Investigating the C2 Modulation of the Imidazo[1,2-a]pyrazine-Based Hit Compound CTN1122: Synthesis, in vitro Antileishmanial Activity, Cytotoxicity and Casein Kinase 1 Inhibition.

Our research group previously discovered CTN1122, an imidazo[1,2-a]pyrazine compound with promising antileishmanial activity against intramacrophage amastigotes of Leishmania major and L. donovani strains. CTN1122 effectively targets Leishmania casein kinase 1 (L-CK1.

Chemical Composition, Antifungal, Antioxidant, and Hemolytic Activities of Moroccan Thymus capitatus Essential Oil.

This study aimed to define the chemical composition of Moroccan Thymus capitatus essential oil, and to investigate its in vitro antioxidant and antifungal activities against human pathogenic fungi. Chemical analysis using GC-FID and GC-MS system revealed 28 constituents, representing 99 % of total compounds. Oxygenated monoterpenes represented the highest proportion (79.

Oral Health and the Association with Blood Parameters in Neurogeriatric Inpatients without Relevant Systemic Inflammation: An Observational Study.

As little evidence is available, we report the oral health of neurogeriatric inpatients and the association with hematological parameters representing systemic health. We performed a cross-sectional investigation of 30 patients undergoing neurogeriatric early rehabilitation and excluded systemic inflammation as a trigger for oral infection (C-reactive protein >5 mg/dL). Outcomes included oral health and hygiene status and routine laboratory parameters.

Precise genome editing underlines the distinct contributions of mutations in , , , and genes to antifungal resistance in .

has recently emerged as a major threat due to the worldwide emergence of fluconazole-resistant strains causing clonal outbreaks in hospitals and poses a therapeutic challenge due to the limited antifungal armamentarium. Here, we used precise genome editing using CRISPR-Cas9 to gain further insights into the contribution of mutations in , , , and genes and the influence of allelic dosage to antifungal resistance in . Seven of the most common amino acid substitutions previously reported in fluconazole-resistant clinical isolates (including Y132F in ) were engineered in two fluconazole-susceptible lineages (ATCC 22019 and STZ5).

Think TB! A rare case of influenza and rapid progressive neurotuberculosis coinfection.

An Indian migrant presented with increasing neurological symptoms after an acute influenza B infection. We diagnosed progressive neurotuberculosis—a rare and difficult case of tuberculosis and influenza co-infection. It highlights the importance of broad-based diagnostics in people from low- and middle-income countries, taking into account unusual manifestations of tuberculosis.

Is the -Terminal Domain an Effective and Selective Target for the Design of Hsp90 Inhibitors against Yeast?

Improving the armamentarium to treat invasive candidiasis has become necessary to overcome drug resistance and the lack of alternative therapy. In the pathogenic fungus , the 90-kDa Heat-Shock Protein (Hsp90) has been described as a major regulator of virulence and resistance, offering a promising target. Some human Hsp90 inhibitors have shown activity against spp.

Antifungal efficacy of imidazo[1,2-]pyrazine-based thiosemicarbazones and thiazolidinediones against species.

To evaluate antifungal potential of 5,6,7,8-tetrahydroimidazo[1,2-]pyrazine hybrids based on thiosemicarbazones and thiazolidinediones against pathogenic species. Antifungal activity of nine compounds were assessed by broth microdilution. Interactions between active compounds and itraconazole were evaluated by the checkerboard assay using non-wild-type isolates.

Discovery of New Broad-Spectrum Anti-Infectives for Eukaryotic Pathogens Using Bioorganometallic Chemistry.

Unlabelled: Drug resistance observed with many anti-infectives clearly highlights the need for new broad-spectrum agents to treat especially neglected tropical diseases (NTDs) caused by eukaryotic parasitic pathogens including fungal infections. Since these diseases target the most vulnerable communities who are disadvantaged by health and socio-economic factors, new agents should be, if possible, easy-to-prepare to allow for commercialization based on their low cost. In this study, we show that simple modification of one of the most well-known antifungal drugs, fluconazole, with organometallic moieties not only improves the activity of the parent drug but also broadens the scope of application of the new derivatives.

Reply to Hall et al. Comment on "Dinesen et al. Diphoterine for Chemical Burns of the Skin: A Systematic Review. 2023, , 55-68".

We thank Hall et al. [..

Production of carbon-containing pyrite spherules induced by hyperthermophilic Thermococcales: a biosignature?

Thermococcales, a major order of hyperthermophilic archaea inhabiting iron- and sulfur-rich anaerobic parts of hydrothermal deep-sea vents, are known to induce the formation of iron phosphates, greigite (FeS) and abundant quantities of pyrite (FeS), including pyrite spherules. In the present study, we report the characterization of the sulfide and phosphate minerals produced in the presence of Thermococcales using X-ray diffraction, synchrotron-based X ray absorption spectroscopy and scanning and transmission electron microscopies. Mixed valence Fe(II)-Fe(III) phosphates are interpreted as resulting from the activity of Thermococcales controlling phosphorus-iron-sulfur dynamics.

The Mortality Attributable to Candidemia in Is Higher than That in Other Species: Myth or Reality?

has become a major health threat due to its transmissibility, multidrug resistance and severe outcomes. In a case-control design, 74 hospitalised patients with candidemia were enrolled. In total, 22 cases (29.

Transcutaneous carbon dioxide monitoring during prolonged apnoea with high-flow nasal oxygen.

Background: The duration of apnoeic oxygenation with high-flow nasal oxygen is limited by hypercapnia and acidosis and monitoring of arterial carbon dioxide level is therefore essential. We have performed a study in patients undergoing prolonged apnoeic oxygenation where we monitored the progressive hypercapnia with transcutaneous carbon dioxide. In this paper, we compared the transcutaneous carbon dioxide level with arterial carbon dioxide tension.

Diphoterine for Chemical Burns of the Skin: A Systematic Review.

The incidence of chemical burns appears to be increasing. Diphoterine is an amphoteric, chelating, polyvalent solution used for the decontamination of chemical splashes. In this systematic review, we aimed to assess the effect of diphoterine on chemical burns compared with water or no treatment.

Fate of antimony contamination generated by road traffic - A focus on Sb geochemistry and speciation in stormwater ponds.

Although antimony (Sb) contamination has been documented in urban areas, knowledge gaps remain concerning the contributions of the different sources to the Sb urban biogeochemical cycle, including non-exhaust road traffic emissions, urban materials leaching/erosion and waste incineration. Additionally, details are lacking about Sb chemical forms involved in urban soils, sediments and water bodies. Here, with the aim to document the fate of metallic contaminants emitted through non-exhaust traffic emissions in urban aquatic systems, we studied trace element contamination, with a particular focus on Sb geochemistry, in three highway stormwater pond systems, standing as models of surface environments receiving road-water runoff.

Methoxyflurane for Relief of Procedural Pain in Burn Patients: A Prospective Single-Centre Evaluation Study.

: Procedural pain in burn patients continues to be a major problem. Frequently used analgesics, such as opioids, may have various side effects, including respiratory depression, nausea, and vomiting. Inhaled methoxyflurane has been used in the pre-hospital setting for trauma-related pain.

Otomycosis caused by the cryptic and emerging species : two case reports.

Two cases of otomycosis have been reported in patients undergoing tympanomastoidectomy. The first one had chronic otitis media, hypertrophic concha and nasal septum deviation, tympanic perforation and otorrhea. The second had otalgia, pruritus, chronic otitis media and cholesteatoma.

Comparison of onset time, duration of action, and intubating conditions after cisatracurium 0.15 mg/kg in young and elderly patients.

Introduction: Tracheal intubation during anesthesia can be facilitated by the neuromuscular blocking agent cisatracurium. However, limited data exists about onset time, duration of action and effect on intubating conditions in elderly patients above 80 years of age. We hypothesized that elderly patients would present a longer onset time and duration of action compared to younger adults.

Time to CT scan for patients with acute severe neurological symptoms: a quality assurance study.

Emergent brain computed tomography (CT) scan allows for identification of patients presenting with acute severe neurological symptoms in whom medical and surgical interventions may be lifesaving. The aim of this study was to evaluate if time to CT from arrival at the emergency department exceeded 30 min in patients admitted with acute severe neurological symptoms. This was a retrospective register-based quality assurance study.

Rocuronium 0.3 or 0.9 mg/kg comparing onset time, duration of action, and intubating conditions in patients 80 years and older: A randomized study.

Background: Limited data exist about the optimal dose of rocuronium for intubation in elderly patients. We hypothesized that rocuronium 0.9 mg/kg would lead to a shorter onset time than 0.

Infections and Ecology from a One Health Perspective.

microalgae were only recognized as pathogens of both humans and animals in the 1960s; however, since then, these microbes have been drawing increasing interest in both human and veterinary medicine. The first human outbreak of protothecosis in a tertiary care chemotherapy ward in 2018 further highlighted the need to understand in more depth and detail their ecology, etiology, pathogenesis and routes of transmission between different hosts, environments and habitats from a One Health perspective. Protothecal infections have been reported in a growing number of cattle herds around the world in recent decades, and has become an important bovine mastitis pathogen in certain countries and regions.

Therapeutic Potential of Electromyostimulation (EMS) in Critically Ill Patients-A Systematic Review.

Ample evidence exists that intensive care unit (ICU) treatment and invasive ventilation induce a transient or permanent decline in muscle mass and function. The functional deficit is often called ICU-acquired weakness with critical illness polyneuropathy (CIP) and/or myopathy (CIM) being the major underlying causes. Histopathological studies in ICU patients indicate loss of myosin filaments, muscle fiber necrosis, atrophy of both muscle fiber types as well as axonal degeneration.

The Novodiag Stool parasites assay, an innovative high-plex technique for fast detection of protozoa, helminths and microsporidia in stool samples: a retrospective and prospective study.

Objectives: We provide the first evaluation of the CE-IVD marked Novodiag stool parasites assay (NVD), allowing rapid and high-plex detection of 26 distinct targets, encompassing protozoans, helminths and microsporidia in stool samples.

Methods: A total of 254 samples (n = 205 patients) were prospectively processed by the NVD and our routine procedure (RP). Performances of the NVD were compared with RP.

Bioavailability of chromium, nickel, iron and manganese in relation to their speciation in coastal sediments downstream of ultramafic catchments: A case study in New Caledonia.

Coastal sediments downstream of ultramafic catchments can show Ni and Cr concentration well above sediment quality guidelines. Despite their potential ecological impact, the bioavailability of these trace metals in such sedimentary settings has been poorly investigated. In this study, we tried to fill this gap by performing kinetic EDTA-extractions across a shore-to-reef gradient in lagoon sediments downstream of an ultramafic catchment in New Caledonia and interpreting the results in regard of synchrotron-derived speciation.