Kinin B1 receptor and TLR4 interaction in inflammatory response.

OBJECTIVE: We aimed to broaden our understanding of a potential interaction between B1R and TLR4, considering earlier studies suggesting that lipopolysaccharide (LPS) may trigger B1R stimulation. METHODS: We assessed the impact of DBK and LPS on the membrane potential of thoracic aortas from C57BL/6, B1R, or TLR4 knockout mice. Additionally, we examined the staining patterns of these receptors in the thoracic aortas of C57BL/6 and in endothelial cells (HBMEC). RESULTS: DBK does not affect the resting membrane potential of aortic rings in C57BL/6 mice, but it hyperpolarizes preparations in B1KO and TLR4KO mice. The hyperpolarization mechanism in B1KO mice involves B2R, and the TLR4KO response is independent of cytoplasmic calcium influx but relies on potassium channels. Conversely, LPS hyperpolarizes thoracic aorta rings in both C57BL/6 and B1KO mice, with the response unaffected by a B1R antagonist. Interestingly, the absence of B1R alters the LPS response to potassium channels. These activities are independent of nitric oxide synthase (NOS). While exposure to DBK and LPS does not alter B1R and TLR4 mRNA expression, treatment with these agonists increases B1R staining in endothelial cells of thoracic aortic rings and modifies the staining pattern of B1R and TLR4 in endothelial cells. Proximity ligation assay suggests a interaction between the receptors. CONCLUSION: Our findings provide additional support for a putative connection between B1R and TLR4 signaling. Given the involvement of these receptors and their agonists in inflammation, it suggests that drugs and therapies targeting their effects could be promising therapeutic avenues worth exploring.

Next-generation IEDB tools: a platform for epitope prediction and analysis.

The Next-Generation (NG) IEDB Tools website (https://nextgen-tools.iedb.org) provides users with a redesigned interface to many of the algorithms for epitope prediction and analysis that were originally released on the legacy IEDB Tools website. The initial release focuses on consolidation of all tools related to HLA class I epitopes (MHC binding, elution, immunogenicity, and processing), making all of these predictions accessible from a single application and allowing for their simultaneous execution with minimal user inputs. Additionally, the PEPMatch tool for identifying highly similar epitopes in a set of curated proteomes, as well as a tool for epitope clustering, are available on the site. The NG Tools site allows users to build data pipelines by sending the output of one tool as input for the next. Over the next several years, all pre-existing IEDB Tools, and any newly developed tools, will be integrated into this new site. Here we describe the philosophy behind the redesign and demonstrate the utility and productivity enhancements that are enabled by the new interface.

Infectious etiology and indicators of malabsorption or intestinal injury in childhood diarrhea. / Etiología infecciosa e indicadores de malabsorción o daño intestinal en diarrea infantil

INTRODUCTION: The multifactorial etiology of gastroenteritis emphasizes the need for different laboratory methods to identify or exclude infectious agents and evaluate the severity of diarrheal disease. OBJECTIVE: To diagnose the infectious etiology in diarrheic children and to evaluate some fecal markers associated with intestinal integrity. MATERIALS AND METHODS: The study group comprised 45 children with diarrheal disease, tested for enteropathogens and malabsorption markers, and 76 children whose feces were used for fat evaluation by the traditional and acid steatocrit tests. RESULTS: We observed acute diarrhea in 80% of the children and persistent diarrhea in 20%. Of the diarrheic individuals analyzed, 40% were positive for enteropathogens, with rotavirus (13.3%) and Giardia duodenalis (11.1%) the most frequently diagnosed. Among the infected patients, occult blood was more evident in those carrying pathogenic bacteria (40%) and enteroviruses (40%), while steatorrhea was observed in infections by the protozoa G. duodenalis (35.7%). Children with diarrhea excreted significantly more lipids in feces than non-diarrheic children, as determined by the traditional (p<0.0003) and acid steatocrit (p<0.0001) methods. Moreover, the acid steatocrit method detected 16.7% more fecal fat than the traditional method. CONCLUSIONS: Childhood diarrhea can lead to increasingly severe nutrient deficiencies. Steatorrhea is the hallmark of malabsorption, and a stool test, such as the acid steatocrit, can be routinely used as a laboratory tool for the semi-quantitative evaluation of fat malabsorption in diarrheic children.

Introducción. La etiología multifactorial de la gastroenteritis enfatiza la necesidad de usar diferentes métodos de laboratorio para identificar o excluir agentes infecciosos y evaluar la gravedad de la enfermedad diarreica. Objetivo. Diagnosticar la etiología infecciosa de la diarrea en niños y evaluar algunos marcadores fecales asociados con la integridad intestinal. Materiales y métodos. Se estudiaron 45 niños con enfermedad diarreica, en los cuales se evaluaron la presencia de enteropatógenos y los marcadores de malabsorción. Se analizaron las muestras fecales de 76 niños, mediante las pruebas de esteatocrito tradicional y esteatocrito ácido, para la cuantificación de la grasa. Resultados. Se observó diarrea aguda en el 80 % de los niños y diarrea persistente en el 20 %. De los individuos con diarrea, el 40 % fue positivo para enteropatógenos; los más diagnosticados fueron rotavirus (13,3 %) y Giardia duodenalis (11,1 %). Entre los pacientes infectados, la sangre oculta fue más evidente en aquellos portadores de bacterias patógenas (40 %) o enterovirus (40%), mientras que la esteatorrea se observó en infecciones por el protozoo G. duodenalis (35,7 %). Los niños con diarrea excretaron significativamente más lípidos en las heces que aquellos sin diarrea, según lo determinado por los métodos de esteatocrito tradicional (p<0,0003) y esteatocrito ácido (p<0,0001). Conclusiones. La diarrea infantil puede provocar deficiencias graves de nutrientes. La esteatorrea es distintiva de la malabsorción intestinal y puede detectarse mediante la estimación del esteatocrito ácido. Esta prueba podría utilizarse de forma rutinaria como una herramienta de laboratorio para la evaluación semicuantitativa de la malabsorción de grasas en niños con diarrea.

Absolute intensity thresholds for tri-axial wrist and waist accelerometer-measured movement behaviors in adults.

AIM: This study was aimed to: (1) compare raw triaxial acceleration data from GENEActiv (GA) and ActiGraph GT3X+ (AG) placed on the non-dominant wrist; (2) compare AG placed on the non-dominant and dominant wrist, and waist; (3) derive brand- and placement-specific absolute intensity thresholds for inactive and sedentary time, and physical activity intensity in adults. METHODS: Eighty-six adults (44 men; 34.6 ± 10.8 years) performed nine activities while simultaneously wearing GA and AG on wrist and waist. Acceleration (in gravitational equivalent units; mg) was compared with oxygen uptake (measured with indirect calorimetry). RESULTS: Increases in acceleration mirrored increases in intensity of activities, regardless of device brand and placement. Differences in acceleration between GA and AG worn at the non-dominant wrist were small but tended to be high at lower intensity activities. Thresholds for differentiating inactivity (<1.5 MET) from activity (≥1.5 MET) ranged from 25 mg (AG non-dominant wrist; sensitivity 93%, specificity 95%) to 40 mg (AG waist; sensitivity 78%, specificity 100%). For moderate intensity (≥3 METs), thresholds ranged from 65 mg (AG waist; sensitivity 96%, specificity 94%) to 92 mg (GA non-dominant; sensitivity 93%, specificity 98%); vigorous intensity (≥6 METs) thresholds ranged from 190 mg (AG waist; sensitivity 82%, specificity 92%) to 283 mg (GA non-dominant; sensitivity 93%, specificity 98%). CONCLUSION: Raw triaxial acceleration outputs from two widely used accelerometer brands may have limited comparability in low intensity activities. Thresholds derived in this study can be utilized in adults to reasonably classify movement behaviors into categories of intensity.

Characteristics, mortality, associated variables with death, and therapeutic response among HIV-positive, solid organ transplant (SOT), and non-HIV-positive/non-transplant (NHNT) patients with cryptococcosis: First multicenter cohort study in Brazil.

Cryptococcosis is traditionally associated with immunocompromised patients but is increasingly being identified in those without the human immunodeficiency virus (HIV) or other immunocompetent individuals. We aim to describe the characteristics, mortality, and associated variables with death among hospitalized patients with cryptococcosis in Brazil. This is the first multicenter retrospective cohort study conducted in seven public tertiary Brazilian hospitals. A total of 384 patients were included; the median age was 39 years and 283 (73.7%) were men. In all, 304 HIV-positive were hosts (79.2%), 16 (4.2%) solid organ transplant (SOT), and 64 (16.7%) non-HIV-positive/non-transplant (NHNT). Central nervous system (CNS) cryptococcosis had a significantly higher number across disease categories, with 313 cases (81.5%). A total of 271 (70.6%) patients were discharged and 113 (29.4%) died during hospitalization. In-hospital mortality among HIV-positive, SOT, and NHNT was 30.3% (92/304), 12.5% (2/16), and 29.7% (19/64), respectively. Induction therapy with conventional amphotericin B (AMB) mainly in combination with fluconazole (234; 84.2%) was the most used. Only 80 (22.3%) patients received an AMB lipid formulation: liposomal (n = 35) and lipid complex (n = 45). Most patients who died belong to the CNS cryptococcosis category (83/113; 73.4%) when compared with the others (P = .017). Multivariate analysis showed that age and disseminated cryptococcosis had a higher risk of death (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.05; P = .008 and OR, 1.84; 95% CI, 1.01-3.53; P = .048, respectively). Understanding the epidemiology of cryptococcosis in our settings will help to recognize the burden and causes of mortality and identify strategies to improve this scenario.

This multicenter cohort study included 384 hospitalized individuals with cryptococcosis in Brazil. Most individuals were men (74%), HIV-positive (79%), had central nervous system involvement (82%), and received conventional amphotericin plus fluconazole (84%). In-hospital mortality was high (29%).

Heterologous versus homologous COVID-19 booster vaccination in previous recipients of two doses of CoronaVac COVID-19 vaccine in Brazil (RHH-001): a phase 4, non-inferiority, single blind, randomised study.

INTRODUCTION: The inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac, Sinovac) has been widely used in a two-dose schedule. We assessed whether a third dose of the homologous or a different vaccine could boost immune responses. METHODS: RHH-001 is a phase 4, participant masked, two centre, safety and immunogenicity study of Brazilian adults (18 years and older) in São Paulo or Salvador who had received two doses of CoronaVac 6 months previously. The third heterologous dose was of either a recombinant adenoviral vectored vaccine (Ad26.COV2-S, Janssen), an mRNA vaccine (BNT162b2, Pfizer-BioNTech), or a recombinant adenoviral-vectored ChAdOx1 nCoV-19 vaccine (AZD1222, AstraZeneca), compared with a third homologous dose of CoronaVac. Participants were randomly assigned (5:6:5:5) by a RedCAP computer randomisation system stratified by site, age group (18-60 years or 61 years and over), and day of randomisation, with a block size of 42. The primary outcome was non-inferiority of anti-spike IgG antibodies 28 days after the booster dose in the heterologous boost groups compared with homologous regimen, using a non-inferiority margin for the geometric mean ratio (heterologous vs homologous) of 0·67. Secondary outcomes included neutralising antibody titres at day 28, local and systemic reactogenicity profiles, adverse events, and serious adverse events. This study was registered with Registro Brasileiro de Ensaios Clínicos, number RBR-9nn3scw. FINDINGS: Between Aug 16, and Sept 1, 2021, 1240 participants were randomly assigned to one of the four groups, of whom 1239 were vaccinated and 1205 were eligible for inclusion in the primary analysis. Antibody concentrations were low before administration of a booster dose with detectable neutralising antibodies of 20·4% (95% CI 12·8-30·1) in adults aged 18-60 years and 8·9% (4·2-16·2) in adults 61 years or older. From baseline to day 28 after the booster vaccine, all groups had a substantial rise in IgG antibody concentrations: the geometric fold-rise was 77 (95% CI 67-88) for Ad26.COV2-S, 152 (134-173) for BNT162b2, 90 (77-104) for ChAdOx1 nCoV-19, and 12 (11-14) for CoronaVac. All heterologous regimens had anti-spike IgG responses at day 28 that were superior to homologous booster responses: geometric mean ratios (heterologous vs homologous) were 6·7 (95% CI 5·8-7·7) for Ad26.COV2-S, 13·4 (11·6-15·3) for BNT162b2, and 7·0 (6·1-8·1) for ChAdOx1 nCoV-19. All heterologous boost regimens induced high concentrations of pseudovirus neutralising antibodies. At day 28, all groups except for the homologous boost in the older adults reached 100% seropositivity: geometric mean ratios (heterologous vs homologous) were 8·7 (95% CI 5·9-12·9) for Ad26.COV2-S vaccine, 21·5 (14·5-31·9) for BNT162b2, and 10·6 (7·2-15·6) for ChAdOx1 nCoV-19. Live virus neutralising antibodies were also boosted against delta (B.1.617.2) and omicron variants (B.1.1.529). There were five serious adverse events. Three of which were considered possibly related to the vaccine received: one in the BNT162b2 group and two in the Ad26.COV2-S group. All participants recovered and were discharged home. INTERPRETATION: Antibody concentrations were low at 6 months after previous immunisation with two doses of CoronaVac. However, all four vaccines administered as a third dose induced a significant increase in binding and neutralising antibodies, which could improve protection against infection. Heterologous boosting resulted in more robust immune responses than homologous boosting and might enhance protection. FUNDING: Ministry of Health, Brazil.

Intraoperative evaluation of tunneled dialysis catheter mobility and function with arm movement.

OBJECTIVE: The main objectives of the present study were to analyze the right internal jugular vein tunneled dialysis catheter (TDC) tip displacements, functional changes, pathway deformities, and angulations associated with different arm positions. METHODS: We prospectively studied 21 patients who had undergone TDC implantation for hemodialysis via the right internal jugular vein at a single center from February to September 2020. After implantation, a baseline resting fluoroscopy image was taken, and three movement-mimicking images of the ipsilateral arm were obtained for comparison, with the arm in maximum abduction, maximum flexion, and maximum adduction. Device function was analyzed for each movement-mimicking position and correlated with catheter tip displacement, catheter deformity, and catheter pathway angulation. RESULTS: TDC pathway deformity occurred in 16 patients (69.5%). Deformities were more frequent in the movement-mimicking positions than in to the control resting baseline images (P = .004). The different arm positions did not lead to significant tip displacement (either horizontal or vertical; P > .05), nor did they result in significant pathway angulation between the subcutaneous and intravenous regions (P = .114). However, in the maximum abduction position, a positive relationship was present between the catheter pathway angle and impairment of catheter function (P = .028). CONCLUSIONS: Catheter deformity was more frequent and more severe with maximum adduction and flexion of the arm. Although no significant changes were observed in the tip of the catheter with the movements, a positive relationship was found between the catheter pathway angle and impairment of catheter function with the arm in the maximum abduction position.

Evaluation of the biological and physicochemical properties of calcium silicate-based and epoxy resin-based root canal sealers.

Biocompatibility, dimensional stability, radiopacity, flow, and low solubility are the characteristics of an ideal endodontic sealer. This study evaluated and compared in vivo and in vitro biological and physicochemical properties of calcium silicate-based sealers: Sealer Plus BC (BC), MTA Fillapex (MF); and resin-based sealers: AH Plus (AHP) and Sealer Plus (SP). Apical papilla cells were exposed to sealer extracts and subjected to MTT, SRB, scratch, alkaline phosphatase enzyme activity (ALP) and Alizarin red staining (ALZ) assays. Sealers were histologically evaluated in connective tissue of Wistar rats in different periods. Radiopacity, film thickness, flow, setting time, pH and element analyses were investigated. BC had better results compared to AHP and MF at hour 72 for MTT assay (p < .05), and the highest cell viability under SRB (p < .05). All sealers presented ALP activity. BC presented the highest mineralized deposition under ALZ (p < .05). BC and MF promoted wound healing. All sealers induced an initial inflammation reaction that decreased over time. Eosinophils were observed at day 7 in MF (p < .05). Despite MF did not present final setting time, the sealers properties were in accordance to ISO 6876/2012 and ASTM C266-08. All sealers presented cell viability and biocompatibility. BC presented higher pH values and bioactivity. The materials tested showed physico-chemical properties in accordance with standards, except for MF setting time.

Conventional Varicose Vein Surgery: Comparison between Single versus Staged Surgery Using Patient Reported Outcomes.

BACKGROUND: In the Brazilian public health system, conventional surgery is the standard procedure for treatment of varicose veins (VV). We aimed to compare clinical and quality of life (QoL) results of patients subjected to bilateral treatment of VV by a single-procedure or staged-procedure approach. METHODS: A total of 111 patients undergoing bilateral treatment for VV were treated either by a single-surgery or 2 staged procedures (minimal: 30-day interval) depending on institutional protocol. Patients were evaluated with respect to clinical symptoms and quality of life markers before and after treatment, by use of the VEINES-Sym/QoL and EQ5D-5L scores, and these results were then compared between groups. RESULTS: QoL scores improved in general after treatment. VV specific symptoms and QoL aspects improved equally between the Staged-procedure and Single-surgery groups (VEINES-Sym mean variation 29.7 ± 2.1 vs. 29.9 ± 2.7, respectively; P = 0.340 and VEINES-QoL mean variation 5.5 ± 3.4 vs. 4.5 ± 4.3, respectively; P = 0.369). General QoL, however, showed more improvement in the Staged-procedure than the Single-surgery group (EQD5-5L mean increase 0.1678 ± 0.1555 and 0.0785 ± 0.1384, respectively; P = 0.007). When propensity matched, patient subgroups maintained this same differences in QoL results. CONCLUSIONS: Our findings suggest that the both the Staged- and Single-surgery approach for VV surgical treatment incur similar improvement in disease-specific QoL, and that the Staged-approach may impose less of a burden in the patients' recovery.

Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 lineages circulating in Brazil.

Several COVID-19 vaccines have shown good efficacy in clinical trials, but there remains uncertainty about the efficacy of vaccines against different variants. Here, we investigate the efficacy of ChAdOx1 nCoV-19 (AZD1222) against symptomatic COVID-19 in a post-hoc exploratory analysis of a Phase 3 randomised trial in Brazil (trial registration ISRCTN89951424). Nose and throat swabs were tested by PCR in symptomatic participants. Sequencing and genotyping of swabs were performed to determine the lineages of SARS-CoV-2 circulating during the study. Protection against any symptomatic COVID-19 caused by the Zeta (P.2) variant was assessed in 153 cases with vaccine efficacy (VE) of 69% (95% CI 55, 78). 49 cases of B.1.1.28 occurred and VE was 73% (46, 86). The Gamma (P.1) variant arose later in the trial and fewer cases (N = 18) were available for analysis. VE was 64% (-2, 87). ChAdOx1 nCoV-19 provided 95% protection (95% CI 61%, 99%) against hospitalisation due to COVID-19. In summary, we report that ChAdOx1 nCoV-19 protects against emerging variants in Brazil despite the presence of the spike protein mutation E484K.

Efficacy of propolis as an adjunct treatment for hospitalized COVID-19 patients: a randomized, controlled clinical trial

Among candidate treatment options for COVID-19, propolis, produced by honey bees from bioactive plant exudates, has shown potential against viral targets and has demonstrated immunoregulatory properties. We conducted a randomized, controlled, open-label, single center trial, with a standardized propolis product (EPP-AF) on hospitalized adult COVID-19 patients. Patients received standard care plus propolis at an oral dose of 400mg/day (n=40) or 800mg/day (n=42) for seven days, or standard care alone (n=42). Standard care included all necessary interventions, as determined by the attending physician. The primary end point was the time to clinical improvement defined as the length of hospital stay or oxygen therapy dependency. Secondary outcomes included acute kidney injury and need for intensive care or vasoactive drugs. Time in the hospital after intervention was significantly shortened in both propolis groups compared to the controls; median 7 days with 400mg/day and 6 days with 800mg/day, versus 12 days for standard care alone. Propolis did not significantly affect the need for oxygen supplementation. With the higher dose, significantly fewer patients developed acute kidney injury than in the controls (2 versus 10 of 42 patients). Propolis as an adjunct treatment was safe and reduced hospitalization time. The registration number for this clinical trial is: NCT04480593 (20/07/2020).

Epidemiology and Estimated Cost of Brachial Plexus Surgeries Performed through the Unified Health System in Brazil (2008­2016)

Introduction The brachial plexus is responsible for the innervation of the upper extremity of the body. About 10 to 20% of the peripheral nerve lesions are brachial plexus lesions. Objective To describe the epidemiology of the brachial plexus microsurgery with exploration and neurolysis (BPMEN) and the brachial plexus microsurgery with nerve graft (BPMNG) performed through the Brazilian Unified Health System (SUS, in the Portuguese acronym) from 2008 to 2016. Methodology A descriptive epidemiological study whose data were obtained from the Department of Informatics of the SUS (Datasus, in the Portuguese acronym). The study consisted of all patients submitted to BPMEN (code: 0403020034) and to BPMNG (code: 0403020042). Result/Discussion A total of 5,295 procedures were performed with an annual incidence of 2.94/1 million inhabitants. The hospital expenses of these 2 codes totaled R$ 4,492,603.88 (US$ 1,417,225.10). The BPMNG code presented an annual average of expenses with professional services of R$ 99,732.20 (US$ 31,461.26), and total expenses of R$ 897,589.83 (US$ 283,151.36). The amount transferred to the physician in this code in 2008 was R$ 294.56 (US$ 92.92), and currently it is R$ 441.84 (US$ 139.38). The BPMEN code presented an annual average of expenses of R$ 68,579.15 (US$ 21,633.80), with total expenses of R$ 617,212.40 (US$ 194,704.22). The amount transferred to the physician in this code in 2008 was R$ 153.44 (US$ 48.40), and currently it is R$ 230.16 (US$72.60). Both codes presented a lag in the transfer values to the physician that ranged from 16.55 to 17.64% when using the Brazilian national price index for the general consumer (IPCA, in the Portuguese acronym) as an inflation parameter during the period studied. The mean number of hospitalization days for these 2 codes was 3.79. Conclusion The absence of deaths and the low rate of hospital stay confirm that the procedure is safe, with a low morbimortality rate. Both codes presented a lag in the transfer values to the physician at the end of the period.

Quality of Life, Mental Health, Personality and Patterns of Use in Self-Medicated Cannabis Users with Chronic Diseases: A 12-Month Longitudinal Study.

The number of patients using cannabis for therapeutic purposes is growing worldwide. While research regarding the treatment of certain diseases/disorders with cannabis and cannabinoids is also expanding, only a few longitudinal studies have assessed the mid-term impacts of medical cannabis use on psychological variables and quality of life (QoL). The aim of the study was to assess the psychological safety and QoL of patients with chronic diseases who self-medicate with cannabis over time. We recruited patients with various chronic diseases who use cannabis and collected data regarding patterns of cannabis use as well as mental health, personality and QoL. Participants were followed-up at baseline, 4, 8 and 12 months. Hair analysis was conducted to confirm the presence of cannabinoids. Personality assessment showed a consistent decrease in self-transcendence and self-directedness scores. Neither cognitive nor psychopathological deterioration was found. There were also no variations in QoL. Mid-term use of medical cannabis seems to show adequate tolerability regarding cognitive and psychopathological abilities, and it may help patients with chronic diseases to maintain an acceptable QoL.

Evaluation of the Activity of Heparin Injected into the Fully Implantable Catheter for Chemotherapy (Portocath) between Two Moments of Use.

BACKGROUND: The aim of this study is to analyze whether heparin, used as a lock in fully implantable catheter for chemotherapy (portocath), maintains its activity even if it remains in the catheter for a long period of time. METHODS: According to the institutional protocol, all catheters routinely use the lock solution with 3 mL of heparinized solution after chemotherapy and the time interval between each change as lock in the catheters studied ranged from 7 to 30 days. A total of 25 blood samples from 22 patients with 6 types of neoplasia on chemotherapy or not were collected according to routine, and the 10 mL of liquid contained in the first aspirated reservoir/catheter (corresponding to the lock of the last section), were sent for laboratory analysis for prospectively studied with the following tests: anti-Xa, partially activated thromboplastin time (APTT), thrombin time (TT), reptilase, and thromboelastogram. RESULTS: Heparin activity was found in 96% of the anti-Xa and APTT tests. In relation to TT, 92% presented activity. The reptilase test was performed on 24 samples with significant time reduction in all of them. In the INTEM stage, the thromboelastometry test showed activity in 92% of samples and in the HEPTEM phase there was reduction in time in all samples. In all samples, the heparin activity was found to be independent of the time of use. CONCLUSIONS: We can conclude that lock of heparinized solution used in our service in fully implantable central venous catheters for chemotherapy was maintained with active heparin even after a long period of time (up to 30 days), demonstrating that the half-life of the substance within the catheter is greater than its plasma half-life.

Epidemiology and Estimated Cost of Microsurgical Treatment of Peripheral Nerve Tumor Conducted by the Brazilian Unified Health Care System (2008­2016)

Introduction Primary nerve tumors correspond to 5% of the soft tissue neoplasms affecting the upper limbs, with benign lesions being more frequent than malignant lesions. Objective To describe the epidemiological data of the microsurgical treatment of peripheral nerve tumors performed by the Brazilian Unified Health System (SUS, in the Portuguese acronym), with the code 0403020131, from 2008 to 2016, regarding the number of annual procedures, hospital and professional expenses, the average duration of hospital stay, and the number of deaths. Methods This is a descriptive epidemiological study whose data were obtained by consulting the database provided by the Health Informatics Department of the Brazilian Ministry of Health (DATASUS, in the Portuguese acronym). Results/Discussion A total of 6,012 procedures were performed during the period studied, with an average of 688 procedures per year. The average hospital stay was of 2.13 days. There was nomortality rate. The average annual cost of the professional was BRL 50,091.45; and the average hospital expenses were BRL111,887.94. Conclusion The microsurgical treatment of peripheral nerve tumors is a safe surgical procedure with zero mortality rate and short hospital stay. There was no national data on tumors of this nature in the medical literature.

Detection of post-vaccination enhanced dengue virus infection in macaques: An improved model for early assessment of dengue vaccines.

The need for improved dengue vaccines remains since the only licensed vaccine, Dengvaxia, shows variable efficacy depending on the infecting dengue virus (DENV) type, and increases the risk of hospitalization for severe dengue in children not exposed to DENV before vaccination. Here, we developed a tetravalent dengue purified and inactivated vaccine (DPIV) candidate and characterized, in rhesus macaques, its immunogenicity and efficacy to control DENV infection by analyzing, after challenge, both viral replication and changes in biological markers associated with dengue in humans. Although DPIV elicited cross-type and long-lasting DENV-neutralizing antibody responses, it failed to control DENV infection. Increased levels of viremia/RNAemia (correlating with serum capacity at enhancing DENV infection in vitro), AST, IL-10, IL-18 and IFN-γ, and decreased levels of IL-12 were detected in some vaccinated compared to non-vaccinated monkeys, indicating the vaccination may have triggered antibody-dependent enhancement of DENV infection. The dengue macaque model has been considered imperfect due to the lack of DENV-associated clinical signs. However, here we show that post-vaccination enhanced DENV infection can be detected in this model when integrating several parameters, including characterization of DENV-enhancing antibodies, viremia/RNAemia, and biomarkers relevant to dengue in humans. This improved dengue macaque model may be crucial for early assessment of efficacy and safety of future dengue vaccines.

Calibration of raw accelerometer data to measure physical activity: A systematic review.

Most of calibration studies based on accelerometry were developed using count-based analyses. In contrast, calibration studies based on raw acceleration signals are relatively recent and their evidences are incipient. The aim of the current study was to systematically review the literature in order to summarize methodological characteristics and results from raw data calibration studies. The review was conducted up to May 2017 using four databases: PubMed, Scopus, SPORTDiscus and Web of Science. Methodological quality of the included studies was evaluated using the Landis and Koch's guidelines. Initially, 1669 titles were identified and, after assessing titles, abstracts and full-articles, 20 studies were included. All studies were conducted in high-income countries, most of them with relatively small samples and specific population groups. Physical activity protocols were different among studies and the indirect calorimetry was the criterion measure mostly used. High mean values of sensitivity, specificity and accuracy from the intensity thresholds of cut-point-based studies were observed (93.7%, 91.9% and 95.8%, respectively). The most frequent statistical approach applied was machine learning-based modelling, in which the mean coefficient of determination was 0.70 to predict physical activity energy expenditure. Regarding the recognition of physical activity types, the mean values of accuracy for sedentary, household and locomotive activities were 82.9%, 55.4% and 89.7%, respectively. In conclusion, considering the construct of physical activity that each approach assesses, linear regression, machine-learning and cut-point-based approaches presented promising validity parameters.

Complexity of the Wnt/ß­catenin pathway: Searching for an activation model.

Wnt signaling refers to a conserved signaling pathway, widely studied due to its roles in cellular communication, cell fate decisions, development and cancer. However, the exact mechanism underlying inhibition of the GSK phosphorylation towards ß-catenin and activation of the pathway after biding of Wnt ligand to its cognate receptors at the plasma membrane remains unclear. Wnt target genes are widely spread over several animal phyla. They participate in a plethora of functions during the development of an organism, from axial specification, gastrulation and organogenesis all the way to regeneration and repair in adults. Temporal and spatial oncogenetic re-activation of Wnt signaling almost certainly leads to cancer. Wnt signaling components have been extensively studied as possible targets in anti-cancer therapies. In this review we will discuss one of the most intriguing questions in this field, that is how ß-catenin, a major component in this pathway, escapes the destruction complex, gets stabilized in the cytosol and it is translocated to the nucleus where it acts as a co-transcription factor. Four major models have evolved during the past 20years. We dissected each of them along with current views and future perspectives on this pathway. This review will focus on the molecular mechanisms by which Wnt proteins modulate ß-catenin cytoplasmic levels and the relevance of this pathway for the development and cancer.