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Introduction: Diarrheal diseases constitute a significant public health problem in terms of mortality and morbidity. In Honduras and around the world, RVs have consistently emerged as the single most important etiologic agent in acute childhood diarrhea. However, other viruses, such as NoVs and HAstVs, have also been shown to be responsible for viral gastroenteritis. Unfortunately, the country has limited information concerning the etiologic role of these viral agents in acute gastroenteritis. This study investigated the frequency, genotypes, and epidemiological characteristics of RV-A, NoVs, and HAstVs among children under 5 years old in Distrito Central, Honduras. Methods: Stool samples and their corresponding epidemiological data were collected from children with acute gastroenteritis in three healthcare centers in Distrito Central. All samples were screened by immunoassays for RV-A and HAstVs. RV-A-positive samples were molecularly characterized by RT-PCR and genotyping assays. RT-PCR was also applied to confirm HAstVs positivity and to detect NoVs, followed by nucleotide sequencing to assign their genotypes. Results: Our results show that at least one viral agent was detected in 31% of the children. The frequency of RV-A, NoVs, and HAstVs was 14%, 13%, and 5%, respectively. The most frequent RV-A genotype was G2P[4], occurring in 93% of cases. 92.3% of NoVs-positive samples belonged to genogroup II, with GII.4 and GII.16 being the most common. HAstVs were clustered into three genotypes: HAstV-1, HAstV-2, and HAstV-8. Only one sample showed coinfection with NoVs and HAstVs. Conclusion: This comprehensive molecular and epidemiological characterization of enteric viruses demonstrates the vast diversity of these agents and describes for the first time NoVs and HAstVs as causative agents of acute childhood gastroenteritis in Distrito Central, Honduras. This suggests that further in-depth studies of the pediatric population are necessary to develop and implement effective preventive and control measures in the country.

BackgroundSevere eosinophilic asthma (SEA) is often linked to a dysregulation in the Interleukin-(IL)-5 axis. Mepolizumab, a humanized monoclonal antibody, reduces eosinophils by directly binging to IL-5, potentially restoring homeostatic eosinophil biology, with a significant impact on quality of life, acute exacerbations and oral corticosteroids (OCS) elimination in SEA patients. While its short- and middle-term effects are well described, no study has so far investigated its long-lasting effects in SEA patients. The aim of our study was therefore to explore the effects of a long-term, six-year continuous treatment with mepolizumab on clinical control and clinical remission in a cohort of SEA patients.MethodsWe conducted a retrospective review of clinical records of patients who were prescribed mepolizumab between June 2017 and April 2018. We collected demographical, functional, and clinical data from visits performed at baseline and then at the specified timepoints and checked if patients had reached clinical remission after 6 years. We assessed asthma control test (ACT), exacerbation rate, and OCS elimination dose at 6 years. Clinical Remission (CR) was defined on the basis of the elimination of OCS and the contemporary presence of all the following: 1) stable lung function; 2) no exacerbation in the previous 12 months; 3) acceptable symptom control (ACT ≥ 20).ResultsOf 86 patients screened, 62 were included in the final analysis. Our study suggests that mepolizumab is effective and well tolerated after a six-year course of continuous treatment in patients with SEA. We reported a prevalence of 28 (46.8%) patients who reached complete CR at 72 months from the treatment start. 75% of patients eliminated the maintenance OCS already after 1 year of treatment; this proportion reached the 87% within the sixth year of treatment.ConclusionMepolizumab proved to be effective in real-life after 6 years of treatment, inducing a complete clinical remission in the 46.8% of patients, with sustained improvements in quality of life, exacerbation rate, OCS intake and lung function.

The present report investigates the impact of a Telemedicine Service (TMS) on the management of Idiopathic Pulmonary Fibrosis (IPF) during coronavirus disease of 2019 (COVID-19) outbreak in Italy. The TMS comprised 3 phone numbers, active 12 h per day, and an email address, monitored every 4 h by trained physicians; chat- and videoconference-services were also offered. At the end of the study period, our staff contacted all patients, to get information about the final outcome (i.e. composite hospitalisations/all causes of death). Outcomes were compared with a cohort of patients who attended our unit in the same period of the previous year (when no TMS was available). 189 patients participated in the present study. From 11th March to 4th May 2020, 61% of patients made at least one TMS access, mostly by emails (53%), followed by phone calls (33%). With regard to the primary outcome, TMS patients experienced a significant lower rate of events of the 182 patients of the no-TMS cohort (p < 0.001). Specifically, a significant difference was observed for IPF hospitalisation (p < 0.001) whereas no differences were observed with regard to deaths (p = 0.64). TMS permits patients to be followed up even during COVID-19 lockdown, with an encouraging impact on outcomes.

We present an open-source differentiable acoustic simulator, j-Wave, which can solve time-varying and time-harmonic acoustic problems. It supports automatic differentiation, which is a program transformation technique that has many applications, especially in machine learning and scientific computing. j-Wave is composed of modular components that can be easily customized and reused. At the same time, it is compatible with some of the most popular machine learning libraries, such as JAX and TensorFlow. The accuracy of the simulation results for known configurations is evaluated against the widely used k-Wave toolbox and a cohort of acoustic simulation software. j-Wave is available from https://github.com/ucl-bug/jwave.

Introduction Nintedanib (NTD) has been shown to be effective in systemic sclerosis (SSc)-interstitial lung disease (ILD). Here we describe the efficacy and safety of NTD in a real-life setting.Methods Patients with SSc-ILD treated with NTD were retrospectively evaluated at 12 months prior to NTD introduction; at baseline and at 12 months after NTD introduction. The following parameters were recorded: SSc clinical features, NTD tolerability, pulmonary function tests and modified Rodnan skin score (mRSS).Results 90 patients with SSc-ILD (65% female, mean age 57.6±13.4 years, mean disease duration 8.8±7.6 years) were identified. The majority were positive for anti-topoisomerase I (75%) and 77 (85%) patients were on immunosuppressants. A significant decline in %predicted forced vital capacity (%pFVC) in the 12 months prior to NTD introduction was observed in 60%. At 12 months after NTD introduction, follow-up data were available for 40 (44%) patients and they showed a stabilisation in %pFVC (64±14 to 62±19, p=0.416). The percentage of patients with significant lung progression at 12 months was significantly lower compared with the previous 12 months (60% vs 17.5%, p=0.007). No significant mRSS change was observed. Gastrointestinal (GI) side effects were recorded in 35 (39%) patients. After a mean time of 3.6±3.1 months, NTD was maintained after dose adjustment in 23 (25%) patients. In nine (10%) patients, NTD was stopped after a median time of 4.5 (1–6) months. During the follow-up, four patients died.Conclusions In a real-life clinical scenario, NTD, in combination with immunosuppressants, may stabilise lung function. GI side effects are frequent and NTD dose adjustment may be necessary to retain the drug in patients with SSc-ILD.

Abstract Body composition and muscle strength are emerging aspects in idiopathic pulmonary fibrosis (IPF) clinical assessment. We aimed to study the relationships of handgrip strength (HGS) with anthropometric variables, body composition, and disease staging, and to evaluate the prevalence of dynapenia in 102 clinically stable IPF patients (70 M; mean age: 69.4 years). Fat-free mass (FFM), skeletal muscle (SM) were estimated with bioimpedance analysis. HGS was measured with a digital handle dynamometer for both dominant and non-dominant body sides. Dynapenia was identified according to six recognized criteria sets. Mean body mass index (BMI) was 28.2 ± 4.7 kg/m2, with a prevalence of overweight (BMI > 25 and

BackgroundSystemic biomarkers for severity of SARS-CoV-2 infection are of great interest. In this study, we evaluated a set of collagen metabolites and extracellular matrix remodeling biomarkers including procollagen type III amino terminal propeptide (PIIINP), tissue inhibitor of metalloproteinases 1 (TIMP-1) and hyaluronic acid (HA) as prognostic indicators in COVID-19 patients.MethodsNinety COVID-19 patients with the absence of chronic liver diseases were enrolled. Serum PIIINP, TIMP-1, and HA were measured and correlated with inflammatory indices and clinical variables. Patients were stratified for disease severity according to WHO criteria in two groups, based on the requirement of oxygen support.ResultsSerum TIMP-1, but not PIIINP and HA was significantly higher in patients with WHO score ≥5 compared to patients with WHO score

Abstract Purpose This study was a quality-control study of resting and exercise Doppler echocardiography (EDE) variables measured by 19 echocardiography laboratories with proven experience participating in the RIGHT Heart International NETwork. Methods All participating investigators reported the requested variables from ten randomly selected exercise stress tests. Intraclass correlation coefficients (ICC) were calculated to evaluate the inter-observer agreement with the core laboratory. Inter-observer variability of resting and peak exercise tricuspid regurgitation velocity (TRV), right ventricular outflow tract acceleration time (RVOT Act), tricuspid annular plane systolic excursion (TAPSE), tissue Doppler tricuspid lateral annular systolic velocity (S’), right ventricular fractional area change (RV FAC), left ventricular outflow tract velocity time integral (LVOT VTI), mitral inflow pulsed wave Doppler velocity (E), diastolic mitral annular velocity by TDI (e’) and left ventricular ejection fraction (LVEF) were measured. Results The accuracy of 19 investigators for all variables ranged from 99.7 to 100%. ICC was > 0.90 for all observers. Inter-observer variability for resting and exercise variables was for TRV = 3.8 to 2.4%, E = 5.7 to 8.3%, e’ = 6 to 6.5%, RVOT Act = 9.7 to 12, LVOT VTI = 7.4 to 9.6%, S’ = 2.9 to 2.9% and TAPSE = 5.3 to 8%. Moderate inter-observer variability was found for resting and peak exercise RV FAC (15 to 16%). LVEF revealed lower resting and peak exercise variability of 7.6 and 9%. Conclusions When performed in expert centers EDE is a reproducible tool for the assessment of the right heart and the pulmonary circulation.

Coronavirus disease-2019 (COVID-19) is a systemic disorder with the lung and the vasculature being the preferred targets. Patients with interstitial lung diseases represent a category at high risk of progression in the case of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection, and as such deserve special attention. We first describe the combination of acute exacerbation and pulmonary embolism in an elderly ILD patient after booster anti-COVID-19 mRNA vaccination. Vaccines availability had significantly and safety impacted COVID-19 morbidity and mortality worldwide. Immunization against COVID-19 is indisputable but must not be separated from the awareness of potential adverse effects in fragile patients.

Background: Severe eosinophilic asthma (SEA) is often linked to a dysregulation in the Interleukin-(IL)-5 axis. Mepolizumab, a humanized monoclonal antibody, reduces eosinophils by directly binging to IL-5, potentially restoring homeostatic eosinophil biology, with a significant impact on quality of life, acute exacerbations and oral corticosteroids (OCS) elimination in SEA patients. While its short-and middle-term effects are well described, no study has so far investigated its longlasting effects in SEA patients. The aim of our study was therefore to explore the effects of a long-term, six-year continuous treatment with mepolizumab on clinical control and clinical remission in a cohort of SEA patients. Methods: We conducted a retrospective review of clinical records of patients who were prescribed mepolizumab between June 2017 and April 2018. We collected demographical, functional, and clinical data from visits performed at baseline and then at the specified timepoints and checked if patients had reached clinical remission after 6 years. We assessed asthma control test (ACT), exacerbation rate, and OCS elimination dose at 6 years. Clinical Remission (CR) was defined on the basis of the elimination of OCS and the contemporary presence of all the following: 1) stable lung function; 2) no exacerbation in the previous 12 months; 3) acceptable symptom control (ACT ≥ 20). Results: Of 86 patients screened, 62 were included in the final analysis. Our study suggests that mepolizumab is effective and well tolerated after a six-year course of continuous treatment in patients with SEA. We reported a prevalence of 28 (46.8%) patients who reached complete CR at 72 months from the treatment start. 75% of patients eliminated the maintenance OCS already after 1 year of treatment; this proportion reached the 87% within the sixth year of treatment. Conclusion: Mepolizumab proved to be effective in real-life after 6 years of treatment, inducing a complete clinical remission in the 46.8% of patients, with sustained improvements in quality of life, exacerbation rate, OCS intake and lung function. [ABSTRACT FROM AUTHOR]

Sandbox is a non-accredited training programme in the performing arts and digital technologies for young people in four blighted neighbourhoods in Panama. In this paper, I reflect on my role in the design of this programme, how it was later implemented and whether it contributed to processes of economic development. To guide this reflection, I use a social capacities framework, where economic development is seen as a set of dynamics that enhances human flourishing (James 2018). The paper uses a wide range of data sources, including interviews with participants of the programme. My reflection concludes that programmes such as Sandbox work more effectively not when looking to create jobs and income, but when they aim to develop the capacities of participants to discover who they are within their own social context, helping them come closer to the labour market. [ABSTRACT FROM AUTHOR]

Severe asthma comprises several heterogeneous phenotypes, underpinned by complex pathomechanisms known as endotypes. The latter are driven by intercellular networks mediated by molecular components which can be targeted by specific monoclonal antibodies. With regard to the biological treatments of either allergic or non-allergic eosinophilic type 2 asthma, currently available antibodies are directed against immunoglobulins E (IgE), interleukin-5 (IL-5) and its receptor, the receptors of interleukins-4 (IL-4) and 13 (IL-13), as well as thymic stromal lymphopoietin (TSLP) and other alarmins. Among these therapeutic strategies, the best choice should be made according to the phenotypic/endotypic features of each patient with severe asthma, who can thus respond with significant clinical and functional improvements. Conversely, very poor options so far characterize the experimental pipelines referring to the perspective biological management of non-type 2 severe asthma, which thereby needs to be the focus of future thorough research.

Abstract Background The query “are there animals at home?” is usually administered for collecting information on anamnesis. This modality to consider exposure to pet allergens constitutes a potential bias in epidemiological studies and in clinical practice. The aim of our study was to evaluate/quantify different modalities of exposure to cat/dog in inducing allergic sensitization. Methods Thirty Italian Allergy units participated in this study. Each centre was required to collect the data of at least 20 consecutive outpatients sensitized to cat/dog allergens. A standardized form reported all demographic data and a particular attention was paid in relieving possible modalities of exposure to cat/dog. Results A total 723 patients sensitized to cat/dog were recorded, 359 (49.65%) reported direct pet contact, 213 patients (29.46%) were pet owners, and 146 subjects (20.19%) were exposed to pets in other settings. Other patients were sensitized by previous pet ownership (150–20.75%) or indirect contact (103–14.25%), in 111 subjects (15.35%) any contact was reported. Conclusions Only 213 patients (29.46%) would be classified as “exposed to animals” and 510 (70.54%) as “not exposed” according to usual query. Our classification has shown that many “not-exposed” subjects (399–55.19%) were “really exposed”. The magnitude of exposure to pet allergens at home is not related exclusively to pet ownership. These considerations should be taken into account during the planning of epidemiological studies and in clinical practice for the management of pet allergic individuals.

Abstract Background Small airways are considered the major site of airflow limitation in COPD. Impulse oscillometry (IOS) is a forced oscillation technique, which provides passive measurement of lung mechanics. It can differentiate small airway from large airway obstruction and is more sensitive than spirometry for peripheral airway disease. In this study the efficacy of the combination of Indacaterol/Glycopirronium (IND/GLY) versus Tiotropium on airway resistance (R5, R20, R5–20), lung reactance (X) and resonant frequency in moderate to severe COPD patients has been evaluated. We also evaluated inspiratory capacity (IC), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), exacerbation rate and quality of life. Methods Forty patients were monitored with forced oscillation technique and spirometry. Patients were randomized in 2 groups: 20 received fixed dose once daily Indacaterol/Glycopyrronium (Group A) and 20 received single Tiotropium (Group B). The oscillometry parameters were the measure of resistance in the airways at 5 Hz (R5), at 20 Hz (R20) and the lung reactance (X). Results There was a statistically significant difference between pre-dosing at V1 and at follow up visits in R5, R20 and X values in patients receiving dual bronchodilation but not in control group. Pre-dosing IC value at follow up visits in patients receiving dual bronchodilation had a statistical significant variation. Conclusions The “new” bronchodilator combination LABA/LAMA significantly reduces bronchial obstruction in small airways too. The oscillometry demonstrated greater sensitivity compared with spirometry for monitoring outcome measures of airway obstruction and the effect of long-term therapy.

This article, prepared according to the deductive method, seeks to identify the phenomenon of climate change protection within the scope of national constitutions, treaties, and transnational jurisprudence, concerning carbon metrics and their impacts on the economy and historicity of nations, as the colony-metropolis binomial. The objective is to reveal the justice or not of the current transnational impositions of carbon metrics. It is intended to identify the characteristics of the intergenerational climate law norm that imposes sanctions and rewards according to the carbon economy of each member state, as well as the analysis of intergenerational historical justice since future generations will suffer the impact of the actions of past generations. It also seeks to analyze how transactions and carbon metrics between exporting and importing countries of agricultural, extractive, and mineral products are processed in the new context of the Paris Agreement under the historical perspective of colony-metropolis relations, as well as what the rewards are. Historical and restorative measures would be necessary to neutralize this new climate colonialism so that progress in reducing greenhouse gas emissions does not become a trap for domination by developed and historically polluting states. [ABSTRACT FROM AUTHOR]

Public libraries in Europe have supported lifelong learning for the past 500 years. Since the Lisbon Strategy emphasized the role of lifelong learning in economic policy, public libraries have been repositioning their services to respond to this new context. In some cases, these roles are undertaken with limited legislative or strategic changes and stagnant levels of funding. As a result, the sector receives little recognition of its role in lifelong learning amongst policy-makers. A consortium representing 12 EU countries, ENTITLE, was formed to increase awareness of the role public libraries play in this area. It undertook a survey amongst its members to scope relevant policies, strategies and evaluation efforts. This paper presents an analysis of this survey. It shifts the focus away from debates about the instrumental value of libraries. Instead, it explores the role that evaluation plays in policy implementation. It argues that participatory evaluation can help reduce conflict and ambiguity amongst the stakeholders involved in delivering symbolic implementation of policies. So far, however, current evaluation efforts in most ENTITLE countries have played a limited role in supporting coordination and, for some countries, may in fact remove resources away from more effective development efforts, including pedagogical training. (Contains 1 note, 3 tables and 1 figure.)

Public libraries have traditionally provided key inputs to support lifelong learning. More recently, significant social and technological changes have challenged this sector to redefine their role in this field. For most public libraries in Europe this has meant continuing their role as providers of information and advice while increasing services to help learners with processing and evaluating knowledge. In some cases, new roles are undertaken with limited legislative changes and stagnant levels of funding. A consortium representing 12 European Union (EU) countries, ENTITLE, undertook a survey amongst its members in 2008-09 to scope policies and strategies linking learning and public libraries. This paper uses results from this survey to establish a typology of lifelong learning in public libraries in these countries. It explores how traditions, institutions, and policies influence learning provision at public libraries. The results show strong provision of learning services for children in almost all these countries, but inconsistent provision for adults. The paper argues that there is a divergence amongst these 12 countries in terms of innovation and resourcing. Those with a stronger provision benefit from local autonomy, the drive and skills to create partnerships, and formal legal and strategic recognition as partners in this agenda. (Contains 3 tables.)

O presente trabalho aborda a vulnerabilidade ambiental ante os desastres ecológicos como fator de violação de direitos humanos. Analisa as relações entre desastres ecológicos, vul- nerabilidade, direitos humanos e direito ambiental a par r da jus ça ambiental. Apresenta como perspec vas para uma resposta jurídica aos desastres ecológicos numa dimensão de jus ça ambiental a jurisprudência da Corte Europeia de Direitos Humanos quanto à proteção do direito à vida diante dos desastres ecológicos, e a criação de um estatuto jurídico internacional referente aos deslocamentos ambientais gerados por esses desastres, enfa zando a contribuição do Projeto de Convenção sobre o Estatuto Internacional dos Deslocados Ambientais.

A myotoxin phospholipase A2 homologue, BmooMtx, was isolated from the venom of Bothrops moojeni by a combination of ion-exchange chromatography on DEAE-Sephacel column and gel filtration on Sephadex G-75. SDS-PAGE showed the enzyme to be a monomer with a molecular weight of 16,500. BmooMtx induced release of creatine kinase and morphological analyses indicated that it provoked an intense myonecrosis, with visible leukocyte infiltrate and damaged muscle cells 24 hours after injection. Anti-BmooMTx antibodies partially neutralized the myotoxic activity of BmooMtx and crude B. moojeni venom, as judged by determination of plasma creatine kinase levels and histological evaluation of skeletal muscle in mice. Anti-BmooMTx antibodies were effective in reducing the plasma creatine kinase levels of crude B. alternatus and B. leucurus venoms, evidencing immunological cross-reactivity between BmooMTx and other bothropic venoms. Intraplantar (i.pl.) injection of BmooMtx (1 to 15 μg/animal) caused a dose- and time-dependent hyperalgesia and edematogenic responses. Dexamethasone (0.4 mg/kg), meloxicam (2 mg/kg) and promethazine (5 mg/kg) markedly reduced the hyperalgesia. Our data suggest that these drugs may likely serve as complementary therapies in cases of accidents with Bothrops moojeni, provided that such pharmacological treatments are administered immediately after the incident.