Theoretical rejection of fifty-four antineoplastic drugs by different nanofiltration membranes

The rise of nanofiltration technologies holds great promise for creating more effective and affordable techniques aiming to remove undesirable pollutants from wastewaters. Despite nanofiltration's promising potential in removing antineoplastic drugs from liquid matrices, the limited information on this topic makes it important to estimate the rejection rates for a larger number of compounds, particularly the emerging ones, in order to preview the nanofiltration performance. Aiming to have preliminary estimations of the rejection rates of antineoplastic drugs by nanofiltration, 54 antineoplastic drugs were studied in 5 nanofiltration membranes (Desal 5DK, Desal HL, Trisep TS-80, NF270, and NF50), using a quantitative structure-activity relationship (QSAR) model. While this methodology provides useful and reliable predictions of the rejections of compounds by nanofiltration, particularly for hydrophilic and neutral compounds, it is important to note that QSAR results should always be corroborated by experimental assays, as predictions were confirmed to have their limitations (especially for hydrophobic and charged compounds). Out of the 54 studied antineoplastic drugs, 29 were predicted to have a rejection that could go up to 100%, independent of the membrane used. Nonetheless, there were 2 antineoplastic drugs, fluorouracil and thiotepa, for which negligible removals were obtained (<21%). This study's findings may contribute (i) to the selection of the most appropriate nanofiltration membranes for removing antineoplastic drugs from wastewaters and (ii) to assist in the design of effective treatment approaches for their removal.Open access funding provided by FCT|FCCN (b-on). This research was financially supported by (i) POCI-01-0145-FEDER-031297 (CytoStraTech) - funded by FEDER funds through COMPETE2020 - Programa Operacional Competitividade e Inter nacionalizacao (POCI) and by national funds (PIDDAC) through FCT/MCTES; (ii) UIDB/04750/2020 (EPIUnit) and LA/P/0064/2020 (ITR), funded by national funds through the FCT - Foundation for Science and Technology, I.P.; (iii) LA/P/0045/2020 (ALiCE), Base Fundings UIDB/00511/2020 and UIDP/00511/2020 (LEPABE), funded by national funds through FCT/MCTES (PIDDAC). This work is a result of Agenda Embal-agem do Futuro | + ECOLOGICA + DIGITAL + INCLUSIVA, nr. C644931699-00000 042, investment project nr. 59, financed by the Recovery and Resilience Plan (PRR) and by European Union -NextGeneration EU. Teresa I. A. Gouveia also received Ph.D.& grant (SFRH/BD/147301/2019) from the Portuguese Foundation for Science and Technology (FCT)

Adsorption Technologies for the Removal of Cytostatics in Water: A Review

One of the most common treatments for cancer disease requires the administration of cytostatics, which are very effective drugs in the elimination of cancerous cells, but are toxic for healthy tissues. After being administered to patients, they are excreted and frequently reach natural water bodies, due to their poor degradation in wastewater treatment plants (WWTPs), posing a global threat to the environment and human health. The study of proper treatment approaches for the effective removal of these hazardous drugs in WWTPs is thus a topic of concern and of utmost importance to ensure environmental integrity, resilience and sustainability. The aim of this work is to perform a comprehensive review of the application of adsorption-based processes for the treatment of aqueous matrices contaminated with cytostatics, which has never been addressed before. A detailed discussion on the operating conditions, type and concentrations of sorbents used, toxicity of the effluents and other relevant parameters is presented. This paper aims to help identify the most promising sorbents and conditions, the current knowledge gaps, and future challenges/perspectives on adsorption technologies (isolated or coupled with other processes) to tackle the problem of cytostatic fingerprints in water courses. Additionally, information concerning the implementation of these technologies from an environmental and economic (life cycle assessment) perspective is given.This research was funded by: Project POCI-01-0145-FEDER-031297 (CytoStraTech)—funded by the FEDER funds through COMPETE2020—Programa Operacional Competitividade e Internacionalização (POCI) and by the national funds (PIDDAC) through FCT/MCTES; Base Funding—UIDB/00511/2020 of the LEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy; UIDB/04750/2020 (EPIUnit) and LA/P/0064/2020 (ITR), funded by the national funds through the FCT—Foundation for Science and Technology. I.P. Teresa I.A. Gouveia would like to thank the Portuguese Foundation for Science and Technology (FCT) for her PhD grant (SFRH/BD/147301/2019)

An Improved LC-MS/MS Method for the Analysis of Thirteen Cytostatics on Workplace Surfaces

This research was funded by Project POCI-01-0145-FEDER-031297 (CytoStraTech).—funded by FEDER funds through COMPETE2020—Programa Operacional Competitividade e Internacionalização (POCI) and by national funds (PIDDAC) through FCT/MCTES; Base Funding—UIDB/00511/2020 of the LEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy; and UIDB/50020/2020 of the Associate Laboratory LSRE-LCM—funded by national funds through FCT/MCTES (PIDDAC). The APC was funded by Project POCI-01-0145-FEDER-031297 (CytoStraTech)

COVID-19 Mortality and Case-Fatality Rates in Sergipe State, Northeast Brazil, From April to June 2020

Information on how coronavirus disease 2019 (COVID-19) mortality is related to population characteristics in low- and middle-income countries is still limited. We described the deaths from COVID-19 in Sergipe state, Northeast Brazil, from April 2 to June 27, 2020. For this purpose, we conducted a study composed of (i) a case series study of all deaths due to COVID-19 and (ii) a population-based study to verify the behavior of the mortality and case-fatality rates (CFR) related to COVID-19. Data from 605 deaths due to COVID-19 were used to describe the characteristics of individuals with the disease, as well as the differences in gender, age, and comorbidities. Additionally, population data were extracted to estimate the mortality and CFR by population stratum. We also performed an adjusted CFR analysis including a time lag of 14 days between the onset of symptoms and reporting deaths. Of the 605 patients included in this study, 321 (53.1%) were males and the median age was 67.0 years. Most patients (n = 447, 73.9%) who died from COVID-19 had at least one pre-existing clinical condition. The mortality rate was 29.3 deaths per 100,000 inhabitants and the crude CRF was 2.6% (95% CI 2.4–2.8). CFR was higher in males (3.1%, 95% CI 2.8–3.4; p < 0.001) and people aged =60 years (14.2%, 95% CI 13.0–15.6; p = 0.042). About 25% of patients died during the first 24-h post-hospital admission. The adjusted CFR for a 14-day time lag was ~2-fold higher than the crude CFR over the study period.We dedicated this article to all health professionals who are facing COVID-19. This study was part of the EpiSERGIPE project. NM thanks the Portuguese Foundation for Science and Technology under the Horizon 2020 Program (PTDC/PSI-GER/280 76/2017)

Antineoplastic drugs in urban wastewater: Occurrence, nanofiltration treatment and toxicity screening*

Antineoplastic drugs are pharmaceuticals that have been raising concerns among the scientific community due to: (i) their increasing prescription in the fight against the disease of the twentieth century (cancer); (ii) their recalcitrance to conventional wastewater treatments; (iii) their poor environmental biodegradability; and (iv) their potential risk to any eukaryotic organism. This emerges the urgency in finding solutions to mitigate the entrance and accumulation of these hazardous chemicals in the environment. Advanced oxidation processes (AOPs) have been taken into consideration to improve the degradation of antineoplastic drugs in wastewater treatment plants (WWTPs), but the formation of by-products that are more toxic or exhibit a different toxicity profile than the parent drug is frequently reported. This work evaluates the performance of a nanofiltration pilot unit, equipped with a Desal 5DK membrane, in the treatment of real WWTP effluents contaminated (without spiking) with eleven pharmaceuticals, five of which were never studied before. Average removals of 68 & PLUSMN; 23% were achieved for the eleven compounds, with decreasing risks from feed to permeate for aquatic organisms from receiving waterbodies (with the exception of cyclophosphamide, for which a high risk was estimated in the permeate). Aditionally, no significative impact on the growth and germination of three different seeds (Lepidium sativum, Sinapis alba, and Sorghum saccharatum) were determined for permeate matrix in comparison to the control.& nbsp;This research was financially supported by: (i) Project POCI-01-0145-FEDER-031297 (CytoStraTech) -funded by FEDER funds through COMPETE2020-Programa Operacional Competitividade e Internacionalizacao (POCI) and by national funds (PIDDAC) through FCT/MCTES; (ii) NORTE-01-0145-FEDER-000069 (Healthy Waters) co-funded by European Regional Development Fund (ERDF) , through North Portugal Regional Operational Programme (NORTE 2020) , under the PORTUGAL 2020 Partnership Agreement; (iii) UIDB/04750/2020 (EPIUnit) and LA/P/0064/2020 (ITR) , funded by national funds through the FCT-Foundation for Science and Technology, I.P.; (iv) LA/P/0045/2020 (ALiCE) , Base Fundings UIDB/00511/2020 and UIDP/00511/2020 (LEPABE) and UIDB/50020/2020 and UIDP/50020/2020 (LSRE-LCM) , funded by national funds through FCT/MCTES (PIDDAC) . This work was also funded by Fundacao para a Ciencia e Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior (FCT/MCTES, Portugal) through national funds to iNOVA4Health (UIDB/04462/2020 and UIDP/04462/2020) and the Associate Laboratory LS4FUTURE (LA/P/0087/2020) . Teresa I.A. Gouveia and Vanessa Jorge Pereira would like to thank the Portuguese Foundation for Science and Technology (FCT) for Ph.D. (SFRH/BD/147301/2019) and CEECIND/02919/2018 grants, respectively

Nanofiltration combined with ozone-based processes for the removal of antineoplastic drugs from wastewater effluents

Over the past years, there has been an increasing concern about the occurrence of antineoplastic drugs in water bodies. The incomplete removal of these pharmaceuticals from wastewaters has been confirmed by several scientists, making it urgent to find a reliable technique or a combination of techniques capable to produce clean and safe water. In this work, the combination of nanofiltration and ozone (O3)-based processes (NF + O3, NF + O3/H2O2 and NF + O3/H2O2/UVA) was studied aiming to produce clean water from wastewater treatment plant (WWTP) secondary effluents to be safely discharged into water bodies, reused in daily practices such as aquaculture activities or for recharging aquifers used as abstraction sources for drinking water production. Nanofiltration was performed in a pilot-scale unit and O3-based processes in a continuous-flow column. The peroxone process (O3/H2O2) was considered the most promising technology to be coupled to nanofiltration, all the target pharmaceuticals being removed at an extent higher than 98% from WWTP secondary effluents, with a DOC reduction up to 92%. The applicability of the clean water stream for recharging aquifers used as abstraction sources for drinking water production was supported by a risk assessment approach, regarding the final concentrations of the target pharmaceuticals. Moreover, the toxicity of the nanofiltration retentate, a polluted stream generated from the nanofiltration system, was greatly decreased after the application of the peroxone process, which evidences the positive impact on the environment of implementing a NF + O3/H2O2 process

Antimicrobial peptides as novel anti-tuberculosis therapeutics

"Available online 24 May 2016"Tuberculosis (TB), a disease caused by the human pathogen Mycobacterium tuberculosis, has recently joined HIV/AIDS as the world's deadliest infectious disease, affecting around 9.6 million people worldwide in 2014. Of those, about 1.2 million died from the disease. Resistance acquisition to existing antibiotics, with the subsequent emergence of Multi-Drug Resistant mycobacteria strains, together with an increasing economic burden, has urged the development of new anti-TB drugs. In this scope, antimicrobial peptides (AMPs), which are small, cationic and amphipathic peptides that make part of the innate immune system, now arise as promising candidates for TB treatment. In this review, we analyze the potential of AMPs for this application. We address the mechanisms of action, advantages and disadvantages over conventional antibiotics and how problems associated with its use may be overcome to boost their therapeutic potential. Additionally, we address the challenges of translational development from benchside to bedside, evaluate the current development pipeline and analyze the expected global impact from a socio-economic standpoint. The quest for more efficient and more compliant anti-TB drugs, associated with the great therapeutic potential of emerging AMPs and the rising peptide market, provide an optimal environment for the emergence of AMPs as promising therapies. Still, their pharmacological properties need to be enhanced and manufacturing-associated issues need to be addressed.Portuguese Foundation for Science and Technology (FCT) - UID/ BIO/04469/2013 unit ; COMPETE 2020 (POCI-01-0145-FEDER- 006684) ; SFRH/BPD/64958/2010Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030