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Environmental Pollution (Barking, Essex... Jun 2024Water pollution caused by antibiotics and synthetic dyes and imminent energy crises due to limited fossil fuel resources are issues of contemporary decades. Herein, we...
Water pollution caused by antibiotics and synthetic dyes and imminent energy crises due to limited fossil fuel resources are issues of contemporary decades. Herein, we address them by enabling the multifunctionality in dual Z-scheme MoS/WO/AgBiS across photolysis, photo Fenton-like, and night catalysis. Defect, basal, and facet-engineered WO is modified with MoS and AgBiS, which extended its photoresponse from the UV-NIR region, inhibited carrier recombination, and reduced carrier transfer resistance. The electric field rearrangement leads to a flow of electrons from MoS and AgBiS to WO and intensifies the electron population, which is crucial for night catalysis. When MoS/WO/AgBiS was employed against doxycycline hydrochloride (DOXH), it removed 95.65, 81.11, and 77.92 % of DOXH in 100 min during photo-Fenton (PFR), night-Fenton (NFR), and photocatalytic (PCR) reactions, respectively. It also effectively removed 91.91, 98.17, 99.01, and 98.99 % of rhodamine B (RhB), Congo red (CR), methylene blue (MB), and methylene orange (MO) in Fenton reactions, respectively. ESR analysis consolidates the ROS generation feature of MoS/WO/AgBiS using HO with and without irradiation. This work provides a strategy to eliminate the deficiencies of WO and is conducive to the evolution of applications seeking to combat environmental and energy crises.
PubMed: 38880327
DOI: 10.1016/j.envpol.2024.124375 -
Journal of Neuropathology and... Jun 2024In patients with TDP43 proteinopathy, phosphorylated TDP43 (p-TDP43) accumulates in the cytoplasm of neurons. The accumulation of p-TDP43 has also been reported in...
In patients with TDP43 proteinopathy, phosphorylated TDP43 (p-TDP43) accumulates in the cytoplasm of neurons. The accumulation of p-TDP43 has also been reported in patients with tauopathy and α-synucleinopathy. We investigated spatiotemporal changes in p-TDP43 accumulation in the brains of rTg4510 mice that overexpressed human mutant tau (P301L) and exhibited hyperphosphorylated tau (hp-tau) and phosphorylated αSyn (p-αSyn) accumulation. Immunohistochemically, p-TDP43 aggregates were observed in the cytoplasm of neurons, which increased with age. A significant positive correlation was observed between the number of cells with p-TDP43 aggregates and hp-tau and p-αSyn aggregates. Suppression of the human mutant tau (P301L) expression by doxycycline treatment reduces the accumulation of p-TDP43, hp-tau, and p-αSyn. Proteinase K-resistant p-TDP43 aggregates were found in regions with high hp-tau, and p-αSyn accumulation. Western blotting of the sarkosyl-insoluble fraction revealed bands of monomeric TDP43 and p-TDP43. These results indicate that the accumulation of mouse p-TDP43 is associated with the accumulation of human mutant tau (P301L) in rTg4510 mouse brains. The accumulation of hp-tau and p-αSyn may promote sarkosyl-insoluble p-TDP43 aggregates that are resistant to proteinase K. The synergistic effects of tau, TDP43, and αSyn may be involved in the pathology of proteinopathies, leading to the accumulation of multiple abnormal proteins.
PubMed: 38879441
DOI: 10.1093/jnen/nlae063 -
Journal of Zoo and Wildlife Medicine :... Jun 2024Rodents are typically viewed as asymptomatic reservoirs for leptospirosis infection, as clinical disease in rodents is rarely described. This report includes three...
Rodents are typically viewed as asymptomatic reservoirs for leptospirosis infection, as clinical disease in rodents is rarely described. This report includes three separate cases of leptospirosis in Patagonian maras () over a 3-yr period in multiple locations within a single zoo. All three cases presented with varying clinical signs including lethargy, conjunctival hyperemia, hyperbilirubinemia, and presumed renal azotemia. Infection with spp. was diagnosed antemortem by PCR on whole blood ( = 1, Case 1) or urine ( = 2, Cases 2 and 3). antibody titers measured by serum microagglutination testing ( = 3) were elevated or increased in all three animals over a 1-3-wk period for serovars Bratislava and Hardjo (Case 1) and Grippotyphosa (Case 2 and 3). Two of the three animals responded to treatment with penicillin and doxycycline and supportive care, whereas one animal did not respond to treatment. Postmortem findings in this individual included conjunctivitis, chemosis, dehydration, icterus, tricavitary serosanguinous effusions, necrotizing hepatitis, diffuse pulmonary congestion, and edema. Immunohistochemical examination identified scattered organisms within hepatocytes and renal tubular epithelial cells. A wild raccoon () at the institution tested positive by PCR on kidney tissue for the same spp. serovar and was the suspected source of infection. This case series highlights the clinical importance of leptospirosis as a differential for Patagonian maras presenting with lethargy, ocular signs, acute hepatic disease, and azotemia.
Topics: Animals; Leptospirosis; Male; Female; Animals, Zoo; Anti-Bacterial Agents; Leptospira; Rodent Diseases; Rodentia
PubMed: 38875208
DOI: 10.1638/2023-0042 -
The Journal of Clinical and Aesthetic... Jun 2024Mantle cell lymphoma (MCL) can, in a few reported cases, create an exaggerated mosquito bite response, leading to numerous bullae and significant edema. The phenomenon...
Mantle cell lymphoma (MCL) can, in a few reported cases, create an exaggerated mosquito bite response, leading to numerous bullae and significant edema. The phenomenon is further complicated by the observance of a concurrent Epstein-Barr virus (EBV) reactivation. The current literature provides general information on treatment that most practitioners would consider when attempting to treat an arthropod hypersensitivity reaction, such as topical or systemic corticosteroids. However, no information has been published to date that details a preventive and steroid-sparing approach to treating this phenomenon, without simultaneously treating the MCL. MCL can be indolent in nature and does not always require prompt treatment. The purpose of this case report is to discuss the successful treatment of a rare disorder with a steroid-sparing regimen. The steroid-sparing regimen used consisted of oral doxycycline 100mg twice daily, cetirizine 20mg once daily, and valacyclovir 1g daily, which resulted in sustained reduction in bullous eruptions.
PubMed: 38872927
DOI: No ID Found -
Scientific Reports Jun 2024Transplantation of stem cell-derived β-cells is a promising therapeutic advancement in the treatment of type 1 diabetes mellitus. A current limitation of this approach...
Transplantation of stem cell-derived β-cells is a promising therapeutic advancement in the treatment of type 1 diabetes mellitus. A current limitation of this approach is the long differentiation timeline that generates a heterogeneous population of pancreatic endocrine cells. To address this limitation, an inducible lentiviral overexpression system of mature β-cell markers was introduced into human induced-pluripotent stem cells (hiPSCs). Following the selection of the successfully transduced hiPSCs, the cells were treated with doxycycline in the pancreatic progenitor induction medium to support their transition toward the pancreatic lineage. Cells cultured with doxycycline presented the markers of interest, NGN3, PDX1, and MAFA, after five days of culture, and glucose-stimulated insulin secretion assays demonstrated that the cells were glucose-responsive in a monolayer culture. When cultured as a spheroid, the markers of interest and insulin secretion in a static glucose-stimulated insulin secretion assay were maintained; however, insulin secretion upon consecutive glucose challenges was limited. Comparison to human fetal and adult donor tissues identified that although the hiPSC-derived spheroids present similar markers to adult insulin-producing cells, they are functionally representative of fetal development. Together, these results suggest that with optimization of the temporal expression of these markers, forward programming of hiPSCs towards insulin-producing cells could be a possible alternative for islet transplantation.
Topics: Humans; Insulin-Secreting Cells; Homeodomain Proteins; Trans-Activators; Induced Pluripotent Stem Cells; Basic Helix-Loop-Helix Transcription Factors; Nerve Tissue Proteins; Cell Differentiation; Maf Transcription Factors, Large; Insulin; Glucose; Insulin Secretion; Cells, Cultured; Doxycycline
PubMed: 38871849
DOI: 10.1038/s41598-024-64346-4 -
The Science of the Total Environment Sep 2024Antibiotics are commonly released into paddy fields as mixtures via human activities. However, the simultaneous extraction and detection of these chemicals from multiple...
Antibiotics are commonly released into paddy fields as mixtures via human activities. However, the simultaneous extraction and detection of these chemicals from multiple media are technically challenging due to their different physicochemical properties, resulting in unclear patterns of their transport in the soil-rice system. In this study, a "quick, easy, cheap, effective, rugged, and safe" (QuEChERS) method was developed for the simultaneous analysis of 4 tetracyclines (TCs) and 4 fluoroquinolones (FQs) in the soil and rice tissues from a local poultry farm, and thereby the distribution patterns of the target antibiotics in the soil-rice system and their risk levels to the soil were analyzed. After parameter optimization, the calibration range used for the target antibiotics was 0.1-50 μg/L and each calibration curve was linear with a coefficient of determination (R > 0.995); The QuEChERS method achieved satisfactory recovery rates (70.3-124.6%) along with sensitive detection limits (0.005-0.21 ng/g) for TCs and FQs in the soil, root, stem, leaf, and grain. Among the 8 antibiotics, enrofloxacin (ENX), ciprofloxacin (CIP), oxytetracycline (OTC), and doxycycline (DOX) were detected around a poultry farm. The four antibiotics in the collected paddy soils around the poultry farm ranged from 7.1 ng/g to 395.5 ng/g. Notably, ENX and DOX had higher ecological risks (risk quotient values >1) than CIP and OTC in soil. ENX, CIP, and DOX were highly enriched in rice roots with concentrations up to 471.9, 857.3, and 547.4 ng/g, respectively, which were also detected in rice aboveground tissues. The findings may provide both technical and practical guidance for the understanding of antibiotic environmental behavior and risks.
Topics: Anti-Bacterial Agents; Soil Pollutants; Oryza; Environmental Monitoring; Soil; Fluoroquinolones; Tetracyclines
PubMed: 38871311
DOI: 10.1016/j.scitotenv.2024.173929 -
International Journal of Surgery... Jun 2024Despite advanced infection control practices including preoperative antibiotic prophylaxis, surgical site infection (SSI) remains a challenge. This study aimed to test...
INTRODUCTION
Despite advanced infection control practices including preoperative antibiotic prophylaxis, surgical site infection (SSI) remains a challenge. This study aimed to test whether local administration of a novel prolonged-release Doxycycline-Polymer-Lipid Encapsulation matriX (D-PLEX) before wound closure, concomitantly with standard of care (SOC), reduces the incidence of incisional SSI after elective abdominal colorectal surgery.
MATERIALS AND METHODS
This was a phase 3 randomized, controlled, double-blind, multinational study (SHIELD 1) between June 2020 to June 2022. Patients with at least one abdominal incision length >10 cm were randomized 1:1 to the investigational arm (D-PLEX+SOC) or control (SOC) arm . The primary outcome was a composite of incisional SSI, incisional reintervention, and all-cause mortality.
RESULTS
A total of 974 patients were analyzed, of whom 579 (59.4%) were male. The mean age (±SD) was 64.2±13.0 years. The primary outcome occurred in 9.3% of D-PLEX patients versus 12.1% (SOC) (risk difference estimate [RDE], -2.8%; 95% CI [-6.7%, 1.0%], P=0.1520). In a pre-specified analysis by incision length, a reduction in the primary outcome was observed in the >20 cm subpopulation: 8% (D-PLEX) versus 17.5% (SOC) (RDE, -9.4%; 95% CI [-15.5%, -3.2%], P=0.0032). In the >10 to ≤20 cm subgroup, no reduction was observed: 9.9% versus 7.9% (RDE, 2.0%; 95% CI [-2.8%, 6.7%], P=0.4133). Exploratory post-hoc analyses of patients with increased SSI risk (≥1 patient-specific comorbidity) indicated a reduction in the incidence of the primary outcome: 9.0% (D-PLEX) versus 13.7% (SOC) (RDE, -4.8%; 95% CI [-9.5%, -0.1%], P=0.0472). The D-PLEX safety profile was good (no difference in treatment-emergent adverse events between the groups).
CONCLUSIONS
The SHIELD-1 study did not meet its primary outcome of reduced incisional SSI, incisional reinterventions, or all-cause mortality. Pre-specified and post-hoc analyses suggested that D-PLEX may reduce the incidence of the primary outcome event in patients with increased SSI risk, including lengthy incisions.
PubMed: 38869970
DOI: 10.1097/JS9.0000000000001824 -
Open Forum Infectious Diseases Jun 2024Identifying and treating patients with acute Q fever who are at an increased risk of progressing to persistent disease is crucial for preventing future complications. In...
BACKGROUND
Identifying and treating patients with acute Q fever who are at an increased risk of progressing to persistent disease is crucial for preventing future complications. In this study, we share our decade-long clinical experience with acute Q fever, highlighting the challenges that clinicians encounter from making an initial diagnosis and performing risk stratification to determining the appropriate prophylaxis regimen and duration.
METHODS
We retrieved records of adult Mayo Clinic patients (≥18 years) with positive serology results between 1 January 2012 and 31 March 2022. Patients with Q fever anti-phase II immunoglobulin G ≥1:256 by indirect immunofluorescence were further analyzed.
RESULTS
Thirty-one patients were included. Their median age was 58 years (IQR, 50-64), and the majority were men (84%). Acute hepatitis (29%), flu-like illness (25.8%), and pneumonia (16%) were the most common presentations. Thirteen patients (42%) received antibiotic prophylaxis to prevent disease progression, with significant variation in the indications and duration across physicians. The combination of doxycycline and hydroxychloroquine was the preferred regimen. Prophylaxis was administered for a median 333 days (IQR, 168-414). Four patients (13%) progressed to Q fever native valve infective endocarditis, with elevated anticardiolipin immunoglobulin G levels being the sole risk factor in 2 cases. The small sample size precluded drawing conclusions on the impact of prophylaxis in preventing disease progression.
CONCLUSIONS
Management of acute Q fever is complicated by the lack of comprehensive clinical guidelines leading to varied clinical practices. There is a critical need for randomized trials to establish robust evidence-based protocols for management.
PubMed: 38868311
DOI: 10.1093/ofid/ofae277 -
Open Forum Infectious Diseases Jun 2024Osteoarticular infections (OAIs) are commonly treated with prolonged intravenous (IV) antimicrobials. The Oral versus Intravenous Antibiotics for Bone and Joint...
Variation in North American Infectious Disease Specialists' Practice Regarding Oral and Suppressive Antibiotics for Adult Osteoarticular Infections: Results of an Emerging Infections Network (EIN) Survey.
BACKGROUND
Osteoarticular infections (OAIs) are commonly treated with prolonged intravenous (IV) antimicrobials. The Oral versus Intravenous Antibiotics for Bone and Joint Infection (OVIVA) trial demonstrated that oral (PO) antibiotics are noninferior to IV antibiotics in the treatment of OAIs. We surveyed infectious disease (ID) physicians about their use of PO antibiotics in the treatment of OAIs.
METHODS
An Emerging Infection Network survey with 9 questions regarding antibiotic prescribing for the treatment of OAIs was sent to 1475 North American ID physicians. The questions were mostly multiple choice and focused on the use of definitive oral antibiotic therapy (defined as oral switch within 2 weeks of starting antibiotics) and chronic suppressive antibiotic therapy (SAT).
RESULTS
Of the 413 physicians who reported treating OAIs, 91% used oral antibiotics at least sometimes and 31% used them as definitive therapy, most often for diabetic foot osteomyelitis and native joint septic arthritis. The oral antibiotics most frequently used for OAIs included trimethoprim-sulfamethoxazole, doxycycline/minocycline, and linezolid for , amoxicillin/cefadroxil/cephalexin for streptococci, and fluoroquinolones for gram-negative organisms. The most common rationales for not transitioning to oral antibiotics included nonsusceptible pathogens, comorbidities preventing therapeutic drug levels, and concerns about adherence. SAT use was variable but employed by a majority in most cases of periprosthetic joint infection managed with debridement and implant retention.
CONCLUSIONS
North American ID physicians utilize oral antibiotics and SAT for the management of OAIs, although significant practice variation exists. Respondents voiced a need for updated guidelines.
PubMed: 38868304
DOI: 10.1093/ofid/ofae280 -
Cureus May 2024This report describes a patient with pneumonia. The patient was a man in his 70s with significant comorbid conditions, including chronic obstructive pulmonary disease...
Successful Management of Pasteurella multocida Pneumonia in a Chronic Obstructive Pulmonary Disease Patient: A Case Report Highlighting the Importance of Tailored Antibiotic Therapy.
This report describes a patient with pneumonia. The patient was a man in his 70s with significant comorbid conditions, including chronic obstructive pulmonary disease (COPD), and is an example of the diverse presentations of infections increasingly found in the literature. The novelty of this case lies in the manifestation of pneumonia in a patient with underlying respiratory conditions and its successful management, outlining a unique clinical scenario and a tailored therapeutic approach. A 71-year-old male with a medical history of COPD, asthma, tremors, hypertension, and arthritis presented to the emergency department with progressive shortness of breath, productive cough, and chest tightness. The initial diagnosis was COPD exacerbation and left lower lobe pneumonia, for which a regimen of ceftriaxone and azithromycin was initiated. The patient's condition was further complicated by the persistence of symptoms. Following sputum culture analysis, infection was identified. Consequently, the antibiotic regimen was tailored, transitioning the patient to doxycycline, which led to substantial clinical improvement, enabling discharge with a 10-day course of oral doxycycline. This case elucidates the importance of precise microbiological diagnosis in patients with complex respiratory conditions, as it guides more targeted antibiotic therapy. It highlights the need for clinical vigilance for atypical pathogens like in patients with COPD exacerbations, especially when conventional treatment strategies yield suboptimal responses. The successful resolution of the pneumonia underscores the effectiveness of antibiotic stewardship guided by sputum culture findings.
PubMed: 38868278
DOI: 10.7759/cureus.60210