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The separation of P, K, and Mg from surplus activated sludge (SAS) was investigated using existing sludge treatment facilities and the thickened primary sludge (TPS). The addition of the TPS to the SAS storage tank accelerated the anaerobic release of the three elements from SAS with maximum efficiencies of about 60%. The efficiency of P release showed a significant correlation with the oxidation-reduction potential. Increasing the total solid concentration increased the release of elements. The released elements could be transferred to a separate liquid (SL) from a screw-press thickener, and maximum concentrations of P, K, and Mg were about 200, 60, and 35 mg/L, respectively. The addition of CaCl2 and NaOH solutions to SL precipitated P as hydroxyapatite. However, no precipitation of K and Mg occurred simultaneously with P, even when the pH of SL was increased to 9. These findings suggest that about 60% of P, K, and Mg can be separated from SAS into SL using existing sludge treatment facilities and TPS; however, a method other than precipitation would be needed to recover P and K from SL simultaneously.
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Magnesio , Aguas del Alcantarillado , Fósforo , PotasioRESUMEN
A 46-year-old female presented persistent right lower abdominal pain for 4 days. Computed tomography revealed an enlarged appendix with a surrounding low-attenuation mass. The patient was diagnosed with appendiceal abscess-forming appendicitis and initially treated with antibiotics. However, owing to the manifestation of nausea as a side effect, laparoscopic appendectomy was performed 3 days after the initial consultation. Intraoperative examination revealed mucinous material on the surface of the appendix and within the abdominal cavity, leading to the decision to perform an appendectomy with partial cecum resection and excision of the omentum with mucinous deposits. Pathological examination confirmed the diagnosis of a perforating low-grade appendiceal mucinous neoplasm and pseudomyxoma peritonei. The patient was subsequently referred to a specialized center for ongoing management, and at 9 months postoperatively, surveillance is being conducted. Low-grade appendiceal mucinous neoplasms can progress to pseudomyxoma peritonei through perforation; however, an optimal treatment approach has not yet been established. In particular, patients in advanced stages of the disease often require challenging management decisions. This case is reported along with a review of the literature to provide further guidance.
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Apendicectomía , Neoplasias del Apéndice , Clasificación del Tumor , Humanos , Femenino , Neoplasias del Apéndice/patología , Neoplasias del Apéndice/cirugía , Persona de Mediana Edad , Adenocarcinoma Mucinoso/cirugía , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/patología , Neoplasias Peritoneales/cirugía , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/diagnóstico , Tomografía Computarizada por Rayos X , Seudomixoma Peritoneal/cirugía , Seudomixoma Peritoneal/patología , Seudomixoma Peritoneal/diagnósticoRESUMEN
Compound 5 was identified from a high-throughput screening campaign as a small molecule pharmacological chaperone of glucocerebrocidase (GCase), a lysosomal hydrolase encoded by the GBA1 gene, variants of which are associated with Gaucher disease and Parkinson's disease. Further investigations revealed that compound 5 was slowly transformed into a regio-isomeric compound (6) in PBS buffer, plausibly via a ring-opening at hemiaminal moiety accompanied by subsequent intramolecular CC bond formation. Utilising this unexpected skeletal rearrangement reaction, a series of compound 6 analogues was synthesized which yielded multiple potent GCase pharmacological chaperones with sub-micromolar EC50 values as exemplified by compound 38 (EC50 = 0.14 µM).
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Enfermedad de Gaucher , Enfermedad de Parkinson , Humanos , Glucosilceramidasa/genética , Mutación , Enfermedad de Gaucher/tratamiento farmacológico , Chaperonas MolecularesRESUMEN
Glucocerebrosidase (GCase) is a lysosomal enzyme encoded by the GBA1 gene, loss of function variants of which cause an autosomal recessive lysosomal storage disorder, Gaucher disease (GD). Heterozygous variants of GBA1 are also known as the strongest common genetic risk factor for Parkinson's disease (PD). Restoration of GCase enzymatic function using a pharmacological chaperone strategy is considered a promising therapeutic approach for PD and GD. We identified compound 4 as a GCase pharmacological chaperone with sub-micromolar activity from a high-throughput screening (HTS) campaign. Compound 4 was further optimised to ER-001230194 (compound 25). ER-001230194 shows improved ADME and physicochemical properties and therefore represents a novel pharmacological chaperone with which to investigate GCase pharmacology further.
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Enfermedad de Gaucher , Enfermedad de Parkinson , Humanos , Glucosilceramidasa/genética , Mutación , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Gaucher/tratamiento farmacológico , LisosomasRESUMEN
The use of composted sewage sludge (CSS) and centrate as alternatives to synthetic fertilizers in rice cultivation holds great promise. This study aims to determine the effects of varying doses and timings of centrate derived from anaerobically digested sewage sludge on rice yield, nutrient quality, and soil fertility when applied as a topdressing to rice fields fertilized with CSS. At the panicle initiation (PI) stage, 100, 300, and 500 kg N ha-1 of centrate topdressing (CT100, CT300, and CT500, respectively) was applied. In addition, different topdressing timings at a total dose of 500 kg N ha-1 were evaluated, including a two-split application (40% at active tillering (AT) and 60% at PI; CT500S2) and a three-split application (40% at AT + 40% at PI + 20% at heading; CT500S3). At a rate of 160 kg N ha-1, CSS was used as a base fertilizer in all treatments. A control treatment received synthetic fertilizers at a rate of 160 kg N ha-1 as a base application and 100 kg N ha-1 as a topdressing. Results showed that CSS-treated rice plants exhibited a lower N status and leaf chlorophyll content during the vegetative growth stage; however, the split application of centrate topdressing improved plant N status, resulting in an increase in biomass and grain yield. Centrate and CSS tended to increase the mineral content of rice; nevertheless, a significant accumulation of As in grains raised concerns about food safety. Combining CSS and centrate has the potential to increase rice production, improve grain nutritional value, and decrease reliance on synthetic fertilizers. However, it is essential to optimize this fertilization, mitigate environmental risks, and ensure food safety by employing appropriate fertilization dosing and timing as well as appropriate field management strategies.
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Candida lusitaniae is an uncommon pathogen that accounts for approximately 1% of patients with candidiasis. In this report, we present the case of a 24-year-old woman with severe pancreatitis who was emergently admitted to Northern Yokohama Hospital. We started treating the pancreatitis and infections according to her culture results. However, her symptoms, accompanied by a necrotic pancreas, did not improve. Finally, C. lusitaniae was detected in the blood and catheter samples. We started antifungal treatment according to the culture results, but the patient died. Generally, the mortality rate for acute pancreatitis ranges from 3% for patients with interstitial edematous pancreatitis to 17% for those who develop pancreatic necrosis. Although we chose appropriate antibiotics and antifungal agents based on the culture results, the treatments failed. Early detection, sufficient doses of antimicrobials and frequent monitoring using sample culture are crucial because infection control may be inadequate, especially in tissues with low blood flow, such as necrotic tissues.
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Candidiasis , Pancreatitis , Humanos , Femenino , Adulto Joven , Adulto , Enfermedad Aguda , Candida , Pancreatitis/complicaciones , Pancreatitis/tratamiento farmacológico , Candidiasis/complicaciones , Candidiasis/tratamiento farmacológico , Candidiasis/diagnóstico , Antifúngicos/uso terapéuticoRESUMEN
The dissemination of antimicrobial resistance in the environment is an emerging global health problem. Wastewater treatment effluent and combined sewer overflows (CSOs) are major sources of antimicrobial resistance in urban rivers. This study aimed to clarify the effect of municipal wastewater treatment effluent and CSO on antimicrobial resistance genes (ARGs), mobile gene elements, and the microbial community in an urban river. The ARG abundance per 16S-based microbial population in the target river was 0.37-0.54 and 0.030-0.097 during the CSO event and dry weather, respectively. During the CSO event, the antimicrobial resistome in the river shifted toward a higher abundance of ARGs to clinically important drug classes, including macrolide, fluoroquinolone, and ß-lactam, whereas ARGs to sulfonamide and multidrug by efflux pump were relatively abundant in dry weather. The abundance of intI1 and tnpA genes were highly associated with the total ARG abundance, suggesting their potential application as an indicator for estimating resistome contamination. Increase of prophage during the CSO event suggested that impact of CSO has a greater potential for horizontal gene transfer (HGT) via transduction. Consequently, CSO not only increases the abundance of ARGs to clinically important antimicrobials but also possibly enhances potential of HGT in urban rivers.
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Antiinfecciosos , Microbiota , Ríos , Antibacterianos/farmacología , MacrólidosRESUMEN
PURPOSE: To identify the processes of cancer-related pain relief and exacerbation faced by outpatients in an acute care hospital and to examine the support needed for outpatient pain control. METHODS: We conducted semi-structured, in-depth interviews with patients from the outpatient department of Showa University Northern Yokohama Hospital in Kanagawa Prefecture, Japan. Participants were recruited by purposive sampling. From the recorded data, verbatim transcripts were made and used as textual data for analysis by consistent comparative method. RESULTS: Between April 2018 and April 2022, interviews were conducted with 30 participants. Analysis of the verbatim transcripts generated 13 categories from 27 concepts. Category relationships were examined, and a conceptual framework was developed. Outpatients went from being in a state of hesitation towards consultation with medical professionals to receiving individual consistent follow-ups by medical professionals in the hospital and community pharmacies, which led to patient teleconsultations when their physical condition changed, leading to an improvement of pain. CONCLUSION: The process of relief and exacerbation of cancer-related pain experienced by outpatients in the acute care hospital reveals that the provision of consistent follow-up through remote or in-person interviews has an important role to play in pain management, as it helps to build relationships between patients and medical professionals. Alternatively, when outpatients exhibited endurance, their pain worsened, and they fell into a negative cycle of poor pain control.
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Dolor en Cáncer , Neoplasias , Humanos , Dolor en Cáncer/terapia , Pacientes Ambulatorios , Dolor/etiología , Manejo del Dolor , Investigación Cualitativa , Hospitales Universitarios , Neoplasias/complicacionesRESUMEN
PURPOSE: The efficiency and safety of routine intravenous administration of acetaminophen after highly invasive hepatobiliary pancreatic surgery remain unclear. In particular, there have been no studies focusing on pancreatoduodenectomy. The present study clarified its clinical utility for patients undergoing pancreatoduodenectomy. METHODS: We retrospectively collected 179 patients who underwent open pancreatoduodenectomy from 2015 to 2020. The analgesic effects and adverse events in patients with scheduled intravenous administration of acetaminophen were evaluated using propensity score matching. RESULTS: After 40 patients from each group were selected by propensity score matching, the postoperative liver function tests were not significantly different between the control and acetaminophen groups. No significant differences were found in the self-reported pain intensity score or postoperative nausea and vomiting; however, the rate of pentazocine use and the total number of additional analgesics were significantly lower in the acetaminophen group than in the control group (p = 0.003 and 0.002, respectively). CONCLUSION: The scheduled intravenous administration of acetaminophen did not affect the postoperative liver function and had a good analgesic effect after pancreatoduodenectomy.
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Acetaminofén , Analgésicos no Narcóticos , Humanos , Puntaje de Propensión , Pancreaticoduodenectomía , Estudios Retrospectivos , Estudios de Factibilidad , Analgésicos Opioides/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Administración Intravenosa , Analgésicos/uso terapéuticoRESUMEN
Mitochondrial dysfunction is implicated in Parkinson disease (PD). Mutations in Parkin, an E3 ubiquitin ligase, can cause juvenile-onset Parkinsonism, probably through impairment of mitophagy. Inhibition of the de-ubiquitinating enzyme USP30 may counter this effect to enhance mitophagy. Using different tools and cellular approaches, we wanted to independently confirm this claimed role for USP30. Pharmacological characterisation of additional tool compounds that selectively inhibit USP30 are reported. The consequence of USP30 inhibition by these compounds, siRNA knockdown and overexpression of dominant-negative USP30 on the mitophagy pathway in different disease-relevant cellular models was explored. Knockdown and inhibition of USP30 showed increased p-Ser65-ubiquitin levels and mitophagy in neuronal cell models. Furthermore, patient-derived fibroblasts carrying pathogenic mutations in Parkin showed reduced p-Ser65-ubiquitin levels compared with wild-type cells, levels that could be restored using either USP30 inhibitor or dominant-negative USP30 expression. Our data provide additional support for USP30 inhibition as a regulator of the mitophagy pathway.
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Proteínas Mitocondriales/metabolismo , Mitofagia , Enfermedad de Parkinson/metabolismo , Proteínas Quinasas/metabolismo , Tioléster Hidrolasas/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Línea Celular , Fibroblastos , HumanosRESUMEN
BACKGROUND: Local duodenectomy and primary closure is a simple option for some nonampullary duodenal neoplasms. Minimizing the resection area while ensuring curability is necessary for safe primary duodenal closure. However, it is often difficult to determine the appropriate resection line from the serosal side. We developed clip-guided local duodenectomy to easily determine the resection range and perform local duodenectomy safely, then performed a retrospective observational study to confirm the safety of clip-guided local duodenectomy. METHODS: The procedure is as follows: placing endoscopic metal clips at four points on the margin around the tumor within 3 days before surgery, identifying the tumor extent with the clips under X-ray imaging during surgery, making an incision to the duodenum just outside of the clips visualized by X-ray imaging, full-thickness resection of the duodenum with the clips as guides of tumor demarcation, and transversely closure by Gambee suture. We evaluated clinicopathological data and surgical outcomes of patients who underwent clip-guided local duodenectomy at two surgical centers between January 2010 and May 2020. RESULTS: Eighteen patients were included. The pathological diagnosis was adenoma (11 cases), adenocarcinoma (6 cases), and GIST (1 case). The mean ± SD tumor size was 18 ± 6 mm, and the tumor was mainly located in the second portion of the duodenum (66%). In all cases, the duodenal defect was closed with primary sutures. The mean operation time and blood loss were 191 min and 79 mL, respectively. The morbidity was 22%, and all complications were Clavien-Dindo grade II. No anastomotic leakage or stenosis was observed. In the 6 adenocarcinoma patients, all were diagnosed with pT1a, and postoperative recurrence was not observed. The 1-year overall and recurrence free survival rate was 100%. CONCLUSIONS: Clip-guided local duodenectomy is a safe and useful surgical option for minimally local resection of nonampullary duodenal neoplasms such as duodenal adenoma, GIST, and early adenocarcinoma.
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Adenocarcinoma , Adenoma , Neoplasias Duodenales , Tumores del Estroma Gastrointestinal , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adenoma/cirugía , Neoplasias Duodenales/cirugía , Duodeno/cirugía , Tumores del Estroma Gastrointestinal/patología , Humanos , Estudios Retrospectivos , Instrumentos Quirúrgicos , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the efficacies of cyclophosphamide, methotrexate, and fluorouracil (CMF) and tegafur-uracil (UFT) as adjuvant therapy in patients with resected stage I-IIIA breast cancer by immunohistochemistry (IHC)-based subtype and to determine the relationships between clinicopathological factors and long-term outcomes. METHODS: A pooled analysis of the randomized controlled N·SAS-BC 01 and CUBC studies was conducted. Expression of hormone receptors (HRs; estrogen and progesterone receptors), human epidermal growth factor receptor 2 (HER2), and Ki67were assessed by IHC. Tumor-infiltrating lymphocytes (TILs) and nuclear/histological grades were determined by hematoxylin and eosin staining. Relapse-free survival (RFS) and overall survival (OS) were estimated by Kaplan-Meier analysis and hazard ratios were determined by Cox model adjusted for baseline tumor size and nodal status. RESULTS: A total of 689 patients (342 CMF and 347 UFT) were included in the analyses with a median follow-up of 11.1 years. There was no significant difference in RFS or OS between the two cohorts (RFS: 0.96 [95% confidence interval: 0.71-1.30], log-rank test p = 0.80; OS: 0.93 [0.64-1.35], p = 0.70). There was no difference in RFS or OS between the two cohorts for HR+/HER2- and HR+/HER2+ subtypes. RFS was significantly longer in patients treated with UFT compared with CMF in patients with HR-/HER2+ subtype (0.30 [0.10-0.88], p = 0.03). A high TILs level was associated with a better OS compared with low TILs level (p = 0.02). CONCLUSIONS: This long-term follow-up study showed that RFS and OS were similar in patients with luminal-type breast cancer treated with CMF and UFT.
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Neoplasias de la Mama , Tegafur , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Ciclofosfamida/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/uso terapéutico , Estudios de Seguimiento , Humanos , Metotrexato/uso terapéutico , Recurrencia Local de Neoplasia , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Rotavirus is one of the major causes of infectious gastroenteritis among infants and children, and live attenuated vaccines for rotavirus A (RVA), namely, Rotarix and RotaTeq, have recently become available in Japan. Rotavirus is known to be excreted from patients and accumulated in oysters similar to norovirus; however, the vaccine strains in aquatic environments or oysters have not yet been analyzed. In this study, we focused on wild-type RVA, which is highly important in considering the risk of infectious diseases. We quantified total RVA, Rotarix, and RotaTeq strains in oyster and sewage samples collected between September 2014 and July 2016 to assess the contamination levels of wild-type RVA by subtracting the quantitative value of rotavirus vaccine strains from that of total RVA. The positive rates of wild-type RVA, Rotarix, and RotaTeq in oysters were 54, 14, and 31%, respectively. These rates were comparable to those of wild-type RVA (57%) and RotaTeq (35%) in sewage; however, Rotarix was not detected in any sewage samples. The comparison of viral concentrations in oysters and sewage suggested more efficient accumulation of the vaccine strains in oysters than the wild-type RVA. The concentration of wild-type RVA in oysters was significantly correlated with that in sewage with a lag time of -6 to 0 weeks which is required for viral transportation from wastewater treatment plants to oysters. On the other hand, no significant correlation was observed between wild-type RVA concentration in sewage and the number of rotavirus-associated gastroenteritis cases, implying the existence of asymptomatic RVA-infected individuals.IMPORTANCE We quantified rotavirus A (RVA), Rotarix, and RotaTeq strains in oyster and sewage samples during two gastroenteritis seasons and revealed the exact contamination of wild-type RVA by subtracting the quantitative value of rotavirus vaccine strains from that of RVA. The concentration of wild-type RVA was significantly correlated between oysters and sewage, although no significant correlation was seen between wild-type RVA concentration in sewage and the number of rotavirus-associated gastroenteritis cases. This finding suggested the existence of asymptomatic patients and that monitoring of rotavirus vaccine strain could be useful to understand the trend of wild-type RVA and rotavirus outbreak in detail. We believe that our study makes a significant contribution to the literature because it reports the detection of rotavirus vaccine strains in oysters.
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Ostreidae/virología , Rotavirus/aislamiento & purificación , Aguas del Alcantarillado/virología , Animales , Monitoreo del Ambiente , Epidemias , Gastroenteritis/epidemiología , Japón/epidemiología , ARN Viral/genética , Rotavirus/genética , Infecciones por Rotavirus/prevención & control , Vacunas contra RotavirusRESUMEN
AIM: The new guidelines in Japan do not recommend a vancomycin (VCM) loading dose for patients with an estimated glomerular filtration rate (eGFR) 30 < and ≤ 80 mL×min-1×1.73m-2 (moderate renal dysfunction) or administration to those with the eGFR < 30 mL×min-1×1.73m-2 (severe renal dysfunction). We investigated the safety and efficiency of VCM in patients with moderate and severe renal dysfunction based on the new guidelines. MATERIALS AND METHODS: The study involved patients admitted to our hospital between April 2014 and March 2018 with an eGFR < 80 mL×min-1×1.73m-2 and treated with VCM. VCM trough concentration and pre- and post-administration renal function were investigated retrospectively. The primary endpoints were the proportion of patients who achieved an effective trough concentration of 10 - 20 µg/mL and rate of acute kidney injury (AKI). RESULTS: We included 64 patients (32 moderate, 32 severe). The mean VCM trough concentration achieved for the first time was 9.3 and 11.6 µg/mL in the moderate and severe renal dysfunction groups, respectively (p = 0.91). The effective trough concentration endpoint was achieved by 50% and 43% of the patients in the severe and moderate renal dysfunction groups, respectively, and no significant difference was found in the AKI rate. The serum creatinine change was significantly different between the groups - the moderate group showed a slight deterioration and the severe renal dysfunction group an improvement. CONCLUSION: It may be necessary to increase the dose for these patients with severe renal dysfunction while implementing a VCM loading dose and monitoring trough concentrations and adverse effects.
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Lesión Renal Aguda , Vancomicina , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/diagnóstico , Antibacterianos/efectos adversos , Humanos , Riñón/fisiología , Estudios Retrospectivos , Vancomicina/efectos adversosRESUMEN
PURPOSE: A high vancomycin trough concentration during therapy is associated with increased nephrotoxicity, and the recent guidelines for therapeutic monitoring of vancomycin recommend target of the ratio of area under the curve (AUC) to minimum inhibitory concentration. We aimed to determine vancomycin trough concentration and AUC that induce nephrotoxicity and evaluate predictive factors associated with a high serum vancomycin trough level according to the initial dosing strategy. METHODS: We conducted a retrospective cohort study in patients administered intravenous vancomycin from June 2013 to February 2017. Totally, 346 patients were included. RESULTS: 38 experienced nephrotoxicity during therapy. The both trough level and AUC were significant risk factors for the occurrence of vancomycin induced-nephrotoxicity (p < 0.001, p = 0.001). The exposure-response analysis revealed that the trough level of 15 µg/mL was associated with 12.0% nephrotoxicity incidence and AUC of 600 was associated with 12.9% nephrotoxicity incidence. During the treatment, 90 patients had an initial trough concentration of ≥15 µg/mL, and 124 patients had AUC of ≥600 µg h/mL. The multiple logistic regression analysis revealed body weight (p = 0.001), serum creatinine level (p = 0.028), daily vancomycin dose (p = 0.001), and ICU (p = 0.015) were independent predictive factors for a high trough concentration. And same factors were selected for the high AUC. CONCLUSION: The risk factors for vancomycin induced nephrotoxicity were comparable in both trough concentration and AUC. The incidence of nephrotoxicity can be reduced by controlling vancomycin trough concentration similarly AUC and promoting antimicrobial stewardship.
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Antibacterianos , Vancomicina , Antibacterianos/toxicidad , Área Bajo la Curva , Humanos , Incidencia , Estudios Retrospectivos , Vancomicina/toxicidadRESUMEN
Extracellular antibiotic resistance genes (eARG) are considered to play an important role in spread of antimicrobial resistance (AMR) in wastewater treatment and water environment. Membrane bioreactor (MBR) reportedly has better removal of ARGs in wastewater than conventional activated sludge process. However, removal of eARG is possibly limited because eARG is small to pass through microfiltration (MF) membranes. To evaluate potential removal of eARG in MBR, this study aimed to understand the initial behaviors of eARG received in MBR. The recombinant plasmid with artificial marker gene was spiked in lab-scale MBR to trace fate of eARG in MBR. Among 10 10 copies/L of the spiked gene, 2.6 × 109 copies/L was adsorbed on sludge particles at 6 h after spiking, while only 2.2 × 108-3.6 × 108 copies/L of the spiked gene was remained but constant in sludge liquid phase from 6 until 48 h. This result suggests that adsorption on sludge particles served as the main mechanism to govern the initial fate of eARG in MBR. Meanwhile, the spiked gene concentrations in membrane permeate was lower than sludge liquid phase and decreased overtime, suggesting retention of eARG in membrane filtration. Total LRV of the spiked extracellular gene were 3.4 ± 0.8 log at 48 h after spiking. LRV by adsorption corresponded to 1.7 ± 0.7 log constantly since 3 h after spiking, while LRV by membrane filtration increased from 0 to 1.7 ± 0.6 log. Linear correlation of LRV by membrane filtration with transmembrane pressure (TMP) suggested that foulant deposition on membrane governs removal of eARG by membrane filtration in MBR.
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Reactores Biológicos , Membranas Artificiales , Plásmidos/genética , Aguas del Alcantarillado , Eliminación de Residuos Líquidos , Aguas ResidualesRESUMEN
BACKGROUND: Chemotherapy-induced amenorrhea (CIA) is one of the critical side effects from the chemotherapy in premenopausal patients with breast cancer. The goals of our study are the following: (1) to investigate the factors affecting the incidence of CIA; and (2) to evaluate the prognostic role of CIA in premenopausal patients with breast cancer. METHODS: We conducted a post hoc retrospective substudy to examine the incidence of the CIA and the relationship between CIA and prognosis in NSAS-BC02 that compared taxane alone to Doxorubicin(A) Cyclophosphamide(C) followed by taxane in postoperative patients with node-positive breast cancer RESULTS: Of 395 premenopausal women, 287 (72.7%) had CIA due to protocol treatment. Regarding type of protocol regimen, proportion of CIA was 76.9% in AC Paclitaxel(P), 75.2% in AC Docetaxel(D), 62.8% in PTX, and 75.2% in DTX. Predictive factors of CIA were age increase by 5 years (OR 1.50), ER positivity (OR 2.08), and HER2 3 + ( OR 0.40) according to logistic regression analysis. According to the log rank test and the Cox proportional hazards model, CIA group had significantly better disease-free survival than non-CIA group (P < .0001). However, according to time-dependent Cox model that was used to reduce guarantee-time bias, CIA was not a statistically significant prognostic factor in both ER-positive and ER-negative patients. CONCLUSION: Treatment with taxane alone caused high frequency of CIA in premenopausal women with breast cancer. CIA did not turn out to be an independent prognostic factor, taking guarantee-time bias into consideration. Further clinical studies are needed to validate these findings.
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Amenorrea/epidemiología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/terapia , Metástasis Linfática/terapia , Premenopausia/efectos de los fármacos , Adulto , Amenorrea/inducido químicamente , Mama/patología , Mama/cirugía , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Hidrocarburos Aromáticos con Puentes/efectos adversos , Quimioterapia Adyuvante/efectos adversos , Quimioterapia Adyuvante/métodos , Ciclofosfamida/efectos adversos , Supervivencia sin Enfermedad , Doxorrubicina/efectos adversos , Femenino , Humanos , Incidencia , Mastectomía , Persona de Mediana Edad , Paclitaxel/efectos adversos , Pronóstico , Estudios Prospectivos , Receptores de Estrógenos/metabolismo , Estudios Retrospectivos , Taxoides/efectos adversos , Adulto JovenRESUMEN
INTRODUCTION: Combination chemotherapy of gemcitabine and cisplatin (GC) is the standard treatment for patients with urothelial cancer (UC). However, hematological toxicity is a major side effect of GC therapy in patients with UC. In particular, discontinuation of the GC therapy is associated to adverse events such as hematological toxicity. Some studies have reported general risk factors of hematological toxicity such as age. However, little is known about risk factors for GC therapy-associated hematological toxicity in patients with UC. OBJECTIVE: We aimed to identify risk factors for hematological toxicity in patients with UC receiving GC therapy. METHODS: We performed a retrospective evaluation of the data of 128 patients with UC who received GC therapy. The study end point was defined as the occurrence of grade 4 neutropenia and grade ≥3 thrombocytopenia. Logistic regression analysis was used to determine risk factors that were significantly associated with neutropenia and thrombocytopenia. RESULTS: In total, 62 (48.4%) patients experienced grade 4 neutropenia, and 27 (21.1%) patients experienced grade ≥3 thrombocytopenia. In the multivariate analysis, performance status (PS) ≥1 (odds ratio [OR] 3.764, 95% confidence interval [CI] 1.410-10.047, p = 0.008) and neutrophil count (OR 0.648, 95% CI 0.468-0.898, p = 0.009) were significantly associated with grade 4 neutropenia. Platelet count (PLT) (OR 0.896, 95% CI 0.832-0.966, p = 0.004) and potassium (K) level (OR 6.966, 95% CI 1.313-36.989, p = 0.023) were also significantly associated with grade ≥3 thrombocytopenia. CONCLUSIONS: PS ≥ 1, neutrophil count, PLT, and K level were important risk factors for GC therapy-induced hematological toxicity in patients with UC. To continue GC therapy, further management systems by hematological toxicity risk factors for patients with UC will be required.
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Antineoplásicos/efectos adversos , Cisplatino/uso terapéutico , Desoxicitidina/análogos & derivados , Neutropenia/etiología , Trombocitopenia/etiología , Neoplasias Urológicas/tratamiento farmacológico , Anciano , Antineoplásicos/uso terapéutico , Cisplatino/efectos adversos , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Supervivencia sin Enfermedad , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Neoplasias Urológicas/mortalidad , Neoplasias Urológicas/patología , GemcitabinaRESUMEN
PURPOSE: Postoperative early ambulation contributes to the improvement of postoperative outcomes; however, the definition of "early" ambulation is unclear. In this study, we aimed to define desirable "early" ambulation after digestive surgery in terms of short-term outcomes and to identify the risk factors for delayed ambulation. METHODS: We retrospectively analyzed 718 patients who underwent major digestive surgery between January 2016 and May 2019 in our hospital. The timing of first ambulation after surgery was reviewed and correlated with short-term postoperative outcomes and perioperative patient characteristics. RESULTS: Of 718 patients, 55% underwent first ambulation at postoperative day (POD) 1, 31% at POD 2, and the remaining patients at POD 3 or later. Whereas short-term outcomes were equivalent among patients with first ambulation at POD 1 and those at POD 2, patients who delayed ambulation until POD 3 or after had an increased incidence of infectious complications (P = 0.004), longer hospitalization (P < 0.001), and a decreased home discharge rate (P < 0.001). Multivariate analysis showed that significant predictors of delayed ambulation (POD ≥ 3) were poor Eastern Cooperative Oncology Group performance status (ECOG-PS), low controlling nutritional status (CONUT), nonlaparoscopic surgery, and transvenous opioid use. Of these factors, the combination of ECOG-PS, CONUT, and nonlaparoscopic surgery clearly stratified patients into four-grade risk groups regarding delayed ambulation (P for trend < 0.001). CONCLUSION: Our results suggest that first ambulation before POD 2 could be desirable for better short-term outcomes. Active preoperative intervention, such as nutritional care and prehabilitation, in patients with multiple risk factors for delayed ambulation could improve the postoperative course.
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Procedimientos Quirúrgicos del Sistema Digestivo , Ambulación Precoz , Complicaciones Posoperatorias/prevención & control , Anciano , Femenino , Humanos , Masculino , Estudios Retrospectivos , Factores de RiesgoRESUMEN
This study investigated the impact of each treatment stage of the activated sludge process on the fate of antibiotic resistant bacteria (ARB) in wastewater treatment plants (WWTPs). Wastewater and sludge samples were collected monthly at each stage of a commercial-scale WWTP. After 20-25 strains of indicator Escherichia coli were isolated from each sample on Chromocult Coliform Agar, antibiotic resistance of the isolates to amoxicillin (AMX), ciprofloxacin (CIP), norfloxacin (NFX), kanamycin (KM), sulfamethoxazole/trimethoprim (ST) and tetracycline (TC) were tested with the Kirby-Bauer disk diffusion method. As a result, activated sludge in the aeration tank and return sludge had higher abundance of antibiotic resistant E. coli than influent wastewater and secondary treatment effluent. AMX resistant E. coli was enriched in return sludge at the secondary clarifier. Higher temperature was also likely to cause an increase of AMX resistant E. coli in sludge. The antibiotic resistance profile of E. coli in secondary treatment effluent was more dependent on activated sludge than influent wastewater. These results suggested that activated sludge in WWTP possibly serves as a reservoir of ARB, and that behavior of ARB in WWTP differs by antibiotic classes.