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.

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.

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.

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.

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.

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.

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.

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.

Cerebrospinal Fluid Ion Analysis in Neonatal Seizures.

BACKGROUND: There is a gap of knowledge regarding cerebrospinal fluid (CSF) ion concentrations in normal and pathological states, particularly during the neonatal period. We aim to compare CSF ion concentrations in newborns with different causes of neonatal-onset epilepsy (NOE) and acute symptomatic seizures (ASS) and controls, to examine their usefulness for diagnostic purposes. METHODS: A descriptive retrospective study was conducted from January 2019 to June 2020 in a tertiary hospital. We analyzed CSF K+, Na+, Cl-, and Ca2+ concentrations in frozen samples from patients with neonatal seizures (NS) secondary to NOE and ASS (neonatal arterial ischemic stroke [NAIS] and hypoxic-ischemic encephalopathy). As the control group, we selected CSF samples from newborns who had undergone CSF analysis as part of the diagnostic workup and in whom central nervous system infections had been ruled out, without signs of dehydration, gastroenteritis, or history of seizures. RESULTS: Sixty-eight newborns were included, 16 with NOE, 13 with ASS, and 39 without NS (control group). In comparison with the control group, [K+]CSF was lower in patients with KCNQ2-related epilepsy (P = 0.007), other causes of NOE (P = 0.010), and NAIS (P = 0.002). Changes in [Na+]CSF, [Cl-]CSF, and [Ca2+]CSF were less consistent among subgroups. CONCLUSIONS: Here we report for the first time ionic imbalances in the CSF of neonates with NOE and NAIS. No differences were observed between newborns with different causes of NS. Further studies should be undertaken to investigate the physiopathology behind these changes and their impact on biological function.

A 10-Year-Old Boy with Short Stature and Microcephaly, Diagnosed with Moyamoya Syndrome and Microcephalic Osteodysplastic Primordial Dwarfism Type II (MOPD II).

BACKGROUND Moyamoya syndrome is a rare cerebrovascular condition caused by blockage of the arteries of the basal ganglia. The Japanese word "moyamoya" means "a puff of smoke" which describes the appearance of the collateral compensatory vessels that develop over time. Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a rare genetic syndrome characterized by microcephaly and short stature. In up to 25% of patients with MOPD II, there is an association with moyamoya syndrome. This report is of a Syrian boy diagnosed with moyamoya syndrome and MOPD II. CASE REPORT A 10-year-old boy was referred to our pediatric endocrinology unit for short stature (-11.1 standard deviations). Exploration of the oral cavity showed dental malposition. Laboratory tests revealed mild thrombocytosis and hypernatremia. Glucagon-based growth hormone-stimulation testing revealed pathology, with growth hormone levels peaked at 30 minutes below 1 ng/ml. No abnormalities of carbohydrate metabolism or heart function were identified. Neuropsychological assessment found moderate to severe intellectual disability. Imaging studies showed osteoporosis, bilateral coxa vara, diffuse platyspondyly without scoliosis, malrotation of the left kidney, severe microcephaly with simplified convolution pattern, and moyamoya features with secondary brain atrophy. A genetic study identified a mutation in both alleles of the pericentrin (PCNT) gene, enabling the diagnosis of microcephalic osteodysplastic primordial dwarfism type II. CONCLUSIONS This case highlights the importance of identifying the cause of short stature in children and genetic syndromes that may be linked with other abnormalities. MOPDII associated with moyamoya syndrome was diagnosed by cerebrovascular imaging, which led to a multidisciplinary approach to management.

Quality of Life and Autonomy in Patients with Intermittent Bladder Catheterization Trained by Specialized Nurses.

Intermittent bladder catheterization (IBC) involves regular urine draining using a catheter, which is removed immediately after urinary elimination. It allows for the patient's urological health to be managed and their renal function to be preserved, and it promotes autonomy. Compliance with the prescribed number of daily catheterizations, which must be conducted by the patient, and infection prevention measures are crucial. To identify the patients requiring IBC, and to determine their adherence (whether they followed the prescribed guidelines and their difficulty in carrying out the procedure, as well as to assess how the IBC influences their quality of life and state of mind after receiving self-care training from a specialized nurse), we carried out a prospective, multicenter observational study in 24 Spanish hospitals with one month of monitoring and a sample of 99 patients. The sources of information were the patients' clinical records, the King's Health Questionnaire, the Mini-Mental State Examination (MMSE), and the hospital anxiety and depression scale (HADS). Descriptive and bivariate statistics were used to analyses the paired data. After recruitment (n = 99), 79 patients completed the questionnaire at a mean age of 35.2 years (SD = 20.5 years). In total, 53.5% (53) of the sample consisted of men and 32.3% (32) had neurological damage as the reason for prescription; 67% (67.7) performed self-catheterization and 86.7% adhered to the IBC. After one month of monitoring, a statistically significant improvement in quality of life was observed in all criteria, with the exception of personal relationships (p < 0.005), as well as an improvement in anxiety and depression levels (p < 0.001). Patients who require IBC show good adherence to the IBC with a significant percentage of self-catheterization. After one month of IBC, a significant improvement in the patients' quality of life and mood was observed. These results could be attributed to adequate patient training and adequate personalization of the IBC materials by the specialized nurses.

Characterization of cytochrome P450s (CYP)-overexpressing HepG2 cells for assessing drug and chemical-induced liver toxicity.

Hepatic metabolism catalyzed by the cytochrome P450 (CYP) superfamily affects liver toxicity associated with exposures to natural compounds and xenobiotic agents. Previously we generated a battery of HepG2-derived stable cell lines that individually express 14 CYPs (1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5, and 3A7). In this study, we comprehensively characterized each cell line for its CYP expression and enzyme activity. Specifically, we measured the mRNA expression, protein expression, and metabolite formation. Using CYP3A4, 2D6, and 2C9-overexpressing cells as representatives, we examined the stability of these cells in long-term cultures for up to 10 passages. The results showed that CYPs can be stably overexpressed for up to 10 cell culture passages without losing their activities. The robustness of responses to stimuli among the cells at different passages was also investigated in CYP3A4-overexpressing cells and the response to amiodarone and dronedarone showed no difference between the cells at the passage 2 and 10. Moreover, the mRNA expression level of most CYPs was higher in CYP-overexpressing HepG2 cells than that in HepaRG cells and primary human hepatocytes. This study confirmed the stability of CYP-overexpressing HepG2 cell lines and provided useful information for a broader use of these cells in pharmacologic and toxicologic research.

Occurrence, toxicity and risk assessment of plastic additives in Besos river, Spain.

The objective of the present study is to evaluate the presence, seasonal variability and impact of plastic additives along the Besos river basin (Catalonia, Spain). This river flows through a highly urbanized and industrialized area with discharge of >25 Wastewater Treatment Plants (WWTPs) and with large amounts of floating plastics. Compounds studied included 5 phthalates, its substitutes acetyl tributyl citrate (ATBC) and bis(2-ehtylhexyl) adipate, 12 long and short chain alkylphenols, bisphenol A and benzophenone, most of them high volume production chemicals. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) was used to determine ng/L concentrations. Toxicity evaluation was performed for each individual compound using Daphnia magna as test organism and it was found that the effect concentration (EC50) decreased with increasing octanol-water partition coefficients. The EC50 values calculated and Measured Environmental Concentrations were used to determine the risk quotients. Only diethylhexylphthalate, nonylphenol and octylphenol, with median concentrations from 41.9 to 826 ng/L, caused a small risk mostly in downstream waters with 50-75% of the samples overpassing the Environmental Quality Standards set by the European Union. Seasonal variations were observed with higher levels in summer due to low water flows. WWTPs effluents and leaching from floating plastics or microplastics were presumably main sources of pollution.

Multiresidue method for the determination of high production volume plastic additives in river waters.

The aim of this study was to develop a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)-based method for the multiresidue analysis of 21 plastic additives in river water. Analysed compounds included phthalates, benzophenone, bisphenol A and long- and short-chain alkylphenols (APs), which are of relevance because most of them are high production volume chemicals largely used in the plastic industry. These compounds can reach river waters due to direct discharge from wastewater treatment plants and leaching from plastic materials and microplastics present in rivers. In a first step, ionisation and acquisition parameters were optimised to obtain high sensitivity and structural information. Then, different solid-phase extraction cartridges and elution conditions were tested using Milli-Q and river water. With the optimised conditions, quality control parameters (recoveries, limits of detection, intra- and inter-day variability and blank contribution) proved that the method was accurate and selective for the trace monitoring of these compounds in river water. For nonylphenol, octylphenol and bis(2-ethylhexyl)phthalate, included in the Water Framework Directive, limits of detection were below environmental quality standard concentrations considering blank contributions. All other compounds were efficiently detected at trace levels, and focus was given to o- and p-substituted and di- and tri-substituted APs, which are first reported in the present study. A pilot survey was finally carried out to determine the occurrence of plastic additives in river waters surrounding the city of Barcelona.

Lessons Learned to Date on COVID-19 Hyperinflammatory Syndrome: Considerations for Interventions to Mitigate SARS-CoV-2 Viral Infection and Detrimental Hyperinflammation.

The first case of human transmission of SARS-CoV-2 was reported in China in December 2019. A few months later, this viral infection had spread worldwide and became a pandemic. The disease caused by SARS-CoV-2, termed COVID-19, is multifactorial and associated with both specific antiviral as well as inflammatory responses, the extent of which may determine why some individuals are asymptomatic while others develop serious complications. Here we review possible life-threating immune events that can occur during disease progression to uncover key factors behind COVID-19 severity and provide suggestions for interventions with repurposed drugs in well-controlled and randomized clinical trials. These drugs include therapeutics with potential to inhibit SARS-CoV-2 entry into host cells such as serine protease inhibitors of the cellular protease TMPS2 and drugs targeting the renin-angiotensin system; antivirals with potential to block SARS-CoV-2 replication or factors that could boost the antiviral response; monoclonal antibodies targeting pro-inflammatory cytokines that drive the hyperinflammatory response during COVID-19 progression toward the severe stage and therapeutics that could ameliorate the function of the lungs. Furthermore, in order to help make more informed decisions on the timing of the intervention with the drugs listed in this review, we have grouped these therapeutics according to the stage of COVID-19 progression that we considered most appropriate for their mechanism of action.

Bats actively prey on mosquitoes and other deleterious insects in rice paddies: Potential impact on human health and agriculture.

BACKGROUND: The fact that bats suppress agricultural pests has been measured for some particular dyads of predator and prey species in both economic and food security terms. The recent emergence of new molecular techniques allows for more precise screenings of bat's diet than the traditional visual identification systems and provides further evidence that bats consume an ample array of agricultural pest species. The main focus of the regulatory services that bats provide in agroecosystems has been on crop pests that cause yield losses. Rice paddies constitute a particular agronomic system with specific challenges, not only related to crop productivity but also to human health. Dipteran density in such ecosystems poses a serious threat to human wellbeing and hinders crop production. Mosquitoes cause direct harm to human populations, transmitting a number of infectious diseases. Non-biting midges (Chironomidae) can consume and weaken rice seedlings and can cause major yield losses. RESULTS: Mosquito populations and bat activity were assessed in rice paddies of Montgrí, Medes i Baix Ter Natural Park (NE Iberian Peninsula). Molecular analyses of bats faeces (6-weekly samples of 15 faeces each between mid-August and September) proved the presence of both mosquitoes and nonbiting midges in all diet samples. Furthermore, bat activity at the sampling locations was related to adult mosquito density. CONCLUSION: Our results suggest that bats actively exploit the emergence of adult mosquitoes and further prove that they prey on mosquitoes, nonbiting midges and other deleterious insects. Promoting the presence of bats next to human settlements in such agroecosystems may constitute a biological control system with direct impact on both human health and crop yield. © 2020 Society of Chemical Industry.

Moderately elevated first trimester fasting plasma total homocysteine is associated with increased probability of miscarriage. The Reus-Tarragona Birth Cohort Study.

The association between elevated early pregnancy fasting plasma total homocysteine (tHcy) and miscarriage risk was investigated prospectively in participants (n = 544) from the Reus-Tarragona Birth Cohort study. Pregnancy was confirmed before 12 gestational weeks (GW) by ultrasound scan and a fasting blood sample collected. Pregnancies with complications other than miscarriages were excluded. Miscarriages were diagnosed by ultrasound scan and gestational age at the time of miscarriage estimated by embryo size, where possible. Cases in which blood samples were collected more than a week after the miscarriage, or the miscarriage was of known cause, were excluded. Fasting plasma folate, vitamin B12, tHcy, cotinine (biomarker of smoking), red blood cell (RBC) folate, MTHFR 677C > T (rs1801133) and SLC19A1 80G>A (rs1051266) genotypes were determined. The exposed group consisted of participants with first trimester tHcy ≥ P90 (7.1 µmol/L) (n = 57) and unexposed of those with tHcy < P90 (n = 487). Adherence to folic acid supplement recommendations, plasma folate, plasma vitamin B12, RBC folate and prevalence of optimal RBC folate status (≥ 906 µmol/L) were lower in the exposed compared to unexposed group. The prevalences of the MTHFR 677 TT genotype and miscarriage were higher in the exposed group. The relative risks (95% CI) of pregnancy ending in miscarriage were 2.5 (1.1, 5.7) and 2.1 (1.0, 4.5) for participants in the high tHcy and suboptimal RBC folate groups (compared to the reference groups) respectively. Adherence to folic acid supplement recommendations was positively associated, while the MTHFR 677 TT versus CC genotype and smoking versus non-smoking were negatively associated, with RBC folate status.

Alterations in the HLA-B*57:01 Immunopeptidome by Flucloxacillin and Immunogenicity of Drug-Haptenated Peptides.

Neoantigen formation due to the interaction of drug molecules with human leukocyte antigen (HLA)-peptide complexes can lead to severe hypersensitivity reactions. Flucloxacillin (FLX), a ß-lactam antibiotic for narrow-spectrum gram-positive bacterial infections, has been associated with severe immune-mediated drug-induced liver injury caused by an influx of T-lymphocytes targeting liver cells potentially recognizing drug-haptenated peptides in the context of HLA-B*57:01. To identify immunopeptidome changes that could lead to drug-driven immunogenicity, we used mass spectrometry to characterize the proteome and immunopeptidome of B-lymphoblastoid cells solely expressing HLA-B*57:01 as MHC-I molecules. Selected drug-conjugated peptides identified in these cells were synthesized and tested for their immunogenicity in HLA-B*57:01-transgenic mice. T cell responses were evaluated in vitro by immune assays. The immunopeptidome of FLX-treated cells was more diverse than that of untreated cells, enriched with peptides containing carboxy-terminal tryptophan and FLX-haptenated lysine residues on peptides. Selected FLX-modified peptides with drug on P4 and P6 induced drug-specific CD8+ T cells in vivo. FLX was also found directly linked to the HLA K146 that could interfere with KIR-3DL or peptide interactions. These studies identify a novel effect of antibiotics to alter anchor residue frequencies in HLA-presented peptides which may impact drug-induced inflammation. Covalent FLX-modified lysines on peptides mapped drug-specific immunogenicity primarily at P4 and P6 suggesting these peptide sites as drivers of off-target adverse reactions mediated by FLX. FLX modifications on HLA-B*57:01-exposed lysines may also impact interactions with KIR or TCR and subsequent NK and T cell function.