Fidelity evaluation of the compared procedures for conducting the PVS-PREDIAPS implementation strategy to optimize diabetes prevention in primary care.

BACKGROUND: Assessing the fidelity of an implementation strategy is important to understand why and how the strategy influences the uptake of evidence-based interventions. The present study aims to assess the fidelity of the two procedures for engaging primary care (PC) professionals and for the deployment of an implementation strategy for optimizing type 2 diabetes prevention in routine PC within the PREDIAPS randomized cluster implementation trial. METHOD: We conducted a mixed-method fidelity evaluation study of the PVS-PREDIAPS implementation strategy. Nine PC centers from the Basque Health Service (Osakidetza) were allocated to two different procedures to engage physicians and nurses and deploy a implementation strategy to model and adapt the clinical intervention and its implementation to their specific contexts: a Global procedure, promoting the cooperation of all healthcare professionals from the beginning; or a Sequential procedure, centered first on nurses who then pursued the pragmatic cooperation of physicians. Process indicators of the delivery and receipt of implementation strategy actions, documented modifications to the planned implementation strategy, and a structured group interview with centers' leaders were all used to assess the following components of fidelity: adherence, dose, quality of delivery, professionals' responsiveness and program differentiation. RESULTS: Generally, the procedures compared for professionals engagement and deployment of the implementation strategy were carried out with the planned differentiation. Nonetheless, some unexpected between-group differences were observed, the initial rate of collaboration of nurses being higher in the Sequential (93%) than in the Global (67%) groups. Exposure rate to the programed implementation actions (% of hours received out of those delivered) were similar in both groups by professional category, with nurses (86%) having a higher rate of exposure than physicians (75%). Professionals identified half of the planned discrete strategies and their rating of strategies' perceived usefulness was overwhelmingly positive, with few differences between Sequential and Global centers. CONCLUSIONS: The PVS-PREDIAPS implementation strategy has been implemented with high fidelity and minor unplanned reactive modifications. Professionals' exposure to the implementation strategy was high in both groups. The centers' organizational context (i.e., work overload) led to small mismatches between groups in participation and exposure of professionals to implementation actions. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03254979 . Registered 16 August 2017.

Applying Learning Analytics to Detect Sequences of Actions and Common Errors in a Geometry Game.

Games have become one of the most popular activities across cultures and ages. There is ample evidence that supports the benefits of using games for learning and assessment. However, incorporating game activities as part of the curriculum in schools remains limited. Some of the barriers for broader adoption in classrooms is the lack of actionable assessment data, the fact that teachers often do not have a clear sense of how students are interacting with the game, and it is unclear if the gameplay is leading to productive learning. To address this gap, we seek to provide sequence and process mining metrics to teachers that are easily interpretable and actionable. More specifically, we build our work on top of Shadowspect, a three-dimensional geometry game that has been developed to measure geometry skills as well other cognitive and noncognitive skills. We use data from its implementation across schools in the U.S. to implement two sequence and process mining metrics in an interactive dashboard for teachers. The final objective is to facilitate that teachers can understand the sequence of actions and common errors of students using Shadowspect so they can better understand the process, make proper assessment, and conduct personalized interventions when appropriate.

Smad2/3-pathway ligand trap luspatercept enhances erythroid differentiation in murine ß-thalassaemia by increasing GATA-1 availability.

In ß-thalassaemia, anaemia results from ineffective erythropoiesis characterized by inhibition of late-stage erythroid differentiation. We earlier used luspatercept and RAP-536 protein traps for certain Smad2/3-pathway ligands to implicate Smad2/3-pathway overactivation in dysregulated erythroid differentiation associated with murine ß-thalassaemia and myelodysplasia. Importantly, luspatercept alleviates anaemia and has been shown to reduce transfusion burden in patients with ß-thalassaemia or myelodysplasia. Here, we investigated the molecular mechanisms underlying luspatercept action and pSmad2/3-mediated inhibition of erythroid differentiation. In murine erythroleukemic (MEL) cells in vitro, ligand-mediated overactivation of the Smad2/3 pathway reduced nuclear levels of GATA-1 (GATA-binding factor-1) and its transcriptional activator TIF1γ (transcription intermediary factor 1γ), increased levels of reactive oxygen species, reduced cell viability and haemoglobin levels, and inhibited erythroid differentiation. Co-treatment with luspatercept in MEL cells partially or completely restored each of these. In ß-thalassaemic mice, RAP-536 up-regulated Gata1 and its target gene signature in erythroid precursors determined by transcriptional profiling and gene set enrichment analysis, restored nuclear levels of GATA-1 in erythroid precursors, and nuclear distribution of TIF1γ in erythroblasts. Bone marrow cells from ß-thalassaemic mice treated with luspatercept also exhibited restored nuclear availability of GATA-1 ex vivo. Our results implicate GATA-1, and likely TIF1γ, as key mediators of luspatercept/RAP-536 action in alleviating ineffective erythropoiesis.

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: the ZIKAlliance consortium.

BACKGROUND: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. METHODS: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmission clustering, disabilities and health economics, viral kinetics, the potential role of antibody enhancement, and co-infections will be linked to the cohort studies. DISCUSSION: Results of these large cohort studies will provide better risk estimates for birth defects and other developmental abnormalities associated with ZIKV infection including possible co-factors for the variability of risk estimates between other countries and regions. Additional outcomes include incidence and transmission estimates of ZIKV during and after pregnancy, characterization of short and long-term clinical course following infection and viral kinetics of ZIKV. STUDY REGISTRATIONS: clinicaltrials.gov NCT03188731 (PW cohort), June 15, 2017; clinicaltrials.gov NCT03393286 (CH cohort), January 8, 2018; clinicaltrials.gov NCT03204409 (NH cohort), July 2, 2017.

A CMOS Self-Contained Quadrature Signal Generator for SoC Impedance Spectroscopy.

This paper presents a low-power fully integrated quadrature signal generator for system-on-chip (SoC) impedance spectroscopy applications. It has been designed in a 0.18 μm-1.8 V CMOS technology as a self-contained oscillator, without the need for an external reference clock. The frequency can be digitally tuned from 10 to 345 kHz with 12-bit accuracy and a relative mean error below 1.7%, thus supporting a wide range of impedance sensing applications. The proposal is experimentally validated in two impedance spectrometry examples, achieving good magnitude and phase recovery results compared to the results obtained using a commercial LCR-meter. Besides the wide frequency tuning range, the proposed programmable oscillator features a total power consumption lower than 0.77 mW and an active area of 0.129 mm², thus constituting a highly suitable choice as stimulation module for instrument-on-a-chip devices.

A Compact Energy Harvesting System for Outdoor Wireless Sensor Nodes Based on a Low-Cost In Situ Photovoltaic Panel Characterization-Modelling Unit.

This paper presents a low-cost high-efficiency solar energy harvesting system to power outdoor wireless sensor nodes. It is based on a Voltage Open Circuit (VOC) algorithm that estimates the open-circuit voltage by means of a multilayer perceptron neural network model trained using local experimental characterization data, which are acquired through a novel low cost characterization system incorporated into the deployed node. Both units-characterization and modelling-are controlled by the same low-cost microcontroller, providing a complete solution which can be understood as a virtual pilot cell, with identical characteristics to those of the specific small solar cell installed on the sensor node, that besides allows an easy adaptation to changes in the actual environmental conditions, panel aging, etc. Experimental comparison to a classical pilot panel based VOC algorithm show better efficiency under the same tested conditions.

Programmed death 1-mediated T cell exhaustion during visceral leishmaniasis impairs phagocyte function.

Control of Leishmania infantum infection is dependent upon Th1 CD4(+) T cells to promote macrophage intracellular clearance of parasites. Deficient CD4(+) T cell effector responses during clinical visceral leishmaniasis (VL) are associated with elevated production of IL-10. In the primary domestic reservoir of VL, dogs, we define occurrence of both CD4(+) and CD8(+) T cell exhaustion as a significant stepwise loss of Ag-specific proliferation and IFN-γ production, corresponding to increasing VL symptoms. Exhaustion was associated with a 4-fold increase in the population of T cells with surface expression of programmed death 1 (PD-1) between control and symptomatic populations. Importantly, exhausted populations of CD8(+) T cells and to a lesser extent CD4(+) T cells were present prior to onset of clinical VL. VL-exhausted T cells did not undergo significant apoptosis ex vivo after Ag stimulation. Ab block of PD-1 ligand, B7.H1, promoted return of CD4(+) and CD8(+) T cell function and dramatically increased reactive oxygen species production in cocultured monocyte-derived phagocytes. As a result, these phagocytes had decreased parasite load. To our knowledge, we demonstrate for the first time that pan-T cell, PD-1-mediated, exhaustion during VL influenced macrophage-reactive oxygen intermediate production. Blockade of the PD-1 pathway improved the ability of phagocytes isolated from dogs presenting with clinical VL to clear intracellular parasites. T cell exhaustion during symptomatic canine leishmaniasis has implications for the response to vaccination and therapeutic strategies for control of Leishmania infantum in this important reservoir species.

Acid-Triggered Degradable Reagents for Differentiation of Adaptive and Innate Immune Responses to Leishmania-Associated Sugars.

Lipopolysaccharides (LPS) of Leishmania spp are known to alter innate immune responses. However, the ability of these sugars to specifically alter adaptive T-cell responses is unclear. To study cap sugar-T-cell interactions, pathogen mimics (namely glycodendrimer-coated latex beads with acid-labile linkers) were synthesized. Upon lysosomal acidification, linker breakdown releases glycodendrimers for possible loading on antigen presenting molecules to induce T-cell growth. T-cell proliferation was indeed higher after macrophage exposure to mannobioside or -trioside-containing glycodendrimers than to non-functionalized beads. Yet, blocking phagolysosomal acidification only reduced T-cell proliferation with macrophages exposed to beads with an acid-labile-linker and not to covalently-linked beads. These sugar-modified reagents show that oligosaccharides alone can drive T-cell proliferation by acidification-requiring presentation, most significantly in NKT receptor (CD160)-restricted T cells.

Tracking Small Animals in Complex Landscapes: A Comparison of Localisation Workflows for Automated Radio Telemetry Systems.

Automated radio telemetry systems (ARTS) have the potential to revolutionise our understanding of animal movement by providing a near-continuous record of individual locations in the wild. However, localisation errors in ARTS data can be very high, especially in natural landscapes with complex vegetation structure and topography. This curtails the research questions that may be addressed with this technology. We set up an ARTS grid in a valley with heterogeneous vegetation cover in the Colombian high Andes and applied an analytical pipeline to test the effectiveness of localisation methods. We performed calibration trials to simulate animal movement in high- or low-flight, or walking on the ground, and compared workflows with varying decisions related to signal cleaning, selection, smoothing, and interpretation, along with four multilateration approaches. We also quantified the influence of spatial features on the system's accuracy. Results showed large variation in localisation error, ranging between 0.4-43.4 m and 474-1929 m, depending on the localisation method used. We found that the selection of higher radio signal strengths and data smoothing based on the temporal autocorrelation are useful tools to improve accuracy. Moreover, terrain ruggedness, height of movement, vegetation type, and the location of animals inside or outside the grid area influence localisation error. In the case of our study system, thousands of location points were successfully estimated for two high-altitude hummingbird species that previously lacked movement data. Our case study on hummingbirds suggests ARTS grids can be used to estimate small animals' home ranges, associations with vegetation types, and seasonality in occurrence. We present a comparative localisation pipeline, highlighting the variety of possible decisions while processing radio signal data. Overall, this study provides guidance to improve the resolution of location estimates, broadening the application of this tracking technology in the study of the spatial ecology of wild populations.

Los sistemas de radio telemetría automatizada (ARTS, por sus siglas en inglés) tienen el potencial de revolucionar nuestro entendimiento de los movimientos de animales, ya que pueden generar registros de individuos en la naturaleza a escalas temporales muy finas. Sin embargo, el error de localización asociado a los datos generados por un sistema ARTS puede ser muy alto, especialmente en paisajes naturales con complejidad en su estructura vegetal y su topografía. Esto necesariamente limita las preguntas de investigación que se pueden abordar con dicha tecnología. En este estudio, instalamos una grilla ARTS en un valle con una cobertura vegetal heterogénea en ecosistemas altoandinos de Colombia, y evaluamos la efectividad de métodos de localización. Hicimos ensayos de calibración para simular el movimiento de animales tanto en vuelo alto y bajo como caminando sobre el piso, y comparamos procesos de localización con diferentes decisiones en los pasos de limpieza, selección, atenuación e interpretación de las señales de radio registradas. Además, probamos cuatro métodos de multilateración diferentes. También cuantificamos el efecto de características espaciales sobre la exactitud de la grilla ARTS. Los resultados muestran una gran variación en el error de localización, con coordenadas estimadas a sólo 0.4­43.4 m de la ubicación real hasta 474­1929 m, dependiendo del método de localización empleado. Encontramos que la selección de señales de radio más altas y la atenuación de los datos con base en la autocorrelación temporal de los datos de movimiento, son herramientas útiles para mejorar la exactitud del sistema. Además, la rugosidad del terreno, la altura del movimiento, el tipo de vegetación y la ubicación de los animales dentro o fuera de la grilla son variables que afectan el error de localización. Para nuestro caso de estudio, miles de puntos de ubicación fueron estimados para dos especies de colibríes que previamente no tenían datos de movimiento. Nuestro caso de estudio sobre colibríes de alta montaña sugiere que grillas ARTS son útiles para inferir rangos de hogar, asociaciones con tipos de vegetación y ocurrencia estacional de especies de animales pequeños. Presentamos una metodología comparativa de localización, resaltando la variedad de posibles decisiones durante el procesamiento de datos de señales de radio. Este estudio provee una guía para mejorar la resolución de estimados de ubicación, y amplía la aplicación de esta tecnología para el estudio de la ecología espacial de poblaciones silvestres.

Early diagnostic indicators of dengue versus other febrile illnesses in Asia and Latin America (IDAMS study): a multicentre, prospective, observational study.

BACKGROUND: Improvements in the early diagnosis of dengue are urgently needed, especially in resource-limited settings where the distinction between dengue and other febrile illnesses is crucial for patient management. METHODS: In this prospective, observational study (IDAMS), we included patients aged 5 years and older with undifferentiated fever at presentation from 26 outpatient facilities in eight countries (Bangladesh, Brazil, Cambodia, El Salvador, Indonesia, Malaysia, Venezuela, and Viet Nam). We used multivariable logistic regression to investigate the association between clinical symptoms and laboratory tests with dengue versus other febrile illnesses between day 2 and day 5 after onset of fever (ie, illness days). We built a set of candidate regression models including clinical and laboratory variables to reflect the need of a comprehensive versus parsimonious approach. We assessed performance of these models via standard measures of diagnostic values. FINDINGS: Between Oct 18, 2011, and Aug 4, 2016, we recruited 7428 patients, of whom 2694 (36%) were diagnosed with laboratory-confirmed dengue and 2495 (34%) with (non-dengue) other febrile illnesses and met inclusion criteria, and were included in the analysis. 2703 (52%) of 5189 included patients were younger than 15 years, 2486 (48%) were aged 15 years or older, 2179 (42%) were female and 3010 (58%) were male. Platelet count, white blood cell count, and the change in these variables from the previous day of illness had a strong association with dengue. Cough and rhinitis had strong associations with other febrile illnesses, whereas bleeding, anorexia, and skin flush were generally associated with dengue. Model performance increased between day 2 and 5 of illness. The comprehensive model (18 clinical and laboratory predictors) had sensitivities of 0·80 to 0·87 and specificities of 0·80 to 0·91, whereas the parsimonious model (eight clinical and laboratory predictors) had sensitivities of 0·80 to 0·88 and specificities of 0·81 to 0·89. A model that includes laboratory markers that are easy to measure (eg, platelet count or white blood cell count) outperformed the models based on clinical variables only. INTERPRETATION: Our results confirm the important role of platelet and white blood cell counts in diagnosing dengue, and the importance of serial measurements over subsequent days. We successfully quantified the performance of clinical and laboratory markers covering the early period of dengue. Resulting algorithms performed better than published schemes for distinction of dengue from other febrile illnesses, and take into account the dynamic changes over time. Our results provide crucial information needed for the update of guidelines, including the Integrated Management of Childhood Illness handbook. FUNDING: EU's Seventh Framework Programme. TRANSLATIONS: For the Bangla, Bahasa Indonesia, Portuguese, Khmer, Spanish and Vietnamese translations of the abstract see Supplementary Materials section.

Assessment of infection with polyomaviruses BKV, JCV and SV40 in different groups of Cuban individuals.

We investigated the frequency of BKV, JCV and SV40 reactivation in three groups of Cuban patients by multiplex nested PCR assay of 40 paraffin-embedded colorectal neoplasm tissues, 113 urine samples, and 125 plasma samples from 27 transplant recipients, and cerebrospinal fluid (CSF) from 67 HIV-1-infected individuals with central nervous system (CNS) disorders. None of these polyomaviruses were detected in colorectal neoplasms. JCV DNA was detected in 2 of 67 patients (2.9%) with CNS disorders, but neither BKV nor SV40 was identified. BKV was found in urine from 38.5% and 28.6% of adult and pediatric transplant recipients, respectively. In adult renal transplant recipients, excretion of BKV in urine was significantly associated with episodes of acute rejection (p=0.012) and with excretion of HCMV in urine (p= 0.008). In Cuba, the polyomaviruses studied here could not be related to colorectal neoplasms, and JCV was rarely detected in CSFs of HIV-1-infected individuals, whilst BKV reactivation was found to occur frequently in organ transplant recipients.

Stable isotopes reveal seasonal dietary responses to agroforestry in a venomous mammal, the Hispaniolan solenodon (Solenodon paradoxus).

While trends in tropical deforestation are alarming, conservation biologists are increasingly recognizing the potential for species survival in human-modified landscapes. Identifying the factors underlying such persistence, however, requires basic ecological knowledge of a species' resource use. Here, we generate such data to guide conservation of an understudied venomous mammal, the Hispaniolan solenodon (Solenodon paradoxus), that occupies a mosaic landscape of agriculture and forest fragments in the western Dominican Republic. Using feces collected in both wet and dry seasons, we found significant differences in the stable isotope values of carbon (δ13C) between pasture (-24.63 ± 2.31‰, Las Mercedes) and agroforestry (-28.07 ± 2.10‰, Mencia). Solenodon populations in agricultural areas occupied wider isotopic niche spaces, which may be explained by more diverse resource within these patches or individuals combining resources across habitats. We detected elevated δ15N values in the dry season of pasture areas (8.22 ± 2.30‰) as compared to the wet season (5.26 ± 2.44‰) and overall narrower isotopic niche widths in the dry season, suggestive of the impacts of aridity on foraging behavior. Our work highlights the importance of considering a more nuanced view of variations in 'modified' or "agricultural" landscapes as compared with strictly protected national parks. We suggest that seasonal differences in foraging should be considered as they intersect with landscape modification by landowners for maintaining resources for focal consumers. This work adds to a growing body of literature highlighting that fecal stable isotopes are a non-invasive and cost-effective monitoring tool that is particularly well-suited for cryptic small mammal species, ensuring actionable and evidenced-based conservation practices in the tropic's rapidly changing landscapes.

Molecular and genomic investigation of an urban outbreak of dengue virus serotype 2 in Angola, 2017-2019.

BACKGROUND: The transmission patterns and genetic diversity of dengue virus (DENV) circulating in Africa remain poorly understood. Circulation of the DENV serotype 1 (DENV1) in Angola was detected in 2013, while DENV serotype 2 (DENV2) was detected in 2018. Here, we report results from molecular and genomic investigations conducted at the Ministry of Health national reference laboratory (INIS) in Angola on suspected dengue cases detected between January 2017 and February 2019. METHODS: A total of 401 serum samples from dengue suspected cases were collected in 13 of the 18 provinces in Angola. Of those, 351 samples had complete data for demographic and epidemiological analysis, including age, gender, province, type of residence, clinical symptoms, as well as dates of onset of symptoms and sample collection. RNA was extracted from residual samples and tested for DENV-RNA using two distinct real time RT-PCR protocols. On-site whole genome nanopore sequencing was performed on RT-PCR+ samples. Bayesian coalescent models were used to estimate date and origin of outbreak emergence, as well as population growth rates. RESULTS: Molecular screening showed that 66 out of 351 (19%) suspected cases were DENV-RNA positive across 5 provinces in Angola. DENV RT-PCR+ cases were detected more frequently in urban sites compared to rural sites. Of the DENV RT-PCR+ cases most were collected within 6 days of symptom onset. 93% of infections were confirmed by serotype-specific RT-PCR as DENV2 and 1 case (1.4%) was confirmed as DENV1. Six CHIKV RT-PCR+ cases were also detected during the study period, including 1 co-infection of CHIKV with DENV1. Most cases (87%) were detected in Luanda during the rainy season between April and October. Symptoms associated with severe dengue were observed in 11 patients, including 2 with a fatal outcome. On-site nanopore genome sequencing followed by genetic analysis revealed an introduction of DENV2 Cosmopolitan genotype (also known as DENV2-II genotype) possibly from India in or around October 2015, at least 1 year before its detection in the country. Coalescent models suggest relatively moderately rapid epidemic growth rates and doubling times, and a moderate expansion of DENV2 in Angola during the studied period. CONCLUSION: This study describes genomic, epidemiological and demographic characteristic of predominately urban transmission of DENV2 in Angola. We also find co-circulation of DENV2 with DENV1 and CHIKV and report several RT-PCR confirmed severe dengue cases in the country. Increasing dengue awareness in healthcare professional, expanding the monitorization of arboviral epidemics across the country, identifying most common mosquito breeding sites in urban settings, implementing innovative vector control interventions and dengue vaccination campaigns could help to reduce vector presence and DENV transmission in Angola.

ActRIIB:ALK4-Fc alleviates muscle dysfunction and comorbidities in murine models of neuromuscular disorders.

Patients with neuromuscular disorders suffer from a lack of treatment options for skeletal muscle weakness and disease comorbidities. Here, we introduce as a potential therapeutic agent a heterodimeric ligand-trapping fusion protein, ActRIIB:ALK4-Fc, which comprises extracellular domains of activin-like kinase 4 (ALK4) and activin receptor type IIB (ActRIIB), a naturally occurring pair of type I and II receptors belonging to the TGF-ß superfamily. By surface plasmon resonance (SPR), ActRIIB:ALK4-Fc exhibited a ligand binding profile distinctly different from that of its homodimeric variant ActRIIB-Fc, sequestering ActRIIB ligands known to inhibit muscle growth but not trapping the vascular regulatory ligand bone morphogenetic protein 9 (BMP9). ActRIIB:ALK4-Fc and ActRIIB-Fc administered to mice exerted differential effects - concordant with SPR results - on vessel outgrowth in a retinal explant assay. ActRIIB:ALK4-Fc induced a systemic increase in muscle mass and function in wild-type mice and in murine models of Duchenne muscular dystrophy (DMD), amyotrophic lateral sclerosis (ALS), and disuse atrophy. Importantly, ActRIIB:ALK4-Fc improved neuromuscular junction abnormalities in murine models of DMD and presymptomatic ALS and alleviated acute muscle fibrosis in a DMD model. Furthermore, in combination therapy ActRIIB:ALK4-Fc increased the efficacy of antisense oligonucleotide M12-PMO on dystrophin expression and skeletal muscle endurance in an aged DMD model. ActRIIB:ALK4-Fc shows promise as a therapeutic agent, alone or in combination with dystrophin rescue therapy, to alleviate muscle weakness and comorbidities of neuromuscular disorders.

Bioethical Concerns During the COVID-19 Pandemic: What Did Healthcare Ethics Committees and Institutions State in Spain?

Objectives: Each new wave of the COVID-19 pandemic invites the possible obligation to prioritize individuals' access to vital resources, and thereby leads to unresolved and important bioethical concerns. Governments have to make decisions to protect access to the health system with equity. The prioritization criteria during a pandemic are both a clinical and legal-administrative decision with ethical repercussion. We aim to analyse the prioritization protocols used in Spain during the pandemic which, in many cases, have not been updated. Method: We carried out a narrative review of 27 protocols of prioritization proposed by healthcare ethics committees, scientific societies and institutions in Spain for this study. The review evaluated shared aspects and unique differences and proffered a bioethical reflection. Results: The research questions explored patient prioritization, the criteria applied and the relative weight assigned to each criterion. There was a need to use several indicators, being morbidity and mortality scales the most commonly used, followed by facets pertaining to disease severity and functional status. Although age was initially considered in some protocols, it cannot be the sole criterion used when assigning care resources. Conclusions: In COVID-19 pandemic there is a need for a unified set of criteria that guarantees equity and transparency in decision-making processes. Establishing treatment indications is not the aim of such criteria, but instead prioritizing access to care resources. In protocols of prioritization, the principle of efficiency must vary according to the principle of equity and the criteria used to guarantee such equity.

Diagnostic performance of anti-Zika virus IgM, IgAM and IgG ELISAs during co-circulation of Zika, dengue, and chikungunya viruses in Brazil and Venezuela.

BACKGROUND: Serological diagnosis of Zika virus (ZIKV) infection is challenging because of the antibody cross-reactivity among flaviviruses. At the same time, the role of Nucleic Acid Testing (NAT) is limited by the low proportion of symptomatic infections and the low average viral load. Here, we compared the diagnostic performance of commercially available IgM, IgAM, and IgG ELISAs in sequential samples during the ZIKV and chikungunya (CHIKV) epidemics and co-circulation of dengue virus (DENV) in Brazil and Venezuela. METHODOLOGY/PRINCIPAL FINDINGS: Acute (day of illness 1-5) and follow-up (day of illness ≥ 6) blood samples were collected from nine hundred and seven symptomatic patients enrolled in a prospective multicenter study between June 2012 and August 2016. Acute samples were tested by RT-PCR for ZIKV, DENV, and CHIKV. Acute and follow-up samples were tested for IgM, IgAM, and IgG antibodies to ZIKV using commercially available ELISAs. Among follow-up samples with a RT-PCR confirmed ZIKV infection, anti-ZIKV IgAM sensitivity was 93.5% (43/46), while IgM and IgG exhibited sensitivities of 30.3% (10/33) and 72% (18/25), respectively. An additional 24% (26/109) of ZIKV infections were detected via IgAM seroconversion in ZIKV/DENV/CHIKV RT-PCR negative patients. The specificity of anti-ZIKV IgM was estimated at 93% and that of IgAM at 85%. CONCLUSIONS/SIGNIFICANCE: Our findings exemplify the challenges of the assessment of test performance for ZIKV serological tests in the real-world setting, during co-circulation of DENV, ZIKV, and CHIKV. However, we can also demonstrate that the IgAM immunoassay exhibits superior sensitivity to detect ZIKV RT-PCR confirmed infections compared to IgG and IgM immunoassays. The IgAM assay also proves to be promising for detection of anti-ZIKV seroconversions in sequential samples, both in ZIKV PCR-positive as well as PCR-negative patients, making this a candidate assay for serological monitoring of pregnant women in future ZIKV outbreaks.

Chronic effects and optimal dosage of strength training on SBP and DBP: a systematic review with meta-analysis.

BACKGROUND AND OBJECTIVES: Hypertension is a disease affecting a large part of the world's population that causes millions of deaths annually. Physical exercise is proposed as an alternative to pharmacologic therapies used to reduce blood pressure. The main objective was to compare the effect of different types of strength training in blood pressure, as well as to analyse several variables that can modify the effect of strength training not combined with medication in SBP and DBP (SBP-DBP). METHODS: The search was carried out in two scientific databases: PubMed and Web of Science. Articles were included following three criteria: analysing the chronic effect of strength training in blood pressure; the studies were conducted at least during 4 weeks; and the articles were published in English. RESULTS: The analysis showed a significant decrease of blood pressure for all types of training. The effect on SBP was greater when training without medication was carried out with isometric exercises than when training was performed with dynamic exercises. Moreover, the effects were no longer significant when the duration of the training programme exceeded 20 weeks as well as when training frequency was lower than three times per week were found. CONCLUSION: Strength training is effective in reducing both blood pressures (SBP-DBP). Training programmes, consisting of dynamic strength training without medication at a moderate intensity and with a frequency of three times per week, seem to be optimal in order to reduce blood pressure.Prospective register of Systematic Reviews: CRD42019122421.

First report on fatal myocarditis associated with adenovirus infection in Cuba.

Myocarditis is caused frequently by viral infections of the myocardium. In the past, enteroviruses (EV) were considered the most common cause of myocarditis in all age groups. Other viruses that cause myocarditis are adenovirus and influenza viruses. Parvovirus B19 infection is associated sometimes with myocarditis. Members of the Herpesviridae family, cytomegalovirus (CMV), and human herpesvirus 6 (HHV-6) have been associated occasionally with myocarditis. During an atypical outbreak of acute febrile syndrome, eight children, with ages from 5 months to 15 years, died in cardiogenic shock due to myocarditis in July-August 2005, in the city of Havana, Cuba. Nested polymerase chain reaction (nPCR) and nested reverse transcription-PCR (nRT-PCR) were carried out on fresh heart muscle and lung tissue to analyze the genomic sequences of adenovirus, CMV, HHV-6, herpes simplex virus, Epstein-Barr virus (EBV), varizella zoster virus, influenza virus A, B, C, respiratory syncytial virus (RSV) A and B, parainfluenza viruses, rhinoviruses, coronavirus, flaviruses and enteroviruses. Evidence was for the presence of the adenovirus genome in 6 (75%) of the children. Phylogenetic analyses of a conserved hexon gene fragment in four cases showed serotype 5 as the causal agent. No others viruses were detected. Histological examination was undertaken to detect myocardial inflammation. After exclusion of other possible causes of death, the results indicated that viral myocarditis was the cause of death in patients with adenovirus infection.

A myocarditis outbreak with fatal cases associated with adenovirus subgenera C among children from Havana City in 2005.

BACKGROUND: Among multiple causes of acute myocarditis, viral infection, especially that due to enteroviruses and adenoviruses, is the leading cause. In the summer 2005 an outbreak of a febrile syndrome accompanied by acute cardiac decompensation occurred in infants and young children in Havana City. Eleven patients had a rapid evolution of disease and there were 8 fatalities from cardiac failure secondary to myocarditis. OBJECTIVE: The aim of the present study was to determine the etiological agent responsible for this outbreak. STUDY DESIGN: Children admitted to the pediatric hospitals of Havana City from July 3 to August 2 with this clinical presentation were studied. Forty samples of necropsy tissue, cerebrospinal fluid, stools and serum were tested by molecular methods for 14 respiratory viruses, 6 herpesviruses and generic enteroviruses and flavirus and alfaviruses. Viral isolation was performed in A-549 cells. Isolated viruses were typed by sequence analysis. RESULTS: Adenovirus genome was detected in 6 of the 8 fatal cases-the lungs in 5 (63%) and the myocardium in 3 (37%). In two fatal cases, viral genome was detected in both lung and myocardium. Adenovirus was isolated in five fatal cases. In all three non-fatal cases, adenovirus genome was detected and adenovirus was isolated into two. Sequence analysis showed that adenovirus type 5 was the only isolate from fatal cases and adenovirus 1 the only isolate in non-fatal cases. No other viruses were found by PCR or isolation techniques. CONCLUSION: Adenovirus was the etiologic agent implicated in this myocarditis outbreak and adenovirus type 5 was associated with fatal outcome.

Characterization of Different Cable Ferrite Materials to Reduce the Electromagnetic Noise in the 2-150 kHz Frequency Range.

The gap of standardization for conducted and field coupled electromagnetic interferences (EMI) in the 2-150 kHz frequency range can lead to Electromagnetic Compatibility (EMC) problems. This is caused by power systems such as Pulse Width Modulation (PWM) controlled rectifiers, photovoltaic inverters or charging battery units in electric vehicles. This is a very important frequency spectral due to interferences generated in a wide range of devices and, specifically, communication problems in the new technologies and devices incorporated to the traditional grid to convert it into a Smart Grid. Consequently, it is necessary to provide new solutions to attenuate this kind of interference, which involves finding new materials that are able to filter the electromagnetic noise. This contribution is focused on characterizing the performance of a novel material based on nanocrystalline and comparing it to most common material compositions such as MnZn and NiZn. This research is carried out from the point of view of the manufacturing process, magnetic properties and EMI suppression ability. This last item is carried out through two analysis procedures: a theoretical method by determining the attenuation ratio by measuring impedance parameter and proposing a new empirical technique based on measuring directly the insertion loss parameter. Therefore, the main aim of this characterization process is to determine the performance of nanocrystalline compared to traditional cable ferrite compositions to reduce the interferences in this controversial frequency range. From the results obtained, it is possible to deduce that nanocrystalline cable ferrite provides the best performance to filter the electromagnetic noise in the 2-150 kHz frequency range.