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Veterinary Pathology Jun 2024is a genus of nonphotosynthetic, green algae in the family , closely related to . It is a known pathogen of invertebrates, and its occurrence in vertebrates has not...
is a genus of nonphotosynthetic, green algae in the family , closely related to . It is a known pathogen of invertebrates, and its occurrence in vertebrates has not been documented. A captive, 10-month-old, male, albino California kingsnake () was submitted for necropsy. Gross examination revealed hemorrhagic laryngitis and a red mottled liver. Histologically, intravascular, intramonocytic/macrophagic and extracellular, eukaryotic organisms were observed in all tissues. These organisms stained positive with Grocott-Gomori methenamine silver and periodic acid-Schiff and were variably acid-fast and gram-positive. Ultrastructural analysis revealed approximately 4 µm vegetative multiplication forms and cysts with 3 parallel ovoid cells and a helically coiled filamentous cell. A polymerase chain reaction with primers targeting , amplicon sequencing, and Bayesian phylogenetic analysis confirmed it clustered within sp. with 100% posterior probability. The genus was found to nest within the genus , forming a clade with with 80% posterior probability.
PubMed: 38881033
DOI: 10.1177/03009858241259179 -
PLoS Pathogens May 2024The role of bacteria in the etiology of dental caries is long established, while the role of fungi has only recently gained more attention. The microbial invasion of...
The role of bacteria in the etiology of dental caries is long established, while the role of fungi has only recently gained more attention. The microbial invasion of dentin in advanced caries especially merits additional research. We evaluated the fungal and bacterial community composition and spatial distribution within carious dentin. Amplicon 16S rRNA gene sequencing together with quantitative PCR was used to profile bacterial and fungal species in caries-free children (n = 43) and 4 stages of caries progression from children with severe early childhood caries (n = 32). Additionally, healthy (n = 10) and carious (n = 10) primary teeth were decalcified, sectioned, and stained with Grocott's methenamine silver, periodic acid Schiff (PAS) and calcofluor white (CW) for fungi. Immunolocalization was also performed using antibodies against fungal β-D-glucan, gram-positive bacterial lipoteichoic acid, gram-negative endotoxin, Streptococcus mutans, and Candida albicans. We also performed field emission scanning electron microscopy (FESEM) to visualize fungi and bacteria within carious dentinal tubules. Bacterial communities observed included a high abundance of S. mutans and the Veillonella parvula group, as expected. There was a higher ratio of fungi to bacteria in dentin-involved lesions compared to less severe lesions with frequent preponderance of C. albicans, C. dubliniensis, and in one case C. tropicalis. Grocott's silver, PAS, CW and immunohistochemistry (IHC) demonstrated the presence of fungi within carious dentinal tubules. Multiplex IHC revealed that fungi, gram-negative, and gram-positive bacteria primarily occupied separate dentinal tubules, with rare instances of colocalization. Similar findings were observed with multiplex immunofluorescence using anti-S. mutans and anti-C. albicans antibodies. Electron microscopy showed monomorphic bacterial and fungal biofilms within distinct dentin tubules. We demonstrate a previously unrecognized phenomenon in which fungi and bacteria occupy distinct spatial niches within carious dentin and seldom co-colonize. The potential significance of this phenomenon in caries progression warrants further exploration.
Topics: Humans; Dental Caries; Dentin; Male; Child; Female; Child, Preschool; Bacteria; Fungi; RNA, Ribosomal, 16S
PubMed: 38805482
DOI: 10.1371/journal.ppat.1011865 -
Clinical Kidney Journal May 2024[F] AlF-NOTA-FAPI-04 is a novel positron emission tomography (PET) ligand, which specifically targets fibroblast activation protein (FAP) expression as a FAP inhibitor...
BACKGROUND
[F] AlF-NOTA-FAPI-04 is a novel positron emission tomography (PET) ligand, which specifically targets fibroblast activation protein (FAP) expression as a FAP inhibitor (FAPI). We analysed the diagnostic value of [F] AlF-NOTA-FAPI-04 PET/CT for the non-invasive assessment of kidney interstitial inflammation and fibrosis in different renal pathologies.
METHODS
Twenty-six patients (14 males and 12 females; mean age, 50.5 ± 16.5 years) with a wide range of kidney diseases and 10 patients (six males and four females; mean age, 55.4 ± 8.6 years) without known evidence of renal disease as disease controls underwent [F] AlF-NOTA-FAPI-04 PET/CT imaging. Kidney tissues obtained from kidney biopsies were stained with haematoxylin and eosin, periodic acid-Schiff, Masson's trichome, and periodic acid-silver methenamine. Immunohistochemical staining was also performed to assess the expression of α-smooth muscle actin (αSMA) and FAP. Renal parenchymal FAPI uptake reflected by maximum standardized uptake value (SUV) and mean standardized uptake value (SUV) measurements on PET/CT was analysed against pathohistological findings.
RESULTS
We found that renal parenchymal FAPI uptake was significantly higher in patients with various kidney diseases than in control patients in this study (SUV = 4.3 ± 1.8 vs 1.9 ± 0.4, SUV=3.9 ± 1.7 vs 1.5 ± 0.4, respectively; all < 0.001). All kidney diseases, both in acute and chronic kidney disease, had increased renal parenchymal uptake to varying degrees. The correlation analysis indicated a positive association between the SUV and the tubulointerstitial inflammation (TII), interstitial fibrosis and tubular atrophy (IF/TA), and TII + IF/TA scores ( = 0.612, 0.681, and 0.754, all < 0.05), and between the SUV and the TII, IF/TA, and TII + IF/TA scores ( = 0.603, 0.700, and 0.748, all < 0.05). Furthermore, we found significant positive correlations between both SUV and the SUV with SMA and FAP staining scores ( = 0.686 and 0.732, = 0.667 and 0.739, respectively; both < 0.001).
CONCLUSIONS
[F] AlF-NOTA-FAPI-04 PET/CT is clinically available for the comprehensive and non-invasive assessment of tubular injury in various kidney diseases.
PubMed: 38803395
DOI: 10.1093/ckj/sfae064 -
Clinical, Cosmetic and Investigational... 2024Protothecosis, an infrequent human infection, is caused by achlorophyllic algae belonging to the genus Prototheca, particularly Prototheca wickerhamii. The skin stands...
Protothecosis, an infrequent human infection, is caused by achlorophyllic algae belonging to the genus Prototheca, particularly Prototheca wickerhamii. The skin stands as the most commonly affected organ. This report documents a case involving an 82-year-old male with Protothecosis. Histopathological analysis revealed granulomatous inflammation in the dermis, exhibiting necrotic features and hosting numerous non-budding spherical organisms. These organisms were positively stained using methenamine silver and periodic acid-Schiff stains, confirming identification as after validation through tissue culture and sequencing procedures. Initially, the patient received oral itraconazole at a dosage of 200 mg daily, accompanied by topical 1% naftifine-0.25% ketoconazole cream for a duration of 4 weeks, resulting in significant improvement. Subsequently, due to gastrointestinal discomfort presumably linked to itraconazole, terbinafine was administered. Over a span of 3 months, the patient received oral terbinafine at a dosage of 250 mg/day alongside the application of topical 1% naftifine-0.25% ketoconazole cream, leading to complete healing of the skin lesion, leaving behind a fibrotic scar.
PubMed: 38689756
DOI: 10.2147/CCID.S453620 -
BMJ Open Apr 2024To estimate the cost-effectiveness of methenamine hippurate compared with antibiotic prophylaxis in the management of recurrent urinary tract infections. (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Cost-effectiveness of methenamine hippurate compared with antibiotic prophylaxis for the management of recurrent urinary tract infections in secondary care: a multicentre, open-label, randomised, non-inferiority trial.
OBJECTIVES
To estimate the cost-effectiveness of methenamine hippurate compared with antibiotic prophylaxis in the management of recurrent urinary tract infections.
DESIGN
Multicentre, open-label, randomised, non-inferiority trial.
SETTING
Eight centres in the UK, recruiting from June 2016 to June 2018.
PARTICIPANTS
Women aged ≥18 years with recurrent urinary tract infections, requiring prophylactic treatment.
INTERVENTIONS
Women were randomised to receive once-daily antibiotic prophylaxis or twice-daily methenamine hippurate for 12 months. Treatment allocation was not masked and crossover between arms was allowed.
PRIMARY AND SECONDARY OUTCOME MEASURES
The primary economic outcome was the incremental cost per quality-adjusted life year (QALY) gained at 18 months. All costs were collected from a UK National Health Service perspective. QALYs were estimated based on responses to the EQ-5D-5L administered at baseline, 3, 6, 9, 12 and 18 months. Incremental costs and QALYs were estimated using an adjusted analysis which controlled for observed and unobserved characteristics. Stochastic sensitivity analysis was used to illustrate uncertainty on a cost-effectiveness plane and a cost-effectiveness acceptability curve. A sensitivity analysis, not specified in the protocol, considered the costs associated with antibiotic resistance.
RESULTS
Data on 205 participants were included in the economic analysis. On average, methenamine hippurate was less costly (-£40; 95% CI: -684 to 603) and more effective (0.014 QALYs; 95% CI: -0.05 to 0.07) than antibiotic prophylaxis. Over the range of values considered for an additional QALY, the probability of methenamine hippurate being considered cost-effective ranged from 51% to 67%.
CONCLUSIONS
On average, methenamine hippurate was less costly and more effective than antibiotic prophylaxis but these results are subject to uncertainty. Methenamine hippurate is more likely to be considered cost-effective when the benefits of reduced antibiotic use were included in the analysis.
TRIAL REGISTRATION NUMBER
ISRCTN70219762.
Topics: Humans; Urinary Tract Infections; Cost-Benefit Analysis; Female; Hippurates; Middle Aged; Methenamine; Quality-Adjusted Life Years; Adult; Antibiotic Prophylaxis; Recurrence; United Kingdom; Anti-Bacterial Agents; Aged
PubMed: 38684270
DOI: 10.1136/bmjopen-2023-074445 -
The Journal of Antimicrobial... May 2024Despite a lack of conclusive evidence of effect, methenamine hippurate is widely prescribed as preventive treatment for recurrent urinary tract infections (UTIs) in...
BACKGROUND
Despite a lack of conclusive evidence of effect, methenamine hippurate is widely prescribed as preventive treatment for recurrent urinary tract infections (UTIs) in Norway. A national discontinuation of methenamine hippurate treatment due to a 4-month drug shortage in 2019 presented an opportunity to evaluate its preventive effect on UTIs among regular users.
OBJECTIVE
To estimate the impact of the methenamine hippurate drug shortage on prescription frequency of UTI antibiotics.
METHODS
Data from The Norwegian Prescription Database was analysed using an interrupted time series design. The time series consisted of 56 time periods of 14 days. The model included two naturally occurring interruptions: (i) the methenamine hippurate drug shortage, and (ii) reintroduction of the drug. The study population were 18 345 women ≥50 years receiving ≥2 prescriptions of methenamine hippurate in the study period before the shortage. Main outcome measure was number of prescriptions of UTI antibiotics per 1000 methenamine hippurate users. Prescription rates of antibiotics for respiratory tract infections were analysed to assess external events affecting antibiotic prescribing patterns.
RESULTS
We found a significant increase of 2.41 prescriptions per 1000 methenamine hippurate users per 14-day period during the drug shortage (95%CI 1.39, 3.43, P < 0.001), followed by a significant reduction of -2.64 prescriptions after reintroduction (95%CI -3.66, -1.63, P < 0.001).
CONCLUSIONS
During the methenamine hippurate drug shortage, we found a significant increase in prescribing trend for UTI antibiotics followed by a significant decrease in prescribing trend after reintroduction. This change in trend seems to reflect a preventive effect of the drug on recurrent UTIs.
Topics: Humans; Urinary Tract Infections; Norway; Anti-Bacterial Agents; Interrupted Time Series Analysis; Female; Hippurates; Methenamine; Middle Aged; Aged; Drug Prescriptions; Practice Patterns, Physicians'; Aged, 80 and over; Drug Utilization
PubMed: 38635298
DOI: 10.1093/jac/dkae078 -
Revista Espanola de Enfermedades... Apr 2024A 62-year-old woman, originally from Peru, with rheumatoid arthritis under treatment with anti-tumor necrosis factor (anti-TNF) therapy, was admitted due to...
A 62-year-old woman, originally from Peru, with rheumatoid arthritis under treatment with anti-tumor necrosis factor (anti-TNF) therapy, was admitted due to constitutional syndrome and suspicion of neoplasia. Computed tomography (CT) scan revealed involvement of three segments of the colon, ascites, and likely peritoneal implants. Ascitic fluid analysis showed elevated adenosine deaminase (ADA) levels and lymphocytosis. The patient presented with hematemesis and hematochezia with hemodynamic instability. Upper gastrointestinal endoscopy identified an extensive ulcer in the middle esophagus with a granular base, elevated and defined edges, indeterminate for malignancy and without blood residues. Colonoscopy also revealed multiple extensive ulcers in the transverse colon, with whitish bases and thickened and necrotic-looking surrounding mucosal edges. Histology showed granulomas and yeast-like fungal structures with methenamine silver staining in both tissues, consistent with disseminated histoplasmosis. Antifungal treatment was initiated with good clinical evolution.
PubMed: 38634865
DOI: 10.17235/reed.2024.10432/2024 -
Cureus Mar 2024Musculoskeletal coccidioidomycosis is a rare disseminated fungal infection caused by either or endemic to the southwestern United States and northwestern Mexico, as...
Musculoskeletal coccidioidomycosis is a rare disseminated fungal infection caused by either or endemic to the southwestern United States and northwestern Mexico, as well as Guatemala, Brazil, and other locations in Central and South America. Symptomatic primary infection of coccidioidomycosis can present as pneumonia with influenza-like symptoms, but the majority of cases remain asymptomatic. When dissemination occurs, the most common extrapulmonary sites include the skin, lymph nodes, musculoskeletal system, and meninges. We present a case of a 53-year-old female with a history of breast cancer and ankylosing spondylitis treated with adalimumab who presented with disseminated coccidioidomycosis. On presentation, she reported subcutaneous nodules on the right forearm and elbow. Radiologic evaluation utilizing magnetic resonance imaging (MRI) and positron emission tomography (PET) scan revealed multiple subcutaneous and bony enhancing lesions in her right forearm, lumbar spine, iliac wing, and axillary lymphadenopathy. Given the patient's history of breast cancer, there was concern for metastatic disease. Axillary lymph node biopsies were negative for malignancy, but immunoreactive for with a positive Grocott methenamine silver (GMS) stain and a antibody panel confirmed the diagnosis of disseminated coccidioidomycosis. Treatment with fluconazole was initiated along with discontinuation of adalimumab. Fluconazole was transitioned to itraconazole due to adverse effects. Treatment was successful as evidenced by improved PET imaging and downtrending antibody titers. This case highlights the concerning potential for dissemination of endemic mycoses with anti-tumor necrosis factor-α (TNF-α) therapies and the unique ways in which they can present. Further investigation is needed to determine the long-term implications of the disease and the role that immunosuppressive medications play in disease susceptibility.
PubMed: 38629004
DOI: 10.7759/cureus.56321 -
International Archives of... Apr 2024Many patients suffered from rhino-orbital-cerebral mucormycosis during the coronavirus disease 2019 (COVID-19) pandemic in India. Diabetes is a known risk factor of...
Many patients suffered from rhino-orbital-cerebral mucormycosis during the coronavirus disease 2019 (COVID-19) pandemic in India. Diabetes is a known risk factor of COVID-19 infection and mucormycosis. The present study was done to describe the clinical spectrum and histopathological findings of mucormycosis in COVID-19 patients and their outcomes. A cross-sectional study was done over a period of two and half months. The biopsy samples or scrapings from sinonasal or periorbital tissue of 38 patients were analyzed. Hematoxylin & Eosin (H&E stain) slides were evaluated along with Grocott-Gomori methenamine-silver and Periodic acid-Schiff stains to highlight the fungal elements. The male to female ratio was 2.5:1, and the mean age of the subjects was 53 years old. A total of 68.4% ( = 26/38) of the patients had diabetes as a comorbidity, 84.2% ( = 32/38) had a history of steroid intake, and 55.3% ( = 21/38) were given supplemental oxygen during their treatment. The common presentations were nasal blockage, discharge, eye pain, headache, and altered mentation. The sites of biopsy were: nasal cavity 76.3% ( = 29/38), periorbital fat/orbit 21.1% ( = 8/38), maxillary sinus 15.8% ( = 6/38) and ethmoid sinus 13.2% ( 5/38). In 76.3% ( = 29/38) cases, broad, irregular, nonseptate, and right-angle branching hyphae were seen on H&E-stained tissue sections. COVID-19 led to various complications in individuals affected by it. Mucormycosis was one such lethal complication. An early diagnosis and prompt treatment is crucial to control the progression of the disease and improve outcomes.
PubMed: 38618587
DOI: 10.1055/s-0043-1776729 -
Pharmaceutics Jan 2024Onchocerciasis treatment and control relies mainly on the use of ivermectin which has high activity against the microfilarial stage of but limited activity against the...
Onchocerciasis treatment and control relies mainly on the use of ivermectin which has high activity against the microfilarial stage of but limited activity against the long-lived, tissue dwelling adult nematodes. As this neglected tropical disease has now been targeted for elimination, there is an urgent need for new drugs to combat these parasites, ideally with macrofilaricidal activity. In this study, we have examined the anti- activity of a range of existing FDA-approved drugs with a view to repurposing, which can lead to rapid and relatively inexpensive development. From the Pharmakon-1600 library, 106 drugs were selected and tested against adult male parasites using a concentration of 1.25 × 10 M in an in vitro 5-day standard assay to assess motility and viability (using MTT/formazan colorimetry). The findings revealed that 44 drugs produced marginal/moderate activity (50-99% motility and/or MTT reductions) including cefuroxime sodium, methenamine, primaquine phosphate and rivastigmine tartrate, while 23 drugs produced good activity (100% motility reductions and significant MTT reductions), including atovaquone, isradipine, losartan, rifaximin, cefaclor and pyrantel pamoate. Although this study represents only a first step, some of the identified hits indicate there are potential anti- drug candidates worthy of further investigation.
PubMed: 38399264
DOI: 10.3390/pharmaceutics16020210