Knockdown of microglial iron import gene, Slc11a2, worsens cognitive function and alters microglial transcriptional landscape in a sex-specific manner in the APP/PS1 model of Alzheimer's disease.

Background: Microglial cell iron load and inflammatory activation are significant hallmarks of late-stage Alzheimer's disease (AD). In vitro, microglia preferentially upregulate the iron importer, divalent metal transporter 1 (DMT1, gene name Slc11a2) in response to inflammatory stimuli, and excess iron can augment cellular inflammation, suggesting a feed-forward loop between iron import mechanisms and inflammatory signaling. However, it is not understood whether microglial iron import mechanisms directly contribute to inflammatory signaling and chronic disease in vivo.

College students' utilization of the Internet to search for mental health information: Effects on mental health literacy, stigma, and help-seeking.

Objective: The current study examined how college students search online for mental health information and the impact of these searches on mental health literacy, stigma, and help-seeking.

Method: Undergraduate participants ( = 270; Fall 2015 to Spring 2019) were randomly assigned to search online for information about coping with anxiety for themselves or a friend (experimental activity), or to utilize Google Maps to answer navigational questions (control).

Results: Participants who conducted an online search demonstrated greater mental health literacy including optimism about psychotherapy, and lower levels of certain types of stigma, but lower willingness to seek/recommend professional help.

A new model of endotracheal tube biofilm identifies combinations of matrix-degrading enzymes and antimicrobials able to eradicate biofilms of pathogens that cause ventilator-associated pneumonia.

Ventilator-associated pneumonia is defined as pneumonia that develops in a patient who has been on mechanical ventilation for more than 48 hours through an endotracheal tube. It is caused by biofilm formation on the indwelling tube, which introduces pathogenic microbes such as , and into the patient's lower airways. Currently, there is a lack of accurate models of ventilator-associated pneumonia development.

Ascorbate insufficiency disrupts glutamatergic signaling and alters electroencephalogram phenotypes in a mouse model of Alzheimer's disease.

Clinical studies have reported that increased epileptiform and subclinical epileptiform activity can be detected in many patients with an Alzheimer's disease (AD) diagnosis using electroencephalogram (EEG) and this may correlate with poorer cognition. Ascorbate may have a specific role as a neuromodulator in AD as it is released concomitantly with glutamate reuptake following excitatory neurotransmission. Insufficiency may therefore result in an exacerbated excitatory/inhibitory imbalance in neuronal signaling.

Knockdown of microglial iron import gene, DMT1, worsens cognitive function and alters microglial transcriptional landscape in a sex-specific manner in the APP/PS1 model of Alzheimer's disease.

Background: Microglial cell iron load and inflammatory activation are significant hallmarks of late-stage Alzheimer's disease (AD). , microglia preferentially upregulate the iron importer, divalent metal transporter 1 (DMT1, gene name ) in response to inflammatory stimuli, and excess iron can augment cellular inflammation, suggesting a feed-forward loop between iron import mechanisms and inflammatory signaling. However, it is not understood whether microglial iron import mechanisms directly contribute to inflammatory signaling and chronic disease .

Modulation of microglia activation by the ascorbic acid transporter SVCT2.

Neuroinflammation is a major characteristic of pathology in several neurodegenerative diseases. Microglia, the brain's resident myeloid cells, shift between activation states under neuroinflammatory conditions, both responding to, but also driving damage in the brain. Vitamin C (ascorbate) is an essential antioxidant for central nervous system function that may have a specific role in the neuroinflammatory response.

How Does Airway Surface Liquid Composition Vary in Different Pulmonary Diseases, and How Can We Use This Knowledge to Model Microbial Infections?

Growth environment greatly alters many facets of pathogen physiology, including pathogenesis and antimicrobial tolerance. The importance of host-mimicking environments for attaining an accurate picture of pathogen behaviour is widely recognised. Whilst this recognition has translated into the extensive development of artificial cystic fibrosis (CF) sputum medium, attempts to mimic the growth environment in other respiratory disease states have been completely neglected.

Systemic inflammation and delirium during critical illness.

Purpose: The purpose of this study was to determine associations between markers of inflammation and endogenous anticoagulant activity with delirium and coma during critical illness.

Methods: In this prospective cohort study, we enrolled adults with respiratory failure and/or shock treated in medical or surgical intensive care units (ICUs) at 5 centers. Twice per day in the ICU, and daily thereafter, we assessed mental status using the Richmond Agitation Sedation Scale (RASS) and the Confusion Assessment Method-Intensive Care Unit (CAM-ICU).

Differential development of antibiotic resistance and virulence between species.

Unlabelled: The two species that account for most cases of -associated bacteremia in the United Kingdom are , often a commensal but also an emerging pathogen, and , a well-known antibiotic-resistant species. While these species both cause similar types of human infection and occupy the same niche, (unlike ) has thus far remained susceptible to antibiotics. Comparatively little is known about the biology of , and this is the largest study on it conducted to date, providing valuable insights into its behaviour and potential threat to human health.

Improving Healthcare Quality and Clinical Outcomes for Persons with Dementia in the Sub-Acute Hospital Through Person-Centered Care Practice.

Background: Person-centered care is considered beneficial for persons with dementia.

Objective: To evaluate the impact of a person-centered knowledge translation intervention on the quality of healthcare and outcomes for persons with dementia.

Methods: Over nine months, sub-acute hospital nursing, allied health, and medical staff (n = 90) participated in online and/or face-to-face person-centered education and were supported by senior nursing, allied health, and medical staff champions (n = 8) to implement person-centered healthcare.

Ascorbic acid and its transporter SVCT2, affect radial glia cells differentiation in postnatal stages.

Radial glia (RG) cells generate neurons and glial cells that make up the cerebral cortex. Both in rodents and humans, these stem cells remain for a specific time after birth, named late radial glia (lRG). The knowledge of lRG and molecules that may be involved in their differentiation is based on very limited data.

Partial Egg Consumption Modifies the Diagnostic Performance of Allergy Tests to Predict Outcome of Double-Blind Placebo-Controlled Food Challenges to Egg.

Background: Many children are consuming some egg when they are diagnosed with egg allergy. We hypothesized that egg consumption could modify the diagnostic performance of allergy tests.

Objective: To stratify diagnostic performance of tests according to egg consumption status.

Microglial-specific knockdown of iron import gene, Slc11a2, blunts LPS-induced neuroinflammatory responses in a sex-specific manner.

Neuroinflammation and microglial iron load are significant hallmarks found in several neurodegenerative diseases. In in vitro systems, microglia preferentially upregulate the iron importer, divalent metal transporter 1 (DMT1, gene name Slc11a2) in response to inflammatory stimuli, and it has been shown that iron can augment cellular inflammation, suggesting a feed-forward loop between mechanisms involved in iron import and inflammatory signaling. However, it is not understood how microglial iron import mechanisms contribute to inflammation in vivo, or whether altering a microglial iron-related gene affects the inflammatory response.

Development of a Peripherally Restricted 5-HT Partial Agonist for Treatment of Pulmonary Arterial Hypertension.

Ligands for the serotonin 2B receptor (5-HT) have shown potential to treat pulmonary arterial hypertension in preclinical models but cannot be used in humans because of predicted off-target neurological effects. The aim of this study was to develop novel systemically restricted compounds targeting 5-HT. Here, we show that mice treated with VU6047534 had decreased RVSP compared with control treatment in both the prevention and intervention studies using Sugen-hypoxia.

Insight into What Is inside Swift Heavy Ion Latent Tracks in PET Film.

We present here a novel experimental study of changes after contact electrification in the optical transmission spectra of samples of both pristine and irradiated PET film treated with Kr ions of energy of 1.75 MeV and a fluence of 3 × 10 cm. We used a non-standard electrification scheme for injecting electrons into the film by applying negative electrodes to both its surfaces and using the positively charged inner regions of the film itself as the positive electrode.

Basophil activation test as predictor of severity and threshold of allergic reactions to egg.

Background: Identifying patients at risk of severe allergic reactions and/or low threshold of reactivity is very important, particularly for staple foods like egg.

Methods: One hundred and fifty children underwent double-blind placebo-controlled food challenge (DBPCFC) to baked egg (BE), skin prick testing and blood collection for serology and basophil activation test (BAT). Patients who passed BE DBPCFC underwent loosely cooked egg (LCE) DBPCFC.

Have you tried turning it off and on again? Oscillating selection to enhance fitness-landscape traversal in adaptive laboratory evolution experiments.

Adaptive Laboratory Evolution (ALE) is a powerful tool for engineering and understanding microbial physiology. ALE relies on the selection and enrichment of mutations that enable survival or faster growth under a selective condition imposed by the experimental setup. Phenotypic fitness landscapes are often underpinned by complex genotypes involving multiple genes, with combinatorial positive and negative effects on fitness.

Mechanism of Action of Oxazoline-Based Antimicrobial Polymers Against Staphylococcus aureus: In Vivo Antimicrobial Activity Evaluation.

Antimicrobial-resistant pathogens have reached alarming levels, becoming one of the most pressing global health issues. Hence, new treatments are necessary for the fight against antimicrobial resistance. Synthetic nanoengineered antimicrobial polymers (SNAPs) have emerged as a promising alternative to antimicrobial peptides, overcoming some of their limitations while keeping their key features.

Pilot Randomized, Double-Blind, Placebo-Controlled Crossover Trial Evaluating the Feasibility of an Intranasal Oxytocin in Improving Social Cognition in Individuals Living with Alzheimer's Disease.

Background: Individuals living with Alzheimer's disease (AD) demonstrate extensive deficits in social cognition. To date, no studies have investigated the feasibility of an intranasal oxytocin (INOT) treatment to improve social cognition in individuals living with AD.

Objective: We conducted a pilot trial to determine recruitment feasibility, enrolment acceptability, and adherence to an INOT treatment to inform on the subsequent design of a future randomized controlled trial (RCT).

Mitigating neurological, cognitive, and psychiatric sequelae of COVID-19-related critical illness.

Despite advances in the treatment and mitigation of critical illness caused by infection with SARS-CoV-2, millions of survivors have a devastating, post-acute infection syndrome known as long COVID. A large proportion of patients with long COVID have nervous system dysfunction, which is also seen in the distinct but overlapping condition of post-intensive care syndrome (PICS), putting survivors of COVID-19-related critical illness at high risk of long-lasting morbidity affecting multiple organ systems and, as a result, engendering measurable deficits in quality of life and productivity. In this Series paper, we discuss neurological, cognitive, and psychiatric sequelae in patients who have survived critical illness due to COVID-19.

Sweet and sour synergy: exploring the antibacterial and antibiofilm activity of acetic acid and vinegar combined with medical-grade honeys.

, a combination of honey and vinegar, has been used as a remedy for wounds and infections in historical and traditional medical settings. While honey is now clinically used to treat infected wounds, this use of a complex, raw natural product (NP) mixture is unusual in modern western medicine. Research into the antimicrobial activity of NPs more usually focuses on finding a single active compound.

Diagnostic utility of allergy tests to predict baked egg and lightly cooked egg allergies compared to double-blind placebo-controlled food challenges.

Background: Double-blind placebo-controlled food challenges (DBPCFC) are the gold-standard to diagnose food allergy. However, they can cause allergic reactions of unpredictable severity. We assessed accuracy of current and new diagnostic tests compared to DBPCFC to baked egg (BE) and to lightly cooked egg (LCE).