Destruction of the brush border by sv. Typhimurium subverts resorption by polarized epithelial cells.

serovar Typhimurium is an invasive, facultative intracellular gastrointestinal pathogen that destroys the brush border of polarized epithelial cells (PEC). The brush border is critical for the functions of PEC because it resorbs nutrients from the intestinal lumen and builds a physical barrier to infecting pathogens. The manipuation of PEC during infection by was investigated by live-cell imaging and ultrastructural analysed of the brush border.

Cell death induction facilitates egress of Coxiella burnetii from infected host cells at late stages of infection.

Intracellular bacteria have evolved mechanisms to invade host cells, establish an intracellular niche that allows survival and replication, produce progeny, and exit the host cell after completion of the replication cycle to infect new target cells. Bacteria exit their host cell by (i) initiation of apoptosis, (ii) lytic cell death, and (iii) exocytosis. While bacterial egress is essential for bacterial spreading and, thus, pathogenesis, we currently lack information about egress mechanisms for the obligate intracellular pathogen C.

Balloon Eustachian tuboplasty for obstructive Eustachian tube dysfunction: retrospective multicentre cohort study of 248 patients.

Objective: To present the results after balloon eustachian tuboplasty (BET) in patients with obstructive Eustachian tube dysfunction (OETD) grouped up into: baro-challenge, chronic serous otitis media and adhaesive otitis media.

Methods: A retrospective study was carried out on patients who underwent BET surgery. As outcome measures, otoscopy, tympanometry, Eustachian tube dysfunction questionnaire-7 (ETDQ-7) and ability to perform the Valsalva manoeuvre were recorded at baseline and at 3, 12 and 24 months after BET.

Manipulation of microvillar proteins during invasion results in brush border effacement and actin remodeling.

Enterocyte invasion by the gastrointestinal pathogen is accompanied by loss of brush border and massive remodeling of the actin cytoskeleton, leading to microvilli effacement and formation of membrane ruffles. These manipulations are mediated by effector proteins translocated by the Pathogenicity Island 1-encoded type III secretion system (SPI1-T3SS). To unravel the mechanisms of microvilli effacement and contribution of SPI1-T3SS effector proteins, the dynamics of host-pathogen interactions was analyzed using live cell imaging (LCI) of polarized epithelial cells (PEC) expressing LifeAct-GFP.

The Public Discussion on Flat Earth Movement: An Analysis Based on the Esperantist‑Epideictic Discourse.

The paper reflects on public discourses about science and pseudoscience, proposing the same discursive structure for both-the Esperantist-Epideictic genre. This genre of discourse might bring together characteristics that we understand as constituents of the public discourse on science. It also enables us to depict the process by which to maintain cohesion on a group's values.

Promoting critical thinking in an online, project-based course.

Education institutions are expected to contribute to the development of students' critical thinking skills. Due to COVID-19, there has been a surge in interest in online teaching. The aim of this study is therefore to design a strategy to promote critical thinking in an online setting for first year undergraduates.

Taking critical thinking, creativity and grit online.

Technology has the potential to facilitate the development of higher-order thinking skills in learning. There has been a rush towards online learning by education systems during COVID-19; this can therefore be seen as an opportunity to develop students' higher-order thinking skills. In this short report we show how critical thinking and creativity can be developed in an online context, as well as highlighting the importance of grit.

Methicillin-resistant colonization in patients undergoing primary total hip arthroplasty.

Nasal and skin colonization by methicillin-resistant (MRSA) are linked to a higher incidence of infection after total joint replacement. The prevalence of colonization is poorly defined in Latin American countries. The aim of the present study was to determine the prevalence of MRSA colonization in the nostrils and groin using real-time polymerase chain reaction (RT-PCR) in patients undergoing total hip arthroplasty (THA).

A Plasmid-Encoded FetMP-Fls Iron Uptake System Confers Selective Advantages to Serovar Typhimurium in Growth under Iron-Restricted Conditions and for Infection of Mammalian Host Cells.

The resistance plasmid pUO-StVR2, derived from virulence plasmid pSLT, is widespread in clinical isolates of serovar Typhimurium recovered in Spain and other European countries. pUO-StVR2 carries several genes encoding a FetMP-Fls system, which could be involved in iron uptake. We therefore analyzed .

Aged garlic extract and S-allylcysteine increase the GLUT3 and GCLC expression levels in cerebral ischemia.

Background: During cerebral ischemia, energy restoration through the regulation of glucose transporters and antioxidant defense mechanisms is essential to maintain cell viability. Antioxidant therapy has been considered effective to attenuate brain damage; moreover, the regulation of transcription factors that positively regulate the expression of glucose transporters is associated with this therapy. Recently, it has been reported that the use of antioxidants such as S-allylcysteine (SAC), a component of aged garlic extract (AGE), improves survival in experimental models of cerebral ischemia.

In vitro and sensory tests to design easy-to-swallow multi-particulate formulations.

Flexible dosing and ease of swallowing are key factors when designing oral drug delivery systems for paediatric and geriatric populations. Multi-particulate oral dosage forms can offer significant benefits over conventional capsules and tablets. This study proposes the use of an in vitro model to quantitatively investigate the swallowing dynamics in presence of multi-particulates.

High cortactin expression in B-cell acute lymphoblastic leukemia is associated with increased transendothelial migration and bone marrow relapse.

Cancer is a major cause of death in children worldwide, with B-lineage cell acute lymphoblastic leukemia (B-ALL) being the most frequent childhood malignancy. Relapse, treatment failure and organ infiltration worsen the prognosis, warranting a better understanding of the implicated mechanisms. Cortactin is an actin-binding protein involved in cell adhesion and migration that is overexpressed in many solid tumors and in adult B-cell chronic lymphocytic leukemia.

Homoectoine Protects Against Colitis by Preventing a Claudin Switch in Epithelial Tight Junctions.

Background: Inflammatory bowel diseases (IBD) are multifactorial disorders affecting millions of people worldwide with alarmingly increasing incidences every year. Dysfunction of the intestinal epithelial barrier is associated with IBD pathogenesis, and therapies include anti-inflammatory drugs that enhance intestinal barrier function. However, these drugs often have adverse side effects thus warranting the search for alternatives.

The effect of administration media on palatability and ease of swallowing of multiparticulate formulations.

Multiparticulate formulations based on pellets, granules or beads, could be advantageous for paediatrics, geriatrics and patients with swallowing difficulties. However, these formulations may require suitable administration media to facilitate administration. The aim of this work was to investigate the effect of administration media properties on palatability and ease of swallowing of multiparticulates.

Co-Processed Excipients for Dispersible Tablets-Part 2: Patient Acceptability.

Palatability and patient acceptability are critical attributes of dispersible tablet formulation. Co-processed excipients could provide improved organoleptic profile due to rational choice of excipients and manufacturing techniques. The aim of this study was to identify the most suitable co-processed excipient to use within directly compressible dispersible tablet formulations.

Co-Processed Excipients for Dispersible Tablets-Part 1: Manufacturability.

Co-processed excipients may enhance functionality and reduce drawbacks of traditional excipients for the manufacture of tablets on a commercial scale. The following study aimed to characterise a range of co-processed excipients that may prove suitable for dispersible tablet formulations prepared by direct compression. Co-processed excipients were lubricated and compressed into 10.

Acceptability of placebo multiparticulate formulations in children and adults.

Patient acceptability is an important consideration in the design of medicines for children. The aim of this study was to investigate acceptability of multiparticulates in healthy children and adults. A randomised, single-blind acceptability testing was performed involving 71 children (4-12 years) and 61 adults (18-37 years).

Methodologies for assessing the acceptability of oral formulations among children and older adults: a systematic review.

Acceptability of medicinal products in children and older populations is pivotal in ensuring adherence and therapeutic outcomes. This review systematically identifies studies reporting on formulation aspects of oral medications that affect their acceptability in these patient groups. Particular emphasis is placed on the evaluation of the methodologies employed in the studies.

Identifying uncertainty in laser powder bed fusion additive manufacturing models.

As additive manufacturing (AM) matures, models are beginning to take a more prominent stage in design and process planning for AM. A limitation frequently encountered in AM models is a lack of indication about their precision and accuracy. Often overlooked, information on model uncertainty is required for validation of AM models, qualification of AM-produced parts, and uncertainty management.

Effect of formulation variables on oral grittiness and preferences of multiparticulate formulations in adult volunteers.

Multiparticulate formulations are composed of multiple solid dosage units which can be administered directly to the mouth or sprinkled on food. Oral grittiness (i.e.

Patient centric formulations for paediatrics and geriatrics: Similarities and differences.

Paediatrics and geriatrics both represent highly heterogenous populations and require special consideration when developing appropriate dosage forms. This paper discusses similarities, differences and considerations with respect to the development of appropriate medicine formulations for paediatrics and geriatrics. Arguably the most significant compliance challenge in older people is polypharmacy, whereas for children the largest barrier is taste.

Formulation approaches to pediatric oral drug delivery: benefits and limitations of current platforms.

Introduction: Most conventional drug delivery systems are not acceptable for pediatric patients as they differ in their developmental status and dosing requirements from other subsets of the population. Technology platforms are required to aid the development of age-appropriate medicines to maximize patient acceptability while maintaining safety, efficacy, accessibility and affordability.

Areas Covered: The current approaches and novel developments in the field of age-appropriate drug delivery for pediatric patients are critically discussed including patient-centric formulations, administration devices and packaging systems.

Amorphous formulations of indomethacin and griseofulvin prepared by electrospinning.

Following an array of optimization experiments, two series of electrospun polyvinylpyrrolidone (PVP) fibers were prepared. One set of fibers contained various loadings of indomethacin, known to form stable glasses, and the other griseofulvin (a poor glass former). Drug loadings of up to 33% w/w were achieved.

Salmonella enterica invasion of polarized epithelial cells is a highly cooperative effort.

The invasion of polarized epithelial cells by Salmonella enterica requires the cooperative activity of the Salmonella pathogenicity island 1 (SPI1)-encoded type III secretion system (T3SS) and the SPI4-encoded adhesin SiiE. The invasion of polarized cells is more efficient than that of nonpolarized cells, and we observed the formation of clusters of bacteria on infected cells. Here we demonstrate that the invasion of polarized cells is a highly cooperative activity.

A trimeric lipoprotein assists in trimeric autotransporter biogenesis in enterobacteria.

Trimeric autotransporter adhesins (TAAs) are important virulence factors of many Gram-negative bacterial pathogens. TAAs form fibrous, adhesive structures on the bacterial cell surface. Their N-terminal extracellular domains are exported through a C-terminal membrane pore; the insertion of the pore domain into the bacterial outer membrane follows the rules of β-barrel transmembrane protein biogenesis and is dependent on the essential Bam complex.