We have previously reported on neurogenic bladder dysfunction among Congenital Zika Vírus Syndrome (CZS) patients, but it is unknown how they will respond to treatment.
To assess whether children ...with neurological lower urinary tract dysfunction and CZS will respond to Standard therapies.
A prospective observational cohort study of children with CZS referred for urological assessment between 2016 and 2020 to our quaternary center in Brazil. Urological protocol included clinical history, urinalysis and culture, renal and bladder ultrasonography and urodynamic study. Patients were treated based on findings from the first evaluation, with oxybutynin chloride for overactive bladder and low bladder compliance, clean intermittent catheterization for ineffective bladder emptying, or dual therapy when both were observed. Urological outcomes were evaluated between the first and second visits considering patient's adherence. Outcomes measured included clinical, imaging, and urodynamic variables. Data was analyzed using the IBM SPSS 22 software.
From the cohort of 90 patients, 56 completed the second urodynamic assessment and were included. One presented underactive bladder and 55 overactive bladder. Among these 55, 39 were adherent and 16 non-adherents to the prescribed treatment.
Among the 39 adherents, 8 adhered regularly to oxybutynin and clean intermittent catheterization (CIC), 29 to oxybutynin alone, and two to catheterization alone. During follow-up, the number of patients with urinary tract infection and postvoid residual increased, but all other parameters had improved. Renal and bladder ultrasonography improved in 10, maximum bladder pressure decreased in 22 and maximum cystometric capacity and compliance increased in 14 patients.
Sixteen patients did not adhere regularly to the prescribed treatment and although the number of patients with urinary tract infection reduced with antibiotic therapy, their bladder capacity and compliance did not improve during follow-up.
Ultrasonographic and urodynamic improvements were observed after 10.8 ± 7.5 months of treatment, including one patient with ureterohydronephrosis that resolved. Adherence to CIC remains a challenge and reflected in the number of patients presenting urinary tract infection and postvoid residual. The immediate clinical relevance is the major study strength, given the previously uncharacterized therapy options for this patient population.
The number of patients remains one of the study limitations, reducing our ability to perform more advanced statistical analyses.
Patients with Zika-related neurological lower urinary tract dysfunction may benefit from conventional therapies. Results confirmed ultrasonographic and urodynamic improvements after treatment, although not statically significant. Adherence to treatment, specifically to CIC, remains a challenge.Summary TableSummary TableClinical outcomes reported by adherence to treatment algorithms among the 39 adherent patients.Oxybutynin + CIC (n = 8)Oxybutynin alone (n = 29)CIC alone (n = 2)Total (n = 39)Improvement bladder and renal US3 (37.5%)5 (17%)210 (25.6%)Improvement max. bladder pressure4 (50%)17 (59%)122 (56.4%)Improvement max. cystometric capacity3 (37.5%)10 (35%)114 (35.8%)Improvement bladder compliance4 (50%)9 (31%)114 (35.8%)Improvement postvoid residual5 (63%)4 (14%)211 (28.2%)
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Acute kidney injury (AKI) is a critical systemic complication caused by Bothrops envenoming, a neglected health problem in the Brazilian Amazon. Understanding the underlying mechanisms leading to AKI ...is crucial for effectively mitigating the burden of this complication. This study aimed to characterize the urinary protein profile of Bothrops atrox snakebite victims who developed AKI. We analyzed three groups of samples collected on admission: healthy subjects (controls, n = 10), snakebite victims who developed AKI (AKI, n = 10), and those who did not evolve to AKI (No-AKI, n = 10). Using liquid-chromatography tandem mass spectrometry, we identified and quantified (label-free) 1190 proteins. A panel of 65 proteins was identified exclusively in the urine of snakebite victims, with 32 exclusives to the AKI condition. Proteins more abundant or exclusive in AKI's urine were associated with acute phase response, endopeptidase inhibition, complement cascade, and inflammation. Notable proteins include serotransferrin, SERPINA-1, alpha-1B-glycoprotein, and NHL repeat-containing protein 3. Furthermore, evaluating previously reported biomarkers candidates for AKI and renal injury, we found retinol-binding protein, beta-2-microglobulin, cystatin-C, and hepcidin to be significant in cases of AKI induced by Bothrops envenoming. This work sheds light on physiological disturbances caused by Bothrops envenoming, highlighting potential biological processes contributing to AKI. Such insights may aid in better understanding and managing this life-threatening complication.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The sepsis burden on acute care services in middle-income countries is a cause for concern. We estimated incidence, prevalence, and mortality of sepsis in adult Brazilian intensive care units (ICUs) ...and association of ICU organisational factors with outcome.
We did a 1-day point prevalence study with follow-up of patients in ICU with sepsis in a nationally representative pseudo-random sample. We produced a sampling frame initially stratified by geographical region. Each stratum was then stratified by hospitals' main source of income (serving general public vs privately insured individuals) and ICU size (ten or fewer beds vs more than ten beds), finally generating 40 strata. In each stratum we selected a random sample of ICUs so as to enrol the total required beds in 1690 Brazilian adult ICUs. We followed up patients until hospital discharge censored at 60 days, estimated incidence from prevalence and length of stay, and generated national estimates. We assessed mortality prognostic factors using random-effects logistic regression models.
On Feb 27, 2014, 227 (72%) of 317 ICUs that were randomly selected provided data on 2632 patients, of whom 794 had sepsis (30·2 septic patients per 100 ICU beds, 95% CI 28·4–31·9). The ICU sepsis incidence was 36·3 per 1000 patient-days (95% CI 29·8–44·0) and mortality was observed in 439 (55·7%) of 788 patients (95% CI 52·2–59·2). Low availability of resources (odds ratio OR 1·67, 95% CI 1·02–2·75, p=0·045) and adequacy of treatment (OR 0·56, 0·37–0·84, p=0·006) were independently associated with mortality. The projected incidence rate is 290 per 100 000 population (95% CI 237·9–351·2) of adult cases of ICU-treated sepsis per year, which yields about 420 000 cases annually, of whom 230 000 die in hospital.
The incidence, prevalence, and mortality of ICU-treated sepsis is high in Brazil. Outcome varies considerably, and is associated with access to adequate resources and treatment. Our results show the burden of sepsis in resource-limited settings, highlighting the need to establish programmes aiming for sepsis prevention, early diagnosis, and adequate treatment.
Fundação de Apoio a Pesquisa do Estado de São Paulo (FAPESP).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Iron deficiency impairs the formation of hemoglobin, red blood cells, as well the transport of oxygen. The wound healing process involves numerous functions, many of which are dependent on the ...presence of oxygen. Laser has been shown to improve angiogenesis, increases blood supply, cell proliferation and function. We aimed to study the effect of λ660 nm laser and λ700 nm light-emitting diode (LED) on fibroblastic proliferation on cutaneous wounds on iron-deficient rodents. Induction of iron anemia was carried out by feeding 105 newborn rats with a special iron-free diet. A 1 × 1 cm wound was created on the dorsum of each animal that were randomly distributed into seven groups: I, control anemic; II, anemic no treatment; III, anemic + L; IV, anemic + LED; V, healthy no treatment; VI, healthy + laser; VII, healthy + LED (
n
= 15 each). Phototherapy was carried out using either a diode laser (λ660 nm, 40 mW, 10 J/cm
2
) or a prototype LED device (λ700 ± 20 nm, 15 mW, 10 J/cm
2
). Treatment started immediately after surgery and was repeated at 48-h interval during 7, 14, and 21 days. After animal death, specimens were taken, routinely processed, cut, stained with hematoxylin-eosin, and underwent histological analysis and fibroblast counting. Significant difference between healthy and anemic subjects on regards the number of fibroblast between treatments was seen (
p
< 0.008,
p
< 0.001). On healthy animals, significant higher count was seen when laser was used (
p
< 0.008). Anemic subjects irradiated with LED showed significantly higher count (
p
< 0.001). It is concluded that the use of LED light caused a significant positive biomodulation of fibroblastic proliferation on anemic animals and laser was more effective on increasing proliferation on non-anemics.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Protecting riparian vegetation around streams is vital in reducing the detrimental effects of environmental change on freshwater ecosystems and in maintaining aquatic biodiversity. Thus, identifying ...ecological thresholds is useful for defining regulatory limits and for guiding the management of riparian zones towards the conservation of freshwater biota.
Using nationwide data on fish and invertebrates occurring in small Brazilian streams, we estimated thresholds of native vegetation loss in which there are abrupt changes in the occurrence and abundance of freshwater bioindicators and tested whether there are congruent responses among different biomes, biological groups and riparian buffer sizes.
Mean thresholds of native vegetation cover loss varied widely among biomes, buffer sizes and biological groups: ranging from 0.5% to 77.4% for fish, from 2.9% to 37.0% for aquatic invertebrates and from 3.8% to 43.2% for a subset of aquatic invertebrates. Confidence intervals for thresholds were wide, but the minimum values of these intervals were lower for the smaller riparian buffers (50 and 100 m) than larger ones (200 and 500 m), indicating that land use should be kept away from the streams. Also, thresholds occurred at a lower percentage of riparian vegetation loss in the smaller buffers, and were critically lower for invertebrates: reducing only 6.5% of native vegetation cover within a 50‐m riparian buffer is enough to cross thresholds for invertebrates.
Synthesis and applications. The high variability in biodiversity responses to loss of native riparian vegetation suggests caution in the use of a single riparian width for conservation actions or policy definitions nationwide. The most sensitive bioindicators can be used as early warning signals of abrupt changes in freshwater biodiversity. In practice, maintaining at least 50‐m wide riparian reserves on each side of streams would be more effective to protect freshwater biodiversity in Brazil. However, incentives and conservation strategies to protect even wider riparian reserves (~100 m) and also taking into consideration the regional context will promote a greater benefit. This information should be used to set conservation goals and to create complementary mechanisms and policies to protect wider riparian reserves than those currently required by the federal law.
Resumo
Proteger a vegetação no entorno de riachos é vital para reduzir os efeitos das mudanças ambientais sobre os ecossistemas aquáticos e para a manutenção de sua biodiversidade. Assim, a identificação de limiares ecológicos é útil para regular os limites de uso e para orientar o manejo de zonas ripárias, visando a conservação da biota aquática.
Usando dados de peixes e invertebrados aquáticos de pequenos riachos do Brasil, nós estimamos os limiares de perda de vegetação nativa nos quais ocorrem mudanças abruptas na ocorrência e abundância de bioindicadores aquáticos. Também testamos se existem respostas congruentes entre os diferentes biomas, grupos biológicos e áreas de vegetação ripária (buffers).
Os valores médios dos limiares de perda de vegetação nativa variaram marcadamente entre biomas, tamanhos de buffer e grupos biológicos: entre 0,5% e 77,4% para peixes, entre 2,9% e 37,0% para invertebrados aquáticos e entre 3,8% e 43,2% para um subconjunto de invertebrados aquáticos. Os intervalos de confiança dos limiares foram amplos, mas os valores mínimos dos intervalos foram reduzidos para os menores buffers ripários (50 e 100 m) em comparação com os maiores (200 e 500 m), indicando que o uso do solo deve ser mantido longe dos riachos. Além disso, os limiares ocorreram em menores porcentagens de perda de vegetação ripária nos buffers menores, e foram criticamente baixos para invertebrados aquáticos: uma redução de apenas 6,5% da cobertura de vegetação nativa no buffer ripário de 50 m é suficiente para ultrapassar os limiares de perda de invertebrados.
Síntese e aplicações. A elevada variabilidade dos limiares de declínio abrupto da biodiversidade aquática em resposta a perda de vegetação ripária nativa sugere cautela no uso de uma largura única de proteção ripária para ações de conservação e definição de políticas nacionais. Os bioindicadores mais sensíveis podem ser usados como sinais precoces que alertam a aproximação de mudanças abruptas na biodiversidade aquática. Na prática, manter reservas ripárias (áreas de preservação permanente—APP) de pelo menos 50 m de largura, em ambos os lados dos riachos, parece ser mais efetivo em proteger a biodiversidade de água doce do Brasil. Contudo, incentivos e estratégias de conservação que protejam reservas ripárias ainda maiores (~100 m de largura) e que levem em consideração o contexto regional podem promover um maior benefício. Essas informações podem ser usadas para definir metas de conservação e para criar mecanismos e políticas complementares para proteger reservas ripárias (APP) ainda maiores do que aquelas atualmente requeridas pela lei federal.
The high variability in biodiversity responses to loss of native riparian vegetation suggests caution in the use of a single riparian width for conservation actions or policy definitions nationwide. The most sensitive bioindicators can be used as early warning signals of abrupt changes in freshwater biodiversity. In practice, maintaining at least 50‐m wide riparian reserves on each side of streams would be more effective to protect freshwater biodiversity in Brazil. However, incentives and conservation strategies to protect even wider riparian reserves (~100 m) and also taking into consideration the regional context will promote a greater benefit. This information should be used to set conservation goals and to create complementary mechanisms and policies to protect wider riparian reserves than those currently required by the federal law.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
To investigate the association between postpartum depression and the occurrence of exclusive breastfeeding.
This is a cross-sectional study conducted in the states of the Northeast region, during the ...vaccination campaign in 2010. The sample consisted of 2583 mother–child pairs, with children aged from 15 days to 3 months. The Edinburgh Postnatal Depression Scale was used to screen for postpartum depression. The outcome was lack of exclusive breastfeeding, defined as the occurrence of this practice in the 24h preceding the interview. Postpartum depression was the explanatory variable of interest and the covariates were: socioeconomic and demographic conditions; maternal health care; prenatal, delivery, and postnatal care; and the child's biological factors. Multivariate logistic regression analysis was conducted to control for possible confounding factors.
Exclusive breastfeeding was observed in 50.8% of the infants and 11.8% of women had symptoms of postpartum depression. In the multivariate logistic regression analysis, a higher chance of exclusive breastfeeding absence was found among mothers with symptoms of postpartum depression (OR=1.67; p<0.001), among younger subjects (OR=1.89; p<0.001), those who reported receiving benefits from the Bolsa Família Program (OR=1.25; p=0.016), and those started antenatal care later during pregnancy (OR=2.14; p=0.032).
Postpartum depression contributed to reducing the practice of exclusive breastfeeding. Therefore, this disorder should be included in the prenatal and early postpartum support guidelines for breastfeeding, especially in low socioeconomic status women.
Verificar a associação entre a depressão pós-parto e a ocorrência do aleitamento materno exclusivo.
Estudo de corte transversal realizado nos estados da região Nordeste, durante a campanha de vacinação de 2010. A amostra consistiu de 2583 binômios mães-crianças com idade entre 15 dias e 3 meses. Utilizou-se a Escala de Depressão Pós-Parto de Edimburgo para rastrear a depressão pós-parto. O desfecho consistiu da ausência de aleitamento materno exclusivo nas 24 horas que antecederam a entrevista. A depressão pós-parto foi variável explanatória de interesse e as covariáveis foram: as condições socioeconômicas e demográficas, assistência pré-natal, ao parto e pós-natal, e fatores da criança. Realizou-se análise de regressão logística multivariada com o objetivo de controlar possíveis fatores de confusão.
A amamentação exclusiva foi observada em 50,8% das crianças e 11,8% das mulheres apresentaram sintomatologia indicativa de depressão pós-parto. Na análise de regressão logística multivariada foi verificada uma maior chance de ausência do aleitamento materno exclusivo entre as mães com sintomas de depressão pós-parto (OR=1,67; p<0,001).
A depressão pós-parto contribuiu para redução da prática do aleitamento materno exclusivo. Assim sendo, esse transtorno deveria ser incluído nas orientações de suporte desde o pré-natal e nos primeiros meses pós-parto, especialmente, em mulheres de baixo nível socioeconômico.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
COVID-19 can result in severe lung injury. It remained to be determined why diabetic individuals with uncontrolled glucose levels are more prone to develop the severe form of COVID-19. The molecular ...mechanism underlying SARS-CoV-2 infection and what determines the onset of the cytokine storm found in severe COVID-19 patients are unknown. Monocytes and macrophages are the most enriched immune cell types in the lungs of COVID-19 patients and appear to have a central role in the pathogenicity of the disease. These cells adapt their metabolism upon infection and become highly glycolytic, which facilitates SARS-CoV-2 replication. The infection triggers mitochondrial ROS production, which induces stabilization of hypoxia-inducible factor-1α (HIF-1α) and consequently promotes glycolysis. HIF-1α-induced changes in monocyte metabolism by SARS-CoV-2 infection directly inhibit T cell response and reduce epithelial cell survival. Targeting HIF-1ɑ may have great therapeutic potential for the development of novel drugs to treat COVID-19.
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•Elevated glucose levels regulate viral replication and cytokine production in monocytes•Glycolysis sustains CoV-2-induced monocyte response and viral replication•mtROS/HIF-1α is necessary for CoV-2 replication and monocyte cytokine production•Monocyte-derived cytokines drive T cell dysfunction and epithelial cell death
Diabetic people with uncontrolled blood glucose levels have a greater risk to develop severe COVID-19 disease. Codo et al. show that elevated glucose levels and glycolysis promote SARS-CoV-2 (CoV-2) replication and cytokine production in monocytes through a mitochondrial ROS/hypoxia-inducible factor-1α dependent pathway, resulting in T cell dysfunction and epithelial cell death.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Sporisorium scitamineum is a biotrophic fungus responsible for the sugarcane smut, a worldwide spread disease. This study provides the complete sequence of individual chromosomes of S. scitamineum ...from telomere to telomere achieved by a combination of PacBio long reads and Illumina short reads sequence data, as well as a draft sequence of a second fungal strain. Comparative analysis to previous available sequences of another strain detected few polymorphisms among the three genomes. The novel complete sequence described herein allowed us to identify and annotate extended subtelomeric regions, repetitive elements and the mitochondrial DNA sequence. The genome comprises 19,979,571 bases, 6,677 genes encoding proteins, 111 tRNAs and 3 assembled copies of rDNA, out of our estimated number of copies as 130. Chromosomal reorganizations were detected when comparing to sequences of S. reilianum, the closest smut relative, potentially influenced by repeats of transposable elements. Repetitive elements may have also directed the linkage of the two mating-type loci. The fungal transcriptome profiling from in vitro and from interaction with sugarcane at two time points (early infection and whip emergence) revealed that 13.5% of the genes were differentially expressed in planta and particular to each developmental stage. Among them are plant cell wall degrading enzymes, proteases, lipases, chitin modification and lignin degradation enzymes, sugar transporters and transcriptional factors. The fungus also modulates transcription of genes related to surviving against reactive oxygen species and other toxic metabolites produced by the plant. Previously described effectors in smut/plant interactions were detected but some new candidates are proposed. Ten genomic islands harboring some of the candidate genes unique to S. scitamineum were expressed only in planta. RNAseq data was also used to reassure gene predictions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Low‐pass whole genome sequencing (LP‐WGS) has been applied as alternative method to detect copy number variants (CNVs) in the clinical setting. Compared with chromosomal microarray analysis ...(CMA), the sequencing‐based approach provides a similar resolution of CNV detection at a lower cost. In this study, we assessed the efficiency and reliability of LP‐WGS as a more affordable alternative to CMA. A total of 1363 patients with unexplained neurodevelopmental delay/intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies were enrolled. Those patients were referred from 15 nonprofit organizations and university centers located in different states in Brazil. The analysis of LP‐WGS at 1x coverage (>50kb) revealed a positive testing result in 22% of the cases (304/1363), in which 219 and 85 correspond to pathogenic/likely pathogenic (P/LP) CNVs and variants of uncertain significance (VUS), respectively. The 16% (219/1363) diagnostic yield observed in our cohort is comparable to the 15%–20% reported for CMA in the literature. The use of commercial software, as demonstrated in this study, simplifies the implementation of the test in clinical settings. Particularly for countries like Brazil, where the cost of CMA presents a substantial barrier to most of the population, LP‐WGS emerges as a cost‐effective alternative for investigating copy number changes in cytogenetics.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract Nowadays cancer is one of the most common causes of deaths worldwide. Conventional antitumor agents still present various problems related to specificity for tumor cells often leading to ...therapeutic failure. Nanoscale particles are considered potential alternative to direct access of drugs into tumor cells, therefore increasing the drug accumulation and performance. The aim of this study was to evaluate the antitumor activity of doxorubicin (DOX)-loaded nanostructured lipid carriers (NLC) versus liposomes against a breast cancer animal experimental model. NLC-DOX and liposomes-DOX were successfully prepared and characterized. Tumor-bearing mice were divided into five groups (blank-NLC, blank-liposome, DOX, NLC-DOX, liposome-DOX). Each animal received by the tail vein four doses of antitumoral drugs (total dose, 16 mg/kg), every 3 days. Antitumor efficacy was assessed by measuring 1) tumor volume, calculating the inhibitory ratio (TV-IR, see after) and 2) acquiring scintigraphic images of the tumor using doxorubicin radiolabeled with technetium-99m as an imaging tumor probe. Liposome-DOX and free DOX did not showed differences in the tumor mean volume, whereas NLC-DOX proved to be the best treatments in controlling the tumor growth. NLC-DOX showed an inhibition ration (TV-IR) of 73.5% while free DOX and liposome-DOX decreased TV-RI of 48.8% and 68.0%, respectively. Tumor was clearly visualized in controls, DOX, and liposome-DOX groups. Yet, regarding the NLC-DOX group, tumor was barely identified by the image, indicating antitumor efficacy. Moreover, both NLC and liposomes proved to be able to delay the occurrence of lung metastasis. In conclusion, results of this study indicated that NLC-DOX might be an alternative strategy to achieve an efficient antitumor activity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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