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Chronic otitis media, inflammation of the middle ear, is a sequel to acute otitis media in ∼8% of children. Chronic otitis media with effusion is the most common cause of childhood deafness and is characterised by effusion of white blood cells into the auditory bulla cavity. Skull flat bones have trans-cortical vessels which are responsible for the majority of blood flow in and out of the bone. In experimental models of stroke and aseptic meningitis there is preferential recruitment of myeloid cells (neutrophils and monocytes) from the marrow in skull flat bones. We report trans-cortical vessels in the mouse temporal bone connect to the bulla mucosal vasculature and potentially represent a means to recruit myeloid cells directly into the inflamed bulla. The mutant mouse strains Junbo (MecomJbo/+) and Jeff (Fbxo11Jf/+) develop chronic otitis spontaneously; MecomJbo/+ mice have highly cellular neutrophil (90%) rich bulla exudates whereas Fbxo11Jf/+ mice have low cellularity serous effusions (5% neutrophils) indicating differing demand for neutrophil recruitment. However we found peripheral leukograms of MecomJbo/+ and Fbxo11Jf/+ mice are similar to their respective wild-type littermate controls with healthy bullae and infer preferential mobilization of myeloid cells from temporal bulla bone marrow may mitigate the need for a systemic inflammatory reaction. The cytokines, chemokines and haematopoietic factors found in the inflamed bulla represent candidate signalling molecules for myeloid cell mobilization from temporal bone marrow. The density of white blood cells in the bulla cavity is positively correlated with extent of mucosal thickening in MecomJbo/+, Fbxo11Jf/+, and EdaTa mice and is accompanied by changes in epithelial populations and bone remodelling. In MecomJbo/+ mice there was a positive correlation between bulla cavity WBC numbers and total bacterial load. The degree of inflammation varies between contralateral bullae and between mutant mice of different ages suggesting inflammation may wax and wane and may be re-initiated by a new wave of bacterial infection. Clearance of white blood cells and inflammatory stimuli from the bulla cavity is impaired and this may create a pro-inflammatory feedback loop which further exacerbates otitis media and delays its resolution.

Introduction: The aim of the study is to evaluate the effect of metformin in complication improvement of hospitalized patients with COVID-19. Methods: This was a randomized clinical trial that involved 189 patients with confirmed COVID-19 infection. Patients in the intervention group received metformin-500 mg twice daily. Patients who received metformin before admission were excluded from the control group. Patients who were discharged before taking at least 2000 mg of metformin were excluded from the study. Primary outcomes were vital signs, need for ICU admission, need for intubation, and mortality. Results: Data showed that patients with diabetes with previous metformin in their regimen had lower percentages of ICU admission and death in comparison with patients without diabetes (11.3% vs. 26.1% (p=0.014) and 4.9% vs. 23.9% (p=

In mice, rats, dogs and humans the growth and function of sebaceous glands and eyelid Meibomian glands depend on the ectodysplasin signalling pathway. Mutation of genes encoding the ligand EDA, its transmembrane receptor EDAR, and the intracellular signal transducer EDARADD leads to Hypohidrotic Ectodermal Dysplasia characterised by impaired development of teeth and hair as well as cutaneous glands. The rodent ear canal has a large auditory sebaceous gland, the Zymbal’s gland, whose function in the health of the ear canal and tympanic membrane has not been determined. We report that the EDA deficient Tabby (EdaTa) mouse, the EDAR deficient mouse (EdarOVE1B/OVE1B) and the EDARADD deficient sparse and wavy hair rat (Edaraddswh/swh) have Zymbal’s gland hypoplasia. EdaTa mice also have ear canal hypotrichosis and a 25% prevalence of otitis externa at P21. Treatment with agonist anti-EDAR antibodies rescues Zymbal’s glands and ear canal pilosebaceous units. The aetiopathogenesis of otitis externa involves infection with Gram-positive cocci and dosing pregnant and lactating EdaTa females and pups with Enrofloxacin reduces the prevalence of otitis externa. We infer the deficit of sebum is the principal factor in predisposition to bacterial infection and the EdaTa mouse is a potentially useful microbial challenge model for human acute otitis externa, commonly known as swimmer’s ear.

Acute otitis media, inflammation of the middle ear, is the most common bacterial infection in children and, as a consequence, is the most common reason for antimicrobial prescription to this age group. There is currently no effective vaccine for the principal pathogen involved, non-typeable Haemophilus influenzae (NTHi). The most frequently used and widely accepted experimental animal model of middle ear infection is in chinchillas, but mice and gerbils have also been used. We have established a robust model of middle ear infection by NTHi in the Junbo mouse, a mutant mouse line that spontaneously develops chronic middle ear inflammation in specific pathogen-free conditions. The heterozygote Junbo mouse (Jbo/+) bears a mutation in a gene (Evi1, also known as Mecom) that plays a role in host innate immune regulation; pre-existing middle ear inflammation promotes NTHi middle ear infection. A single intranasal inoculation with NTHi produces high rates (up to 90%) of middle ear infection and bacterial titres (104-105 colony-forming units/µl) in bulla fluids. Bacteria are cleared from the majority of middle ears between day 21 and 35 post-inoculation but remain in approximately 20% of middle ears at least up to day 56 post-infection. The expression of Toll-like receptor-dependent response cytokine genes is elevated in the middle ear of the Jbo/+ mouse following NTHi infection. The translational potential of the Junbo model for studying antimicrobial intervention regimens was shown using a 3 day course of azithromycin to clear NTHi infection, and its potential use in vaccine development studies was shown by demonstrating protection in mice immunized with killed homologous, but not heterologous, NTHi bacteria., Summary: Acute otitis media is an important disease in children. We describe a new infection model for translational research that uses the Junbo mouse mutant intranasally inoculated with non-typeable Haemophilus influenzae.

Summary Acute myeloid leukemia (AML) is an aggressive clonal disorder of hematopoietic stem cells (HSCs) and primitive progenitors that blocks their myeloid differentiation, generating self-renewing leukemic stem cells (LSCs). Here, we show that the mRNA m6A reader YTHDF2 is overexpressed in a broad spectrum of human AML and is required for disease initiation as well as propagation in mouse and human AML. YTHDF2 decreases the half-life of diverse m6A transcripts that contribute to the overall integrity of LSC function, including the tumor necrosis factor receptor Tnfrsf2, whose upregulation in Ythdf2-deficient LSCs primes cells for apoptosis. Intriguingly, YTHDF2 is not essential for normal HSC function, with YTHDF2 deficiency actually enhancing HSC activity. Thus, we identify YTHDF2 as a unique therapeutic target whose inhibition selectively targets LSCs while promoting HSC expansion., Graphical Abstract, Highlights • YTHDF2 is highly expressed across human AML and is essential for leukemia initiation • YTHDF2 shortens the half-life of m6A-modified transcripts in AML • Loss of YTHDF2 expands HSCs but does not derail hematopoiesis • YTHDF2 protects AML cells from apoptosis by downregulating TNFR2, Elimination of cancer stem cells in acute myeloid leukemia (AML) while preserving hematopoiesis is a challenge in leukemia treatment. Paris et al. demonstrate that inactivation of the RNA m6A reader YTHDF2 increases the half-life of m6A-modified transcripts and specifically compromises cancer stem cells, highlighting YTHDF2 as an essential regulator of AML.

Hypohidrotic ectodermal dysplasia (HED) results from mutation of the EDA, EDAR or EDARADD genes and is characterized by reduced or absent eccrine sweat glands, hair follicles and teeth, and defective formation of salivary, mammary and craniofacial glands. Mouse models with HED also carry Eda, Edar or Edaradd mutations and have defects that map to the same structures. Patients with HED have ear, nose and throat disease, but this has not been investigated in mice bearing comparable genetic mutations. We report that otitis media, rhinitis and nasopharyngitis occur at high frequency in Eda and Edar mutant mice and explore the pathogenic mechanisms related to glandular function, microbial and immune parameters in these lines. Nasopharynx auditory tube glands fail to develop in HED mutant mice and the functional implications include loss of lysozyme secretion, reduced mucociliary clearance and overgrowth of nasal commensal bacteria accompanied by neutrophil exudation. Heavy nasopharynx foreign body load and loss of gland protection alters the auditory tube gating function and the auditory tubes can become pathologically dilated. Accumulation of large foreign body particles in the bulla stimulates granuloma formation. Analysis of immune cell populations and myeloid cell function shows no evidence of overt immune deficiency in HED mutant mice. Our findings using HED mutant mice as a model for the human condition support the idea that ear and nose pathology in HED patients arises as a result of nasal and nasopharyngeal gland deficits, reduced mucociliary clearance and impaired auditory tube gating function underlies the pathological sequelae in the bulla.

Developed countries are initiating and implementing effective and appropriate technics in the field of teacher training. In Turkey, much research has been done in order to determine the qualification of teachers and, by this way, to train qualified teachers. Ministry of Education, Turkish Council of Higher Education, Faculties of Education and Faculties of Sciences have cooperated some certification systems, however, the research which is not supported by preliminary studies but exposured to political coercions lowered the quality of education. Besides, quantity is increased by pedagogical formation programs. In this study, Turkish teacher training system is analyzed with respect to quantity and quality.

Enerji ve enerji ile ilgili kavramların, soyut yapıları ve günlük hayatta bilimsel anlamlarından farklı olarak kullanılmalarından dolayı geleneksel yaklaşımlar ile öğretilmesinde ve öğrenilmesinde zorluklar yaşanmaktadır. Bu kavramların öğretilmesinde karşılaşılan diğer bir sorun ise, bu gibi soyut kavramların öğretiminde kullanılabilecek uygun öğretim materyallerinin yetersizliğidir. Yapılandırmacı yaklaşım öğrencilerin günlük yaşam deneyimlerine dayanmaktadır ve öğretim alanında soyut kavramların öğretiminde karşılaşılan zorlukların çözümünde bilgisayar teknolojisinin kullanımını tavsiye etmektedir. Bu nedenle öğrencilerin, görmelerinin imkânsız olduğu kadar küçük, sınıf ortamına getirilemeyecek kadar büyük ve günlük hayatta örnekleri gösterilemeyecek teorik kavramları somutlaştıracak ve öğrencilerin öğrenmelerini kolaylaştıracak bilgisayar destekli öğretim materyallerinin geliştirilmesi gerekmektedir. Bu çalışmanın amacı; 10. sınıf düzeyinde iş, güç ve enerji ünitesinin öğretiminde yapılandırmacı öğrenme yaklaşımına dayalı 5E öğrenme modeline göre bilgisayar destekli eğitime örnek oluşturacak bir öğretim materyali sunmaktır. Bu çalışmada olduğu gibi FATİH projesinde de 5E modeline uygun e-içerikler hazırlanabilir. Teaching and learning of the concept of energy and related concepts through traditional teaching methods are difficult since these concepts are abstract and their scientific meanings are different from their daily-life meanings. Moreover, another source of this difficulty is due to deficiency of appropriate teaching materials for such abstract concepts. Constructivist approach derives from students' real-world experiences and suggests the use of computer technology for solving these problems. Due to these reasons, there is a need to develop teaching materials in order to make science concepts concrete that are too theoretical to grab, too small to see, and too big to bring to class. The aim of this study is to introduce a computer-supported instructional material based upon 5E learning model regarding the “work, power and energy” unit for 10th grade level. Finally, e-contents of the FATIH Project might be designed according to the 5E learning model as done in this study.