The role of spinal injections towards optimizing patient selection for spinal surgery: A proof-of-concept study in 176 lower back pain patients.

Background: Managing degenerative lumbar diseases is challenging due to the complexity of identifying symptom causes, especially when multiple pathologies coexist. This study evaluated the impact of patient-specific lumbar spine infiltrations on therapeutic strategies in patients with multiple spinal pathologies (MSP) or specific spinal pathologies (SSP).

Methods: A retrospective cohort of 176 patients treated for subacute or chronic lumbar pain with targeted spinal infiltrations was analyzed.

Convolutional Neural Networks in Spinal Magnetic Resonance Imaging: A Systematic Review.

Objective: Convolutional neural networks (CNNs) are being increasingly used in the medical field, especially for image recognition in high-resolution, large-volume data sets. The study represents the current state of research on the application of CNNs in image segmentation and pathology detection in spine magnetic resonance imaging.

Methods: For this systematic literature review, the authors performed a systematic initial search of the PubMed/Medline and Web of Science (Core collection) databases for eligible investigations.

Filaggrin-stratified transcriptomic analysis of pediatric skin identifies mechanistic pathways in patients with atopic dermatitis.

Background: Atopic dermatitis (AD; eczema) is characterized by a widespread abnormality in cutaneous barrier function and propensity to inflammation. Filaggrin is a multifunctional protein and plays a key role in skin barrier formation. Loss-of-function mutations in the gene encoding filaggrin (FLG) are a highly significant risk factor for atopic disease, but the molecular mechanisms leading to dermatitis remain unclear.

The microtubule poison vinorelbine kills cells independently of mitotic arrest and targets cells lacking the APC tumour suppressor more effectively.

Colorectal cancers commonly carry truncation mutations in the adenomatous polyposis coli (APC) gene. The APC protein contributes to the stabilization of microtubules. Consistently, microtubules in cells lacking APC depolymerize more readily in response to microtubule-destabilizing drugs.

Filaggrin loss-of-function mutations are associated with enhanced expression of IL-1 cytokines in the stratum corneum of patients with atopic dermatitis and in a murine model of filaggrin deficiency.

Background: Filaggrin (FLG) mutations result in reduced stratum corneum (SC) natural moisturizing factor (NMF) components and consequent increased SC pH. Because higher pH activates SC protease activity, we hypothesized an enhanced release of proinflammatory IL-1 cytokines from corneocytes in patients with atopic dermatitis (AD) with FLG mutations (AD(FLG)) compared with that seen in patients with AD without these mutations (AD(NON-FLG)).

Objectives: We sought to investigate SC IL-1 cytokine profiles in the uninvolved skin of controls and patients with AD(FLG) versus patients with AD(NON-FLG).

Intragenic copy number variation within filaggrin contributes to the risk of atopic dermatitis with a dose-dependent effect.

Loss-of-function variants within the filaggrin gene (FLG) increase the risk of atopic dermatitis. FLG also demonstrates intragenic copy number variation (CNV), with alleles encoding 10, 11, or 12 filaggrin monomers; hence, CNV may affect the amount of filaggrin expressed in the epidermis. A total of 876 Irish pediatric atopic dermatitis cases were compared with 928 population controls to test the hypothesis that CNV within FLG affects the risk of atopic dermatitis independently of FLG-null mutations.

Wide spectrum of filaggrin-null mutations in atopic dermatitis highlights differences between Singaporean Chinese and European populations.

Background: Null mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris (IV) and predispose to atopic dermatitis (AD). Cohort studies in Europe and Japan have reported an FLG mutation carrier frequency of between 14% and 56%, but the prevalent European FLG mutations are rare or absent in Chinese patients with IV and AD.

Objectives: To investigate further the spectrum of FLG-null mutations in Chinese patients and to compare it with that in other populations.

Levels of filaggrin degradation products are influenced by both filaggrin genotype and atopic dermatitis severity.

Background: Filaggrin, coded by FLG, is the main source of several major components of natural moisturizing factor (NMF) in the stratum corneum (SC), including pyrrolidone carboxylic acid (PCA) and urocanic acid (UCA). Loss-offunction mutations in FLG lead to reduced levels of filaggrin degradation products in the SC. It has recently been suggested that expression of filaggrin may additionally be influenced by the atopic inflammatory response.

Defining the role of APC in the mitotic spindle checkpoint in vivo: APC-deficient cells are resistant to Taxol.

Mutations in the adenomatous polyposis coli (APC) tumour suppressor are the key initiating event of colorectal cancer. Although the control of WNT signalling is well established as a central tumour-suppressive function, the significance of APC in regulating chromosome instability is less well established. In this study, we test whether APC-deficient cells have a functional spindle assembly checkpoint (SAC) in vivo by examining the response of these cells to Taxol and Vinorelbine.

Raman profiles of the stratum corneum define 3 filaggrin genotype-determined atopic dermatitis endophenotypes.

Background: Filaggrin (FLG) has a central role in the pathogenesis of atopic dermatitis (AD). FLG is a complex repetitive gene; highly population-specific mutations and multiple rare mutations make routine genotyping complex. Furthermore, the mechanistic pathways through which mutations in FLG predispose to AD are unclear.

Novel self-association of the APC molecule affects APC clusters and cell migration.

Truncation mutations in the adenomatous polyposis coli (APC) gene are responsible for familial and sporadic colorectal cancer. APC is a multifunctional protein involved in cell migration, proliferation and differentiation. The APC protein forms specific clusters in the cell periphery that correlate with sites of active cell migration.

Loss of APC induces polyploidy as a result of a combination of defects in mitosis and apoptosis.

Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene initiate a majority of colorectal cancers. Acquisition of chromosomal instability is an early event in these tumors. We provide evidence that the loss of APC leads to a partial loss of interkinetochore tension at metaphase and alters mitotic progression.

Lack of adenomatous polyposis coli protein correlates with a decrease in cell migration and overall changes in microtubule stability.

Most sporadic colorectal tumors carry truncation mutations in the adenomatous polyposis coli (APC) gene. The APC protein is involved in many processes that govern gut tissue. In addition to its involvement in the regulation of beta-catenin, APC is a cytoskeletal regulator with direct and indirect effects on microtubules.

Transcriptional regulation by the repressor of estrogen receptor activity via recruitment of histone deacetylases.

Histone acetyltransferases and deacetylases are recruited by transcription factors and adapter proteins to regulate specific subsets of target genes. We were interested in identifying interaction partners of histone deacetylase 1 (HDAC1) that might be involved in conferring target or substrate specificity. Using the yeast two-hybrid system, we isolated the repressor of estrogen receptor activity (REA) as a novel HDAC1-associated protein.

Homo-oligomerisation and nuclear localisation of mouse histone deacetylase 1.

Reversible histone acetylation changes the chromatin structure and can modulate gene transcription. Mammalian histone deacetylase 1 (HDAC1) is a nuclear protein that belongs to a growing family of evolutionarily conserved enzymes catalysing the removal of acetyl residues from core histones and other proteins. Previously, we have identified murine HDAC1 as a growth factor-inducible protein in murine T-cells.