Case report: Cyclophosphamide pulse therapy for chronic recalcitrant erythema nodosum leprosum

Chronic recalcitrant erythema nodosum leprosum (ENL) or type 2 reaction (T2R) is a severe condition found in approximately 50% of multibacillary leprosy subjects. T2R is associated with important morbidities and may lead to several disabilities, not only due to nerve damage but also due to the prolonged use of corticosteroids, thalidomide, or immunosuppressors. We describe here four leprosy patients with chronic recalcitrant ENL treated with cyclophosphamide pulse therapy. All subjects had been on prednisone and thalidomide therapy for at least 30 months but showed inflammatory activity when doses were reduced. Pulse therapy with 1.0 g of cyclophosphamide was used every 4–6 weeks for a minimum of three applications. After pulse therapy, all cases presented total or partial regression of symptoms, and we were able to taper thalidomide and prednisone doses, with better control of ENL, avoiding further hospital admissions and disabilities. No side effects were observed during or after infusion therapy. Cyclophosphamide pulse therapy may be useful and safe to control chronic recalcitrant ENL

The Impact of Duration of Organ Dysfunction on the Outcome of Patients with Severe Sepsis and Septic Shock

OBJECTIVES: This study aimed to assess the impact of the duration of organ dysfunction on the outcome of patients with severe sepsis or septic shock. METHODS: Clinical data were collected from hospital charts of patients with severe sepsis and septic shock admitted to a mixed intensive care unit from November 2003 to February 2004. The duration of organ dysfunction prior to diagnosis was correlated with mortality. Results were considered significant if p<0.05. RESULTS: Fifty-six patients were enrolled. Mean age was 55.6 ± 20.7 years, mean APACHE II score was 20.6 ± 6.9, and mean SOFA score was 7.9 ± 3.7. Thirty-six patients (64.3%) had septic shock. The mean duration of organ dysfunction was 1.9 ± 1.9 days. Within the univariate analysis, the variables correlated with hospital mortality were: age (p=0.015), APACHE II (p=0.008), onset outside the intensive care unit (p=0.05), blood glucose control (p=0.05) and duration of organ dysfunction (p=0.0004). In the multivariate analysis, only a duration of organ dysfunction persisting longer than 48 hours correlated with mortality (p=0.004, OR: 8.73 (2.37-32.14)), whereas the APACHE II score remained only a slightly significant factor (p=0.049, OR: 1.11 (1.00-1.23)). Patients who received therapeutic interventions within the first 48 hours after the onset of organ dysfunction exhibited lower mortality (32.1% vs. 82.1%, p=0.0001). CONCLUSIONS: These findings suggest that the diagnosis of organ dysfunction is not being made in a timely manner. The time elapsed between the onset of organ dysfunction and initiation of therapeutic intervention can be quite long, and this represents an important determinant of survival in cases of severe sepsis and septic shock

Magneto-structural versatility of copper(ii)-3-phenylpropionate coordination polymers with N-donor coligands

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)A novel series of copper(II) coordination polymers [Cu-2(O2CC8H9)(4)(pyz)](n) (1), [Cu-2(O2CC8H9)(4)(dps)](n) (2), {[Cu(O2CC8H9)(2)(dps)(H2O)]center dot H2O}(n) (3), {[NaCu(O2CC8H9)(2)(bpm)(NO3)]center dot H2O}(n) (4), and [Cu-4(O2CC8H9)(6)-(OH)(2)(bpp)(2)](n) (5) [O2CC8H9- = 3-phenylpropionate anion, pyz = pyrazine, dps = di(4-pyridyl)sulfide, bpm = 2,2'-bipyrimidine, and bpp = 1,3-bis(4-pyridyl)propane] have been synthesized and magneto-structurally investigated. Compounds 1 and 2 belong to a large group of copper(II) carboxylates where bis-monodentate pyz (1) and dps (2) ligands connect the paddle-wheel [Cu-2(II)(mu-O2CC8H9)(4)] units leading to alternating copper(II) chains. The structure of 3 consists of uniform chains of trans-[Cu-II(O2CC8H9)(2)] units linked by the bis-monodentate dps ligand. Compound 4 consists of heterobimetallic chains where [(Na2Cu2II)-Cu-I(mu-O2CC8H9)(4)(NO3)(2)] units are doubly bridged by bis-bidentate bpm ligands. Compound 5 is also a chain compound whose structure is made up by tetranuclear [Cu-4(II)(mu(3)-OH)(2)(mu-O2CC8H9)(4)(O2CC8H9)(2)] units which are doubly bridged by bis-monodentate bpp ligands. The magnetic properties were investigated in the temperature range 1.8-300 K. Strong antiferromagnetic interactions across the quadruple syn-syn carboxylate are observed in 1 and 2 [J = -378 (1) and -348 cm(-1) (2)] whereas a weak ferromagnetic coupling through the double out-of-plane oxo(carboxylate) bridge occurs in 4 [J = +2.66 cm(-1)], the spin Hamiltonian being defined as H = -JS(1).S-2 with S-1 = S-2 = S-Cu = 1/2. A quasi Curie law is observed for 3 (theta = -0.36 cm(-1)), the bis-monodentate dps ligand being a very poor mediator of magnetic interactions. The analysis of the magnetic properties of 5 is quite complex because of the presence of two crystallographically independent tetracopper(II) units with single-mu-hydroxo, di-mu-hydroxo, mu(3)-hydroxo and single-mu-hydroxo plus double syn, syn carboxylate bridges in each one. The nature and values of the magnetic couplings for 5 obtained by fitting (intermediate, strong and weak antiferromagnetic interactions for the three former exchange pathways respectively, and intermediate ferromagnetic interactions for the latter one) were substantiated by DFT type calculations.A novel series of copper(II) coordination polymers [Cu2(O2CC8H9)4(pyz)]n (1), [Cu2(O2CC8H9)4(dps)]n (2), {[Cu(O2CC8H9)2(dps)(H2O)]·H2O}n (3), {[NaCu(O2CC8H9)2(bpm)(NO3)]·H2O}n (4), and [Cu4(O2CC8H9)6(OH)2(bpp)2]n (5) [O2CC8H9− = 3-phenylpropionate anion,451172189CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAIS - FAPEMIGCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)sem informaçãosem informaçãosem informaçãoThe authors thank the Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq), the Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), FINEP (ref. 134/08

Cross-cultural adaptation of the City Birth Trauma Scale for the Brazilian context

Background: Posttraumatic stress disorder consists of a set of symptoms that occurs in response to one or more traumatic events and can occur in postpartum, from traumatic situations related to the birth or to the baby’s health in the first days of life. It is important tracking the presence of birth trauma, but there is not available instruments in the Brazilian context for this purpose. Objectives: To present the cross-cultural adaptation of City Birth Trauma Scale (BiTS) into Brazilian portuguese. Methods: Cross-cultural adaptation involved independent translations, synthesis,back-translation, and submission to the original author’s appreciation. After the scale was subjected to face validity, followed by a pilot study with postpartum mothers. Results: All steps were performed for the cross-cultural adaptation. Regarding face validity, items evaluated concerning different types of equivalence, presented satisfactory agreement values (≥4.20). Most of the expert’s suggestions were followed, being the main ones related to adjustments in prepositions, pronouns and verbal subjects. Pilot study showed that the mothers had been able to understand and respond to the instrument without adjustments. Discussion: BiTS’s Brazilian version proved to be cross-culturally adapted, ensuring the possibility of intercultural data comparison from the semantic, idiomatic, cultural, and conceptual perspectives. New studies are being conducted to attest its psychometric adequac

Roles of non-coding RNA in sugarcane-microbe interaction

Studies have highlighted the importance of non-coding RNA regulation in plant-microbe interaction. However, the roles of sugarcane microRNAs (miRNAs) in the regulation of disease responses have not been investigated. Firstly, we screened the sRNA transcriptome of sugarcane infected with Acidovorax avenae. Conserved and novel miRNAs were identified. Additionally, small interfering RNAs (siRNAs) were aligned to differentially expressed sequences from the sugarcane transcriptome. Interestingly, many siRNAs aligned to a transcript encoding a coppertransporter gene whose expression was induced in the presence of A. avenae, while the siRNAs were repressed in the presence of A. avenae. Moreover, a long intergenic non-coding RNA was identified as a potential target or decoy of miR408. To extend the bioinformatics analysis, we carried out independent inoculations and the expression patterns of six miRNAs were validated by quantitative reverse transcription-PCR (qRT-PCR). Among these miRNAs, miR408—a copper- microRNA—was downregulated. The cleavage of a putative miR408 target, a laccase, was confirmed by a modified 50RACE (rapid amplification of cDNA ends) assay. MiR408 was also downregulated in samples infected with other pathogens, but it was upregulated in the presence of a beneficial diazotrophic bacteria. Our results suggest that regulation by miR408 is important in sugarcane sensing whether microorganisms are either pathogenic or beneficial, triggering specific miRNA-mediated regulatory mechanisms accordingly

Fetal-Derived MyD88 Signaling Contributes to Poor Pregnancy Outcomes During Gestational Malaria

Placental malaria (PM) remains a severe public health problem in areas of high malaria transmission. Despite the efforts to prevent infection poor outcomes in Plasmodium endemic areas, there is still a considerable number of preterm births and newborns with low birth weight resulting from PM. Although local inflammation triggered in response to malaria is considered crucial in inducing placental damage, little is known about the differential influence of maternal and fetal immune responses to the disease progression. Therefore, using a PM mouse model, we sought to determine the contribution of maternal and fetal innate immune responses to PM development. For this, we conducted a series of cross-breeding experiments between mice that had differential expression of the MyD88 adaptor protein to obtain mother and correspondent fetuses with distinct genetic backgrounds. By evaluating fetal weight and placental vascular spaces, we have shown that the expression of MyD88 in fetal tissue has a significant impact on PM outcomes. Our results highlighted the existence of a distinct contribution of maternal and fetal immune responses to PM onset. Thus, contributing to the understanding of how inflammatory processes lead to the dysregulation of placental homeostasis ultimately impairing fetal development

The influence of behavioral enrichment on dry food consumption by the black tufted-ear marmoset, Callithrix penicillata (Mammalia: Callithricidae): a pilot study

Stereotyped behaviors in captive primates are often caused by unsuitable conditions. Environmental enrichment has been used to reduce these behaviors, and also to increase the frequency of behaviors appropriate to the species. In this pilot study we evaluated whether behavioral enrichment influences food intake by the black tufted-ear marmoset, Callithrix penicillata (É. Geoffroy Saint-Hilaire, 1812), by calculating energy maintenance requirements. We evaluated 16 individually housed, healthy adult black tufted-ear marmosets, randomly divided into two treatment groups, one with behavioral enrichment and one without. The enrichment techniques included structural aspects, such as placing fixed and mobile objects in the cage and supplying dry foods in an enriched form, in order to stimulate cognition. Based on the metabolic weight of the animals, we calculated the energy requirements for their maintenance. The animals that received behavioral enrichment consumed more food than those that did not. We also observed that the animals that did not receive enrichment consumed 9.85% less food than had been calculated for energy maintenance requirements, while the animals that received enrichment consumed 24.97% more food than had been calculated. Results indicate that the use of behavioral enrichment items raised the energy requirements of the black tufted-ear marmoset and, therefore, the consumption of dry food, suggesting that environmental enrichment plays a role in stimulating food consumption. This conclusion should alert scientists, technicians and primatologists to the importance of controlling body weight of marmosets when introducing environmental enrichment to avoid overfeeding and obesity. To verify this conclusion, a study is needed with a longer time frame and more parameters, such as behavior observation and body weight

Decreased expression of ADAMTS-1 in human breast tumors stimulates migration and invasion

Abstract\ud \ud \ud \ud Background\ud \ud ADAMTS-1 (a disintegrin and metalloprotease with thrombospondin motifs) is a member of the ADAMTS family of metalloproteases. Here, we investigated mRNA and protein levels of ADAMTS-1 in normal and neoplastic tissues using qPCR, immunohistochemistry and immunoblot analyses, and we addressed the role of ADAMTS-1 in regulating migration, invasion and invadopodia formation in breast tumor cell lines.\ud \ud \ud \ud Results\ud \ud In a series of primary breast tumors, we observed variable levels of ADAMTS-1 mRNA expression but lower levels of ADAMTS-1 protein expression in human breast cancers as compared to normal tissue, with a striking decrease observed in high-malignancy cases (triple-negative for estrogen, progesterone and Her-2). This result prompted us to analyze the effect of ADAMTS-1 knockdown in breast cancer cells in vitro. MDA-MB-231 cells with depleted ADAMTS-1 expression demonstrated increased migration, invasion and invadopodia formation. The regulatory mechanisms underlying the effects of ADAMTS-1 may be related to VEGF, a growth factor involved in migration and invasion. MDA-MB-231 cells with depleted ADAMTS-1 showed increased VEGF concentrations in conditioned medium capable of inducing human endothelial cells (HUVEC) tubulogenesis. Furthermore, expression of the VEGF receptor (VEGFR2) was increased in MDA-MB-231 cells as compared to MCF7 cells. To further determine the relationship between ADAMTS-1 and VEGF regulating breast cancer cells, MDA-MB-231 cells with reduced expression of ADAMTS-1 were pretreated with a function-blocking antibody against VEGF and then tested in migration and invasion assays; both were partially rescued to control levels.\ud \ud \ud \ud Conclusions\ud \ud ADAMTS-1 expression was decreased in human breast tumors, and ADAMTS-1 knockdown stimulated migration, invasion and invadopodia formation in breast cancer cells in vitro. Therefore, this series of experiments suggests that VEGF is involved in the effects mediated by ADAMTS-1 in breast cancer cells.This investigation was supported by The State of São Paulo Research Foundation (FAPESP grants 2006/54963-0, 2006/01026-0, 2008/57103-8, 2010/07699-1), and Brazilian National Council for Scientific and Technological Development (CNPq grant 470779/2007-1). The authors also want to thank Dr. Stanley Zucker (Stony Brook University; Stony Brook, NY, USA) and Dr. Rama Khokha (University of Western Ontario, Toronto, Canada) for suggestions made on data analysis

Social distancing measures to control the COVID-19 pandemic: potential impacts and challenges in Brazil.

The COVID-19 pandemic has challenged researchers and policy makers to identify public safety measures forpreventing the collapse of healthcare systems and reducingdeaths. This narrative review summarizes the available evidence on the impact of social distancing measures on the epidemic and discusses the implementation of these measures in Brazil. Articles on the effect of social distancing on COVID-19 were selected from the PubMed, medRXiv and bioRvix databases. Federal and state legislation was analyzed to summarize the strategies implemented in Brazil. Social distancing measures adopted by the population appear effective, particularly when implemented in conjunction with the isolation of cases and quarantining of contacts. Therefore, social distancing measures, and social protection policies to guarantee the sustainability of these measures, should be implemented. To control COVID-19 in Brazil, it is also crucial that epidemiological monitoring is strengthened at all three levels of the Brazilian National Health System (SUS). This includes evaluating and usingsupplementary indicators to monitor the progression of the pandemic and the effect of the control measures, increasing testing capacity, and making disaggregated notificationsand testing resultstransparentand broadly available