Scoliosis instrumentation alters primary and coupled motions of the spine: An in vitro study using entire thoracolumbar spine and rib cage specimens.

Background: Effects of rigid posterior instrumentation on the three-dimensional post-operative spinal flexibility are widely unknown. Purpose of this in vitro study was to quantify these effects for characteristic adolescent idiopathic scoliosis instrumentations.

Methods: Six fresh frozen human thoracic and lumbar spine specimens (C7-S) with entire rib cage from young adult donors (26-45 years) without clinically relevant deformity were loaded quasi-statically with pure moments of 5 Nm in flexion/extension, lateral bending, and axial rotation.

Spinal instrumentation length affects adjacent segment range of motion and intradiscal pressure.

Scoliosis instrumentation length depends on the type and degree of deformity and the individual preference of the surgeon. This in vitro study aimed to explore effects of increasing instrumentation length on adjacent segment mobility and intervertebral disc loading. Six fresh frozen human spine specimens (C7-sacrum) with entire rib cage from young adult donors (26-45 years) were loaded with pure moments of 5 Nm.

How does thoracic scoliosis surgery affect thoracolumbar spinal flexibility and lumbar intradiscal pressure? An in vitro study confirming the importance of the rib cage.

Purpose: To evaluate effects of spinal and rib osteotomies on the resulting spinal flexibility for surgical correction of thoracic scoliosis and to explore effects of posterior fixation on thoracolumbar segmental range of motion and lumbar intervertebral disc loading.

Methods: Six fresh frozen human thoracolumbar spine and rib cage specimens (26-45 years, two female / four male) without clinically relevant deformity were loaded with pure moments of 5 Nm in flexion/extension, lateral bending, and axial rotation. Optical motion tracking of all segmental levels (C7-S) and intradiscal pressure measurements of the lumbar spine (L1-L5) were performed (1) in intact condition, (2) after Schwab grade 1, (3) Schwab grade 2, and (4) left rib osteotomies at T6-T10 levels, as well as (5) after posterior spinal fixation with pedicle screw-rod instrumentation at T4-L1 levels.

Patients at risk of nontuberculous mycobacterial pulmonary disease who need testing evaluated using a modified Delphi process by European experts.

Background: Identifying patients at risk of nontuberculous mycobacterial pulmonary disease (NTM-PD) is challenging. Delays in NTM-PD identification and management are associated with declining lung function and increased morbidity and mortality.

Study Design And Methods: European NTM-PD experts (n=12) participated in a three-round modified Delphi process to score symptoms and comorbidities potentially associated with NTM-PD as reasons to test for nontuberculous mycobacteria.

A meta-analysis and real-world cohort study on the sex-related differences in efficacy and safety of immunotherapy for hepatocellular carcinoma.

Background & Aims: Sex-related differences in the immune pathogenesis of hepatocellular carcinoma (HCC), particularly related to oestrogen-dependent secretion of pro-tumourigenic cytokines, are well-known. Whether sex influences the efficacy and safety of immunotherapy is not known.

Methods: We performed a restricted maximum likelihood random effects meta-analysis of five phase III trials that evaluated immune checkpoint inhibitors (ICIs) in advanced HCC and reported overall survival (OS) hazard ratios (HRs) stratified by sex to evaluate sex-related differences in OS.

Tiza-itre ncrease and enhanced immunity through an adjuvanted, recombinant herpes oster subunit vccine in patients with liver cirrhosis and post-liver transplantation: a study protocol for a prospective cohort study.

Introduction: Shingrix, an effective adjuvanted, recombinant herpes zoster vaccine (RZV), has been available since 2018. Immunocompromised patients are known to be predisposed to vaccine failure. In-vitro testing of immunological surrogates of vaccine protection could be instrumental for monitoring vaccination success.

Retinoic acid signaling acts as a rheostat to balance Treg function.

Regulatory T cells (Tregs) promote immune homeostasis by maintaining self-tolerance and regulating inflammatory responses. Under certain inflammatory conditions, Tregs can lose their lineage stability and function. Previous studies have reported that ex vivo exposure to retinoic acid (RA) enhances Treg function and stability.

Prevalence of Tympanostomy Tube Placement in Relation to Cleft Width and Type.

Objectives/hypothesis: The prevalence of tympanostomy tube surgery (TTS) in patients with a cleft deformity was investigated, in relation to cleft width and cleft type.

Study Design: Retrospective review of medical health records.

Methods: Retrospective review of medical health records.

Advances in understanding the pathogenesis of graft-versus-host disease.

Acute graft-versus-host disease (GVHD) remains a major complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT). The emergence of different immuno-prophylaxis strategies, such as post-transplant cyclophosphamide or anti-thymocyteglobulin has reduced the incidence of acute GVHD in recent years. The biology of the acute GVHD we observe in the clinic may change due to the use of novel immuno-stimulatory agents, including immune checkpoint inhibitors or anti-neoplastic immune-modifiers, like lenalidomide, given before or after allo-HSCT.

Type I Interferon Receptor Signaling of Neurons and Astrocytes Regulates Microglia Activation during Viral Encephalitis.

In sterile neuroinflammation, a pathological role is proposed for microglia, whereas in viral encephalitis, their function is not entirely clear. Many viruses exploit the odorant system and enter the CNS via the olfactory bulb (OB). Upon intranasal vesicular stomatitis virus instillation, we show an accumulation of activated microglia and monocytes in the OB.

Immune modulatory effects of statins.

Despite major advances in recent years, immunosuppressive regimens for multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus and graft-versus-host disease still have major adverse effects and immunomodulation rather than immune paralysis would be desirable. Statins inhibit the rate-limiting enzyme of the l-mevalonate pathway, the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase. It was shown that blocking the l-mevalonate pathway reduces inflammation through effects on downstream metabolites of the pathway including farnesylpyrophosphates and geranylgeranylpyrophosphates, which are essential for the attachment of GTPases like RhoA, Rac and Ras to the cell membrane.

Homogenous and Microbeam X-Ray Radiation Induces Proteomic Changes in the Brains of Irradiated Rats and in the Brains of Nonirradiated Cage Mate Rats.

To evaluate microbeam radiation therapy (MRT), for brain tumor treatment, the bystander effect in nonirradiated companion animals was investigated. Adult rats were irradiated with 35 or 350 Gy at the European Synchrotron Research Facility using homogenous irradiation (HR) or MRT to the right brain hemisphere. The irradiated rats were housed with nonirradiated rats.

Pathogenesis of acute graft-versus-host disease: from intestinal microbiota alterations to donor T cell activation.

Acute graft-versus-host disease (aGVHD) is a major life-threatening complication of allogeneic haematopoietic cell transplantation (allo-HCT). Here we discuss the aGVHD pathophysiology initiated by multiple signals that cause alloreactive T-cell activation. The outcome of such donor T-cell activation is influenced by T-cell receptor-signal strength, anatomical location, co-stimulatory/co-inhibitory signals and differentiation stage (naive, effector/memory) of T-cells.

Multivariable fractional polynomial interaction to investigate continuous effect modifiers in a meta-analysis on higher versus lower PEEP for patients with ARDS.

Objectives: A recent individual patient data (IPD) meta-analysis suggested that patients with moderate or severe acute respiratory distress syndrome (ARDS) benefit from higher positive end-expiratory pressure (PEEP) ventilation strategies. However, thresholds for continuous variables (eg, hypoxaemia) are often arbitrary and linearity assumptions in regression approaches may not hold; the multivariable fractional polynomial interaction (MFPI) approach can address both problems. The objective of this study was to apply the MFPI approach to investigate interactions between four continuous patient baseline variables and higher versus lower PEEP on clinical outcomes.

Coincident signals from GPCRs and receptor tyrosine kinases are uniquely transduced by PI3Kβ in myeloid cells.

Class I phosphoinositide 3-kinases (PI3Ks) catalyze production of the lipid messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3), which plays a central role in a complex signaling network regulating cell growth, survival, and movement. This network is overactivated in cancer and inflammation, and there is interest in determining the PI3K catalytic subunit (p110α, p110β, p110γ, or p110δ) that should be targeted in different therapeutic contexts. Previous studies have defined unique regulatory inputs for p110β, including direct interaction with Gβγ subunits, Rac, and Rab5.

On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver.

Iron is an essential component of the erythrocyte protein hemoglobin and is crucial to oxygen transport in vertebrates. In the steady state, erythrocyte production is in equilibrium with erythrocyte removal. In various pathophysiological conditions, however, erythrocyte life span is compromised severely, which threatens the organism with anemia and iron toxicity.

German registry of paediatric deep brain stimulation in patients with childhood-onset dystonia (GEPESTIM).

Background: Data on paediatric deep brain stimulation (DBS) is limited, especially for long-term outcomes, because of small numbers in single center series and lack of systematic multi-center trials.

Objectives: We seek to systematically evaluate the clinical outcome of paediatric patients undergoing DBS.

Methods: A German registry on paediatric DBS (GEPESTIM) was created to collect data of patients with dystonia undergoing DBS up to the age of 18 years.

CatacLysMic specificity when targeting myeloid cells?

The antibacterial enzyme lysozyme M (LysM) encoded by the Lyz2 gene is broadly expressed in myeloblasts, macrophages, and neutrophils, and thus has been used for a long time as a cell-specific marker for myeloid cells in mice. In order to delete loxP-site flanked genes in myeloid cells, a Cre-recombinase (Cre) expressing mouse line was created by inserting Cre-coding sequence into the translational start site of the LysM gene. In this issue of the European Journal of Immunology [2016.

Origin, fate and dynamics of macrophages at central nervous system interfaces.

Perivascular, subdural meningeal and choroid plexus macrophages are non-parenchymal macrophages that mediate immune responses at brain boundaries. Although the origin of parenchymal microglia has recently been elucidated, much less is known about the precursors, the underlying transcriptional program and the dynamics of the other macrophages in the central nervous system (CNS). It was assumed that they have a high turnover from blood-borne monocytes.

Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia.

Disease relapse is the most common cause of treatment failure after allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndromes, yet treatment options for such patients remain extremely limited. Azacitidine is an important new therapy in high-risk myelodysplastic syndromes and acute myeloid leukemia but its role in patients who relapse post allograft has not been defined. We studied the tolerability and activity of azacitidine in 181 patients who relapsed after an allograft for acute myeloid leukemia (n=116) or myelodysplastic syndromes (n=65).

Modeling continuous covariates with a "spike" at zero: Bivariate approaches.

In epidemiology and clinical research, predictors often take value zero for a large amount of observations while the distribution of the remaining observations is continuous. These predictors are called variables with a spike at zero. Examples include smoking or alcohol consumption.

Oblique Axis Body Fracture: An Unstable Subtype of Anderson Type III Odontoid Fractures-Apropos of Two Cases.

Purpose. Anderson type III odontoid fractures have traditionally been considered stable and treated conservatively. However, unstable cases with unfavorable results following conservative treatment have been reported.

Pattern injuries from blows with the muzzle end of a handgun.

Pistols, revolvers and blank guns are not only used to discharge cartridges, but also for hits to the victim. In such cases, the blows preferably affect the head and/or the interposed hands protecting the body. The impact is mostly exerted either by the grip of a pistol or the butt of a revolver.

Common and distinct networks for self-referential and social stimulus processing in the human brain.

Self-referential processing is a complex cognitive function, involving a set of implicit and explicit processes, complicating investigation of its distinct neural signature. The present study explores the functional overlap and dissociability of self-referential and social stimulus processing. We combined an established paradigm for explicit self-referential processing with an implicit social stimulus processing paradigm in one fMRI experiment to determine the neural effects of self-relatedness and social processing within one study.