajennense at different stages of the haematophagy. The A. cajennense saliva and salivary gland extract (SGE) were able to inhibit the complement classical pathway through haemolytic assays with higher activity observed when saliva was used. The anti-complement activity is present in the salivary glands of starving females and also in females throughout the whole feeding process, with significant higher activity soon after tick detachment. The SGE activity from both females fed on mice or horses had no significant correlation (p > 0.05) with tick body weight. The pH found in the intestinal lumen of A. cajennense was 8.04 ± 0.08 and haemolytic assays performed at pH 8.0 showed activation of the classical pathway similarly to what occurs at pH 7.4. Consequently, inhibition could be necessary to protect the tick enterocytes. Indeed, the inhibition observed by SGE was higher in pH 8.0 in comparison to pH 7.4 reinforcing the role of saliva in protecting the intestinal cells. Further studies should be carried out in order to identify the inhibitor molecule and characterise its inhibition mechanism.

Demethylation profile of the TNF-α promoter gene is associated with high expression of this cytokine in Dengue virus patients.

Dengue is the most prevalent arthropod-borne viral illness in humans. The overexpression of cytokines by Dengue virus (DENV) infected cells is associated with the most severe forms of the disease. Unmethylated CpG islands are related to a transcriptionally active structure, whereas methylated DNA recruits methyl-binding proteins that inhibit gene expression. Several studies have described the importance of epigenetic events in the regulation and expression of many cytokines. The purpose of the present study was to evaluate the methylation status of the IFN-γ and TNF-α promoters in DNA extracted from dengue infected patients using methylation-specific polymerase chain reaction. A high frequency of demethylation was observed in the TNF-α promoter of DENV infected patients when compared to non-infected controls. The patients with an unmethylated profile showed higher expression of TNF-α mRNA than patients with the methylated status. No difference was found in the methylation frequency between the two analyzed groups regarding the IFN-γ promoter or in the expression of IFN-γ transcripts. The present study provides the first association of TNF-α promoter demethylation in DENV infected individuals and demonstrates a correlation between the methylation status of the region analyzed and the expression of TNF-α transcripts in DENV infected patients. J. Med. Virol. 88:1297-1302, 2016. © 2016 Wiley Periodicals, Inc.

High spatial resolution land use and land cover mapping of the Brazilian Legal Amazon in 2008 using Landsat-5/TM and MODIS data / Mapeamento do uso e cobertura da terra na Amazônia Legal Brasileira com alta resolução espacial utilizando dados Landsat-5/TM e MODIS

Understanding spatial patterns of land use and land cover is essential for studies addressing biodiversity, climate change and environmental modeling as well as for the design and monitoring of land use policies. The aim of this study was to create a detailed map of land use land cover of the deforested areas of the Brazilian Legal Amazon up to 2008. Deforestation data from and uses were mapped with Landsat-5/TM images analysed with techniques, such as linear spectral mixture model, threshold slicing and visual interpretation, aided by temporal information extracted from NDVI MODIS time series. The result is a high spatial resolution of land use and land cover map of the entire Brazilian Legal Amazon for the year 2008 and corresponding calculation of area occupied by different land use classes. The results showed that the four classes of Pasture covered 62% of the deforested areas of the Brazilian Legal Amazon, followed by Secondary Vegetation with 21%. The area occupied by Annual Agriculture covered less than 5% of deforested areas; the remaining areas were distributed among six other land use classes. The maps generated from this project - called TerraClass - are available at INPE's web site (http://www.inpe.br/cra/projetos_pesquisas/terraclass2008.php).

Entender o padrão espacial do uso e cobertura da terra é essencial para estudos de biodiversidade, mudanças climáticas e modelagem ambiental, bem como para concepção e acompanhamento de políticas direcionadas ao uso da terra. O objetivo deste estudo foi criar um mapa detalhado do uso e cobertura da terra para a porção desflorestada da Amazônia Legal Brasileira, até 2008. Dados de desflorestamento e uso foram mapeados usando imagens Landsat-5/TM analisadas com técnicas como modelo linear de mistura espectral, fatiamento e interpretação visual, auxiliados por informações temporais de NDVI extraídas de série temporal de dados MODIS. O resultado deste estudo é um mapa de uso e cobertura da terra com alta resolução espacial para toda Amazônia Legal Brasileira, para o ano de 2008, e os respectivos percentuais da área ocupada por diferentes classes de uso da terra. O resultado mostrou que, quatro classes de pastagens cobrem 62% da área desflorestada da Amazônia Legal Brasileira, seguida pela vegetação secundária com 21%. A área ocupada pela agricultura anual cobriu menos de 5% das áreas desflorestadas; as áreas restantes estavam distribuídas em outras seis classes de uso da terra. Os mapas gerados por este projeto, chamado TerraClass, estão disponíveis no site do INPE (http://www.inpe.br/cra/projetos_pesquisas/terraclass2008.php).