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1.
Pediatr Infect Dis J ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916929

RESUMO

Central nervous system infections in children caused by group A Streptococcus are rare. This study, conducted across 52 hospitals in Spain from 2019 to 2023, identified 32 cases of central nervous system infections in children caused by group A Streptococcus, with a significant increase from October 2022 onward (1.1% vs. 5.9%, P = 0.002). Half required pediatric intensive care unit admission, 12.5% exhibited sequelae and the mortality rate was 6.2%. Mastoiditis was the predominant primary infection.

2.
Sci Rep ; 14(1): 10396, 2024 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710724

RESUMO

Regulatory T cells (Tregs) is a subtype of CD4+ T cells that produce an inhibitory action against effector cells. In the present work we interrogated genomic datasets to explore the transcriptomic profile of breast tumors with high expression of Tregs. Only 0.5% of the total transcriptome correlated with the presence of Tregs and only four transcripts, BIRC6, MAP3K2, USP4 and SMG1, were commonly shared among the different breast cancer subtypes. The combination of these genes predicted favorable outcome, and better prognosis in patients treated with checkpoint inhibitors. Twelve up-regulated genes coded for proteins expressed at the cell membrane that included functions related to neutrophil activation and regulation of macrophages. A positive association between MSR1 and CD80 with macrophages in basal-like tumors and between OLR1, ABCA1, ITGAV, CLEC5A and CD80 and macrophages in HER2 positive tumors was observed. Expression of some of the identified genes correlated with favorable outcome and response to checkpoint inhibitors: MSR1, CD80, OLR1, ABCA1, TMEM245, and ATP13A3 predicted outcome to anti PD(L)1 therapies, and MSR1, CD80, OLR1, ANO6, ABCA1, TMEM245, and ATP13A3 to anti CTLA4 therapies, including a subgroup of melanoma treated patients. In this article we provide evidence of genes strongly associated with the presence of Tregs that modulates the response to check point inhibitors.


Assuntos
Neoplasias da Mama , Linfócitos T Reguladores , Transcriptoma , Humanos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica , Prognóstico
3.
Mol Ther Methods Clin Dev ; 32(1): 101193, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38352270

RESUMO

Friedreich's ataxia (FRDA) is an autosomal-recessive disorder primarily attributed to biallelic GAA repeat expansions that reduce expression of the mitochondrial protein frataxin (FXN). FRDA is characterized by progressive neurodegeneration, with many patients developing cardiomyopathy that progresses to heart failure and death. The potential to reverse or prevent progression of the cardiac phenotype of FRDA was investigated in a mouse model of FRDA, using an adeno-associated viral vector (AAV8) containing the coding sequence of the FXN gene. The Fxnflox/null::MCK-Cre conditional knockout mouse (FXN-MCK) has an FXN gene ablation that prevents FXN expression in cardiac and skeletal muscle, leading to cardiac insufficiency, weight loss, and morbidity. FXN-MCK mice received a single intravenous injection of an AAV8 vector containing human (hFXN) or mouse (mFXN) FXN genes under the control of a phosphoglycerate kinase promoter. Compared to vehicle-treated FXN-MCK control mice, AAV-treated FXN-MCK mice displayed increases in body weight, reversal of cardiac deficits, and increases in survival without apparent toxicity in the heart or liver for up to 12 weeks postdose. FXN protein expression in heart tissue was detected in a dose-dependent manner, exhibiting wide distribution throughout the heart similar to wild type, but more speckled. These results support an AAV8-based approach to treat FRDA-associated cardiomyopathy.

4.
Arch Bronconeumol ; 60(3): 133-142, 2024 Mar.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38238188

RESUMO

OBJECTIVE: The aim of this study was to elucidate the impact of pleural lavage cytology positivity on early recurrence in patients operated on non-small cell lung cancer (NSCLC). METHODS: This is a multicentre prospective cohort study of 684 patients undergoing an anatomical lung resection for NSCLC between October 2015 and October 2017 at 12 national centres. A pleural lavage was performed before and after lung resection. The association between the different predictors of early recurrence and PLC positivity was performed using univariate and multivariate logistic regression models. A propensity score analysis was performed by inverse probability weighting (IPSW) using average treatment effect (ATE) estimation to analyse the impact of PLC positivity on early recurrence. RESULTS: Overall PLC positivity was observed in 15 patients (2.2%). After two years, 193 patients (28.2%) relapsed, 182 (27.2%) with a negative PLC and 11 (73.3%) with a positive PLC (p<0.001). Factors associated to early recurrence were adenocarcinoma histology (OR=1.59, 95%CI 1.06-2.38, p=0.025), visceral pleural invasion (OR=1.59, 95%CI 1.04-2.4, p=0.03), lymph node involvement (OR=1.84, 95%CI 1.14-2.96, p=0.013), advanced pathological stage (OR=2.12, 95%CI 1.27-3.54, p=0.004) and PLC positivity (OR=4.14, 95%CI 1.25-16.36, p=0.028). After IPSW, PLC positivity was associated with an increased risk of early recurrence (OR=3.46, 95%CI 2.25-5.36, p<0.001). CONCLUSIONS: Positive pleural lavage cytology was found to be the strongest predictor of early recurrence.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Estudos Prospectivos , Irrigação Terapêutica , Citologia , Estadiamento de Neoplasias , Doença Crônica , Recidiva Local de Neoplasia/epidemiologia , Prognóstico
5.
ACS Appl Mater Interfaces ; 15(38): 44786-44795, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37699547

RESUMO

AIEgens have emerged as a promising alternative to molecular rotors in bioimaging applications. However, transferring the concept of aggregation-induced emission (AIE) from solution to living systems remains a challenge. Given the highly heterogeneous nature and the compartmentalization of the cell, different approaches are needed to control the self-assembly within the crowded intricate cellular environment. Herein, we report for the first time the self-assembly mechanism of an anthracene-guanidine derivative (AG) forming the rare and highly emissive T-shaped dimer in breast cancer cell lines as a proof of concept. This process is highly sensitive to the local environment in terms of polarity, viscosity, and/or water quantity that should enable the use of the AG as a fluorescence lifetime imaging biosensor for intracellular imaging of cellular structures and the monitoring of intracellular state parameters. Different populations of the monomer and T-shaped and π-π dimers were observed in the cell membrane, cytoplasm, and nucleoplasm, related to the local viscosity and presence of water. The T-shaped dimer is formed preferentially in the nucleus because of the higher density and viscosity compared to the cytoplasm. The present results should serve as a precursor for the development of new design strategies for molecular systems for a wide range of applications such as cell viscosity, density, or temperature sensing and imaging.


Assuntos
Antracenos , Imagem Óptica , Citoplasma , Membrana Celular , Polímeros , Água
6.
Pediatr Infect Dis J ; 42(10): 837-843, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37410579

RESUMO

BACKGROUND: To assess the prevalence and characteristics of nonsevere TB among children in Spain. It has been recently demonstrated that these children can be treated with a 4-month regimen instead of the classical 6-month treatment regimen, with the same effectivity and outcomes, decreasing toxicity and improving adherence. METHODS: We conducted a retrospective cohort study in a cohort of children ≤16 years of age with TB. Nonsevere TB cases included smear-negative children with respiratory TB confined to 1 lobe, with no significant airway obstruction, no complex pleural effusion, no cavities and no signs of miliary disease, or with peripheral lymph-node disease. The remaining children were considered to have severe TB. We estimated the prevalence of nonsevere TB and compared the clinical characteristics and outcomes between children with nonsevere and severe TB. RESULTS: A total of 780 patients were included [46.9% males, median age 5.5 years (IQR: 2.6-11.1)], 477 (61.1%) of whom had nonsevere TB. Nonsevere TB was less frequent in children <1 year (33% vs 67%; P < 0.001), and >14 years of age (35% vs 65%; P = 0.002), mostly diagnosed in contact tracing studies (60.4% vs 29.2%; P < 0.001) and more frequently asymptomatic (38.3% vs 17.7%; P < 0.001). TB confirmation in nonsevere disease was less frequent by culture (27.0% vs 57.1%; P < 0.001) and by molecular tests (18.2% vs 48.8%; P < 0.001). Sequelae were less frequent in children with nonsevere disease (1.7 vs 5.4%; P < 0.001). No child with nonsevere disease died. CONCLUSIONS: Two-thirds of children had nonsevere TB, mostly with benign clinical presentation and negative microbiologic results. In low-burden countries, most children with TB might benefit from short-course regimens.


Assuntos
Tuberculose Pulmonar , Tuberculose , Masculino , Humanos , Criança , Pré-Escolar , Feminino , Tuberculose Pulmonar/diagnóstico , Estudos Retrospectivos , Prevalência , Espanha/epidemiologia , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia
8.
Arch Dis Child ; 108(6): 445-450, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37019466

RESUMO

OBJECTIVE: To determine the incidence and clinical predictors of invasive bacterial infection (IBI) in well-appearing children who present to the emergency department (ED) with fever and petechiae. DESIGN: A prospective, observational, multicentre study was conducted in 18 hospitals between November 2017 and October 2019. PATIENTS: A total of 688 patients were recruited. MAIN OUTCOME MEASURES: The primary outcome was the presence of IBI. Clinical features and laboratory test results were described and related to the presence of IBI. RESULTS: Ten IBIs were found (1.5%), comprising eight cases of meningococcal disease and two of occult pneumococcal bacteraemia. Median age was 26.2 months (IQR 15.3-51.2). Blood samples were obtained from 575 patients (83.3%). Patients with an IBI had a shorter time from fever to ED visit (13.5 hours vs 24 hours) and between fever and rash onset (3.5 hours vs 24 hours). Values for absolute leucocyte count, total neutrophil count, C reactive protein and procalcitonin were significantly higher in patients with an IBI. Significantly fewer patients with a favourable clinical status while in the observation unit were found to have an IBI (2/408 patients, 0.5%) than when clinical status was unfavourable (3/18, 16.7%). CONCLUSIONS: The incidence of IBI among children with fever and petechial rash is lower than previously reported (1.5%). The time from fever to ED visit and to rash onset was shorter in patients with an IBI. Patients with a favourable clinical course during observation in the ED are at lower risk of IBI.


Assuntos
Infecções Bacterianas , Exantema , Púrpura , Infecções Estreptocócicas , Humanos , Criança , Lactente , Pré-Escolar , Estudos Prospectivos , Infecções Bacterianas/epidemiologia , Febre/etiologia , Febre/microbiologia , Serviço Hospitalar de Emergência , Púrpura/diagnóstico , Púrpura/epidemiologia , Púrpura/etiologia , Exantema/epidemiologia , Exantema/etiologia
9.
Science ; 379(6637): 1140-1149, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36927019

RESUMO

Loss of nuclear TDP-43 is a hallmark of neurodegeneration in TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP-43 mislocalization results in cryptic splicing and polyadenylation of pre-messenger RNAs (pre-mRNAs) encoding stathmin-2 (also known as SCG10), a protein that is required for axonal regeneration. We found that TDP-43 binding to a GU-rich region sterically blocked recognition of the cryptic 3' splice site in STMN2 pre-mRNA. Targeting dCasRx or antisense oligonucleotides (ASOs) suppressed cryptic splicing, which restored axonal regeneration and stathmin-2-dependent lysosome trafficking in TDP-43-deficient human motor neurons. In mice that were gene-edited to contain human STMN2 cryptic splice-polyadenylation sequences, ASO injection into cerebral spinal fluid successfully corrected Stmn2 pre-mRNA misprocessing and restored stathmin-2 expression levels independently of TDP-43 binding.


Assuntos
Proteínas de Ligação a DNA , Edição de Genes , Poliadenilação , Splicing de RNA , Estatmina , Proteinopatias TDP-43 , Animais , Humanos , Camundongos , Proteínas de Ligação a DNA/metabolismo , Precursores de RNA/genética , Precursores de RNA/metabolismo , Estatmina/genética , Estatmina/metabolismo , Proteinopatias TDP-43/genética , Proteinopatias TDP-43/terapia , Sítios de Splice de RNA , Oligonucleotídeos Antissenso/genética , Crescimento Neuronal
10.
Materials (Basel) ; 15(20)2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36295320

RESUMO

In this study, functional nanocoatings for water-repellent footwear leather materials were investigated by chemical plasma polymerisation by implanting and depositing the organosilicon compound hexamethyldisiloxane (HMDSO) using a low-pressure plasma system. To this end, the effect of monomers on leather plasma deposition time was evaluated and both the resulting plasma polymers and the deposited leather samples were characterised using different experimental techniques, such as: Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). In addition, leather samples were tested by standard tests for color change, water resistance, surface wetting resistance and dynamic water contact angle (DWCA). The resulting polysiloxane polymers exhibited hydrophobic properties on leather. Furthermore, these chemical surface modifications created on the substrate can produce water repellent effects without altering the visual leather appearance and physical properties. Both plasma coating treatments and nanocoatings with developed water-repellency properties can be considered as a more sustainable, automated and less polluting alternative to chemical conventional processing that can be introduced into product-finishing processes in the footwear industry.

11.
Laryngoscope Investig Otolaryngol ; 7(2): 417-424, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35434333

RESUMO

Background: The standard treatment for endemic goiter is usually total thyroidectomy. In low- and middle-income countries, the management of thyroid disease, which is commonplace in fully developed countries, is not always possible. The purpose of this study is to establish a treatment algorithm to calculate the extent of thyroidectomy based on the risk factors of each patient. Methods: This is a retrospective observational study conducted during the period between 2017 and 2019. A total of 287 patients with thyroid pathology were treated in Maragua Hospital (Kenya). The results of surgical treatment were analyzed after the implementation of an individualized treatment protocol. Results: One hundred and sixty patients with different types of goiter underwent surgery: solitary nodule (54.4%), multi-nodular goiter (30.6%), diffuse goiter (10.6%), and intrathoracic goiter (3.8%). The techniques used were hemithyroidectomy (78.8%), Dunhill thyroidectomy (9.4%), bilateral subtotal thyroidectomy (6.9%), and total thyroidectomy (3.1%). There was no mortality. The surgical morbidity rate was 16% (only one major complication (3b)). Two cases of dysphonia were resolved in the first week. There were three cases of symptomatic hypocalcaemia, two of which resolved in the first week and the other of which was definitive. The follow-up at 6 months was 67%. The cancer rate found in the resection specimens was 5%. Discussion: The implementation of individualized surgical protocols for thyroid surgery in sub-Saharan Africa can improve outcomes. The cooperation projects can increase access to complex surgical treatment for patients with limited resources in low- and middle-income countries.

12.
Polymers (Basel) ; 13(20)2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34685306

RESUMO

The aim of this work is to develop hydrophobic coatings on leather materials by plasma polymerisation with a low-pressure plasma system using an organosilicon compound, such as hexamethyldisiloxane (HMDSO), as chemical precursor. The hydrophobic coatings obtained by this plasma process were evaluated with different experimental techniques such as Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and standardised tests including colour measurements of the samples, surface coating thickness and water contact angle (WCA) measurements. The results obtained indicated that the monomer had polymerised correctly and completely on the leather surface creating an ultra-thin layer based on polysiloxane. The surface modification produced a water repellent effect on the leather that does not alter the visual appearance and haptic properties. Therefore, the application of the plasma deposition process showed promising results that makes it a more sustainable alternative to conventional functional coatings, thus helping to reduce the use of hazardous chemicals in the finishing process of footwear manufacturing.

13.
Front Psychiatry ; 12: 692215, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34354613

RESUMO

Purpose: This study aims to analyze from a gender perspective the psychological distress experienced by the medical workforce during the peak of the pandemic in Spain. Methods: This is a single-center, observational analytic study. The study population comprised all associated health workers of the Cruces University Hospital, invited by email to participate in the survey. It consisted of a form covering demographic data, the general health questionnaire-28 (GHQ-28), and the perceived stress scale (PSS-14). We used multivariant regression analysis to check the effect of gender on the scores. We used gender analysis in both design and interpretation of data following SAGER guidelines. Results: Females made 74.6% of our sample, but their proportion was higher in lower-paid positions such as nursery (89.9%) than in higher-paid ones. The percentage of women categorized as cases with the GHQ-28 was 78.4%, a proportion significantly higher than in the male population (61.3%, p < 0.001). The multivariant regression analysis showed that being women, working as orderly hospital porters, and having a past psychiatric history were risk factors for higher scores in both the GHQ-28 and PSS-14. Conclusion: Women and those with lower-paid positions were at risk of higher psychological distress and worse quality of life within the medical workforce during the first wave of the pandemic. Gender analysis must be incorporated to analyze this fact better.

14.
J Maxillofac Oral Surg ; 20(3): 464-469, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34408375

RESUMO

Rhabdomyosarcoma (RMS) is a malignant soft tissue neoplasm with its origin in the skeletal muscle and is extremely rare in adults. By the World Health Organization (WHO), a new variant of RMS has been classified, i.e. the spindle cell (Sc) and sclerosing (S) RMS. While the Sc-RMS shows intersecting fascicles of nonpleomorphic spindle cells, the S-RMS is characterized by a marked hyalinization in a pseudovascular growth pattern associated with round-to-spindled tumour cells. According to the analysed data, the Sc/S-RMS variant has a worse outcome than other variants. The new classification of the Sc/S-RMS variant is valuable to the clinical practice. There are not many oral Sc/S-RMS cases reported. The aim of this paper is to demonstrate that an early diagnosis, an adequate treatment and a multidisciplinary approach have a positive effect on the prognosis of the patient. In this study, we analyse a new case of Sc-RMS variant in a young adult with an early diagnosis and a favourable outcome as a result of an appropriated multidisciplinary treatment: early surgery, radiotherapy and chemotherapy treatment.

15.
J Pers Med ; 11(8)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34442453

RESUMO

BACKGROUND: Dysmenorrhoea is the medical term for menstrual pain. The World Health Organization estimates that up to 81% of women of childbearing age are affected by this condition, and it is one of the leading causes of absenteeism from work and school among women. Although there are pharmacological treatments available for menstrual-pain relief, they do not respond to all women's needs. Therefore, there is a need to study and develop non-pharmacological alternatives to broaden the individualised treatment options for dysmenorrhea. There are scarce studies published on non-pharmacological treatments, such as kinesio tape and auricular acupressure for the relief of menstrual pain, but the scientific evidence available suggest that these techniques may be beneficial in addressing this problem. The objective of this pilot study was to assess and compare the effectiveness of kinesio tape and auricular acupressure to decrease pain and drug intake in women with primary dysmenorrhoea. METHODS: This was a double-blind randomized clinical controlled trial. The period of study was from September 2017 to August 2018. Women enrolled in the University of Extremadura and who had primary dysmenorrhoea were randomized to five groups: control (n = 23), kinesio tape (n = 23), placebo kinesio tape (n = 23), auricular acupressure (n = 23) and placebo auricular acupressure (n = 22). Measures were taken during the pretreatment phase (at four menstrual cycles), during the post-intervention phase (at four menstrual cycles) and during the follow-up phase (at the first and third menstrual cycles after the treatment was completed). The primary outcome measures were mean pain intensity, maximum pain intensity, number of painful days and dose of drug intake during menstruation, measured with the Visual Analogue Scale. The secondary outcome measures were the length of the cycle, the length of menstruation, the drug intake and the type of drug. RESULTS: In all, 108 participants completed the study. The statistical analysis (MANOVA, ANOVA, t-paired and McNemar tests) showed that kinesio tape and auricular acupressure have a beneficial effect on pain relief (mean pain intensity, p < 0.001; maximum pain intensity, p < 0.001; number of painful days, p = 0.021; dose of drug intake, p < 0.001). In addition, once the treatments were withdrawn, the auricular-acupressure group maintained lower scores during the first follow-up cycle (p < 0.001). CONCLUSIONS: Kinesio tape and auricular acupressure decrease pain and drug intake in women with primary dysmenorrhoea. The changes in the auricular-acupressure group seemed to last longer. The results suggest that these techniques could be used as complementary personalised therapies to the pharmacological treatment and not as a substitution.

17.
An Pediatr (Engl Ed) ; 94(1): 11-18, 2021 Jan.
Artigo em Espanhol | MEDLINE | ID: mdl-32386933

RESUMO

INTRODUCTION: The admission of minors into adult psychiatric units is a problem and is due to the lack of adequate resources and epidemiology data. OBJECTIVE: The aim of this study is to describe and analyse the sociodemographic and clinical characteristics of minors that were admitted into the Short-Stay Psychiatric Hospitalisation Unit of Caceres, Spain. MATERIALS AND METHODS: A retrospective, observational, and descriptive study was conducted on a sample of patients between 12 and 18 years-old admitted to the Psychiatric Unit. The study period was between January 1, 2014 and December 31, 2018. RESULTS: A total of 79 patients, with a mean age of 15.72 (± 1.65) years, were included. Almost all of them (93.6%) had a personal psychiatric history. The most common diagnoses at discharge in males were disruptive, impulse-control and conduct disorders, and mood disorders in females. A history of substance consumption was present in 40.6%, and was more common in males, which led to a worse prognosis. The mean stay was 5.4 (± 4.7) days. Prolongation of the mean stay was associated with a history of previous psychiatric admissions, the number of diagnoses at discharge, a greater number of drugs at discharge, and those that received long-acting injectable antipsychotic drugs (p < 0.005 in all cases). CONCLUSIONS: The study identified the sociodemographic and clinical profile of the minor admitted to the Psychiatric Unit, and how the hospital stay was associated with previous psychiatric history, as well as diagnostic and clinical complexity.


Assuntos
Hospitalização , Menores de Idade , Adolescente , Criança , Feminino , Hospitais Psiquiátricos , Humanos , Tempo de Internação , Masculino , Alta do Paciente , Estudos Retrospectivos , Espanha
18.
Sci Total Environ ; 755(Pt 2): 142971, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172636

RESUMO

Despite an improvement of water quality across Europe there are many pollution hotspots for both nitrates and PPPs, mainly due to agricultural activities. The BMPs and MMs to reduce pollution from agriculture are well known, and there are policy instruments in place to ensure drinking water standards, but the current approach has not been efficient enough. Within the H2020 Water Protect project the premise was that there is a need for a multi-actor, participatory approach to tackle the issue from a new angle, and to assess why the uptake of known BMPs and MMs was not better among farmers. Seven "Action Labs" were selected that represent major physical, socio-economical, cultural and farming settings across Europe. A methodology of multi-actor engagement was chosen but with different approaches due to the local context. Initially the level of farmers' awareness about water quality issues was matched to the observed uptake rates of BMPs and MMs. In a second survey barriers hindering the uptake of measures were identified. The first survey revealed a low general awareness on the potential pollution to drinking water sources. Despite this, between 24% to 88% of the surveyed farmers per Action Lab were already voluntarily adopting one quarter of the selected BMPs and MMs. The second survey demonstrated the need to address organisational, legislative, sociological and technical barriers. The lack of coordination between different institutional bodies promoting measures and the financial incentives needed to invest and operate these often-costly measures need to be considered. The multi-actor, participatory approach with its improved awareness and collaboration made it possible to identify the crucial factors for improvement - to build a social acceptance among all actors and communicate the issues and solutions from the start.

19.
Cancers (Basel) ; 12(8)2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32796628

RESUMO

Treatment with anti-PD-L1 antibodies has shown efficacy in basal-like breast cancer. In this context, identification of pre-activated immune tumors is a main goal. Here we explore mutations in PD1 and PD-L1 high-expressing tumors to identify genomic correlates associated with outcome. To do so, RNA-seq and mutation data from 971 breast cancer patients from the TCGA dataset were used to identify most prevalent mutations in patients with high levels of PD1 and PD-L1. Transcriptomic signatures associated with the selected mutations were identified and analyzed in terms of outcome and immune cell infiltration. We identified co-occurrent mutations in RYR2 and AHNAK in 8% and 5% of basal-like tumors respectively, which conferred good prognosis in patients with high expression of PD1 and PD-L1 genes. The transcriptomic signature associated with these mutations, composed of CXCL9, GBP5, C1QA, IL2RG, CSF2RB, IDO1 and LAG3 genes, also conferred good prognosis and correlated with immune infiltrations within the tumors. The joint signature classified patients with favorable relapse-free survival (HR: 0.28; CI: 0.2-0.38; p = 1.7 × 10-16) and overall survival (HR: 0.18; CI: 0.09-0.34; p = 6.8 × 10-9), showing a stronger prediction capacity than previous reported signatures. In conclusion, we describe two novel mutations and their transcriptomic signature, both associated with a favorable outcome and immune infiltrates in PD1 and PD-L1 high-expressing basal-like tumors.

20.
Vaccines (Basel) ; 8(1)2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32059491

RESUMO

In vitro neutralizing antibodies have been often correlated with protection against Rift Valley fever virus (RVFV) infection. We have reported previously that a single inoculation of sucrose-purified modified vaccinia Ankara (MVA) encoding RVFV glycoproteins (rMVAGnGc) was sufficient to induce a protective immune response in mice after a lethal RVFV challenge. Protection was related to the presence of glycoprotein specific CD8+ cells, with a low-level detection of in vitro neutralizing antibodies. In this work we extended those observations aimed to explore the role of humoral responses after MVA vaccination and to study the contribution of each glycoprotein antigen to the protective efficacy. Thus, we tested the efficacy and immune responses in BALB/c mice of recombinant MVA viruses expressing either glycoprotein Gn (rMVAGn) or Gc (rMVAGc). In the absence of serum neutralizing antibodies, our data strongly suggest that protection of vaccinated mice upon the RVFV challenge can be achieved by the activation of cellular responses mainly directed against Gc epitopes. The involvement of cellular immunity was stressed by the fact that protection of mice was strain dependent. Furthermore, our data suggest that the rMVA based single dose vaccination elicits suboptimal humoral immune responses against Gn antigen since disease in mice was exacerbated upon virus challenge in the presence of rMVAGnGc or rMVAGn immune serum. Thus, Gc-specific cellular immunity could be an important component in the protection after the challenge observed in BALB/c mice, contributing to the elimination of infected cells reducing morbidity and mortality and counteracting the deleterious effect of a subneutralizing antibody immune response.

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