Nanohydroxyapatite-Blasted Bioactive Surface Drives Shear-Stressed Endothelial Cell Growth and Angiogenesis.

Nanosized crystalline hydroxyapatite coating (HAnano®) accelerates the osteointegration of dental implants which is hypothesized to drive angiogenesis. In order to test this hypothesis, we have subjected shear-stressed human umbilical vein endothelial cells (HUVECs) to a HAnano®-enriched medium, as well as to surface presenting dual acid etching (DAE) as a control. To note, the titanium implants were coated with 10 nm in diameter HA particles using the Promimic HAnano method. Our data reveals that HAnano® modulates higher expression of genes related with endothelial cell performance and viability, such as VEGF, eNOS, and AKT, and further angiogenesis in vitro by promoting endothelial cell migration. Additionally, the data shows a significant extracellular matrix (ECM) remodeling, and this finding seems developing a dual role in promoting the expression of VEGF and control endothelial cell growth during angiogenesis. Altogether, these data prompted us to further validate this phenomenon by exploring genes related with the control of cell cycle and in fact our data shows that HAnano® promotes higher expression of CDK4 gene, while p21 and p15 genes (suppressor genes) were significantly lower. In conjunction, our data shows for the first time that HAnano®-coated surfaces drive angiogenesis by stimulating a proliferative and migration phenotype of endothelial cells, and this finding opens novel comprehension about osseointegration mechanism considering nanosized hydroxyapatite coating dental implants.

Biobancos en otorrinolaringología / Biobanks in otolaryngology

Resumen Los biobancos son una innovadora herramienta biotecnológica y un recurso fundamental para el continuo avance en la investigación científica biomédica, y para el advenimiento de la medicina de precisión. Se han desarrollado de forma exponencial durante los últimos 20 años en el mundo, como también a nivel de nuestro país, con la creación de 10 biobancos desde el año 2004. En ellos se almacenan y organizan distintos tipos de muestras biológicas, asociadas a datos epidemiológicos y genéticos de donantes voluntarios. Todos los especímenes almacenados deben ser preservados con estándares de calidad garantizados, a modo de asegurar trazabilidad, integridad y calidad de las muestras. A pesar de que la mantención de un biobanco puede significar altos costos, a fin de cuentas, abaratan costos de los estudios clínicos, dado que es precisamente el biobanco quien se encarga de la obtención de datos y muestras clínicas confiables, permitiendo realizar múltiples estudios a partir de las mismas muestras. A través de este proceso, los biobancos permiten mantener una fuente confiable de recur-sos para la investigación en diversas áreas de la medicina, dentro de ellas la otorrinolaringología. En otorrinolaringología, los biobancos han significado un gran avance, facilitando la investigación en relación con hipoacusia, presbiacusia y tinnitus, así como en el área oncológica. En un futuro, se espera que la comunidad científica haga uso de este recurso, pudiendo expandir su utilidad no solo en el área médica, sino también en otras profesiones de la salud, maximizando así su gigantesco potencial.

Abstract Biobanks are novel biotechnological tools and a fundamental resource for the constant development of biomedical research, as much as for the growing practice of precision medicine. They have proliferated worldwide over the past 20 years and Chile has not been left behind with the creation of 10 bio-banks since 2004. Biobanks store and organize different types of biological samples associated with epidemiological and genetic data from volunteer donors. These samples are stored and preserved under guaranteed quality standards to ensure their traceability, integrity, and quality. Even though the price of maintaining a biobank may seem high, after all, they reduce the costs of research, since biobanks are responsible of the acquisition and storage of data and samples, allowing the performance of multiple studies from the same collection of specimens. In this direction, biobanks grant a constant source of well-founded scientific material for investigation in a wide range of medical fields, such as otolaryngology among them. In otolaryngology, the biobanks have meant a great improvement, facilitating investigations related to deafness, presbycusis, tinnitus and oncology. In the future we hope the scientific community will expand the use this innovative tool over a broader medical field and towards other health-related professions, making the most of its enormous potential.

Changes in the distribution of muscle activity when using a passive trunk exoskeleton depend on the type of working task: A high-density surface EMG study.

Exoskeleton effectiveness in reducing muscle efforts has been usually assessed from surface electromyograms (EMGs) collected locally. It has been demonstrated, however, muscle activity redistributes within the low back muscles during static and dynamic contractions, suggesting the need of detecting surface EMGs from a large muscle region to reliably investigate changes in global muscle activation. This study used high-density surface EMG to assess the effects of a passive trunk exoskeleton on the distribution of low back muscles' activity during different working tasks. Ten, male volunteers performed a static and a dynamic task with and without the exoskeleton. Multiple EMGs were sampled bilaterally from the lumbar erector spinae muscles while the hip and knee angles were measured unilaterally. Key results revealed for the static task exoskeleton led to a decrease in the average root mean square (RMS) amplitude (∼10%) concomitantly with a stable mean frequency and a redistribution of muscle activity (∼0.5 cm) in the caudal direction toward the end of the task. For the dynamic task, the exoskeleton reduced the RMS amplitude (∼5%) at the beginning of the task and the variability in the muscle activity distribution during the task. Moreover, a reduced range of motion in the lower limb was observed when using the exoskeleton during the dynamic task. Current results support the notion the passive exoskeleton has the potential to alleviate muscular loading at low back level especially for the static task.

Noninvasive ventilatory support in morbid obesity.

BACKGROUND: In the conventional management of the morbidly obese that normalizes the apnea-hypopnea index (AHI), CO2 levels often remain elevated. METHODS: A retrospective review of morbidly obese patients using volume preset settings up to 1800ml to positive inspiratory pressures (PIPs) of 25-55cm H2O, or pressure control at 25-50cm H2O pressure via noninvasive interfaces up to continuously (CNVS). RESULTS: Twenty-six patients, mean 55.6±14.8 years of age, weight 108-229kg, mean BMI 56.1 (35.5-77)kg/m2, mean AHI 69.0±24.9, depended on up to CNVS for 3 weeks to up to 66 years. There were eleven extubations and seven decannulations to CNVS despite failure to pass spontaneous breathing trials. Thirteen were CNVS dependent for 92.2 patient-years with little to no ventilator free breathing ability (VFBA). Six used NVS from 10 to 23h a day, and others only for sleep. Fifteen patients with cough peak flows (CPF) less than 270L/m had access to mechanical insufflation-exsufflation (MIE) in the peri-extubation/decannulation period and long-term. The daytime end-tidal (Et)CO2 of 14 who were placed on sleep NVS without extubation or decannulation to it decreased from mean EtCO2 61.0±9.3-38.5±3.6mm Hg and AHI normalized to 2.2. Blood gas levels were normal while using NVS/CNVS. Pre-intubation PaCO2 levels, when measured, were as high as 183mm Hg before extubation to CNVS. CONCLUSIONS: Ventilator unweanable morbidly obese patients can be safely extubated/decannulated and maintained indefinitely using up to CNVS rather than resort to tracheotomies.

Early use of alcohol associated with sociodemographic, nutritional and lifestyle factors: survival analysis with Brazilian students.

BACKGROUND: To evaluate the early age of onset (AOO) of alcohol consumption and its association with sociodemographic, nutritional and lifestyle characteristics. METHODS: A national cross-sectional multi-centered study assessed 12-17-year old adolescents from 1247 public and private schools in 124 Brazilian municipalities with more than 100 000 habitants. Our variable of interest was the AOO of alcohol consumption. Covariates comprised sociodemographic status, lifestyle habits and nutritional parameters. We used adapted survival models to investigate the association between covariates and the AOO of alcohol consumption. RESULTS: From a sample of 67 672 adolescents, 50% were females. The mean AOO of alcohol consumption was 12.9 years. Male adolescents had a lower mean age of alcohol experimentation when compared to females in Northeast and South regions. The difference between private and public school for AOO was observed only for the Northeast Region (12.6 versus 13.1, respectively). Adolescents who reported smoking or mental health problems or from the Southern Region presented earlier alcohol use. Physical activity and overweight were positively associated with earlier use of alcohol. CONCLUSIONS: There is no homogeneity in the AOO of alcohol consumption among adolescents, which should be considered when formulating public policies and government campaigns directed toward reducing alcohol consumption.

Recurrence quantification analysis with wavelet denoising and the characterization of magnetic flux emergence regions in solar photosphere.

Solar systems complexity, multiscale, and nonlinearity are governed by numerous and continuous changes where the sun magnetic fields can successfully represent many of these phenomena. Thus, nonlinear tools to study these challenging systems are required. The dynamic system recurrence approach has been successfully used to deal with this kind challenge in many scientific areas, objectively improving the recognition of state changes, randomness, and degrees of complexity that are not easily identified by traditional techniques. In this work we introduce the use of these techniques in photospheric magnetogram series. We employ a combination of recurrence quantification analysis with a preprocessing denoising wavelet analysis to characterize the complexity of the magnetic flux emergence in the solar photosphere. In particular, with the developed approach, we identify regions of evolving magnetic flux and where they present a large degree of complexity, i.e., where predictability is low, intermittence is high, and low organization is present.

Does the amplitude of biceps brachii M waves increase similarly in both limbs during staircase, electrically elicited contractions?

OBJECTIVE: Humans usually tend to control more finely muscle force production in dominant than non-dominant upper limbs. It is well established that motor unit recruitment is a key mechanism by which muscle force is controlled, and we hypothesized that a relatively smaller number of motor units may be recruited in muscles of dominant than non-dominant limbs for any given increase in synaptic input. Hence, we investigated peripheral properties of dominant and non-dominant biceps brachii through the analysis of M-wave responses to incremental electrical stimulation. APPROACH: Current pulses at progressively greater intensities were applied in the proximal region of biceps brachii of 16 subjects while surface electromyograms were recorded with a grid of electrodes in the distal region. M-wave amplitude was averaged across channels and normalized with respect to the maximum amplitude value, separately for each stimulation intensity and limb. Amplitude-current intensity curves were interpolated to provide an equal number of stimulation levels between limbs. Differences between dominant and non-dominant arms were assessed through the average increase in M-wave amplitude for consecutive stimulation intensities (increments). MAIN RESULTS: Wilcoxon's signed-rank test showed that increments in the M-wave amplitude were significantly smaller (p = 0.017) in dominant than non-dominant biceps brachii. SIGNIFICANCE: The results suggest that there was a more gradual recruitment of motor units in biceps brachii of dominant than non-dominant arms. This is in agreement with the hypothesis of a broader spectrum of motor unit recruitment thresholds in the dominant arm, which may contribute to a finer regulation of force production.

Hepatitis C in Brazil: lessons learned with boceprevir and telaprevir.

In 2012, the first-generation protease inhibitors telaprevir (TVR) and boceprevir (BOC) were introduced in the Brazilian health system for treatment of chronic hepatitis C, after their approval by the National Committee for Health Technology Incorporation (CONITEC). However, these medicines were discontinued in 2015. The short period of use in therapy and their high cost require a discussion about the consequences for patients and for the health system of the early incorporation of new therapies. The article presents a qualitative analysis of the incorporation process of both medications in Brazil and the results of a multicenter study that included patients treated with BOC or TVR between January 2011 and December 2015 in five Brazilian cities. The study included 855 patients (BOC: n=247) and (TVR: n=608). The document analysis showed that CONITEC's decision to incorporate BOC and TVR was based on results of phase III clinical trials that compared sustained virologic response (SVR) rates of patients treated with BOC and TVR with rates of those that received placebo. However, these studies included a low percentage of cirrhotic patients. The SVR rates observed in this multicenter study were worse than clinical trials pointed out (BOC: 45.6%; TVR: 51.8%), but similar to those achieved with previously adopted therapies. The discontinuation rate due to adverse events was (BOC: 15.4%; TVR: 12.7%). Based on these unsatisfactory results, the study brings a discussion that goes beyond the therapy outcomes, exploring the incorporation of these high-cost medicines and the related decision-making process, contributing to future decisions in medicine policies and in the treatment of chronic hepatitis C.

Interannual variability in Dinophysis spp. abundance and toxin accumulation in farmed mussels (Perna perna) in a subtropical estuary.

This study evaluated an 8-year dataset (2007 to 2015, except 2008) in the attempt to identify the most susceptible periods for the occurrence of diarrheic shellfish poisoning (DSP) episodes associated with the presence of toxigenic dinoflagellates, Dinophysis spp., in the mussel farming area of Babitonga Bay (southern Brazil). Dinophysis acuminata complex was the most frequent (present in 66% of the samples) and abundant (max. 4100 cells L-1) taxon, followed by D. caudata (14%; max. 640 cells L-1) and D. tripos (0.9%; max. 50 cells L-1). There was a marked onset of the annual rise in Dinophysis spp. abundance during weeks 21-25 (early winter) of each year, followed by a second peak on week 35 (spring). Mussel (Perna perna) samples usually started testing positive in DSP mouse bioassays (MBA) in late winter. Positive results were more frequent in 2007 and 2011 when the mean D. acuminata complex abundance was ~ 500 cells L-1. Although positive DSP-MBA results were observed in only 11% of the samples during the studied period, the toxin okadaic acid (OA) was present in 90% of the analyzed mussels (max. 264 µg kg-1). MBA results were positive when D. acuminata complex cell densities exceed 1200 ± 300 cells L-1, while trace toxin amounts could be detected at cell densities as low as 150 ± 50 cells L-1 (free OA) to 200 ± 100 cells L-1 (conjugated OA). Low salinity and the meteorological conditions triggered by La Niña events were the main factors associated with both Dinophysis abundance and OA accumulation in mussels.

Antenatal paternal adjustment and paternal attitudes after infertility treatment.

STUDY QUESTION: Do mode of conception [ART versus Natural (NC)] and depression have an interactive effect on antenatal paternal adjustment and paternal attitudes? SUMMARY ANSWER: Depression increased the negative effect of ART on antenatal paternal adjustment and paternal attitudes, specifically on antenatal marital relationship satisfaction. WHAT IS KNOWN ALREADY: Research on antenatal paternal adjustment and paternal attitudes after ART is scarce and has produced inconsistent results. STUDY DESIGN, SIZE, DURATION: This cross-sectional study assessed 197 primiparous men (71 ART and 126 NC) during their partner's second trimester of gestation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were derived from three larger longitudinal studies recruited at public Health Services in Northern Portugal. All men, for who this was their first child and had filled in a socio-demographic questionnaire, measures of depression and anxiety, and antenatal paternal adjustment and paternal attitudes were selected. MAIN RESULTS AND THE ROLE OF CHANCE: An interaction effect of mode of conception and depression was found on antenatal paternal adjustment and paternal attitudes. ART men showing high depressive symptomatology had lower antenatal marital relationship satisfaction than ART men showing low depressive symptomatology and NC men showing high or low depressive symptomatology. LIMITATIONS, REASONS FOR CAUTION: Due to the cross-sectional design of this study and the small sample size in the depression groups, the findings should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: Specialized psychological support should be available for ART men screened with high depressive symptomatology as part of routine prenatal care appointments. STUDY FUNDING/COMPETING INTEREST(S): This study was conducted at Psychology Research Centre (UID/PSI/ 01662/2013), University of Minho, and at the Unidade de Investigação em Epidemiologia-Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (UID/DTP/04750/2013). It was supported by the Foundation for Science and Technology (Portuguese Ministry of Education and Science) through National funds and co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653) and through the Operational Programme Factors of Competitiveness-COMPETE within the project 'Health, Governance and Accountability in Embryo Research: Couples' Decisions About the Fates of Embryos' (FCOMP-01-0124-FEDER-014453), the FCT Investigator contract IF/01674/2015 and PhD grants (SFRH/BD/115048/2016, SFRH/BD/75807/2011 and SFRH/BD/40146/2007). The authors have no conflicts of interest.

Pneumococcal nasopharyngeal carriage among children in Brazil prior to the introduction of the 10-valent conjugate vaccine: a culture- and PCR-based survey.

We performed two different approaches (broth enrichment step prior to culture (BEC) and PCR (BEPCR)) for detecting Streptococcus pneumoniae from nasopharyngeal specimens collected from 242 children aged <6 years attending one hospital (n = 140) and one childcare centre (n = 102) in a major urban area in Brazil. These specimens were collected immediately before the introduction of the 10-valent pneumococcal conjugate vaccine (PCV10) and the 13-valent vaccine (PCV13) for routine use in Brazil. Results were compared with previous findings obtained with direct culture (DC) on a selective medium. Colonisation prevalence was 58·3% (n = 141), being higher among children attending the childcare centre (62·7% vs. 55%). The culture-based methods (DC and BEC) enabled the detection of S. pneumoniae in 119 (49·2%) and 115 (47·5%) children, respectively. The PCR-based method (BEPCR) was more sensitive and 137 (56·6%) carriers were identified. Twenty-six serogroups/serotypes were identified, predominantly 6B, 19F, 14, 6A, 15C and 23F. Multiple colonisation was observed in 13 (5·4%) children. The estimated serotypes coverage of available PCVs was 40·4% for the 10-valent (included in the Brazilian immunisation programme) and 55·8% for the 13-valent (only available in private clinics). The use of robust approaches to obtain a more realistic insight about the asymptomatic carrier status is of paramount importance to estimate and assess the impact of vaccine implementation. The combination between culture-based and molecular methods constitutes a suitable strategy.

Serum n-3 polyunsaturated fatty acids are inversely associated with longitudinal changes in depressive symptoms during pregnancy.

BACKGROUNDS: N-3 polyunsaturated fatty acids (PUFAs) have been hypothesised to be protective for depression during pregnancy. However, there are few data and no consensus regarding this association. In this line, we aim to evaluate if the concentration of n-3 and n-6 PUFAs, and their ratio, are associated with depressive symptoms throughout pregnancy. METHOD: A prospective cohort of 172 Brazilian women was followed at 5-13th, 20-26th and 30-36th weeks of gestation. The presence of depressive symptoms was evaluated using the Edinburgh Postnatal Depression Scale (EPDS) at each pregnancy trimester. Depression was defined as an EPDS score ≥11. The concentrations of n-3 [α-linolenic acid; eicosapentaenoic acid (EPA); docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA)] and n-6 PUFAs [linoleic acid; γ linolenic acid; eicosadienoic acid; eicosatrienoic acid; arachidonic acid; docosatetraenoic acid and docosapentaenoic acid] were expressed as absolute (µg/ml) values. The total n-6/n-3 ratio was calculated. Statistical analyses were performed using univariate and adjusted random intercept logistic model for each fatty acid (FA) considering the longitudinal nature of data. Covariates were selected as potential confounders based on their biological plausibility of having an association with the concentration of FA and depressive symptoms during pregnancy. RESULTS: The prevalence of depressive symptoms was high in all pregnancy trimesters (1st = 33.7%; 2nd = 18.9%; 3rd = 17.4%). We did not find differences in means FA concentrations by depressive symptom classification, for each follow-up visit. The women presented a 5% decrease in the odds of having depressive symptoms for each one-week increase in the gestational age. As individual women progressed through pregnancy, higher concentrations of EPA (odds ratio (OR) = 0.92; 95% CI: 0.86-0.99), DHA (OR = 0.96; 95% CI: 0.93-0.99), DPA (OR = 0.87; 95% CI: 0.77-0.99) and total n-3 (OR = 0.98; 95% CI: 0.96-0.99) were associated with a lower odds of depressive symptoms, while higher total n-6/n-3 ratio were associated with greater odds of depressive symptoms (OR = 1.40; 95% CI: 1.09-1.79). We detected a decrease in the probability of depressive symptoms as concentrations of total n-3 FA, α-linolenic acid, DPA, and DHA increased. We also observed a sharper decline for women with initial greater chance of depressive symptoms compared with those with lower chance of having these symptoms. CONCLUSIONS: We found a high prevalence of depressive symptoms in low-income Brazilian pregnant women and no significant associations between n-6 FA and depressive symptoms. Lower serum concentrations of DHA, EPA and DPA and a higher n-6/n-3 ratio at each pregnancy trimester were associated with higher odds of depressive symptoms throughout pregnancy.