A conceptual framework for landscape-based environmental risk assessment (ERA) of pesticides.

While pesticide use is subject to strict regulatory oversight worldwide, it remains a main concern for environmental protection, including biodiversity conservation. This is partly due to the current regulatory approach that relies on separate assessments for each single pesticide, crop use, and non-target organism group at local scales. Such assessments tend to overlook the combined effects of overall pesticide usage at larger spatial scales. Integrative landscape-based approaches are emerging, enabling the consideration of agricultural management, the environmental characteristics, and the combined effects of pesticides applied in a same or in different crops within an area. These developments offer the opportunity to deliver informative risk predictions relevant for different decision contexts including their connection to larger spatial scales and to combine environmental risks of pesticides, with those from other environmental stressors. We discuss the needs, challenges, opportunities and available tools for implementing landscape-based approaches for prospective and retrospective pesticide Environmental Risk Assessments (ERA). A set of "building blocks" that emerged from the discussions have been integrated into a conceptual framework. The framework includes elements to facilitate its implementation, in particular: flexibility to address the needs of relevant users and stakeholders; means to address the inherent complexity of environmental systems; connections to make use of and integrate data derived from monitoring programs; and options for validation and approaches to facilitate future use in a regulatory context. The conceptual model can be applied to existing ERA methodologies, facilitating its comparability, and highlighting interoperability drivers at landscape level. The benefits of landscape-based pesticide ERA extend beyond regulation. Linking and validating risk predictions with relevant environmental impacts under a solid science-based approach will support the setting of protection goals and the formulation of sustainable agricultural strategies. Moreover, landscape ERA offers a communication tool on realistic pesticide impacts in a multistressors environment for stakeholders and citizens.

Analysis of the optical performance of intraocular lenses using profilometric measurements.

PURPOSE: The aim of this study was to develop a methodology, based on profilometer measurements to assess the optical behaviour of Intraocular Lenses (IOls). The "Modulation Transfer Function through-object" (MTF through-object) based on vergence object displacement was calculated for different pupil sizes and pseudophakic eyes. Tilt and decentration were also analysed in a realistic cornea eye model. METHODS: For comparison between the different IOLs, an optical quality criterion based on a minimum value the MTF through-object and the recognition of simulated vision optotypes was introduced. Five IOLs were used in this study: Tecnis Eyhance, Mini Well, Tecnis Symfony, Tecnis Synergy and RayOne EMV. RESULTS: The technique was validated with previous methodologies. A general narrowing of the through-object MTF curve compared to the through-focus MTF curve was shown, resulting in greater distances between near and intermediate points and less depth of field around the far peak. The comparison between the IOLs showed that variations in corneal aberrations, pupil size and decentration caused relevant changes in IOL performance. A decrease of the SA produced a hypermetropic shift of the far focus between + 0.3 D and + 0.4 D. Most of IOLs worsen the optical quality as pupil size increased, even the MTF through-object shape changed. Decentration was an important factor in IOL implantation, causing a significant change in MTF through-object shape in most of IOLs. CONCLUSIONS: This study highlights the need to evaluate pre-operative patients for corneal aberrations and pupillary size to have the best optical success after cataract surgery in multifocal or extended depth of focus IOLs. KEY MESSAGES: What is known MTF(Modulation Transfer Function) through-focus curves (calculated in image space by moving the detector plane) can be obtained from optical bench assembly or from commercial devices. Recently, some studies proposed to characterize the lens surface design based on the profilometric measurements What is new A novel methodology based on profilometer measurements to assess the optical behaviour of Intraocular Lenses (IOls) was shown. The "Modulation Transfer Function through-object" based on vergence object displacement was introduced in order to analyse five premium IOLs. MTF through-object curve is more appropriate for studying clinical behaviour, as it provides further near and intermediate points distances and lower depth of focus around far peak compare to MTF through-focus curves. The optical behaviour of the five IOLs can vary considerably depending on the eye model and pupil size. The effect of tilt and decentration on the MTF through-object the IOLs was analysed.

Prevalence of Fabry disease in patients with left ventricular hypertrophy and renal involvement (PrEFaCe). / Prevalencia de la enfermedad de Fabry en los pacientes con hipertrofia ventricular izquierda e insuficiencia renal (PrEFaCe).

INTRODUCTION AND AIMS: Fabry disease (FD) causes glycosphingolipid accumulation in the vascular endothelium, with predominantly cardiac and renal involvement. Its prevalence in patients with concomitant involvement of these two organs is unknown. The objective of the study was to determine the prevalence of FD in patients with left ventricular hypertrophy and any degree of chronic kidney disease. PATIENTS AND METHODS: Patients with ventricular thickness ≥13mm and kidney disease from 29 Spanish hospitals were included. Sociodemographic variables and target organ involvement of FD were collected. Laboratory determinations of EF were carried out, with an enzymatic activity test±genetic test in men and direct genetic test in women. RESULTS: Eight hundred ninety-eight patients with left ventricular hypertrophy and chronic kidney disease were included. The presence of heart failure and cardiorenal syndrome was common (46.1% and 40.1%). Three patients (2 men and 1 woman) were diagnosed with FD, based on the presence of a pathogenic variant in the GLA gene and classic signs of FD, resulting in a prevalence of 0.33% (CI 95% 0.06-1%). Six patients (0.66%) presented genetic variants of unknown significance, without showing classic signs of FD, while in 13 patients (3.2%) performing the blood test was impossible. CONCLUSIONS: FD is an important cause of left ventricular hypertrophy and chronic kidney disease. Genetic diagnosis is crucial for avoiding biases and ensuring accurate identification of FD, especially in women. The results support the inclusion of this disease in the differential diagnosis of patients with ventricular hypertrophy ≥13mm and chronic kidney disease.

Effectiveness of digital interventions to reduce school-age adolescent sexual risks: A systematic review.

INTRODUCTION: The increase in risky sexual behaviors among adolescent students has sparked alarm and has become an area of research interest. As adolescents prioritize confidentiality and accessibility, digital interventions are becoming increasingly relevant in sex education. We therefore posed the following research question: Are digital application interventions effective to prevent risky sexual behaviors in school adolescents? DESIGN: A systematic peer review was conducted between January and December 2023 in five databases (PubMed, Web of Science, Scopus, EMBASE, and PsycINFO) without restricting for language or year of publication. METHOD: We included randomized control trials or quasi-experimental studies that measured the effectiveness of interventions targeting young people aged 10-19 years or their parents and developed in a school setting. Interventions aimed at young people with intellectual disabilities, learning difficulties, or any disease requiring a specific intervention were excluded. RESULTS: The search ultimately yielded 27 studies covering a total of 18 digital interventions that demonstrated positive effects, not maintained over time, on knowledge, attitudes, and behaviors, although the latter to a lesser extent. DISCUSSION: We have found very interesting digital interventions with effects, among others, on knowledge, attitudes, and contraceptive use in adolescents. In general, digital interventions have positive effects on knowledge and attitudes, but it is more difficult to modify behaviors with strictly digital interventions or combined with complementary face-to-face sessions or group class activities. CONCLUSION: We thus believe that digital interventions are adequate to reduce adolescent sexual risk behaviors, and our systematic review facilitates the implementation of these interventions by sharing existing digital interventions that have had positive effects, as well as the main characteristics a digital intervention should possess to reduce sexually risky behaviors in adolescents. CLINICAL RELEVANCE: Digital interventions with adolescents improve sexual behaviors and can be a valuable resource in education on this topic due to their accessibility and confidentiality, two key points for young people.

Combination of toxicological and epidemiological approaches for estimating the health impact of atmospheric pollutants. A proof of concept for NO2.

BACKGROUND: Regular monitoring of the air pollutant nitrogen dioxide (NO2), an indicator for traffic-related emissions, is a priority in urban environments. The health impacts associated with NO2 exposure are the result of a combination of factors, including concentration, duration of exposure, and interactions with other pollutants. WHO has established air quality guidelines based on epidemiological studies. OBJECTIVE: This study develops a new concept "Health Impact Pathways (HIPs)" using adversity as a probabilistic indicator of health effects. For this purpose, it integrates available toxicological and epidemiological information, using Adverse Outcome Pathways (AOPs), in order to understand chemical-biological interactions and their consequences on health. METHODS: Literature review and meta-analysis of toxicological data supported by expert judgment were performed to establish: a) adversity pathways, b) quantitative criteria for scoring the observed toxicological effects (adversity indicators), c) NO2 exposure - adversity relationship for both long-term (1-36 months) and shortterm (1-7 days). The NO2 daily concentrations from January 2001 to December 2022, were obtained from Madrid city Air Quality network monitoring database. Adversity levels were compared with relative risk levels for all-cause and respiratory mortality estimated using linear equations from WHO 2021 guidelines. RESULTS: Non-linear relations were obtained for all long- and short-term NO2 related adversity indicators; for long-term effects, the best fitting was obtained with a modified Haber's law model with an exponential coefficient for the exposure time of 0.25. Estimations are presented for a set of case studies for Madrid city, covering temporal and spatial variability. A clear improvement trend along the two decades was observed, as well as high inter- and intra-station variability; the adversity indicators provided integrated information on the temporal and spatial evolution of population level risk. DISCUSSION: The proposed HIP conceptual approach offers promising advances for integrating experimental and epidemiological data. The next step is linking the concentration-adversity relationship with population health impacts through probability estimations, the preliminary estimations confirm the need for assessing independently different population groups.

Ibrutinib in Combination with R-GemOx in Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma of Nongerminal Center B-cell-like Type: Phase II Clinical Trial of the Spanish GELTAMO Group.

PURPOSE: This phase II clinical trial evaluated the combination of ibrutinib with rituximab, gemcitabine, and oxaliplatin (R-GemOx) in patients with nongerminal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: The IBDCL trial (NCT02692248) included patients with histologic diagnosis of non-GCB DLBCL with relapsed or refractory disease and non-candidates for stem-cell transplantation. Patients received an induction treatment consisting of six or eight cycles of R-GemOx at standard doses every 2 weeks, in combination with ibrutinib (560 mg daily), followed by a maintenance treatment with ibrutinib for a maximum of 2 years. The primary objective was to evaluate the overall response rate after four cycles. RESULTS: Sixty-four patients were included, 72% of them refractory to the last regimen. The overall response rate and complete remission rate after the fourth cycle were 53% [95% confidence interval (CI), 41-65] and 34% (95% CI, 24-46), respectively. Twenty-four (37%) patients started maintenance, and 7 (11%) completed the planned 2 years. After a median follow-up of 29.7 months (range: 0.4-48.6), the estimated 2-year progression-free survival and overall survival were 18% (95% CI, 8-28) and 26% (95% CI, 14-37), respectively. The most common grade ≥3 treatment-related adverse events were thrombocytopenia (44%), neutropenia (30%), and anemia (14%). Grade ≥3 infectious and cardiovascular treatment-related adverse events were reported in 6 (9%) and 1 (2%) patient, respectively. CONCLUSIONS: Ibrutinib in combination with R-GemOx, followed by ibrutinib maintenance, demonstrated encouraging antitumor activity with durable responses and a manageable toxicity in patients with non-GCB DLBCL.

Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease.

Circulating tumour DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a next-generation sequencing (NGS) approach (EuroClonality-NDC), we evaluated the clinical and prognostic value of ctDNA in a series of R-CHOP-treated diffuse large B-cell lymphoma (DLBCL) patients at baseline (n = 68) and after two cycles (n = 59), monitored by metabolic imaging (positron emission tomography combined with computed tomography [PET/CT]). A molecular marker was identified in 61/68 (90%) ctDNA samples at diagnosis. Pretreatment high ctDNA levels significantly correlated with elevated lactate dehydrogenase, advanced stage, high-risk International Prognostic Index and a trend to shorter 2-year progression-free survival (PFS). Valuable NGS data after two cycles of treatment were obtained in 44 cases, and 38 achieved major molecular response (MMR; 2.5-log drop in ctDNA). PFS curves displayed statistically significant differences among those achieving MMR versus those not achieving MMR (2-year PFS of 76% vs. 0%, p < 0.001). Similarly, more than 66% reduction in ΔSUVmax by PET/CT identified two subgroups with different prognosis (2-year PFS of 83% vs. 38%; p < 0.001). Combining both approaches MMR and ΔSUVmax reduction, a better stratification was observed (2-year PFS of 84% vs. 17% vs. 0%, p < 0.001). EuroClonality-NDC panel allows the detection of a molecular marker in the ctDNA in 90% of DLBCL. ctDNA reduction at two cycles and its combination with interim PET results improve patient prognosis stratification.

Genomic Context of SARS-CoV-2 Outbreaks in Farmed Mink in Spain during Pandemic: Unveiling Host Adaptation Mechanisms.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects various mammalian species, with farmed minks experiencing the highest number of outbreaks. In Spain, we analyzed 67 whole genome sequences and eight spike sequences from 18 outbreaks, identifying four distinct lineages: B.1, B.1.177, B.1.1.7, and AY.98.1. The potential risk of transmission to humans raises crucial questions about mutation accumulation and its impact on viral fitness. Sequencing revealed numerous not-lineage-defining mutations, suggesting a cumulative mutation process during the outbreaks. We observed that the outbreaks were predominantly associated with different groups of mutations rather than specific lineages. This clustering pattern by the outbreaks could be attributed to the rapid accumulation of mutations, particularly in the ORF1a polyprotein and in the spike protein. Notably, the mutations G37E in NSP9, a potential host marker, and S486L in NSP13 were detected. Spike protein mutations may enhance SARS-CoV-2 adaptability by influencing trimer stability and binding to mink receptors. These findings provide valuable insights into mink coronavirus genetics, highlighting both host markers and viral transmission dynamics within communities.

Complementary and Alternative Medicine to Treat Fibromyalgia Symptoms. A Systematic Review.

This study aims to investigate the current evidence for the use of complementary and alternative medicine (CAM) in fibromyalgia (FM). A systematic review was conducted searching for PubMed, Scopus, CINAHL, PsycInfo, and Web of Science databases. Randomized controlled trials published up to December 2023 in peer-reviewed journals were included. Methodological quality was assessed by the Quality Assessment of Controlled Intervention Studies tool. A total of 216 articles were identified and 15 constituted the final sample. The type of CAM most used was traditional Chinese medicine (60%), and the most common instrument used was the Fibromyalgia Impact Questionnaire (60%). Our review was grouped into four themes based on the origin of the therapies: 1) Traditional Chinese Medicine; 2) Japanese natural harmonization (eg, Reiki); 3) Ayurvedic Medicine; and 4) Other non-drug therapies. Our systematic review showed that there is a wide range of CAMs used to treat FM. Most of the clinical trials have shown significant results for the effectiveness of these interventions in both physical and mental health outcomes of FM as compared to control groups. However, the heterogeneity of the interventions and outcomes warrants further studies on this topic.

Perceptions, Beliefs, and Experiences about the Menstrual Cycle and Menstruation among Young Women: A Qualitative Approach.

The experience of menstruation is often associated with negative connotations and gender stereotypes, which results in making it invisible. This research aimed to explore the perceptions, beliefs, and knowledge of young Spanish women regarding the menstrual cycle and menstruation and their impact on their lives. The study delves into their understanding, menstrual management practices, the types of menstrual products employed, and their experiences related to menstrual health. Qualitative methodology was used with discussion groups as a data collection technique. The participants comprised 45 young Spanish women, aged between 18 and 23, hailing from both rural and urban areas. The majority were university students, with some engaged in part-time work, and one participant working full-time. While many experienced menstrual pain ranging from mild to debilitating, a normalization of this pain often led them to forego seeking specialist assistance. Disposable menstrual products (DMPs) are the most used by participants, despite limited awareness of their absorption capacity. Regarding reusable menstrual products (RMPs), menstrual cup users emphasized comfort but expressed a need for proper training. Negative menstruation experiences could evoke fear and difficulties, underscoring the importance of providing comprehensive menstrual health education encompassing both theoretical and practical components.

Magnetic-Assisted Control of Eggs and Embryos via Zona Pellucida-Linked Nanoparticles.

Eggs and embryo manipulation is an important biotechnological challenge to enable positioning, entrapment, and selection of reproductive cells to advance into a new era of nature-like assisted reproductive technologies. Oviductin (OVGP1) is an abundant protein in the oviduct that binds reversibly to the zona pellucida, an extracellular matrix that surrounds eggs and embryos. Here, the study reports a new method coupling OVGP1 to magnetic nanoparticles (NP) forming a complex (NPOv). NPOv specifically surrounds eggs and embryos in a reversible manner. Eggs/embryos bound to NPOv can be moved or retained when subjected to a magnetic force, and interestingly only mature-competent eggs are attracted. This procedure is compatible with normal development following gametes function, in vitro fertilization, embryo development and resulting in the birth of healthy offspring. The results provide in vitro proof-of-concept that eggs and embryos can be precisely guided in the absence of physical contact by the use of magnets.

Study of histopathology on Arbacia lixula (Arbaciidae: Arbacioida) and Paracentrotus lividus (Parachinidae: Camarodonta) with bald sea urchin disease symptoms in Gran Canaria Island, Spain / Estudio de histopatología en Arbacia lixula (Arbaciidae: Arbacioida) y Paracentrotus lividus (Parachinidae: Camarodonta) con síntomas de la enfermedad del erizo desnudo en la Isla de Gran Canaria, España

Abstract Introduction: Sea urchin diseases have been documented in several locations worldwide, with reported occurrences of bacterial, protozoan, fungal, and algal infections. Objective: This study aimed to investigate pathogen agents in populations of Arbacia lixula and Paracentrotus lividus along the coast of Gran Canaria Island (Central-East Atlantic, Spain). Methods: Sampling was conducted at San Cristobal beach, on the Northeast side of the island, where sea urchins were manually collected from depths of 1-3 m during June, July, and October 2022. Swab samples were taken from the external and internal areas of the lesions and cultured on various media plates. Results: Eight different pathogen agents, including bacteria and fungi, were identified, with Vibrio alginolyticus being the most frequently observed bacteria in all diseased sea urchin samples. Additionally, ciliated protozoans were found within the tests, potentially acting as opportunistic parasites. Conclusions: This research provides a unique perspective on bald sea urchin disease by identifying a significant number of associated pathogens, including Candida, previously unreported in diseased organisms. Furthermore, the study highlights the presence of an inflammatory response in tissues with bacterial colonies, offering crucial insights into understanding this sea urchin disease.

Resumen Introducción: Las enfermedades en los erizos de mar han sido descritas en muchas localidades alrededor del mundo, y se han asociado con la presencia de infecciones por bacterias, protozoarios, hongos y algas. Objetivo: Este estudio tuvo como finalidad investigar sobre los agentes patógenos que afectan a las poblaciones de Arbacia lixula y Paracentrotus lividus a lo largo de la costa de la Isla de Gran Canaria (Atlántico Centro-Oriental, España). Métodos: El muestreo fue llevado a cabo en la playa de San Cristóbal, al noreste de la isla, dónde los organismos fueron capturados entre 1-3 metros de profundidad, durante junio, julio y octubre del año 2022. Se tomaron muestras en la zona interna y externa de la lesión en cada organismo, y se cultivaron en varios medios de cultivo. Resultados: Fueron identificados ocho agentes patógenos diferentes, incluyendo bacterias y hongos, y siendo Vibrio alginolyticus la bacteria más frecuentemente observada en todas las muestras de erizos enfermos. Además, se observaron protozoarios ciliados dentro de los caparazones, actuando potencialmente como parásitos oportunistas. Conclusiones: Esta investigación proporciona una perspectiva única sobre la enfermedad del erizo desnudo al identificar un número significativo de patógenos asociados, incluida Candida, que no se había reportado previamente en organismos enfermos. Además, el estudio destaca la presencia de una respuesta inflamatoria en tejidos con colonias bacterianas, lo que ofrece información crucial para comprender esta enfermedad de los erizos de mar.

The social and health consequences of the war for Ukrainian children and adolescents: a rapid systematic review.

OBJECTIVES: Despite the growing interest on the Russian-Ukrainian war and its repercussion on the children's health, there is no previous systematic review compiling the current evidence on this topic. This study conducted a rapid systematic review to investigate the current findings concerning the impact of the Ukraine war on the social and health aspects of the Ukrainian pediatric population. METHODS: A rapid systematic review was conducted. PubMed, Scopus, CINAHL, PsycINFO, Web of Science, and Virtual Health Library (BVS Spain) were searched between February and April 2023. In addition, high-impact journals and institutions focused on pediatric health and human rights were also consulted. All relevant original articles, letters, editorials, and policy papers assessing the health and social repercussions of the war on Ukrainian children were included. RESULTS: From 134 publications matching the search criteria, 23 were included. These publications were categorized into three distinct domains: 'Public health challenges for the physical and mental health of children and adolescents', 'Lack of Healthcare resources and initiatives to mitigate suffering', and 'Policies, Government, and Children's rights'. Our findings revealed that the war is seriously impacting the life and the health of Ukrainian children, resulting in worse physical and mental health outcomes and perpetrating a deprived situation. To overcome such problems, several initiatives have been proposed by European and non-European countries, relying mostly on receiving refugees, providing mental health support, complementing lack of resources, and establishing policies to improve health care. CONCLUSION: It could help health professionals, policy makers, and governments to plan preventive, promotive, and therapeutic strategies for Ukrainian children.

Comparative severity of COVID-19 cases caused by Alpha, Delta or Omicron SARS-CoV-2 variants and its association with vaccination.

BACKGROUND: This study compares the severity of SARS-CoV-2 infections caused by Alpha, Delta or Omicron variants in periods of co-circulation in Spain, and estimates the variant-specific association of vaccination with severe disease. METHODS: SARS-CoV-2 infections notified to the national epidemiological surveillance network with information on genetic variant and vaccination status were considered cases if they required hospitalisation or controls otherwise. Alpha and Delta were compared during June-July 2021; and Delta and Omicron during December 2021-January 2022. Adjusted odds ratios (aOR) were estimated using logistic regression, comparing variant and vaccination status between cases and controls. RESULTS: We included 5,345 Alpha and 11,974 Delta infections in June-July and 5,272 Delta and 10,578 Omicron in December-January. Unvaccinated cases of Alpha (aOR: 0.57; 95% CI: 0.46-0.69) or Omicron (0.28; 0.21-0.36) had lower probability of hospitalisation vs. Delta. Complete vaccination reduced hospitalisation, similarly for Alpha (0.16; 0.13-0.21) and Delta (June-July: 0.16; 0.14-0.19; December-January: 0.36; 0.30-0.44) but lower from Omicron (0.63; 0.53-0.75) and individuals aged 65+ years. CONCLUSION: Results indicate higher intrinsic severity of the Delta variant, compared with Alpha or Omicron, with smaller differences among vaccinated individuals. Nevertheless, vaccination was associated to reduced hospitalisation in all groups.

A neutralizing single-domain antibody that targets the trimer interface of the human metapneumovirus fusion protein.

IMPORTANCE: Human metapneumovirus (hMPV) is an important respiratory pathogen for which no licensed antivirals or vaccines exist. Single-domain antibodies represent promising antiviral biologics that can be easily produced and formatted. We describe the isolation and detailed characterization of two hMPV-neutralizing single-domain antibodies that are directed against the fusion protein F. One of these single-domain antibodies broadly neutralizes hMPV A and B strains, can prevent proteolytic maturation of F, and binds to an epitope in the F trimer interface. This suggests that hMPV pre-F undergoes trimer opening or "breathing" on infectious virions, exposing a vulnerable site for neutralizing antibodies. Finally, we show that this single-domain antibody, fused to a human IgG1 Fc, can protect cotton rats against hMPV replication, an important finding for potential future clinical applications.

Behavioural traits related with resilience or vulnerability to the development of cocaine-induced conditioned place preference after exposure of female mice to vicarious social defeat.

Exposure to stress induced by intermittent repeated social defeat (IRSD) increases vulnerability to the development of cocaine-induced conditioned place preference (CPP) among male mice; however, some defeated mice are resilient to these effects of stress. In the present study we evaluated the effects of vicarious IRSD (VIRSD) in female mice and explored behavioural traits that are potentially predictive of resilience. C57BL/6 female mice (n = 28) were exposed to VIRSD, which consisted of the animals witnessing a short experience of social defeat by a male mouse on postnatal day (PND) 47, 50, 53 and 56. The control group (n = 10) was not exposed to stress. Blood samples were collected on PND 47 and 56 for corticosterone and interleukin-6 determinations. On PND 57-58, female mice performed several behavioural tests (elevated plus maze, hole-board, object recognition, social interaction, TST and splash tests). Three weeks later, the effects of cocaine (1.5 mg/kg) on the CPP paradigm were assessed. VIRSD decreased corticosterone levels (on PND 56), increased interleukin-6 levels, enhanced novelty-seeking, improved recognition memory and induced anxiety- and depression-like symptoms. Control and VIRSD female mice did not acquire CPP, although some stressed individuals with certain behavioural traits - including a high novelty-seeking profile or the development of depression-like behaviour in the splash test shortly after VIRSD - acquired cocaine CPP. Our results confirm that some behavioural traits of female mice are associated with vulnerability or resilience to the long-term effects of social stress on cocaine reward, as previously observed in males.

Genomic characterisation of respiratory syncytial virus: a novel system for whole genome sequencing and full-length G and F gene sequences.

To advance our understanding of respiratory syncytial virus (RSV) impact through genomic surveillance, we describe two PCR-based sequencing systems, (i) RSVAB-WGS for generic whole-genome sequencing and (ii) RSVAB-GF, which targets major viral antigens, G and F, and is used as a complement for challenging cases with low viral load. These methods monitor RSV genetic diversity to inform molecular epidemiology, vaccine effectiveness and treatment strategies, contributing also to the standardisation of surveillance in a new era of vaccines.

Five-year serological and clinical evolution of chronic Chagas disease patients in Cochabamba, Bolivia.

BACKGROUND: Chagas disease, caused by the parasite Trypanosoma cruzi, is a neglected infectious disease that exerts the highest public health burden in the Americas. There are two anti-parasitic drugs approved for its treatment-benznidazole and nifurtimox-but the absence of biomarkers to early assess treatment efficacy hinders patients´ follow-up. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a longitudinal, observational study among a cohort of 106 chronically T. cruzi-infected patients in Cochabamba (Bolivia) who completed the recommended treatment of benznidazole. Participants were followed-up for five years, in which we collected clinical and serological data, including yearly electrocardiograms and optical density readouts from two ELISAs (total and recombinant antigens). Descriptive and statistical analyses were performed to understand trends in data, as well as the relationship between clinical symptoms and serological evolution after treatment. Our results showed that both ELISAs documented average declines up to year three and slight inclines for the following two years. The recorded clinical parameters indicated that most patients did not have any significant changes to their cardiac or digestive symptoms after treatment, at least in the timeframe under investigation, while a small percentage demonstrated either a regression or progression in symptoms. Only one participant met the "cure criterion" of a negative serological readout for both ELISAs by the final year. CONCLUSIONS/SIGNIFICANCE: The study confirms that follow-up of benznidazole-treated T. cruzi-infected patients should be longer than five years to determine, with current tools, if they are cured. In terms of serological evolution, the single use of a total antigen ELISA might be a more reliable measure and suffice to address infection status, at least in the region of Bolivia where the study was done. Additional work is needed to develop a test-of-cure for an early assessment of drugs´ efficacy with the aim of improving case management protocols.