Orm proteins control ceramide synthesis and endocytosis via LCB-mediated Ypk1 regulation.

Sphingolipids (SPLs) are major components of cell membranes with significant functions. Their production is a highly-regulated multi-step process with the formation of two major intermediates, long chain bases (LCBs) and ceramides. Homologous Orm proteins in both yeast and mammals negatively regulate LCB production by inhibiting serine palmitoyltransferase (SPT), the first enzyme in SPL de novo synthesis.

Step-wise evolution of azole resistance through copy number variation followed by KSR1 loss of heterozygosity in Candida albicans.

Antimicrobial drug resistance poses a global health threat, requiring a deeper understanding of the evolutionary processes that lead to its emergence in pathogens. Complex evolutionary dynamics involve multiple mutations that can result in cooperative or competitive (clonal interference) effects. Candida albicans, a major fungal pathogen, displays high rates of copy number variation (CNV) and loss of heterozygosity (LOH).

With age comes resilience: how mitochondrial modulation drives age-associated fluconazole tolerance in .

Unlabelled: () is an opportunistic fungal microorganism that causes life-threatening meningoencephalitis. During the infection, the microbial population is heterogeneously composed of cells with varying generational ages, with older cells accumulating during chronic infections. This is attributed to their enhanced resistance to phagocytic killing and tolerance of antifungals like fluconazole (FLC).

Distinct effect of calorie restriction between congenic mating types of Cryptococcus neoformans.

Cryptococcus neoformans (Cn) is an opportunistic yeast that causes meningoencephalitis in immunocompromised individuals. Calorie restriction (CR) prolongs Cn replicative lifespan (RLS) and mimics low-glucose environments in which Cn resides during infection. The effects of CR-mediated stress can differ among strains and have only been studied in MATα cells.

Erg251 has complex and pleiotropic effects on sterol composition, azole susceptibility, filamentation, and stress response phenotypes.

Ergosterol is essential for fungal cell membrane integrity and growth, and numerous antifungal drugs target ergosterol. Inactivation or modification of ergosterol biosynthetic genes can lead to changes in antifungal drug susceptibility, filamentation and stress response. Here, we found that the ergosterol biosynthesis gene ERG251 is a hotspot for point mutations during adaptation to antifungal drug stress within two distinct genetic backgrounds of Candida albicans.

MBX-7591: a promising drug candidate against drug-resistant fungal infections.

Invasive fungal infections (IFIs) caused by pathogenic fungi pose a significant public health concern, particularly for immunocompromised individuals. Mortality rates for IFIs remain high, and currently available treatment options are limited. Existing antifungal agents often suffer from limited clinical efficacy, poor fungicidal activity within the host, potential toxicity, and increasing ineffectiveness due to emerging resistance, especially against triazole drugs, the current mainstay of antifungal treatment.

Pertussis outbreak in neonates and young infants across Italy, January to May 2024: implications for vaccination strategies.

Since January 2024, Italy experiences a pertussis outbreak, primarily affecting neonates and unvaccinated infants at high risk of severe complications and mortality; 11 major paediatric centres noted 108 hospitalisations and three deaths by 10 May. The outbreak reflects increased circulation of and non-adherence to immunisation recommendations during pregnancy. Public health interventions, including maternal immunisation, vaccination of infants as early as possible and post-exposure prophylaxis, are critical for reducing the burden of pertussis and preventing further mortality.

Vaccine Strategies for Cryptococcus neoformans.

Cryptococcus neoformans infections are a major worldwide concern as current treatment strategies are becoming less effective in alleviating the infection. The most extreme and fatal cases are those of immunocompromised individuals. Clinical treatments for cryptococcosis are limited to a few classes of approved drugs, and due to a rise in drug resistance, these drugs are becoming less effective.

Biofilm-associated metabolism via ERG251 in Candida albicans.

Biofilm formation by the fungal pathogen Candida albicans is the basis for its ability to infect medical devices. The metabolic gene ERG251 has been identified as a target of biofilm transcriptional regulator Efg1, and here we report that ERG251 is required for biofilm formation but not conventional free-living planktonic growth. An erg251Δ/Δ mutation impairs biofilm formation in vitro and in an in vivo catheter infection model.

Dalbavancin for Acute Bacterial Skin and Skin Structure Infections in Pediatrics: Insights from Continuation Therapy Experience.

Acute Bacterial Skin and Skin Structure Infections (ABSSSI) are marked by substantial morbidity, frequent need for hospitalization, and long courses of intravenous antibiotic therapy. Herein, we report four cases of pediatric patients admitted for ABSSSI and managed with a combination antibiotic regimen incorporating dalbavancin: a second-generation lipoglycopeptide active against Gram-positive bacteria, including methicillin-resistant . In our experience, particularly in a setting with a high methicillin-resistance rate, dalbavancin demonstrated safety and efficacy, simplifying ABSSSI management in childhood.

Combination therapy of itraconazole and an acylhydrazone derivative (D13) for the treatment of sporotrichosis in cats.

Unlabelled: Acylhydrazone (AH) derivatives represent a novel category of anti-fungal medications that exhibit potent activity against sp., both and in a murine model of sporotrichosis. In this study, we demonstrated the anti-fungal efficacy of the AH derivative D13 [4-bromo-'-(3,5-dibromo-2-hydroxybenzylidene)-benzohydrazide] against both planktonic cells and biofilms formed by .

SAR study of N'-(Salicylidene)heteroarenecarbohydrazides as promising antifungal agents.

Clinically available antifungal drugs have therapeutic limitations due to toxicity, narrow spectrum of activity, and intrinsic or acquired drug resistance. Thus, there is an urgent need for new broad-spectrum antifungal agents with low toxicity and a novel mechanism of action. In this context, we have successfully identified several highly promising lead compounds, i.

Aetiology, risk factors and microbiota composition in children with prolonged diarrhoea: A prospective case-controlled cohort study.

Aim: Prolonged diarrhoea (ProD) refers to acute-onset diarrhoea that persists for longer than 1 week. As the aetiology, risk factors and management are poorly defined, we prospectively enrolled children hospitalised in a high-income setting to assess these outcomes and investigate the potential role of gut microbiota.

Methods: All children aged 30 days to 14 years admitted for acute-onset diarrhoea lasting 7-14 days were included.

Solid Lipid Nanoparticles Containing Dopamine and Grape Seed Extract: Freeze-Drying with Cryoprotection as a Formulation Strategy to Achieve Nasal Powders.

(1) Background: DA-Gelucire 50/13-based solid lipid nanoparticles (SLNs) administering the neurotransmitter dopamine (DA) and the antioxidant grape-seed-derived proanthocyanidins (grape seed extract, GSE) have been prepared by us in view of a possible application for Parkinson's disease (PD) treatment. To develop powders constituted by such SLNs for nasal administration, herein, two different agents, namely sucrose and methyl-β-cyclodextrin (Me-β-CD), were evaluated as cryoprotectants. (2) Methods: SLNs were prepared following the melt homogenization method, and their physicochemical features were investigated by Raman spectroscopy, Scanning Electron Microscopy (SEM), atomic force microscopy (AFM) and X-ray Photoelectron Spectroscopy (XPS).

Postbiotic Preparation of against Diarrhea and Oxidative Stress Induced by Spike Protein of SARS-CoV-2 in Human Enterocytes.

The Spike protein of SARS-CoV-2 acts as an enterotoxin able to induce chloride secretion and production of reactive oxygen species (ROS), involved in diarrhea pathogenesis. (LGG) is recommended in pediatric acute gastroenteritis guidelines as a therapy independent of infectious etiology. We tested a postbiotic preparation of LGG (mLGG) in an in vitro model of COVID-associated diarrhea.

Role of sphingolipids in the host-pathogen interaction.

Fungal pathogens have been under the spotlight as their expanding geographic range combined with their potential harm to vulnerable populations turns them into increasingly threats to public health. Therefore, it is ultimately important to unveil the mechanisms associated with their infection process for further new treatment discovery. With this purpose, sphingolipid-based research has gained attention over the last years as these molecules have key properties that can regulate fungal pathogenicity.

Altered plasma levels of apixaban in major gastrointestinal tract surgery: A case report and review of the literature.

Altered direct oral anticoagulant (DOAC) plasma levels can lead either to spontaneous hemorrhagic or thrombotic complications. We describe a case of suspected altered apixaban disposition in a patient with an upper gastrointestinal cancer resection treated with apixaban for non-valvular atrial fibrillation. Diagnosis of ischemic stroke for left hemiparesis was confirmed due to recent emergence of a hypodense area in the posterior capsular nucleus of ischemic reference in a context of binuclear capsular lacunar lesions.

Gastroenteritis is Less Severe But is More Often Associated With Systemic Inflammation in SARS-CoV-2-positive Than in SARS-CoV-2-Negative Children.

This study aims to characterize the clinical and metabolic features of acute gastroenteritis in children with and without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A multicenter case-control study was conducted in 2022 including 200 children. Clinical data and laboratory tests were analyzed.