The Role of Erection Hardness in Determining Erectile Dysfunction (ED) Treatment Outcome

e u r o p e a n u r o l o g y s u p p l e m e n t s 5 ( 2 0 0 6 ) 7 6 7 -7 7 2 a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e u r o p e a n u r o l o g y . c o m Article info Keywords: Erectile dysfunction Erection hardness Intimacy PDE5 inhibitor Self-esteem Sexual satisfaction Abstract Whatever the cause of a man's erectile dysfunction (ED), the result is a loss of penile rigidity that impairs or precludes his ability to achieve or maintain vaginal penetration for sexual intercourse. Identification of the degree of impairment of penile rigidity and durability is an important component in the assessment of ED in both clinical practice and in clinical trials of oral drug treatments for ED. This focus on erection hardness is appropriate because men themselves emphasise this quality when they judge the effectiveness of treatment for ED. This attitude is because the ability to achieve a rigid and durable erection is frequently perceived by affected men as central to their sexual satisfaction and selfimage as sexually competent; loss of this ability may have important adverse effects on their self-esteem, their sexual confidence, and, directly or indirectly, their relationship with their partner. There is a significant positive correlation between improvement in erection hardness and men's sexual self-confidence, sexual enjoyment, and satisfaction with their sexual relationship. Improvement in the rigidity and durability of erections following successful treatment of ED has the potential to allow men to experience better sex, not only by improving erection hardness, but also by restoring their emotional well-being and their partner's satisfaction

LPS Regulates SOCS2 Transcription in a Type I Interferon Dependent Autocrine-Paracrine Loop

Recent studies suggest that SOCS2 is involved in the regulation of TLR signaling. In this study, we found that the expression of SOCS2 is regulated in human monocyte-derived DC by ligands stimulating TLR2, 3, 4, 5, 8 and 9 signaling. SOCS2 induction by LPS was dependent on the type I IFN regulated transcription factors IRF1 and IRF3 as shown by using silencing RNAs for IRFs. Blocking endogenous type I IFN signaling, by neutralizing antibodies to the receptor IFNAR2, abolished SOCS2 mRNA expression after TLR4 stimulation. Transcription factors STAT3, 5 and 6 displayed putative binding sites in the promoter regions of the human SOCS2 gene. Subsequent silencing experiments further supported that STAT3 and STAT5 are involved in LPS induced SOCS2 regulation. In mice we show that SOCS2 mRNA induction is 45% lower in bone marrow derived macrophages derived from MyD88−/− mice, and do not increase in BMMs from IRF3−/− mice after BCG infection. In conclusion, our results suggest that TLR4 signaling indirectly increases SOCS2 in late phase mainly via the production of endogenous type I IFN, and that subsequent IFN receptor signaling activates SOCS2 via STAT3 and STAT5

The Role of the Pharmacist Caring for People Living with HIV/AIDS: A Canadian Position Paper

ABSTRACTThe degree of complexity involved in caring for patients with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) has increased dramatically since 1996. The Canadian Collaborative HIV/AIDS Pharmacy Network was developed to bring together pharmacists with a clinical and research focus in HIV/AIDS to optimize patient outcomes and to promote the profession of pharmacy through communication, education, research, and clinical practice. The purpose of this Canadian position paper is to provide pharmacists with guidelines for the role that a pharmacist may have in caring for HIV/AIDS patients. The Network identified several areas in which pharmacists need guidelines for practice: adherence with therapy, patient counselling, management of drug interactions and adverse reactions, medication acquisition and payment, drug information, research, complementary and alternative therapy, pediatric issues, and the needs of special populations. Each of these areas is covered in this position paper. Pharmacists caring for HIV/AIDS patients in the hospital, the community, and other ambulatory settings have an important opportunity to positively affect patient outcome. This position paper is based on currently available information, and as new information becomes available, our role in the care of these patients must also evolve.RÉSUMÉL’étendue et la complexité des soins à donner aux patients infectés par le virus d’immunodéficience humaine (VIH) ou du syndrome d’immunodéficience acquise (SIDA) se sont accrues considérablement depuis 1996. Le « Canadian Collaborative HIV/AIDS Pharmacy Network » a été mis sur pied pour rassembler les pharmaciens ayant un intérêt en pratique clinique et en recherche sur le VIH/SIDA dans le but d’optimiser les résultats des traitements et de promouvoir la profession de pharmacien par le biais des communications, de l’éducation, de la recherche et de la pratique clinique. Le but de cette déclaration de principe canadienne est d’offrir aux pharmaciens des lignes directrices sur le rôle du pharmacien dans les soins qu’il pourrait apporter aux patients souffrant du VIH/SIDA. Le réseau a identifié plusieurs domaines pour lesquels les pharmaciens ont besoin de lignes directrices dans leur pratique : la fidélité au traitement, le counselling, la prise en charge des réactions indésirables et des interactions médicamenteuses, l’obtention et le paiement des médicaments, l’information sur les médicaments, la recherche, la médecine douce ou parallèle, les questions pédiatriques, et les besoins des populations spéciales. Chacun de ces domaines est traité dans cette déclaration de principe. Les pharmaciens qui donnent des soins aux patients atteints du VIH/SIDA en établissement de santé, dans la communauté ou dans d’autres milieux ambulatoires ont une occasion unique d’influer positivement sur l’issue du traitement de ces patients. Cette déclaration de principe s’appuie sur l’information actuellement disponible, et le rôle du pharmacien dans les soins à prodiguer à de tels patients doit évoluer à la lumière des nouvelles informations

Modeling SHH-driven medulloblastoma with patient iPS cell-derived neural stem cells

Medulloblastoma is the most common malignant brain tumor in children. Here we describe a medulloblastoma model using In-duced pluripotent stem (iPS) cell-derived human neuroepithelial stem (NES) cells generated from a Gorlin syndrome patient carry-ing a germline mutation in the sonic hedgehog (SHH) receptor PTCH1. We found that Gorlin NES cells formed tumors in mouse cerebellum mimicking human medulloblastoma. Retransplantation of tumor-isolated NES (tNES) cells resulted in accelerated tumor formation, cells with reduced growth factor dependency, en-hanced neurosphere formation in vitro, and increased sensitivity to Vismodegib. Using our model, we identified LGALS1 to be a GLI target gene that is up-regulated in both Gorlin tNES cells and SHH-subgroup of medulloblastoma patients. Taken together, we dem-onstrate that NES cells derived from Gorlin patients can be used as a resource to model medulloblastoma initiation and progression and to identify putative targets