445 research outputs found

    Survival of branching random walks in random environment

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    We study survival of nearest-neighbour branching random walks in random environment (BRWRE) on Z{\mathbb Z}. A priori there are three different regimes of survival: global survival, local survival, and strong local survival. We show that local and strong local survival regimes coincide for BRWRE and that they can be characterized with the spectral radius of the first moment matrix of the process. These results are generalizations of the classification of BRWRE in recurrent and transient regimes. Our main result is a characterization of global survival that is given in terms of Lyapunov exponents of an infinite product of i.i.d. 2×22\times 2 random matrices.Comment: 17 pages; to appear in Journal of Theoretical Probabilit

    26S PROTEASOME AND PKA MODULATE MAMMALIAN SPERM CAPACITATION BY CREATING AN INTEGRATED DIALOGUE: A COMPUTATIONAL ANALYSIS

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    Recent experimental evidence suggests the involvement of the 26S proteasome, the main protease active in eukaryotic cells, in the process that leads mammalian sperm to become fully fertile, so-called capacitation. Unfortunately, its role in male gametes signaling is still far from being completely understood. For this reason, here, we realized a computational model as an attempt to rebuild and explore 26S proteasome signaling cascade, aggregating all the molecular data available to date and realizing the Proteasome Interactome Network (PIN). Once obtained the network (i.e., a graph to represent the molecules as nodes and the interactions among them as links), we assessed its topology to infer important biological information. PIN is composed of 157 nodes, 248 links and it is characterized by a scale-free topology, following the Barabasi Albert model. In other words, it possesses a large amount of scarcely linked nodes and a small set of highly linked nodes, the hubs, which act as system controllers. This peculiar topology confers to the network relevant biological features: it is robust against random attacks, easily navigable and controllable and it is possible to infer new information from it. Indeed, the analysis of PIN showed that PKA and 26S proteasome were strongly interconnected and both were active in sperm signaling by influencing the protein phosphorylation pattern and then controlling several key events in sperm capacitation, such as membrane and cytoskeleton remodeling. In conclusion, the network model could explain many biological aspects of sperm physiology that are out of focus looking at the single molecular determinant, overcoming the reductionist approach which did not consider the complexity of molecules and their interactions. This could be helpful to identify potential diagnostic markers and therapeutic strategies concurring in explaining and approaching male infertility

    Effectiveness of surgery for lumbar spinal stenosis

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    Background: The management of spinal stenosis by surgery has increased rapidly in the past two decades, however, there is still controversy regarding the efficacy of surgery for this condition. Our aim was to investigate the efficacy and comparative effectiveness of surgery in the management of patients with lumbar spinal stenosis. Methods: Electronic searches were performed on MEDLINE, EMBASE, AMED, CINAHL, Web of Science, LILACS and Cochrane Library from inception to November 2014. Hand searches were conducted on included articles and relevant reviews. We included randomised controlled trials evaluating surgery compared to no treatment, placebo/sham, or to another surgical technique in patients with lumbar spinal stenosis. Primary outcome measures were pain, disability, recovery and quality of life. The PEDro scale was used for risk of bias assessment. Data were pooled with a random-effects model, and the GRADE approach was used to summarise conclusions. Results: Nineteen published reports (17 trials) were included. No trials were identified comparing surgery to no treatment or placebo/sham. Pooling revealed that decompression plus fusion is not superior to decompression alone for pain (mean difference -3.7, 95% confidence interval -15.6 to 8.1), disability (mean difference 9.8, 95% confidence interval -9.4 to 28.9), or walking ability (risk ratio 0.9, 95% confidence interval 0.4 to 1.9). Interspinous process spacer devices are slightly more effective than decompression plus fusion for disability (mean difference 5.7, 95% confidence interval 1.3 to 10.0), but they resulted in significantly higher reoperation rates when compared to decompression alone (28% v 7%, P < 0.001). There are no differences in the effectiveness between other surgical techniques for our main outcomes. Conclusions: The relative efficacy of various surgical options for treatment of spinal stenosis remains uncertain. Decompression plus fusion is not more effective than decompression alone. Interspinous process spacer devices result in higher reoperation rates than bony decompression

    Nemaline Myopathy in Brazilian Patients: Molecular and Clinical Characterization

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    Nemaline myopathy (NM), a structural congenital myopathy, presents a significant clinical and genetic heterogeneity. Here, we compiled molecular and clinical data of 30 Brazilian patients from 25 unrelated families. Next-generation sequencing was able to genetically classify all patients: sixteen families (64%) with mutation in NEB, five (20%) in ACTA1, two (8%) in KLHL40, and one in TPM2 (4%) and TPM3 (4%). In the NEB-related families, 25 different variants, 11 of them novel, were identified; splice site (10/25) and frame shift (9/25) mutations were the most common. Mutation c.24579 G>C was recurrent in three unrelated patients from the same region, suggesting a common ancestor. Clinically, the “typical” form was the more frequent and caused by mutations in the different NM genes. Phenotypic heterogeneity was observed among patients with mutations in the same gene. Respiratory involvement was very common and often out of proportion with limb weakness. Muscle MRI patterns showed variability within the forms and genes, which was related to the severity of the weakness. Considering the high frequency of NEB mutations and the complexity of this gene, NGS tools should be combined with CNV identification, especially in patients with a likely non-identified second mutation

    Nemaline Myopathy in Brazilian Patients: Molecular and Clinical Characterization

    Get PDF
    Nemaline myopathy (NM), a structural congenital myopathy, presents a significant clinical and genetic heterogeneity. Here, we compiled molecular and clinical data of 30 Brazilian patients from 25 unrelated families. Next-generation sequencing was able to genetically classify all patients: sixteen families (64%) with mutation in NEB, five (20%) in ACTA1, two (8%) in KLHL40, and one in TPM2 (4%) and TPM3 (4%). In the NEB-related families, 25 different variants, 11 of them novel, were identified; splice site (10/25) and frame shift (9/25) mutations were the most common. Mutation c.24579 G>C was recurrent in three unrelated patients from the same region, suggesting a common ancestor. Clinically, the “typical” form was the more frequent and caused by mutations in the different NM genes. Phenotypic heterogeneity was observed among patients with mutations in the same gene. Respiratory involvement was very common and often out of proportion with limb weakness. Muscle MRI patterns showed variability within the forms and genes, which was related to the severity of the weakness. Considering the high frequency of NEB mutations and the complexity of this gene, NGS tools should be combined with CNV identification, especially in patients with a likely non-identified second mutation

    Co-infections and superinfections complicating COVID-19 in cancer patients: A multicentre, international study

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    Background: We aimed to describe the epidemiology, risk factors, and clinical outcomes of co-infections and superinfections in onco-hematological patients with COVID-19. Methods: International, multicentre cohort study of cancer patients with COVID-19. All patients were included in the analysis of co-infections at diagnosis, while only patients admitted at least 48 h were included in the analysis of superinfections. Results: 684 patients were included (384 with solid tumors and 300 with hematological malignancies). Co-infections and superinfections were documented in 7.8% (54/684) and 19.1% (113/590) of patients, respectively. Lower respiratory tract infections were the most frequent infectious complications, most often caused by Streptococcus pneumoniae and Pseudomonas aeruginosa. Only seven patients developed opportunistic infections. Compared to patients without infectious complications, those with infections had worse outcomes, with high rates of acute respiratory distress syndrome, intensive care unit (ICU) admission, and case-fatality rates. Neutropenia, ICU admission and high levels of C-reactive protein (CRP) were independent risk factors for infections. Conclusions: Infectious complications in cancer patients with COVID-19 were lower than expected, affecting mainly neutropenic patients with high levels of CRP and/or ICU admission. The rate of opportunistic infections was unexpectedly low. The use of empiric antimicrobials in cancer patients with COVID-19 needs to be optimized

    Atuação do enfermeiro da atenção básica na assistência ao pré-natal de baixo risco frente a COVID-19: Performance of the primary care nurse in low-risk prenatal care in the face of COVID-19

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    Objetivo-. Este estudo teve por objetivo analisar a assistência ao pré-natal de baixo risco prestada, pelo enfermeiro, na atenção básica durante a pandemia de Sars- CoV-2. Métodos - Foi utilizada a revisão literária do tipo integrativa descritiva, os artigos foram retirados das bases de dados eletrônicas BVS, PubMed e Google acadêmico, com base nos relatos da literatura no período de 2020 a 2022. Resultados- Os fatores de risco e comorbidades como: diabetes mellitus (DM), hipertensão arterial sistêmica (HAS), sobrepeso, doenças respiratórias e cardiovasculares, tornaram a gestante mais suscetível a complicações após a infecção pelo SARS-CoV-2. Com isso, foi necessário readaptar fluxogramas já existentes para realizar as consultas de pré-natal, o teleatendimento e reagendar as consultas quando as gestantes testarem positivo para COVID-19. Os principais desafios do enfermeiro foram: se adaptar aos novos protocolos, conseguir dar continuidade ao pré-natal e gerenciar a escassez de materiais e profissionais. Conclusão- Portanto, fica em evidência a importância do papel do enfermeiro da atenção básica no gerenciamento da unidade e na assistência a gestante com confirmação ou suspeita para o novo Coronavírus, informando a mesma sobre a necessidade de continuar as consultas
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