Purpose: Conventional therapies and surgery remain the standard treatment for breast cancer. However, combating the eventual development of metastasis is still a challenge.Newcastle disease virus (NDV) is one of the various species of viruses under clinical evaluation as a vector for oncolytic, gene-, and immune-stimulating therapies. The purpose of this study was to evaluate the antitumor activity of a recombinant NDV (rNDV-P05) in a breast cancer murine model. Methods: Tumors were induced by injecting the cellular suspension (4T1 cell line) subcutaneously. The virus strain P05 was applied three times at intervals of seven days, starting seven days after tumor induction, and was completed 21 days later. Determination of tumor weight, spleen index, and lung metastasis were done after sacrificing the mice.Serum levels of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, and TNF-related apoptosis-inducing ligand (TRAIL) were quantified by enzyme-linked immunosorbent assay.CD8+ infiltrated cells were analyzed by immunofluorescence. Results: rNDV-P05 showed a route-of-administration-dependent effect, demonstrating that the systemic administration of the virus significantly reduces the tumor mass and volume, spleen index, and abundance of metastatic clonogenic colonies in lung tissue, and increases the inhibition rate of the tumor. The intratumoral administration of rNDV-P05 was ineffective for all the parameters evaluated. Antitumor and antimetastatic capability of rNDV-P05 is mediated, at least partially, through its immune-stimulatory effect on the upregulation of TNF-α, TRAIL, IFN-α, and IFN-γ, and its ability to recruit CD8+ T cells into tumor tissue. Conclusion Systemic treatment with rNDV-P05 decreases the tumoral parameters in the breast cancer murine model.

Objectives: This paper presents a systematic mapping of studies related to information systems and technology in the field of healthcare, enabling a visual mapping of the different lines of knowledge that can provide an overview of the scientific literature in this field. This map can help to clarify critical aspects of healthcare informatics, such as the main types of information systems, the ways in which they integrate with each other, and the technological trends in this field. Methods: Systematic mapping refers to a process of classifying information in a given area of knowledge. It provides an overview of the state of the art in a particular discipline or area of knowledge, establishing a map that describes how knowledge is structured in that particular area. In this study, we proposed and carried out a specific implementation of the methodology for mapping. In total, 1,619 studies that combine knowledge related to information systems, computer science, and healthcare were selected and compiled from prestigious publications. Results: The results established a distribution of the available literature and identified papers related to certain research questions, thereby providing a map of knowledge that structures the different trends and main areas of research, making it possible to address the research questions and serving as a guide to deepen specific aspects of the field of study. Conclusions We project and propose future research for the trends that stand out because of their interest and the possibility of exploring these topics in greater depth.

Objective: To describe the roadmapping technique and our three-year experience in the management of intracranial aneurysms in the hybrid operating room. Methods: We analyzed all patients who underwent surgical clipping for cerebral aneurysms with the roadmapping technique from January 2017 to September 2019. We report demographic, clinical, and morphological variables, as well as clinical and radiological outcomes. We further describe three illustrative cases of the technique. Results: A total of 13 patients were included, 9 of which (69.2%) presented with subarachnoid hemorrhage, with a total of 23 treated aneurysms. All patients were female, with a mean age of 47.7 years (range 31-63). All cases were anterior circulation aneurysms, the most frequent location being the ophthalmic segment of the internal carotid artery (ICA) in 11 cases (48%), followed by posterior communicating in 8 (36%), and ICA bifurcation in 2 (8%). Intraoperative clip repositioning was required in 9 aneurysms (36%) as a result of the roadmapping technique in the hybrid operating room. There were no residual aneurysms in our series, nor reported mortality. Conclusions The roadmapping technique in the hybrid operating room offers a complementary tool for the adequate occlusion of complex intracranial aneurysms, as it provides a real time fluoroscopic-guided clipping technique, and clip repositioning is possible in a single surgical stage, whenever a residual portion of the aneurysm is identified. This technique also provides some advantages, such as immediate vasospasm identification and treatment with intra-arterial vasodilators, balloon proximal control for certain paraclinoid aneurysms, and simultaneous endovascular treatment in selected cases during a single stage.

Objective: To describe and molecularly characterize an outbreak of dengue virus (DENV) infection in Cajamarca, an Andean region in Peru. Methods: A total of 359 serum samples from patients with acute febrile illness were assessed for the presence of DENV via RT-PCR, ELISA NS1, IgM and IgG in Cajamarca, Peru from January 2017 to June 2017. The evaluation of the different diagnostic tests and their applicability was performed. Results: Dengue virus was detected in 24.7% of samples by RTPCR. Meanwhile, serological analysis detected 30.3% positive cases via ELISA NS1 antigen, 16.7% via ELISA IgG and 9.7% via ELISA IgM. Most of the cases corresponded to DENV-3 (77.5%). The use of RT-PCR performed better in primary infections (P<0.01), while detection of ELISA IgM performed better in secondary infections (P<0.01). The combination of NS1 and IgM performed better than the other assays in detecting primary (92.5%) and secondary infections (96.6%). The most frequent symptoms associated with fever were headaches, myalgias, and arthralgias across all groups. Conclusions: We report an important outbreak of dengue infection caused by DENV-3 in Cajamarca, Peru. Our findings encourage the use of NS1 antigen and IgM co-detection. These findings demonstrate an increasing expansion of DENV-3 in Peru and highlight the importance of molecular diagnosis and serotype characterization among the clinically defined dengue cases to strengthen the Peruvian epidemiological surveillance.

Arylamine -acetyltransferase (NAT; E.C. 2.3.1.5) enzymes are responsible for the biotransformation of several arylamine and hydrazine drugs by acetylation. In this process, the acetyl group transferred to the acceptor substrate produces NAT deacetylation and, in consequence, it is susceptible of degradation. Sirtuins are protein deacetylases, dependent on nicotine adenine dinucleotide, which perform post-translational modifications on cytosolic proteins. To explore possible sirtuin participation in the enzymatic activity of arylamine NATs, the expression levels of NAT1, NAT2, SIRT1 and SIRT6 in peripheral blood mononuclear cells (PBMC) from healthy subjects were examined by flow cytometry and Western blot. The activity of the sirtuins on NAT enzymatic activity was analyzed by HPLC, in the presence or absence of an agonist (resveratrol) and inhibitor (nicotinamide) of sirtuins. We detected a higher percentage of positive cells for NAT2 in comparison with NAT1, and higher numbers of SIRT1+ cells compared to SIRT6 in lymphocytes. NAT2 activity in the presence of NAM inhibitors was higher than in the presence of its substrate, but not in the presence of resveratrol. In contrast, the activity of NAT1 was not affected by sirtuins. These results showed that NAT2 activity might be modified by sirtuins.

The chronic indeterminate phase of Chagas’ disease is asymptomatic despite positive test results for antibodies specific to Trypanosoma cruzi. CD62P-APC (P-selectin) and PAC-1 FITC (GpIIb/IIIa) may improve diagnosis as biomarkers of platelet activity. Nine asymptomatic seropositive subjects, previously untreated, were selected from a blood bank within a year of Chagas’ disease detection, in addition to a control group of four. All subjects were evaluated by flow cytometry for CD62P, PAC-1 and CD41, and in a complementary study, by Tissue Doppler Echocardiography for isovolumic relaxation times (IVRT) and E/A ratios. The subjects were classified as positive or negative for CD62P and PAC-1 by a cut off obtained from their mean±2SD. For IVRT and E/A ratios, cut offs were obtained from the American Society of Echocardiography and the European Association of Cardiovascular Imaging recommendations. Fisher’s exact test was used for associated findings. Pre-test and post-test probability, sensitivity, specificity, positive and negative predictive values and likelihood ratios were calculated. Abnormalities were expressed as platelet hyperactivity and ventricular dysfunction in CD62P, PAC-1, IVRT and E/A ratios. CD62P appears to have greater sensitivity (0.75) and PAC-1, more accurate specificity (0.75), which may explain thrombotic events in Chagas’ disease. We recommend the use of CD62P and PAC-1 as biomarkers of platelet hyperactivity in patients in the chronic indeterminate phase of Chagas’ disease.

BACKGROUND/AIMS: The development of therapeutic strategies for the treatment of cirrhosis has become an important focus for basic and clinical researchers. Adrenergic receptor antagonists have been evaluated as antifibrotic drugs in rodent models of carbon tetrachloride (CCl4)-induced cirrhosis. The aim of the present study was to evaluate the effects of carvedilol and doxazosin on fibrosis/cirrhosis in a hamster animal model. METHODS: Cirrhotic-induced hamsters were treated by daily administration of carvedilol and doxazosin for 6 weeks. Hepatic function and histological evaluation were conducted by measuring biochemical markers, including total bilirubin, aspartate aminotransferase, alanine aminotransferase and albumin, and liver tissue slices. Additionally, transforming growth factor beta (TGF-beta) immunohistochemistry was analyzed. RESULTS: Biochemical markers revealed that hepatic function was restored after treatment with doxazosin and carvedilol. Histological evaluation showed a decrease in collagen type I deposits and TGF-beta-secreting cells. CONCLUSIONS: Taken together, these results suggest that the decrease in collagen type I following treatment with doxazosin or carvedilol is achieved by decreasing the profibrotic activities of TGF-beta via the blockage of alpha1- and beta-adrenergic receptor. Consequently, a diminution of fibrotic tissue in the CCl4-induced model of cirrhosis is achieved.
Adrenergic alpha-1 Receptor Antagonists/*pharmacology ; Alanine Transaminase/blood ; Animals ; Aspartate Aminotransferases/blood ; Bilirubin/blood ; Carbazoles/*pharmacology ; Carbon Tetrachloride ; Collagen Type I/drug effects/metabolism ; Cricetinae ; Doxazosin/*pharmacology ; Liver/metabolism/pathology ; Liver Cirrhosis/blood/chemically induced/*drug therapy ; Liver Function Tests ; Propanolamines/*pharmacology ; Serum Albumin/analysis ; Transforming Growth Factor beta/blood/*drug effects

Anterior exposure for cervical chordomas remains challenging because of the anatomical complexities and the restoration of the dimensional balance of the atlanto-axial region. In this report, we describe and analyze the transmandibular transoral approach and multilevel spinal reconstruction for upper cervical chordomas. We report two cases of cervical chordomas (C2 and C2-C4) that were treated by marginal en bloc resection with a transmandibular approach and anterior-posterior multilevel spinal reconstruction/fixation. Both patients showed clinical improvement. Postoperative imaging was negative for any residual tumor and revealed adequate reconstruction and stabilization. Marginal resection requires more extensive exposure to allow the surgeon access to the entire pathology, as an inadequate tumor margin is the main factor that negatively affects the prognosis. Anterior and posterior reconstruction provides a rigid reconstruction that protects the medulla and decreases axial pain by properly stabilizing the cervical spine.
Chordoma* ; Humans ; Neoplasm, Residual ; Pathology ; Prognosis ; Spinal Neoplasms ; Spine