Analysis of pharmaceuticals in wastewater of three hospitals in the city of Puebla, Mexico

[EN] Through their effluents, hospitals contribute to the occurrence of emerging micro-pollutants, such as pharmaceutical products, in the water. This work quantified the presence of nine pharmaceuticals in the wastewater of three private hospitals in Mexico with 66, 92 and 120 beds, respectively. The samples were characterized physicochemically and, using high-performance liquid chromatography coupled to mass spectrometry (UPLC-MS / MS), the following average maximum concentrations were reported: acetaminophen(38740.11±33832.15 ng/L), naproxen (6321.42±11074.86 ng/L), ketorolac (1429.80±237.94 ng/L), ibuprofen (249.46±143.68 ng/L), ranitidine (149.60±303.70 ng/L), hydrocortisone (96.72±57.21 ng/L), dexamethasone (33.02±41.23 ng/L), esomeprazole (22.85±24.12 ng/L) and omeprazole (22.50±23.97 ng/L). In treated water, a reduction from 67 to 100% in hydrocortisone, naproxen, paracetamol and ranitidine levels was detected. The results obtained inform the presence of pharmaceuticals that had not been previously reported in Mexican hospital effluents and demonstrate the impact of treatment plants, contributing to the existing evidence to promote regulatory actions, technological innovation and monitoring.[ES] Mediante sus efluentes, los hospitales contribuyen a la ocurrencia de microcontaminantes emergentes como los fármacos, en el agua. Este trabajo cuantificó la presencia de nueve fármacos en las aguas residuales de tres hospitales privados de México con 66, 92 y 120 camas, respectivamente. Las muestras se caracterizaron fisicoquímicamente y, empleando cromatografía líquida de alta resolución acoplada a espectrometría de masas (UPLC-MS/MS), se reportaron las siguientes concentraciones máximas promedio: paracetamol (38740.11±33832.15 ng/L), naproxeno (6321.42±11074.86 ng/L), ketorolaco (1429.80±237.94 ng/L), ibuprofeno (249.46±143.68 ng/L), ranitidina (149.60±303.70 ng/L), hidrocortisona (96.72±57.21 ng/L), dexametasona (33.02±41.23 ng/L), esomeprazol (22.85±24.12 ng/L) y omeprazol (22.50±23.97 ng/L). En aguas tratadas se detectó una reducción del 67 al 100% en los niveles de hidrocortisona, naproxeno, paracetamol y ranitidina. Los resultados obtenidos informan la presencia de fármacos que no habían sido reportados previamente en efluentes hospitalarios mexicanos y demuestran el impacto de las plantas de tratamiento, contribuyendo a la evidencia existente para impulsar acciones de regulación, innovación tecnológica y monitoreo.Los autores agradecen al Consejo Nacional de Ciencia y Tecnología (CONACYT) de México por el apoyo para la realización de esta investigación dentro del marco del Proyecto No. PN 2016 - 3620. Esta investigación también fue parcialmente apoyada por la Vicerrectoría Académica de la UDLAP (proyecto de investigación interno 2019).Castro-Pastrana, L.; Cerro-López, M.; Toledo-Wall, M.; Gómez-Oliván, L.; Saldívar-Santiago, M. (2021). Análisis de fármacos en aguas residuales de tres hospitales de la ciudad de Puebla, México. Ingeniería del agua. 25(1):59-73. https://doi.org/10.4995/ia.2021.13660OJS5973251Aedo, R. 2014. SINGREM, Sistema Nacional de Gestión de Residuos de Envases y Medicamentos A.C. Casos de éxito, XXIII Convención de la Industria Farmacéutica, CANIFARMA, Junio 26, Puerto Vallarta, México.Alder, A.C., Siegrist, H., Fent, K., Egli, T., Molnar, E., Poiger, T., Schaffner, C., Giger, W. 1997. The Fate of Organic Pollutants in Wastewater and Sludge Treatment: Significant Processes and Impact of Compound Properties. Chimia, 51, 922-928.Bedner, M., MacCrehan, W.A. 2006. Transformation of acetaminophen by chlorination produces the toxicants 1,4-benzoquinone and N-acetyl-p-benzoquinone imine. Environmental Science & Technology, 40(2), 516-22, https://doi.org/10.1021/es0509073Boix, C., Ibáñez, M., Zamora, T., Sancho, J.V., Niessen, W.M., Hernández, F. 2014. Identification of new omeprazole metabolites in wastewaters and surface waters. Science of the Total Environment, 468-469, 706-14, https://doi.org/10.1016/j.scitotenv.2013.08.095Boix, C., Ibáñez, M., Bagnati, R., Zuccato, E., Sancho, J.V., Hernández, F., Castiglioni, S. 2016. High resolution mass spectrometry to investigate omeprazole and venlafaxine metabolites in wastewater. Journal of Hazardous Materials, 302, 332-340, https://doi.org/10.1016/j.jhazmat.2015.09.05

Mitogen-Activated Protein Kinase Phosphatase-1 Is Overexpressed in Non-Small Cell Lung Cancer and Is an Independent Predictor of Outcome in Patients

An increase in the activity of the mitogen-activated protein kinases (MAPKs) has been correlated with a more malignant phenotype in several tumor models in vitro and in vivo. A key regulatory mechanism of the MAPKs [extracellular signal-regulated kinase (ERK); c-jun NH(2)-terminal kinase (JNK); and p38] is the dual specificity phosphatase CL100, also called MAPK phosphatase-1 (MKP-1). This study was designed to examine the involvement of CL100/MKP-1 and stress-related MAPKs in lung cancer. EXPERIMENTAL DESIGN: We assessed the expression of CL100/MKP-1 and the activation of the MAPKs in a panel of 18 human cell lines [1 primary normal bronchial epithelium, 8 non-small cell lung cancer (NSCLC), 7 small cell lung cancer (SCLC), and 2 carcinoids] and in 108 NSCLC surgical specimens. RESULTS: In the cell lines, CL100/MKP-1 expression was substantially higher in NSCLC than in SCLC. P-ERK, P-JNK, and P-p38 were activated in SCLC and NSCLC, but the degree of their activation was variable. Immunohistochemistry in NSCLC resection specimens showed high levels of CL100/MKP-1 and activation of the three MAPK compared with normal lung. In univariate analysis, no relationship was found among CL100/MKP-1 expression and P-ERK, P-JNK, or P-p38. Interestingly, high CL100/MKP-1 expression levels independently predicted improved survival in multivariate analysis. JNK activation associated with T(1-2) and early stage, whereas ERK activation correlated with late stages and higher T and N. Neither JNK nor ERK activation were independent prognostic factors when studied for patient survival. CONCLUSIONS: Our data indicate the relevance of MAPKs and CL100/MKP-1 in lung cancer and point at CL100/MKP-1 as a potential positive prognostic factor in NSCLC. Finally, our study supports the search of new molecular targets for lung cancer therapy within the MAPK signaling pathway

Altered patterns of expression of members of the heterogeneous nuclear ribonucleoprotein (hnRNP) family in lung cancer

hnRNP A2/B1 has been suggested as a useful early detection marker for lung carcinoma. hnRNP A2/B1 is a member of a large family of heterogeneous nuclear ribonucleoproteins (hnRNP proteins) involved in a variety of functions, including regulation of transcription, mRNA metabolism, and translation. In lung cancer, we have evaluated the expression and cellular localization of several members of the hnRNP family, hnRNP A1, A2, B1, C1, C2 and K. 16 cell lines (SCLC and NSCLC) and biopsies from 32 lung cancer patients were analyzed. Our results suggest that, besides hnRNP A2/B1, the expression of other members of the hnRNP family is altered both in SCLC and NSCLC. In the biopsies, negative or low expression of the hnRNP proteins analyzed was observed in normal epithelial cells whereas lung cancer cells showed highly intense nuclear or cytoplasmic immunolocalization. In all the lung cancer cell lines, the mRNA for all the hnRNP proteins was detected. In general, higher levels of hnRNP mRNAs were found in SCLC as compared with NSCLC. Our results also suggest that the expression and processing of each hnRNP protein in lung cancer is independently regulated and is not exclusively related to proliferation status. In SCLC cell lines, hnRNP A1 protein expression correlated with that of Bcl-x(L). In the lung cancer cell lines, hnRNP K protein localization varied with the cellular confluence

ERK1/2 is activated in non-small-cell lung cancer and associated with advanced tumours

Activation of the ERK1/2 pathway is involved in malignant transformation both in vitro and in vivo. Little is known about the role of activated ERK1/2 in non-small cell lung cancer (NSCLC). The purpose of this study was to characterise the extent of the activation of ERK1/2 by immunohistochemistry in patients with NSCLC, and to determine the relationship of ERK1/2 activation with clinicopathological variables. Specimens from 111 patients with NSCLC (stages I-IV) were stained for P-ERK. Staining for epidermal growth factor receptor (EGFR) and Ki-67 was also performed. In all, 34% of the tumour specimens showed activation for ERK1/2, while normal lung epithelial tissue was consistently negative. There was a strong statistical correlation between nuclear and cytoplasmic P-ERK staining and advanced stages (P<0.05 and P<0.001, respectively), metastatic hilar or mediastinal lymph nodes (P<0.01, P<0.001), and higher T stages (P<0.01, P<0.001). We did not find correlation of nuclear or cytoplasmic P-ERK staining with either EGFR expression or Ki-67 expression. Total ERK1/2 expression was evaluated with a specific ERK1/2 antibody and showed that P-ERK staining was not due to ERK overexpression but rather to hyperactivation of ERK1/2. Patients with a positive P-ERK cytoplasmic staining had a significant lower survival (P<0.05). However, multivariate analysis did not show significant survival difference. Our study indicates that nuclear and cytoplasmic ERK1/2 activation positively correlates with stage, T and lymph node metastases, and thus, is associated with advanced and aggressive NSCLC tumours

Evaluation of turbulent dissipation rate retrievals from Doppler Cloud Radar

Turbulent dissipation rate retrievals from cloud radar Doppler velocity measurements are evaluated using independent, in situ observations in Arctic stratocumulus clouds. In situ validation data sets of dissipation rate are derived using sonic anemometer measurements from a tethered balloon and high frequency pressure variation observations from a research aircraft, both flown in proximity to stationary, ground-based radars. Modest biases are found among the data sets in particularly low- or high-turbulence regimes, but in general the radar-retrieved values correspond well with the in situ measurements. Root mean square differences are typically a factor of 4-6 relative to any given magnitude of dissipation rate. These differences are no larger than those found when comparing dissipation rates computed from tetheredballoon and meteorological tower-mounted sonic anemometer measurements made at spatial distances of a few hundred meters. Temporal lag analyses suggest that approximately half of the observed differences are due to spatial sampling considerations, such that the anticipated radar-based retrieval uncertainty is on the order of a factor of 2-3. Moreover, radar retrievals are clearly able to capture the vertical dissipation rate structure observed by the in situ sensors, while offering substantially more information on the time variability of turbulence profiles. Together these evaluations indicate that radar-based retrievals can, at a minimum, be used to determine the vertical structure of turbulence in Arctic stratocumulus clouds

Single Spin Asymmetry ANA_N in Polarized Proton-Proton Elastic Scattering at s=200\sqrt{s}=200 GeV

We report a high precision measurement of the transverse single spin asymmetry $A_N$ at the center of mass energy $\sqrt{s}=200$ GeV in elastic proton-proton scattering by the STAR experiment at RHIC. The $A_N$ was measured in the four-momentum transfer squared $t$ range $0.003 \leqslant |t| \leqslant 0.035$ \GeVcSq, the region of a significant interference between the electromagnetic and hadronic scattering amplitudes. The measured values of $A_N$ and its $t$-dependence are consistent with a vanishing hadronic spin-flip amplitude, thus providing strong constraints on the ratio of the single spin-flip to the non-flip amplitudes. Since the hadronic amplitude is dominated by the Pomeron amplitude at this $\sqrt{s}$, we conclude that this measurement addresses the question about the presence of a hadronic spin flip due to the Pomeron exchange in polarized proton-proton elastic scattering.Comment: 12 pages, 6 figure

Evolution of the differential transverse momentum correlation function with centrality in Au+Au collisions at sNN=200\sqrt{s_{NN}} = 200 GeV

We present first measurements of the evolution of the differential transverse momentum correlation function, {\it C}, with collision centrality in Au+Au interactions at $\sqrt{s_{NN}} = 200$ GeV. {\it C} exhibits a strong dependence on collision centrality that is qualitatively similar to that of number correlations previously reported. We use the observed longitudinal broadening of the near-side peak of {\it C} with increasing centrality to estimate the ratio of the shear viscosity to entropy density, $\eta/s$, of the matter formed in central Au+Au interactions. We obtain an upper limit estimate of $\eta/s$ that suggests that the produced medium has a small viscosity per unit entropy.Comment: 7 pages, 4 figures, STAR paper published in Phys. Lett.

Acceptability and feasibility of a virtual community of practice to primary care professionals regarding patient empowerment : A qualitative pilot study

Background: Virtual communities of practice (vCoPs) facilitate online learning via the exchange of experiences and knowledge between interested participants. Compared to other communities, vCoPs need to overcome technological structures and specific barriers. Our objective was to pilot the acceptability and feasibility of a vCoP aimed at improving the attitudes of primary care professionals to the empowerment of patients with chronic conditions. Methods: We used a qualitative approach based on 2 focus groups: one composed of 6 general practitioners and the other of 6 practice nurses. Discussion guidelines on the topics to be investigated were provided to the moderator. Sessions were audio-recorded and transcribed verbatim. Thematic analysis was performed using the ATLAS-ti software. Results: The available operating systems and browsers and the lack of suitable spaces and time were reported as the main difficulties with the vCoP. The vCoP was perceived to be a flexible learning mode that provided up-to-date resources applicable to routine practice and offered a space for the exchange of experiences and approaches. Conclusions: The results from this pilot study show that the vCoP was considered useful for learning how to empower patients. However, while vCoPs have the potential to facilitate learning and as shown create professional awareness regarding patient empowerment, attention needs to be paid to technological and access issues and the time demands on professionals. We collected relevant inputs to improve the features, content and educational methods to be included in further vCoP implementation. Trial registration: ClinicalTrials.gov, NCT02757781. Registered on 25 April 2016