Risk stratification of prostate cancer 2016

Abstract

Prostate cancer is a common malignancy in men, but its management is fraught with controversy owing to its variable biologic and clinical behavior. Despite evidence that PSA screening reduces prostate cancer specific metastasis and death, it has not gained acceptance by various health authorities. Nevertheless, recent advances in biomarker development potentially address many of the shortcomings of routine PSA testing alone, including improved specificity for the detection of clinically significant cancer, optimized risk stratification to aid clinical management decisions, and discovery of genetic variants that may guide optimized therapy of advanced disease.     

Epstein-Barr virus genome load is increased by therapeutic vaccination in HIV-l carriers, and further enhanced in patients with a history of symptomatic primary infection

Objective

Epstein–Barr virus (EBV) infection is an established risk factor for B-cell lymphomas in Human Immunodeficiency virus (HIV)-1 infected patients. A disturbed EBV-host relationship is seen in patient groups with a high risk for EBV-associated lymphomas. We have analysed this relationship by measuring EBV-DNA in the blood of HIV-1 carriers.

Method

EBV-DNA load in B-cells was monitored by PCR in non- or insufficiently antiretroviral treated and rgp160-vaccinated HIV-patients.

Results

Both asymptomatic HIV-infected and AIDS-patients showed a 25–40-fold increase in the number of B cell associated EBV-DNA copies compared to healthy controls. Patients included in a vaccine trial with recombinant HIV gp160 showed a 5-fold increase of EBV load compared to non-immunised patients and a 50-fold increase compared to healthy controls. There was no difference whether they received vaccine or “placebo”. Vaccinated patients with a history of symptomatic primary HIV-1 infection (PHI) had a 280-fold increase in median EBV load compared to healthy controls, thus suggesting a synergistic effect between the vaccination and PHI, which hypothetically could affect lymphoma risk.

Conclusions

We recommend analysis of EBV-load and long term follow up of lymphoma risk in all therapeutic HIV-1 vaccination trials.     

在校医学生心理健康状况调查

目的：了解目前大学生的心理健康状况，学生的主要心理障碍的性质，以便针对性地开心理咨询与治疗工作，方法：使用《心理健康测查表》（PHI）对在校学生进行心理测验，首先从整体上与常模做对照，与常模的差异，再统计各分量表标准分（T分）超过70的人类，统计心理障碍的发生人数，再将各分量表分数明显升高的人类进行统计，了解各类心理障碍发生的频率。结果：在校学生PHI各分量表原始分与常模没有明显差异，各分量表分数均在正常范围。某一分量表或多个分量表T分超过70的人数为115个，占总数的10．79％。，其中男性占12．30％，女生占8．64％，按超过的人数将各分量表排位，由高到低依此为：男生－躯体化，焦虑、抑郁，病态人格，脱离现实、兴奋状态，结论：有障碍的学生中主要是SOM、ANX、DEP分量表升高明显，学生的心理障碍主要是神经症性障碍。PHI测查简易易行，对及时，有针对性地开展心理咨询与治疗工作有重要意义。     

Challenges Associated with Privacy in Health Care Industry: Implementation of HIPAA and the Security Rules

This paper discusses the challenges associated with privacy in health care in the electronic information age based on the Health Insurance Portability and Accountability Act (HIPAA) and the Security Rules. We examine the storing and transmission of sensitive patient data in the modern health care system and discuss current security practices that health care providers institute to comply with HIPAA Security Rule regulations. Based on our research results, we address current outstanding issues that act as impediments to the successful implementation of security measures and conclude the discussion and offer possible avenues of future research.     

Excitatory actions of peptide histidine isoleucine on thalamic relay neurons

Peptide histidine isoleucine (PHI) and vasoactive intestinal peptide (VIP) are neuropeptides synthesized from a common precursor, prepro-VIP, and share structural similarity and biological functions in many systems. Within the central nervous system and peripheral tissues, PHI and VIP have overlapping distribution. PHI-mediated functions are generally via activation of VIP receptors; however, the potency and affinity of PHI for VIP receptors are significantly lower than VIP. In addition, several studies suggest distinct PHI receptors that are independent of VIP receptors. PHI receptors have been cloned and characterized in fish, but their existence in mammals is still unknown. This study focuses on the functional role of PHI in the thalamus because of the localization of both PHI and VIP receptors in this brain region. Using extracellular multiple-unit recording techniques, we found that PHI strongly attenuated the slow intrathalamic rhythmic activity. Using intracellular recording techniques, we found that PHI selectively depolarized thalamic relay neurons via an enhancement of the hyperpolarization-activated mixed cation current, Ih. Further, the actions of PHI were occluded by VIP and dopamine, indicating these modulators converge onto a common mechanism. In contrast to previous work, we found that PHI was more potent than VIP in producing excitatory actions on thalamic neurons. We next used the transgenic mice lacking a specific VIP receptor, VPAC2, to identify its possible role in PHI-mediated actions in the thalamus. PHI depolarized all relay neurons tested from wild-type mice (VPAC2(+/+)); however, in knockout mice (VPAC2(-/-)), PHI produced no change in membrane potential in all neurons tested. Our findings indicate that excitatory actions of PHI are mediated by VPAC2 receptors, not by its own PHI receptors and the excitatory actions of PHI clearly attenuate intrathalamic rhythmic activities, and likely influence information transfer through thalamocortical circuits.     

Immunocytochemical evidence for a diurnal rhythm of neurons showing colocalization of VIP with GRP in the rat suprachiasmatic nucleus

The suprachiasmatic nucleus (SCN), which functions as a biological clock, contains several neuropeptides such as vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), and gastrin-releasing peptide (GRP). Studies from several laboratories have provided evidence for the coexistence of VIP with PHI and GRP, but reliable data about the proportions of colocalization and a possible diurnal rhythmicity are lacking. In the present study, we therefore aimed at studying these aspects. To this end, rats were killed by perfusion fixation during the middle of the day (Zeitgeber time [ZT] 7) and during the second part of the night (ZT 19). Coronal Vibratome sections through the SCN were double-immunolabeled for the presence of VIP and PHI or for VIP and GRP. Analysis of the sections was done by semi-quantitative confocal laser scanning fluorescence microscopy. It turned out that, in keeping with previous literature data, VIP and PHI always coexist at the cellular level. This was seen in all possible ratios, both during the day and at night. Part of these VIP/PHI-containing neurons (21%) and part of the GRP-containing neurons (33%) showed colocalization during the middle of the day. During the second part of the night, these percentages increased significantly to 28% and 40%, respectively. This increase in percentages was due to a significant, nocturnal increase of the number of profiles showing colocalization, in contrast to the number of profiles exclusively immunoreactive for VIP or GRP. J. Comp. Neurol. 391:397–405, 1998. © 1998 Wiley-Liss, Inc.     

Prognostic accuracy of Prostate Health Index and urinary Prostate Cancer Antigen 3 in predicting pathologic features after radical prostatectomy

ObjectiveTo compare the prognostic accuracy of Prostate Health Index (PHI) and Prostate Cancer Antigen 3 in predicting pathologic features in a cohort of patients who underwent radical prostatectomy (RP) for prostate cancer (PCa).Methods and materialsWe evaluated 156 patients with biopsy-proven, clinically localized PCa who underwent RP between January 2013 and December 2013 at 2 tertiary care institutions. Blood and urinary specimens were collected before initial prostate biopsy for [-2] pro–prostate-specific antigen (PSA), its derivates, and PCA3 measurements. Univariate and multivariate logistic regression analyses were carried out to determine the variables that were potentially predictive of tumor volume >0.5 ml, pathologic Gleason sum≥7, pathologically confirmed significant PCa, extracapsular extension, and seminal vesicles invasions.ResultsOn multivariate analyses and after bootstrapping with 1,000 resampled data, the inclusion of PHI significantly increased the accuracy of a baseline multivariate model, which included patient age, total PSA, free PSA, rate of positive cores, clinical stage, prostate volume, body mass index, and biopsy Gleason score (GS), in predicting the study outcomes. Particularly, to predict tumor volume>0.5, the addition of PHI to the baseline model significantly increased predictive accuracy by 7.9% (area under the receiver operating characteristics curve [AUC] = 89.3 vs. 97.2, P>0.05), whereas PCA3 did not lead to a significant increase.Although both PHI and PCA3 significantly improved predictive accuracy to predict extracapsular extension compared with the baseline model, achieving independent predictor status (all P׳s<0.01), only PHI led to a significant improvement in the prediction of seminal vesicles invasions (AUC = 92.2, P<0.05 with a gain of 3.6%).In the subset of patients with GS≤6, PHI significantly improved predictive accuracy by 7.6% compared with the baseline model (AUC = 89.7 vs. 97.3) to predict pathologically confirmed significant PCa and by 5.9% compared with the baseline model (AUC = 83.1 vs. 89.0) to predict pathologic GS≥7. For these outcomes, PCA3 did not add incremental predictive value.ConclusionsIn a cohort of patients who underwent RP, PHI is significantly better than PCA3 in the ability to predict the presence of both more aggressive and extended PCa.     

Roles of PACAP and PHI as inhibitory neurotransmitters in the circular muscle of mouse antrum

Mediators of neurogenic responses of the gastric antrum were studied in wild-type and pituitary adenylate cyclase-activating polypeptide (PACAP) -knockout (KO) mice. Electrical field stimulation (EFS) to the circular muscle strips of the wild-type mouse antrum induced a triphasic response; rapid transient relaxation and contraction, and sustained relaxation that was prolonged for an extended period after the end of EFS. The transient relaxation and contraction were completely inhibited by L-nitroarginine and atropine, respectively. The sustained relaxation was significantly inhibited by a PACAP receptor antagonist, PACAP_6-38. The antral strips prepared from PACAP-KO mice unexpectedly exhibited a tri-phasic response. However, the sustained relaxation was decreased to about one-half of that observed in wild-type mice. PACAP_6-38 inhibited EFS-induced sustained relaxation (33.5% of control) in PACAP-KO mice. Anti-peptide histidine isoleucine (PHI) serum partially (the 30% inhibition) or significantly (the 60% inhibition) inhibited the sustained relaxations in the wild-type and PACAP-KO mice, respectively. The immunoreactivities to the anti-PACAP and anti-PHI serums were found in myenteric ganglia of the mouse antrum. These results suggest that nitric oxide and acetylcholine mediate the transient relaxation and contraction, respectively, and that PACAP and PHI separately mediate the sustained relaxation in the antrum of the mouse stomach.