ABSTRACT
Naturally occurring iron (Fe) minerals have been proved to activate persulfate (PS) to generate reactive species, but the role of soil-inherent Fe minerals in activating PS as well as the underlying mechanisms remains poorly understood. Here, we investigated sulfamethoxazole (SMX) degradation by PS in two Fe-rich soils and one Fe-poor soil. Unlike with the radical-dominant oxidation processes in Fe-poor soil, PS was effectively activated through nonradical pathways (i.e., surface electron-transfer) in Fe-rich soils, accounting for 68.4%-85.5% of SMX degradation. The nonradical mechanism was evidenced by multiple methods, including electrochemical, in situ Raman, and competition kinetics tests. Inherent Fe-based minerals, especially those containing Fe(II) were the crucial activators of PS in Fe-rich soils. Compared to Fe(III) minerals, Fe(II) minerals (e.g., ilmenite) were more liable to form Fe(II) mineral-PS* complexes to initiate the nonradical pathways, oxidizing adjacent SMX via electron transfer. Furthermore, mineral structural Fe(II) was the dominant component to coordinate such a direct oxidation process. After PS oxidation, low-crystalline Fe minerals in soils were transformed into high-crystalline Fe phases. Collectively, our study shows that soil-inherent Fe minerals can effectively activate PS in Fe-rich soils, so the addition of exogenous iron might not be required for PS-based in situ chemical oxidation. Outcomes also provide new insights into the activation mechanisms when persulfate is used for the remediation of contaminated soils.
Subject(s)
Soil , Sulfamethoxazole , Sulfamethoxazole/analysis , Sulfamethoxazole/chemistry , Ferric Compounds , Iron/chemistry , Minerals/chemistry , Oxidation-Reduction , Ferrous Compounds/chemistryABSTRACT
BACKGROUND: The survey of Copeia captured early 2022 patient-reported outcomes (PRO) in Germany under cannabis medicinal product (CAM) therapy, with particular attention to symptoms, symptom changes, indications, side effects, dosages, and cost bearers. GOAL: This study investigated the question of whether associations emerge from the results that could play a role in the indication and treatment monitoring of CAM in chronically ill patients. MATERIALS AND METHODS: A standardized questionnaire was administered online nationwide in dialogue form over a 15-week period to collect itemized symptoms and PRO. Recruitment was supported by pharmacies, prescribing physicians, and patient associations. Inclusion criteria included physician-prescribed CAM therapy. RESULTS AND DISCUSSION: Of 1582 participants, 1030 data sets (65%) could be completely analyzed. There was a heterogeneous patient population, whose common feature was disease chronicity. The frequency distribution of symptoms showed a homogeneous pattern for the respective indications, in which the most frequent six (pain 71%, sleep disturbance 64%, stress/tension 52%, inner restlessness 52%, depressive mood 44% and muscle tension 43%) seem to have a special significance. According to subjective assessment, quality of life improved significantly in 84% of all participating patients. CONCLUSION: A symptom matrix (SMX) composed of different symptoms seems to play a special role in CAM therapy to improve the quality of life of chronically ill patients, regardless of the underlying disease. The SMX could contribute to the identification of an indication and to targeted treatment monitoring.
Subject(s)
Medical Marijuana , Patient Reported Outcome Measures , Quality of Life , Adult , Aged , Female , Humans , Male , Middle Aged , Chronic Disease , Germany , Medical Marijuana/therapeutic use , Medical Marijuana/adverse effects , Quality of Life/psychology , Surveys and QuestionnairesABSTRACT
SLX4 provides a molecular scaffold for the assembly of multiple protein complexes required for the maintenance of genome stability. It is involved in the repair of DNA crosslinks, the resolution of recombination intermediates, the response to replication stress and the maintenance of telomere length. To carry out these diverse functions, SLX4 interacts with three structure-selective endonucleases, MUS81-EME1, SLX1 and XPF-ERCC1, as well as the telomere binding proteins TRF2, RTEL1 and SLX4IP. Recently, SLX4 was shown to interact with MutSß, a heterodimeric protein involved in DNA mismatch repair, trinucleotide repeat instability, crosslink repair and recombination. Importantly, MutSß promotes the pathogenic expansion of CAG/CTG trinucleotide repeats, which is causative of myotonic dystrophy and Huntington's disease. The colocalization and specific interaction of MutSß with SLX4, together with their apparently overlapping functions, are suggestive of a common role in reactions that promote DNA maintenance and genome stability. This review will focus on the role of SLX4 in DNA repair, the interplay between MutSß and SLX4, and detail how they cooperate to promote recombinational repair and DNA crosslink repair. Furthermore, we speculate that MutSß and SLX4 may provide an alternative cellular mechanism that modulates trinucleotide instability.
Subject(s)
DNA Repair , Genomic Instability , MutS Homolog 3 Protein/metabolism , Recombinases/metabolism , Animals , DNA Damage , Humans , MutS Homolog 3 Protein/genetics , Neoplasms/genetics , Neoplasms/metabolism , Protein Interaction Maps , Recombinases/geneticsABSTRACT
Sulfonamide antibiotics (SAs) are serious pollutants to ecosystems and environments. Previous studies showed that microbial degradation of SAs such as sulfamethoxazole (SMX) proceeds via a sad-encoded oxidative pathway, while the sulfonamide-resistant dihydropteroate synthase gene, sul, is responsible for SA resistance. However, the co-occurrence of sad and sul genes, as well as how the sul gene affects SMX degradation, was not explored. In this study, two SMX-degrading bacterial strains, SD-1 and SD-2, were cultivated from an SMX-degrading enrichment. Both strains were Paenarthrobacter species and were phylogenetically identical; however, they showed different SMX degradation activities. Specifically, strain SD-1 utilized SMX as the sole carbon and energy source for growth and was a highly efficient SMX degrader, while SD-2 did could not use SMX as a sole carbon or energy source and showed limited SMX degradation when an additional carbon source was supplied. Genome annotation, growth, enzymatic activity tests, and metabolite detection revealed that strains SD-1 and SD-2 shared a sad-encoded oxidative pathway for SMX degradation and a pathway of protocatechuate degradation. A new sulfonamide-resistant dihydropteroate synthase gene, sul918, was identified in strain SD-1, but not in SD-2. Moreover, the lack of sul918 resulted in low SMX degradation activity in strain SD-2. Genome data mining revealed the co-occurrence of sad and sul genes in efficient SMX-degrading Paenarthrobacter strains. We propose that the co-occurrence of sulfonamide-resistant dihydropteroate synthase and sad genes is crucial for efficient SMX biodegradation. KEY POINTS: ⢠Two sulfamethoxazole-degrading strains with distinct degrading activity, Paenarthrobacter sp. SD-1 and Paenarthrobacter sp. SD-2, were isolated and identified. ⢠Strains SD-1 and SD-2 shared a sad-encoded oxidative pathway for SMX degradation. ⢠A new plasmid-borne SMX resistance gene (sul918) of strain SD-1 plays a crucial role in SMX degradation efficiency.
Subject(s)
Dihydropteroate Synthase , Sulfamethoxazole , Sulfamethoxazole/metabolism , Dihydropteroate Synthase/genetics , Ecosystem , Anti-Bacterial Agents/metabolism , Sulfonamides/metabolism , Sulfanilamide , Biodegradation, Environmental , CarbonABSTRACT
Nitrate and SMX both play a critical role in their biotransformation in biodegradable polymer-supported denitrification biofilters. However, the mutual influences of nitrate and SMX on their biotransformation for long-term operation remained obscure. Results showed SMX and nitrate had divergent effects on SMX removal. SMX removal rates was positively related with its loading rates, whereas they were negatively related to NLRs. The most abundant metabolite C10H14O3N3S (the reduced form of SMX moiety) from the N-O bond cleavage pathway by UHPLC-LTQ-Orbitrap-MS/MS and effluent TOC variations confirmed the presence of electron donor competition between nitrate and SMX. SMX less than 1000 µg/L had a negligible influence on denitrification performance. Denitrifiers such as Azospira and Denitratisoma were still enriched after chronic exposure, and nosZ/narG positively correlated with sul1/sul2 resistance genes, which were both responsible for the negligible influence of SMX. This work could guide the operational management of denitrification biofilters for simultaneous nitrate and antibiotics removal.
Subject(s)
Nitrates , Sulfamethoxazole , 3-Hydroxybutyric Acid , Denitrification , Tandem Mass Spectrometry , Biotransformation , HydroxybutyratesABSTRACT
Solid-phase denitrification (SPD) has been used in wastewater treatment plant effluent to enhance nitrate removal, and antibiotics co-existing in the effluent is a common environmental problem. In this study, it was systematically investigated the effect of single trace sulfamethoxazole (SMX)/trimethoprim (TMP) and their mixture on microbial denitrification performance, the antibiotics removal, and antibiotics resistance genes (ARGs) in corncob supported SPD system. The average denitrification rate was improved by 46.90% or 61.09% with single 50 µg/L SMX or TMP, while there was no significant inhibition with mixed SMX and TMP. The abundance of dominant denitrifiers (Comamonadaceae family and Azospia) and fermentation bacteria (Ancalomicrobium) were consistent with the denitrification performance of different antibiotics groups. Single SMX and TMP achieved relatively higher denitrification gene and enzyme abundance. Mixed SMX and TMP improved the denitrification gene copies, but they reduced the key denitrification enzymes except for EC 1.7.7.2. Additionally, the removal efficiency of TMP (56.70% ± 3.18%) was higher than that of SMX (25.44% ± 2.62%) in single antibiotic group, and the existence of other antibiotics (i.e. SMX or TMP) had no significant impact on the TMP or SMX removal performance. Biodegradation was the main removal mechanism of SMX and TMP, while sludge and corncob adsorption contributed a little to their removal. SMX had the risk of sulfanilamide resistance genes (SRGs) dissemination. Furthermore, network analysis indicated that Niveibacterium and Bradyrhizobium were the potential hosts of SRGs, which promoted the horizontal transmission of ARGs.
Subject(s)
Anti-Bacterial Agents , Zea mays , Anti-Bacterial Agents/pharmacology , Denitrification , Trimethoprim, Sulfamethoxazole Drug Combination , Drug Resistance, Microbial/genetics , SulfamethoxazoleABSTRACT
BACKGROUND: Disseminated nocardiosis still causes significant morbidity and mortality and is often caused by Nocardia asteroides, N. basiliensis, and N. farcinica and are often treated with trimethoprim-sulfamethoxazole (TMP-SMX). Nocardia otitidiscaviarum (N. otitidiscaviarum) rarely causes disseminated disease and resistance to TMP-SMX is even more rare. CASE PRESENTATION: A 37-year-old woman with metastatic breast cancer and right ear deafness with recent occupational gardening and manipulating soil, presented to the hospital with first time seizure and multiple skin nodules. Magnetic resonance imaging (MRI) showed ring enhancing lesions, biopsy of the skin and brain lesions grew N. otitidiscaviarum. She was empirically treated with TMP-SMX and Imipenem-Cilastatin, however, almost three weeks into therapy, susceptibility results revealed it to be resistant to both antimicrobials, she was subsequently changed to Amikacin, Linezolid, Moxifloxacin, and Doxycycline but ultimately died. CONCLUSIONS: This case report highlights the importance of suspecting a rare Nocardia species in patients at risk with proper occupational exposure, moreover, TMP-SMX resistance should be suspected with lack of clinical response, this may have important implications on clinical practice when facing similar infections.
Subject(s)
Anti-Infective Agents , Nocardia Infections , Nocardia , Adult , Anti-Infective Agents/therapeutic use , Female , Humans , Nocardia Infections/diagnosis , Nocardia Infections/drug therapy , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic useABSTRACT
UV/peroxymonosulfate (UV/PMS) advanced oxidation process has attracted significant attention for removal of micropollutants in water. However, during practical water treatment applications, the PMS treatment must be performed before the UV treatment to achieve full contact. In this study, sulfamethoxazole (SMX) was selected as the target micropollutant. Four different operational approaches, including UV alone, PMS alone, simultaneous UV/PMS and sequential PMS-UV, were compared for their differences in SMX removal and disinfection by-product (DBP) formation potentials during chlorine-driven disinfection. Among the four approaches, UV/PMS and PMS-UV achieved over 90% removal efficiencies for SMX without substantial differences. For raw water, the trichloronitromethane (TCNM) formation potential after treatment with PMS-UV was lower than that after UV/PMS treatment. The time interval over which the PMS-UV process was conducted had little effect on the final removal efficiency for SMX. However, a brief (5 min) pre-PMS treatment significantly reduced the TCNM formation potential and the genotoxicity from DBPs. The formation risk for TCNM during chlorination increased markedly with increasing PMS dosages, and the appropriate dosage under these experimental conditions was suggested to be 0.5-1.0 mmol/L. Under alkaline conditions, PMS-UV treatment can enhance SMX degradation as well as dramatically reduced the formation potentials for haloketones, haloacetonitriles and halonitromethanes. This study suggests that proper optimization of UV/PMS processes can remove SMX and reduce its DBP formation.
Subject(s)
Water Pollutants, Chemical , Water Purification , Chlorine , Disinfection , Halogenation , Peroxides , Sulfamethoxazole , Water Pollutants, Chemical/analysisABSTRACT
BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic fungal infection causing significant morbidity and mortality in immunocompromised patients. The conventional treatment of PJP is sulfamethoxazole-trimethoprim (SMX-TMP) dosed at 15-20 mg/kg/day of the trimethoprim component. Several studies have suggested similar mortality outcomes and an improved adverse effect profile using a lower dose (<15 mg/kg/day) SMX-TMP regimen. Our objective of this meta-analysis was to evaluate the safety and efficacy of lower dose SMX-TMP for PJP pneumonia. METHODS: We conducted a systematic review and meta-analysis of the existing literature according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. MEDLINE and Embase databases were searched from inception to January 15, 2020, for studies in English evaluating low-dose SMX-TMP (<15 mg/kg/day) compared to conventional dosing for the treatment of PJP. Outcomes evaluated in our meta-analysis include survival and adverse reactions. RESULTS: After excluding studies that did not meet our inclusion criteria, four studies were analyzed for adverse reactions and three for mortality. Overall, there was no significant difference in mortality between low-dose and conventional-dose SMX-TMP groups (relative risk [RR]: 0.55, 95% confidence interval [CI], 0.18-1.70). There was a significant decrease in the rate of adverse reactions for the low-dose group compared with the conventional-dose group (RR: 0.70, 95% CI, 0.53-0.91). CONCLUSIONS: This meta-analysis shows a significant decrease in adverse reactions and similar mortality rates with lower-dose SMX-TMP compared to conventional dosing. A low-dose SMX-TMP regimen in the treatment of PJP should be considered a viable option as it could potentially decrease treatment discontinuation rates and reduce patient harm.
Subject(s)
Opportunistic Infections , Pneumocystis carinii , Pneumonia, Pneumocystis , Anti-Bacterial Agents/therapeutic use , Humans , Opportunistic Infections/drug therapy , Pneumonia, Pneumocystis/drug therapy , Retrospective Studies , Trimethoprim, Sulfamethoxazole Drug Combination/adverse effectsABSTRACT
This study investigated whether bioaugmentation improves sulfamethoxazole (SMX) degradation and nitrogen removal in the Moving Bed Biofilm Reactor (MBBR) system. The effects of the C/N ratio on SMX degradation and nitrogen removal were also evaluated. Using MBBR system operation experiments, the bioaugmented reactor was found to perform more effectively than the non-bioaugmentation reactor, with the highest SMX, nitrate-N, and ammonia-N removal efficiencies of 80.49, 94.70, and 96.09%, respectively. The changes in the sulfonamide resistance genes and bacterial communities were detected at various operating conditions. The results indicate that the diversity of the bacterial communities and the abundance of resistance genes were markedly influenced by bioaugmentation and the C/N ratio, with Achromobacter among the dominant genera in the MBBR system. The bio-toxicity of samples, calculated as the inhibition percentage (IP) toward Escherichia coli, was found to decrease to non-toxic ranges after treatment.
Subject(s)
Aquaculture , Sulfamethoxazole/metabolism , Waste Disposal, Fluid/methods , Water Pollutants, Chemical/metabolism , Achromobacter/metabolism , Ammonia , Biofilms , Bioreactors/microbiology , Nitrates , Nitrogen , Wastewater/microbiologyABSTRACT
In this study, a sequencing batch reactor (SBR) with aerobic granular sludge (AGS) was operated with synthetic wastewater containing environmental relevant concentrations of 17ß-estradiol (E2), 17α-ethinylestradiol (EE2) and sulfamethoxazole (SMX). Despite the presence of the studied PhAC, the granular fraction clearly predominated (TSSgran/TSS ranging from 0.82 to 0.98) throughout the monitoring period, presenting aggregates with high organic fraction (VSS/TSS above 0.83) and good settling characteristics (SVI5 ranging from 15 to 39 mL/gTSS). A principal component analysis (PCA) with quantitative image analysis (QIA) based data allowed to distinguish the different operational periods, namely with mature granules (CONT), and the E2, EE2, and SMX feeding periods. It further revealed a positive relationship between the biomass density, sludge settling ability, overall and granular biomass contents, granulation properties, granular biomass fraction and large granules fraction and size. Moreover, a discriminant analysis (DA) allowed to successfully discriminate not only the different operational periods, mainly by using the floccular apparent density, granular stratification and contents data, but also the PhAC presence in samples. The filamentous bacteria contents, sludge settling properties, settling properties stability and granular stratification, structure and contents parameters were found to be crucial for that purpose.
Subject(s)
Sewage , Waste Disposal, Fluid , Aerobiosis , Biomass , Bioreactors , WastewaterABSTRACT
BACKGROUND: Several studies have reported the incidence of interstitial pneumonia (IP) among patients with non-Hodgkin lymphoma (NHL) that are undergoing combination chemotherapy plus rituximab; however, the effective prophylactic treatment for IP remains unclear. This study aims to explore the prophylactic effect of trimethoprim-sulfamethoxazole (TMP-SMX) on IP and identify IP-associated risk factors in NHL patients. METHODS: Between March 2013 and April 2018, 498 patients (264 males, 53%) with B-cell NHL undergoing first-line RCHOP-like chemotherapy treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone were enrolled in this study. RESULTS: These patients had a median age of 56 years, and 311 of the 498 patients (62.4%) were administered once daily with the prophylactic treatment of TMP-SMX. IP occurred in 65 patients (13.1%), indicating a significant reduction in the IP incidence rate (21.4% vs. 8.0%; p < 0.001). Among patients treated with TMP-SMX, 2 (1.2%) exhibited rashes, 38 (12.2%) suffered from nausea and vomiting, 52 (16.7%) showed signs of neutropenia, and 18 (5.8%) suffered from kidney dysfunction. Both univariate and multivariate analysis showed that gender (male), history of diabetes, and absence of prophylactic TMP-SMX treatment were significant risk factors associated with IP. Disease progression was observed in 55/311 (17.7%) patients that underwent prophylactic TMP-SMX treatment and in 63/187 (33.7%) patients that did not (p < 0.001). CONCLUSIONS: This study revealed that the occurrence of IP was common in B-cell NHL patients undergoing combined chemotherapy plus rituximab treatment. IP could be reduced with prophylactic treatment of once-daily oral TMP-SMX.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lung Diseases, Interstitial/prevention & control , Lymphoma, B-Cell/drug therapy , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Analysis of Variance , Anti-Bacterial Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Doxorubicin/analogs & derivatives , Etoposide/administration & dosage , Female , Humans , Incidence , Lung Diseases, Interstitial/epidemiology , Lung Diseases, Interstitial/mortality , Lymphoma, B-Cell/mortality , Male , Middle Aged , Prednisone/administration & dosage , Risk Factors , Rituximab/administration & dosage , Trimethoprim, Sulfamethoxazole Drug Combination/adverse effects , Vincristine/administration & dosage , Young AdultABSTRACT
The bacteriostatic antibiotics, sulfamethoxazole (SMX) and trimethoprim (TMP), have frequently been found in wastewater and surface water, which raises the concerns about their ecotoxicological effects. The indirect photochemical transformation has been proven to be an efficient way to degrade SMX and TMP. In this study, the reaction mechanisms of the degradation by SMX and TMF by OH radicals were investigated by theoretical calculations. Corresponding rate constants were determined and the eco-toxicity of SMX and TMP and its degradations products were predicted using theoretical models. The results indicate that the most favorable pathways for the transformation of SMX and TMP are both â¢OH-addition reaction of benzene ring site with lowest Gibbs free energy barriers (6.86 and 6.21 kcal mol-1). It was found that the overall reaction rate constants of â¢OH-initial reaction of SMX and TMP are 1.28 × 108 M-1 s-1 and 6.21 × 108 M-1 s-1 at 298 K, respectively. When comparing the eco-toxicity of transformation products with parent SMX and TMP, it can be concluded that the acute and chronic toxicities of the degraded products are reduced, but some products remain harmful for organisms, especially for daphnid (toxic or very toxic level). This study can give greater insight into the degradation of SMX and TMP by â¢OH through theoretical calculations in aquatic environment.
Subject(s)
Anti-Infective Agents/toxicity , Aquatic Organisms/drug effects , Ecotoxicology , Hydroxyl Radical/toxicity , Photolysis , Sulfamethoxazole/toxicity , Trimethoprim/toxicity , Anti-Infective Agents, Urinary/toxicityABSTRACT
Serial crystallography (SX) provides an opportunity to observe the molecular dynamics of macromolecular structures at room temperature via pump-probe studies. The delivery of crystals embedded in a viscous medium via an injector or syringe is widely performed in synchrotrons or X-ray free-electron laser facilities with low repetition rates. Various viscous media have been developed; however, there are cases in which the delivery material undesirably interacts chemically or biologically with specific protein samples, or changes the stability of the injection stream, depending on the crystallization solution. Therefore, continued discovery and characterization of new delivery media is necessary for expanding future SX applications. Here, the preparation and characterization of new polysaccharide (wheat starch (WS) and alginate)-based sample delivery media are introduced for SX. Crystals embedded in a WS or alginate injection medium showed a stable injection stream at a flow rate of < 200 nL/min and low-level X-ray background scattering similar to other hydrogels. Using these media, serial millisecond crystallography (SMX) was performed, and the room temperature crystal structures of glucose isomerase and lysozyme were determined at 1.9-2.0 Å resolutions. WS and alginate will allow an expanded application of sample delivery media in SX experiments.
Subject(s)
Crystallization/methods , Crystallography, X-Ray/methods , Polysaccharides/chemistry , Synchrotrons/instrumentation , Aldose-Ketose Isomerases/chemistry , Alginates/chemistry , Crystallization/instrumentation , Crystallography, X-Ray/instrumentation , Muramidase/chemistry , Starch/chemistry , Syringes , Temperature , ViscosityABSTRACT
Central nervous system infections in immunosuppressed patients are rare but potentially lethal complications that require swift diagnoses and intervention. While the differential diagnosis for new lesions on neuroradiological imaging of immunosuppressed patients typically includes infections and neoplasms, image-based heuristics to differentiate the two has been shown to have variable reliability.The authors describe 2 rare CNS infections in immunocompromised patients with atypical physical and radiological presentations. In the first case, a 59-year-old man, who had recently undergone a renal transplantation, was found to have multifocal Nocardia amikacinitolerans abscesses masquerading as neoplasms on diffusion-weighted imaging (DWI); in the second case, a 33-year-old man with suspected recurrent Hodgkin's lymphoma was found to have a nonpyogenic abscess with cytomegalovirus (CMV) encephalitis.As per review of the literature, this appears to be the first case of brain abscess caused by N. amikacinitolerans, a recently isolated superbug. Despite confirmation through brain biopsy later on in case 1, the initial radiological appearance was atypical, showing subtle diffusion restriction on DWI. Similarly, the authors present a case of CMV encephalitis that presented as a ring-enhancing lesion, which is extremely rare. Both cases draw attention to the reliability of neuroimaging in differentiating an abscess from a neoplasm.
Subject(s)
Brain Abscess/virology , Brain Neoplasms/surgery , Cytomegalovirus/pathogenicity , Nocardia/pathogenicity , Adult , Brain/pathology , Brain/surgery , Brain Abscess/diagnosis , Brain Neoplasms/diagnosis , Brain Neoplasms/virology , Diagnosis, Differential , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/virology , Reproducibility of ResultsABSTRACT
X-ray crystallographic methods can be used to visualize macromolecules at high resolution. This provides an understanding of molecular mechanisms and an insight into drug development and rational engineering of enzymes used in the industry. Although conventional synchrotron-based X-ray crystallography remains a powerful tool for understanding molecular function, it has experimental limitations, including radiation damage, cryogenic temperature, and static structural information. Serial femtosecond crystallography (SFX) using X-ray free electron laser (XFEL) and serial millisecond crystallography (SMX) using synchrotron X-ray have recently gained attention as research methods for visualizing macromolecules at room temperature without causing or reducing radiation damage, respectively. These techniques provide more biologically relevant structures than traditional X-ray crystallography at cryogenic temperatures using a single crystal. Serial femtosecond crystallography techniques visualize the dynamics of macromolecules through time-resolved experiments. In serial crystallography (SX), one of the most important aspects is the delivery of crystal samples efficiently, reliably, and continuously to an X-ray interaction point. A viscous delivery medium, such as a carrier matrix, dramatically reduces sample consumption, contributing to the success of SX experiments. This review discusses the preparation and criteria for the selection and development of a sample delivery medium and its application for SX.
Subject(s)
Crystallography, X-Ray/methods , Macromolecular Substances/chemistry , Specimen Handling/methods , Crystallization , Drug Development/methods , Electrons , Lasers , Macromolecular Substances/pharmacology , Viscosity/drug effectsABSTRACT
Although Pneumocystis pneumonia (PCP), a life-threatening infection, has been reported in patients with non-Hodgkin B-cell lymphoma (BNHL) who were treated with rituximab-containing chemotherapies (R-CTX), the PCP prophylaxis regimen awaits establishment to date. This study reports a retrospective analysis of the efficacy and safety of a low-dose trimethoprim/sulfamethoxazole (TMP/SMX) in patients with BNHL receiving R-CTX. We retrospectively analyzed 156 patients newly diagnosed with BNHL who received R-CTX at our institute from 2010 to 2015. We collected patients' clinical and laboratory data, including lymphocytes count, IgG level, PCP prophylaxis regimens, and adverse events (AEs). Patients were categorized into the following two groups based on the TMP/SMX regimen: group A (33 patients; 80 mg/400 mg×3/week) or group B (65 patients; 160 mg/800 mg×2/week). Both lymphocytes count and IgG level declined during R-CTX. No patient developed PCP. Patients in group B exhibited a significantly higher incidence of AEs (18.2% vs. 63.1%; p<0.05) and increased AST (6.1% vs. 26.6%; p<0.05), compared with those in group A. Thus, TMP/SMX (80 mg/400 mg×3/week) effectively prevents PCP and is preferable because of the lower rates of AEs.
Subject(s)
Lymphoma, Non-Hodgkin/drug therapy , Pneumonia, Pneumocystis/prevention & control , Rituximab/therapeutic use , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Humans , Retrospective StudiesABSTRACT
BACKGROUND: Nocardiosis is a life-threatening opportunistic infection. Solid organ transplant (SOT) recipients are at higher risk (incidence 0.04%-3.5%) of developing nocardiosis. Rate of nocardiosis in the Southwestern US may be high due to environmental factors. METHODS: We performed a retrospective review study on 54 SOT patients diagnosed with Nocardia between 1997 and 2016 at our center. To explore the association of various risk factors with both the development of disseminated disease and mortality, a series of Fisher's exact tests was used. FINDINGS: Incidence of nocardiosis in SOT patients was 2.65%. Fisher's exact tests revealed no association between development of disseminated disease and the following variables: transplant rejection (P = 1), elevated tacrolimus levels (P = .4), and CMV viremia (P = .06). Also, we did not find any association between mortality and the variables we evaluated: type of transplant, transplant rejection, renal failure, disseminated nocardia, and patient's age. Overall mortality and 1-year mortality were 17% and 11%. INTERPRETATION: Based on our findings, daily 1 DS TMP/SMX prophylaxis did not appear to provide reliable protection against nocardiosis. However, we could not state definitely that TMP/SMX prophylaxis was or wasn't protective because of lack control group. None of the Fisher's exact tests revealed associations between the tested risk factors and either disease dissemination or mortality. This could be due to a true lack of association between the variables in each pair. However, it is also likely that our relatively small sample size limited our power to detect underlying relationships that may be present. Compared with other studies, 1-year mortality was lower at our institution (11% vs 16%).
Subject(s)
Graft Rejection/epidemiology , Nocardia Infections/epidemiology , Nocardia/isolation & purification , Opportunistic Infections/epidemiology , Organ Transplantation/adverse effects , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Female , Graft Rejection/prevention & control , Humans , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Incidence , Male , Middle Aged , Nocardia Infections/immunology , Nocardia Infections/microbiology , Nocardia Infections/prevention & control , Opportunistic Infections/immunology , Opportunistic Infections/microbiology , Opportunistic Infections/prevention & control , Retrospective Studies , Risk Factors , Southwestern United States/epidemiology , Tacrolimus , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Young AdultABSTRACT
Sulfamethoxazole (SMX) is a common medicine prescribed to treat infections. Due to vast use, SMX has been detected in different parts of the world. Hence, it has become a high risk because of its long term persistence with high biological activity in the ecosystem. Therefore, it is necessary to understand the mechanism of SMX degradation in different genus of bacteria, which is presently unclear. In the present study, degradation of 5 mg L-1 SMX was studied in three isolated pure bacterial cultures, Ochrobactrum sp. SMX-PM1-SA1, Labrys sp. SMX-W1-SC11 and Gordonia sp. SMX-W2-SCD14 and results showed up to 45.2%, 62.2% and 51.4% degradation, respectively within 288 h. Additionally, strain SA1 and strain SCD14 showed up to 66.2% and 69.2% of 4-aminophenol degradation at an initial concentration of 5 mg L-1 within 216 h whereas Labrys sp. SMX-W1-SC11 completely degraded 4-aminophenol at the same concentration within 120 h. Moreover, all three pure bacteria also completely degraded 3-amino-5-methylisoxazole at initial concentration of 4 mg L-1 within 120 h. Furthermore, gas chromatography-mass spectrometry and quadrupole time-of-flight mass spectrometry analysis results revealed that 3-amino-5-methylisoxazole, 4-aminophenol and hydroquinone were the three main by-products of SMX catabolism. In addition, cell free extracts of both Labrys sp. SMX-W1-SC11 and Gordonia sp. SMX-W2-SCD14 showed hydroquinone dioxygenase activity. Besides, all three bacterial strains showed resistance to different heavy metals. Moreover, all three pure bacterial cultures also showed positive chemotactic response toward 3-amino-5-methylisoxazole and hydroquinone based on the drop plate assay. The results of this study recommend these microorganisms for bioremediation of SMX contaminated sites.