Why social media is good for medicine and why pharmaceutical companies should engage online

There’s nothing more important than our health, but should we trust the Internet when we seek information on medicines? In advance of a free public Polis seminar on social media and pharmaceuticals this Thursday Katherine Relle describes her new research looking at what we can learn from what people say about medicines in online forums

Voyage au Liban

Les relations historiques entretenues par l’ABF-Paca avec les bibliothécaires libanais ont débouché sur un voyage exceptionnel d’une semaine de 15 professionnels de la région au pays du cèdre. Ce riche tour d’horizon englobe les bibliothèques de lecture publique, les bibliothèques universitaires et passe par la Bibliothèque nationale avant de saluer les efforts de toute la chaîne du livre en direction du jeune public

Mast cell-derived mediators promote murine neutrophil effector functions

Mast cells are able to trigger life-saving immune responses in murine models for acute inflammation. In such settings, several lines of evidence indicate that the rapid and protective recruitment of neutrophils initiated by the release of mast cell-derived pro-inflammatory mediators is a key element of innate immunity. Herein, we investigate the impact of mast cells on critical parameters of neutrophil effector function. In the presence of activated murine bone marrow-derived mast cells, neutrophils freshly isolated from bone marrow rapidly lose expression of CD62L and up-regulate CD11b, the latter being partly driven by mast cell-derived TNF and GM-CSF. Mast cells also strongly enhance neutrophil phagocytosis and generation of reactive oxygen species. All these phenomena partly depend on mast cell-derived TNF and to a greater extend on GM-CSF. Furthermore, spontaneous apoptosis of neutrophils is greatly diminished due to the ability of mast cells to deliver antiapoptotic GM-CSF. Finally, we show in a murine model for acute lung inflammation that neutrophil phagocytosis is impaired in mast cell-deficient Kit W-sh /Kit W-sh mice but can be restored upon mast cell engraftment. Thus, a previously underrated feature of mast cells is their ability to boost neutrophil effector functions in immune response

Role of MHC-Linked Susceptibility Genes in the Pathogenesis of Human and Murine Lupus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies against nuclear antigens and a systemic inflammation that can damage a broad spectrum of organs. SLE patients suffer from a wide variety of symptoms, which can affect virtually almost any tissue. As lupus is difficult to diagnose, the worldwide prevalence of SLE can only be roughly estimated to range from 10 and 200 cases per 100,000 individuals with dramatic differences depending on gender, ethnicity, and location. Although the treatment of this disease has been significantly ameliorated by new therapies, improved conventional drug therapy options, and a trained expert eye, the underlying pathogenesis of lupus still remain widely unknown. The complex etiology reflects the complex genetic background of the disease, which is also not well understood yet. However, in the past few years advances in lupus genetics have been made, notably with the publication of genome-wide association studies (GWAS) in humans and the identification of susceptibility genes and loci in mice. This paper reviews the role of MHC-linked susceptibility genes in the pathogenesis of systemic lupus erythematosus

Epigenetic Aspects of Systemic Lupus Erythematosus

Autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, multiple sclerosis, autoimmune hepatitis, and inflammatory bowel disease have complex pathogeneses and the courses of events leading to these diseases are not well understood. The immune surveillance is a delicate balance between self and foreign as well as between tolerance and immune response. Exposure to certain environmental factors may impair this equilibrium, leading to autoimmune diseases, cancer, and the so-called “lifestyle diseases” such as atherosclerosis, heart attack, stroke, and obesity, among others. These external stimuli may also alter the epigenetic status quo and may trigger autoimmune diseases such as SLE in genetically susceptible individuals. This review aims to highlight the role of epigenetic (dys-)regulation in the pathogenesis of SLE. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40744-015-0014-y) contains supplementary material, which is available to authorized users

HEDI: First-Time Clinical Application and Results of a Biomechanical Evaluation and Visualisation Tool for Incisional Hernia Repair

Abdominal wall defects often lead to pain, discomfort, and recurrence of incisional hernias, resulting in significant morbidity and repeated surgical repairs worldwide. Mesh repair for large hernias is usually based on the defect area with a fixed overlap, neglecting biomechanical factors such as muscle activation, intra-abdominal pressure, tissue elasticity, and abdominal wall distension. To address this issue, we present a biomechanical approach to incisional hernia repair that takes into account the unstable abdominal wall. Additionally, we introduce HEDI, a tool that uses computed tomography with Valsalva maneuver to automatically detect and assess hernia size, volume, and abdominal wall instability. Our first clinical application of HEDI in the preoperative evaluation of 31 patients shows significantly improved success rates compared to reported rates, with all patients remaining pain-free and experiencing no hernia recurrence after three years of follow-up

New perspectives on the renal slit diaphragm protein podocin

Podocin is a critical component of the glomerular filtration barrier, its mutations causing recessive steroid-resistant nephrotic syndrome. A GenBank analysis of the human podocin (NPHS2) gene resulted in the possible existence of a new splice variant of podocin in the kidney, missing the in-frame of exon 5, encoding the prohibitin homology domain. Using RT–polymerase chain reaction and immunoblotting followed by sequence analysis, we are for the first time able to prove the expression of a novel podocin isoform (isoform 2), exclusively and constitutively expressed in human podocytes. Furthermore, we reveal singular extrarenal podocin expression in human and murine testis. Our data show the Sertoli cells of the seminiferous tubules to be the origin of testicular podocin. Confocal laser microscopy illustrates the co-localization of podocin with filamentous actin within Sertoli cells, suggesting a role of podocin in the blood/testis barrier. These results led to the rationale to examine podocin expression in testes of men with Sertoli cell-only syndrome, a disorder characterized by azoospermia. Interestingly, we observed a complete down-regulation of podocin mRNA in Sertoli cell-only syndrome, indicating a possible role of podocin in the pathogenesis of this germinal aplasia. Men with Sertoli cell-only syndrome show normal renal podocin expression, suggesting an alternate regulation of the testicular promoter. Our findings may change the perception of podocin and give new insights into the ultrastructure of glomerular slit diaphragm and the blood/testis barrier

Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Cancer

Purpose: Magnetic resonance imaging-guided transurethral ultrasound ablation uses directional thermal ultrasound under magnetic resonance imaging thermometry feedback control for prostatic ablation. We report 12-month outcomes from a prospective multicenter trial (TACT). Materials and methods: A total of 115 men with favorable to intermediate risk prostate cancer across 13 centers were treated with whole gland ablation sparing the urethra and apical sphincter. The co-primary 12-month endpoints were safety and efficacy. Results: In all, 72 (63%) had grade group 2 and 77 (67%) had NCCN® intermediate risk disease. Median treatment delivery time was 51 minutes with 98% (IQR 95-99) thermal coverage of target volume and spatial ablation precision of ±1.4 mm on magnetic resonance imaging thermometry. Grade 3 adverse events occurred in 9 (8%) men. The primary endpoint (U.S. Food and Drug Administration mandated) of prostate specific antigen reduction ≥75% was achieved in 110 of 115 (96%) with median prostate specific antigen reduction of 95% and nadir of 0.34 ng/ml. Median prostate volume decreased from 37 to 3 cc. Among 68 men with pretreatment grade group 2 disease, 52 (79%) were free of grade group 2 disease on 12-month biopsy. Of 111 men with 12-month biopsy data, 72 (65%) had no evidence of cancer. Erections (International Index of Erectile Function question 2 score 2 or greater) were maintained/regained in 69 of 92 (75%). Multivariate predictors of persistent grade group 2 at 12 months included intraprostatic calcifications at screening, suboptimal magnetic resonance imaging thermal coverage of target volume and a PI-RADS™ 3 or greater lesion at 12-month magnetic resonance imaging (p <0.05). Conclusions: The TACT study of magnetic resonance imaging-guided transurethral ultrasound whole gland ablation in men with localized prostate cancer demonstrated effective tissue ablation and prostate specific antigen reduction with low rates of toxicity and residual disease