Identification of clinical predictors of flare in systemic lupus erythematosus patients: a 24-month prospective cohort study

Objective. SLE has a relapsing-remitting course with disease activity flares over time. This study aims to identify clinical predictors of SLE flares.Methods. This prospective cohort study over 24 months included all SLE patients on follow-up at one academic lupus clinic. Flare was defined as an increase in SLEDAI-2K score ≥4 points. Baseline clinical and demographic parameters were compared using survival analysis for time-to-flare outcome with univariate log-rank tests. Variables with significant differences were further evaluated as predictors with multivariate Cox regression models adjusting for potential confounding or contributing factors and hazard ratio (HR) calculation.Results. A total of 202 SLE patients were included. Over the follow-up period, 1083 visits were documented and 16.8% of patients presented with flares. In multivariate analysis, the following parameters emerged as flare predictors: SLE diagnosis up to 25 years of age (HR = 2.14, P = 0.03), lupus nephritis previous to baseline visit (HR = 4.78, P < 0.0001) and immunosuppressor treatment for severe SLE (HR = 3.22, P < 0.001). Baseline disease activity, disease duration and treatment with prednisone or HCQ were not predictive factors.Conclusion. Patients with an SLE diagnosis before age 25 years, lupus nephritis or immunosuppressor treatment for severe SLE present greater HRs for flares, suggesting the need for tighter clinical monitoring. Current immunosuppressive strategies seem to be inefficient in providing flare prevention

Microbial community dynamics in diesel waste biodegradation using sequencing batch bioreactor operation mode (SBR)

The dynamic of molecular microbial community during diesel waste biodegradation was investigated. The waste was treated in bioreactors operated in sequencing batch operation mode (SBR) in four cycles of 72 h, using optimized setpoints (pH, initial waste load, C:N ratio, aeration). Optimal conditions allowed the system to reach biodegradation of 53.3, 96.0, 76.2 and 75.0% at the end of cycles one, two three and four, respectively. Oxygen uptake rate (OUR) indicated increases in microbial activity from cycle one to cycle two (124.9 to 252.9 mgO2/L/h) and decreases in cycles three and four (120.4 to 108.8 mgO2/L/h, respectively). Investigations of microbial diversity showed changes in the microbial community members at the end of the cycle one. Significant reductions in the relative ecotoxicity were observed beginning with cycle two, and the reductions extended until the end of process. The SBR operation mode proved to be an efficient method for treating the diesel waste, and the process allowed for relevant reductions in the hydrocarbon content of the waste along with an increase in its environmental quality. Changes in the microbial members are evidence of the synergistic action of the microbiota in the process.Key words: Microbial diversity, denaturing gradient gel electrophoresis, sequencing batch, biodegradation

Microtubule detyrosination guides chromosomes during mitosis

Before chromosomes segregate into daughter cells, they align at the mitotic spindle equator, a process known as chromosome congression. Centromere-associated protein E (CENP-E)/Kinesin-7 is a microtubule plus-end-directed kinetochore motor required for congression of pole-proximal chromosomes. Because the plus-ends of many astral microtubules in the spindle point to the cell cortex, it remains unknown how CENP-E guides pole-proximal chromosomes specifically toward the equator. We found that congression of pole-proximal chromosomes depended on specific posttranslational detyrosination of spindle microtubules that point to the equator. In vitro reconstitution experiments demonstrated that CENP-E-dependent transport was strongly enhanced on detyrosinated microtubules. Blocking tubulin tyrosination in cells caused ubiquitous detyrosination of spindle microtubules, and CENP-E transported chromosomes away from spindle poles in random directions. Thus, CENP-E-driven chromosome congression is guided by microtubule detyrosination.We thank F. I. Ataullakhanov for help with the laser trap and data analysis; A. Kiyatkin, V. Mustyatsa, M. Molodtsov, A. Gautreau, G. Lakisic, and M. Barisic for technical assistance; and members of our laboratories for stimulating discussions. This work was supported by National Institutes of Health grant R01-GM098389 and RSG-14-018-01-CCG from the American Cancer Society to E.L.G.; by the Institut Curie, the Centre National de la Recherche Scientifique, the Institut National de la Sante et de la Recherche Medicale, the L'Agence Nationale de la Recherche (ANR) award ANR-12-BSV2-0007, INCA_6517, ANR-10-LBX-0038, part of the IDEX Idex PSL, ANR-10-IDEX-0001-02 PSL to C.J.; and Fundacao Luso-Americana para o Desenvolvimento (FLAD) Life Science 2020 and PRECISE grant from the European Research Council to H.M. A.V.Z. is supported by the RAS Presidium Grants "Mechanisms of the Molecular Systems Integration," " Molecular and Cell Biology programs," and Russian Fund for Basic Research Grant 12-04-00111-a and 13-00-40188. R.S.S. is supported by a fellowship from the Programa Graduado em Areas da Biologia Basica e Aplicada (GABBA) PhD program from the University of Porto. A.L.P. is supported by fellowship SFRH/BPD/66707/2009 from Fundacao para a Ciencia e a Tecnologia of Portugal. M.B., R.S.S., S.K.T., M.M.M., C.J., E.L.G., and H.M. designed the experiments; M.B. performed all experiments in cells; M. M. M. established and performed the tubulin purification protocol from HeLa cells; R.S.S. performed single-molecule experiments; S.K.T. performed force measurements; A.L.P. provided reagents; all authors analyzed data; H.M., E.L.G., and M.B. wrote the paper, with contributions from all authors; H.M. conceived and coordinated the project. Data described can be found in the main figures and supplementary materials. The authors declare no conflict of interests

APOE polymorphism is associated with lipid profile, but not with arterial stiffness in the general population

<p>Abstract</p> <p>Background</p> <p>Cardiovascular diseases (CVD) are the main cause of death and disability in developed countries. In most cases, the progress of CVD is influenced by environmental factors and multifactorial inheritance. The purpose of this study was to investigate the association between <it>APOE </it>genotypes, cardiovascular risk factors, and a non-invasive measure of arterial stiffness in the Brazilian population.</p> <p>Methods</p> <p>A total of 1493 urban Brazilian individuals were randomly selected from the general population of the Vitoria City Metropolitan area. Genetic analysis of the <it>APOE </it>polymorphism was conducted by PCR-RFLP and pulse wave velocity analyzed with a noninvasive automatic device.</p> <p>Results</p> <p>Age, gender, body mass index, triglycerides, creatinine, uric acid, blood glucose, blood pressure phenotypes were no different between ε2, ε3 and ε4 alleles. The ε4 allele was associated with higher total-cholesterol (p < 0.001), LDL-C (p < 0.001), total-cholesterol/HDL-C ratio (p < 0.001), LDL/HDL-C ratio (p < 0.001), lower HDL-C values (p < 0.001) and higher risk to obesity (OR = 1.358, 95% CI = 1.019-1.811) and hyperuricemia (OR = 1.748, 95% CI = 1.170-2.611). Nevertheless, pulse wave velocity (p = 0.66) measures were no different between genotypes. The significant association between APOE genotypes and lipid levels persisted after a 5-year follow-up interval, but no interaction between time and genotype was observed for lipids longitudinal behavior.</p> <p>Conclusion</p> <p>The ε4 allele of the <it>APOE </it>gene is associated with a worse lipid profile in the Brazilian urban population. In our relatively young sample, the observed effect of <it>APOE </it>genotype on lipid levels was not translated into significant effects in arterial wall stiffness.</p

Assessment of the effect of phenytoin on cutaneous healing from excision of melanocytic nevi on the face and on the back

<p>Abstract</p> <p>Background</p> <p>Topical phenytoin is a powerful skin wounds healing and it may be useful in clinical practice. The purpose of this study was to evaluate the effect of topical phenytoin 0.5%, by comparing it with cream (control) in wounds resulting from excision of two melanocytic nevi in the same patient. Our purpose was also to assess if phenytoin had better therapeutic and cosmetic outcomes when compared with cream (control).</p> <p>Methods</p> <p>This study evaluated 100 patients with skin wounds from excision of melanocytic nevi. 50 patients with lesions on the face and 50 patients with lesions on the back, totalizing 200 lesions excised with modified punch. The resulting superficial skin wounds had the same diameter and depth, and second intention healing followed.</p> <p>Patients were followed for 60 days. Student's t-test, Mann Whitney nonparametric test, analysis of variance, LSD test, Shapiro-Wilks test and Fisher test were used to analyze the results, depending on the nature of the variables being studied.</p> <p>Results</p> <p>Phenytoin showed better therapeutic and cosmetic results, by healing faster, with more intense epithelization in wounds in comparison with cream (control). Phenytoin showed a statistically significant difference regarding the following parameters (p < 0.05): wounded area and healing time. Phenytoin application resulted in a smaller area and a shorter healing time. Also the intensity of exudates, bleeding, and the epithelization were more intense in phenytoin-treated wounds. Regarding the shape and thickness of the scar, injuries treated with phenytoin had round and flat shaped scars in most of the cases. Considering patient's gender and phototype, female patients presented smaller wounds and scar areas; and phototype I had the largest scar areas. Contact eczema was an adverse reaction in 7 injuries located on the back caused by cream (control) and hypoallergenic tape.</p> <p>Conclusions</p> <p>Phenytoin showed better therapeutic and cosmetic results compared with cream (control). Phenytoin is a low cost drug, which accelerates skin wounds healing in human patients. Trial registration: ISRCTN96539803</p

Zika virus impairs the development of blood vessels in a mouse model of congenital infection

Zika virus (ZIKV) is associated with brain development abnormalities such as primary microcephaly, a severe reduction in brain growth. Here we demonstrated in vivo the impact of congenital ZIKV infection in blood vessel development, a crucial step in organogenesis. ZIKV was injected intravenously in the pregnant type 2 interferon (IFN)-deficient mouse at embryonic day (E) 12.5. The embryos were collected at E15.5 and postnatal day (P)2. Immunohistochemistry for cortical progenitors and neuronal markers at E15.5 showed the reduction of both populations as a result of ZIKV infection. Using confocal 3D imaging, we found that ZIKV infected brain sections displayed a reduction in the vasculature density and vessel branching compared to mocks at E15.5; altogether, cortical vessels presented a comparatively immature pattern in the infected tissue. These impaired vascular patterns were also apparent in the placenta and retina. Moreover, proteomic analysis has shown that angiogenesis proteins are deregulated in the infected brains compared to controls. At P2, the cortical size and brain weight were reduced in comparison to mock-infected animals. In sum, our results indicate that ZIKV impairs angiogenesis in addition to neurogenesis during development. The vasculature defects represent a limitation for general brain growth but also could regulate neurogenesis directly

Asymmetrical hippocampal connectivity in mesial temporal lobe epilepsy: evidence from resting state fMRI

<p>Abstract</p> <p>Background</p> <p>Mesial temporal lobe epilepsy (MTLE), the most common type of focal epilepsy in adults, is often caused by hippocampal sclerosis (HS). Patients with HS usually present memory dysfunction, which is material-specific according to the hemisphere involved and has been correlated to the degree of HS as measured by postoperative histopathology as well as by the degree of hippocampal atrophy on magnetic resonance imaging (MRI). Verbal memory is mostly affected by left-sided HS, whereas visuo-spatial memory is more affected by right HS. Some of these impairments may be related to abnormalities of the network in which individual hippocampus takes part. Functional connectivity can play an important role to understand how the hippocampi interact with other brain areas. It can be estimated via functional Magnetic Resonance Imaging (fMRI) resting state experiments by evaluating patterns of functional networks. In this study, we investigated the functional connectivity patterns of 9 control subjects, 9 patients with right MTLE and 9 patients with left MTLE.</p> <p>Results</p> <p>We detected differences in functional connectivity within and between hippocampi in patients with unilateral MTLE associated with ipsilateral HS by resting state fMRI. Functional connectivity resulted to be more impaired ipsilateral to the seizure focus in both patient groups when compared to control subjects. This effect was even more pronounced for the left MTLE group.</p> <p>Conclusions</p> <p>The findings presented here suggest that left HS causes more reduction of functional connectivity than right HS in subjects with left hemisphere dominance for language.</p

Psychological morbidity as a moderator of intention to quit smoking : a study of smokers and former smokers

Objective: To analyze psychological morbidity as a moderator of the relationship between smoking representations and quality of life in smokers and former smokers, as well as to determine which psychological variables discriminate between smokers with and without the intention to quit smoking. Methods: This was a quantitative, correlational cross-sectional study involving a convenience sample of 224 smokers and 169 former smokers. Results: In smokers and former smokers, psychological morbidity had a moderating effect on the relationship between mental/physical quality of life and smoking representations (cognitive representations, emotional representations, and comprehensibility). Smokers with the intention to quit smoking more often presented with low comprehensibility, threatening emotional representations, behavioral beliefs, and perceived behavioral control, as well as with normative/control beliefs, than did those without the intention to quit. Conclusions: The results of this study underscore the importance of the moderating effect exerted by psychological morbidity, as well as that of sociocognitive variables, among smokers who have the intention to quit smoking.ResumoObjetivo: Analisar a morbidade psicológica como um moderador na relação entre as representações do tabaco e a qualidade de vida em fumantes e ex-fumantes, assim como conhecer as variáveis psicológicas que discriminam os fumantes com e sem intenção para deixar de fumar. Métodos: Estudo quantitativo, correlacional e transversal com uma amostra de conveniência constituída por 224 fumantes e 169 ex-fumantes. Resultados: Verificou-se um efeito moderador da morbidade psicológica na relação entre a qualidade de vida (física e mental) e as representações do tabaco (representações cognitivas e emocionais e compreensão) nos fumantes e nos ex-fumantes. Os fumantes com intenção para deixar de fumar apresentavam menor compreensão, representações emocionais mais ameaçadoras, mais crenças de comportamento, maior controle comportamental percebido e mais crenças normativas/controle do que aqueles sem essa intenção. Conclusões: Os resultados deste estudo enfatizam a importância da morbidade psicológica como moderadora, bem como das variáveis sociocognitivas, junto dos fumantes que querem deixar de fumar