Design and Interrater Reliability of the Pediatric Version of the Race Scale: PedRACE.

BACKGROUND: Acute ischemic stroke is a leading cause of pediatric death and disability. A clinical scale adapted for children can ensure early detection of candidates for urgent acute ischemic stroke treatment. The Rapid Arterial Occlusion Evaluation (RACE) scale for adults, which scores 5 items (facial palsy 0-2; arm motor function 0-2; leg motor function 0-2; head/gaze deviation 0-1; and aphasia or agnosia 0-2), has good sensitivity and specificity in detecting large vessel occlusion. METHODS: We adapted the previously validated RACE scale for use in children as the Pediatric RACE scale. This adapted scale was tested by prehospital/emergency room staff attending to patients covered by the Catalan Pediatric Stroke Code and child neurologists for its correlation with the Pediatric National Institutes of Health Stroke Scale and for interrater reliability. RESULTS: The study included 50 children, 18 with confirmed strokes (7 acute ischemic strokes and 11 hemorrhagic strokes). Prehospital/emergency staff and child neurologists agreed fully regarding 82% of patients and 100% regarding head/gaze deviation and agnosia. The Pediatric RACE scale correlated strongly with the Pediatric National Institutes of Health Stroke Scale in evaluations by child neurologists (Spearman ρ, 0.852; P<0.001) and prehospital/emergency staff (Spearman ρ, 0.781; P<0.001). The median Pediatric RACE score was significantly higher in patients with large vessel occlusion (6.5; interquartile range, 6-7) than with other etiologies. CONCLUSIONS: Pediatric RACE, showing good interrater reliability and correlation with the Pediatric National Institutes of Health Stroke Scale, is a simple scale to detect candidates for pediatric acute stroke treatment, designed for both prehospital and in-hospital use by non-neurologist medical staff.

Development of mouse models with restricted HLA-B∗57:01 presentation for the study of flucloxacillin-driven T-cell activation and tolerance in liver injury.

BACKGROUND: Flucloxacillin (FLX)-induced liver injury is immune-mediated and highly associated to HLA-B∗57:01 expression. Host factors leading to drug-induced liver injury are not yet well understood. OBJECTIVE: Characterize in vivo immune mechanisms determining the development of CD8+ T cells reactive to FLX in animals expressing the risk human leukocyte antigen (HLA) allotype. METHODS: HLA-B∗57:01 transgenic mice (Tg) or Tg strains with H2-KbDb knockout (Tg/KO) or H2-KbDb/PD-1 double knockout (Tg/DKO) were treated with drug and/or anti-CD4 antibody. Drug-induced liver injury was evaluated on the basis of liver enzyme and histologic changes at day 10 of treatment. FLX-reactive CD8+ T cells were characterized in vitro by release of effector molecules on drug restimulation, gene expression, and flow cytometry analysis, and functionality tested for hepatic cytotoxicity. RESULTS: CD8+ T-cell responses to FLX in Tg were dependent on both HLA and mouse major histocompatibility complex I presentation and in vivo priming. Eliminating H2-KbDb in Tg/KO to allow exclusive presentation of FLX by HLA resulted in a less robust drug-specific CD8+T-cell response unless CD4+ cells, including regulatory T cells, were depleted. Treatment of Tg/KO with anti-CD4 antibody and FLX led to subclinical liver inflammation associated with an increase in PD1+CD8+ T cells in the lymphoid organs and liver. Impaired PD-1 expression in Tg/DKO led to liver histopathologic and transcriptional alterations but without hepatic enzyme elevations. Moreover, effector lymphocytes accumulated in the liver and showed FLX-dependent hepatic cytotoxicity in vitro when tolerogenic liver cells were depleted. CONCLUSIONS: In our in vivo models, FLX primes CD8+ T cells to recognize drug presented by HLA-B∗57:01 and murine major histocompatibility complex I. HLA-B∗57:01-dependent CD8+ T-cell reaction to FLX is limited by the presence of CD4+ cells, presumably regulatory T cells, and PD-1 expression. Tolerogenic hepatic cells limit clinical disease through PD-L1 or additional unexplored mechanisms.

Design and content validation of a checklist about infection-prevention performance of intensive care nurses in simulation-based scenarios.

OBJECTIVE: To design, develop and validate a new tool, called NEUMOBACT, to evaluate critical care nurses' knowledge and skills in ventilator-associated pneumonia (VAP) and catheter-related bacteraemia (CRB) prevention through simulation scenarios involving central venous catheter (CVC), endotracheal suctioning (ETS) and mechanically ventilated patient care (PC) stations. BACKGROUND: Simulation-based training is an excellent way for nurses to learn prevention measures in VAP and CRB. DESIGN: Descriptive metric study to develop NEUMOBACT and analyse its content and face validity that followed the COSMIN Study Design checklist for patient-reported outcome measurement instruments. METHODS: The first version was developed with the content of training modules in use at the time (NEUMOBACT-1). Delphi rounds were used to assess item relevance with experts in VAP and CRB prevention measures, resulting in NEUMOBACT-2. Experts in simulation methods then assessed feasibility, resulting in NEUMOBACT-3. Finally, a pilot test was conducted among 30 intensive care unit (ICU) nurses to assess the applicability of the evaluation tool in clinical practice. RESULTS: Seven national experts in VAP and CRB prevention and seven national simulation experts participated in the analysis to assess the relevance and feasibility of each item, respectively. After two Delphi rounds with infection experts, four Delphi rounds with simulation experts, and pilot testing with 30 ICU nurses, the NEUMOBACT-FINAL tool consisted of 17, 26 and 21 items, respectively, for CVC, ETS and PC. CONCLUSION: NEUMOBACT-FINAL is useful and valid for assessing ICU nurses' knowledge and skills in VAP and CRB prevention, acquired through simulation. RELEVANCE FOR CLINICAL PRACTICE: Our validated and clinically tested tool could facilitate the transfer of ICU nurses' knowledge and skills learning in VAP and CRB prevention to critically ill patients, decreasing infection rates and, therefore, improving patient safety. PATIENT OR PUBLIC CONTRIBUTION: Experts participated in the Delphi rounds and nurses in the pilot test.

Transitions in smoking status in nursing students: A prospective longitudinal study.

AIM: To describe transitions in smoking status and their determining factors among nursing students between baseline (2015-2016) and follow-up (2018-2019). DESIGN: Observational prospective longitudinal study of 4381 nursing students in Catalonia (Spain). METHODS: We examined transitions in smoking status from: (i) current smokers to recent quitters, (ii) never smokers to new smokers and (iii) former smokers to quitters who relapsed. We fitted logistic regression models to assess the predictors of quitting smoking. RESULTS: The proportion of current smokers decreased from 29.7% at baseline to 23.6% at follow-up, with a cumulative incidence rate of quitting of 28.3% during follow-up. Nondaily smokers were more likely to quit than daily smokers. Of those who were never smokers at baseline, 4.6% were smokers at follow-up, and 23.2% of former smokers at baseline had relapsed at follow-up. CONCLUSIONS: Nondaily smokers were more likely to have quit smoking at follow-up among this cohort of nursing students. The early implementation of a comprehensive tobacco control program that includes tobacco-free campus policies, tobacco prevention interventions and cessation support during college years may decrease tobacco use among nursing students. IMPACT: Nursing students' tobacco use is concerning, as they are the future workforce of nurses who have a key role in tobacco product use prevention and cessation. During college years, nursing students have a greater likelihood of experimenting with several smoking status changes as well as to consolidate smoking behaviors. This is the first longitudinal study to highlight the factors associated with quitting smoking among a cohort of Spanish nursing students. Being a nondaily smoker at baseline predicted quitting at follow-up. Our findings support the early implementation of a comprehensive tobacco control program that includes tobacco-free campus policies, tobacco prevention interventions and tobacco cessation support during college years to decrease tobacco product use prevalence among nursing students. REPORTING METHOD: We have adhered to STROBE guidelines. No Patient or Public Contribution. This observational study has not been registered.

The ANGPTL3-4-8 Axis in Normal Gestation and in Gestational Diabetes, and Its Potential Involvement in Fetal Growth.

Dyslipidemia in gestational diabetes has been associated with worse perinatal outcomes. The ANGPTL3-4-8 axis regulates lipid metabolism, especially in the transition from fasting to feeding. In this study, we evaluated the response of ANGPTL3, 4, and 8 after the intake of a mixed meal in women with normal glucose tolerance and gestational diabetes, and we assessed their gene expressions in different placental locations. Regarding the circulating levels of ANGPTL3, 4, and 8, we observed an absence of ANGPTL4 response after the intake of the meal in the GDM group compared to its presence in the control group. At the placental level, we observed a glucose tolerance-dependent expression pattern of ANGPTL3 between the two placental sides. When we compared the GDM pregnancies with the control pregnancies, a downregulation of the maternal side ANGPTL3 expression was observed. This suggests a dysregulation of the ANGPTL3-4-8 axis in GDM, both at the circulating level after ingestion and at the level of placental expression. Furthermore, we discerned that the expressions of ANGPTL3, 4, and 8 were related to birth weight and placental weight in the GDM group, but not in the control group, which suggests that they may play a role in regulating the transplacental passage of nutrients.

Severity of dementia, anosognosia, and depression in relation to the quality of life of patients with Alzheimer disease: discrepancies between patients and caregivers.

OBJECTIVE: To investigate the factors associated with discrepancies between patient and caregiver reports of the quality of life of patients (QoLp) with Alzheimer disease. METHODS: Cross-sectional analytic study of 141 patients and their caregivers. The instruments used were the Quality of Life in AD, the Global Deterioration Scale (GDS), the Geriatric Depression Scale, and the Anosognosia Questionnaire-Dementia. Differences were analyzed according to GDS stage. A linear regression analysis was conducted using the difference between the absolute QoLp scores of patients and caregivers. A cluster analysis involving patient variables was then performed. RESULTS: The discrepancy between patient and caregiver QoLp ratings increased in line with GDS stages (χ(2) (2) = 8.7, p = 0.013). In the regression model (F [7,133] = 16.6, p <0.001; R(2) = 0.477), discrepancies in QoLp reports were associated with greater anosognosia, less depression, and a better cognitive status in patients and with female gender among caregivers. The cluster analysis showed that patients with the lowest ratings of QoLp had a better cognitive status, more depression, and less anosognosia. Conversely, the highest ratings were given by patients with a poorer cognitive status, less depression, and greater anosognosia. CONCLUSIONS: The factors associated with greater discrepancies between patient and caregiver ratings of QoLp were severity of dementia, anosognosia, depression, and cognitive status in patients and female gender in caregivers. In patients with advanced dementia, greater anosognosia leads to more positive ratings in QoLp and complementary observations are required.

[WOMEN AND RETIREMENT: KNOWLEDGE OF THE TRANSITION OF RETIREMENT OF WOMEN]. / Mujer y jublación conocimientos sobre a transción de la jubilación.

OBJECTIVE: To describe the transition involved in the retirement process for women who have worked in the Barcelona work context. DESIGN: Methodology qualitative, exploratory study. LOCATION: The study was carried out in Barcelona, between the years 2008-2011. PARTICIPANTS: Users of health centers that serve two profiles by type of work activity developed as managers and technical, or professional activity with little or no autonomy. MAIN INTERVENTTON: A technique discussion group was used until narratives did not add significantly to the information available. Transcription, analysis, coding, categorization, and content analysis to obtain the results. RESULTS: The results reflected differences between these profiles involved in the sample when analyzing data related to the meaning of their working lives, expectations of retirement, the motives which determine it, their health during the initial period and their adaptation to retirement. There were many similarities and few differences when analyzing family responsibilities/ workloads before and after retirement. CONCLUSIONS: These were based on the results described of the two distinct typologies of transition to retirement among women involved in the study in accordance with their profile of working life (the description used concepts and elements which model the Meleis Transition Theories as its basis). Some aspects of their experiences and needs are also stressed which, from a nursing perspective, lead to the identification of ambits, means of intervention which enable them to prepare and address this transition in a healthy way.

Metabolism and liver toxicity of cannabidiol.

Increasing public interest has resulted in the widespread use of non-pharmaceutical cannabidiol (CBD) products. The sales of CBD products continue to rise, accompanied by concerns regarding unsubstantiated benefits, lack of product quality control, and potential health risks. Both animal and human studies have revealed a spectrum of toxicological effects linked to the use of CBD. Adverse effects related to exposure of humans to CBD include changes in appetite, gastrointestinal discomfort, fatigue, and elevated liver aminotransferase enzymes. Animal studies reported changes in organ weight, reproduction, liver function, and the immune system. This review centers on human-derived data, including clinical studies and in vitro investigations. Animal studies are also included when human data is not available. The objective is to offer an overview of CBD-related hepatotoxicity, metabolism, and potential CBD-drug interactions, thereby providing insights into the current understanding of CBD's impact on human health. It's important to note that this review does not serve as a risk assessment but seeks to summarize available information to contribute to the broader understanding of potential toxicological effects of CBD on the liver.

Investigation of cannabidiol-induced cytotoxicity in human hepatic cells.

Cannabidiol (CBD) is one of the primary cannabinoids present in extracts of the plant Cannabis sativa L. A CBD-based drug, Epidiolex, has been approved by the U.S. FDA for the treatment of seizures in childhood-onset epileptic disorders. Although CBD-associated liver toxicity has been reported in clinical studies, the underlying mechanisms remain unclear. In this study, we demonstrated that CBD causes cytotoxicity in primary human hepatocytes and hepatic HepG2 cells. A 24-h CBD treatment induced cell cycle disturbances, cellular apoptosis, and endoplasmic reticulum (ER) stress in HepG2 cells. A potent ER stress inhibitor, 4-phenylbutyrate, markedly attenuated CBD-induced apoptosis and cell death. Additionally, we investigated the role of cytochrome P450 (CYP)-mediated metabolism in CBD-induced cytotoxicity using HepG2 cell lines engineered to express 14 individual CYPs. We identified CYP2C9, 2C19, 2D6, 2C18, and 3A5 as participants in CBD metabolism. Notably, cells overexpressing CYP2C9, 2C19, and 2C18 produced 7-hydroxy-CBD, while cells overexpressing CYP2C9, 2C19, 2D6, and 2C18 generated 7-carboxy-CBD. Furthermore, CBD-induced cytotoxicity was significantly attenuated in the cells expressing CYP2D6. Taken together, these data suggest that cell cycle disturbances, apoptosis, and ER stress are associated with CBD-induced cytotoxicity, and CYP2D6-mediated metabolism plays a critical role in decreasing the cytotoxicity of CBD.

Determinants of tobacco use transitions in smoker nursing students in Catalonia: A prospective longitudinal study.

INTRODUCTION: The use of emerging tobacco and nicotine products affects tobacco use behaviors among college students. Thus, we aimed to examine transitions in tobacco use patterns and identify their predictors among smokers in a cohort of nursing students in Catalonia (Spain). METHODS: We conducted a prospective longitudinal study of Catalan nursing students between 2015-2016 and 2018-2019. We examined transitions in tobacco use patterns between baseline and follow-up among smokers from: 1) daily to non-daily smoking, 2) non-daily to daily smoking, 3) cigarette-only use to poly-tobacco use, 4) poly-tobacco use to cigarette-only use, 5) between products, 6) reducing consumption by ≥5 cigarettes per day (CPD); and 7) quitting smoking. We applied a Generalized Linear Model with a log link (Poisson regression) and robust variance to identify predictors of reducing cigarette consumption by ≥5 CPD and quitting smoking, obtaining both crude and adjusted (APR) prevalence ratios and their 95% confidence intervals (CIs). RESULTS: Among daily smokers at baseline, 12.1% transitioned to non-daily smoking at follow-up, while 36.2% of non-daily smokers shifted to daily smoking. Among cigarette-only users, 14.2% transitioned to poly-tobacco use, while 48.4% of poly-tobacco users switched to exclusive cigarette use. Among all smokers (daily and non-daily smokers), 60.8% reduced their cigarette consumption by ≥5 CPD and 28.3% quit smoking. Being a non-daily smoker (APR=0.33; 95% CI 0.19-0.55) and having lower nicotine dependence (APR=0.78; 95% CI 0.64-0.96) were inversely associated with reducing cigarette consumption, while being a non-daily smoker (APR=1.19; 95% CI: 1.08-1.31) was directly associated with quitting smoking. CONCLUSIONS: Nursing students who smoked experienced diverse transitions in tobacco use patterns over time. Evidence-based tobacco use preventive and cessation interventions are needed to tackle tobacco use among future nurses.

Factors associated with the variability in caregiver assessments of the capacities of patients with Alzheimer disease.

BACKGROUND: Several studies have identified certain caregiver factors that can produce variability in their assessments of the capacities of patients with Alzheimer disease (AD). OBJECTIVES: To identify the caregiver variables associated with variability in their ratings of patients' capacities. METHODS: Consecutive sample of 221 outpatients with AD and their family caregivers. The capacities evaluated by caregivers were the degree of functional disability, using the Disability Assessment for Dementia (DAD); psychological and behavioral symptoms, via the Neuropsychiatric Inventory (NPI); anosognosia, with the Anosognosia Questionnaire-Dementia (AQ-D); and quality of life, using the Quality of Life in AD (QOL-AD). The relationship between these measures and caregiver's gender, burden, depression, and health was analyzed by means of a bivariate analysis, calculating the effect size (Cohen d) and subsequently by a regression analysis, calculating the contribution coefficient (CC). RESULTS: The greatest variability in caregiver assessments was observed in relation to patients with early-stage dementia, where caregiver's burden was the main factor associated with a more negative evaluation (d = 1.02-1.25). Depression in the caregiver was associated with less variability and only in the assessments of patients with moderate dementia (d = 0.38-0.69). In the regression analysis, caregiver factors were associated with greater variance in scores on the NPI (CC = 37.4%) and QOL-AD (CC = 27.2%), and lower variance in AQ-D (CC = 21.6%) and DAD (CC = 10.3%) scores. CONCLUSIONS: Caregiver's burden and depression were associated with more negative assessments of patients' psychological and behavioral symptoms and quality of life.

Transgenic murine models for the study of drug hypersensitivity reactions linked to HLA-I molecules.

PURPOSE OF REVIEW: Immune-mediated drug hypersensitivity reactions (DHRs) can be life-threatening and an impediment to drug development. Mechanism of disease studies are difficult to perform in humans. Here we review human leukocyte antigens class I (HLA-I) transgenic murine models and highlight how these systems have helped to elucidate drug-specific and host immune factors that initiate, propagate and control severe drug toxicities to skin and liver. RECENT FINDINGS: HLA transgenic mice have been developed and used to study immune-mediated drug reactions in vitro and in vivo . CD8+ T cells from HLA-B∗57:01-expressing mice respond strongly to abacavir (ABC) in vitro but have self-limited responses to drug exposure in vivo . Immune tolerance can be overcome by depleting regulatory T cells (Treg) allowing antigen-presenting dendritic cells to express CD80/86 costimulatory molecules and signal through CD28 on the CD8+ T cell. Depletion of Treg also removes competition for interleukin 2 (IL-2) to allow T cell expansion and differentiation. Fine tuning of responses depends on inhibitory checkpoint molecules such as PD-1. Improved mouse models express only HLA in the absence of PD-1. These models show enhanced liver injury to flucloxacillin (FLX) which depends on drug priming, CD4+ T cell depletion, and lack of PD-1 expression. Drug-specific HLA-restricted cytotoxic CD8+ T cells can infiltrate the liver but are suppressed by Kupffer and liver sinusoidal endothelial cells. SUMMARY: HLA-I transgenic mouse models are now available to study ABC, FLX and carbamazepine-induced adverse reactions. In vivo studies range from characterizing drug-antigen presentation, T cell activation, immune-regulatory molecules and cell-cell interaction pathways that are specifically involved in causing or controlling unwanted DHRs.

Global change effects on Mediterranean small mammal population dynamics: Demography of Algerian mice (Mus spretus) along land use and climate gradients.

Climate and land use change are key global change drivers shaping future species' distributions and abundances. Negative interactions among effects of drivers can reduce the accuracy of models aimed at predicting such distributions. Here we analyse how climate and land use affected population dynamics and demography of the Algerian mouse (Mus spretus), an open-land thermophilic Mediterranean small mammal. Change to a warmer and drier climate would facilitate the expansion of the species, whereas landscape change (forest encroachment following extensive land abandonment) would produce its retreat. We correlated abundance and demography parameters computed from captures obtained in 16 plots during a 10-years period (2008-2017; SEMICE small mammal monitoring) with climate, vegetation and land use change. Climate became warmer and dryer, and afforestation due to encroachment occurred in 81 % of plots. Expected positive effects of climate warming, derived from bioclimatic niche models, were counterbalanced by negative effects of both increasing hydric deficit and changes in vegetation and landscape structure. Abundance showed a slight but significant decline (-5 %). The species' range was more resilient to change, as shown by occupancy analyses, apparently due to strong local effects of vegetation structure on occupancy. This result highlighted that negative population trends would not necessarily produce range retractions. Simultaneously analysing both abundance trends and occupancy patterns may thus allow for deeper understanding and more accurate predictions of expected population trends in response to interacting global change drivers.

Pest suppression by bats and management strategies to favour it: a global review.

Fighting insect pests is a major challenge for agriculture worldwide, and biological control and integrated pest management constitute well-recognised, cost-effective ways to prevent and overcome this problem. Bats are important arthropod predators globally and, in recent decades, an increasing number of studies have focused on the role of bats as natural enemies of agricultural pests. This review assesses the state of knowledge of the ecosystem services provided by bats as pest consumers at a global level and provides recommendations that may favour the efficiency of pest predation by bats. Through a systematic review, we assess evidence for predation, the top-down effect of bats on crops and the economic value of ecosystem services these mammals provide, describing the different methodological approaches used in a total of 66 reviewed articles and 18 agroecosystem types. We also provide a list of detailed conservation measures and management recommendations found in the scientific literature that may favour the delivery of this important ecosystem service, including actions aimed at restoring bat populations in agroecosystems. The most frequent recommendations include increasing habitat heterogeneity, providing additional roosts, and implementing laws to protect bats and reduce agrochemical use. However, very little evidence is available on the direct consequences of these practices on bat insectivory in farmland. Additionally, through a second in-depth systematic review of scientific articles focused on bat diet and, as part of the ongoing European Cost Action project CA18107, we provide a complete list of 2308 documented interactions between bat species and their respective insect pest prey. These pertain to 81 bat species belonging to 36 different genera preying upon 760 insect pests from 14 orders in agroecosystems and other habitats such as forest or urban areas. The data set is publicly available and updatable.

Evolution of Quality of Life and Treatment Adherence after One Year of Intermittent Bladder Catheterisation in Functional Urology Unit Patients.

OBJECTIVE: To determine patient difficulties and concerns when performing IBC (Intermittent Bladder Catheterisation), as well as the evolution of adherence, quality of life, and emotional state of patients one year after starting IBC. METHOD: A prospective, observational, multicentre study conducted in 20 Spanish hospitals with a one-year follow-up. Data sources were patient records and the King's Health Questionnaire on quality of life, the Mini-Mental State Examination (MMSE), and the Hospital Anxiety and Depression Scale (HADS). Perceived adherence was measured using the ICAS (Intermittent Catheterization Adherence Scale) and perceived difficulties with IBC were assessed using the ICDQ (Intermittent Catheterization Difficulty Questionnaire). For data analysis, descriptive and bivariate statistics were performed for paired data at three points in time (T1: one month, T2: three months, T3: one year). RESULTS: A total of 134 subjects initially participated in the study (T0), becoming 104 subjects at T1, 91 at T2, and 88 at T3, with a mean age of 39 years (standard deviation = 22.16 years). Actual IBC adherence ranged from 84.8% at T1 to 84.1% at T3. After one year of follow-up, a statistically significant improvement in quality of life (p ≤ 0.05) was observed in all dimensions with the exception of personal relationships. However, there were no changes in the levels of anxiety (p = 0.190) or depression (p = 0.682) at T3 compared to T0. CONCLUSIONS: Patients requiring IBC exhibit good treatment adherence, with a significant proportion of them performing self-catheterisation. After one year of IBC, a significant improvement in quality of life was noted, albeit with a significant impact on their daily lives and their personal and social relationships. Patient support programmes could be implemented to improve their ability to cope with difficulties and thus enhance both their quality of life and the maintenance of their adherence.

Expression profiles of human interferon-alpha and interferon-lambda subtypes are ligand- and cell-dependent.

Recent genome-wide association studies suggest distinct roles for 12 human interferon-alpha (IFN-α) and 3 IFN-λ subtypes that may be elucidated by defining the expression patterns of these sets of genes. To overcome the impediment of high homology among each of the sets, we designed a quantitative real-time PCR assay that incorporates the use of molecular beacon and locked nucleic acid (LNA) probes, and in some instances, LNA oligonucleotide inhibitors. We then measured IFN subtype expression by human peripheral blood mononuclear cells and by purified monocytes, myeloid dendritic cells (mDC), plasmacytoid dendritic cells (pDC), and monocyte-derived macrophages (MDM), and -dendritic cells (MDDC) in response to poly I:C, lipopolysaccharide (LPS), imiquimod and CpG oligonucleotides. We found that in response to poly I:C and LPS, monocytes, MDM and MDDC express a subtype pattern restricted primarily to IFN-ß and IFN-λ1. In addition, while CpG elicited expression of all type I IFN subtypes by pDC, imiquimod did not. Furthermore, MDM and mDC highly express IFN-λ, and the subtypes of IFN-λ are expressed hierarchically in the order IFN-λ1 followed by IFN-λ2, and then IFN-λ3. These data support a model of coordinated cell- and ligand-specific expression of types I and III IFN. Defining IFN subtype expression profiles in a variety of contexts may elucidate specific roles for IFN subtypes as protective, therapeutic or pathogenic mediators.

Persistent growth of a human plasma-derived hepatitis C virus genotype 1b isolate in cell culture.

HCV (hepatitis C virus) research, including therapeutics and vaccine development, has been hampered by the lack of suitable tissue culture models. Development of cell culture systems for the growth of the most drug-resistant HCV genotype (1b) as well as natural isolates has remained a challenge. Transfection of cultured cells with adenovirus-associated RNA(I) (VA RNA(I)), a known interferon (IFN) antagonist and inhibitor of dsRNA-mediated antiviral pathways, enhanced the growth of plasma-derived HCV genotype 1b. Furthermore, persistent viral growth was achieved after passaging through IFN-alpha/beta-deficient VeroE6 cells for 2 years. Persistently infected cells were maintained in culture for an additional 4 years, and the virus rescued from these cells induced strong cytopathic effect (CPE). Using a CPE-based assay, we measured inhibition of viral production by anti-HCV specific inhibitors, including 2'-C-Methyl-D-Adenosine, demonstrating its utility for the evaluation of HCV antivirals. This virus constitutes a novel tool for the study of one of the most relevant strains of HCV, genotype 1b, which will now be available for HCV life cycle research and useful for the development of new therapeutics.

Winter bat activity: The role of wetlands as food and drinking reservoirs under climate change.

Bat arousals during hibernation are related to rises in environmental temperature, body water loss and increasing body heat. Therefore, bats either hibernate in cold places or migrate to areas with mild winters to find water and insects to intake. During winter, insects are relatively abundant in wetlands with mild climates when low temperatures hamper insect activity in other places. However, the role of wetlands to sustain winter bat activity has never been fully assessed. To further understand bat behaviour during hibernation, we evaluated how the weather influenced hibernating bats, assessed the temperature threshold that increased bat arousals, and discussed how winter temperatures could affect bat activity under future climate change scenarios. The effects of weather and landscape composition on winter bat activity were assessed by acoustically sampling four different habitats (wetlands, rice paddies, urban areas and salt marshes) in the Ebro Delta (Spain). Our results show one of the highest winter bat foraging activities ever reported, with significantly higher activity in wetlands and urban areas. Most importantly, we found a substantial increase in bat activity triggered when nocturnal temperatures reached ca. 11 °C. By contrasting historical weather datasets, we show that, since the 1940s, there has been an increase by ca. 1.5 °C in winter maximum temperatures and a 180% increase in the number of nights with mean temperatures above 11 °C in the Ebro Delta. Temperature trends suggest that in 60-80 years, winter months will reach average temperatures of 11 °C (except maybe in January), which suggest a potential coming interruption or disappearance of bat hibernation in coastal Mediterranean habitats. This study highlights the significant role of wetlands in bat conservation under a climate change scenario as these humid areas represent one of the few remaining winter foraging habitats.

Determinants of participation in an online follow-up survey among nursing students.

INTRODUCTION: Determinants of participation in longitudinal studies are crucial for prevent attrition. AIM: To analyze determinants of participation in a follow-up survey among nursing students. MATERIALS AND METHODS: Prospective longitudinal study among nursing students. We examined individual and contextual determinants of participation in an online follow-up survey (2018) among nursing students that had completed the paper-and-pencil questionnaire in baseline (2015-2016), using a multilevel logistic regression models. RESULTS: From the 4381 baseline participants, we identified 3440 eligible persons. The number of participants in the follow-up survey was 1252 (28.6%). Determinants of participation at follow-up were being female, aged ≤19 year-old in comparison with those older than 20, and being a never smoker compared with a current smoker. CONCLUSIONS: Nursing students' participation at the online follow-up survey was moderate. Being female, aged ≤19 year-old, and being never smoker were determinants of participation. To boost participation in online surveys, some strategies such as adapted communications channels, the use of reminders and incentives should be included.