A first report on the efficacy of a single intra-articular administration of blood cell secretome, triamcinolone acetonide, and the combination of both in dogs with osteoarthritis

Research Areas: Veterinary SciencesBackground: Osteoarthritis represents a signifcant welfare problem for many dogs, with limited therapeutic options other than palliative pain control. To evaluate the efect of the intra-articular administration of blood cell secretome and triamcinolone, 15 dogs with bilateral hip osteoarthritis were randomly assigned to a blood cell secretome (BCSG, n=5), triamcinolone (TG) or their combination group (BCS+TG, n=5). BCSG received a single intra-articular administration of 3 ml of blood cell secretome, TG 0.5 ml of triamcinolone acetonide 40 mg/ml, and BCS+TG received the combined products. The volume to administrate was corrected to 3.5 ml with saline. On days 0, 8, 15, 30, 60, 90, 120, 150, and 180, a copy of the Canine Brief Pain Inventory (divided into pain interference score—PIS and Pain Severity Score—PSS), Liverpool Osteoarthritis in Dogs (LOAD), Hudson Visual Analogue Scale (HVAS), and Canine Orthopedic Index (COI, divided into function, gait, stifness, and quality of life) was completed. Results were analyzed with the Kruskal–Wallis test and the Kaplan–Meier estimators were conducted and compared with the Log Rank test, p<0.05. Results: Animals in the sample had a mean age of 9.0±2.9 years and a bodyweight of 28.8±4.1 kg. Hips were classifed as moderate (8) and severe (7) osteoarthritis. No diferences were found between groups at T0 regarding considered evaluations. Signifcant diferences were observed between groups in pain scores from+8d-+150d, with BCS+TG exhibiting better results. The same was observed for HVAS and LOAD, from+8d-+120d. Improvements were also observed in several dimensions of the COI. Kaplan–Meier estimators showed that BCS+TG produced longer periods with better results, followed by BCSG and TG. Conclusion: The intra-articular administration of blood cell secretome improved the clinical signs and scores of several clinical metrology instruments in dogs with hip OA, particularly when combined with triamcinolone. Further studies are required.info:eu-repo/semantics/publishedVersio

Characterization of weight-bearing compensation in dogs with bilateral hip osteoarthritis

Área de pesquisa: Veterinary SciencesTo describe the weight-bearing compensation in working dogs with bilateral hip osteoarthritis (OA), 50 police working dogs were evaluated with a weight distribution platform at the initial evaluation and after intra-articular treatment (a negative control 0.9% sodium chloride (NaCl), a platelet concentrate, Hylan G-F 20, triamcinolone hexacetonide or stanozolol). Six evaluation sessions were performed, over a 180-day period. Results were compared by breed, age, sex, weight and Orthopedic Foundation for Animals hip grade scores with the Independent Samples T-Test, repeated samples Analysis of variance and Pearson correlation coefficient, P < .05. Animals had a mean age of 6.5 § 2.4 years and a bodyweight of 26.7 § 5.2kg. No significant differences were observed when comparing weight-bearing for different breeds, sex, hip grades or weight during the initial evaluation. Significant differences were observed in deviation (P < .01) and symmetry index (P < .01) between the control and treatment groups during the follow-up period. A weight shift from pelvic to thoracic limbs was observed, with a weak, although a significant, correlation between a pelvic limb and the opposing contralateral thoracic limb. Labrador Retrievers showed higher symmetry index and deviation from normal values during the follow-up period than German Shepherd Dogs and Dutch Shepherd Dogs. Male dogs also showed higher symmetry index and deviation compared with females. At this period, the symmetry index showed a weak, although significant, correlation with body weight. Weight-bearing of all limbs correlated with the remaining limbs, reflecting a more balanced weight distribution than the initial evaluation. The weight distribution platform can be used to evaluate patients, at the initial presentation and during the assessment of response to treatment.info:eu-repo/semantics/publishedVersio

Screening for Autism Spectrum Disorders-Validation of the Portuguese Version of the Social Communication Questionnaire

There are no assessment and screening tools for Autism Spectrum Disorders (ASD) validated for the Portuguese population. The Social Communication Questionnaire (SCQ) is an useful screening tool of ASD diagnosis. The main objectives of our study were to produce a Portuguese version of the SCQ (SCQ-PF), study its internal consistency, sensitivity and specificity in order to evaluate its validity as a screening instrument for ASD. We also wanted to study the impact of intellectual disability and verbal impairment and other mental disorders on SCQ-PF psychometric properties. The study included 211 children and adolescents, aged 4-17, divided in three groups: ASD Group (n = 96), Other Mental Disorders Group (OMD) (n = 63) and No Mental Disorders (NMD) Group (n = 52). Parents or other primary caregiver provided information on the SCQ items. The SCQ-PF score was significantly higher in the ASD group than in the other groups (p < 0.001). As to internal consistency, Cronbach's alpha was 87%. ASD subjects were distinguished from subjects without ASD (OMD and NMD Groups) and the area under the curve (AUC) was 0.897 (95% Confidence Interval: 0.852-0.943), for a cutoff of 14, which yielded the highest AUC, with values of sensitivity and specificity 0.76 and 0.93, respectively. These findings show that SCQ- PF with a cutoff of 14 is an acceptable and useful screening tool for ASD in the Portuguese population

Coherent imager module with a large field of view for synthetic aperture interferometry applications

Optical areal profilometry of large precision-engineered surfaces require high-resolution measurements over large fields of view. Synthetic Aperture Interferometry (SAI) offers an alternative to the conventional approach of stitching small fields of view (FOV) obtained with Coherent Scanning Interferometry (CSI) using high-NA objectives. In SAI, lowresolution digital holograms are recorded for different illumination and observation directions and they are added coherently to produce a high-resolution reconstruction over a large FOV. This paper describes the design, fabrication and characterization of a large FOV, compact and low-cost coherent imager (CI) as a building block of a coherent sensor array for a SAI system. The CI consists of a CMOS photodetector array with 1.12 µm pixel pitch, a square entrance pupil and a highly divergent reference beam that emerges from a pinhole milled with a focused ion beam on the cylindrical cladding at the tip of an optical fibre. In order to accurately reconstruct the digital holograms, the wavefront of the reference beam is estimated by localizing the reference source relative to the photodetector array. This is done using an optimization approach that simultaneously reconstructs plane waves that reach the aperture from 121 different illumination directions and guarantees a phase root-mean-squared (RMS) error of less than a fifth of the wavelength across the CI entrance pupil at a boundary of the FOV. The CI performance is demonstrated with a holographic reconstruction of a 0.110 m wide object placed at a distance of 0.085 m, i.e. a FOV = ±0.57 rad, the highest reported to date with a holographic camera.</div

Linear Mode Stability of the Kerr-Newman Black Hole and Its Quasinormal Modes

We provide strong evidence that, up to 99.999% of extremality, Kerr-Newman black holes (KNBHs) are linear mode stable within Einstein-Maxwell theory. We derive and solve, numerically, a coupled system of two partial differential equations for two gauge invariant fields that describe the most general linear perturbations of a KNBH. We determine the quasinormal mode (QNM) spectrum of the KNBH as a function of its three parameters and find no unstable modes. In addition, we find that the lowest radial overtone QNMs that are connected continuously to the gravitational ℓ=m=2 Schwarzschild QNM dominate the spectrum for all values of the parameter space (m is the azimuthal number of the wave function and ℓ measures the number of nodes along the polar direction). Furthermore, the (lowest radial overtone) QNMs with ℓ=m approach Reω=mΩH(ext) and Imω=0 at extremality; this is a universal property for any field of arbitrary spin |s|≤2 propagating on a KNBH background (ω is the wave frequency and ΩH(ext) the black hole angular velocity at extremality). We compare our results with available perturbative results in the small charge or small rotation regimes and find good agreement.Some of the computations were performed at the cluster ‘BaltasarSete-Sóis’ and supported by the ERC Starting Grant No. DyBHo-256667. O. J. C. D. acknowledges the kind hospitality of the Yukawa Institute for Theoretical Physics, where part of this work has been done during the workshop “Holographic vistas on Gravity and Strings,” YITP-T-14-1. O. J. C. D. is supported by the STFC Ernest Rutherford Grants No. ST/K005391/1 and No. ST/M004147/1. M. G. is supported by King’s College, Cambridge. The research leading to these results has received funding from the European Research Council under the European Community’s Seventh Framework Programme (No. FP7/ 2007-2013)/ERC Grant Agreement No. [247252]

Strong cosmic censorship for charged de Sitter black holes with a charged scalar field

It has been shown recently that the strong cosmic censorship conjecture is violated by near-extremal Reissner–Nordström–de Sitter black holes. We investigate whether the introduction of a charged scalar field can rescue strong cosmic censorship. We find that such a field improves the situation but there is always a neighbourhood of extremality in which strong cosmic censorship is violated by perturbations arising from smooth initial data.OJCD is supported by the STFC Ernest Rutherford Grants No. ST/K005391/1 and No. ST/M004147/1, and by the STFC "Particle Physics Grants Panel (PPGP) 2016" Grant No. ST/P000711/1. HSR and JES were supported in part by STFC Grants No. PHY-1504541 and ST/P000681/1

Does native Trypanosoma cruzi calreticulin mediate growth inhibition of a mammary tumor during infection?

Indexación: Web of Science.Background: For several decades now an antagonism between Trypanosoma cruzi infection and tumor development has been detected. The molecular basis of this phenomenon remained basically unknown until our proposal that T. cruzi Calreticulin (TcCRT), an endoplasmic reticulum-resident chaperone, translocated-externalized by the parasite, may mediate at least an important part of this effect. Thus, recombinant TcCRT (rTcCRT) has important in vivo antiangiogenic and antitumor activities. However, the relevant question whether the in vivo antitumor effect of T. cruzi infection is indeed mediated by the native chaperone (nTcCRT), remains open. Herein, by using specific modified anti-rTcCRT antibodies (Abs), we have neutralized the antitumor activity of T. cruzi infection and extracts thereof, thus identifying nTcCRT as a valid mediator of this effect. Methods: Polyclonal anti-rTcCRT F(ab')(2) Ab fragments were used to reverse the capacity of rTcCRT to inhibit EAhy926 endothelial cell (EC) proliferation, as detected by BrdU uptake. Using these F(ab')(2) fragments, we also challenged the capacity of nTcCRT, during T. cruzi infection, to inhibit the growth of an aggressive mammary adenocarcinoma cell line (TA3-MTXR) in mice. Moreover, we determined the capacity of anti-rTcCRT Abs to reverse the antitumor effect of an epimastigote extract (EE). Finally, the effects of these treatments on tumor histology were evaluated. Results: The rTcCRT capacity to inhibit ECs proliferation was reversed by anti-rTcCRT F(ab')(2) Ab fragments, thus defining them as valid probes to interfere in vivo with this important TcCRT function. Consequently, during infection, these Ab fragments also reversed the in vivo experimental mammary tumor growth. Moreover, anti-rTcCRT Abs also neutralized the antitumor effect of an EE, again identifying the chaperone protein as an important mediator of this anti mammary tumor effect. Finally, as determined by conventional histological parameters, in infected animals and in those treated with EE, less invasive tumors were observed while, as expected, treatment with F(ab')(2) Ab fragments increased malignancy. Conclusion: We have identified translocated/externalized nTcCRT as responsible for at least an important part of the anti mammary tumor effect of the chaperone observed during experimental infections with T. cruzi.http://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2764-

Micro-costing analysis of guideline-based treatment by direct-acting agents: the real-life case of hepatitis C management in Brazil

Background Eradication of hepatitis C virus (HCV) using direct-acting agents (DAA) has been associated with a financial burden to health authorities worldwide. We aimed to evaluate the guideline-based treatment costs by DAAs from the perspective of the Brazilian Ministry of Health (BMoH). Methods The activity based costing method was used to estimate the cost for monitoring/treatment of genotype-1 (GT1) HCV patients by the following strategies: peg-interferon (PEG-IFN)/ribavirin (RBV) for 48 weeks, PEG-IFN/RBV plus boceprevir (BOC) or telaprevir (TEL) for 48 weeks, and sofosbuvir (SOF) plus daclastavir (DCV) or simeprevir (SIM) for 12 weeks. Costs were reported in United States Dollars without (US$) and with adjustment for purchasing power parity (PPP$). Drug costs were collected at the National Database of Health Prices and an overview of the literature was performed to assess effectiveness of SOF/DCV and SOF/SIM regimens in real-world cohorts. Results Treatment costs of GT1-HCV patients were PPP$43,176.28 (US$ 24,020.16) for PEG-IFN/RBV, PPP$71,196.03 (US$ 39,578.23) for PEG-IFN/RBV/BOC and PPP$86,250.33 (US$ 47,946.92) for PEG-IFN/RBV/TEL. Treatment by all-oral interferon-free regimens were the less expensive approach: PPP$19,761.72 (US$ 10,985.90) for SOF/DCV and PPP$21,590.91 (US$ 12,002.75) for SOF/SIM. The overview reported HCV eradication in up to 98% for SOF/DCV and 96% for SOF/SIM. Conclusion Strategies with all oral interferon-free might lead to lower costs for management of GT1-HCV patients compared to IFN-based regimens in Brazil. This occurred mainly because of high discounts over international DAA prices due to negotiation between BMoH and pharmaceutical industries

Diets containing sea cucumber (Isostichopus badionotus) meals are hypocholesterolemic in young rats

Peer reviewedPublisher PD

Determination of an optimal response cut-off able to predict progression-free survival in patients with well-differentiated advanced pancreatic neuroendocrine tumours treated with sunitinib: an alternative to the current RECIST-defined response.

BACKGROUND: Sunitinib prolongs progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumours (pNET). Response Evaluation Criteria in Solid Tumors (RECIST)-defined partial responses (PR; classically defined as ⩾30% size decrease from baseline) are infrequent. METHODS: Individual data of pNET patients from the phase II [NCT00056693] and pivotal phase III [NCT00428597] trials of sunitinib were analysed in this investigator-initiated, post hoc study. The primary objective was to determine the optimal RECIST (v.1.0) response cut-off value to identify patients who were progression-free at 11 months (median PFS in phase III trial); and the most informative time-point (highest area under the curve (AUC) by receiver operating characteristic (ROC) analysis and logistic regression) for prediction of benefit (PFS) from sunitinib. RESULTS: Data for 237 patients (85 placebo; 152 sunitinib (n=66.50 mg \u274-weeks on/2-weeks off\u27 schedule; n=86 \u2737.5 mg continuous daily dosing (CDD)\u27)) and 788 scans were analysed. The median PFS for sunitinib and placebo were 9.3 months (95% CI 7.6-12.2) and 5.4 months (95% CI 3.5-6.01), respectively (hazard ratio (HR) 0.43 (95% CI 0.29-0.62); P CONCLUSIONS: A 10% reduction within marker lesions identifies pNET patients benefiting from sunitinib treatment with implications for maintenance of dose intensity and future trial design