In vivo knockdown of TAK1 accelerates bone marrow proliferation/differentiation and induces systemic inflammation.

TAK1 (TGF-β Activated Kinase 1) is a MAPK kinase kinase, which activates the p38- and JNK-MAPK and NF-κB pathways downstream of receptors such as Toll-Like-, cytokine- and T-cell and B-cell receptors. Representing such an important node in the pro-inflammatory signal-transduction network, the function of TAK1 has been studied extensively. TAK1 knock-out mice are embryonic lethal, while conditional knock-out mice demonstrated either a pro- or anti-inflammatory function.

Interferon-γ impairs proliferation of hematopoietic stem cells in mice.

Balancing the processes of hematopoietic stem cell (HSC) differentiation and self-renewal is critical for maintaining a lifelong supply of blood cells. The bone marrow (BM) produces a stable output of newly generated cells, but immunologic stress conditions inducing leukopenia increase the demand for peripheral blood cell supply. Here we demonstrate that the proinflammatory cytokine interferon-γ (IFN-γ) impairs maintenance of HSCs by directly reducing their proliferative capacity and that IFN-γ impairs restoration of HSC numbers upon viral infection.

HIF proteins connect the RB-E2F factors to angiogenesis.

Recently, we showed that E2F7 and E2F8 (E2F7/8) are critical regulators of angiogenesis through transcriptional control of VEGFA in cooperation with HIF. (1) Here we investigate the existence of other novel putative angiogenic E2F7/8-HIF targets, and discuss the role of the RB-E2F pathway in regulating angiogenesis during embryonic and tumor development.

Detection of Coxiella burnetii DNA in the environment during and after a large Q fever epidemic in the Netherlands.

Aim: To investigate the Coxiella burnetii DNA content in environmental samples that may contribute to the transmission of C. burnetii.

Methods And Results: During a large Q fever outbreak in the Netherlands, surface swabs and aerosol samples were collected inside stables and around six Q fever-affected ruminant farms, which are located in municipalities varying in Q fever incidence.

Checklists improve experts' diagnostic decisions.

Context: Checklists are commonly proposed tools to reduce error. However, when applied by experts, checklists have the potential to increase cognitive load and result in 'expertise reversal'. One potential solution is to use checklists in the verification stage, rather than in the initial interpretation stage of diagnostic decisions.

Do you have to re-examine to reconsider your diagnosis? Checklists and cardiac exam.

Background: Few studies have investigated whether clinicians can use checklists to verify their diagnostic decisions. Checklists may improve accuracy by prompting clinicians to reconsider or recollect information but might impair decision making by adding to clinicians' cognitive load. This study assessed whether checklists improve cardiac exam diagnostic accuracy, and whether this benefit is dependent on collecting additional information.

An ex vivo porcine nasal mucosa explants model to study MRSA colonization.

Staphylococcus aureus is an opportunistic pathogen able to colonize the upper respiratory tract and skin surfaces in mammals. Methicillin-resistant S. aureus ST398 is prevalent in pigs in Europe and North America.

Protection against allergic airway inflammation during the chronic and acute phases of Trichinella spiralis infection.

Background: Modulation of the host immune response by helminths has been reported to be essential for parasite survival and also to benefit the host by suppressing inflammatory diseases such as allergies. We have previously shown that excretory-secretory products of Trichinella spiralis muscle larvae have immunomodulatory properties and induce in vitro the expansion of CD4(+) CD25(+) FOXP3(+) Treg cells in a TGF-β-dependent manner.

Objective: We aimed at determining the effect of the acute (intestinal) and the chronic (muscle) phase of T.

Smooth incidence maps give valuable insight into Q fever outbreaks in The Netherlands.

From 2007 through 2009, The Netherlands faced large outbreaks of human Q fever. Control measures focused primarily on dairy goat farms because these were implicated as the main source of infection for the surrounding population. However, in other countries, outbreaks have mainly been associated with non-dairy sheep and The Netherlands has many more sheep than goats.

E2F8 is essential for polyploidization in mammalian cells.

Polyploidization is observed in all mammalian species and is a characteristic feature of hepatocytes, but its molecular mechanism and biological significance are unknown. Hepatocyte polyploidization in rodents occurs through incomplete cytokinesis, starts after weaning and increases with age. Here, we show in mice that atypical E2F8 is induced after weaning and required for hepatocyte binucleation and polyploidization.

Molecular typing of Coxiella burnetii from animal and environmental matrices during Q fever epidemics in the Netherlands.

Background: The bacterium Coxiella burnetii has caused unprecedented outbreaks of Q fever in the Netherlands between 2007 and 2010. Since 2007, over 4000 human cases have been reported, with 2354 cases in 2009 alone. Dairy goat farms were identified as most probable sources for emerging clusters of human Q fever cases in their vicinity.

Tumor necrosis factor receptor 1 gain-of-function mutation aggravates nonalcoholic fatty liver disease but does not cause insulin resistance in a murine model.

Unlabelled: Ectodomain shedding of tumor necrosis factor receptor 1 (TNFR1) provides negative feedback to the inflammatory loop induced by TNFα. As the significance of this mechanism in obesity-associated pathologies is unclear, we aimed to unravel how much TNFR1 ectodomain shedding controls the development of nonalcoholic fatty liver disease (NAFLD), as well as its role in the development of insulin resistance. We used knockin mice expressing a mutated TNFR1 ectodomain (p55(Δns)), incapable of shedding and dampen the inflammatory response.

Abdominal plain film before gastrostomy tube placement to predict success of percutaneous endoscopic procedure.

Objectives: Percutaneous endoscopic gastrostomy (PEG) tube feeding is a convenient method for children requiring long-term enteral nutrition. Preoperative fitness of the majority of pediatric PEG candidates is graded as American Society of Anesthesiologists physical status ≥ III, indicating increased risk for peri- and postoperative morbidity. The success rate of endoscopic insertion is high, but variations in the anatomy may lead to failure of PEG placement and repeated exposure to anesthesia for surgical gastrostomy.

Q fever: single-point source outbreak with high attack rates and massive numbers of undetected infections across an entire region.

Background: In early 2009, a dairy-goat annex care farm in South Limburg, the Netherlands, reported 220 Coxiella burnetii-related abortions in 450 pregnant goats. These preceded human cases and occurred in a region that was Q-fever free before 2009, providing a unique quasi-experimental setting for investigating regional transmission patterns associated with a Q-fever point source.

Methods: Index-farm residents/employees, visitors, and their household contacts were traced and screened for C.

E2F7 and E2F8 promote angiogenesis through transcriptional activation of VEGFA in cooperation with HIF1.

The E2F family of transcription factors plays an important role in controlling cell-cycle progression. While this is their best-known function, we report here novel functions for the newest members of the E2F family, E2F7 and E2F8 (E2F7/8). We show that simultaneous deletion of E2F7/8 in zebrafish and mice leads to severe vascular defects during embryonic development.

Constructive, collaborative, contextual, and self-directed learning in surface anatomy education.

Anatomy education often consists of a combination of lectures and laboratory sessions, the latter frequently including surface anatomy. Studying surface anatomy enables students to elaborate on their knowledge of the cadaver's static anatomy by enabling the visualization of structures, especially those of the musculoskeletal system, move and function in a living human being. A recent development in teaching methods for surface anatomy is body painting, which several studies suggest increases both student motivation and knowledge acquisition.

Local application of gentamicin-containing collagen implant in the prophylaxis of surgical site infection following gastrointestinal surgery.

Background: Gastrointestinal surgery is associated with one of the highest rates of SSI due to the nature of the surgery and to the added complication of operating on patients with significant co-morbidities. This high rate of SSI may negatively impact wound healing, patient recovery time, length of hospital stay and associated healthcare costs. This article provides an overview of the efficacy and safety of prophylactic application of resorbable gentamicin-containing collagen implants (GCCI) in the prevention of SSI following GI surgical procedures.

Detection of Coxiella burnetii DNA in inhalable airborne dust samples from goat farms after mandatory culling.

Coxiella burnetii is thought to infect humans primarily via airborne transmission. However, air measurements of C. burnetii are sparse.

Atypical E2F repressors and activators coordinate placental development.

The evolutionarily ancient arm of the E2f family of transcription factors consisting of the two atypical members E2f7 and E2f8 is essential for murine embryonic development. However, the critical tissues, cellular processes, and molecular pathways regulated by these two factors remain unknown. Using a series of fetal and placental lineage-specific cre mice, we show that E2F7/E2F8 functions in extraembryonic trophoblast lineages are both necessary and sufficient to carry fetuses to term.

The group medical appointment (GMA) in haemophilia and von Willebrand's disease: a new development in outpatient paediatric care.

The Group Medical Appointment (GMA) is a novel consultation form in which patients undergo individual consultations in each other's presence. To compare participants' experiences with GMA and Individual Medical Appointments (IMA), the usual standard of care, our team recently implemented the GMA for children aged 0-18 years with haemophilia or von Willebrand's disease. Participants' experiences with GMA were measured using a standardized QUOTE-questionnaire.

In vivo biocompatibility and biodegradation of 3D-printed porous scaffolds based on a hydroxyl-functionalized poly(ε-caprolactone).

The aim of this study was to evaluate the in vivo biodegradation and biocompatibility of three-dimensional (3D) scaffolds based on a hydroxyl-functionalized polyester (poly(hydroxymethylglycolide-co-ε-caprolactone), PHMGCL), which has enhanced hydrophilicity, increased degradation rate, and improved cell-material interactions as compared to its counterpart poly(ε-caprolactone), PCL. In this study, 3D scaffolds based on this polymer (PHMGCL, HMG:CL 8:92) were prepared by means of fiber deposition (melt-plotting). The biodegradation and tissue biocompatibility of PHMGCL and PCL scaffolds after subcutaneous implantation in Balb/c mice were investigated.

Detection of Coxiella burnetii DNA on small-ruminant farms during a Q fever outbreak in the Netherlands.

During large Q fever outbreaks in the Netherlands between 2007 and 2010, dairy goat farms were implicated as the primary source of human Q fever. The transmission of Coxiella burnetii to humans is thought to occur primarily via aerosols, although available data on C. burnetii in aerosols and other environmental matrices are limited.

Genotypic diversity of Coxiella burnetii in the 2007-2010 Q fever outbreak episodes in The Netherlands.

The genotypic diversity of Coxiella burnetii in clinical samples obtained from the Dutch Q fever outbreak episodes of 2007-2010 was determined by using a 6-locus variable-number tandem repeat analysis panel. The results are consistent with the introduction of one founder genotype that is gradually diversifying over time while spreading throughout The Netherlands.

E2F7 represses a network of oscillating cell cycle genes to control S-phase progression.

E2F transcription factors are known to be important for timely activation of G(1)/S and G(2)/M genes required for cell cycle progression, but transcriptional mechanisms for deactivation of cell cycle-regulated genes are unknown. Here, we show that E2F7 is highly expressed during mid to late S-phase, occupies promoters of G(1)/S-regulated genes and represses their transcription. ChIP-seq analysis revealed that E2F7 binds preferentially to genomic sites containing the TTCCCGCC motif, which closely resembles the E2F consensus site.

BH3-only protein Noxa regulates apoptosis in activated B cells and controls high-affinity antibody formation.

The efficiency of humoral immune responses depends on the selective outgrowth of B cells and plasma cells that produce high affinity antibodies. The factors responsible for affinity maturation of B cell clones in the germinal center (GC) have been well established but selection mechanisms that allow clones to enter the GC are largely unknown. Here we identify apoptosis, regulated by the proapoptotic BH3-only member Noxa (Pmaip1), as a critical factor for the selection of high-affinity clones during B cell expansion after antigen triggering.