Lipid Profile Changes During the First Year After Kidney Transplantation: Risk Factors and Influence of the Immunosuppressive Drug Regimen

Aim. This study analyzed the incidence, time course, and risk factors associated with dyslipidemia during the first year after kidney transplantation among patients receiving various immunosuppressive regimens.Methods. the analysis included 474 kidney transplant recipients receiving cyclosporine (CSA) combined with sirolimus (SRL; n = 137) or mycophenolate (MMF, n = 58) or everolimus (EVR, n = 47); or SRL combined with MMF (n = 32); or tacrolimus (TAC) combined with SRL (n = 86) or MMF (n = 114). All patients received prednisone. We evaluated the influence of demographic features, clinical outcomes, and statin use on lipid profiles during the first year after transplantation. total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-HDL-C, TC:HDL-C, LDL-C:HDL-C, TG:HDL-C.Results. Lipid profiles were within the recommended ranges in 28% of patients pretransplantation and in 10% at 1 year; 27% of them received statins. At 1 year, LDL-C 100 mg/dL, almost 70% to 80% had other lipid fractions or ratios within target ranges. A logistic regression analysis showed age, gender, time on dialysis, diabetes, type of calcineurin inhibitor (CSA vs TAC), adjunctive therapy (SRL/EVR vs MMF) and prednisone dose to be associated with dyslipidemia.Conclusion. Dyslipidemia is frequent at 1 year after transplantation. the lack of agreement among changes observed in lipid fractions and ratios suggests that more studies are necessary to guide therapy besides targeting LDL-C concentrations as recommended by current guidelines.Universidade Federal de São Paulo UNIFESP, Div Nephrol, Hosp Rim & Hipertensao, BR-04038002 São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Div Nephrol, Hosp Rim & Hipertensao, BR-04038002 São Paulo, BrazilWeb of Scienc

Geochemical modeling of gold precipitation conditions in the Bloco do Butiá Mine, Lavras do Sul/Brazil

Com auxílio dos pacotes de programas EQ3/EQ6 foi realizado um modelamento geoquímico deposicional para ouro e comparado com dados geológicos, petrográficos, geoquímicos e de inclusões fluidas da mina de ouro do Bloco do Butiá, Lavras do Sul/RS. O ouro ocorre na estrutura da pirita (ouro invisível) associado a mica branca (fengita) na alteração fílica. Foi demonstrado que os processos que levamà deposição do ouro são aqueles relacionados ao decréscimo da temperatura e ao abaixamento do pH. O pH também mostrou ser fundamental para a deposição do ouro com as espécies de enxofre [Au(HS)−2 , HAu(HS)02 e Au(HS)0], em razão de potencializar sua desestabilização, sendo Au(HS)0 a principal espécie complexante. A entrada de KCl é de difícil aceitação como causa da precipitação do ouro visto que não foi identificado Cl− na fengita, apesar de que em todos os cálculos de balanço geoquímico de massa sempre foi necessário admitir a entrada de um pouco de potássio na alteração fílica. A precipitação da pirita (± aurífera) deve ter sido fortemente influenciada pela disponibilidade de ferro de clorita ferrosa, quando da sua dissolução pelos fluidos que depositaram fengita. As baixas salinidades verificadas nas inclusões fluidas dos grãos de quartzo da encaixante propilitizada também advogam para a pouca importância do cloro como agente transportador de ouro. Compostos de enxofre e não de cloro devemter dominado como complexos transportadores de ouro na área do Bloco do Butiá.A geochemical modeling of gold deposition was performed using the EQ3/EQ6 software package using conditions inferred from geological, petrographic, geochemical and fluid inclusion data from the Bloco do Butiá gold mine, Lavras do Sul, RS. Gold in the mine occurs only in the pyrite structure (invisible gold). The pyrite occurs associated with white mica (phengite) in the zone of phyllic alteration. The process of gold deposition showed to be related to temperature and pH decrease. The pH decrease was fundamental to gold deposition by destabilization of sulfur species [Au(HS)−2 , HAu(HS)02 and Au(HS)0] dissolved in the aqueous solution, being Au(HS)0 the main gold transporting complex. The addition of KCl is hard to accept as cause of gold precipitation because no Cl– was detected in phengite. However, the geochemical mass balance calculation resulted in the gain of some potassium in the zone of phyllic alteration. The precipitation of pyrite (± auriferous) may have been strongly influenced by iron availability resulting from dissolution of ferrous chlorites by the fluids responsible for phengite deposition. The low salinity in quartz grain fluid inclusions from the propylitized wall rock also indicates the little importance of chlorine as gold transporting agent. Sulfur, and not chlorine, compounds must have dominated the gold transporting complexes in the Bloco do Butiá gold area

Combined effects of CXCL8 and CXCR2 gene polymorphisms on susceptibility to systemic sclerosis

A previous study suggested that the CXCR2 (+1208) TT genotype was associated with increased risk of systemic sclerosis (SSc). In the present study, we investigated the influence of variation in the CXCL8 and CXCR2 genes on susceptibility to SSc and combined the variant alleles of these genes to analyze their effects on SSc. Methods: One fifty one patients with SSc and 147 healthy bone marrow donors were enrolled in a casecontrol study. Blood was collected for DNA extraction; typing of CXCL8 (251) T/A and CXCR2 (+1208) T/ C genes was made by polymerase chain reaction with sequence specific primers (PCR-SSP), followed by agarose gel electrophoresis. Results: The CXCR2-TC genotype was significantly less frequent in patients (23.8% versus 55.1% in controls; P < 0.001, OR = 0.26, 95%CI = 0.15–0.43), whereas the CXCR2-CC genotype was significantly more frequent (44.4% versus 22.4% in controls; P < 0.001, OR = 2.76, 95%CI, 1.62–4.72). When CXCR2 and CXCL8 combinations were analyzed, the presence of CXCR2 T in the absence of CXCL8 A (CXCR2 T+/CXCL8 A) was more frequent in patients than in controls (34.5% versus 3.5%; P < 0.001, OR = 14.50, 95%CI = 5.04– 41.40). However, CXCR2 TT and CXCL8 A were significantly more common in controls (100%) than in patients (58.3%) (P < 0.001). Likewise, the presence of CXCR2 TC and CXCL8 A was more frequent in controls (95.1%) than in patients (75%) (P = 0.004). Furthermore, the CXCR2-CC genotype in CXCL8 A was more frequent in patients (59.7% versus 0% in controls; P < 0.001, adjusted OR = 98.67, 95%CI = 6.04– 1610.8). In patients, a high frequency was observed in combination with the CXCL8 TA and AA genotypes (P < 0.001; OR = 28.92), whereas in controls, there was a high frequency of combination with CXCL8 T (P < 0.001; OR = 0.03) and TT (P < 0.001; OR = 0.01). ). Conclusions: These findings suggest a protective role of CXCL8 (251) A in the CXCR2 (+1208) TT and TC genotypes and an increased risk of CXCL8 (251) A in association with the CXCR2 (+1208) CC genotype in SSc patient

Aplicação de Modelos Intencionais e Sistemas Multiagentes para Estabelecer Políticas de Monitoração de Transparência de Software

O artigo apresenta uma proposta de monitoração de características de transparência de software a partir de sistemas multiagentes. É um primeiro esforço para o entendimento de políticas e modelos intencionais aplicados a agentes autônomos monitores

Alemtuzumab induction in kidney transplant recipients

INTRODUCTION: Induction therapy has been used in sensitized patients, re-transplants, and in patients who have high risk to delayed graft function (DGF) after renal transplantation. METHODS: Retrospective study with aim to compare transplant endpoints between recipients of deceased donors which have received induction with alemtuzumab (n = 9) versus thymoglobulin (n = 18). Patients were matched for age, duration of dialysis treatment and cold ischemia time. RESULTS: There were no differences at demographic characteristics. All patients received kidney grafts from deceased donors and 67% of these donors met the expanded criteria. The incidence of DFG was similar in alemtuzumab and thymoglobulin groups, 55% and 56%. At 12 months, rates of rejection free survival (67% versus 89%, p = 0,13), graft survival (62,5% versus 76,6%; p = 0,73), graft with death censored (62,5% versus 76,6%; p = 0,82) and patient survival (83,3% versus 81,2%; p = 0,63) were similar between the two groups. Viral infections and renal function were similar between groups. At the end of the first month, alemtuzumab patients displayed a fewer lymphocyte number (135 ± 78 versus 263 ± 112 N/mm³, p < 0,05) followed by a more rapid recovery after 3 months (day 90: 683 ± 367 versus 282 ± 72 N/mm³; p < 0,05). Cost associated with alemtuzumab and thymoglobulin inductions therapies were R$1,388.00 and R$ 7,398.00. CONCLUSION: In this cohort of patients, alemtuzumab induction showed efficacy and safety comparable to thymoglobulin but with significant cost reduction.INTRODUÇÃO: Terapias de indução são usualmente utilizadas em receptores sensibilizados contra antígenos HLA, retransplantes e pacientes com risco de apresentar função tardia do enxerto (FTE). MÉTODO: Estudo retrospectivo com objetivo de avaliar os desfechos do transplante renal com doador falecido em pacientes que receberam indução com alentuzumabe (n = 9). Os pacientes do grupo controle, pareados conforme idade do receptor, tempo em diálise e tempo de isquemia fria, receberam timoglobulina (n = 18). RESULTADOS: Não houve diferença nas características demográficas entre os grupos. A idade média dos receptores foi de 47 anos e dos doadores, de 59 anos. Entre os doadores, 67% apresentavam critério expandido. A incidência de FTE foi de 55% e 56%, respectivamente. Ao final do primeiro ano, não houve diferença nas sobrevidas livre de rejeição aguda comprovada por biópsia (67,0% e 84,6%, p = 0,26), do paciente (83,3% e 81,2%; p = 0,63), do enxerto (62,5% e 66,7%; p = 0,82), do enxerto com óbito censorado (62,5% e 76,6%; p = 0,73) e na função renal (depuração de creatinina: 61,6 ± 18,2 versus 52,7 ± 26,1 mL/min, p = 0,503). Houve maior redução na contagem de linfócitos no sangue periférico no grupo alentuzumabe (dia 14:172 ± 129 versus 390 ± 195 N/mm³, p < 0,05; dia 30: 135 ± 78 versus 263±112 N/mm³, p < 0,05), porém com retorno mais rápido a valores normais após o transplante (dia 90: 683 ± 367 versus 282 ± 72 N/mm³, p < 0,05; dia 360: 1269 ± 806 versus 690±444 N/mm³, p < 0,05). O custo do tratamento com alentuzumabe foi de R$1.388,00, enquanto que o custo médio com timoglobulina foi de R$ 7.398,00. CONCLUSÃO: Essa experiência com alentuzumabe não demonstrou eficácia e/ou segurança superiores aos regimes com timoglobulina, apesar do custo ser em média cinco vezes menor.Universidade Federal de São Paulo (UNIFESP) Departamento de Medicina Hospital do Rim e HipertensãoUniversidade Federal de São Paulo (UNIFESP) Departamento de Patologia, Transplante Renal e NefropatologiaUNIFESP, Depto. de Medicina Hospital do Rim e HipertensãoUNIFESP, Depto. de Patologia, Transplante Renal e NefropatologiaSciEL

Enhancing Network Slicing Architectures with Machine Learning, Security, Sustainability and Experimental Networks Integration

Network Slicing (NS) is an essential technique extensively used in 5G networks computing strategies, mobile edge computing, mobile cloud computing, and verticals like the Internet of Vehicles and industrial IoT, among others. NS is foreseen as one of the leading enablers for 6G futuristic and highly demanding applications since it allows the optimization and customization of scarce and disputed resources among dynamic, demanding clients with highly distinct application requirements. Various standardization organizations, like 3GPP's proposal for new generation networks and state-of-the-art 5G/6G research projects, are proposing new NS architectures. However, new NS architectures have to deal with an extensive range of requirements that inherently result in having NS architecture proposals typically fulfilling the needs of specific sets of domains with commonalities. The Slicing Future Internet Infrastructures (SFI2) architecture proposal explores the gap resulting from the diversity of NS architectures target domains by proposing a new NS reference architecture with a defined focus on integrating experimental networks and enhancing the NS architecture with Machine Learning (ML) native optimizations, energy-efficient slicing, and slicing-tailored security functionalities. The SFI2 architectural main contribution includes the utilization of the slice-as-a-service paradigm for end-to-end orchestration of resources across multi-domains and multi-technology experimental networks. In addition, the SFI2 reference architecture instantiations will enhance the multi-domain and multi-technology integrated experimental network deployment with native ML optimization, energy-efficient aware slicing, and slicing-tailored security functionalities for the practical domain.Comment: 10 pages, 11 figure

HOPX homeobox methylation in differentiated thyroid cancer and its clinical relevance

Background: The inactivation of the tumor-suppressor homeodomain-only protein X (HOPX) usually involves promoter methylation in several cancer types. This study aimed to investigate the HOPX-β mRNA expression and promoter methylation and their clinical relevance in differentiated thyroid cancer (DTC). Patients and methods: Clinicopathological data and paraffin-embedded thyroid tumor tissues from 21 patients with DTC and 6 with benign tumors (T) and their non-tumor parenchyma (NT) were investigated. Tumor cell lines (FTC238, FTC236 and WRO) were treated with demethylating agent. HOPX-β mRNA expression was assessed by qRT-PCR and methylation status by Q-MSP. Thyroid cancer data from Cancer Genome Atlas (TCGA) was also collected. Results: HOPX-β mRNA re-expression in two cell lines treated with demethylating agent was observed concomitantly with reduced promoter methylation. Reduced mRNA expression in T group compared to their NT was observed, and reduced protein expression in T compared to NT was observed in three cases. Low mRNA expression with high methylation status was detected in 6/14 DTC samples. High methylation status was associated with older age at diagnosis, recurrent or progressive disease and with the presence of new neoplasm event post initial therapy while hyper-methylation correlated with worse overall survival, worse disease-free status and older age. Conclusion: A moderate coupling of downregulation of HOPX-β mRNA expression in DTC followed by high HOPX-β promoter methylation was observed however; high HOPX promoter methylation status was associated with the worse prognosis of DTC patients

Variation in stem mortality rates determines patterns of above-ground biomass in Amazonian forests: implications for dynamic global vegetation models

Understanding the processes that determine above-ground biomass (AGB) in Amazonian forests is important for predicting the sensitivity of these ecosystems to environmental change and for designing and evaluating dynamic global vegetation models (DGVMs). AGB is determined by inputs from woody productivity [woody net primary productivity (NPP)] and the rate at which carbon is lost through tree mortality. Here, we test whether two direct metrics of tree mortality (the absolute rate of woody biomass loss and the rate of stem mortality) and/or woody NPP, control variation in AGB among 167 plots in intact forest across Amazonia. We then compare these relationships and the observed variation in AGB and woody NPP with the predictions of four DGVMs. The observations show that stem mortality rates, rather than absolute rates of woody biomass loss, are the most important predictor of AGB, which is consistent with the importance of stand size structure for determining spatial variation in AGB. The relationship between stem mortality rates and AGB varies among different regions of Amazonia, indicating that variation in wood density and height/diameter relationships also influences AGB. In contrast to previous findings, we find that woody NPP is not correlated with stem mortality rates and is weakly positively correlated with AGB. Across the four models, basin-wide average AGB is similar to the mean of the observations. However, the models consistently overestimate woody NPP and poorly represent the spatial patterns of both AGB and woody NPP estimated using plot data. In marked contrast to the observations, DGVMs typically show strong positive relationships between woody NPP and AGB. Resolving these differences will require incorporating forest size structure, mechanistic models of stem mortality and variation in functional composition in DGVMs

Variation in stem mortality rates determines patterns of above-ground biomass in Amazonian forests: implications for dynamic global vegetation models

This is the final version of the article. Available from Wiley via the DOI in this record.Understanding the processes that determine above-ground biomass (AGB) in Amazonian forests is important for predicting the sensitivity of these ecosystems to environmental change and for designing and evaluating dynamic global vegetation models (DGVMs). AGB is determined by inputs from woody productivity [woody net primary productivity (NPP)] and the rate at which carbon is lost through tree mortality. Here, we test whether two direct metrics of tree mortality (the absolute rate of woody biomass loss and the rate of stem mortality) and/or woody NPP, control variation in AGB among 167 plots in intact forest across Amazonia. We then compare these relationships and the observed variation in AGB and woody NPP with the predictions of four DGVMs. The observations show that stem mortality rates, rather than absolute rates of woody biomass loss, are the most important predictor of AGB, which is consistent with the importance of stand size structure for determining spatial variation in AGB. The relationship between stem mortality rates and AGB varies among different regions of Amazonia, indicating that variation in wood density and height/diameter relationships also influences AGB. In contrast to previous findings, we find that woody NPP is not correlated with stem mortality rates and is weakly positively correlated with AGB. Across the four models, basin-wide average AGB is similar to the mean of the observations. However, the models consistently overestimate woody NPP and poorly represent the spatial patterns of both AGB and woody NPP estimated using plot data. In marked contrast to the observations, DGVMs typically show strong positive relationships between woody NPP and AGB. Resolving these differences will require incorporating forest size structure, mechanistic models of stem mortality and variation in functional composition in DGVMs.This paper is a product of the European Union's Seventh Framework Programme AMAZALERT project (282664). The field data used in this study have been generated by the RAINFOR network, which has been supported by a Gordon and Betty Moore Foundation grant, the European Union's Seventh Framework Programme projects 283080, ‘GEOCARBON’; and 282664, ‘AMAZALERT’; ERC grant ‘Tropical Forests in the Changing Earth System’), and Natural Environment Research Council (NERC) Urgency, Consortium and Standard Grants ‘AMAZONICA’ (NE/F005806/1), ‘TROBIT’ (NE/D005590/1) and ‘Niche Evolution of South American Trees’ (NE/I028122/1). Additional data were included from the Tropical Ecology Assessment and Monitoring (TEAM) Network – a collaboration between Conservation International, the Missouri Botanical Garden, the Smithsonian Institution and the Wildlife Conservation Society, and partly funded by these institutions, the Gordon and Betty Moore Foundation, and other donors. Fieldwork was also partially supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico of Brazil (CNPq), project Programa de Pesquisas Ecológicas de Longa Duração (PELD-403725/2012-7). A.R. acknowledges funding from the Helmholtz Alliance ‘Remote Sensing and Earth System Dynamics’; L.P., M.P.C. E.A. and M.T. are partially funded by the EU FP7 project ‘ROBIN’ (283093), with co-funding for E.A. from the Dutch Ministry of Economic Affairs (KB-14-003-030); B.C. [was supported in part by the US DOE (BER) NGEE-Tropics project (subcontract to LANL). O.L.P. is supported by an ERC Advanced Grant and is a Royal Society-Wolfson Research Merit Award holder. P.M. acknowledges support from ARC grant FT110100457 and NERC grants NE/J011002/1, and T.R.B. acknowledges support from a Leverhulme Trust Research Fellowship

Cardiovascular Statistics - Brazil 2021.

This is the 2021 edition of the Cardiovascular Statistics – Brazil , a multi-institutional effort to periodically provide updated information on the epidemiology of heart diseases and stroke in Brazil. The report incorporates official statistics provided by the Brazilian Ministry of Health and other government agencies, by the GBD project led by the IHME of the University of Washington, as well as data generated by other sources and scientific studies, such as cohorts and registries, on CVDs and their risk factors. The document is directed to researchers, clinicians, patients, healthcare policy makers, media professionals, the public, and others who seek comprehensive national data available on heart disease and stroke