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Herein this study, we sequenced the genome of a multidrug-resistant Salmonella enterica serovar Typhimurium strain MBR-MFRK-23 isolated from the liver tissue of a diseased layer chicken. The 4,964,854-bp draft genome comprises 50 contigs with 50.5× coverage and 52.1% GC content and is typed as S. enterica sequence type 19., Competing Interests: The authors declare no conflict of interest.

Natural killer group 2D (NKG2D) is a homodimeric activating immunoreceptor whose function is to detect and eliminate compromised cells upon binding to the NKG2D ligands (NKG2DL) major histocompatibility complex (MHC) molecules class I-related chain A (MICA) and B (MICB) and UL16 binding proteins (ULBP1-6). While typically present at low levels in healthy cells and tissue, NKG2DL expression can be induced by viral infection, cellular stress or transformation. Aberrant activity along the NKG2D/NKG2DL axis has been associated with autoimmune diseases due to the increased expression of NKG2D ligands in human disease tissue, making NKG2D inhibitors an attractive target for immunomodulation. Herein we describe the discovery and optimization of small molecule PPI (protein-protein interaction) inhibitors of NKG2D/NKG2DL. Rapid SAR was guided by structure-based drug design and accomplished by iterative singleton and parallel medicinal chemistry synthesis. These efforts resulted in the identification of several potent analogs (14, 21, 30, 45) with functional activity and improved LLE., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Pomegranate, scientifically known as Punica granatum, has been a traditional medicinal remedy since ancient times. Research findings have shown that using pomegranate extracts can positively affect a variety of signaling pathways, including those involved in angiogenesis, inflammation, hyperproliferation, cellular transformation, the beginning stages of tumorigenesis, and lastly, a reduction in the final stages of metastasis and tumorigenesis. This is due to the fact that pomegranate extracts are rich in polyphenols, which are known to inhibit the activity of certain signaling pathways. In the United States, cancer is the second biggest cause of death after heart disease. The number of fatalities caused by cancer in the United States escalates yearly. Altering one's diet, getting involved in regular physical activity, and sustaining a healthy body weight are three easy steps an individual may follow to lower their cancer risk. Simply garnishing one's diet with vegetables and fruits has the potential to avert at least 20% of all cancer diagnoses and around 200,000 deaths caused by cancer each year. Vegetables, fruits, and other dietary constituents, such as minerals and phytochemicals, are currently being researched for their potential to prevent cancer. It is being done because they are safe, have minimal toxicity, possess antioxidant properties, and are universally accepted as dietary supplements. Ancient civilizations used the fruit of pomegranate ( Punica granatum L.) to prevent and cure a number of diseases. The anti-tumorigenic, anti-inflammatory and anti-proliferative qualities of pomegranate have been shown in studies with the fruit, juice, extract, and oil of the pomegranate. Pomegranate has the capacity to affect several signaling pathways, which implies that it may have the potential to be employed not only as a chemopreventive agent but also as a chemotherapeutic drug. This article elaborates on some recent preclinical and clinical research which shows that pomegranate seems to have a role in the prevention and treatment of a number of cancers, including but not limited to breast, bladder, skin, prostate, colon, and lung cancer, among others., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

NKG2D (natural-killer group 2, member D) is a homodimeric transmembrane receptor that plays an important role in NK, γδ + , and CD8 + T cell-mediated immune responses to environmental stressors such as viral or bacterial infections and oxidative stress. However, aberrant NKG2D signaling has also been associated with chronic inflammatory and autoimmune diseases, and as such NKG2D is thought to be an attractive target for immune intervention. Here, we describe a comprehensive small-molecule hit identification strategy and two distinct series of protein-protein interaction inhibitors of NKG2D. Although the hits are chemically distinct, they share a unique allosteric mechanism of disrupting ligand binding by accessing a cryptic pocket and causing the two monomers of the NKG2D dimer to open apart and twist relative to one another. Leveraging a suite of biochemical and cell-based assays coupled with structure-based drug design, we established tractable structure-activity relationships with one of the chemical series and successfully improved both the potency and physicochemical properties. Together, we demonstrate that it is possible, albeit challenging, to disrupt the interaction between NKG2D and multiple protein ligands with a single molecule through allosteric modulation of the NKG2D receptor dimer/ligand interface.

Nowadays, environmental pollution has become a critical issue for both developed and developing countries. Because of excessive industrialization, burning of fossil fuels, mining and exploration, extensive agricultural activities, and plastics, the environment is being contaminated rapidly through soil, air, and water. There are a variety of approaches for treating environmental toxins, but each has its own set of restrictions. As a result, various therapies are accessible, and approaches that are effective, long-lasting, less harmful, and have a superior outcome are extensively demanded. Modern research advances focus more on polymer-based nanoparticles, which are frequently used in drug design, drug delivery systems, environmental remediation, power storage, transformations, and other fields. Bioinorganic nanomaterials could be a better candidate to control contaminants in the environment. In this article, we focused on their synthesis, characterization, photocatalytic process, and contributions to environmental remediation against numerous ecological hazards. In this review article, we also tried to explore their recent advancements and futuristic contributions to control and prevent various pollutants in the environment., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Md. Mominur Rahman et al.)

Despite the rapid growth of online shopping and research interest in the relationship between online and in-store shopping, national-level modeling and investigation of the demand for online shopping with a prediction focus remain limited in the literature. This paper differs from prior work and leverages two recent releases of the U.S. National Household Travel Survey (NHTS) data for 2009 and 2017 to develop machine learning (ML) models, specifically gradient boosting machine (GBM), for predicting household-level online shopping purchases. The NHTS data allow for not only conducting nationwide investigation but also at the level of households, which is more appropriate than at the individual level given the connected consumption and shopping needs of members in a household. We follow a systematic procedure for model development including employing Recursive Feature Elimination algorithm to select input variables (features) in order to reduce the risk of model overfitting and increase model explainability. Among several ML models, GBM is found to yield the best prediction accuracy. Extensive post-modeling investigation is conducted in a comparative manner between 2009 and 2017, including quantifying the importance of each input variable in predicting online shopping demand, and characterizing value-dependent relationships between demand and the input variables. In doing so, two latest advances in machine learning techniques, namely Shapley value-based feature importance and Accumulated Local Effects plots, are adopted to overcome inherent drawbacks of the popular techniques in current ML modeling. The modeling and investigation are performed at the national level, with a number of findings obtained. The models developed and insights gained can be used for online shopping-related freight demand generation and may also be considered for evaluating the potential impact of relevant policies on online shopping demand., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.)

One of the leading global causes of death is cancer; even though several treatment methods have improved survival rates, the incidence and fatality rates remain high. Naphthoquinones are a type of quinone that is found in nature and has vital biological roles. These chemicals have anticancer (antineoplastic), analgesic, anti-inflammatory, antimalarial, antifungal, antiviral, antitrypanosomal, antischistosomal, leishmanicidal, and anti-ulcerative effects. Direct addition of a substituent group to the 1,4-naphthoquinone ring can alter the naphthoquinone's oxidation/reduction and acid/base characteristics, and the activity can be altered. Because of their pharmacological properties, such as anticancer activity and probable therapeutic application, naphthoquinones have greatly interested the scientific community. Some chemicals having a quinone ring in malignant cells have been found to have antiproliferative effects. Naphthoquinones' deadly impact is connected with the inhibition of electron transporters, the uncoupling of oxidative phosphorylation, the creation of ROS, and the formation of protein adducts, notably with -SH enzyme groups. This review article aims to discuss naphthoquinones and their derivatives, which act against cancer and their future perspectives. This review covers several studies highlighting the potent anticancer properties of naphthoquinones. Further, various proposed mechanisms of anticancer actions of naphthoquinones have been summarized in this review., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Countries depending on small-scale agriculture, such as Bangladesh, are susceptible to climate change and variability. Changes in the frequency and intensity of drought are a crucial aspect of this issue and the focus of this research. The goal of this work is to use SPI (standardized precipitation index) and SPEI (standardized precipitation evapotranspiration index) to investigate the differences in drought characteristics across different physiognomy types in Bangladesh and to highlight how drought characteristics change over time and spatial scales when considering different geomorphologies. This study used monthly precipitation and temperature data from 29 metrological stations for 39 years (1980-2018) for calculating SPI and SPEI values. To determine the significance of drought characteristic trends over different temporal and spatial scales, the modified Mann-Kendall trend test and multivariable linear regression (MLR) techniques were used. The results are as follows: (1) Overall, decreasing dry trend was found in Eastern hill regions, whereas an increasing drought trends were found in the in the rest of the regions in all time scaless (range is from - 0.08 decade -1  to - 0.15 decade -1  for 3-month time scale). However, except for the one-month time scale, the statistically significant trend was identified mostly in the north-central and northeast regions, indicating that drought patterns migrate from the northwest to the center region. (2) SPEI is anticipated to be better at capturing dry/wet cycles in more complex regions than SPI. (3) According to the MLR, longitude and maximum temperature can both influence precipitation. (4) Drought intensity increased gradually from the southern to the northern regions (1.26-1.56), and drought events occurred predominantly in the northwestern regions (27-30 times), indicating that drought meteorological hotspots were primarily concentrated in the Barind Tract and Tista River basin over time. Findings can be used to improve drought evaluation, hazard management, and application policymaking in Bangladesh. This has implications for agricultural catastrophe prevention and mitigation., (© 2022. The Author(s).)

Diabetes mellitus (DM) is a metabolic syndrome. Diabetes has become more common in recent years. Chemically generated drugs are used to lessen the effects of DM and its following repercussions due to unpleasant side effects such as weight gain, gastrointestinal issues, and heart failure. On the other hand, medicinal plants could be a good source of anti-diabetic medications. This article aims to determine any plant matrix's positive potential. Food restriction, physical activity, and the use of antidiabetic plant-derived chemicals are all being promoted as effective ways to manage diabetes because they are less expensive and have fewer or no side effects. This review focuses on antidiabetic plants, along with their bioactive constituent, chemically characterization, and plant-based diets for diabetes management. There is minimal scientific data about the mechanism of action of the plant-based product has been found. The purpose of this article is to highlight anti-diabetic plants and plant-derived bioactive compounds that have anti-diabetic properties. It also provides researchers with data that may be used to build future strategies, such as identifying promising bioactive molecules to make diabetes management easier., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: This study investigates whether there is a relationship between alcohol and cocaine use in deaths where suicide by self-injury is the suspected cause of death., Methods: Adults referred by coroners to the Imperial College London Toxicology Unit for toxicological analysis between 2012 and 2016 were reviewed for inclusion criteria. Those who died by self-injury reasoned to be deliberate were included in the analysis. Femoral blood alcohol concentration (BAC) and presence of cocaine or benzoylecognine (a metabolite of cocaine) in blood and/or urine were tabulated and odds ratios calculated., Results: A total of 1722 decedents met inclusion criteria. BAC was ≥50 mg/dL in 29% of decedents. Cocaine was detected in 8.4% of cases. The likelihood of testing positive for cocaine increased with BAC and was most frequent between 100 and 199 mg/dL, consistent with moderate to severe intoxication (odds ratio 5.88, 95% confidence interval 3.80, 9.09; P ≤ 0.001) compared to those with BAC <10 mg/dL., Discussion and Conclusions: This study demonstrates a correlation between increasing BAC and likelihood of cocaine use prior to suspected suicide, up to a level consistent with severe intoxication. Cocaine use was found in a high proportion of cases relative to the general population reporting regular use. This pattern of drug and alcohol use has previously been given little attention in suicide prevention strategies and clinical prioritisation., (© 2021 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

The objective of this study is to assess the classification accuracy of dental caries on panoramic radiographs using deep-learning algorithms. A convolutional neural network (CNN) was trained on a reference data set consisted of 400 cropped panoramic images in the classification of carious lesions in mandibular and maxillary third molars, based on the CNN MobileNet V2. For this pilot study, the trained MobileNet V2 was applied on a test set consisting of 100 cropped PR(s). The classification accuracy and the area-under-the-curve (AUC) were calculated. The proposed method achieved an accuracy of 0.87, a sensitivity of 0.86, a specificity of 0.88 and an AUC of 0.90 for the classification of carious lesions of third molars on PR(s). A high accuracy was achieved in caries classification in third molars based on the MobileNet V2 algorithm as presented. This is beneficial for the further development of a deep-learning based automated third molar removal assessment in future.

Background: Myclobutanil is one of the most widely used demethylation inhibitor (DMI) fungicides for the management of apple scab, caused by Venturia inaequalis. Strains of V. inaequalis resistant to myclobutanil have been reported across the world. Tebuconazole, another DMI fungicide, has been proposed as an alternative to myclobutanil, and the extent of cross-resistance with myclobutanil therefore needs to be evaluated. The sensitivity to tebuconazole and myclobutanil of a total of 40 isolates was determined. Half the isolates came from an isolated orchard which had never been sprayed with fungicides and half from orchards sprayed regularly with myclobutanil, but still with disease control problems. The progeny of a tebuconazole resistant (R) × sensitive (S) V. inaequalis cross were analyzed in order to improve understanding of the genetic control of tebuconazole sensitivity., Results: There is cross-resistance between myclobutanil and tebuconazole (r = 0.91; P < 0.001). Sensitivity to tebuconazole of the progeny of a R × S cross varied quantitatively in a pattern which implied at least two gene loci differing between the parental strains. In addition, the asymmetric distribution of the sensitivity in the progeny implied possible epistatic effects., Conclusion: Resistance to myclobutanil and tebuconazole is strongly correlated. At least two genes are involved in the control of tebuconazole resistance in V. inaequalis., (© 2020 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Background: The efficacy of prothrombin complex concentrate (PCC) compared with fresh frozen plasma (FFP) for reversal of oral anticoagulants has not been investigated in geriatric patients suffering intracranial hemorrhage (ICH) due to a ground-level fall (GLF)., Methods: Patients 65 years and older who were treated at Santa Barbara Cottage Hospital between January 2011 and March 2018 with ICH after a GLF while taking warfarin were reviewed. Patients were reversed with either FFP (n=25) or PCC (n=27) and patient outcomes were compared. Separate analyses were conducted for patients who received adjuvant vitamin K administration and those who did not., Results: Mortality rates, hospital length of stay, intensive care unit admission and length of stay were similar for both FFP and PCC intervention. There was no difference in radiological progression of hemorrhage within the first 24 hours of admission (FFP: 36%, PCC: 43%, p=0.365). In patients who had international normalized ratio (INR) values measured prior to intervention, 81% (17 out of 21) of the PCC group reached an INR value below 1.5 within an 8-hour period, whereas only 29% (4 out of 14) of the FFP group did (p=0.002). Vitamin K was concomitantly given to 28% of the patients receiving FFP, and 81% of those patients receiving PCC. No significant differences in outcomes were found whether adjunctive vitamin K was administered or not, in either FFP or PCC group. However, when vitamin K was not administered, the PCC group had a higher rate of INR reversal (80% vs. 10% for FFP, p=0.006)., Conclusion: Administration of PCC is as effective in short-term outcomes as FFP in treating geriatric patients on warfarin sustaining an ICH after a GLF. INR reversal was more successful, significantly faster, and required lower infusion volumes in patients receiving PCC., Level of Evidence: Level III., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Synthetic chemists have spent considerable effort optimizing the synthesis of nitrogen and oxygen containing compounds through a number of methods; however, direct introduction of N- and O-functionality remains challenging. Presented herein is a general method to allow for the simultaneous installation of N- and O-functionality to construct unexplored N-O heterocyclic and amino-alcohol scaffolds. This transformation uses earth abundant copper salts to facilitate the formation of a carbon-centered radical and subsequent carbon-nitrogen bond formation. The intermediate aminoxyl radical is terminated by an intramolecularly appended carbon-centered radical. We have exploited this methodology to also access amino-alcohols with a range of aliphatic and aromatic linkers.

There has been a rapid increase in the number of prescriptions for baclofen (BLF), gabapentin (GBP) and pregabalin (PGL) in the UK since their introduction to therapy. Recent studies across the European Union and USA have shown the illicit abuse potential of these drugs and deaths have been observed. A simple, reliable and fully validated method was developed for the screening and quantification of BLF, GBP and PGL in human post-mortem (PM) blood. The analytes and their deuterated analogs as internal standard were extracted from blood using a single addition acetonitrile protein precipitation reaction followed by analysis using liquid chromatography-tandem mass spectrometry (LC-MS-MS) with triggered dynamic multiple reaction monitoring mode for simultaneous confirmation and quantification. The assay was linear from 0.05 to 1.00 µg/mL for BLF and 0.5 to 50.0 µg/mL for GBP and PGL, respectively with r2 > 0.999 (n = 9) for all analytes. Intra-day and inter-day imprecisions (n = 80) were calculated using one-way ANOVA; no significant difference (P > 0.99) was observed for all analytes over 8 non-consecutive days. The average recovery for all analytes was >98.9%. The limits of detection and quantification were both 0.05 µg/mL for BLF, and 0.5 µg/mL for GBP and PGL. The method was highly selective with no interference from endogenous compounds or from 54 drugs commonly encountered in PM toxicology. To prove method applicability, 17 PM blood samples submitted for analysis were successfully analyzed. The concentration range observed in PM blood for BLF was 0.08-102.00 µg/mL (median = 0.25 µg/mL), for GBP 1.0-134.0 µg/mL (median = 49.0 µg/mL) and 2.0-540.0 µg/mL (median = 42.0 µg/mL) for PGL., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Acute cannabis consumption nearly doubles the risk of motor vehicle collision resulting in injury or death. Limited data have been published regarding the concentrations of cannabinoids associated with fatal road traffic collisions (RTCs), and these have not previously been compared to a population of other postmortem cases., Methods: We conducted analysis for cannabinoids [Δ(9)-tetrahydrocannabinol (THC), 11-hydroxy-THC, 11-nor-THC-9-carboxylic acid, cannabidiol, and cannabinol], drugs, and alcohol on consecutive fatal RTC cases (100) and non-RTC cases (114) from coroners' jurisdictions in London and southeast England and compared the data., Results: The incidence of cannabinoids detected in non-RTC and RTC cases was similar (25% vs 21%, P = 0.44), but THC was detected more frequently (90% vs 59%, P = 0.01) and at significantly higher concentrations in the cannabinoid-positive RTC cases than the non-RTC cases (P = 0.01). The distribution of non-RTC and RTC cases over 4 categories of THC concentration was significantly different (P = 0.004). There was no significant difference in the concentrations of other cannabinoids detected between the 2 groups. Cannabinoids were detected in more fatal RTC cases (21) than alcohol >80 mg/dL (17). Detection of other drugs was low compared to cannabis and alcohol., Conclusions: These first data on the concentrations of cannabinoids in the postmortem blood of fatal RTC victims compared with a population of other routine coroners' cases highlight the importance of specifically measuring THC concentrations in the blood to aid interpretation of postmortem cases where cannabis may be implicated., (© 2015 American Association for Clinical Chemistry.)

Objective: To provide a critical and comprehensive review of the literature, specifically case reports and observational studies used to support the concept of cross-reactivity between sulfonylarylamines and non-sulfonylarylamines., Data Sources: A list of medications was formulated from several different review articles. A MEDLINE/PubMed search was conducted (1966-March 2004) using the individual medications and the MeSH terms of drug hypersensitivity/etiology, sulfonamides/adverse effects, and/or cross-reaction., Study Selection and Data Extraction: A critical review of the methodology and conclusions for each article found in the search was conducted. The manufacturer's package insert (MPI) for each drug was examined for a statement concerning possible cross-reactivity in patients with a sulfonamide allergy. If indicated, the manufacturers were contacted to obtain any clinical data supporting the statement., Data Synthesis: A total of 33 medications were identified. Seventeen (51.5%) of the MPIs contained statements of varying degrees concerning use in patients with a "sulfonamide" allergy; 21 case series, case reports, and other articles were found., Conclusions: After a thorough critique of the literature, it appears that the dogma of sulfonylarylamine cross-reactivity with non-sulfonylarylamines is not supported by the data. While many of the case reports on the surface support the concept of cross-reactivity, on closer examination the level of evidence in many of the cases does not conclusively support either a connection or an association between the observed cause and effect.

Much attention recently has focused on drugs that prolong the QT interval, potentially leading to fatal cardiac dysrhythmias (e.g., torsade de pointes). We provide a detailed review of the published evidence that supports or does not support an association between drugs and their risk of QT prolongation. The mechanism of drug-induced QT prolongation is reviewed briefly, followed by an extensive evaluation of drugs associated with QT prolongation, torsade de pointes, or both. Drugs associated with QT prolongation are identified as having definite, probable, or proposed associations. The role of the clinician in the prevention and management of QT prolongation, drug-drug interactions that may occur with agents known to affect the QT interval, and the impact of this adverse effect on the regulatory process are addressed.

Objective: To review information on desloratadine, a nonsedating antihistamine., Data Sources: An English-language MEDLINE search was conducted (1966-July 2002). References of identified articles were subsequently reviewed for additional data. Schering Corporation provided unpublished information., Study Selection/data Extraction: Articles and abstracts pertaining to desloratadine were considered for inclusion, with emphasis on randomized, placebo-controlled, double-blind trials., Data Synthesis: Desloratadine is approved for the treatment of symptoms associated with seasonal allergic rhinitis (SAR), perennial allergic rhinitis (PAR), and chronic idiopathic urticaria (CIU) in patients aged > or =12 years. In placebo-controlled trials, desloratadine demonstrated superior efficacy as a once-daily treatment of SAR, PAR, and CIU. Data suggest that desloratadine has antiinflammatory and decongestant activity., Conclusions: Desloratadine appears to be a "me-too" agent, with no major differences compared with other second-generation antihistamines.

Objective: To report a case of acute renal failure and neurotoxicity following administration of oral acyclovir., Data Sources: Medical record of the patient, case reports identified by MEDLINE., Data Extraction: Data were abstracted from relevant published data by Johnson and reviewed by the remaining authors., Case Summary: A 69-year-old woman was diagnosed with herpes zoster and oral acyclovir was prescribed by her local physician. After approximately two days the patient was taken to the emergency department of a local hospital with signs of acute confusion and acute renal failure. Medications included oxycodone/acetaminophen, alprazolam, prazepam, and digoxin. Pertinent laboratory abnormalities included serum digoxin 4.1 mumol/L, white blood cell count 17.6 x 10(9)/L, blood urea nitrogen (BUN) 24 mmol/L of urea, and serum creatinine 305 mumol/L (patient baseline is 11 mmol/L of urea and 91.5 serum creatinine mumol/L, respectively). Because of increasing lethargy and a focal seizure, she was transferred to our institution. Despite an extensive workup, no organic cause of her altered mental status and acute renal failure was identified. Four days after discontinuation of the acyclovir, without specific intervention, the patient's mental status improved and her BUN and serum creatinine concentrations had decreased to 21 mmol/L of urea and 190.6 mumol/L, respectively. On day 5, the patient was alert and oriented to name, place, year, and month. On day 9, her renal function and mental status had returned to baseline and she was discharged., Conclusions: Acute renal failure and neurotoxicity are usually associated with intravenous acyclovir. The temporal relationship between the initiation of oral acyclovir therapy and the onset of adverse events, supported by published data of a few similar cases, strongly implicate oral acyclovir as the cause of this patient's acute renal failure and neurotoxicity. This case suggests that elderly patients with mild increased serum creatinine concentrations may be at increased risk and should be monitored closely for signs and symptoms of acute renal failure and neurotoxicity.