Construct and discriminant validity of STarT Back Screening Tool – Brazilian version

Background The STarT Back Screening Tool (SBST) was developed to stratify low back pain patients according to their risk of future physical disability so that prognostic subgroups can receive matched treatments in primary care. Objective To measure the construct and discriminative validity of the SBST-Brazil questionnaire. Method A hundred and fifty one patients were recruited to test the construct and discriminative validity comparing the SBST-Brazil to the Brazilian Version of the Oswestry Disability Index (ODI), Roland Morris Disability Questionnaire (RMDQ) and Fear-Avoidance Beliefs Questionnaire-Work (FABQ-W) and Physical Activity (FABQ-PA) subscales at baseline. Spearman's rank-order correlation and area under the curve (AUC) derived from receiver operating curves (ROC) for total scores and psychosocial subscale score of the SBST-Brazil were used for construct and discriminant validity analysis, respectively. Results The SBST-Brazil total and psychosocial subscale scores had good and moderate correlation with ODI (r = 0.61; r = 0.56, respectively) and good with RMDQ (r = 0.70; r = 0.64, respectively). Both scores of the SBST-Brazil total and psychosocial subscale correlated weakly and moderately with the FABQ-PA (r = 0.28; r = 0.34, respectively) and weakly with the FABQ-W (r = 0.18; r = 0.20, respectively). The discriminant validity with AUCs for the total and psychosocial subscale scores against reference standard ranged from 0.66 for kinesiophobia to 0.88 for disability. Conclusion The SBST-Brazil showed a moderate to good correlation with the disability tools, but a weak correlation with fear-avoidance beliefs. The results of discriminant validity suggest that SBST-Brazil is able to discriminate low back pain patients with disability and fear-avoidance beliefs

Patients- and physicians- priorities for improvement: The case of rheumatic diseases

OBJECTIVES: To compare the health priorities elected by patients with rheumatic diseases and by their attending rheumatologists. PATIENTS AND METHODS: We undertook a cross-sectional study among patients and rheumatologists in Portuguese rheumatology outpatient clinics. 75% of all Portuguese Rheumatology Departments agreed to participate. Rheumatologists from non-participating hospital departments were asked to collaborate through their private practices. All patients were eligible for inclusion except if they were under 18 years of age or had a mental disorder that would affect their participation. Data were collected through dedicated questionnaires. Patients were asked to indicate 3 priorities for improvement out of 12 health domains (Arthritis Impact Measurement Scale 2) regarding their rheumatic disease. Rheumatologists were asked similar questions focused around rheumatoid arthritis (RA) and osteoarthritis (OA). RESULTS: 1,868 patients and 56 rheumatologists entered the study. The most commonly selected priorities by patients with rheumatic diseases were: "Rheumatic pain" (70%), "Walking and bending" (45%), and "Hand and Finger Function" (40%). The main priority for improvement among patients with RA was "Rheumatic Pain" (69%), while rheumatologists more commonly elected "Work" (55%) as their main priority for these patients. Among patients with OA, "Rheumatic Pain" was the first priority for both patients and doctors (elected by 75%, and 55% of respondents, respectively). CONCLUSIONS: Our study showed discordance between the priorities for improvement elected by patients and by their respective physicians. This was more pronounced in RA than in OA. Studying and addressing such differences may support physicians and institutions to better achieve the prime goal of incorporating and responding to patients' needs and preferences

Assessment of rotatory laxity in anterior cruciate ligament-deficient knees using magnetic resonance imaging with Porto-knee testing device

Purpose Objective evaluation of both antero-posterior translation and rotatory laxity of the knee remains a target to be accomplished. This is true for both preoperative planning and postoperative assessment of different ACL reconstruction emerging techniques. The ideal measurement tool should be simple, accurate and reproducible, while enabling to assess both ‘‘anatomy’’ and ‘‘function’’ during the same examination. The purpose of this study is to evaluate the clinical effectiveness of a new in-housedeveloped testing device, the so-called Porto-knee testing device (PKTD). The PKTD is aimed to be used on the evaluation of both antero-posterior and rotatory laxity of the knee during MRI exams. Methods Between 2008 and 2010, 33 patients with ACLdeficient knees were enrolled for the purpose of this study. All patients were evaluated in the office and under anesthesia with Lachman test, lateral pivot-shift test and anterior drawer test. All cases were studied preoperatively with KT-1000 and MRI with PKTD, and examinations performed by independent observers blinded for clinical evaluation. During MRI, we have used a PKTD that applies antero-posterior translation and permits free tibial rotation through a standardized pressure (46.7 kPa) in the proximal posterior region of the leg. Measurements were taken for both knees and comparing side-to-side. Five patients with partial ruptures were excluded from the group of 33. Results For the 28 remaining patients, 3 women and 25 men, with mean age of 33.4 ± 9.4 years, 13 left and 15 right knees were tested. No significant correlation was noticed for Lachman test and PKTD results (n.s.). Pivot-shift had a strong positive correlation with the difference in anterior translation registered in lateral and medial tibia plateaus of injured knees (cor. coefficient = 0.80; p\0.05), and with the difference in this parameter as compared to side-to-side (cor. coefficient = 0.83; p\0.05). Considering the KT-1000 difference between injured and healthy knees, a very strong positive correlation was found for side-to-side difference in medial (cor. coeffi- cient = 0.73; p\0.05) and lateral (cor. coefficient = 0.5; p\0.05) tibial plateau displacement using PKTD. Conclusion The PKTD proved to be a reliable tool in assessment of antero-posterior translation (comparing with KT-1000) and rotatory laxity (compared with lateral pivotshift under anesthesia) of the ACL-deficient knee during MRI examinatio

Immune cells and oxidative stress in the endotoxin tolerance mouse model

Sepsis is a systemic inflammatory response that can lead to tissue damage and death. In order to increase our understanding of sepsis, experimental models are needed that produce relevant immune and inflammatory responses during a septic event. We describe a lipopolysaccharide tolerance mouse model to characterize the cellular and molecular alterations of immune cells during sepsis. The model presents a typical lipopolysaccharide tolerance pattern in which tolerance is related to decreased production and secretion of cytokines after a subsequent exposure to a lethal dose of lipopolysaccharide. The initial lipopolysaccharide exposure also altered the expression patterns of cytokines and was followed by an 8- and a 1.5-fold increase in the T helper 1 and 2 cell subpopulations. Behavioral data indicate a decrease in spontaneous activity and an increase in body temperature following exposure to lipopolysaccharide. In contrast, tolerant animals maintained production of reactive oxygen species and nitric oxide when terminally challenged by cecal ligation and puncture (CLP). Survival study after CLP showed protection in tolerant compared to naive animals. Spleen mass increased in tolerant animals followed by increases of B lymphocytes and subpopulation Th1 cells. An increase in the number of stem cells was found in spleen and bone marrow. We also showed that administration of spleen or bone marrow cells from tolerant to naive animals transfers the acquired resistance status. In conclusion, lipopolysaccharide tolerance is a natural reprogramming of the immune system that increases the number of immune cells, particularly T helper 1 cells, and does not reduce oxidative stress.FAPESPCNP

Phytochemicals as antibiotic alternatives to promote growth and enhance host health

There are heightened concerns globally on emerging drug-resistant superbugs and the lack of new antibiotics for treating human and animal diseases. For the agricultural industry, there is an urgent need to develop strategies to replace antibiotics for food-producing animals, especially poultry and livestock. The 2nd International Symposium on Alternatives to Antibiotics was held at the World Organization for Animal Health in Paris, France, December 12-15, 2016 to discuss recent scientific developments on strategic antibiotic-free management plans, to evaluate regional differences in policies regarding the reduction of antibiotics in animal agriculture and to develop antibiotic alternatives to combat the global increase in antibiotic resistance. More than 270 participants from academia, government research institutions, regulatory agencies, and private animal industries from >25 different countries came together to discuss recent research and promising novel technologies that could provide alternatives to antibiotics for use in animal health and production; assess challenges associated with their commercialization; and devise actionable strategies to facilitate the development of alternatives to antibiotic growth promoters (AGPs) without hampering animal production. The 3-day meeting consisted of four scientific sessions including vaccines, microbial products, phytochemicals, immune-related products, and innovative drugs, chemicals and enzymes, followed by the last session on regulation and funding. Each session was followed by an expert panel discussion that included industry representatives and session speakers. The session on phytochemicals included talks describing recent research achievements, with examples of successful agricultural use of various phytochemicals as antibiotic alternatives and their mode of action in major agricultural animals (poultry, swine and ruminants). Scientists from industry and academia and government research institutes shared their experience in developing and applying potential antibiotic-alternative phytochemicals commercially to reduce AGPs and to develop a sustainable animal production system in the absence of antibiotics.Fil: Lillehoj, Hyun. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Liu, Yanhong. University of California; Estados UnidosFil: Calsamiglia, Sergio. Universitat Autònoma de Barcelona; EspañaFil: Fernandez Miyakawa, Mariano Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; ArgentinaFil: Chi, Fang. Amlan International; Estados UnidosFil: Cravens, Ron L.. Amlan International; Estados UnidosFil: Oh, Sungtaek. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Gay, Cyril G.. United States Department of Agriculture. Agricultural Research Service; Argentin

Broadened T-cell Repertoire Diversity in ivIg-treated SLE Patients is Also Related to the Individual Status of Regulatory T-cells

Intravenous IgG (ivIg) is a therapeutic alternative for lupus erythematosus, the mechanism of which remains to be fully understood. Here we investigated whether ivIg affects two established sub-phenotypes of SLE, namely relative oligoclonality of circulating T-cells and reduced activity of CD4 + Foxp3+ regulatory T-cells (Tregs) reflected by lower CD25 surface density.Octapharma research funding; Fundação para a Ciência e a Tecnologia postdoctoral fellowships: (SFRH/BPD/20806/2004, SFRH/BPD/34648/2007); FCT Programa Pessoa travel grant

Molecular Responses of Mussel Mytilus galloprovincialis Associated to Accumulation and Depuration of Marine Biotoxins Okadaic Acid and Dinophysistoxin-1 Revealed by Shotgun Proteomics

The molecular pathways behind the toxicity of diarrheic shellfish toxins (DSTs) in bivalves have been scarcely studied. Thus, a shotgun proteomics approach was applied in this work to understand bivalves’ molecular responses to the dinoflagellate Prorocentrum lima (1.0 × 106 cells/L). Protein expression along with toxins levels were analyzed in the gills and digestive gland of the mussel Mytilus galloprovincialis during and after exposure to this toxic strain. Results revealed an accumulation of OA and DTX1 only in the digestive gland with maximum amounts attained at the end of uptake phase (day 5; 2819.2 ± 522.2 µg OA/kg and 1107.1 ± 267.9 µg DTX1/kg). At the end of the depuration phase (day 20), 16% and 47% of total OA and DTX1 concentrations remained in the digestive gland tissues, respectively. The shotgun proteomic analyses yielded 3051 proteins in both organs. A total of 56 and 54 differentially expressed proteins (DEPs) were revealed in the digestive gland and gills, respectively. Both organs presented the same response dynamics along the experiment, although with tissue-specific features. The early response (3 days uptake) was characterized by a high number of DEPs, being more marked in gills, in relation to the latter time points (5 days uptake and depuration). Functional enrichment analysis revealed the up-regulation of carboxylic (GO:0046943) and organic acid transmembrane transporter activity (GO:0005342) pathways after 3 days uptake for digestive gland. Matching to these pathways are a group of proteins related to transmembrane transport and response to toxic substances and xenobiotics, namely P-glycoprotein (ABCB11), Sodium-dependent proline transporter (SLC6A7), and Sideroflexin-1 (SFXN1). According to Clusters of Orthologous Groups (GOs) categories, most of the DEPs found for digestive gland in all time-points were related with “cellular processes and signaling” and involving signal transduction mechanisms, cytoskeleton and post-translational modification, protein turnover, chaperone functions. In gills, the early uptake phase was marked by a balance between DEPs related with “cellular processes and signaling” and “metabolism.” Depuration is clearly marked by processes related with “metabolism,” mainly involving secondary metabolites biosynthesis, transport, and catabolism. Proteomic data are available via ProteomeXchange with identifier PXD022293.This work was funded by Portuguese Science Foundation (Fundação para a Ciência e a Tecnologia, FCT) and under the Projects MOREBIVALVES (PTDC/ASP-PES/31762/2017) and by the Strategic Funding UIDB/04423/2020 and UIDP/04423/2020 through national funds provided by FCT and European Regional Development Fund (ERDF), in the framework of the program PT2020. This work had also support from the Portuguese Mass Spectrometry Network, integrated in the National Roadmap of Research Infrastructures of Strategic Relevance (ROTEIRO/0028/2013 and LISBOA-01-0145-FEDER-022125)

Yellow fever in Brazil: thoughts and hypotheses on the emergence in previously free areas

This article describes and discusses factors associated to the reemergence of yellow fever and its transmission dynamics in the states of São Paulo (Southeastern Brazil) and Rio Grande do Sul (Southern) during 2008 and 2009. The following factors have played a pivotal role for the reemergence of yellow fever in these areas: large susceptible human population; high prevalence of vectors and primary hosts (non-human primates); favorable climate conditions, especially increased rainfall; emergence of a new genetic lineage; and circulation of people and/or monkeys infected by virus. There is a need for an effective surveillance program to prevent the reemergence of yellow fever in other Brazilian states

Heterogeneity assessment of functional T cell avidity.

The potency of cellular immune responses strongly depends on T cell avidity to antigen. Yet, functional avidity measurements are rarely performed in patients, mainly due to the technical challenges of characterizing heterogeneous T cells. The mean functional T cell avidity can be determined by the IFN-γ Elispot assay, with titrated amounts of peptide. Using this assay, we developed a method revealing the heterogeneity of functional avidity, represented by the steepness/hillslope of the peptide titration curve, documented by proof of principle experiments and mathematical modeling. Our data show that not only natural polyclonal CD8 T cell populations from cancer patients, but also monoclonal T cells differ strongly in their heterogeneity of functional avidity. Interestingly, clones and polyclonal cells displayed comparable ranges of heterogeneity. We conclude that besides the mean functional avidity, it is feasible and useful to determine its heterogeneity (hillslope) for characterizing T cell responses in basic research and patient investigation