Reduced ecotoxicity and improved biodegradability of cationic biocides based on ester-functionalized pyridinium ionic liquids

Abstract

Ester-functionalized pyridinium ionic liquids (ILs), 1-decyloxycarbonylmethylpyridinium chloride (PyrСOOC₁₀-Cl), and 1-dodecyloxycarbonylmethylpyridinium chloride (PyrСOOC₁₂-Cl) have been synthesized and studied for their environmental toxicity. Simple long-chain pyridinium ILs, 1-dodecylpyridinium chloride (PyrC₁₂-Cl), and commercial disinfectant cetylpyridinium chloride (CPC) were used as reference compounds. Both ester-functionalized ILs and CPC showed significantly reduced antibacterial activity compared to PyrC₁₂-Cl. However, ester-functionalized ILs were found to have excellent antifungal activity towards Candida albicans fungus strains, similar to PyrC₁₂-Cl and much higher than for CPC. The molecular docking of ILs in the active site of the known antifungal target N-myristoyltransferase (Nmt) C. albicans has been conducted. The obtained results indicate the possibility of ILs binding into the Nmt pocket. The high stability of the complexes, especially for PyrCOOC₁₀-Cl, is ensured by hydrogen bonding, electrostatic anion-pi interactions, as well as hydrophobic pi-alkyl and alkyl interactions that was confirmed by calculated binding energy values. The acute toxicity studies of ester-functionalized ILs on D. rerio (zebrafish) hydrobiont have shown their dramatically reduced ecotoxicity compared to PyrC₁₂-Cl and CPC. Thus, LD₅₀ values of 15.2 mg/L and 16.8 mg/L were obtained for PyrCOOC₁₀-Cl and PyrCOOC₁₂-Cl, respectively, whereas CPC had LD₅₀ value of 0.018 mg/L. The primary biodegradation test CEC L-33-A93 of ILs indicated an improved biodegradability of ester-functionalized compounds compared to simple long-chain ILs. Based on the obtained results, PyrCOOC₁₀-Cl may be considered as very promising cationic biocide due to the combination of soft antimicrobial activity and reduced ecotoxicity, as well as improved biodegradability.

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Recycling Discarded Drugs: Improving Access to Oral Antineoplastic Drugs

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Prevalence of Burnout and Career Satisfaction Among Oncologists in China: A National Survey

AbstractBackground.Burnout and career satisfaction has been extensively studied among U.S. and European oncologists, although little is known about the situation among Chinese oncologists. Therefore, we conducted this national survey to investigate the prevalence of burnout and career satisfaction among Chinese oncologists.Patients and Methods.Between September 2015 and December 2016, a cross‐sectional field survey was conducted through the Chinese Society of Clinical Oncology and the Chinese Committee of Rehabilitation and Palliative Care. The full‐length survey consisted of 59 questions investigating personal and professional characteristics and standardized instruments to measure burnout (Maslach Burnout Inventory‐Human Service Survey) and career satisfaction. An additional six questions, derived from the National Survey on the Practice of Medicine by Chinese Physicians related to burnout or career satisfaction, were also included.Results.In total, 3,500 oncologists received the questionnaire, and 2,700 (77.1%) responded, of whom 1,620 (46.3%) were eligible for analysis (median age, 36 years; 56.1% male). Overall, 827 oncologists (51.0%) were burned out. Five factors (lower curative rate of patients, more hours devoted to patient care, more nights on call per week, fewer minutes allocated for return outpatient visits, and more weekends rounding per year) were associated with burnout. Meanwhile, burnout was also strongly associated with a negative view of the physician‐patient relationship (p < .001; odds ratio [OR], 2.07). Notably, the career satisfaction (34.4% for career and 52.1% for specialty) of Chinese oncologists was far less than for their U.S. colleagues, which may result from low compensation (p < .001; OR, 1.660).Conclusion.The overall prevalence of burnout among oncologists in China was similar to oncologists in the U.S., whereas personal accomplishment and career satisfaction were lower. Interestingly, the reasons were different. Beside high workload, the low curative rate of patients was found to be another factor associated with Chinese physicians' burnout. The ongoing Chinese health care system reform may improve the current situation.Implications for Practice.Burnout and career satisfaction has been extensively studied among physicians and oncologists in the U.S. and Europe, but little is known about the situation among Chinese oncologists. This study is the first large‐scale national study of Chinese oncologists using standardized instruments to evaluate burnout and career satisfaction. The experience of burnout has been linked to a long list of negative implications. However, this issue has not aroused enough concern in China until now. This study may have a vital significance for the ongoing Chinese health care reform aiming to improve the Chinese health care system.

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Outcomes and Toxicities of Programmed Death‐1 (PD‐1) Inhibitors in Hodgkin Lymphoma Patients in the United States: A Real‐World, Multicenter Retrospective Analysis

AbstractBackground.Although classical Hodgkin lymphoma (cHL) is highly curable, 20%–30% of patients will not be cured with conventional treatments. The programmed death‐1 (PD‐1) inhibitors (PD‐1i) nivolumab and pembrolizumab have been Food and Drug Administration‐approved for relapsed/refractory (R/R) cHL. There is limited data on the real‐world experience with PD‐1i in cHL and it is unknown whether fewer selected patients treated with PD‐1i derive benefits similar to those observed in published trials.Materials and Methods.We performed a multicenter, retrospective analysis of R/R cHL patients treated with PD‐1i in the nontrial setting. The primary objective was to describe progression‐free survival (PFS) and overall survival (OS) in this population. Secondary objectives were to characterize response rates, toxicities, discontinuation patterns, and post‐PD‐1i therapies.Results.The study included 53 patients from nine U.S. centers. Overall response rate (ORR), complete response (CR), and partial response (PR) to PD‐1i were 68%, 45%, and 23%, respectively. Twelve‐month OS and PFS were 89% and 75%, respectively; median PFS was 29 months. Ninety‐six percent of patients with CR continue to respond at a median follow‐up of 20 months. Toxicities were similar to those previously described. Seventy percent of patients treated with systemic therapy after PD‐1i demonstrated objective responses.Conclusion.To our knowledge, this analysis is the first describing real‐world experience with PD‐1i in cHL patients in the U.S. Here, we demonstrate similar response rates compared to prior studies. The toxicity profile of PD‐1i was similar to that seen in previous studies; we further describe toxicity patterns in those with prior autoimmune disease or allogeneic transplant. Post‐PD‐1i systemic therapies appear active. These results support the effectiveness and tolerability of PD‐1i therapy in R/R cHL in a real‐world setting.Implications for Practice.Two PD‐1 inhibitors have recently been approved for patients with relapsed/refractory classical Hodgkin lymphoma based on results from nonrandomized clinical trials. However, to date, there have been no studies evaluating the effectiveness and toxicity profile of these drugs in the real‐world setting in the U.S. The present study demonstrates that patients treated in a real‐world context experience similar rates of overall effectiveness compared with published clinical trials. Patients who discontinue PD‐1 inhibitors may experience clinical responses to subsequent treatment with systemic chemotherapy or targeted therapy. This study provides clinicians with further insight into the effectiveness and tolerability of PD‐1 inhibitors and suggests that when patients progress while on these drugs, conventional systemic chemotherapy may be an effective treatment option.

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Indoor inhalation dose assessment for thoron-rich regions of Indian Himalayan belt

Abstract

²²²Rn, ²²⁰Rn, and their decay products are significant contributors to background radiation dose. Their concentration level, pertaining exposure, and consequent dose are prime concerns in indoor environments. The present study was performed in 101 dwellings of different villages of Almora district situated in Kumaun hills of Indian Himalayan belt. Measurement of gases and decay products were made in three different types of dwellings (i.e., mud, cemented, and stone with plaster) in three seasons (winter, summer, and rainy). Concentration values for ²²²Rn and EERC were found to be varying in the order of winter > summer > rainy while obtained least in rainy season for the case of ²²⁰Rn and EETC. Concentration values for ²²²Rn and EERC were found to be lesser for cemented houses. Relative standard deviation of concentration values was found to be higher for the rainy season. Yearly averaged concentration values for ²²²Rn, EERC, ²²⁰Rn, and EETC were noted to be higher than the global averages but comparable to some Indian studies. Annual inhalation dose due to ²²²Rn, ²²⁰Rn, and their progeny was found to be 0.55–4.71 mSv/year with an average value of 2.36 ± 0.83 mSv/year. These values were measured for the first time in the study area and provide a link for future studies in the dwellings representing higher concentration values.

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Discharge of biocidal products from healthcare activities into a sewage system—a case study at a French university hospital

Abstract

This study focused on the presence of three biocidal products specific to healthcare facilities, i.e. chlorhexidine digluconate (CHD), bis(aminopropyl)laurylamine (BAPLA), and didecyldimethylammonium chloride (DDAC), in a hospital sewage system. Five sampling campaigns were conducted in 2016 and 2017 throughout the entire Poitiers University Hospital sewage system. DDAC concentrations ranging from 933 ± 119 to 3250 ± 482 μg/L were detected in 24-h composite samples, while lower concentrations (both within the same range) were detected for the two other compounds (i.e. 25 ± 5 to 97 ± 39 μg/L for CHD and 18 ± 3 to 142 ± 16 μg/L for BAPLA). Based on these findings, a mass balance was determined for these discharged compounds to compare the quantities detected in discharges to the amounts used for healthcare in the hospital. Hence, 60–90% of the quantities of DDAC used were found to be present at the hospital sewage outfall. Higher percentages of CHD (100–242%) were noted because of the high presumably quantities used for antiseptic applications, which were not considered in mass balance calculation. Finally, only 10–30% of BAPLA quantities used were detected at the site outfall. Analysis of the results for the different sampling points revealed the nature of the emission sources. For surface applications of DDAC and BAPLA, management of hospital linen is thus a major source of discharged biocidal products, probably following the washing of biocide-soaked textiles used for hospital facility maintenance. Moreover, discharge of biocidal products from a healthcare establishment depends especially on biocide handling practices in the emitting establishment. For BAPLA, compliance with hospital recommended dosages and practices whereby operators are required to prepare tailored quantities of detergents and disinfectants for each specific task could largely explain the limited release of this compound.

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Geochemical characterization of soil samples from gold mining areas using PIXE spectroscopy

Abstract

Particle-induced x-ray emission (PIXE) spectroscopy has been used to characterize soil samples from two relatively old gold mine sites (Iperindo and Itagunmodi) in the Ilesha schist belt of Southwestern Nigeria. This is with a view to identifying the indicator or pathfinder elements of gold for fingerprinting and toxicity potential assessment purposes. Average elemental concentrations of 19 major, minor, and trace elements were determined, and the geochemical data of Mn, Ni, Cu, Zn, Ag, As, Pb, and Au together with multivariate factor and cluster statistical analyses allowed to identify As and Ag as the pathfinder elements of gold. The high concentration of the determined pathfinder elements (As and Ag) as well as other toxic metals (Pb and Cu) implies a relatively high metal contamination risk to the miners and the ecosystem. The major hazard is represented by the abandoned mining wastes, pits, and ponds, already serving as fish ponds.

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