‘TB OR NOT TB?’: A Importância de um Rastreio Adequado

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OFF-LABEL USE OF ANTIBACTERIALS IN A CONTEXT OF ANTIMICROBIAL RESISTANCE THREAT

Objective: The objective of the study was to describe the off-label use of antibacterial in prescriptions for hospitalized adult patients as per the Brazilian drug regulatory agency, namely, the National Health Surveillance Agency (ANVISA). Methods: This is a cross-sectional study with prescriptions for inpatients in a teaching hospital. Data collection and analysis were based on the checklist of the Medicine Prescription, Use and Administration Protocol of the Ministry of Health, where the off-label use is classified as per information of ANVISA’s Electronic Bulletin. Descriptive analyses were performed, and the method of logistic regression was used to evaluate the association between the off-label use of antibacterial and the explanatory variables age, gender, hospitalization clinic, and medical specialty. Results: About one-third of the antibacterial was prescribed for off-label use, and the frequency of administration was the primary use outside standards established in the products’ licenses (87.3%), and dose (7.4%) and the administration route was next. The third-generation cephalosporin was the most consumed class in this regimen (69.5%). In some cases, the off-label use was not supported by scientific evidence. The off-label use was positively associated with the variables gender (odds ratio [OR] = 2.48; confidence interval [CI] = 1.23–4.92) and the prescribing clinic (OR = 4.94; CI = 2.61–8.96). Conclusion: Off-label use is a frequent practice in the studied environment, and in the face of a dramatic scenario of increased antibacterial resistance, it is imperative to adopt measures for the standardization of records and the rational use of this class of drugs

Metabolic modelling of polyhydroxyalkanoate copolymers production by mixed microbial cultures

Background: This paper presents a metabolic model describing the production of polyhydroxyalkanoate (PHA) copolymers in mixed microbial cultures, using mixtures of acetic and propionic acid as carbon source material. Material and energetic balances were established on the basis of previously elucidated metabolic pathways. Equations were derived for the theoretical yields for cell growth and PHA production on mixtures of acetic and propionic acid as functions of the oxidative phosphorylation efficiency, P/O ratio. The oxidative phosphorylation efficiency was estimated from rate measurements, which in turn allowed the estimation of the theoretical yield coefficients. Results: The model was validated with experimental data collected in a sequencing batch reactor (SBR) operated under varying feeding conditions: feeding of acetic and propionic acid separately (control experiments), and the feeding of acetic and propionic acid simultaneously. Two different feast and famine culture enrichment strategies were studied: (i) either with acetate or (ii) with propionate as carbon source material. Metabolic flux analysis (MFA) was performed for the different feeding conditions and culture enrichment strategies. Flux balance analysis (FBA) was used to calculate optimal feeding scenarios for high quality PHA polymers production, where it was found that a suitable polymer would be obtained when acetate is fed in excess and the feeding rate of propionate is limited to ∼0.17 C-mol/ (C-mol.h). The results were compared with published pure culture metabolic studies. Conclusion: Acetate was more conducive toward the enrichment of a microbial culture with higher PHA storage fluxes and yields as compared to propionate. The P/O ratio was not only influenced by the selected microbial culture, but also by the carbon substrate fed to each culture, where higher P/O ratio values were consistently observed for acetate than propionate. MFA studies suggest that when mixtures of acetate and propionate are fed to the cultures, the catabolic activity is primarily guaranteed through acetate uptake, and the characteristic P/O ratio of acetate prevails over that of propionate. This study suggests that the PHA production process by mixed microbial cultures has the potential to be comparable or even more favourable than pure cultures.publishersversionpublishe

Diagonal deformations of thin center vortices and their stability in Yang-Mills theories

The importance of center vortices for the understanding of the confining properties of SU(N) Yang-Mills theories is well established in the lattice. However, in the continuum, there is a problem concerning the relevance of center vortex backgrounds. They display the so called Savvidy-Nielsen-Olesen instability, associated with a gyromagnetic ratio $g^{(b)}_m=2$ for the off-diagonal gluons. In this work, we initially consider the usual definition of a {\it thin} center vortex and rewrite it in terms of a local color frame in SU(N) Yang-Mills theories. Then, we define a thick center vortex as a diagonal deformation of the thin object. Besides the usual thick background profile, this deformation also contains a frame defect coupled with gyromagnetic ratio $g^{(d)}_m=1$, originated from the charged sector. As a consequence, the analysis of stability is modified. In particular, we point out that the defect should stabilize a vortex configuration formed by a pair of straight components separated by an appropriate finite distance.Comment: 20 pages, LaTe

Chronic Lymphocytic Leukemia: Insights from Lymph Nodes & Bone Marrow and Clinical Perspectives

B-cell chronic lymphocytic leukemia (B-CLL) is characterized by highly variable distribution of tumor mass between peripheral blood, bone marrow and lymphoid organs which is important for staging, classification and prognosis. These clinical findings with novel data about importance of B-cell receptor and its stimulation with the support of microenvironment indicate important role of tissues (lymphoid organs and bone marrow) in the pathogenesis of B-CLL. Here is presented the novel approach of simultaneous characterization of B-CLL cells form peripheral blood, bone marrow and lymph nodes by flow cytometry and immunocytochemistry, defining inter- and intraclonal diversity with respect to various molecules. These include adhesion molecules (integrins, immunoglobulins, selectins), chemokine receptors (including CXCR-4), signaling molecules and prognostic factors (CD38 and ZAP-70), proliferation and apoptosis markers (including Ki67, AgNORs with PK index, survivin, bcl-2) and therapeutic targets (CD20 and CD52) and residual hematopoietic stem cells. A number of interesting significant interactions have been discovered, pointing to the important role of neoplastic cell microenvironment. These may in addition to insights in pathogenesis and roles of different microenvironments add to diagnosis, prognosis and treatment of B-CLL patients

Calogero-Sutherland Approach to Defect Blocks

Extended objects such as line or surface operators, interfaces or boundaries play an important role in conformal field theory. Here we propose a systematic approach to the relevant conformal blocks which are argued to coincide with the wave functions of an integrable multi-particle Calogero-Sutherland problem. This generalizes a recent observation in 1602.01858 and makes extensive mathematical results from the modern theory of multi-variable hypergeometric functions available for studies of conformal defects. Applications range from several new relations with scalar four-point blocks to a Euclidean inversion formula for defect correlators.Comment: v2: changes for clarit