A pattern of peri-implantitis affecting middle implants in 3-implant splinted prostheses.

Background: Previous investigators have noted an increased risk of crestal bone loss and failure of the middle implant of 3-implant-splinted (3-IS) fixed dental prostheses (FDPs). Possible causes have included ill-fitting prostheses, unhygienic prosthetic contours, and discrepancies in prosthetic platform heights.

Methods & Results: We identified four cases in which the middle implant of a 3-IS multiunit FDP suffered advanced bone loss, ultimately leading to implant removal.

Differential associations of depression-related phenotypes with cardiometabolic risks: Polygenic analyses and exploring shared genetic variants and pathways.

Background: Numerous studies have suggested associations between depression and cardiometabolic (CM) diseases. However, little is known about the mechanism underlying this comorbidity, and whether the relationship differs by depression subtypes.

Methods: Using polygenic risk scores (PRS) and linkage disequilibrium (LD) score regression, we investigated the genetic overlap of various depression-related phenotypes with a comprehensive panel of 20 CM traits.

Beneficial Effects of Metformin and/or Salicylate on Palmitate- or TNFα-Induced Neuroinflammatory Marker and Neuropeptide Gene Regulation in Immortalized NPY/AgRP Neurons.

Neuropeptide Y (NPY)/Agouti-related peptide (AgRP)-expressing neurons in the hypothalamus induce feeding and decrease energy expenditure. With consumption of a diet high in fat, there is an increase in circulating saturated free fatty acids, including palmitate, leading to the development of neuroinflammation and secretion of cytokines, such as TNFα, and in turn activation of the canonical IKKβ/NFκB cascade. We describe a model of palmitate- and TNFα-induced neuroinflammation in a functionally characterized, immortalized NPY/AgRP-expressing cell model, mHypoE-46, to study whether the anti-diabetic metformin alone or in combination with the anti-inflammatory agent salicylate can ameliorate these detrimental effects.

Life Threatening Severe QTc Prolongation in Patient with Systemic Lupus Erythematosus due to Hydroxychloroquine.

We present a case of a syncopal episode resulting from significant QT interval prolongation in a patient on hydroxychloroquine for the treatment of systemic lupus erythematosus and end stage renal disease. The patient had been treated with hydroxychloroquine for two years prior to presentation. After thorough workup for secondary causes of QT interval prolongation hydroxychloroquine was discontinued and the patient's QT interval shortened.

iCartiGD: the Integrated Cartilage Gene Database.

Background: Diseases of cartilage, such as arthritis and degenerative disc disease, affect the majority of the general population, particularly with ageing. Discovery and understanding of the genes and pathways involved in cartilage biology will greatly assist research on the development, degeneration and disorders of cartilage.

Description: We have established the Integrated Cartilage Gene Database (iCartiGD) of genes that are known, based on results from high throughput experiments, to be expressed in cartilage.

Mechanisms associated with IL-6-induced up-regulation of Jak3 and its role in monocytic differentiation.

We report here that Janus kinase 3 (Jak3) is a primary response gene for interleukin-6 (IL-6) in macrophage differentiation, and ectopic overexpression of Jak3 accelerates monocytic differentiation of normal mouse bone marrow cells stimulated with cytokines. Furthermore, we show that incubation of normal mouse bone marrow cells with a JAK3-specific inhibitor results in profound inhibition of myeloid colony formation in response to granulocyte-macrophage colony-stimulating factor or the combination of stem cell factor, IL-3, and IL-6. In addition, mutagenesis of the Jak3 promoter has revealed that Sp1 binding sites within a -67 to -85 element and a signal transducer and activator of transcription (Stat) binding site at position -44 to -53 are critical for activation of Jak3 transcription in murine M1 myeloid leukemia cells stimulated with IL-6.

Activation of the Jak3 pathway is associated with granulocytic differentiation of myeloid precursor cells.

Jak3, a member of the Janus kinase family of cytoplasmic tyrosine kinases, is expressed at low levels in immature hematopoietic cells and its expression is dramatically up-regulated during the terminal differentiation of these cells. To better understand the role of Jak3 in myeloid cell development, we have investigated the role of Jak3 in myeloid cell differentiation using the 32Dcl3 cell system. Our studies show that Jak3 is a primary response gene for granulocyte colony-stimulating factor (G-CSF) and the accumulation of tyrosine phosphorylated Jak3 correlated with cell growth inhibition and terminal granulocytic differentiation in response to G-CSF.