In vitro and in vivo evaluation of novel chromeno[2,3-d]pyrimidinones as therapeutic agents for triple negative breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and the limited therapeutic options show poor efficacy in patients, associated to severe side effects and development of resistance. Considering that chromene-based scaffolds proved to be attractive candidates for cancer therapy, herein we prepared new chromeno[2,3-d]pyrimidinone derivatives by a simple two step procedure, starting from the reaction of cyanoacetamide and a salicylaldehyde. A cell viability screening in several breast cancer cell lines allowed to identify two promising compounds with IC50 values in the low micromolar range for TNBC cells. These chromenes inhibited cell proliferation, induced cell cycle arrest and triggered cell death through apoptosis. In vivo studies revealed a safe profile in invertebrate and vertebrate animal models and confirmed their capacity to inhibit tumor growth in the CAM model, inducing significant tumor regression after 4 days of treatment. The two compounds identified in this study are promising drug candidates for TNBC treatment and valuable hits for future optimization, using the versatile synthetic platform that was developed.

British societies guideline on the management of emergencies in implantable left ventricular assist device recipients in transplant centres.

An implantable left ventricular assist device (LVAD) is indicated as a bridge to transplantation or recovery in the United Kingdom (UK). The mechanism of action of the LVAD results in a unique state of haemodynamic stability with diminished arterial pulsatility. The clinical assessment of an LVAD recipient can be challenging because non-invasive blood pressure, pulse and oxygen saturation measurements may be hard to obtain. As a result of this unusual situation and complex interplay between the device and the native circulation, resuscitation of LVAD recipients requires bespoke guidelines. Through collaboration with key UK stakeholders, we assessed the current evidence base and developed guidelines for the recognition of clinical deterioration, inadequate circulation and time-critical interventions. Such guidelines, intended for use in transplant centres, are designed to be deployed by those providing immediate care of LVAD patients under conditions of precipitous clinical deterioration. In summary, the Joint British Societies and Transplant Centres LVAD Working Group present the UK guideline on management of emergencies in implantable LVAD recipients for use in advanced heart failure centres. These recommendations have been made with a UK resuscitation focus but are widely applicable to professionals regularly managing patients with implantable LVADs.

Effects of Graphene Oxide Nanosheets in Freshwater Biofilms.

Graphene oxide (GO) properties make it a promising material for graphene-based applications in areas such as biomedicine, agriculture, and the environment. Thus, its production is expected to increase, reaching hundreds of tons every year. One GO final destination is freshwater bodies, possibly affecting the communities of these systems. To clarify the effect that GO may impose in freshwater communities, a fluvial biofilm scraped from submerged river stones was exposed to a range (0.1 to 20 mg/L) of GO concentrations during 96 h. With this approach, we hypothesized that GO can: (1) cause mechanical damage and morphological changes in cell biofilms; (2) interfere with the absorption of light by biofilms; (3) and generate oxidative stress, causing oxidative damage and inducing biochemical and physiological alterations. Our results showed that GO did not inflict mechanical damage. Instead, a positive effect is proposed, linked to the ability of GO to bind cations and increase the micronutrient availability to biofilms. High concentrations of GO increased photosynthetic pigment (chlorophyll a, b, and c, and carotenoids) content as a strategy to capture the available light more effectively as a response to the shading effect. A significant increase in the enzymatic (SOD and GSTs activity) and low molecular weight (lipids and carotenoids) antioxidant response was observed, that efficiently reduced oxidative stress effects, reducing the level of peroxidation, and preserving membrane integrity. Being complex entities, biofilms are more similar to environmental communities and may provide more accurate information to evaluate the impact of GO in aquatic systems.

Edible Seaweeds Extracts: Characterization and Functional Properties for Health Conditions.

Seaweeds are popular foods due to claimed beneficial health effects, but for many there is a lack of scientific evidence. In this study, extracts of the edible seaweeds Aramé, Nori, and Fucus are compared. Our approach intends to clarify similarities and differences in the health properties of these seaweeds, thus contributing to target potential applications for each. Additionally, although Aramé and Fucus seaweeds are highly explored, information on Nori composition and bioactivities is scarce. The aqueous extracts of the seaweeds were obtained by decoction, then fractionated and characterized according to their composition and biological activity. It was recognized that fractioning the extracts led to bioactivity reduction, suggesting a loss of bioactive compounds synergies. The Aramé extract showed the highest antioxidant activity and Nori exhibited the highest potential for acetylcholinesterase inhibition. The identification of the bioactive compounds in the extracts allowed to see that these contained a mixture of phloroglucinol polymers, and it was suggested that Nori's effect on acetylcholinesterase inhibition may be associated with a smaller sized phlorotannins capable of entering the enzyme active site. Overall, these results suggest a promising potential for the use of these seaweed extracts, mainly Aramé and Nori, in health improvement and management of diseases, namely those associated to oxidative stress and neurodegeneration.

Mechanical life support algorithm for emergency management of patient receiving extracorporeal membrane oxygenation.

BACKGROUND: There are limited practical advanced life support algorithms to aid teams in the management of cardiac arrest in patients on extracorporeal membrane oxygenation (ECMO). METHODS: In our specialist tertiary referral centre we developed, by iteration, a novel resuscitation algorithm for ECMO emergencies which we validated through simulation and assessment of our multi-disciplinary team. A Mechanical Life Support course was established to provide theoretical and practical education combined with simulation to consolidate knowledge and confidence in algorithm use. We assessed these measures using confidence scoring, a key performance indicator (the time taken to resolve gas line disconnection) and a multiple choice question (MCQ) examination. RESULTS: Following this intervention the median confidence scores increased from 2 (Interquartile range IQR 2, 3) to 4 (IQR 4, 4) out of maximum 5 (n = 53, p < 0.0001). Theoretical knowledge assessed by median MCQ score increased from 8 (6, 9) to 9 (7, 10) out of maximum 11 (n = 53, p0.0001). The use of the ECMO algorithm reduced the time taken by teams in a simulated emergency to identify a gas line disconnection and resolve the problem from median 128 s (65, 180) to 44 s (31, 59) (n = 36, p 0.001) and by a mean of 81.5 s (CI 34, 116, p = 0.001). CONCLUSIONS: We present an evidence based practical ECMO resuscitation algorithm that provides guidance to clinical teams responding to cardiac arrest in ECMO patients covering both patient and ECMO troubleshooting.

Targeted treatment of triple-negative-breast cancer through pH-triggered tumour associated macrophages using smart theranostic nanoformulations.

Triple-negative breast cancer (TNBC) represents 15-25 % of the new breast cancer cases diagnosed worldwide every year. TNBC is among the most aggressive and worst prognosis breast cancer, mainly because targeted therapies are not available. Herein, we developed a magnetic theranostic hybrid nanovehicle for targeted treatment of TNBC through pH-triggered tumour associated macrophages (TAMs) targeting. The lipid core of the nanovehicle was composed of a Carnaúba wax matrix that simultaneously incorporated iron oxide nanoparticles and doxorubicin (DOX) - a chemotherapeutic drug. These drug-loaded wax nanovehicles were modified with a combination of two functional and complementary molecules: (i) a mannose ligand (macrophage targeting) and (ii) an acid-sensitive sheddable polyethylene glycol (PEG) moiety (specificity). The TAMs targeting strategy relied on the mannose - mannose receptor recognition exclusively after acid-sensitive "shedding" of the PEG in the relatively low tumour microenvironment pH. The pH-induced targeting capability towards TAMs was confirmed in vitro in a J774A.1 macrophage cell line at different pH (7.4 and 6.5). Biocompatibility and efficacy of the final targeted formulations were demonstrated in vitro in the TNBC MDA-MB-231 cell line and in vivo in an M-Wnt tumour-bearing (TNBC) mouse model. A preferential accumulation of the DOX-loaded lipid nanovehicles in the tumours of M-Wnt-tumour bearing mice was observed, which resulted both on an efficient tumour growth inhibition and a significantly reduced off-target toxicity compared to free DOX. Additionally, the developed magnetic hybrid nanovehicles showed outstanding performances as T2-contrast agents in magnetic resonance imaging (r2 ≈ 400-600 mM-1·s-1) and as heat generating sources in magnetic hyperthermia (specific absorption rate, SAR ≈ 178 W·g-1Fe). These targeted magnetic hybrid nanovehicles emerge as a suitable theranostic option that responds to the urgent demand for more precise and personalized treatments, not only because they are able to offer localized imaging and therapeutic potential, but also because they allow to efficiently control the balance between safety and efficacy.

Eating Patterns and Dietary Interventions in ADHD: A Narrative Review.

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders in childhood, affecting ~7% of children and adolescents. Given its adverse health outcomes and high healthcare and societal costs, other treatment options beyond pharmacotherapy have been explored. Case-control studies have shown that dietary patterns may influence the risk of ADHD, and specific dietary interventions have been proposed as coadjuvant treatments in this disorder. These include nutritional supplements, gut microbiome-targeted interventions with biotics, and elimination diets. The purpose of this review is to examine which dietary patterns are most associated with ADHD and to summarize the existing evidence for the clinical use of dietary interventions. The literature showed that non-healthy dietary patterns were positively associated with ADHD, whereas healthy patterns were negatively associated. As for nutritional supplements, only vitamin D and vitamin D + magnesium appeared to improve ADHD symptoms when baseline levels of vitamin D were insufficient/deficient. Regarding biotics, evidence was only found for Lactobacillus rhamnosus GG and for multi-species probiotic supplementation. Elimination diets have scarce evidence and lead to nutritional deficiencies, so caution is advised. Overall, more robust scientific evidence is required for these dietary interventions to be implemented as part of ADHD therapy.

Nanoformulation of Seaweed Eisenia bicyclis in Albumin Nanoparticles Targeting Cardiovascular Diseases: In Vitro and In Vivo Evaluation.

Natural products, especially those derived from seaweeds, are starting to be seen as effective against various diseases, such as cardiovascular diseases (CVDs). This study aimed to design a novel oral formulation of bovine albumin serum nanoparticles (BSA NPs) loaded with an extract of Eisenia bicyclis and to validate its beneficial health effects, particularly targeting hypercholesterolemia and CVD prevention. Small and well-defined BSA NPs loaded with Eisenia bicyclis extract were successfully prepared exhibiting high encapsulation efficiency. Antioxidant activity and cholesterol biosynthesis enzyme 3-hydroxy-3 methylutaryl coenzyme A reductase (HMGR) inhibition, as well as reduction of cholesterol permeation in intestinal lining model cells, were assessed for the extract both in free and nanoformulated forms. The nanoformulation was more efficient than the free extract, particularly in terms of HMGR inhibition and cholesterol permeation reduction. In vitro cytotoxicity and in vivo assays in Wistar rats were performed to evaluate its safety and overall effects on metabolism. The results demonstrated that the Eisenia bicyclis extract and BSA NPs were not cytotoxic against human intestinal Caco-2 and liver HepG2 cells and were also safe after oral administration in the rat model. In addition, an innovative approach was adopted to compare the metabolomic profile of the serum from the animals involved in the in vivo assay, which showed the extract and nanoformulation's impact on CVD-associated key metabolites. Altogether, these preliminary results revealed that the seaweed extract and the nanoformulation may constitute an alternative natural dosage form which is safe and simple to produce, capable of reducing cholesterol levels, and consequently helpful in preventing hypercholesterolemia, the main risk factor of CVDs.

Estimating the effect of the wMel release programme on the incidence of dengue and chikungunya in Rio de Janeiro, Brazil: a spatiotemporal modelling study.

BACKGROUND: Introgression of genetic material from species of the insect bacteria Wolbachia into populations of Aedes aegypti mosquitoes has been shown in randomised and non-randomised trials to reduce the incidence of dengue; however, evidence for the real-world effectiveness of large-scale deployments of Wolbachia-infected mosquitoes for arboviral disease control in endemic settings is still scarce. A large Wolbachia (wMel strain) release programme was implemented in 2017 in Rio de Janeiro, Brazil. We aimed to assess the effect of this programme on the incidence of dengue and chikungunya in the city. METHODS: 67 million wMel-infected mosquitoes were released across 28 489 locations over an area of 86·8 km2 in Rio de Janeiro between Aug 29, 2017 and Dec 27, 2019. Following releases, mosquitoes were trapped and the presence of wMel was recorded. In this spatiotemporal modelling study, we assessed the effect of the release programme on the incidence of dengue and chikungunya. We used spatiotemporally explicit mathematical models applied to geocoded dengue cases (N=283 270) from 2010 to 2019 and chikungunya cases (N=57 705) from 2016 to 2019. FINDINGS: On average, 32% of mosquitoes collected from the release zones between 1 month and 29 months after the initial release tested positive for wMel. Reduced wMel introgression occurred in locations and seasonal periods in which cases of dengue and chikungunya were historically high, with a decrease to 25% of mosquitoes testing positive for wMel during months in which disease incidence was at its highest. Despite incomplete introgression, we found that the releases were associated with a 38% (95% CI 32-44) reduction in the incidence of dengue and a 10% (4-16) reduction in the incidence of chikungunya. INTERPRETATION: Stable establishment of wMel in the geographically diverse, urban setting of Rio de Janeiro seems to be more complicated than has been observed elsewhere. However, even intermediate levels of wMel seem to reduce the incidence of disease caused by two arboviruses. These findings will help to guide future release programmes. FUNDING: Bill & Melinda Gates Foundation and the European Research Council.

The Lockdown Impact on the Relations between Portuguese Parents and Their 1- to 3-Year-Old Children during the COVID-19 Pandemic.

Many countries have applied mandatory confinement measures in response to the COVID-19 pandemic, such as school and kindergarten closures, which confined families to their homes. The study concerns the impacts of the first COVID-19 lockdown on the relationships between Portuguese parents and their children, in a non-clinical population composed of fathers and mothers of children between the ages of 12 months and 3 years and 364 days. An online questionnaire (set by the research team) and the Parenting Daily Hassles Scale (PDHS) concerning the confinement period were applied between 17 June and 29 July 2020. To assess the impacts of the lockdown, outcomes regarding the impacts perceived by the parents, the potential regression in the development of children, and the willingness to promote changes in family routines in the future, were considered. Of the total sample (n = 1885), 95.4% of the parents (n = 1798) said that, after confinement, the relationship with their children had improved or remained similar to the pre-confinement period; 97.3% (n = 1835) noticed positive changes in the development of their children, and 63.7% (n = 1200) noted that the relationships with their children during the confinement period would lead to some changes in family routines in the future. Multivariate regression analyses showed that most of the sociodemographic variables chosen were not associated with the outcomes. However, significant levels of pressure over parenting and parental overload (reported by high scores in the PDHS intensity and frequency scales), challenging behaviors of the children, and the impacts they had on parental tasks had negative influences on the studied outcomes. On the contrary, the number of adults living with their children, the perceptions regarding the development of their children, and sharing new experiences with them were significant factors for positively-perceived impacts on the relationships between them or in the desire to bring about changes in family routines in the future. The impacts of the lockdown on the relationships between parents and children aged between 1 and 3 years old were more dependent on relational aspects and on the parents' sense of competence in exercising parental functions. We conclude that, despite the increased demands imposed by the lockdown, nearly all of the parents evaluated the quality of the relationship with their children as positive after this period.

EVITA Dengue: a cluster-randomized controlled trial to EValuate the efficacy of Wolbachia-InfecTed Aedes aegypti mosquitoes in reducing the incidence of Arboviral infection in Brazil.

BACKGROUND: Arboviruses transmitted by Aedes aegypti including dengue, Zika, and chikungunya are a major global health problem, with over 2.5 billion at risk for dengue alone. There are no licensed antivirals for these infections, and safe and effective vaccines are not yet widely available. Thus, prevention of arbovirus transmission by vector modification is a novel approach being pursued by multiple researchers. However, the field needs high-quality evidence derived from randomized, controlled trials upon which to base the implementation and maintenance of vector control programs. Here, we report the EVITA Dengue trial design (DMID 17-0111), which assesses the efficacy in decreasing arbovirus transmission of an innovative approach developed by the World Mosquito Program for vector modification of Aedes mosquitoes by Wolbachia pipientis. METHODS: DMID 17-0111 is a cluster-randomized trial in Belo Horizonte, Brazil, with clusters defined by primary school catchment areas. Clusters (n = 58) will be randomized 1:1 to intervention (release of Wolbachia-infected Aedes aegypti mosquitoes) vs. control (no release). Standard vector control activities (i.e., insecticides and education campaigns for reduction of mosquito breeding sites) will continue as per current practice in the municipality. Participants (n = 3480, 60 per cluster) are children aged 6-11 years enrolled in the cluster-defining school and living within the cluster boundaries who will undergo annual serologic surveillance for arboviral infection. The primary objective is to compare sero-incidence of arboviral infection between arms. DISCUSSION: DMID 17-0111 aims to determine the efficacy of Wolbachia-infected mosquito releases in reducing human infections by arboviruses transmitted by Aedes aegypti and will complement the mounting evidence for this method from large-scale field releases and ongoing trials. The trial also represents a critical step towards robustness and rigor for how vector control methods are assessed, including the simultaneous measurement and correlation of entomologic and epidemiologic outcomes. Data from this trial will inform further the development of novel vector control methods. TRIAL REGISTRATION: ClinicalTrials.gov NCT04514107 . Registered on 17 August 2020 Primary sponsor: National Institute of Health, National Institute of Allergy and Infectious Diseases.

Renal cell carcinoma therapy: Current and new drug candidates.

Renal cell carcinoma (RCC) is the most common and lethal tumor of the urological system. Curative treatment of localized RCC includes nephrectomy, radio-ablation, and active surveillance, whereas metastatic RCC (mRCC) requires a combination of surgery and systemic therapy. Response to conventional therapy is limited but, recently, many novel therapies for mRCC have emerged, including targeted therapies and new immunotherapeutic agents. Nevertheless, development of resistance and limited durable responses demand new anticancer candidates with improved selectivity and efficacy. In this review, we summarize recent preclinical studies of novel natural and synthetic compounds to treat RCC, detailing their mechanisms of action and anticancer activities.

Anxiety, depression and urological cancer outcomes: A systematic review.

PURPOSE: The interplay between physical and mental aspects of a cancer diagnosis are well recognised. However, little consensus exists on the impact of depression and anxiety on urological cancer outcomes. Therefore, this systematic review aimed to investigate the relationship between these conditions and functional or oncological outcomes in urological malignancy. MATERIALS AND METHODS: A systematic search was conducted using PubMed, Embase, PsycINFO and Global Health databases up to June 2020. Studies evaluating the relationship of anxiety and depression disorders or symptoms on functional and mortality outcomes were included. Outcome measures included validated urinary, sexual, body image questionnaire scores and all-cause or disease-specific mortality. RESULTS: Of 3,966 studies screened, 25 studies with a total of 175,047 urological cancer patients were included. Significant anxiety and depressive symptoms and disorders were found to impact functional outcomes in several cancer types. A consistent negative association existed for sexual function in prostate, testicular and penile cancer patients. Additionally, poorer urinary function scores were seen in prostate cancer, with increased body image issues in testicular and prostate cancer. Importantly, both overall and disease-specific mortality outcomes were poorer in bladder and prostate cancer patients. CONCLUSIONS: Co-existing depression and anxiety appears to be negatively associated with functional and mortality outcomes in urological cancers. This appears especially evident in male cancers, including prostate and testicular cancer. Although not proving causation, these findings highlight the importance of considering mental wellbeing during follow-up for early recognition and treatment. However, current evidence remains heterogenous, with further studies required exploring patients at risk.

Large-Scale Deployment and Establishment of Wolbachia Into the Aedes aegypti Population in Rio de Janeiro, Brazil.

Traditional methods of vector control have proven insufficient to reduce the alarming incidence of dengue, Zika, and chikungunya in endemic countries. The bacterium symbiont Wolbachia has emerged as an efficient pathogen-blocking and self-dispersing agent that reduces the vectorial potential of Aedes aegypti populations and potentially impairs arboviral disease transmission. In this work, we report the results of a large-scale Wolbachia intervention in Ilha do Governador, Rio de Janeiro, Brazil. wMel-infected adults were released across residential areas between August 2017 and March 2020. Over 131 weeks, including release and post-release phases, we monitored the wMel prevalence in field specimens and analyzed introgression profiles of two assigned intervention areas, RJ1 and RJ2. Our results revealed that wMel successfully invaded both areas, reaching overall infection rates of 50-70% in RJ1 and 30-60% in RJ2 by the end of the monitoring period. At the neighborhood-level, wMel introgression was heterogeneous in both RJ1 and RJ2, with some profiles sustaining a consistent increase in infection rates and others failing to elicit the same. Correlation analysis revealed a weak overall association between RJ1 and RJ2 (r = 0.2849, p = 0.0236), and an association at a higher degree when comparing different deployment strategies, vehicle or backpack-assisted, within RJ1 (r = 0.4676, p < 0.0001) or RJ2 (r = 0.6263, p < 0.0001). The frequency knockdown resistance (kdr) alleles in wMel-infected specimens from both areas were consistently high over this study. Altogether, these findings corroborate that wMel can be successfully deployed at large-scale as part of vector control intervention strategies and provide the basis for imminent disease impact studies in Southeastern Brazil.

Lignocellulolytic Enzyme Production from Wood Rot Fungi Collected in Chiapas, Mexico, and Their Growth on Lignocellulosic Material.

Wood-decay fungi are characterized by ligninolytic and hydrolytic enzymes that act through non-specific oxidation and hydrolytic reactions. The objective of this work was to evaluate the production of lignocellulolytic enzymes from collected fungi and to analyze their growth on lignocellulosic material. The study considered 18 species isolated from collections made in the state of Chiapas, Mexico, identified by taxonomic and molecular techniques, finding 11 different families. The growth rates of each isolate were obtained in culture media with African palm husk (PH), coffee husk (CH), pine sawdust (PS), and glucose as control, measuring daily growth with images analyzed in ImageJ software, finding the highest growth rate in the CH medium. The potency index (PI) of cellulase, xylanase, and manganese peroxidase (MnP) activities was determined, as well as the quantification of lignin peroxidase (LiP), with the strains Phlebiopsis flavidoalba TecNM-ITTG L20-19 and Phanerochaete sordida TecNM-ITTG L32-1-19 being the ones with the highest PI of hydrolase activities with 2.01 and 1.83 cellulase PI and 1.95 and 2.24 xylanase PI, respectively, while Phlebiopsis flavidoalba TecNM-ITTG L20-19 and Trametes sanguinea TecNM-ITTG L14-19 with 7115 U/L LiP activity had the highest oxidase activities, indicating their ability to oxidize complex molecules such as lignin.

Effectiveness of Wolbachia-infected mosquito deployments in reducing the incidence of dengue and other Aedes-borne diseases in Niterói, Brazil: A quasi-experimental study.

BACKGROUND: The introduction of the bacterium Wolbachia (wMel strain) into Aedes aegypti mosquitoes reduces their capacity to transmit dengue and other arboviruses. Evidence of a reduction in dengue case incidence following field releases of wMel-infected Ae. aegypti has been reported previously from a cluster randomised controlled trial in Indonesia, and quasi-experimental studies in Indonesia and northern Australia. METHODOLOGY/PRINCIPAL FINDINGS: Following pilot releases in 2015-2016 and a period of intensive community engagement, deployments of adult wMel-infected Ae. aegypti mosquitoes were conducted in Niterói, Brazil during 2017-2019. Deployments were phased across four release zones, with a total area of 83 km2 and a residential population of approximately 373,000. A quasi-experimental design was used to evaluate the effectiveness of wMel deployments in reducing dengue, chikungunya and Zika incidence. An untreated control zone was pre-defined, which was comparable to the intervention area in historical dengue trends. The wMel intervention effect was estimated by controlled interrupted time series analysis of monthly dengue, chikungunya and Zika case notifications to the public health surveillance system before, during and after releases, from release zones and the control zone. Three years after commencement of releases, wMel introgression into local Ae. aegypti populations was heterogeneous throughout Niterói, reaching a high prevalence (>80%) in the earliest release zone, and more moderate levels (prevalence 40-70%) elsewhere. Despite this spatial heterogeneity in entomological outcomes, the wMel intervention was associated with a 69% reduction in dengue incidence (95% confidence interval 54%, 79%), a 56% reduction in chikungunya incidence (95%CI 16%, 77%) and a 37% reduction in Zika incidence (95%CI 1%, 60%), in the aggregate release area compared with the pre-defined control area. This significant intervention effect on dengue was replicated across all four release zones, and in three of four zones for chikungunya, though not in individual release zones for Zika. CONCLUSIONS/SIGNIFICANCE: We demonstrate that wMel Wolbachia can be successfully introgressed into Ae. aegypti populations in a large and complex urban setting, and that a significant public health benefit from reduced incidence of Aedes-borne disease accrues even where the prevalence of wMel in local mosquito populations is moderate and spatially heterogeneous. These findings are consistent with the results of randomised and non-randomised field trials in Indonesia and northern Australia, and are supportive of the Wolbachia biocontrol method as a multivalent intervention against dengue, chikungunya and Zika.

Comunicación en el consultorio de medicina familiar: trabajo multicéntrico, cualitativo cuantitativo, en los meses de abril a julio de 2014, en Buenos Aires, Rosario y Tucumán / Communication in Family Medicine practice: multicenter research trial, qualitative and quantitative, from April to June 2014. in the City of Buenos Aires, Rosario and Tucumán

Introducción: la comunicación es trascendental para la vida en sociedad. El éxito de cualquier entrevista clínica depende de la calidad de la comunicación entre el médico y el paciente. Distintos factores pueden interferir en esta, como el ambiente, el tiempo y las interrupciones. Objetivo: Evaluar el grado de comprensión del mensaje transmitido por el médico hacia el paciente. Material y método: Trabajo multicéntrico, cualitativo cuantitativo. Componente cuantitativo: descriptivo de corte transversal de abril a julio de 2014. Se incluyeron 1200 adultos de ambos sexos, que asistieron a los Ce.M.A.P y 40 médicos de familia. Componente cualitativo: Muestreo no probabilístico, intencional, hasta saturación de datos. Triangulación y convergencia de datos. Resultados y discusión: Respecto al componente cuantitativo, se encontró que nuestras hipótesis acerca de la falta de comprensión del mensaje (indicaciones y problema de salud) no pudieron comprobarse. Ya que las indicaciones realizadas por el médico tuvieron una adecuación total del 60% y comprendieron el problema de salud un 77% de los pacientes entrevistados. Para el componente cualitativo luego del análisis temático se obtuvieron barreras (tiempo, paciente polidemandante, ideas previas, omisión de indicaciones no farmacológicas) y facilitadores (conocimiento previo del problema de salud, longitudinalidad, paciente acompañado) para la comprensión del mensaje. Conclusiones: Los pacientes entienden el mensaje de sus médicos de familia, ya que contamos con herramientas concretas como la escucha empática, el proceso clínico centrado en la persona y la longitudinalidad en la atención (AU)

Introduction: communication is important for life in a society. Success in any clinical interview depends on the quality of patient-doctor communication. Different factors may interfere, like the environment, time and interruptions. Objective: Asses the level of understanding of the message given to the patient by the doctor. Material and method: Multicenter research trial, qualitative and quantitative. Quantitative component: cross sectional descriptive from April to June 2014. 1200 adults of both sexes who assisted to the primary health care center: "Ce.M.A.P." in the City of Buenos Aires, Rosario and Tucumán and 40 family practitioners. Qualitative component: nonprobability, intentional sampling upon data saturation. Data triangulation and convergence. Results and discussion: as regards the quantitative component, we found out that our hypothesis in relation to the lack of understanding in the message (indications and health problem) could not be proven. Since 60% of the practitioner's indications were followed and 77% of the interviewed patients understood the health problem. Considering the qualitative component after the thematic analysis, barriers (time, highly demanding patient, previous knowledge, omission of non-pharmacological indications) and facilitators were obtained (previous knowledge of health problem, longitudinality, accompanied patient) to understand the message. Conclusion: patients understand their family practitioner's message since we have specific tools like empathic listening, patient centered healthcare and longitudinality in attention (AU)

A Systematic Review on the Use of Qualitative and Quantitative Contrast-enhanced Ultrasound in Diagnosing Testicular Abnormalities.

Greyscale and color doppler ultrasound are the standard when investigating testicular lesions. However, they cannot provide information on the microvasculature. As such, differentiating benign from malignant tumors is challenging. Contrast-enhanced ultrasound (CEUS) uses ultrasound contrast agents that are exclusively intravascular to image the microvasculature. This review assessed CEUS outcomes in investigating intratesticular lesions and concluded that qualitative CEUS provides the most advantage by confirming vascularity, thus differentiating non-neoplastic from neoplastic lesions with added confidence, allowing for appropriate management. Whilst results for quantitative CEUS are promising in distinguishing malignant from benign neoplasms, further research on its benefits is required.

Phonological characteristics of European and Brazilian Portuguese in children with Speech Sound Disorders.

This study aims to describe and compare the phonological characteristics of European Portuguese and Brazilian Portuguese preschool and school age children with Speech Sound Disorders (SSD). Speech samples for the European Portuguese Group (EPG) (n = 13) were collected using Subteste Fonético e Fonológico of Teste Fonético e Fonológico Avaliação da Linguagem Pré-Escolar. For the Brazilian Portuguese Group (BPG) (n = 13) Prova de Nomeação de Fonologia of Teste de Linguagem Infantil ABFW was applied. Different phonological measures were considered. Groups were matched according to sex, age, and percentage of correct consonants (revised). EPG presented more weak syllable deletion (p = .00); absolute index and relative index had a higher number of omissions (p = .003). BPG had more substitutions (p = .004). Intragroup analysis showed differences between groups in the occurrence of phonological processes (p ≤ 0.00). The most occurring was gliding of liquids, cluster reduction and devoicing in both groups; for the absolute index and relative index, the EPG presented differences in omission (p = .003), and the BPG in substitution (p = .002). Results suggested differences between groups in phonological processes occurrence and a relation with the most frequent type of error. These findings may occur due to the variation of phonetic and phonological characteristics between European Portuguese and Brazilian Portuguese in the two phonological tests. Linguistic variations had not directly influenced the measures studied, which characterized SSD. European Portuguese and Brazilian Portuguese children with SSD demonstrated similar characteristics as to the type of errors and phonological processes.