Dermal exposure assessment of formal e-waste dismantlers to flame retardants and plasticizers using passive sampling methodologies.

The recycling of e-waste can lead to the release of organic chemicals when materials containing additives are subjected to dismantling and grinding. In this context, the exposure of workers from a Catalonian e-waste facility to flame retardants and plasticizers (including organophosphate esters (OPEs), polybrominated diphenyl ethers (PBDEs), novel brominated flame retardants (NBFRs) and dechloranes) was assessed using T-shirts and wristbands as passive samplers. The study area includes an area exclusively dedicated to cathodic ray-tube (CRT) TVs dismantling, and a grinding area where the rest of e-waste is ground. All the families of compounds were detected in both T-shirts and wristbands, with the highest concentration levels corresponding to OPEs, followed by PBDEs, NBFRs, and dechloranes. The CRT area presented higher concentration levels than the grinding area. The compounds with higher concentrations in T-shirts were 2-ethylhexyl diphenyl phosphate (EHDPP), diphenyl cresyl phosphate (DCP) and triphenyl phosphate (TPHP), and the total concentration of all groups ranged between 293 and 8324 ng/dm2-h (hour). In the case of the wristbands, the most abundant compounds were DCP, TPHP, and BDE-209, with total concentrations between 188 and 2248 ng/dm2-h. The two sampling methods appear to be complementary, as T-shirts collect coarser particles, while wristbands also capture volatile compounds. Based on normalized surface and time concentrations, the estimated daily intake (EDI) through dermal contact was calculated and carcinogenic and non-carcinogenic risks (CR and non-CR) associated with this activity assessed. The results show median CR 29 and 16 times below the threshold in CRT and grinding areas respectively. The non-CR medians were 2 and 3 times below the threshold, although in the CRT area one exceptional value surpassed the threshold, suggesting that risk can exist for some workers in the facility.

Pesticides in water and sediments from natural protected areas of Spain and their associated ecological risk.

In the last years, issues related to intensive agriculture have been found in protected areas potentially harming wildlife. This study aimed to analyze a wide range of pesticides in water and sediments of two protected areas namely Doñana Natural Park (DNP) and Tablas de Daimiel National Park (TDNP) performing an environmental risk assessment in order to highlight potential risks to living organisms derived from pesticide burden. Higher pesticide load was found in DNP than TDNP with similar distribution profiles, with pyrethroid insecticides (PYRs) the main detected class. Particularly problematic are two PYRs, cyhalothrin and fenvalerate, which were detected at high concentrations that can pose a high risk to aquatic organisms. In addition, despite being detected at lower concentrations, the presence of chlorpyrifos, cypermethrin, and permethrin in water, and of chlorpyrifos, dicofol, and diflufenican in sediments, must be taken into account due to their potential risks for aquatic organisms. Moreover, some banned pesticides such as dimethoate, terbutryn, diazinon, and tricyclazol were detected in water at levels which deserve further investigation to assess their potential sources, including potential illegal practices.

Pesticide contamination of bird species from Doñana National Park (southwestern Spain): Temporal trends (1999-2021) and reproductive impacts.

Doñana National Park (DNP) is a protected area renowned for hosting a wide variety of birds. However, the agricultural practices in its surroundings might cause pesticide contamination of the park biota. This work aimed to assess temporal trends of a wide variety of pesticides, including organochlorine (OCPs), organophosphate (OPPs) and pyrethroid (PYRs) pesticides, in bird eggs collected for more than twenty years (1999-2021) in DNP. Twenty-six pesticides were detected, being 4,4'-DDE the most frequently detected and also the one with the highest concentrations (up to 2.55 µg g-1 ww), exceeding in some cases the values usually reported to cause detrimental health and reproductive effects in avian species. An overall decreasing trend of OCPs was observed. In contrast, an apparent increase in PYRs was detected from 2013 onwards, especially for fenvalerate, whose median concentration was 3-5 orders of magnitude higher in the most recent samples. Moreover, other pesticides such as oxadiazon, oxyfluorfen and fenitrothion were first detected in 2021 samples. Finally, two variables estimating the cumulative impact of pesticides significantly decreased the breeding performance of a top predator such as the booted eagle. Therefore, it is essential to control the use of pesticides in the agricultural practices surrounding DNP and to study their potential negative impact on the bird populations breeding in this protected area.

Pesticides in sediments of the Ebro River Delta cultivated area (NE Spain): Occurrence and risk assessment for aquatic organisms.

Intense agricultural activities are performed in the Ebro River Delta (NE Spain) with extensive use of pesticides. Medium to highly polar pesticides have not been studied intensively in sediments despite its larger use in the recent years. This work aimed at assessing the occurrence of 69 pesticides, including medium to highly polar compounds, in sediments collected from drainage and irrigation channels of the Ebro River Delta during the main rice growing season. In addition, an environmental risk assessment was performed to evaluate the potential adverse effects to sediment-dwelling organisms with the risk quotient approach. A total of 24 pesticides were detected in sediments with bentazone and cypermethrin exhibiting high detection frequencies (79%) as well as high mean concentration levels (61.9 and 81.8 ng g-1 dw, respectively). Overall, the Alfacs bay, in the South of the delta, presented higher pesticide contamination than the Fangar bay, in the North. A similar pesticide distribution profile was observed in both bays, with oxadiazoles, organochlorines, pyrethroids, benzothiazinones and organophosphates as major, predominant classes. The presence of oxadiazon, pendimethalin and thifensulfuron methyl in the sediments may pose a moderate risk to sediment-dwelling organisms while bentazone, chlorpyrifos, and cypermethrin exhibited a potential high risk. Thus, the importance of the inclusion of medium to highly polar pesticides in the analysis of sediments is emphasized since some polar pesticides such as bentazone, imidacloprid, and thifensulfuron-methyl have been detected at concentrations that may pose a risk to aquatic organisms. Moreover, the co-occurrence of pesticides may potentially pose a high risk to sediment-dwelling organisms in 13 out of the 14 investigated locations. Finally, it could be concluded that the risk derived from the presence of pesticides in sediments must be assessed since some pesticides not detected at concerning levels in water, may pose a moderate/high risk in the sediments.

Comprehending and improving cannabis specialized metabolism in the systems biology era.

Cannabis sativa is a source of food, fiber and specialized metabolites such as cannabinoids, with psychoactive and pharmacological effects. Due to its expanding and increasingly-accepted use in medicine, cannabis cultivation is acquiring more importance and less social stigma. Humans initiated different domestication episodes whose later spread gave rise to a plethora of landrace cultivars. At present, breeders cross germplasms from different gene pools depending on their specific use. The fiber (hemp) and drug (marijuana) types of C. sativa differ in their cannabinoid chemical composition phenotype (chemotype) and also in the accumulation of terpenoid compounds that constitute a strain's particular flavor and scent. Cannabinoids are isoprenylated polyketides among which cannabidiolic acid (CBDA) and (-)-trans-Δ9-tetrahydrocannabinol acid (THCA) have been well-documented for their many effects on humans. Here, we review the most studied specialized metabolic pathways in C. sativa, showing how terpenes and cannabinoids share both part of the isoprenoid pathway and the same biosynthetic compartmentalization (i.e. glandular trichomes of leaves and flowers). We enlist the several studies that have deciphered these pathways in this species including physical and genetic maps, QTL analyses and localization and enzymatic studies of cannabinoid and terpene synthases. In addition, new comparative modeling of cannabinoid synthases and phylogenetic trees are presented. We describe the genome sequencing initiatives of several accessions with the concomitant generation of next-generation genome maps and transcriptomic data. Very recently, proteomic characterizations and systems biology approaches such as those applying network theory or the integration of multi-omics data have increased the knowledge on gene function, enzyme diversity and metabolite content in C. sativa. In this revision we drift through the history, present and future of cannabis research and on how second- and third-generation sequencing technologies are bringing light to the field of cannabis specialized metabolism. We also discuss different biotechnological approaches for producing cannabinoids in engineered microorganisms.

A novel risk score for severe ARDS patients undergoing ECMO after retrieval from peripheral hospitals.

BACKGROUND: Extracorporeal Membrane Oxygenation in severe ARDS unresponsive to conventional protective ventilation is associated with elevated costs, resource and complications, and appropriate risk stratification of candidate patients could be useful to recognize those more likely to benefit from ECMO. We aimed to derive a new outcome prediction score for patients retrieved by our ECMO team from peripheral centers, including systematic echocardiographic evaluation before ECMO start. METHODS: Sixty-nine consecutive patients with refractory ARDS requiring ECMO transferred from peripheral centers to our ICU (a tertiary ECMO referral center), from 1 October 2009 to 31 December 2015, were assessed. RESULTS: All patients were transported on ECMO (distance, median 77, range 4-456 km) The mortality rate was 41% (28/69). Our new risk score included age ≥ 42 years, BMI < 31 kg/m2 , RV dilatation, and pH < 7.35. The proposed cut off (Youden's index method) of nine had a sensitivity of 96% and a specificity of 30% (AUC-ROC: 0.85, 95% CI: 0.76-0.94, P < 0.001). When assessing the discriminatory ability of our risk score in the population of local patients, survivors had a mean value of 15.4 ± 8.6, whereas non-survivors showed a mean value of 20.1 ± 7.4 (P < 0.001). CONCLUSIONS: Our new risk score shows good discriminatory ability both in patients retrieved from peripheral centers and in those implanted at our center. This score includes variables easily available at bedside, and, for the first time, a pathophysiologic element, RV dilatation.

[Involvement of the spinal cord in rheumatoid arthritis]. / Afectacion medular en la artritis reumatoide.

TITLE: Afectacion medular en la artritis reumatoide.

Neurophysiological prediction of neurological good and poor outcome in post-anoxic coma.

OBJECTIVE: Investigation of the utility of association between electroencephalogram (EEG) and somatosensory-evoked potentials (SEPs) for the prediction of neurological outcome in comatose patients resuscitated after cardiac arrest (CA) treated with therapeutic hypothermia, according to different recording times after CA. METHODS: Glasgow Coma Scale, EEG and SEPs performed at 12, 24 and 48-72 h after CA were assessed in 200 patients. Outcome was evaluated by Cerebral Performance Category 6 months after CA. RESULTS: Within 12 h after CA, grade 1 EEG predicted good outcome and bilaterally absent (BA) SEPs predicted poor outcome. Because grade 1 EEG and BA-SEPs were never found in the same patient, the recording of both EEG and SEPs allows us to correctly prognosticate a greater number of patients with respect to the use of a single test within 12 h after CA. At 48-72 h after CA, both grade 2 EEG and BA-SEPs predicted poor outcome with FPR=0.0%. When these neurophysiological patterns are both present in the same patient, they confirm and strengthen their prognostic value, but because they also occurred independently in eight patients, poor outcome is predictable in a greater number of patients. SIGNIFICANCE: The combination of EEG/SEP findings allows prediction of good and poor outcome (within 12 h after CA) and of poor outcome (after 48-72 h). Recording of EEG and SEPs in the same patients allows always an increase in the number of cases correctly classified, and an increase of the reliability of prognostication in a single patient due to concordance of patterns.

Single electroencephalographic patterns as specific and time-dependent indicators of good and poor outcome after cardiac arrest.

OBJECTIVE: To evaluate the prognostic value of single EEG patterns recorded at various time-frames in postanoxic comatose patients. METHODS: This retrospective study included 30-min EEGs, classified according to the definitions of continuity of background activity given by the American Clinical Neurophysiology Society. Isoelectric pattern was distinguished from other suppressed activities. Epileptiform patterns were considered separately. Outcome was dichotomised based on recovery of consciousness as good (Glasgow Outcome Scale [GOS] 3-5) or poor (GOS 1-2). RESULTS: We analysed 211 EEGs, categorised according to time since cardiac arrest (within 12h and around 24, 48 and 72h). In each time-frame we observed at least one EEG pattern which was 100% specific to poor or good outcome: at 12h continuous and nearly continuous patterns predicted good outcome and isoelectric pattern poor outcome; at 24h isoelectric and burst-suppression predicted poor outcome; at 48 and 72h isoelectric, burst-suppression and suppression (2-10µV) patterns predicted poor outcome. CONCLUSIONS: The prognostic value of single EEG patterns, defined according to continuity and voltage of background activity, changes until 48-72h after cardiac arrest and in each time-frame there is at least one pattern which accurately predicts good or poor outcome. SIGNIFICANCE: Standard EEG can provide time-dependent reliable indicators of good and poor outcome throughout the first 48-72h after cardiac arrest.

Cerebral microemboli detected by transcranial doppler in patients treated with extracorporeal membrane oxygenation.

INTRODUCTION: Cerebrovascular complications rate in patients treated with extracorporeal membrane oxygenation (ECMO) is about 7%. Ischemic stroke may be caused by solid or gaseous microemboli due to thrombosis within the circuit or cannula. Transcranial Doppler (TCD) is the only method able to detect microembolic signals (MES) in real time. The objective of this study was to detect possible MES by TCD in patients treated with veno-venous (VV) and veno-arterial (VA) ECMO and to test for a relation between the number of MES and the 6-month clinical outcome of these patients. METHODS: This is a monocentric observational prospective study in patients consecutively admitted and treated with ECMO at our regional ECMO referral center in 18 months. TCD detection of MES was performed in patients upon initiation of treatment and then repeated during treatment. RESULTS: Two hundred and forty-eight TCD monitoring were performed in 42 VV and 11 VA ECMO patients. MES were detected in 26.2% of VV ECMO patients and in 81.8% of VA ECMO patients (P < 0.001). In both subgroups of patients, no correlation was found between MES detection and extracorporeal flow velocities or aPTT values. In VA ECMO patients, an inverse correlation between left ventricular ejection fraction and MES grading was found (P = 0.037). In both groups, no clinical neurological impairments correlated to MES detection were found at 6 months follow-up. CONCLUSIONS: MES were found in both ECMO configurations; independently from their pathophysiology, MES do not seem to influence clinical outcome. Multicenter studies are still required with more extensive cases to confirm these results.

Pulmonary vascular dysfunction in refractory acute respiratory distress syndrome before veno-venous extracorporeal membrane oxygenation.

BACKGROUND: Pulmonary vascular dysfunction has been described in patients with acute respiratory distress syndrome (ARDS). Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a well-established treatment for these patients. We hypothesized that severe pulmonary vascular dysfunction and cor pulmonale identified by echocardiography before cannulation in these patients were associated with worse survival. METHODS: Echocardiography was used to identify pulmonary hypertension in 21 patients with refractory ARDS just before ECMO implantation. Survival was compared for those with and without cor pulmonale. RESULTS: In our series, the overall mortality rate was 57.1% (12/21). Echocardiographic exams were transthoracic in 5 patients (23.8%), transesophageal in 4 patients (19%), and both (transthoracic and transesophageal) in the remaining 12 patients (57.1%). In our series, six patients (28.5%) showed LV dysfunction. Acute cor pulmonale was detectable in 2 patients (9.5%), while the remaining 19 patients showed moderate pulmonary dysfunction. Survivors had a higher pre-cannulation LV ejection fraction (EF) (P = 0.02) and tricuspid annular plane excursion (P = 0.04), and lower peak systolic pulmonary artery pressures (P = 0.02). CONCLUSIONS: In patients with refractory ARDS immediately before ECMO implantation, the prevalence of acute cor pulmonale is low (9.5%). Survival is associated with higher LVEF and lower systolic pulmonary arterial pressure. These findings support the idea that echocardiographic assessment of pulmonary artery pressure in patients with refractory ARDS before VV-ECMO implantation may have value for risk-stratification.

Audits in real time for safety in critical care: definition and pilot study.

UNLABELLED: Adverse events significantly impact upon mortality rates and healthcare costs. PURPOSE: To design a checklist of safety measures based on relevant scientific literature, apply random checklist measures to critically ill patients in real time (safety audits), and determine its utility and feasibility. METHODS: A list of safety measures based on scientific literature was drawn up by investigators. Subsequently, a group of selected experts evaluated these measures using the Delphi methodology. Audits were carried out on 14 days over a period of one month. Each day, 50% of the measures were randomly selected and measured in 50% of the randomized patients. Utility was assessed by measuring the changes in clinical performance after audits, using the variable improvement proportion related to audits. Feasibility was determined by the successful completion of auditing on each of the days on which audits were attempted. RESULTS: The final verified checklist comprised 37 measures distributed into 10 blocks. The improvement proportion related to audits was reported in 83.78% of the measures. This proportion was over 25% in the following measures: assessment of the alveolar pressure limit, checking of mechanical ventilation alarms, checking of monitor alarms, correct prescription of the daily treatment orders, daily evaluation of the need for catheters, enteral nutrition monitoring, assessment of semi-recumbent position, and checking that patient clinical information is properly organized in the clinical history. Feasibility: rounds were completed on the 14 proposed days. CONCLUSIONS: Audits in real time are a useful and feasible tool for modifying clinical actions and minimizing errors.

The role of extracorporeal membrane oxygenation in donation after circulatory death.

Donor scarcity and the increased need for organ transplantation has prompted the development of an alternative source of donors to the more conventional brain dead donor. While in a Beating-Heart donor, abdominal and intrathoracic organs are perfused, in a non-beating heart donor (NHBD, or DCD), perfusion should be maintained, after confirmation of death, by means of ECMO and inflation of intra-aortic balloon accordingly to the localization of the organs that should be transplanted. In this setting, ECMO allows selective perfusion of the organs which should be transplanted ("compartmental ECMO"). The present review is aimed at summarizing the rationale for ECMO use in organ donation in DCD and the available evidence on this topic, as well as available evidence (in clinical studies) on normothermic organ preservation using ECMO in adults. Despite the fact that available studies suffer from methodological limitations (small cohorts, retrospective analysis, not always comparative), they all reach the same conclusion: the concept of extracorporeal support with oxygenation in DCD seems very promising since it has been reported to increase the available organ supply by approximately 20% to 25%2 by increasing the number of donors by approximately 33%. Centres with ECMO facilities should implement local programmes for donation after cardiac death (both in the emergency department and intensive care) using ECMO taking into account that this technique has been proven to increase donor pool.

HA222 polymorphism in Influenza A(H1N1) 2009 isolates from Intensive Care Units and ambulatory patients during three influenza seasons.

Amino acid substitutions which can affect the receptor binding specificity of the influenza virus, like the substitution of aspartic acid with glycine in position 222 of the haemagglutinin (HA) of influenza virus A(H1N1) 2009, have been associated with increased viral pathogenicity and increased tropism for the lower respiratory tract. In this paper, the polymorphic site 222 and the site 223 of the HA1 polypeptide of H1N1 2009 viruses were analyzed in order to better clarify the role of these substitutions in H1N1 2009 virus virulence. Viral strains included in this study were collected in Tuscany during 3 different influenza seasons from patients with severe as well as with mild forms of influenza caused by A(H1N1) 2009 virus. In addition, the oseltamivir resistance of the H1N1 2009 strains circulating during the same seasons was monitored with the aim to evaluate whether these changes in the HA and in neuraminidase (NA) tend to be linked and to influence each other. Altogether, the results indicate that in severe forms of influenza viral population is more variable than in mild influenza, as regards the site 222. The frequency of such substitutions varied among the three seasons, it was highest in the season 2010-2011 and very low in the season 2012-2013. However these differences were not significant.