Spread of SARS-CoV-2 in hospital areas.

We performed a systematic sampling and analysis of airborne SARS-CoV-2 RNA in different hospital areas to assess viral spread. Systematic air filtration was performed in rooms with COVID-19 infected patients, in corridors adjacent to these rooms, to rooms of intensive care units, and to rooms with infected and uninfected patients, and in open spaces. RNA was extracted from the filters and real-time reverse transcription polymerase chain reaction was performed using the LightMix Modular SARS-CoV-2 E-gene. The highest occurrence of RNA was found in the rooms with COVID-19 patients (mean 2600 c/m3) and the adjacent corridor (mean 4000 c/m3) which was statistically significant more exposed (p < 0.01). This difference was related to the ventilation systems. As is commonly found in many hospitals, each of the rooms had an individual air inlet and outlet, while in the corridors these devices were located at the distance of every four rooms. There was a significant transfer of viruses from the COVID-19 patients' rooms to the corridors. The airborne SARS-CoV-2 RNA in the corridors of ICUs with COVID-19 patients or care rooms of uninfected patients were ten times lower, averages 190 c/m3 and 180 c/m3, respectively, without presenting significant differences. In all COVID-19 ICU rooms, patients were intubated and connected to respirators that filtered all exhaled air and prevented virus release, resulting in significantly lower viral concentrations in adjacent corridors. The results show that the greatest risk of nosocomial infection may also occur in hospital areas not directly exposed to the exhaled breath of infected patients. Hospitals should evaluate the ventilation systems of all units to minimize possible contagion and, most importantly, direct monitoring of SARS-CoV-2 in the air should be carried out to prevent unexpected viral exposures.

Vehicle interior air quality conditions when travelling by taxi.

Vehicle interior air quality (VIAQ) was investigated inside 14 diesel/non-diesel taxi pairs operating simultaneously and under normal working conditions over six weekday hours (10.00-16.00) in the city of Barcelona, Spain. Parameters measured included PM10 mass and inorganic chemistry, ultrafine particle number (N) and size, lung surface deposited area (LDSA), black carbon (BC), CO2, CO, and a range of volatile organic compounds (VOCs). Most taxi drivers elected to drive with windows open, thus keeping levels of CO2 and internally-generated VOCs low but exposing them to high levels of traffic-related air pollutants entering from outside and confirming that air exchange rates are the dominant influence on VIAQ. Median values of N and LDSA (both sensitive markers of VIAQ fluctuations and likely health effects) were reduced to around 104 #/cm3 and < 20 µm2/cm3 respectively under closed conditions, but more than doubled with windows open and sometimes approached 105 #/cm3 and 240 µm2/cm3. In exceptional traffic conditions, transient pollution peaks caused by outside infiltration exceeded N = 106 #/cm3 and LDSA= 1000 µm2/cm3. Indications of self-pollution were implicated by higher BC and CO levels, and larger UFP sizes, measured inside diesel taxis as compared to their non-diesel pair, and the highest concentrations of CO (>2 ppm) were commonly associated with older, high-km diesel taxis. Median PM10 concentrations (67 µg/m3) were treble those of urban background, mainly due to increased levels of organic and elemental carbon, with source apportionment calculations identifying the main pollutants as vehicle exhaust and non-exhaust particles. Enhancements in PM10 concentrations of Cr, Cu, Sn, Sb, and a "High Field Strength Element" zircon-related group characterised by Zr, Hf, Nb, Y and U, are attributed mainly to the presence of brake-derived PM. Volatile organic compounds display a mixture which reflects the complexity of traffic-related organic carbon emissions infiltrating the taxi interior, with 2-methylbutane and n-pentane being the most abundant VOCs, followed by toluene, m-xylene, o-xylene, 1,2,4-trimethylbenzene, ethylbenzene, p-xylene, benzene, and 1,3,5-trimethylbenzene. Internally sourced VOCs included high monoterpene concentrations from an air freshener, and interior off-gassing may explain why the youngest taxi registered the highest content of alkanes and aromatic compounds. Carbon dioxide concentrations quickly climbed to undesirable levels (>2500 ppm) under closed ventilation conditions and could stay high for much of the working day. Taxi drivers face daily occupational exposure to traffic-related air pollutants and would benefit from a greater awareness of VIAQ issues, notably the use of ventilation, to encourage them to minimise possible health effects caused by their working environment.

Environmental and personal determinants of the uptake of disinfection by-products during swimming.

BACKGROUND: Trihalomethanes (THMs) in exhaled breath and trichloroacetic acid (TCAA) in urine are internal dose biomarkers of exposure to disinfection by-products (DBPs) in swimming pools. OBJECTIVE: We assessed how these biomarkers reflect the levels of a battery of DBPs in pool water and trichloramine in air, and evaluated personal determinants. METHODS: A total of 116 adults swam during 40min in a chlorinated indoor pool. We measured chloroform, bromodichloromethane, dibromochloromethane and bromoform in exhaled breath and TCAA in urine before and after swimming, trichloramine in air and several DBPs in water. Personal determinants included sex, age, body mass index (BMI), distance swum, energy expenditure, heart rate and 12 polymorphisms in GSTT1, GSTZ1 and CYP2E1 genes. RESULTS: Median level of exhaled total THMs and creatinine adjusted urine TCAA increased from 0.5 to 14.4µg/m(3) and from 2.5 to 5.8µmol/mol after swimming, respectively. The increase in exhaled brominated THMs was correlated with brominated THMs, haloacetic acids, haloacetonitriles, haloketones, chloramines, total organic carbon and total organic halogen in water and trichloramine in air. Such correlations were not detected for exhaled chloroform, total THMs or urine TCAA. Exhaled THM increased more in men, urine TCAA increased more in women, and both were affected by exercise intensity. Genetic variants were associated with differential increases in exposure biomarkers. CONCLUSION: Our findings suggest that, although affected by sex, physical activity and polymorphisms in key metabolizing enzymes, brominated THMs in exhaled breath could be used as a non-invasive DBP exposure biomarker in swimming pools with bromide-containing source waters. This warrants confirmation with new studies.

Influence of physical activity in the intake of trihalomethanes in indoor swimming pools.

This study describes the relationship between physical activity and intake of trihalomethanes (THMs), namely chloroform (CHCl3), bromodichloromethane (CHCl2Br), dibromochloromethane (CHClBr2) and bromoform (CHBr3), in individuals exposed in two indoor swimming pools which used different disinfection agents, chlorine (Cl-SP) and bromine (Br-SP). CHCl3 and CHBr3 were the dominant compounds in air and water of the Cl-SP and Br-SP, respectively. Physical exercise was assessed from distance swum and energy expenditure. The changes in exhaled breath concentrations of these compounds were measured from the differences after and before physical activity. A clear dependence between distance swum or energy expenditure and exhaled breath THM concentrations was observed. The statistically significant relationships involved higher THM concentrations at higher distances swum. However, air concentration was the major factor determining the CHCl3 and CHCl2Br intake in swimmers whereas distance swum was the main factor for CHBr3 intake. These two causes of THM incorporation into swimmers concurrently intensify the concentrations of these compounds into exhaled breath and pointed to inhalation as primary mechanism for THM uptake. Furthermore, the rates of THM incorporation were proportionally higher as higher was the degree of bromination of the THM species. This trend suggested that air-water partition mechanisms in the pulmonary system determined higher retention of the THM compounds with lower Henry's Law volatility constants than those of higher constant values. Inhalation is therefore the primary mechanisms for THM exposure of swimmers in indoor buildings.

Measurement of volatile organic compounds using tethered balloons in a polluted industrial site in Catalonia (Spain).

Understanding the chemical composition of volatile organic compounds (VOCs) near emission sources and in the background atmosphere above the mixing layer height (MLH) provides insight into the fate of VOCs and is essential for developing effective air pollution control strategies. Unfortunately, knowledge of the qualitative and quantitative changes of VOCs and their vertical transport in the atmosphere is limited due to challenging experimental setups. In this study, an innovative method using tethered balloons was tested and implemented to sample 40 VOCs and O3 below and above the MLH at an industrial site in Spain. VOC and O3 samples were collected with different types of sorbent cartridges and analyzed using chromatographic techniques. Overall, a decrease in VOC concentration with altitude was observed along with a homogeneous chemical composition up to 300 m AGL. This decrease with altitude denoted the primary origin of these VOCs, which were strongly influenced by industrial processes and the traffic emissions in the area. Conversely, O3 concentrations were notably higher at balloon level and increased during nighttime temperature inversion episodes in those samples collected above the mixing layer. Ground samples contained freshly emitted pollutants of industrial origin, while balloon samples consisted of aged pollutants from traffic, other combustion sources, or from a secondary origin. This study is the first to assess the vertical composition of VOCs at a site of these characteristics and demonstrates that tethered balloons are a cost-effective method for studying air pollution dynamics from the ground to higher altitudes in the low troposphere.

Parenteral Nutrition: Current Use, Complications, and Nutrition Delivery in Critically Ill Patients.

BACKGROUND: Parenteral nutrition (PN) is needed to avoid the development of malnutrition when enteral nutrition (EN) is not possible. Our main aim was to assess the current use, complications, and nutrition delivery associated with PN administration in adult critically ill patients, especially when used early and as the initial route. We also assessed the differences between patients who received only PN and those in whom EN was initiated after PN (PN-EN). METHODS: A multicenter (n = 37) prospective observational study was performed. Patient clinical characteristics, outcomes, and nutrition-related variables were recorded. Statistical differences between subgroups were analyzed accordingly. RESULTS: From the entire population (n = 629), 186 (29.6%) patients received PN as initial nutrition therapy. Of these, 74 patients (11.7%) also received EN during their ICU stay (i.e., PN-EN subgroup). PN was administered early (<48 h) in the majority of patients (75.3%; n = 140) and the mean caloric (19.94 ± 6.72 Kcal/kg/day) and protein (1.01 ± 0.41 g/kg/day) delivery was similar to other contemporary studies. PN showed similar nutritional delivery when compared with the enteral route. No significant complications were associated with the use of PN. Thirty-two patients (43.3%) presented with EN-related complications in the PN-EN subgroup but received a higher mean protein delivery (0.95 ± 0.43 vs 1.17 ± 0.36 g/kg/day; p = 0.03) compared with PN alone. Once adjusted for confounding factors, patients who received PN alone had a lower mean protein intake (hazard ratio (HR): 0.29; 95% confidence interval (CI): 0.18-0.47; p = 0.001), shorter ICU stay (HR: 0.96; 95% CI: 0.91-0.99; p = 0.008), and fewer days on mechanical ventilation (HR: 0.85; 95% CI: 0.81-0.89; p = 0.001) compared with the PN-EN subgroup. CONCLUSION: The parenteral route may be safe, even when administered early, and may provide adequate nutrition delivery. Additional EN, when possible, may optimize protein requirements, especially in more severe patients who received initial PN and are expected to have longer ICU stays. NCT Registry: 03634943.

Wild fish and seafood species in the western Mediterranean Sea with low safe mercury concentrations.

A total of 1345 specimens belonging to 58 different species of wild fish and seafood from the western Mediterranean Sea were analyzed to assess total mercury levels and to estimate which species meet the EU recommendations for human consumption (0.5 µg g-1 ww) in all cases. All fish species were caught off the Mediterranean coasts and intended for human consumption. All specimens were collected from local markets located in Spain, Italy and France that sell fish caught by local fishermen (Eivissa, Menorca, Mallorca, Alacant, L'Ampolla, Ametlla de Mar, Marseille, Genoa, Civitavecchia, Alghero) at different time periods. Mercury concentrations were measured by thermal decomposition-gold amalgamator-atomic absorption spectrometry. Only thirteen species were found that did not exceed 0.5 µg g-1 ww in any specimen analyzed. These safe species were sardines (Sardina pilchardus), anchovies (Engraulis encrasicolus), blue whiting (Micromesistius poutassou), picarel (Spicara smaris), blackspot seabream (Pagellus bogaraveo), gilthead seabream (Sparus aurata), pearly razorfish (Xyrichtys novacula), surmullet (Mullus surmuletus), painted comber (Serranus scriba), brown meagre (Sciaena umbra), salema (Sarpa salpa), common dolphinfish (Coryphaena hippurus) and squid (Loligo vulgaris). These species occupy different trophic levels, have different lengths and average weights, but show a low mercury concentration than others living in the same environments. Potential human consumption of these species as sole source of fish would imply estimated weekly intakes representing between 49% and 70% of the recommended provisional tolerable weekly intake of methylmercury in the worst case. Health authorities should pay specific attention to species that do not meet EU thresholds and make appropriate precautionary health recommendations, especially for pregnant women and children.

Dysphagia and mechanical ventilation in SARS-COV-2 pneumonia: It's real.

BACKGROUND & AIMS: Dysphagia can be a consequence of prolonged hospitalization in intensive care units (ICUs) due to severe SARS-CoV-2 pneumonia. This study aims at Identifying the risk factors for dysphagia in ICU patients with COVID-19 pneumonia requiring invasive mechanical ventilation, and at determining the frequency of postextubation dysphagia in this population. METHODS: Observational, descriptive, retrospective, cohort study of SARS-CoV-2 pneumonia patients admitted into the ICUs from March to May 2020. The Modified Viscosity Volume Swallowing Test (mV-VST) was used to screening for dysphagia during the first 48 h of extubation in patients requiring mechanical ventilation. Descriptive statistics, univariate and multivariate analyses were conducted. A logistic regression was applied to construct a predictive model of dysphagia. RESULTS: A total of 232 patients were admitted into the ICUs (age [median 60.5 years (95% CI: 58.5 to 61.9)]; male [74.1% (95% CI: 68.1 to 79.4)]; APACHE II score [median 17.7 (95% CI: 13.3 to 23.2)]; length of mechanical ventilation [median 14 days (95% CI: 11 to 16)]; prone position [79% (95% CI: 72.1 to 84.6)]; respiratory infection [34.5% (95% CI: 28.6 to 40.9)], renal failure [38.5% (95% CI: 30 to 50)])). 72% (167) of patients required intubation; 65.9% (110) survived; and in 84.5% (93) the mV-VST was performed. Postextubation dysphagia was diagnosed in 26.9% (25) of patients. APACHE II, prone position, length of ICU and hospital stay, length of mechanical ventilation, tracheostomy, respiratory infection and kidney failure developed during admission were significantly associated (p < 0.05) with dysphagia. Dysphagia was independently explained by the APACHE II score (OR: 1.1; 95% CI: 1.01 to 1.3; p = 0.04) and tracheostomy (OR: 10.2; 95% CI: 3.2 to 32.1) p < 0.001). The predictive model forecasted dysphagia with a good ROC curve (AUC: 0.8; 95% CI: 0.7 to 0.9). CONCLUSIONS: Dysphagia affects almost one-third of patients with SARS-COV-2 pneumonia requiring intubation in the ICU. The risk of developing dysphagia increases with prolonged mechanical ventilation, tracheostomy, and poorer prognosis on admission (worst APACHE II score).

The Effect of Enteral Immunonutrition in the Intensive Care Unit: Does It Impact on Outcomes?

Background: The present research aimed to evaluate the effect on outcomes of immunonutrition (IMN) enteral formulas during the intensive care unit (ICU) stay. Methods: A multicenter prospective observational study was performed. Patient characteristics, disease severity, nutritional status, type of nutritional therapy and outcomes, and laboratory parameters were collected in a database. Statistical differences were analyzed according to the administration of IMN or other types of enteral formulas. Results: In total, 406 patients were included in the analysis, of whom 15.02% (61) received IMN. Univariate analysis showed that patients treated with IMN formulas received higher mean caloric and protein intake, and better 28-day survival (85.2% vs. 73.3%; p = 0.014. Unadjusted Hazard Ratio (HR): 0.15; 95% CI (Confidence Interval): 0.06−0.36; p < 0.001). Once adjusted for confounding factors, multivariate analysis showed a lower need for vasopressor support (OR: 0.49; 95% CI: 0.26−0.91; p = 0.023) and continuous renal replacement therapies (OR: 0.13; 95% CI: 0.01−0.65; p = 0.049) in those patients who received IMN formulas, independently of the severity of the disease. IMN use was also associated with higher protein intake during the administration of nutritional therapy (OR: 6.23; 95% CI: 2.59−15.54; p < 0.001), regardless of the type of patient. No differences were found in the laboratory parameters, except for a trend toward lower triglyceride levels (HR: 0.97; 95% CI: 0.95−0.99; p = 0.045). Conclusion: The use of IMN formulas may be associated with better outcomes (i.e., lower need for vasopressors and continuous renal replacement), together with a trend toward higher protein enteral delivery during the ICU stay. These findings may ultimately be related to their modulating effect on the inflammatory response in the critically ill. NCT Registry: 03634943.

Evaluation of Nutritional Practices in the Critical Care patient (The ENPIC study): Does nutrition really affect ICU mortality?

BACKGROUND & AIMS: The importance of artificial nutritional therapy is underrecognized, typically being considered an adjunctive rather than a primary therapy. We aimed to evaluate the influence of nutritional therapy on mortality in critically ill patients. METHODS: This multicenter prospective observational study included adult patients needing artificial nutritional therapy for >48 h if they stayed in one of 38 participating intensive care units for ≥72 h between April and July 2018. Demographic data, comorbidities, diagnoses, nutritional status and therapy (type and details for ≤14 days), and outcomes were registered in a database. Confounders such as disease severity, patient type (e.g., medical, surgical or trauma), and type and duration of nutritional therapy were also included in a multivariate analysis, and hazard ratios (HRs) and 95% confidence intervals (95%CIs) were reported. RESULTS: We included 639 patients among whom 448 (70.1%) and 191 (29.9%) received enteral and parenteral nutrition, respectively. Mortality was 25.6%, with non-survivors having the following characteristics: older age; more comorbidities; higher Sequential Organ Failure Assessment (SOFA) scores (6.6 ± 3.3 vs 8.4 ± 3.7; P < 0.001); greater nutritional risk (Nutrition Risk in the Critically Ill [NUTRIC] score: 3.8 ± 2.1 vs 5.2 ± 1.7; P < 0.001); more vasopressor requirements (70.4% vs 83.5%; P=0.001); and more renal replacement therapy (12.2% vs 23.2%; P=0.001). Multivariate analysis showed that older age (HR: 1.023; 95% CI: 1.008-1.038; P=0.003), higher SOFA score (HR: 1.096; 95% CI: 1.036-1.160; P=0.001), higher NUTRIC score (HR: 1.136; 95% CI: 1.025-1.259; P=0.015), requiring parenteral nutrition after starting enteral nutrition (HR: 2.368; 95% CI: 1.168-4.798; P=0.017), and a higher mean Kcal/Kg/day intake (HR: 1.057; 95% CI: 1.015-1.101; P=0.008) were associated with mortality. By contrast, a higher mean protein intake protected against mortality (HR: 0.507; 95% CI: 0.263-0.977; P=0.042). CONCLUSIONS: Old age, higher organ failure scores, and greater nutritional risk appear to be associated with higher mortality. Patients who need parenteral nutrition after starting enteral nutrition may represent a high-risk subgroup for mortality due to illness severity and problems receiving appropriate nutritional therapy. Mean calorie and protein delivery also appeared to influence outcomes. TRIAL REGISTRATION: ClinicaTrials.gov NCT: 03634943.

Unmet needs, health policies, and actions during the COVID-19 pandemic: a report from six European countries.

PURPOSE: The United Nations (UN) has published a Policy Brief on the impact of the Coronavirus Disease 2019 (COVID-19) that identifies policies and responses to protect older adults. Our objective was to summarize actions, health policies and clinical guidelines adopted by six European countries (Belgium, France, Italy, Poland, Spain and United Kingdom) during the pandemic, and to assess the impact of national policies on reducing adverse effects of the COVID-19 pandemic in older populations. METHODS: Reports by geriatricians on the measures and actions undertaken by governmental institutions in each country between March and July 2020, as well as the role of primary care during the pandemic, covered three areas: (a) general health strategies related to the pandemic; (b) impact of COVID-19 on health inequity; and (c) initiatives and challenges for the COVID-19 pandemic and beyond. RESULTS: In the six countries, COVID-19 mortality in nursing homes ranged from 26 to 66%. Although all countries endorsed the World Health Organization general recommendations, the reports identified the lack of harmonized European guidelines and policies for nursing homes, with competencies transferred to national (or regional) governments. All countries restricted visits in nursing homes, but no specific action plans were provided. The role of primary care was limited by the centralization of the crisis in hospital settings. CONCLUSIONS: The older population has been greatly affected by COVID-19 and by the policies initiated to control its spread. The right to health and dignity are transgenerational; chronological age should not be the sole criterion in policy decisions.

Protein-protein interactions at an enzyme-substrate interface: characterization of transient reaction intermediates throughout a full catalytic cycle of Escherichia coli thioredoxin reductase.

A large collection of structural snapshots along a full catalytic cycle of Escherichia coli thioredoxin reductase (TrxR) has been generated and characterized using a combination of theoretical methods. Molecular models were built starting from the available X-ray crystallographic structures of dimeric wild-type TrxR in the flavin-oxidizing conformation and a C135S TrxR mutant enzyme in a flavin-reducing conformation "trapped" by a cross-link between Cys138 of TrxR and Cys32 of C35S mutant thioredoxin (Trx). The transition between these two extreme states, which is shown to be reproduced in a normal mode analysis, as well as natural cofactor binding and dissociation, were simulated for the wild-type species using unrestrained and targeted molecular dynamics following docking of oxidized Trx to reduced TrxR. The whole set of simulations provides a comprehensive structural framework for understanding the mechanism of disulfide reduction in atomic detail and identifying the most likely intermediates that facilitate entry of NADPH and exit of NADP(+). The crucial role assigned to Arg73 and Lys36 of Trx in substrate binding and complex stabilization was ascertained when R73G, R73D, and K36A site-directed mutants of Trx were shown to be impaired to different extents in their ability to be reduced by TrxR. On the basis of previous findings and the results reported herein, E. coli TrxR appears as a beautifully engineered molecular machine that is capable of synchronizing cofactor capture and ejection with substrate binding and redox activity through an interdomain twisting motion.

Influence of tumor stage, symptoms, and time of blood draw on serum concentrations of organochlorine compounds in exocrine pancreatic cancer.

BACKGROUND: Knowledge is scant on the relationships between pathophysiologic processes common during cancer progression and changes in blood concentrations of organochlorine compounds (OCs). OBJECTIVE: To analyze the influence of tumor stage, cancer symptoms, and time of blood extraction on serum concentrations of OCs in exocrine pancreatic cancer (EPC). METHODS: Subjects were 144 incident cases of EPC prospectively recruited in eastern Spain. Blood was drawn and face-to-face interviews with patients were conducted during hospital admission. Information on signs and symptoms was obtained from medical records and patient interviews. OCs were analyzed by high-resolution gas chromatography with electron-capture detection. General linear models were applied to analyze log-transformed OCs corrected for total lipids. RESULTS: Lower concentrations of six of the seven OCs analyzed (p,p'-DDE, three polychlorinated biphenyls, hexachlorobenzene, and ß-hexachlorocyclohexane) were observed in patients with cholestatic syndrome (jaundice, hypocholia, and choluria). The constitutional syndrome increased only p,p'-DDT. The lowering effect of the cholestatic syndrome was stronger than the increasing effect of the constitutional syndrome (fatigue, anorexia, and weight loss), except for p,p'-DDT. When symptoms were considered, stage had only weakly inverse relationships with OC levels. The effects of symptoms on p,p'-DDE, p,p'-DDT, and the three PCBs remained significant after adjusting by the interval from blood extraction to first symptom of EPC, and even when further adjusting by stage. CONCLUSIONS: Restriction or adjustment by stage and timing of blood draw may be insufficient to prevent biases associated with cancer progression. Symptoms may enable investigators to assess disease-induced changes in lipophilic exposure biomarkers.

In pancreatic ductal adenocarcinoma blood concentrations of some organochlorine compounds and coffee intake are independently associated with KRAS mutations.

While KRAS activation is a fundamental initiating event in the aetiopathogenesis of pancreatic ductal adenocarcinoma (PDA), environmental factors influencing the occurrence and persistence of KRAS mutations remain largely unknown. The objective was to test the hypothesis that in PDA there are aetiopathogenic relationships among concentrations of some organochlorine compounds (OCs) and the mutational status of the KRAS oncogene, as well as among the latter and coffee intake. Incident cases of PDA were interviewed and had blood drawn at hospital admission (N = 103). OCs were measured by high-resolution gas chromatography with electron capture detection. Cases whose tumours harboured a KRAS mutation had higher concentrations of p,p'-dichlorodiphenyltrichloroethane (DDT), p,p'-dichlorodiphenyldichloroethene (DDE) and polychlorinated biphenyls (PCBs) 138, 153 and 180 than cases with wild-type KRAS, but differences were statistically significant only for p,p'-DDT and PCBs 138 and 153. The association between coffee intake and KRAS mutations remained significant (P-trend < 0.015) when most OCs where accounted for. When p,p'-DDT, PCB 153, coffee and alcohol intake were included in the same model, all were associated with KRAS (P = 0.042, 0.007, 0.016 and 0.025, respectively). p,p'-DDT, p,p'-DDE and PCB 138 were significantly associated with the two most prevalent KRAS mutations (Val and Asp). OCs and coffee may have independent roles in the aetiopathogenesis of PDA through modulation of KRAS activation, acquisition or persistence, plausibly through non-genotoxic or epigenetic mechanisms. Given that KRAS mutations are the most frequent abnormality of oncogenes in human cancers, and the lifelong accumulation of OCs in humans, refutation or replication of the findings is required before any implications are assessed.

Relevance of the Fanconi anemia pathway in the response of human cells to trabectedin.

Trabectedin (Yondelis; ET-743) is a potent anticancer drug that binds to DNA by forming a covalent bond with a guanine in one strand and one or more hydrogen bonds with the opposite strand. Using a fluorescence-based melting assay, we show that one single trabectedin-DNA adduct increases the thermal stability of the double helix by >20 degrees C. As deduced from the analysis of phosphorylated H2AX and Rad51 foci, we observed that clinically relevant doses of trabectedin induce the formation of DNA double-strand breaks in human cells and activate homologous recombination repair in a manner similar to that evoked by the DNA interstrand cross-linking agent mitomycin C (MMC). Because one important characteristic of this drug is its marked cytotoxicity on cells lacking a functional Fanconi anemia (FA) pathway, we compared the response of different subtypes of FA cells to MMC and trabectedin. Our data clearly show that human cells with mutations in FANCA, FANCC, FANCF, FANCG, or FANCD1 genes are highly sensitive to both MMC and trabectedin. However, in marked contrast to MMC, trabectedin does not induce any significant accumulation of FA cells in G2-M. The critical relevance of FA proteins in the response of human cells to trabectedin reported herein, together with observations showing the role of the FA pathway in cancer suppression, strongly suggest that screening for mutations in FA genes may facilitate the identification of tumors displaying enhanced sensitivity to this novel anticancer drug.

Influence of electronic cigarette vaping on the composition of indoor organic pollutants, particles, and exhaled breath of bystanders.

The changes of particles and organic pollutants in indoor atmospheres as consequence of vaping with electronic cigarettes have been analyzed. Changes in the composition of volatile organic compounds (VOCs) in exhaled breath of non-smoking volunteers present in the vaping environments have also been studied. The exposure experiments involved non-vaping (n = 5) and vaping (n = 5) volunteers staying 12 h together in a room (54 m2) without external ventilation. The same experiment was repeated without vaping for comparison. Changes in the distributions of particles in the 8-400 nm range were observed, involving losses of nucleation-mode particles (below 20 nm) and increases of coagulation processes leading to larger size particles. In quantitative terms, vaping involved doubling the indoor concentrations of particles smaller than 10 µm, 5 µm, and 1 µm observed during no vaping. The increase of particle mass concentrations was probably produced from bulk ingredients of the e-liquid exhaled by the e-cigarette users. Black carbon concentrations in the indoor and outdoor air were similar in the presence and absence of electronic cigarette emissions. Changes in the qualitative composition of PAHs were observed when comparing vaping and non-vaping days. The nicotine concentrations were examined separately in the gas and in the particulate phases showing that most of the differences between both days were recorded in the former. The particulate phase should therefore be included in nicotine monitoring during vaping (and smoking). The concentration increases of nicotine and formaldehyde were small when compared with those described in other studies of indoor atmospheres or health regulatory thresholds. No significant changes were observed when comparing the concentrations of exhaled breath in vaping and no vaping days. Even the exhaled breath nicotine concentrations in both conditions were similar. As expected, toluene, xylenes, benzene, ethylbenzene, and naphthalene did not show increases in the vaping days since combustion was not involved.

Efficacy of a nurse-led lipid-lowering secondary prevention intervention in patients hospitalized for ischemic heart disease: A pilot randomized controlled trial.

BACKGROUND AND AIMS: Lack of achievement of secondary prevention objectives in patients with ischaemic heart disease remains an unmet need in this patient population. We aimed at evaluating the six-month efficacy of an intensive lipid-lowering intervention, coordinated by nurses and implemented after hospital discharge, in patients hospitalized for an ischaemic heart disease event. METHODS: Randomized controlled trial, in which a nurse-led intervention including periodic follow-up, serial lipid level controls, and subsequent optimization of lipid-lowering therapy, if appropriate, was compared with standard of care alone in terms of serum lipid-level control at six months after discharge. RESULTS: The nurse-led intervention was associated with an improved management of low-density lipoprotein (LDL) cholesterol levels compared with standard of care alone: LDL cholesterol levels ⩽100 mg/dL were achieved in 97% participants in the intervention arm as compared with 67% in the usual care arm ( p value <0.001), the LDL cholesterol ⩽70 mg/dL target recommended by the 2016 European Society of Cardiology guidelines was achieved in 62% vs. 37% participants ( p value 0.047) and the LDL cholesterol reduction of ⩾50% recommended by the American College of Cardiology/American Heart Association in 2013 was achieved in 25.6% of participants in the intervention arm as compared with 2.6% in the usual care arm ( p value 0.007). The intervention was also associated with improved blood pressure control among individuals with hypertension. CONCLUSIONS: Our findings highlight the opportunity that nurse-led, intensive, post-discharge follow-up plans may represent for achieving LDL cholesterol guideline-recommended management objectives in patients with ischaemic heart disease. These findings should be replicated in larger cohorts.

Exposure to disinfection by-products in swimming pools and biomarkers of genotoxicity and respiratory damage - The PISCINA2 Study.

BACKGROUND: Swimming in pools is a healthy activity that entails exposure to disinfection by-products (DBPs), some of which are irritant and genotoxic. OBJECTIVES: We evaluated exposure to DBPs during swimming in a chlorinated pool and the association with short-term changes in genotoxicity and lung epithelium permeability biomarkers. METHODS: Non-smoker adults (N = 116) swimming 40 min in an indoor pool were included. We measured a range of biomarkers before and at different times after swimming: trihalomethanes (THMs) in exhaled breath (5 min), trichloroacetic acid (TCAA) in urine (30 min), micronuclei in lymphocytes (1 h), serum club cell protein (CC16) (1 h), urine mutagenicity (2 h) and micronuclei in reticulocytes (4 days in a subset, N = 19). Several DBPs in water and trichloramine in air were measured, and physical activity was extensively assessed. We estimated interactions with polymorphisms in genes related to DBP metabolism. RESULTS: Median level of chloroform, brominated and total THMs in water was 37.3, 9.5 and 48.5, µg/L, respectively, and trichloramine in air was 472.6 µg/m3. Median exhaled chloroform, brominated and total THMs increased after swimming by 10.9, 2.6 and 13.4, µg/m3, respectively. Creatinine-adjusted urinary TCAA increased by 3.1 µmol/mol. Micronuclei in lymphocytes and reticulocytes, urine mutagenicity and serum CC16 levels remained unchanged after swimming. Spearman correlation coefficients showed no association between DBP exposure and micronuclei in lymphocytes, urine mutagenicity and CC16. Moderate associations were observed for micronuclei in reticulocytes and DBP exposure. CONCLUSIONS: The unchanged levels of the short-term effect biomarkers after swimming and null associations with personal estimates of exposure to DBPs suggest no measurable effect on genotoxicity in lymphocytes, urine mutagenicity and lung epithelium permeability at the observed exposure levels. The moderate associations with micronuclei in reticulocytes require cautious interpretation given the reduced sample size.

Insights into the binding and activation sites of the receptors for cholecystokinin and gastrin.

CCK receptors represent potential targets in a number of diseases. Knowledge of CCK receptor binding sites is a prerequisite for the understanding of the molecular basis for their ligand recognition, partial agonism, ligand-induced trafficking of signalling. In the current paper, we report studies from our laboratory and others which have provided new data on the molecular basis of the pharmacology and functioning of CCK1 and CCK2 receptors. It has been shown that: 1) homologous regions of the two receptors are involved in the binding site of CCK, however, positioning of CCK slightly differs in agreement with distinct pharmacophores of CCK toward the two receptors and receptor sequence variations; 2) Binding sites of most of non-peptide agonists/ antagonist are buried in the pocket formed by transmembrane helices and overlap that of CCK; Aromatic amino acids within and near the binding site, especially in helix VI, are involved in receptor activation; 4) Like for other members of family A of G-protein coupled receptors, residues of the binding sites as well as of conserved motifs such as E/DRY, NPXXY are crucial for receptor activation.

Differences in serum concentrations of organochlorine compounds by occupational social class in pancreatic cancer.

BACKGROUND: The relationships between social factors and body concentrations of environmental chemical agents are unknown in many human populations. Some chemical compounds may play an etiopathogenic role in pancreatic cancer. OBJECTIVE: To analyze the relationships between occupational social class and serum concentrations of seven selected organochlorine compounds (OCs) in exocrine pancreatic cancer: dichlorodiphenyltrichloroethane (p,p'-DDT), dichlorodiphenyldichloroethene (p,p'-DDE), 3 polychlorinated biphenyls (PCBs), hexachlorobenzene, and beta-hexachlorocyclohexane. METHODS: Incident cases of exocrine pancreatic cancer were prospectively identified, and interviewed face-to-face during hospital admission (n=135). Serum concentrations of OCs were analyzed by high-resolution gas chromatography with electron-capture detection. Social class was classified according to occupation. RESULTS: Multivariate-adjusted concentrations of all seven compounds were higher in occupational social classes IV-V (the less affluent) than in classes I-II; they were higher as well in class III than in classes I-II for four compounds. Concentrations of six OCs were higher in manual workers than in non-manual workers (p<0.05 for PCBs). Social class explained statistically between 3.7% and 5.7% of the variability in concentrations of PCBs, and 2% or less variability in the other OCs. CONCLUSIONS: Concentrations of most OCs were higher in the less affluent occupational social classes. In pancreatic cancer the putative causal role of these persistent organic pollutants may not be independent of social class. There is a need to integrate evidence on the contribution of different social processes and environmental chemical exposures to the etiology of pancreatic and other cancers.