The effector IpaH1.4 facilitates RNF213 degradation and protects cytosolic bacteria against interferon-induced ubiquitylation.

A central signal that marshals host defense against many infections is the lymphocyte-derived cytokine interferon-gamma (IFNγ). The IFNγ receptor is expressed on most human cells and its activation leads to the expression of antimicrobial proteins that execute diverse cell-autonomous immune programs. One such immune program consists of the sequential detection, ubiquitylation, and destruction of intracellular pathogens.

Surgical outcomes in surgical oncology patients who participated in a family involvement program.

Background: There is a lack of evidence regarding the relationship between family involvement and outcomes in gastrointestinal oncology patients after surgery. To evaluate the effect of a family involvement program for patients undergoing oncologic gastrointestinal surgery on unplanned readmissions within 30 days after surgery.

Methods: A multicenter patient-preference cohort study compared 2 groups: patients who participated in the family involvement program versus usual care.

Exploiting bacterial effector proteins to uncover evolutionarily conserved antiviral host machinery.

Arboviruses are a diverse group of insect-transmitted pathogens that pose global public health challenges. Identifying evolutionarily conserved host factors that combat arbovirus replication in disparate eukaryotic hosts is important as they may tip the balance between productive and abortive viral replication, and thus determine virus host range. Here, we exploit naturally abortive arbovirus infections that we identified in lepidopteran cells and use bacterial effector proteins to uncover host factors restricting arbovirus replication.

Case Report: Pediatric alloplastic nose reconstruction with a 3D printed patient specific titanium implant.

An 11-year-old girl presented at the emergency service with a nasal defect caused by a dog bite in the midface. Autologous nose reconstruction in the pediatric population is challenging due to donor site morbidity and remaining facial growth. Temporary prosthetic treatment is difficult to accept due to problems with retention.

Customized Nasal Prosthesis for a Jones Lacrimal Bypass Tube Using 3-Dimensional Planning and Printing Technology.

A 35-year-old woman was treated for extensive squamous cell carcinoma of the nasal septal mucosa with total rhinectomy, including removal of the nasal septum, and chemoradiotherapy. A magnet-retained nasal prosthesis was fitted. She had developed right-sided epiphora from total proximal lacrimal canalicular obstruction, for which an angled Jones lacrimal bypass tube was inserted.

Environmental Selection Shapes Bacterial Community Composition in Traditionally Fermented Maize-Based Foods from Benin, Tanzania and Zambia.

Natural (microbial) communities are complex ecosystems with many interactions and cross-dependencies. Among other factors, selection pressures from the environment are thought to drive the composition and functionality of microbial communities. Fermented foods, when processed using non-industrial methods, harbor such natural microbial communities.

Pathogenic ubiquitination of GSDMB inhibits NK cell bactericidal functions.

Gasdermin B (GSDMB) belongs to a large family of pore-forming cytolysins that execute inflammatory cell death programs. While genetic studies have linked GSDMB polymorphisms to human disease, its function in the immunological response to pathogens remains poorly understood. Here, we report a dynamic host-pathogen conflict between GSDMB and the IpaH7.

Toxins, mutations and adaptations.

The toxins that some bacteria secrete to kill off rival species can also generate mutations that help toxin-resistant populations adapt to new environments.

Erythropoietin, Fibroblast Growth Factor 23, and Death After Kidney Transplantation.

Elevated levels of erythropoietin (EPO) are associated with an increased risk of death in renal transplant recipients (RTRs), but the underlying mechanisms remain unclear. Emerging data suggest that EPO stimulates production of the phosphaturic hormone fibroblast growth factor 23 (FGF23), another strong risk factor for death in RTRs. We hypothesized that the hitherto unexplained association between EPO levels and adverse outcomes may be attributable to increased levels of FGF23.

Digital arterial pressure pulse wave analysis and cardiovascular events in the general population: the Prevention of Renal and Vascular End-stage Disease study.

Background: Arterial stiffness influences the contour of the digital pressure pulse wave.

Method: Here, we investigated whether the digital pulse propagation index (DPPI), based on the digital pressure pulse wave, DPPI is associated with cardiovascular events, heart failure, and mortality in a large population-based cohort. Between 2001 and 2003, DPPI was measured with a PortaPres noninvasive hemodynamic monitoring device (FinaPres Medical Systems, Amsterdam, The Netherlands) in participants of the Prevention of Renal and Vascular End-stage Disease study, a community-based cohort.

Fibroblast growth factor 23 and new-onset chronic kidney disease in the general population: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study.

Background: Fibroblast growth factor 23 (FGF23), a phosphate-regulating hormone that increases early in the course of chronic kidney disease (CKD), is associated with disease progression in patients with established CKD. Here we aimed to investigate the association between plasma FGF23 and new-onset CKD in the general population.

Methods: We included 5253 individuals without CKD who participated in the Prevention of Renal and Vascular Endstage Disease study, a prospective, population-based cohort.

Brucella abortus Infection of Placental Trophoblasts Triggers Endoplasmic Reticulum Stress-Mediated Cell Death and Fetal Loss via Type IV Secretion System-Dependent Activation of CHOP.

Subversion of endoplasmic reticulum (ER) function is a feature shared by multiple intracellular bacteria and viruses, and in many cases this disruption of cellular function activates pathways of the unfolded protein response (UPR). In the case of infection with , the etiologic agent of brucellosis, the unfolded protein response in the infected placenta contributes to placentitis and abortion, leading to pathogen transmission. Here we show that infection of pregnant mice led to death of infected placental trophoblasts in a manner that depended on the VirB type IV secretion system (T4SS) and its effector VceC.

No increased risk of transfusion-transmissible infections after tattooing, body piercing, or acupuncture among blood donors in the Netherlands.

Background: In the Netherlands, needle-related events (NREs) including tattoos, piercings, and acupuncture are a reason for temporary blood donor deferral. This study aims to evaluate whether donors with recent NREs had a higher risk of transfusion-transmissible infections (TTIs) compared to donors without recent NREs.

Study Design And Methods: Data from 2006 through 2015 on all blood donation attempts in the Netherlands were collected.

Iron deficiency, elevated erythropoietin, fibroblast growth factor 23, and mortality in the general population of the Netherlands: A cohort study.

Background: Emerging data in chronic kidney disease (CKD) patients suggest that iron deficiency and higher circulating levels of erythropoietin (EPO) stimulate the expression and concomitant cleavage of the osteocyte-derived, phosphate-regulating hormone fibroblast growth factor 23 (FGF23), a risk factor for premature mortality. To date, clinical implications of iron deficiency and high EPO levels in the general population, and the potential downstream role of FGF23, are unclear. Therefore, we aimed to determine the associations between iron deficiency and higher EPO levels with mortality, and the potential mediating role of FGF23, in a cohort of community-dwelling subjects.

Effects of Dapagliflozin on Circulating Markers of Phosphate Homeostasis.

Background And Objectives: The sodium glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin is a novel drug for the treatment of diabetes mellitus. Recent studies suggest that SGLT-2 inhibitors affect phosphate homeostasis, but their effects on phosphate-regulating hormones in patients with diabetic kidney disease are still unclear.

Design, Setting, Participants, & Measurements: We performed a analysis of a double-blind, randomized, crossover trial in patients with type 2 diabetes with early-stage diabetic kidney disease on stable renin-angiotensin-aldosterone system blockade, with an albumin-to-creatinine ratio between 100 and 3500 mg/g, eGFR≥45 ml/min per 1.

Effects of erythropoietin on fibroblast growth factor 23 in mice and humans.

Background: Erythropoietin (EPO) has been reported as a novel determinant of fibroblast growth factor 23 (FGF23) production; however, it is unknown whether FGF23 is stimulated by chronic exposure to EPO or by EPO administration in nonpolycystic chronic kidney disease (CKD) models.

Methods: We analyzed the effects of chronic EPO on FGF23 in murine models with chronically high EPO levels and normal kidney function. We studied the effects of exogenous EPO on FGF23 in wild-type mice, with and without CKD, injected with EPO.

Cooperative Immune Suppression by Escherichia coli and Shigella Effector Proteins.

The enteric attaching and effacing (A/E) pathogens enterohemorrhagic (EHEC) and enteropathogenic (EPEC) and the invasive pathogens enteroinvasive (EIEC) and encode type III secretion systems (T3SS) used to inject effector proteins into human host cells during infection. Among these are a group of effectors required for NF-κB-mediated host immune evasion. Recent studies have identified several effector proteins from A/E pathogens and EIEC/ that are involved in suppression of NF-κB and have uncovered their cellular and molecular functions.

Computational prediction of new auxetic materials.

Auxetics comprise a rare family of materials that manifest negative Poisson's ratio, which causes an expansion instead of contraction under tension. Most known homogeneously auxetic materials are porous foams or artificial macrostructures and there are few examples of inorganic materials that exhibit this behavior as polycrystalline solids. It is now possible to accelerate the discovery of materials with target properties, such as auxetics, using high-throughput computations, open databases, and efficient search algorithms.

Effects of Vitamin D Receptor Activation and Dietary Sodium Restriction on Residual Albuminuria in CKD: The ViRTUE-CKD Trial.

Reduction of residual albuminuria during single-agent renin-angiotensin-aldosterone blockade is accompanied by improved cardiorenal outcomes in CKD. We studied the individual and combined effects of the vitamin D receptor activator paricalcitol (PARI) and dietary sodium restriction on residual albuminuria in CKD. In a multicenter, randomized, placebo (PLAC)-controlled, crossover trial, 45 patients with nondiabetic CKD stages 1-3 and albuminuria >300 mg/24 h despite ramipril at 10 mg/d and BP<140/90 mmHg were treated for four 8-week periods with PARI (2 g/d) or PLAC, each combined with a low-sodium (LS) or regular sodium (RS) diet.

A Statistical Learning Framework for Materials Science: Application to Elastic Moduli of k-nary Inorganic Polycrystalline Compounds.

Materials scientists increasingly employ machine or statistical learning (SL) techniques to accelerate materials discovery and design. Such pursuits benefit from pooling training data across, and thus being able to generalize predictions over, k-nary compounds of diverse chemistries and structures. This work presents a SL framework that addresses challenges in materials science applications, where datasets are diverse but of modest size, and extreme values are often of interest.

Shigella flexneri suppresses NF-κB activation by inhibiting linear ubiquitin chain ligation.

The linear ubiquitin chain assembly complex (LUBAC) is a multimeric E3 ligase that catalyses M1 or linear ubiquitination of activated immune receptor signalling complexes (RSCs). Mutations that disrupt linear ubiquitin assembly lead to complex disease pathologies including immunodeficiency and autoinflammation in both humans and mice, but microbial toxins that target LUBAC function have not yet been discovered. Here, we report the identification of two homologous Shigella flexneri type III secretion system effector E3 ligases IpaH1.

Phosphate Binding Therapy to Lower Serum Fibroblast-Growth-Factor-23 Concentrations in Chronic Kidney Disease: Rationale and Study Design of the Sevelamer on FGF23 Trial (SoFT).

Background: Increased levels of phosphate and fibroblast growth factor-23 (FGF23) are strong predictors of cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). Preliminary data suggest that interventions lowering gastro-intestinal phosphate uptake lowers serum FGF23 concentrations and improves cardiovascular risk and subsequently survival. However, data are lacking about the magnitude of effects, the effect in different stages of CKD and whether there is a dose-effect relationship.