Integrating virtual patients into undergraduate health professions curricula: a framework synthesis of stakeholders' opinions based on a systematic literature review.

Background: Virtual patients (VPs) are widely used in health professions education. When they are well integrated into curricula, they are considered to be more effective than loosely coupled add-ons. However, it is unclear what constitutes their successful integration.

Medical education in times of war: a mixed-methods needs analysis at Ukrainian medical schools.

Background: As Ukraine struggles with the education of healthcare professionals due to the war, we aimed to identify the specific effects of the war on medical education, the resulting needs, and the expected consequences for schools, faculty, staff, students, and the healthcare system.

Methods: In October and November 2022, we performed a survey of students, faculty, and staff of medical schools in Ukraine and conducted semi-structured interviews with faculty leaders (i.e.

Planning a Collection of Virtual Patients to Train Clinical Reasoning: A Blueprint Representative of the European Population.

Background: Virtual patients (VPs) are a suitable method for students to train their clinical reasoning abilities. We describe a process of developing a blueprint for a diverse and realistic VP collection (prior to VP creation) that facilitates deliberate practice of clinical reasoning and meets educational requirements of medical schools.

Methods: An international and interdisciplinary partnership of five European countries developed a blueprint for a collection of 200 VPs in four steps: (1) Defining the criteria (e.

Paternal Uniparental Isodisomy of Chromosome 2 in a Patient with -Associated Autosomal Recessive Achromatopsia.

Achromatopsia (ACHM) is a rare autosomal recessively inherited retinal disease characterized by congenital photophobia, nystagmus, low visual acuity, and absence of color vision. ACHM is genetically heterogeneous and can be caused by biallelic mutations in the genes , , , , , or . We undertook molecular genetic analysis in a single female patient with a clinical diagnosis of ACHM and identified the homozygous variant c.

Homozygous stop mutation in AHR causes autosomal recessive foveal hypoplasia and infantile nystagmus.

Herein we present a consanguineous family with three children affected by foveal hypoplasia with infantile nystagmus, following an autosomal recessive mode of inheritance. The patients showed normal electroretinography responses, no signs of albinism, and no anterior segment or brain abnormalities. Upon whole exome sequencing, we identified a homozygous mutation (c.

Vulnerability of frontal brain neurons for the toxicity of expanded ataxin-3.

Spinocerebellar ataxia type 3 (SCA3) is caused by the expansion of CAG repeats in the ATXN3 gene leading to an elongated polyglutamine tract in the ataxin-3 protein. Previously, we demonstrated that symptoms of SCA3 are reversible in the first conditional mouse model for SCA3 directing ataxin-3 predominantly to the hindbrain. Here, we report on the effects of transgenic ataxin-3 expression in forebrain regions.

Accessory heterozygous mutations in cone photoreceptor CNGA3 exacerbate CNG channel-associated retinopathy.

Mutations in CNGA3 and CNGB3, the genes encoding the subunits of the tetrameric cone photoreceptor cyclic nucleotide-gated ion channel, cause achromatopsia, a congenital retinal disorder characterized by loss of cone function. However, a small number of patients carrying the CNGB3/c.1208G>A;p.

Correction: Mapping the genomic landscape of inherited retinal disease genes prioritizes genes prone to coding and noncoding copy-number variations.

The original version of this Article contained an error in the spelling of the author Anja K. Mayer, which was incorrectly given as Anja Kathrin Mayer. This has now been corrected in both the PDF and HTML versions of the Article.

CNGB3 mutation spectrum including copy number variations in 552 achromatopsia patients.

Achromatopsia is a rare autosomal recessive cone disorder characterized by color vision defects, photophobia, nystagmus, and severely reduced visual acuity. The disease is caused by mutations in genes encoding crucial components of the cone phototransduction cascade (CNGA3, CNGB3, GNAT2, PDE6C, and PDE6H) or in ATF6, involved in the unfolded protein response. CNGB3 encoding the beta subunit of the cyclic nucleotide-gated ion channel in cone photoreceptors is the major achromatopsia gene.

CDHR1 mutations in retinal dystrophies.

We report ophthalmic and genetic findings in patients with autosomal recessive retinitis pigmentosa (RP), cone-rod dystrophy (CRD) or cone dystrophy (CD) harboring potential pathogenic variants in the CDHR1 gene. Detailed ophthalmic examination was performed in seven sporadic and six familial subjects. Mutation screening was done using a customized next generation sequencing panel targeting 105 genes implicated in inherited retinal disorders.

Mutation Detection in Patients with Retinal Dystrophies Using Targeted Next Generation Sequencing.

Retinal dystrophies (RD) constitute a group of blinding diseases that are characterized by clinical variability and pronounced genetic heterogeneity. The different nonsyndromic and syndromic forms of RD can be attributed to mutations in more than 200 genes. Consequently, next generation sequencing (NGS) technologies are among the most promising approaches to identify mutations in RD.

Homozygosity mapping and whole-genome sequencing reveals a deep intronic PROM1 mutation causing cone-rod dystrophy by pseudoexon activation.

Several genes have been implicated in the autosomal recessive form of cone-rod dystrophy (CRD), but the majority of cases remain unsolved. We identified a homozygous interval comprising two known genes associated with the autosomal recessive form of CRD, namely RAB28 and PROM1, in a consanguineous family with clinical evidence of CRD. Both genes proved to be mutation negative upon sequencing of exons and canonical splice sites but whole-genome sequencing revealed a private variant located deep in intron 18 of PROM1.

Prime/boost immunization with DNA and adenoviral vectors protects from hepatitis D virus (HDV) infection after simultaneous infection with HDV and woodchuck hepatitis virus.

Hepatitis D virus (HDV) superinfection of hepatitis B virus (HBV) carriers causes severe liver disease and a high rate of chronicity. Therefore, a vaccine protecting HBV carriers from HDV superinfection is needed. To protect from HDV infection an induction of virus-specific T cells is required, as antibodies to the two proteins of HDV, p24 and p27, do not neutralize the HBV-derived envelope of HDV.

DNA prime-adenovirus boost immunization induces a vigorous and multifunctional T-cell response against hepadnaviral proteins in the mouse and woodchuck model.

Induction of hepatitis B virus (HBV)-specific cytotoxic T cells by therapeutic immunization may be a strategy to treat chronic hepatitis B. In the HBV animal model, woodchucks, the application of DNA vaccine expressing woodchuck hepatitis virus (WHV) core antigen (WHcAg) in combination with antivirals led to the prolonged control of viral replication. However, it became clear that the use of more potent vaccines is required to overcome WHV persistence.

Extractable organic matter of standard reference material 1649a influences immunological response induced by pathogen-associated molecular patterns.

Background, Aim, And Scope: Lungs are permanently and simultaneously challenged by airborne microorganisms and airborne pollutants. Temporal increase of airborne particulate matter (APM), a potential carrier for extractable organic matter (EOM), degrades the situation of pulmonary patients. The Ah receptor (AhR) has been described as an important factor influencing the immunological challenge by viral infections.

Airway epithelial cells modify immune responses by inducing an anti-inflammatory microenvironment.

The upper airways are prone to contact with pathogenic as well as non-pathogenic microbes, therefore immune recognition principles have to be tightly controlled. Here we show that human BEAS-2B bronchial epithelial cells inhibited secretion of the pro-inflammatory cytokines TNF-alpha and IL-12 by monocytes, macrophages and dendritic cells. This inhibitory effect could be transferred by supernatant of resting BEAS-2B cells and was also observed when primary murine tracheal epithelial cells were prepared.

Regulation of local immunity by airway epithelial cells.

Epithelial cells are the first line of defense against invading microbial pathogens. They are important contributors to innate mucosal immunity and generate various and sophisticated anti-microbial defense mechanisms, including the formation of a tight barrier and secretion of anti-microbial substances as well as inflammatory mediators. To provide these active defense mechanisms, epithelial cells functionally express various pattern-recognition receptors.

Genome wide expression profiling of human peripheral blood mononuclear cells stimulated with BAY 50-4798, a novel T cell selective interleukin-2 analog.

BAY 50-4798, a novel, engineered form of interleukin (IL)-2, is a selective agonist for the high-affinity IL-2 receptor and induces the proliferation of activated human T cells with potency similar to recombinant IL-2 (rIL-2), but has reduced proliferative activity on natural killer cells and is associated with a diminished secondary cytokine cascade. In the current study, the transcriptional profiles of human peripheral blood mononuclear cells (PBMCs) stimulated in vitro with BAY 50-4798 and rIL-2 were compared using Affymetrix microarray technology in combination with Ingenuity Pathway Analysis (IPA) to determine whether there are quantitative or qualitative differences in the molecular networks activated by these IL-2 analogs. A total of 299 genes were differentially expressed in response to the two IL-2 analogs, with an increase in the number of differences over time.

Differential recognition of TLR-dependent microbial ligands in human bronchial epithelial cells.

Bronchial epithelial cells represent the first line of defense against invading airborne pathogens. They are important contributors to innate mucosal immunity and provide a variety of antimicrobial effectors. However, mucosal surfaces are prone to contact with pathogenic, as well as nonpathogenic microbes, and therefore, immune recognition principles have to be tightly controlled to avoid uncontrolled permanent activation.

Urinary and anal incontinence after vacuum delivery.

Objectives: To evaluate urinary and fecal incontinence symptoms, and occult anal sphincter defects in women after vacuum and spontaneous vaginal delivery.

Study Design: In a case-control study, 50 primiparous women delivered by vacuum extraction were compared to 50 women delivered spontaneously. Urinary and anal incontinence symptoms, pelvic floor muscle strength and sphincter defects on endoanal ultrasound were evaluated 6-24 weeks postpartum.

Targeting mammary epithelial cells using a bacterial artificial chromosome.

We describe the generation of transgenic mouse lines expressing Cre recombinase in epithelial cells of the lactating mammary gland. As an expression vector, we used a P1-derived bacterial artificial chromosome (PAC) which harbors the gene for the secretory milk protein, whey acidic protein (Wap). Using homologous recombination in E.