p17 from HIV induces brain endothelial cell angiogenesis through EGFR-1-mediated cell signalling activation

© 2018, United States & Canadian Academy of Pathology. HIV-associated neurocognitive disorder in HIV patients substantially reduces their quality of life. We previously showed that the HIV matrix protein, p17 could stimulate lymph-angiogenesis in vitro potentially contributing to lymphoma tumour growth and in addition is associated with vascular activation in neuro-degenerating brain tissue; here, therefore, we have investigated the detailed molecular mechanisms of this action. We performed in vitro cell culture, angiogenesis experiments, phospho-protein microarrays and Western blotting to identify cellular signalling induced by p17 within human brain endothelial cells (HbMEC), and inhibitor studies to block p17-induced vascular growth. We also characterised the effects of hippocampal CA1 injection of p17 on epidermal growth factor receptor-1 (EGFR1) expression linked to our murine model of dementia. p17 strongly induced angiogenesis of HbMEC (migration, tube formation and spheroid growth). p17 concomitantly increased phosphorylation of EGFR1 as well as down-stream intermediates ERK1/2, FAK, PLC-γ and PKC-β whilst an inhibitor peptide of EGFR, blocked cell signalling and angiogenesis. Finally, Mice that showed reduced cognitive function and behavioural deficiencies after p17 injection, demonstrated that p17 localised in cortical microvessels and also neurones many of which stained positive for p-EGFR1 by histology/IHC. This work provides strong support that p17 may be involved in initiating and/or perpetuating vascular tissue pathophysiology associated with comorbidity in HIV patients

Uterus-Sparing Surgery: Outcomes of Transvaginal Uterosacral Ligament Hysteropexy

Recently, there has been a paradigm shift toward uterine conservation during the surgical management of pelvic organ prolapse (POP), specifically uterine prolapse. There are few reports on transvaginal uterosacral ligament hysteropexy (TULH). This study aimed to describe our surgical technique and outcomes. Retrospective review and description of surgical technique. Anatomic outcome has been reported using the POP quantification system. Complications were segregated. A comparison of parametric continuous variables was performed using paired t test. Categoric variables were evaluated using the Pearson χ test and the Fisher exact test. A p-value <.05 was considered significant. Teaching hospital. Forty patients who underwent TULH from 2009 to 2017. TULH. A total of 40 patients met the inclusion criteria. Of these, 56.1% had preoperative stage 3 prolapse. The median operative time was 116 minutes. The mean estimated blood loss was 158.5 mL. Transient ureteral obstruction occurred in 2 patients. The mean follow-up time was 17.2 months, and all patients had significant improvement of prolapse (p <.001). There was also an improvement in urinary incontinence and bladder storage symptoms (p <.001). None of the patients were reoperated on for recurrent POP. TULH is an effective uterus-preserving surgical alternative for the treatment of uterovaginal prolapse and provides good apical support. It is also associated with a low short-term recurrence and incidence of reoperation. TULH is a viable option for suitable patients with uterovaginal prolapse who desire uterine conservation

Knowledge and Acceptability of Anal Cytology Screening Among Women

Medical providers have initiated anal cytology screening among women to detect anal neoplasia early. Lack of knowledge of the human papillomavirus (HPV) and anticipated screening discomfort may limit patient acceptance. This study investigates attitudes toward anal cytology screening among women. Women seen for gynecologic care at an urban university medical center were invited to complete an anonymous survey assessing their understanding of HPV and interest in anal cytology screening. Subjects reported the level of pain, discomfort, and embarrassment they expected from screening on a 100-mm visual analog scale. Four hundred four women with mean (SD) age 36 (13) years met criteria for participation. Three hundred thirty-five women reported their race: 52% were white and 36% were African American. Three hundred forty-eight women reported their ethnicities: 76% were Hispanic and 12% were Haitian. Twenty-two percent had never heard of HPV, 57% were not familiar with anal cytology screening, 67% acknowledged that screening was very helpful in detecting anal neoplasia early, and 28% were very interested in undergoing screening. Mean (SD) level of anticipated pain, discomfort, and embarrassment during screening was 62 (32), 68 (30), and 58 (34) mm, respectively. Level of familiarity with anal cytology screening (p < .001), belief in its utility in detecting anal neoplasia (p < .001), and level of anticipated pain (p = .004) were significant predictors of acceptability. Medical providers should improve counseling about anal cytology screening among at-risk women to familiarize them with the procedure, describe its role in detecting anal neoplasia, and address expectations surrounding pain to increase its acceptability